474374006http://www.sbir.gov/node/374006OBJECTIVE: This topic seeks to identify and develop high-power Radio Frequency Micro Electro-Mechanical Systems (RF-MEMS) accelerated reliability test methodologies to reduce technology acceptance time for switched phase shifters that utilize capacitive or contact RF MEMS switches. Currently, life testing conducted on RF MEMs switching devices requires significant time and cost due to a lack of physics-based test acceleration methodology. Identification of acceleration protocols, beyond currently conducted real-time life testing approaches, is required to shorten the test time required and accelerate acceptance of these technologies by government programs. The development of an acceptable physics-based model and accelerated test methodology would significantly reduce the cost and time required for system qualification and insertion of high-power RF-MEMS switches and phase shifters for Radar/Electronics Warfare (EW) phased array applications. DESCRIPTION: High power radar and EW modules are required for Electronically Scanned Arrays (ESAs) to provide significant system performance improvements. These modules, from a system perspective, are a major portion of the system cost and they provide thermal and reliability challenges to designers and manufacturers that must be overcome to provide effective ESA solutions. RF MEMS switches and phase shifters have been under development to provide phase control in some ESA architectures. These devices offer the potential of low insertion loss, ultra-linear performance and very low operating power. The qualification and adoption of these technologies by programs requires demonstrated reliability, however current real-time testing is costly because it requires significant time to cycle the RF MEMS switches and phase shifters. R & D efforts are required to identify acceleration mechanisms that allow prediction of device lifetime by means of short-term testing. The goal of this program is to perform the research and development needed to establish RF MEMS device accelerated reliability test methodologies applicable to X-Band (8-12 GHZ) MEMs devices with output power levels of up to 5W peak, 2W average. PHASE I: Identify, model and demonstrate innovative material, design, process and testing methods that lead to accelerated high-power RF MEMs reliability testing. This should include physics-based models, equipment improvements, and test procedure standardization/improvement based on experimental results on capacitive or contact RF MEMS switches that lead to at least a 5X test time reduction over current real-time life test methodologies. PHASE II: Develop and demonstrate a prototype lifetime test methodology for high power RF MEMs switches and phase shifters capable of X-band operation at power levels up to 5W peak, and 2W average that has the test time reduction developed in Phase I. The prototype procedures developed should have dual use/commercial application. PHASE III: Deliver a prototype test station to the government after conducting validation testing of the lifetime of RF MEMs devices having the performance identified in this topic. Transition the test methodologies developed in Phase II to support an MDA system insertion. DUAL USE/COMMERCIALIZATION POTENTIAL: RF MEMS switches and phase shifters are being developed for commercial and military applications, these components are enabling higher performance ESA for EW and Radar, and they would find numerous applications in military systems as well as commercial systems, for example, transportation radar systems. REFERENCES: 1. H. S. Newman, J. L. Ebel, D. Judy, and J. Maciel,"Lifetime Measurements on a High-Reliability RF-MEMS Contact Switch,"IEEE Microwave and Wireless Components Letters, Vol. 18, No. 2, 2008. 2. X. Yuan, Z. Peng, J. C. M. Hwang, D. Forehand, and Charles L. Goldsmith,"Acceleration of Dielectric Charging in RF MEMS Capacitive Switches,"IEEE Transactions on Device and Materials Reliability, Vol. 6, No. 4, 2006. 3. J. Teti, and F. Darreff,"MEMS 2-bit Phase-Shifter Failure Mode and Reliability Considerations for Large X-Band Arrays,"IEEE Trans. Microwave Theory and Tech., Vol. 52, No. 2, pp. 693-701, 2004.MDA201101272011022820110330-1Closed374009http://www.sbir.gov/node/374009OBJECTIVE: Develop a compact multi-input, multi-output Ka-band radar system to provide over-the-horizon maritime target detection and tracking utilizing evaporation duct propagation. DESCRIPTION: The long-range detection, tracking, and classification of maritime surface contacts including detection and discrimination of small targets such as periscope masts is an essential Naval capability. Long-range, over-the-horizon microwave propagation over the sea is a very desirable means to achieve this capability. Over the horizon propagation may occur in the presence of atmospheric and hydrological environments with super-refraction or atmospheric waveguide (low height and evaporation) conditions. These conditions are extremely common. In addition, as a result of changes in the troposphere complex weather phenomena, atmospheric inhomogeneity, turbulence and level of stratification, the recurrent emergence of strong convection can cause scattering layer so that a long-range performance can also be achieved through troposphere scattering. Multiple-input multiple-output (MIMO) radar technology may be particularly well suited for this very wide angle surveillance task. Some analyses indicate that MIMO radar may outperform its phased-array counterpart significantly in parameter identifiability, spatial spectral estimation resolution, clutter suppression capability and transmit beampattern design. Another potential advantage of coherent MIMO radars is that they enable the use of sparse arrays without the adverse effects of sidelobes. For maritime target moving indicator radars MIMO may provide improved angle estimation and minimum detectable velocity. In order to take full advantage of the complex propagation conditions, the adaptive tailoring of the transmitted waveform to the propagation medium and the target scattering characteristics may significant enhance overall detection and false-alarm performance. To date the analyses supporting MIMO performance have not been sufficiently validated through experimentation to the satisfaction of the radar community. In fact, the merits of MIMO radar and a matter of strong dispute in the community with many members polarized on opposite ends of the opinion spectrum. The goal of this work is to design and demonstrate of a proof-of-concept Ka-band MIMO radar system for over-the-horizon maritime target detection and tracking utilizing evaporation duct propagation. The demonstration shall be executed in a manner to allow full assessment of fundamental MIMO radar capabilities. The effort should include the design of signal processing algorithms including adaptive waveform design and receiver signal synthesis. PHASE I: Demonstrate the feasibility of a Ka-band MIMO radar system through modeling and simulation demonstrations. Candidate tasks are (1) comprehensive modeling of evaporation duct propagation as it relates to the radar usage; (2) adaptive waveform designs for improved detection performance; (3) performance evaluations of the design in terms of target detection and localization capabilities; (4) identification of performance limitations and hardware requirements to prepare for Phase II hardware implementation. Preliminary hardware design should be in place and ready for Phase II effort. PHASE II: Develop a prototype Ka-band MIMO radar system. The design initiated in Phase I should be implemented using commercial-of-the-self hardware components. Effort should fully investigate adaptive waveform design and the performance and capability of the demonstration system. PHASE III: Further refine algorithms and the design to improve performance robustness for practical operation scenarios. Effort may be focused on further developing the capability and transition to military programs. PRIVATE SECTOR COMMERCIAL POTENTIAL/DUAL-USE APPLICATIONS: Commercial applications include homeland security maritime area monitoring. REFERENCES: 1. Anderson, K.D. Radar detection of low-altitude targets in a maritime environment. (1995)."Antennas and Propagation, IEEE Transactions on", 43(6), 609 - 613. 2. Li , J. & Stoica, P. (Eds.). (2009)."MIMO Radar Signal Processing."New York: Wiley. 3. Lin, Jiao & Zhang, Yong-gang. The effects of radar detection in heterogeneous evaporation duct conditions."Antennas, Propagation and EM Theory, 2008. ISAPE 2008. 8th International Symposium on", 1402 1405. 4. Yuanwei Jin, Moura, J.M.F., & O'Donoughue, N. Time Reversal Transmission in MIMO Radar."Signals, Systems and Computers, 2007. ACSSC 2007. Conference Record of the Forty-First Asilomar Conference on", 2204 2208.NAVY201101272011022820110330-1Closed374009http://www.sbir.gov/node/374009OBJECTIVE: Develop a non-invasive (non-seeded) approach to measure the unsteady, 3-D velocity field of a supersonic jet plume for a stationary aircraft. Looking also to make high resolution, time resolved measurements of the turbulent flow field for Short Take-Off/Vertical Landing (STOVL) aircraft with both subsonic and supersonic flow regions. DESCRIPTION: Modern supersonic jet aircraft engines produce a high amplitude noise field with complicated characteristics. The apparent dominant noise source as measured and mapped using acoustic holography methods occurs from 1 to 30 nozzle diameters behind the engine due to a variety of turbulent behaviors of the hot jet. This complicated aeroacoustic problem is not easily modeled using classical analytical approaches. Significant effort is being expended to model the flow field aft of the engine exhaust nozzle using Large Eddy Simulation (LES) methods. Researchers are looking to better understand the characteristics of the turbulent structures in the jet plume in the hopes of developing treatments to engines that might reduce the noise emissions. A significant obstacle to making these simulations practical and realistic for engine design purposes is the lack of methodology to measure the velocity field of the jet plume for purposes of correlating computational results. High quality measurements of the velocity field at and ahead of the exhaust nozzle exit plane would improve the upstream boundary condition definition for use by these analytical methods as well. A further need for this technology is for imaging the supersonic and subsonic turbulent flow field around a STOVL aircraft. This is needed to correlate CFD models that seek to understand the safety and other impacts of the flow field on support personnel and equipment. The various commonly used current velocity field measurement methods are inadequate. Hot wire anemometry methods are limited to flows of Mach 0.5 or less. Flow rakes using pitot tubes significantly disrupt the flow field and have very coarse spatial resolution. Supersonic jet flows in wind tunnels have been mapped using Particle Image Velocimetry (PIV) methods. This method makes use of either solid"seed"particles or some other added"seed"material such as olive oil. However, the"seed"particles used are judged to be impractical and damaging to use to image flow velocities in a turbo machine. Laser based methods, such as Light Detection and Ranging (LIDAR) methods have shown very good results for measuring low speed turbulent air flows in large regions of the atmosphere, and is a promising weather tool. This tool does not require a"seed"material (herein termed a"non-invasive"approach), but rather makes use of aerosols naturally occurring in the air, which either phosphoresce from or reflect the projected laser light in order to image the flow. Innovative non-invasive approaches to measure the velocity fields of supersonic jet plumes for a stationary aircraft are sought. Electromagnetic imaging methods may be a good solution to this problem. Light based methods such as LIDAR are expected to hold excellent promise, particularly as various light frequencies have been shown to have the ability to image various gases. It is expected that either one of the various naturally occurring or combustion byproduct gases in a supersonic engine jet plume may be amenable to such an imaging method. Proposed solutions must work without the addition of imaging particles or fluids to the jet engine intake or exhaust. Spatial resolution of measurement methods must capture the features of the unsteady velocity field with fine enough resolution to capture large and small scale eddies, turbulent boundary layer characteristics and shock structures. Method must also work with flows that are not combustion byproducts, and in the subsonic case. Measurement methods must capture results with sufficient time resolution to track the advection of both large and small scale turbulent structures in a supersonic jet plume. Any velocity measurement method that meets the above requirements will be considered. PHASE I: Demonstrate the feasibility of an imaging method capable of measuring the flow field of a subsonic or supersonic jet plume. Evaluate the three dimensional spatial resolution limits and explore methods to improve the resolution. Demonstrate the limits of temporal resolution of the measurement and the technological limits defined. Improvement to temporal resolution is desired. Contractor may make use of public domain jet flow facilities, such as wind tunnels operated by academic institutions for demonstration purposes. PHASE II: Extend the Phase I methodology to improve any deficiencies, such as spatial or temporal resolution issues. Develop and deliver a prototype measurement system capable of meeting the objectives outlined above. Improve upon the Phase I laboratory method to make it practical and affordable for future commercialization. Any differences between Phase I and Phase II methodologies are to be noted and explained. PHASE III: Further develop the measurement method into one that may be sold, or the service provided for private sector and other government uses. PRIVATE SECTOR COMMERCIAL POTENTIAL/DUAL-USE APPLICATIONS: The ability of current technology tools to image high speed flows is limited by several factors. If successful, it is expected that this technology will provide excellent benefits for aircraft designers in both the commercial and military sectors and will be generally useful as a research and engineering tool. Significant benefits will be gained in high speed flow imaging for a wide variety of aerospace applications from rockets to commercial jet engines. A large segment of the aerospace community would be potential customers of this method. REFERENCES: 1. Kelley, N.D., Jonkman, B.J., Scott, G.N., & Pichugina, Y.L. (2007). Presented at the American Wind Energy Association WindPower 2007 Conference and Exhibition:"Comparing Pulsed Doppler LIDAR with SODAR and Direct Measurements for Wind Assessment". Los Angeles, California. 2. Frelich, R., & Cornman, L. (2002). Estimating Spatial Velocity Statistics with Coherent Doppler Lidar."Journal of Atmospheric and Oceanic Technology", 19(3), 355-366. 3. Mikkelsen, T., Hansen, K., Angelou, N., & Sjoholm, M. (2010). Proceedings from European Wind Energy Conference (EWEC) 2010:"LIDAR Wind Speed Measurement From a Rotating Spinner". Warsaw, Poland. 4. Hewitt, J. (03 Jul 2008)."Doppler Lidar Gives Olympic Sailors the Edge". Retreived from http://optics.org/article/34878NAVY201101272011022820110330-1Closed374009http://www.sbir.gov/node/374009OBJECTIVE: Develop robust, versatile and computationally efficient models for an as yet not designed gyroscope based on a four level N-scheme atomic system and a bidirectional ring resonator. DESCRIPTION: It has long been known since the pioneering work of Sagnac that light can be a utilized to perform interferometrically sensitive measurements of rotation. If one considers a ring cavity rotating about an axis perpendicular to the cavity plane, light traveling in one direction experiences a different cavity length than a light beam traveling through the cavity in the opposite direction. Assuming a dispersionless medium, the speed of light is constant, which means that the transit time of the light in the cavity in one direction is different than the transit time of the light in the other direction. This difference in path lengths directly translates to a phase shift. On the other hand, the field of"slow light"is still in its infancy. It has only been since 1999 that researchers have been able to slow the group velocity of light from 300,000 km/s to 100"s of m/s. Through the use of a specially prepared medium consisting of two lasers (a"pump"and a"probe") and an atomic gas, an extremely narrow resonance can be generated in the absorption spectrum of the probe. Using the Kramers-Kroneig relation, this implies a sharp feature in the mediums"index of refraction. Since the group velocity of the probe light is inversely proportional to the derivative of the index of refraction, a sharp feature in the index of refraction directly translates to a decrease in the group velocity of light. For this work, it is noteworthy that if the medium consists of one excited state and two ground states (the configuration that yields the largest amount of light slowing) the two beams of light need to be co-propagating for this effect to take place: a beam that is counter-propagating relative to another will not experience any significant light slowing, due to the Doppler shift. Thus, one can envision the possibility of one pump beam circulating in one direction around a ring cavity and two probe beams, one co-propagating with the pump and the other counter-propagating with the pump. Because of the light slowing effect, one beam will have a dramatically increased cavity transit time as compared to the other. Ultimately, this leads to an increased sensitivity for a gyroscope over a conventional gyroscope. Since the change in the group velocity is on the order of one million, this same factor is the anticipated increase in sensitivity. Slow light gyroscopes have been the focus of some in-house research. The novelty of the scheme currently being investigated is the inclusion of a third field (the"control") that allows optical control over the group velocity. In this four level scheme, the group velocity is a function of the control field intensity in a manner that is fundamentally different than the dependence of the group velocity on the pump laser in a three level scheme. Here, the group velocity can be made arbitrarily small or large (up to c) and can even be made negative. This control over the group velocity translates into the ability to control the dynamic range of the gyroscope. During periods of slow rotation rates, the gyroscope can be operated in"high sensitivity"mode by selecting the correct control intensity for slowest group velocity. During periods of large rotation rates, the group velocity can be changed so as to"degrade"the sensitivity to current fiber-optic gyroscope performance. A full initial model has been developed that includes all laser fields with arbitrary strength and frequency detuning with respect to atomic transitions, all atomic levels with associated decay rates and dynamics, and propagation of all fields. However, the current model is cumbersome to implement, difficult to adapt to changing configurations and computationally intensive. This program seeks to develop robust, versatile and computationally efficient models to help guide experiments and assist in the designing of a gyroscope based on a four-level slow light atomic system. PHASE I: Develop equations necessary to model the full four-level three laser field system, including all atomic parameters, laser parameters and resonator parameters. Develop a methodology that will enable the development of a full scale numerical program in Phase II. A successful Phase I will demonstrate a methodology that is computationally efficient and adaptable to changing configurations. PHASE II: Develop an algorithm and full numerical model based on the methodology developed in Phase I. Initial model and algorithm validation can be performed in collaboration with experiments being performed at Pax River or an outside laboratory. Develop a laboratory proto-type design based on the modeling results. Fabricate and evaluate the prototype for use in operational areas such as long-term GPs denied areas or areas with high rotation rates. PHASE III: Finalize and validate design. Transition the developed technology to appropriate platforms. PRIVATE SECTOR COMMERCIAL POTENTIAL/DUAL-USE APPLICATIONS: Any commercial application that requires a sensitive and stable gyroscope that may also be subject to large and sudden rotations will be able to use this technology. This can include, but is not limited to air navigation and underwater navigation. REFERENCES: 1. Harris, S.E., Yamamoto, Y. (1998). Photon Switching by Quantum Interference."Physical Review Letters,"81(17), 3611-3614. 2. Abi-Salloum, T., Meiselman, S., Davis, J.P., & Narducci, F.A. (2009). Four Level''N-scheme''in bare and quasi-dressed states pictures."Journal of Modern Optics", 56(18 & 19), 1926-1932. 3. Abi-Salloum, T.Y., Henry, B., Davis, J.P., & Narducci, F.A. (2010). Resonances and Excitation Pathways in Four-Level'N-Scheme''Atomic Systems."Physical Review A", 82(1), 013834(1-6).NAVY201101272011022820110330-1Closed374009http://www.sbir.gov/node/374009OBJECTIVE: Develop novel light weight high efficiency thin-film batteries for use in Unmanned Autonomous Vehicles (UAVs), remote sensors, expendables, energy harvesting and in"wearable"flexible electronics. DESCRIPTION: Energy harvesting is important for distributed networks used in remote sensors, perimeter protection, intruder alerts and for widespread monitoring of bio-threats. Most energy harvesting schemes currently under consideration require some means of energy storage. Batteries, with their low internal leakage, long life and their ability to source low levels of power for very long periods of time are ideal for such an application. The development of novel light weight high efficiency thin-film batteries is sought. The anticipated advantage of thin-film cells would be easy, seamless integration with the harvester. For example, thin-film cells could coat housings, structural components or the back-side of a solar panel, eliminating the need for a bulky"battery farm."Proposed solutions must be flexible, so that they can conform to a variety of surfaces or be processed to conform to standard battery formats. For example, they can coat the airframe of an airborne UAV. If successful, this would save cargo space for weaponry and instrumentation packages on board the vehicle. It is also hoped that the thin-film cells could be made to resemble"battery cloth"and as such, could be used as removable jacket liners. This would distribute the weight of the power source over a war-fighter"s body, eliminating the need for bulky, unwieldy batteries. The cloth could also be used to back flexible displays. Areas of research focus should be battery capacity, internal leakage, shelf life and cycle capacity. Proposed materials must be environmentally compatible and low-cost, as large numbers of batteries are required for all envisioned applications. It is not an objective to extend conventional battery technology. PHASE I: Demonstrate proof-of concept for thin-flim batteries. Analyze various battery requirements and target one or more of the key performance parameters (battery capacity, internal leakage, shelf life, cycle capacity, etc.) and carefully benchmark the current state-of development. Analyze compatibility with possible energy harvesting techniques. As a starting point, the demonstration target will include: - Capacity: greater than 1mA.Hr/cm2 - Internal leakage On Charging: less than 100 uA/cm2 - Demonstrated Shelf Life: 1 month at a minimum - Cycle Life: greater than 100 cycles at 80% of capacity, greater than 500 cycles at 20% of capacity Outline an improvement plan for the chosen metric(s) and provide a proof-of-principle demonstration that improvement is possible with the outlined plan. PHASE II: Develop a prototype thin-film battery. Demonstrate significant improvements in the cited metric(s) from Phase I. Demonstrate compatibility of the chosen process technology with volume manufacture. Demonstrate integration of the metric-enhanced battery with some product target as mutually agreed upon by the offeror and the Navy. Demonstrate battery charging techniques to include harvesting. At the end of Phase II, demonstrate the minimum performance targets: - Capacity: greater than 10mA.Hr/cm2 - Internal leakage On Charging: less than 10uA/cm2 - Demonstrated Shelf Life: greater than 6 months (or longer) - Cycle Life: greater than 500 cycles at 80% of capacity, greater than 1000 cycles at 20% of capacity PHASE III: Demonstrate large volume manufacturability of various batteries, conformal coatings and/or battery cloth(s) using the chosen processes. Transition the developed technology for use in DoD platforms. Supply the battery packs to system suppliers in ready-to-use format for the intended applications. PRIVATE SECTOR COMMERCIAL POTENTIAL/DUAL-USE APPLICATIONS: A clear private sector commercial utility will exist for advanced thin-film batteries in any of their potential formats (standard, conformal, wearable). Selected technology may permit routine energy harvesting in the commercial as well as the military environments. The private sector potential includes: powering of"foldable displays,"battery liners for hand-held/lap-top devices, battery inserts for first-responder (e.g., firemen, EMTs, etc.) outfits, power supplies for structural integrity monitors (bridge maintenance and airframe integrity.) REFERENCES:NAVY201101272011022820110330-1Closed374009http://www.sbir.gov/node/374009OBJECTIVE: Develop physics based gear health models to quantify the benefit of superfinish over conventional gear processing techniques with regard to pitting, spalling and tooth bending fatigue failure modes. DESCRIPTION: Superfinish processed gears have demonstrated improved performance and durability over conventionally processed gears. However, this improvement has not been quantified. In addition, there is some concern about the uniformity of the process in key areas such as contour surfaces or the root ends of the gear teeth. The Navy needs modeling capability that will quantify the expected performance improvements of superfinish over conventional processing in order to understand lifecycle expectations of this new technology. The goal of this topic is to develop physics based models which are capable of quantifying the benefits of superfinish processed parts over conventional processing, particularly for key performance metrics including reduced susceptibility to pitting, spalling, and tooth bending fatigue failure modes. The proposed models should also be able to generate accurate virtual test data. End goals are to use the developed model to: 1. Quantify benefits of super finish over conventional processing 2. Determine the optimum amount of processing for super finish for the H-53K application, to minimize processing time and cost 3. Evaluate alternative super finish processes to quantify the benefit of increased uniformity 4. Potentially enable life credits at some point in the future to capture the benefits of the super finish processing, by modeling and quantifying durability improvements 5. Develop a modeling methodology that enables virtual testing (supplemented by smart selection of limited physical tests as needed), and allows for affordable application to additional material systems and geometries. Accuracy of proposed models should be demonstrated through validation of virtual test data with actual test data, and deficiencies should be identified and mitigated to the maximum amount practicable. Refine the physics based models based on data collected from component level gear tests. The capability of the developed models to accurately quantify the advantages of superfinish over conventional processes while capturing the risk areas of the process such as the contour surfaces, or the root ends of the gear teeth should be validated via demonstration tests. Pyrowear 53 is the primary alloy of interest for this effort. Other relevant alloys, such as AISI 9310 may be considered during Phase I if availability of technical data for Pyrowear 53 is an issue. PHASE I: Demonstrate feasibility of physics based gear models to quantify performance advantages of superfinish processing over conventional processing when applied to Pyrowear 53 gears. Alternatively, AISI 9310 steel may be considered during Phase I if Pyrowear 53 technical data is not available to researchers during the limited Phase I timeframe. Demonstrate feasibility of virtual test models to: 1) generate accurate simulated test results; 2) quantify superfinish improvements to the key gear performance metrics described above; and 3) identify the gear features which account for the most uncertainty such as contour surfaces, or the root ends of the gear teeth. Propose a method to address the uncertainty inherent in the models. PHASE II: Continue to refine and develop the superfinish gear models, with specific application to Pyrowear 53. Develop the modeling methodology in such a way that it allows for reapplication to additional material systems and part geometries. Increase accuracy by accounting for surface finish and machining characteristics, alloy composition and materials characteristics, geometry, case and core hardnesses, case depth, and ratio of case thickness to tooth thickness. Incorporate robust methods of handling uncertainty associated with key features identified in Phase I. Develop and demonstrate the capability to determine optimum amount of superfinish processing to maximize the benefit while minimizing processing time and cost. Evaluate benefits of alternative superfinish processes to quantify the benefits of improved uniformity. Validate via demonstration tests the capability of the developed models to accurately quantify the improved performance of superfinish gears and generate virtual test data. Identify shortcomings of the models as revealed by the demonstration tests, and reduce the shortcomings to the maximum extent practicable. PHASE III: Finalize the physics based gear models with major Department of Defense end users, airframe, and engine manufacturers and conduct necessary qualification testing for the applications. PRIVATE SECTOR COMMERCIAL POTENTIAL/DUAL-USE APPLICATIONS: The physics based superfinish gear models developed under this topic would significantly enhance the state of the art for commercial aviation, as well as other areas including ship and ground vehicle applications. The capability would also reduce developmental test costs. The technology is directly transferable to commercial gearbox applications. REFERENCES: 1. Farahmand, B. (2009)."Virtual Testing and Predictive Modeling,"Preface for. Retrieved from http://www.springer.com/cda/content/document/cda_downloaddocument/9780387959238-p1.pdf?SGWID=0-0-45-783503-p173878510 2. Niskanen, P., Manesh, Al, & Morgan, R. (2003). Reducing Wear with Superfinish Technology."AMPTIAC Quarterly,"7(1). Retrieved from http://ammtiac.alionscience.com/pdf/AMPQ7_1ART01.pdf 3. Carpenter Technology Corporation. (2010)."Pyrowear Alloy 53". Retreived September 9, 2010, from http://www.cartech.com/ssalloysprod.aspx?id=2140NAVY201101272011022820110330-1Closed374009http://www.sbir.gov/node/374009OBJECTIVE: Develop, analyze and deploy enhanced techniques to improve emitter detection and geolocation performance for improved time-sensitive targeting and Naval Battlespace Awareness DESCRIPTION: Traditional techniques for emitter geolocation include Angle of Arrival (AOA) for single sensor platform situations and Time Difference of Arrival / Frequency Difference of Arrival (TDOA/FDOA) as a technique involving dual/multiple sensor platforms. These methods provide limited performance due to constraints on platform size, cost, antenna size, instrument errors, processor throughput, signal propagation modeling errors associated with changing geometries, attitude and Doppler changes over a data collection or signal processing time interval, and the types of challenges as itemized below. Performance parameters associated with emitter geolocation include, but are not limited to (1) Time to deploy to region (2) Signal detection sensitivity (3) Geolocation accuracy (4) Time to detect (5) Time to geolocate to a given accuracy. Current emitter geolocation technologies fall short on the needed"time and throughput"requirements. The performance capabilities associated a specific geolocation approach are often interrelated, and scenario and technology dependent. The time to deploy to region often depends on the system size. For example, technologies which require large antennas and high-power, are often deployed on large Unmanned Air Vehicles (UAVs) or manned aircraft, whereas small antenna and technologies which can be implemented with small weight, size and power requirements may be implemented on small, low-cost UAVs, which can often be deployed in theater more quickly. Signal detection sensitivity is an important factor for detecting weak signals or even some relatively strong signals at large ranges. While the processing gain for detection can be increased using large antennas, the use of small antennas is often preferred to allow use of smaller, lower cost sensor platforms as mentioned above. The use of large directional antenna may introduce a larger time for detection as compared to the use of omni-directional antennas due to the time to scan or slew a directional antenna to cover a large region of interest. Improvements in signal processing can enable enhancements in signal-to-noise ratio (SNR) compared to traditional"snapshot"algorithms, by enabling longer coherent integration time intervals. For example, at the Global Positioning System (GPS) L1 frequency, the coherent integration time interval for traditional techniques may be limited not to exceed 1 millisecond for some scenario. However, if precise sensor platform navigation and timing information is utilized, then the coherent integration time interval may be extended by a factor of 100 or more for some scenarios, corresponding to a factor of 100 (20 dB) processing gain enhancement for detection of weak signals. The geolocation accuracy depends on such parameters as the number of sensor platforms, the geometry, the coherent integration time and the observation time. As a numerical example, at the GPS L1 frequency, a 1/2-meter diameter antenna can achieve an ideal geolocation AOA accuracy of about three degrees using the traditional MUltiple SIgnal Classification (MUSIC) algorithm [1]. However, in some cases, the synthetic aperture technique can enable an (effective) antenna size of 50 meters or more, corresponding to a factor of 100 or more improvement in geolocation AOA accuracy. The Cramer Rao bound [2] for the traditional TDOA/FDOA technique typically assumes a single"snapshot"observation, whereas multiple observations over an extended interval of time, can enable improved accuracy which exceeds the Cramer Rao bound for some scenarios. The time to detect depends on such parameters as the emitted power, the range, the processing gain, and the required time to search a certain region. Dual-platform methods require that both platforms be deployed in suitable geometries within the emitter signal antenna beam, whereas single platform methods may require that after an initial detection occurs, that the platform fly to a second location for triangulation. Depending on the technology, the time to search will depend on whether the sensor is directional and so needs to scan a region through multiple looks, or able to scan a wide region in one look. The time to geolocate to a given accuracy depends on such parameters as geometry, SNR and observation time. The Cramer Rao bound applicable to a single"snapshot"look, e.g. 1-second, may be significantly exceeded by tracking an emitter signal over an extended interval of time, e.g. 10 to 100 seconds associated with multiple time-varying geometries. Enhanced techniques for improvement of emitter geolocation performance are sought to enable sensor platforms to operate at much larger stand-off ranges with larger coverage areas for time-sensitive targeting and/or improved naval battlespace awareness. Recent studies have shown that performance may be enhanced through the use of enhanced signal processing techniques (e.g. Kalman tracking filters), improved signal propagation and emitter models, and exploitation of the precise Position-Velocity-Timing (PVT) information provided by GPS carrier phase signal processing. Synthetic aperture signal processing has also been shown to offer great opportunities for improvements in weak signal detection and geolocation accuracy. It is understood that potential enhancement techniques may not function well for all scenarios, but improved performance as compared to traditional techniques are desired even under restrictive scenario conditions for problems of interest. For example, synthetic aperture techniques may work well for a radar signal emitter, but will not function well for an emitter which only remains turned on for a short interval of time. Long coherent integration time intervals to enhance SNR for detection and geolocation accuracy may not be possible for certain types of signals, waveforms and geolocation methods. Some of the additional challenges associated with this research are the development of robust techniques which also address -- Detection and accurate geolocation of low-power emitters & #8804; 1 Watt Mitigation of error sources, e.g. multipath Geolocation of multiple emitters with similar signal characteristics Isolating unauthorized emitters from legitimate signal sources Geolocation of closely spaced emitters Poor geometry conditions Geometry, attitude and Doppler changes over signal processing time intervals Elimination or mitigation of processing latencies to support real-time operations Elimination of latencies, timing and frequency errors Moving emitters and emitters with time-varying signal characteristics Emitters which turn on and off Directional radiators Relativistic effects Extended (i.e. non-point) emitter sources, e.g. IR images Developing efficient search and signal processing techniques, including signal detection, false alarm rejection and selection of signal processing parameters for fast and robust operation PHASE I: Develop concepts for improved emitter detection and geolocation techniques, algorithms and procedures. Perform trade and sensitivity analyses to demonstrate a strong understanding of stressing scenarios, driving requirements and technology limitations and shortcomings for various scenarios and conditions. Demonstrate proof-of-concept through simulation and error analyses which illustrates significant improvement relative to traditional techniques. PHASE II: Develop prototype emitter detection and geolocation techniques, technologies, algorithms, and procedures for incorporation into new and/or existing operational systems. Develop requirements for integration of algorithms into new and/or operational systems. Demonstrate significant performance improvements relative to the traditional and state of the art techniques. PHASE III: Integrate the algorithms and procedures into new and/or operational systems to provide improved emitter geolocation capabilities. PRIVATE SECTOR COMMERCIAL POTENTIAL/DUAL-USE APPLICATIONS: The developed technology could potentially be applied in commercial geolocation services, e.g. location of cell phone transmitters or satellite interference sources. REFERENCES: 1. Schmidt, R. (1986). Multiple emitter location and signal parameter estimation."Antennas and Propagation, IEEE Transactions on,"34(3), 276-280. 2. Sonnenschein, A. Hutchinson, W.K. Cummings, W.C. (1993). Geolocation of Frequency-Hopping Transmitters via Satellite."Aerospace and Electronic Systems, IEEE Transactions on,"29(4), 1228-1236. DOI: 10.1109/7.259526. 3. Broumandan, A., Lin, T., Nielsen, J., & Lachapelle, G. (2008). Practical Results of Hybrid AOA/TDOA Geo-Location Estimation in CDMA Wireless Networks."IEEE 68th Vehicular Technology Conference. VTC 2008-Fall,"Calgary, BC. DOI: 10.1109/VETECF.2008.138. 4. Broumandan, A., Nielsen, J., & Lachapelle, G. (2008). Practical Results of High Resolution AOA Estimation by the Synthetic Array."IEEE 68th Vehicular Technology Conference, VTC 2008-Fall,"Calgary, BC. DOI: 10.1109/VETECF.2008.85. 5. Fowler, M.L., Xi Hu. (2008). Signal Models for TDOA/FDOA Estimation."Aerospace and Electronic Systems, IEEE Transactions on,"44(4), 1543-1550. 6. Pattison, T. & Chou, S.I. (2000). Sensitivity analysis of dual-satellite geolocation."Aerospace and Electronic Systems, IEEE Transactions on,"36(1), 56-71.NAVY201101272011022820110330-1Closed374009http://www.sbir.gov/node/374009OBJECTIVE: The objective is to demonstrate means of transporting high speed, digital data from 4K to 300K via a well integrated set of technologies that will minimize the heat loading on the low temperature stages. DESCRIPTION: After the inherent inefficiency of 4K coolers is considered, the consumption of wall power by Nb superconducting digital logic in performing its calculations is 100x smaller than SOA 22 nm Si. However, for systems with high levels of processing to realize a net energy benefit, parasitic heat loads associated with signal and data communications between room and low temperature need to be severely limited since all that energy must be removed from the low temperature end. Optical data transport from 300 to 4K is well advanced and should be assumed to occur. However, current optical modulators do not exist with V(pi) of less than 25mV for speeds above 50 Gbps per line. Thus the heat load associated with transitioning to optical data transmission at 4K is unacceptable. Therefore some of the temperature gradient must be spanned by electrical signals and an amount of amplification sufficient for the signals to remain visible above the upper end noise floor is essential. Superconducting digital logic operates on the basis of magnetic flux quanta, each of which has a voltage /time area of 2 mVps and current devices produce pulses of ~1 ps duration. The conversion temperature must be selected to minimize the total energy dissipation, including issues such as inherent noise of amplifiers, stage temperature of coolers, and energy efficiency of different stage temperatures of coolers. Moreover, the output data format must be converted from the RZ logic of superconductivity to the NRZ norm of room temperature logic somewhere on its way up the cryopackaging. This situation requires proper co-design of the first stage amplifiers which combine the superconducting output drivers and another digital technology capable of gain, ideally on a single 4K substrate, plus other, higher temperature amplification/signal conditioning stages sufficient to deliver the data without induced errors to 300K. The goal is for the entire chain to minimize total energy consumption for realistic values of cooler efficiency at each heat sink temperature and lead thermal transport. PHASE I: Develop and demonstrate by simulation of energy consumption and bit error rate a complete amplifier chain that deposits via dissipation and thermal conduction less than 1 mW at 4K for each 30 Gbps data link exporting data from 4K to 300K with BER100 simultaneous data streams will be secondary criteria in evaluating the goodness of designs. The phase 1 proposal should include at least a notional definition of the sort of amplifier chain to be worked. PHASE II: Convert the circuit simulations into real demonstration articles and perform multiple fab/test/redesign cycles to produce the desired demonstration. Demonstrate these links operating in a real superconducting dsp processor during the phase 2 second option and confirm the magnitude of the system energy efficiency benefit. PHASE III: Transition the new technology into advanced digital/mixed signal superconducting systems, such as full spectrum RF awareness receivers, beam formers, or high performance computing. PRIVATE SECTOR COMMERCIAL POTENTIAL/DUAL-USE APPLICATIONS: Successful development of this amplifier chain will enable the full speed advantage (>5x fastest semiconductor digital logic demonstration) of superconducting logic to be used in high speed circuits. These are needed in cell phone ground stations (spectrum reuse by multiple subscribers), server farms serving applications such as 4G wireless, Google, and cloud computing, and for computer animation and simulation such as for the entertainment and weather forecasting communities. REFERENCES: 1. A. Kadin et al., IEEE Transactions on Applied Superconductivity, Vol 17, pp. 975-978 (2007). 2. R.J. Webber et al, IEEE Transactions on Applied Superconductivity, Vol 19, pp. 999-1002 (2009). 3. J D Cressler, JOURNAL DE PHYSIQUE IV, Colloque C6 SupplCment au Journal de Physique III, Volume 4, juin 1994 4. Niklas Wadefalk, IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, VOL. 51, NO. 6, JUNE 2003NAVY201101272011022820110330-1Closed374009http://www.sbir.gov/node/374009OBJECTIVE: Design and develop a compact, light weight, low cost, non-inertial sensor capable of providing external navigation reference information for small UUVs conducting environmental and tactical reconnaissance in littorals and riverine areas. The system shall be easily integratable as a module to a number of existing underwater deployed sensors and unmanned underwater vehicles. DESCRIPTION: For naval forces operating in riverine and coastal areas, environmental and tactical reconnaissance is an indispensable part of any operation prior to entry. With on-going advances in capabilities, growing number of unmanned platforms are expected to conduct preoperational reconnaissance missions autonomously. Compared to other unmanned vehicles, UUVs provide unique advantages of conducting reconnaissance missions in riverine and coastal environments including their ability to conduct missions covertly and to employ acoustic sensors that are not affected by water turbidity or surface waves often predominant in such environments. Full submergence in the water column, however, means that UUVs may not have ready access to GPS. For submerged UUVs, there are navigational methods such as dead reckoning, INS, Doppler velocity log (DVL), or acoustic beacon based systems such as LBL and USBL. Among these methods, DVL has a unique capability of directly sensing the vehicle velocity relative to the seabed. It doesn"t require any pre-emplacement of beacon network, thus DVL is an ideal navigation sensor for covert underwater missions. Some of the commercial UUVs offer integrated INS/DVL navigation systems with remarkable accuracies while submerged. There are, however, some issues of integrating a DVL into a man portable UUV for conducting reconnaissance in rivers and coastal areas. For the naval forces operating from a small platform in such areas, key requirements for unmanned vehicles are small, light weight, low cost, and accurate navigation. For a small UUV, DVL integration may take up to forty percent of both the total cost and the weight of the vehicle. An innovative new concept is therefore solicited to develop an affordable, light weight, precision non-inertial underwater navigation sensor capable of providing external reference information suitable for integration into a compact UUV system. Although acoustics may to be the most robust modality for navigational measurements in turbid water, other modalities such as optics may also be considered if an innovative concept is available to alleviate the issue of optical opaqueness of riverine and littoral water. A compact UUV with a vehicle weight less than 10 lb has been viewed as ideal for riverine and littoral reconnaissance missions, therefore the alternative navigation system shall not weight more than 1 lbs with a volume nominally 30 cubic inches. The derived overall navigational accuracy shall be equivalent or better than currently available DVL based sensors, and per unit cost shall be nominally $2000.00 or less. Since the expected operating environment is littoral or riverine, the design depth shall be no more than 40 feet. Phase I: Specific design concepts of material, hardware, and software components of the non-inertial navigation sensor to achieve the objective requirements should be proposed along with an integrated system design. Component level and system level modeling and analyses are to be conducted to justify the proposed design and system integration. The design analyses should focus on feasibility of any new proposed concept of transducer material, component, and integration for overall system performance in the riverine and coastal environments. Phase II: A prototype will be produced and fully demonstrated in Phase II. Test and analysis will document the navigation sensor system performance with respect to the stated objectives as well as performance limitations in laboratory and in near shores and in rivers. In addition to operational performance issues, the Phase II efforts should address issues such as reliability, manufacturability, and toughness in severe environmental conditions. Phase III: Proposer will develop an acquisition-ready alternative navigation sensor system description that meets well defined operation guidelines. Full manufacturing documentation will allow rapid production to occur with the vendor team. PRIVATE SECTOR COMMERCIAL POTENTIAL/DUAL-USE APPLICATIONS: Commercial production and distribution of an affordable, compact, non-inertial navigation system parallels Navy interests. The same alternative concept of the non-inertial measurement of reference environmental motion may lead to new flow velocity field measurements currently done by ADCP type sensors. Affordability and compactness of the alternative concept would attract designers of developing alternative ADCP type sensors for private sector use. Primary applications in the near-term will address environmental baselining, monitoring, and change detection seasonally and in response to incremental or episodic events. Communities, ports, and resource management entities are likely the first customers, and their requirements for affordability and size requirements will be similar to the Navy requirements. REFERENCES: 1) The Navy Unmanned Undersea Vehicle (UUV) Master Plan, 2004: (http://www.navy.mil/navydata/technology/uuvmp.pdf) 2) Autonomous Vehicles in Support of Naval Operations: Naval Studies Board, National Academies Press, 2005: (http://www.nap.edu/catalog.php?record_id=11379) 3) J. J. Leonard, A. A. Bennett, C. M. Smith, H. J. Feder,"Autonomous Underwater Vehicle Navigation,"MIT Marine Robotics Laboratory Technical Memorandum 98-1NAVY201101272011022820110330-1Closed374009http://www.sbir.gov/node/374009OBJECTIVE: Develop a decision aid (selected display and algorithm products) to dramatically enhance submarine decision making by allowing rich multi-perspective interaction between local control room operations and alternative operational command centers. DESCRIPTION: Across warfare and mission areas, and between and across echelons of command, the rate at which information is presented to decision-makers continues to outpace the rate at which Command and Control (C2) systems and human decision-makers have been able to effectively and prioritize, filter, and assimilate the information. In many cases the decision-maker is presented with too much information, while in other cases there is too little critical information. In many of these cases, the information is ambiguous, contradictory, and or contains uncertainties which are not well understood by the decision-maker. Consequently, the commander is increasingly challenged to make good decisions within critical operational timelines given the massive amount of information provided to him, and the increasing difficulty to determine the relevancy and uncertainty of that information. This mismatch between increasing amounts of information and the difficulty in determining relevancy and uncertainty and the need to make decisions within shortening timelines available also hampers the Navy"s desire to migrate to a C2 environment which is flexible and rapidly adaptable to unanticipated changes in C2 organizational structures and missions. Until the root causes for this mismatch are addressed, the decision-maker"s ability to meet critical operational decision timelines will deteriorate as new sensors and systems (such as multiple unmanned vehicles) and information sources are introduced into the operational environment, and manning levels are decreased. Submarine mission scope and complexity continues to grow. Although always a platform of choice for stealthy operations, since the end of the Cold War submarines have been increasingly operated in the littorals. There, submarines are expected to support asymmetric warfare operations and to become full-spectrum participants in net-centric warfare. Reflecting these trends, the submarine fleet is now asked to take on the challenge of incorporating unmanned aerial vehicles (UAVs) as a sensor in support of the Over-the-Horizon Targeting (OTH-T) missions, for strike and littoral surface warfare. This includes both deploying the UAVs while submerged, and ingesting their data to augment the tactical picture to plan and execute OTH-T missions. Robust network investment and advances in computing capabilities combined with the planned development of secure communications at speed and depth for submarines yield the potential to remotely perform (both on- and off-board) command functions currently located within the submarine"s control room. In preparation for this communication bandwidth capability, several technical challenges remain before a decision aid can be used. Specifically, integration of data and information from disparate modalities, mismatch between the temporal rates at which sensors produce the data, management and quantification of uncertainty inherited from all sensors and sources during processing, identification of relevant information and critical decision time-lines, integration of spatially disparate and heterogeneous information, and presentation of information in a manner that human decision-makers to choose from among several alternative COAs. Technological advances suggest ways of improving command effectiveness by escaping the"work station paradigm"(WSP) (Kranz et al., 2010). This traditional paradigm focuses information on single displays and passing information"up the chain"to a single decision-maker. Recent work in the area of teaming computer agents with human agents (Maarten et al., 2003) has developed a human-centered approach to human-agent interaction such as would be required by earth-bound controllers interacting with a remotely deployed vehicle, whether a UAV or Mars-bound explorer. Though this C2 enhancement has the potential to greatly enhance information gathering, analysis, and assimilation capabilities of enhancing team performance (Salas et al., 2007; Kozlowski & Ilgen, 2006) a comprehensive analysis for deployment of those capabilities that minimizes risk and enables comprehensive evaluation of tiered alternatives is needed, i.e., assuming future operational context for the UAV capability is fully networked, so elements of the UAV OTH-T process should be capable of modular offloading to networked elements. The output of this effort would provide a decision-maker multiple automatically generated valid courses-of-action (COAs) for a given mission that are tailored to the cognitive capabilities of the commander or command team. A robust methodology for defining mission-focused, decision-driven cognitive C2 information architectures based on local (control room-based) human control of some functions and decisions but remote participation in some set of operational decisions. Research is required for how decisions are to be divided among the operational (both on- and off-board) teams, how this decision structure changes with operational and environmental conditions, and what roles (both legacy and new) are required to execute in this environment. It is anticipated that scientific inquiry into the nature of decision making, optimal structures and protocols for collective and participatory decision making, and cognitive engagement depending upon decision making responsibility will be required. Especially important will be the avoidance or mitigation of potential"automation surprises"triggered when own ship operators are presented with status changes caused by automated alerts that are generated outside human involvement. The challenge is not only to develop a decision aid for understanding the information architectures that would lead to shared decision making and problem solving, but also to develop a system of mechanisms to allow dispersed teams of individuals to collaborate on operational decisions in ways that are both adaptive and resilient (Wreathall, 2006). Assuming a robust secure communication network is available at speed and depth, the final product may be selected display and algorithm products that adhere and implement elements of the cognitive information architecture, and which measurably demonstrate increased effectiveness in presenting the decision-maker with viable COAs in the time available. Achieving this programmatic vision for submarine decision making will identify (1) which decisions are best left to local command, and under what circumstances, (2) which decisions are best assigned to the off-board team because of analytical perspective or data access, and (3) a structure for assessing these decisions in a dynamic environment. Submarine force would implement this decision aid (selected display and algorithm products) in the command and control center to enhance C2 for on- and off-board communications. PHASE I: Provide a theoretical structure and work model, managing higher levels of risk in a controlled and deliberate manner, for developing operational decision making among local and remote team members. The concept should include strategies for deconstructing decisions, involving teams, and making criteria explicit. Develop a detailed method for evaluating the theory that includes both qualitative and quantitative measures. Enumerate a set of requirements for a proof of concept to be implemented in Phase II. PHASE II: Design, develop, and demonstrate decision aid prototype for the target application environment as investigated in Phase I. The implementation will test the predictions of the theory through measurements of the evaluation criteria developed in Phase I. Phase II will demonstrate the implementation in applications that illustrate the positive and negative consequences of multi-modal, multi-perspective decision making. A useful example would be to demonstrate critical decision making by a submarine command team in a non-routine situation using the proposed structure. Iterative research into cognitive models and workload will be required to assess the impact of the proposed structure. The Phase II effort may or may not be classified due to the content of the decision aid. PHASE III: This topic has many dual use applications, including the development of improved decision making in commercial as well as military environments. Additionally, there are potential total ownership cost implications of reduced recruiting and retention costs as a result of higher levels of employee engagement and control. Critical solutions would benefit industry, the government, and the military, and indeed, all large organizations that manage difficult, complex problems. REFERENCES: 1. Kranz, J, Wein, R & Marquet, L. (2010). Real to Virtual to Real The powerful shadow. Presented at Undersea Human Systems Integration Symposium, Providence RI. 2. Norman, D. (1998). The Design of Everyday Things. The MIT Press. 3. Maarten S., Bradshaw, J.M., Acquisti, A., Hoof, R., Jeffers, R., Uszok, A. (2003). Human-Agent Teamwork and Adjustable Autonomy in Practice. Proceedings of The 7th International Symposium on Artificial Intelligence, Robotics and Automation in Space (i-SAIRAS), Nara, Japan. 4. Salas, E., Rosen, M.A., Burke, C.S., Nicholson, D., and Howse, W.R. (2007). Markers for enhancing team cognition in complex environments: The power of team performance diagnosis. Aviation, Space, and Environmental Medicine, 78, 77-85. 5. Kozlowski S.W.J., and Ilgen, D.R. (2006). Enhancing the effectiveness of work groups and teams. Psychological Science in the Public Interest, 7, 77-124. 6. Wreathall, J. (2006). Properties of Resilient Organizations: An Initial View. In"Resilience EngineeringConcepts and Precepts"(E. Hollnagel, D.D. Woods, and N. G. Leveson, Eds.) Ashgate Press.NAVY201101272011022820110330-1Closed374009http://www.sbir.gov/node/374009OBJECTIVE: Develop lightweight, unobtrusive, modular, and wearable recording device(s) to capture, synchronize, and download environmental, physiological, physical, and subjective measures that contribute, and are associated with physical and cognitive fatigue. The device(s) or system(s) should also be capable of objectively and reliably assessing fatigue uncontaminated by individual factors such as aptitude, learning effects, yet sensitive to phenotypic differences in vulnerability to fatigue. DESCRIPTION: Current Naval platforms and systems require increased operational capability with reduced manpower. The ability to accurately predict warfighter performance (e.g. accuracy and reaction time for job duty tasks) on these platforms and systems is an essential component of conducting cost, schedule, and performance tradeoffs between hardware, software, and human capabilities and limitations. These tradeoffs are increasing done with human performance models such as Total Crew Model and IMPRINT. While the capability to model warfighter performance has made great strides over the last several decades, models still lack the fidelity to support fine grained tradeoff analyses. Furthermore, most models are not validated, and have little capability to account for the impact of environmental stressors. The need to account for environmental stressors such as fatigue, motion, vibration and extreme temperatures is critical because they can result in physical and cognitive fatigue, leading to degradation in warfighter performance. A significant challenge in validating human performance models is the ability to collect environmental and performance data from warfighters in an operational setting. Current methods are primarily paper based, although, standalone recording devices such as actigraph may also be used. Several limitations are associated with these current methods. First, from a participants"perspective, generating responses while performing mission tasks is cumbersome and time consuming. Second, from an experimenters"perspective, coding self-reported responses is time consuming and increases the likelihood of errors in data entry. In addition, experimenters may not be able to attend an experimental event in person (e.g. live fire testing) or collect all the environment conditions that a warfighter experiences (e.g. motion, vibration, noise). Third, data analysis cannot be performed until all data sheets are collected and coded thus delaying when the analysis is performed, and eliminating the possibility of real-time (or near real-time) analysis. Lastly, the lack of synchronization between devices and subjective reporting makes associations between objective and subjective data more difficult. The end result of these limitations is that researchers focus more energy and time on collecting and processing a limited amount of data, then on assessing the impact of environmental stressors on fatigue. Accurately accounting for the effects of environmental stressors on operator performance will allow human performance models to better support assessment, analysis, and mitigation of stressors during system development, testing, and acquisition. To overcome the data collection challenges associated with validating human performance models, and ensure an accurate account for the effects of environmental stressors on performance, a novel, integrated, non-obtrusive data collection and analysis system is needed. The selection of sensors needed for the data collection suite should capable of objectively and reliably assessing fatigue and based on theoretical models (Mallis, Mejdal, Nguyen, and Dinges, 2004). Recent advances in individualization algorithms are making possible a new generation of systems to tailor mathematical model-based assessments of fatigue to track trait-like differences among individual operators. (Van Dongen et al., 2007). Measures of fatigue that do not involve obtrusive or invasive physiological monitoring, that have high face validity for operator performance relative to vigilance based tasks, and that are free of contaminating factors such as aptitude and learning effects should be explored. These measures would be combined with state-of-the-art, mathematical model-based analysis and individualization algorithms to account for individual state and trait related performance changes due to fatigue (Kan et al, 2009; Mollicone, Van Dongen, Rogers & Dinges, 2008; Mott et al., 2009). The system would provide visualization tools based on behavioral alertness data to assess operationally relevant performance features sensitive to fatigue that are associated with phenotypic differences across individuals. Academia and industry are increasingly developing portable and wearable data collection technologies. These systems are part of a larger effort of ubiquitous and pervasive computing applications and often have a set of typical sensors with them (Beigl, Krohn, Zimmer, and Decker, 2004). Some devices such as the iPod touch also have the capability of obtaining subjective responses via an embedded rating system. However, none of these devices nor technologies provide the capability for non-obtrusively collecting and then integrating data spanning environmental, physiological, physical, and subjective measures of fatigue. In addition, to these sensors it is necessary for designers to consider the usability of these systems. Based on prior work, Tapia, Intille, Lopez, and Larson (2006) developed four usability goals (i.e., ease of installation, ease of use, adequate longitudinal performance in natural setting, affordable for researchers) for a portable sensor kit that could be used for non-laboratory studies. Consideration of such usability guidelines is critical for the successful adoption of data collection tools. PHASE I: Develop the framework for a data collection suite for measuring human performance. The components in the framework should build on and extend the state-of-the-art capabilities in portable and wearable sensors / devices and performance measurement (including environmental, physical, physiological, and subjective indices). All sensors / devices must be capable of collecting multiple sources of data simultaneously and synchronizing that data. The selection of sensors needed for the data collection suite should capable of objectively and reliably assessing fatigue and based on theoretical models (Mallis, Mejdal, Nguyen, and Dinges, 2004). In addition, the user software must allow data to be quickly downloaded onto a Windows based-PC, and reset the sensor / device for another data set. The components in the framework should work within an open systems architecture. PHASE II: Develop a prototype suite of data collection tools based on the framework established in Phase I. Submit appropriate and necessary regulatory documents for testing using human participants. Validate the tools through empirical evaluations with the targeted user community. PHASE III: Produce and market the suite of data collection tools for integration with ship and submarine test and evaluation programs. PRIVATE SECTOR COMMERCIAL POTENTIAL/DUAL-USE APPLICATIONS: The suite of tools will have widespread applications to military, government, and private sector organizations in which it is important to assess performance (e.g., when fewer personnel are required to perform the same tasks and missions without degraded performance). REFERENCES: 1. M. Beigl, A. Krohn, T. Zimmer, and C. Decker,"Typical Sensors Needed in Ubiquitous and Pervasive Computing,"in Proceedings of the First International Workshop on Networked Sensing Systems (INSS'04). Tokyo, Japan, 2004, pp. 153-158. 2. M. Tapia, S. Intille., L. Lopez., and K. Larson.,"The Design of a Portable Kit of Wireless Sensors for Naturalistic Data Collection", in Proc. Int'l Conf. Pervasive Comp. 2006: p. 117-134. 3. Van Dongen, HPA, Mott, CG, Huang, J, Mollicone, DJ, McKenzie, FD, and Dinges, DF, Optimization of biomathematical model predictions for cognitive performance impairment in individuals: Accounting for unknown traits and uncertain states in homeostatic and circadian processes. Sleep, 2007. 30(9): p. 1125-1139. 4. Kan, K, Mott, C, Van Dongen, H, Huang, J, Mollicone, D, and Dinges, D., Individualizing predictions of performance impairment across sleep/wake state transitions. in Aerospace Medical Association"s 80th Annual Scientific Meeting. 2009. Los Angeles. 5. Mallis, M.M., Mejdal, S., Nguyen, T.T., Dinges, D.F., Summary of the key features of seven biomathematical models of human fatigue and performance. Aviation, Space & Environmental Medicine 75(3):A4-A14, 2004. 6. Mollicone, DJ, Van Dongen, HPA, Rogers, NL, and Dinges, DF, Response surface mapping of neurobehavioral performance: Testing the feasibility of split sleep schedules for space operations. Acta Astronautica, 2008. 63(7-10): p. 833-840. 7. Mott, C, Van Dongen, H, Kan, K, Dinges, D, Huang, J, and Mollicone, D., Optimizing individual performance predictions in real-time scenarios using Bayesian estimation. in Aerospace Medical Association"s 80th Annual Scientific Meeting. 2009. Los Angeles.NAVY201101272011022820110330-1Closed374009http://www.sbir.gov/node/374009OBJECTIVE: To develop electrochemical materials for high density Li-ion batteries capable of supporting high transient and pulsed loads while offering enhanced safety and lifecycle performance. DESCRIPTION: Future Navy applications will require large amounts of stored energy to support loads which have high discharge and transient characteristics including pulses and similar waveforms. A wide variety of coordinated equipment may be employed to support performance requirements, and lithium-ion batteries are a technology which will likely be part of an energy storage module to support these loads. Current state-of-the-art Lithium-ion energy storage devices extensively utilize energetic metal oxides and flammable electrolytes as a cornerstone for maximizing energy content and providing optimal volumetric and gravimetric densities. These designs provide concern for both safety and cycle life, particularly under high-rate operations. In order to provide the highest performance, most of the current battery chemistries rely on somewhat unstable cathode materials that can undergo runaway reactions and provide their own source of oxygen in the event of a modest temperature rise, due to something such as an internal cell short. Research into advanced electrode materials that do not contribute oxygen or a significant exotherm under a cell failure scenario, while at the same time maintaining the high energy and power density potential that Li-Ion batteries can provide are needed. Materials such as Lithium Iron Phosphate, which appears to offer abuse safety advantages versus"hotter"cathode materials such as Lithium Cobalt Oxide, also provide an electrochemical penalty in reduction potential, thus decreasing overall energy of the battery. Thus, materials that offer safety while also offering higher operational voltages and long-term stability are desired. Innovative R & D is needed to investigate alternative cathode materials that limit the potential for energetic failure in a cell, while also offering high rate discharge performance over a large number of cycles. The intent of this solicitation is to produce advanced materials which overcome some of the typical tradeoffs which may effect operational voltage, energy content, etc. In order to enable widespread utilization of highly dense power and energy storage, advanced technologies must embody designs that are scalable/flexible and have robust design to be applicable to a variety of energy storage requirements with varying bias. These materials should offer long life, and allow a significant number of cycles to be obtained both under pulsed and continuous high-rate deep discharge operations. In the case of the use of dopants to effect cathode characteristics, material migration and agglomeration over long-term use must be addressed with respect to safety and performance. Specifically, this solicitation requests the following characteristics for a lithium-ion battery cathode material: - Average voltage:>4.0V - Gravimetric capacity:>180mAh/g - Cycle life:>2000 deep cycles with>80% original capacity - Cycle life:>10000 pulse discharges @ 10C or higher within range of 25-75% SOC with>80% original capacity - Suitable for combination with current and future anode and electrolyte materials - Scalable to cells with>25Ah capacity - Suitable in batteries with discharge ranging from 5C to 10C or higher and charge rate up to 10C - Minimum onset of thermal runaway: 290 degrees C - Maximum exothermic release @ heating toNAVY201101272011022820110330-1Closed374009http://www.sbir.gov/node/374009OBJECTIVE: Research and develop a RF channel simulation framework to test the next generation of mobile multi-protocol wideband tactical systems. The framework would allow for the generation of a model based scenario via a script based interface or via a GUI that allows the user to model the effects of mixed mobile and fixed multi-link radio network using this real-time channel simulator. The simulator should provide a visualization framework to view a subset of the time varying RF characteristics of interest (i.e. real-time coverage, link connectivity). The simulator should also support interface with live radios so that they can operate in-the-loop with the channel simulation. DESCRIPTION: The Joint Tactical Radio System Program (JTRS) produces a family of multi-functional Software Defined Ratio (SDR) communications systems operating within the 2MHz to 2GHz range that provides the next generation of voice, video and data for Joint and Coalition Warfighter. A core design requirement of this family of radios is the capability to be integrated with existing military and civilian radios. By design, one JTRS radio can support multiple protocols such as UHF SATCOM, EPLRS, SINCGARS, LINK-16, HF SSB/ALE, V/U LOS, WNW, SRW, MUOS, etc. This scope presents a challenge to the development, test and deployment communities with respect to needing multiple channel emulation and channel simulation software solutions that covers (a broad spectrum and in some cases a large operational bandwidths (i.e 225-400 MHz) that emulate/simulate a multitude of environmental effects. In order to measure the effectiveness of JTRS radio protocols, antennas or network layouts a real time channel simulator is necessary to characterize the effectiveness of these radios in the face of environmental impairments (i.e vegetation, terrain, seasonal conditions, atmospheric) in various environments (i.e urban, forest, open ocean, desserts). Factors that are of interest are, standard fading profiles, inter-symbol interference models characterized for the RF modulation techniques being used; the mobility impacts of hills, valleys, foliage, and vehicle speed; the altitude and speed of aircraft; antenna blockages due to host platform characteristics; and the presence of intentional and unintentional interference. When the final product is complete, the capability would allow lab users to specify propagation models, antenna/platform environmental effects, and have the simulator output a script-based scenario. The user could than use this script with a channel emulator to test dozens or hundreds of radios (this capability should be scalable to promote affordability) so that the effects of a mixed mobile, airborne, and fixed multi-link radio network could be emulated and measured in a lab environment. An added benefit is that this system could be used for network deployment analysis to rule out topologies based on environmental conditions. PHASE I: Determine the feasibility of and develop a conceptual design for a modular RF simulation, prediction and visualization tool with the aforementioned environmental influences, which when connected to live radios can apply realistic channel effects to their communications. PHASE II: Develop detailed designs for the Phase I modular RF channel simulator and develop a suitable proof of concept framework for use in a laboratory environment with live radios. Conduct preliminary testing demonstrating channel characterization capability for the 2 MHz to 2GHz range with the implemented channel modeling capabilities identified in Phase 1. PHASE III: Transition the product into a supportable commercial product to be used in characterizing commercial cellular systems and government tactical systems. PRIVATE SECTOR COMMERCIAL POTENTIAL/DUAL-USE APPLICATIONS: The RF impairment simulator proposed within this SBIR is far reaching and can be used to test commercial cellular applications like GSM/GPR/EDGE, PCS, WCDMA, CDMA, 3GPP LTE, WiMAX. REFERENCES: [1] T. K. Sarkar, Z. Ji, K. Kim, A. Medour, and M. Salazar-Palma,"A Survey of Various Propagation Models for Mobile Communication", Antennas and Propagation Magazine, Vol. 45, No. 3, June 2003. [2] J. R. Hampton, N. M. Merheb, W. L. Lain, D. E. Paunil, R. M. Shuford, and W. T. Kasch,"Urban propagation measurements for ground based communication in the military UHF band,"IEEE Trans. Antennas and Propagat., vol. 54, no. 2, pp. 644654, Feb. 2006. [3] A. G. Longley and P. L. Rice,"Prediction of tropospheric radio transmission loss over irregular terrain,"U.S. Department of Commerce, ESSD Res. Lab Rep. ERL-79-ITS-67, U.S. Government Printing Office, 1968, April. 1978.NAVY201101272011022820110330-1Closed67012http://www.sbir.gov/node/67012OBJECTIVE: The objectives of this STTR are to investigate numerical methods for predictably-accurate treatment of boundary conditions in electromagnetic and other wave-dominated phenomena, and to develop algorithms and computer software that can be implemented for military and commercial simulation applications. DESCRIPTION: High fidelity modeling of electromagnetic phenomena has become increasingly important in the design and virtual prototyping of navigation, detection, tracking, and communications systems, helping simulation become widely recognized as the third major component of scientific discovery and development, co-equal with experimentation and theory [9]. However, the simulation of electromagnetic phenomena in the time-domain poses unique computational challenges; these systems are hyperbolic with propagation length scales that are many orders of magnitude greater than the wavelength. Although new algorithmic developments have greatly improved the reliability and efficiency of approximations to Maxwell"s equations within the computational domain [5,6], a major obstacle to accurate long-time solutions is the presence of spurious reflections which occur at the computational boundaries and back-propagate to degrade the solution over the interior. The large propagation length scale makes it impossible to compute over a domain that is large enough that boundary reflections are so far removed as to be insignificant [4]. The widely accepted solution to this problem is to implement algorithms at the boundary which attempt to introduce precisely the right amount of artificial damping (a"perfectly matched layer", or PML) so that incident waves are rapidly damped with no reflection. [3] These models suffer from several deficiencies. They are very problem-specific; every problem, domain, geometry, source and receiver location, etc. has to be treated individually and the PML has to be adjusted for each so as to minimize reflections for that particular case. In addition, every new model requires a new PML, and no general procedure is known to construct a priori stable and accurate layers [2]. Thus in practice, PMLs rely on empirical parameters that must be set by trial and error. This fact hinders the development of high fidelity models; error bounds applicable to the stretched layers required for efficient computations are unknown, and so uncertainties in the error at boundaries propagate into the interior and degrade the accuracy and/or reliability of our computations. With the advent of scalable parallel processing architectures, the need has become apparent for new algorithms that can control reflections at boundaries, can give us guaranteed error bounds so that we can achieve guaranteed high fidelity modeling of these important applications, and can determine a priori the computational load (number of terms required, order of approximation required, etc) to achieve a specified and guaranteed level of accuracy. While some work has been done in a priori methods for nonreflecting boundaries (e.g. [1,7,8]), most of the results to date are restricted to simple artificial boundaries which may be wasteful of computational volume and also require the discretization of nonstandard operators. In particular their implementation using standard methods in the interior has not been demonstrated. What is needed is development of an a priori, error-bounded algorithm that can be encoded in a standard software routine or set of routines and that can be distributed within standard high performance computing (HPC) libraries or computational electrodynamics packages for simulation on parallel, distributed, and Grid-based computing platforms. To ensure the fidelity of simulations and introduce guaranteed error bounds, without intervention or coding by experts, for military and commercial simulations, it is imperative that 1) the various existing techniques for treating computational boundaries for electrodynamics and other wave systems be investigated; 2) efficient numerical methods and their algorithms be developed for minimizing wave reflections at boundaries; 3) prototype computer software for the algorithms be developed for military and commercial applications in computational environments. In order to transfer the technology for commercial use, it is proposed that business technical staffs and university researchers be involved in both the investigation of the numerical methods and the development of the software. It is proposed that the program be carried out in the following two phases. PHASE I: In Phase I the following shall be accomplished: a. A complete assessment of currently available numerical methods and algorithms for reflection control at computational boundaries. b. Development of domain boundary methods for inclusion in standard computational electrodynamics packages. c. Development of methods for the automatic generation of boundary handling, establishment of guaranteed a priori bounds on the error due to reflections, and establishment of the guaranteed resulting computational load. d. Development of new algorithms that are suitable for real time parallel and/or distributed computing environments. PHASE II: In Phase II, a. Computer coding of the algorithms developed in Phase I shall be done primarily by software engineers in private industries and some by university researchers. b. The reliability of the algorithm will be demonstrated by testing on a comprehensive suite of community-recognized benchmark problems. c. The possibility of stably coupling the boundary algorithm with all standard volume discretization techniques will be demonstrated. d. The efficiency of the implementation will be demonstrated by testing on a variety of representative architectures. e. A standard HPC version will be released with licensing requirements for commercial users that incorporates the multi-core and GPU algorithms. f. A complete set of documentation regarding the theoretical results, software design, and implementation shall be delivered with the prototype software to the military for evaluation and implementation at US Government HPC centers, including DoD Major Shared Resource Centers. It shall also be made commercially available to HPC users at academically oriented HPC centers. g. A long-term sustainability plan for development, maintenance and support of the software based on revenue estimates will be developed. h. A website will be launched for the distribution and support of the software to both commercial and noncommercial users. i. A stable support infrastructure to deal with both new and existing users will be created. Support will be maintained that is capable of dealing with installation issues over many platforms as well as bug resolution and usage issues with the existing code base. This will not only include standard release mechanisms, but also a web-based help center that directly interacts with users. PHASE III DUAL USE APPLICATIONS: The technology developed under this topic will improve the performance of software for computational electromagnetics and eliminate the need for empirical parameters for the design of boundary conditions. This will enable a significant reduction in the design cycle time of military electromagnetic systems for ground mobile wireless communications and sensing. The technology will bring similar benefit to system development for applications in commercial wireless networking and communications. REFERENCES: 1. B. Alpert, L. Greengard, and T. Hagstrom, Nonreflecting boundary conditions for the time-dependent wave equation, J. Comput. Phys., 180:270-296, 2002. 2. E. Becache, S. Fauqueux, and P. Joly, Stability of perfectly matched layers, group velocities, and anisotropic waves, J. Comput. Phys., 188:399-433, 2003. 3. J.-P. Berenger, A perfectly matched layer for the absorption of electromagnetic waves, J. Comput. Phys., 114:185-2000, 1994. 4. T. Hagstrom and S. Lau, Radiation boundary conditions for Maxwell"s equations: a review of accurate time-domain formulations, J. Comput. Math., 25:305-336, 2007. 5. W. Henshaw, A high-order accurate parallel solver for Maxwell"s equations on overlapping grids, SIAM J. Sci. Stat. Comp., 28:1730-1765, 2006. 6. J. Hesthaven and T. Warburton, High order/spectral methods on unstructured grids. I. Time-domain solution of Maxwell"s equations, J. Comput. Phys., 161:331-353, 2002. 7. C. Lubich and A. Schadle, Fast convolution for nonreflecting boundary conditions, SIAM J. Sci. Stat. Comp., 24:161-182, 2002. 8. V. Ryaben"kii, S. Tsynkov, and V. Turchaninov, Global discrete artificial boundary conditions for time-dependent wave propagation, J. Comput. Phys., 174:712-758, 2002. 9. Computational Science: Ensuring America"s Competitiveness, President"s Information Technology Advisory Committee, 2005.ARMY201101272011022820110330-1Closed67012http://www.sbir.gov/node/67012OBJECTIVE: The objective of this STTR is to develop a machine that will reliably train small animals to detect explosives or other compounds of interest and will provide an objective unbiased measurement of the animal"s sensitivity and accuracy. DESCRIPTION: The Army is engaged in extensive humanitarian demining efforts. Demining is often necessary to restore farm land to agricultural use, and to enable societies to stabilize after war. Although dogs are the most commonly used animal for mine detection, it has been demonstrated that other animals can reliably smell mines, and smaller animals have advantages over dogs in some situations. The cost of training animals to detect mines is primarily due to the human labor involved. In addition, the actual training of animals to detect mines remains as much of an art as a science. It is desirable to 1) have an automated training system that reduces the human labor cost, and 2) have an automated scoring system that objectively measures the animal"s accuracy and sensitivity. Because much of the demining efforts are happening in third world countries with little access to engineering expertise or parts, this system must be rugged, reliable, inexpensive, simple to operate, and easy to fix. PHASE I: The investigators will design a system to reliably train small animals to detect mines and to objectively evaluate and score their performance. At the end of phase I they will present detailed plans for this system. Phase I will be evaluated on the basis of the proposed system to effectively train and evaluate small animals, and on cost, ruggedness, reliability, simplicity, and ease of maintaining and repairing the system. The system should be usable by animals up to 7 kg. PHASE II: The investigators will build prototype systems and will deliver at least five of these prototypes to locations to be designated by the program manager for field testing. By the end of phase II the investigators will have developed the capability for large scale production of Rugged Automated Training Systems. PHASE III DUAL USE APPLICATIONS: The investigators will produce and sell large numbers of these Rugged Automated Training Systems for worldwide use. Mines are widespread throughout much of Africa, Asia, and Central America and demining operations are expected to continue for decades. Finding and removing mines is necessary to restore mined land to civilian use. REFERENCES: 1) Catania, KC, and Remple, FE. 2004. Tactile foveation in the star-nosed mole. Brain Behav Evol 63(1):1-12. 2) Verhagen, R, Weetjens, F, Cox, C., and Weetjens, B. 2006. Rats to the Rescue: Results of the First Tests on a Real Minefield, Journal of Mine Action 9, 2.ARMY201101272011022820110330-1Closed67012http://www.sbir.gov/node/67012OBJECTIVE: Automated techniques for understanding and classifying behavior of novel malware. DESCRIPTION: The number of new malware being encountered in the wild is steadily and rapidly increasing. Recent reports show that more than 5,000 new, unique malware samples are encountered daily. In order to keep pace and not fall behind in the arms race with malware creators, there is a dire need for a systematic, automated way to process this deluge of malware. When a malware is encountered, there are two questions that need to be answered: (i) what does the malware do? (ii) is the malware a variant of an already known malware? Automated and effective techniques combining static and dynamic analysis of executables, mining techniques for behaviors, and malware classification are needed to address this challenging problem. The same technique may also help understand behavior of COTS from untrusted and unknown sources. Researchers are exploring new techniques that can address these questions, such as the recent work on automated construction of dependence graphs from executions of malware for understanding and summarizing the behavior of the malware. Researchers have also studied mining tools and techniques based on dependence graphs to extract the behavior of malware. Semi-automated specification generation techniques have been explored to help analysts construct detection mechanisms for newly discovered malware behaviors for incorporating them into behavior-based or cloud-based malware detectors. Some researchers (such as Bailey et al. 2007) have addressed the malware classification problem: classifying malware by type (e.g., Virus, Worm, Spyware), family (e.g., Bagle, Netsky, MyDoom), and whether it has been encountered before. The current practice of analysts manually inspecting each individual incoming malware is not a sustainable solution. There is a need for proven and deployable automated techniques that can process and analyze large volumes of malware binaries. PHASE I: 1) Research and develop automated malware understanding and classification technologies based on recent new techniques such as dependence graphs or symbolic execution that can effectively and efficiently analyze and characterize malware behavior and to defeat the use of obfuscation and polymorphism. 2) Demonstrate that the proposed techniques can be implemented successfully in classifying behaviors for a large corpus of malware in near real-time. PHASE II: 1) Extend the techniques proposed in phase I to mine or extract relevant behaviors of malware. 2) Develop and implement techniques for automatically transforming the extracted malware pattern and behaviors into policies or patterns that can be ported into existing malware detectors. 3) Validate the techniques under operational conditions. The goal of this phase will be to demonstrate that a new malware can be analyzed near real-time. The goal will be to analyze, classify, and mine behaviors in less than five minutes with minimum human intervention. PHASE III DUAL USE APPLICATIONS: Effective techniques for understanding and classifying malware are critical for both military and commercial sectors. The developed system will be marketed as a malware-analysis platform which will be attractive to malware-detection companies and defense agencies. The malware-analysis platform can be used by agencies and companies for developing a faster defense against zero-day attacks. REFERENCES: 1. B. Acohido and J. Swartz. Zero Day Threat: The Shocking Truth of How Banks and Credit Bureaus Help Cyber Crooks Steal Your Money and Identity. Union Square Press, April 2008. 2. Michael Bailey, Jon Oberheide, Jon Andersen, Z. Morley Mao, Farnam Jahanian, and Jose Nazario, Automated Classification and Analysis of Internet Malware, Proceedings of Recent Advances in Intrusion Detection (RAID'07), September 2007. 3. Mihai Christodorescu, Somesh Jha, and Christopher Kruegel, Mining specifications of malicious behavior, ESEC/SIGSOFT FSE, 2007. 4. Matt Fredrikson, Mihai Christodorescu, Somesh Jha, Reiner Sailer, and Xifeng Yan, Synthesizing Near-Optimal Malware Specifications from Suspicious Behaviors IEEE Symposium on Security and Privacy, 2010. 5. Lorenzo Martignoni, Elizabeth Stinson, Matt Fredrikson, Somesh Jha, John C. Mitchell, A Layered Architecture for Detecting Malicious Behaviors, RAID 2008. 6. Mila Dalla Preda, Mihai Christodorescu, Somesh Jha, Saumya K. Debray, A semantics-based approach to malware detection, ACM Trans. Program. Lang. Syst., 30(5), 2008 7. David Brumley, Hao Wang, Somesh Jha, Dawn Xiaodong Song, Creating Vulnerability Signatures Using Weakest Preconditions, CSF, 2007: 8. Hao Wang, Somesh Jha, Vinod Ganapathy, NetSpy: Automatic Generation of Spyware Signatures for NIDS, ACSAC, 2006.ARMY201101272011022820110330-1Closed67012http://www.sbir.gov/node/67012OBJECTIVE: To build artificial antibodies using DNA origami and develop novel types of electo-optical based biological sensing methodologies. DESCRIPTION: Nature is adept at producing molecules that can recognize and specifically bind to other molecules. In biological systems, antibodies can search out and selectively bind to specific target molecules in the presence of numerous other substances. Antibodies are a critical component of the immune systems of many organisms. Selective binding allows the body"s immune system to target and eliminate specific antigens. Antibodies have also become the gold standard for many biosensing applications. Natural proteins are widely used in diagnostic tests for many diseases because they recognize and efficiently bind to disease markers. Attempts have been made to synthesize molecules with abilities for selective bonding that are comparable to antibodies. However, protein antibodies are difficult and expensive to synthesize in the laboratory. The precise rules of protein folding are still a mystery and are one of the unsolved problems of modern biology. Attempts to manufacture proteins with predetermined shapes and functionality have met with limited success. Protein antibodies are also perishable and possess a short shelf life. Attempts have been made to manufacture antibodies from polymers using molecular imprinting. In molecular imprinting, a solution containing a polymer grows around a target molecule. The target molecule is then washed away. When the molecular imprinted antibody contacts the target molecule, binding occurs. Molecular imprinted antibodies have had some success, However, in the case of biological warfare agents, the use of antigens during the manufacturing process presents a difficult, if not impossible, situation. The folding of single- and double-stranded DNA is a chemically well-understood and controllable process. DNA is generally associated with the storage of genetic information. However, in many ways, it is also an ideal building material. DNA"s sequence dictates its shape and structure. Recently, progress has facilitated cheap and easy manufacturing of DNA strands with custom sequences. The use of self-assembled DNA sequences is thus a very attractive approach in the search for artificial antibodies. The science of DNA origami has recently progressed to the point that it is now possible to design and manufacture complex structures using DNA folding techniques. Much of the science of DNA origami is centered on producing better design software. The ability to produce better design software is a critical component of the controlled design and production large complex structures using DNA origami. PHASE I: Conduct a feasibility study of producing artificial antibodies using DNA origami. Methods should be developed to design structures with predetermined shapes and functions. Methods for manipulating the physical properties of the self-assembled structures should also be examined, and electro-optical testing methods should be defined for verifying the types of physical properties achieved. In particular, methods should be developed to manipulate the charge on the surface of a DNA self-assembled nanostructure. Also, the production of controlled hydrophobic and hydrophilic surfaces should be examined using DNA origami methods. A preliminary design should be made to produce structures using DNA origami that will function as antibodies. Where possible, target antigens related to biological warfare agents or simulants should be used in the initial design studies. PHASE II: Fabricate artificial antibodies using DNA origami. Test the affinity of the antibodies to known antigens. Based on the results of the tests, refine the design of the antibodies. Examine methods for incorporating the new artificial antibodies into sensors specifically designed for the detection and identification of biological warfare agents and simulants. Here, an emphasis should be placed upon defining and refining electro-optical based transduction methodologies for achieving the detection and identification capability. PHASE III DUAL USE APPLICATIONS: Further research and development during Phase III efforts will be directed toward refining final deployable designs for artificial antibodies. Design modifications based on results from tests conducted during Phase II will be incorporated. Manufacturability specific to U.S. Army CONOPS and end-user requirements should be examined. Artificial antibodies will have numerous commercial applications, particularly in the field of medicine. It is expected that commercialization will accelerate once the antibodies become less expensive and easier to use. It is one of the goals of this effort to produce affordable, stable antibodies that can be reliably mass-produced for battlefield applications, especially in the context of biological agent detection and identification. REFERENCES: 1. Gnter Wulff,"Molecular Imprinting in Cross-Linked Materials with the Aid of Molecular Templates - A Way towards Artificial Antibodies", Angewandte Chemie International Edition, volume 34, issue 17, pages 1812-1832, 2003. 2. Yoshitaka Iba and Yoshikazu Kurosawa,"Comparison of strategies for the construction of libraries of artificial antibodies", Immunology and Cell Biology, volume 75, pages 217-221; 1997. 3. Carl A. K. Borrebaeck,"Antibodies in diagnostics from immunoassays to protein chips", Immunology Today, volume 21, issue 8, pages 379-382, 2000. 4. Paul W. K. Rothemund,"Folding DNA to create nanoscale shapes and patterns", Nature, volume 440, number 7082, pages 297-302, 2006. 5. Anton Kuzyk, Bernard Yurke, J. Jussi Toppari, Veikko Linko, and Pivi Trm,"Dielectrophoretic Trapping of DNA Origami", SMALL, volume 4, number 4, pages 447-450, 2008. 6. James C. Mitchell, J. Robin Harris, Jonathan Malo, Jonathan Bath, and Andrew J. Turberfield,"Self-Assembly of Chiral DNA Nanotubes", Journal of the American Chemical Society, volume 126, number 50, pages 16342-16343, 2004. 7. Faisal A. Aldaye, Alison L. Palmer, and Hanadi F. Sleiman,"Assembling Materials with DNA as the Guide", Science, volume 321, number 5897, pages 1795-1799, 2008. 8. Ebbe S. Andersen, Mingdong Dong, Morten M. Nielsen, Kasper Jahn, Ramesh Subramani, Wael Mamdouh, Monika M. Golas, Bjoern Sander, Holger Stark, Cristiano L. P. Oliveira, Jan Skov Pedersen, Victoria Birkedal, Flemming Besenbacher, Kurt V. Gothelf, and Jrgen Kjems,"Self-assembly of a nanoscale DNA box with a controllable lid", Nature, volume 459, pages 73-76, 2009. 9. Rahul Chhabra, Jaswinder Sharma, Yonggang Ke, Yan Liu, Sherri Rinker, Stuart Lindsay, and Hao Yan,"Spatially Addressable Multiprotein Nanoarrays Templated by Aptamer-Tagged DNA Nanoarchitectures", Journal of the American Chemical Society, volume 129, number 34, pages 10304-10305, 2007. 10. Nadrian C. Seeman,"An Overview of Structural DNA Nanotechnology", Molecular Biotechnology, volume 37, number 3, pages 246-257, 2007. 11. W. Shen, H. Zhong, D. Neff, M. L. Norton,"NTA directed protein nanopatterning on DNA Origami nanoconstructs", Journal of the American Chemical Society, volume 131, number 19, pages 6660-6661, 2009. 12. Constantin Pistol and Chris Dwyer,"Scalable, low-cost, hierarchical assembly of programmable DNA nanostructures", Nanotechnology, volume 18, number 12, pages 125305/1-125305/4, 2007.ARMY201101272011022820110330-1Closed67012http://www.sbir.gov/node/67012OBJECTIVE: We are seeking advanced, robust wavelength tuners for laser transmitters operating in the 3-5 um and 8-12 um bands for application to point and standoff detection of chemical and biological agents. DESCRIPTION: A variety of wavelength agile laser transmitters are contemplated for advanced point and standoff sensors to probe for chemical and biological agents. These include most notably Quantum Cascade Lasers (QCLs), CO2 TEA (Transverse Electric Atmospheric) lasers, CO2 waveguide lasers, and solid state lasers with optical parametric oscillators (OPOs). The CO2 types operate at moderate to high peak or average power and typically use precision rotating gratings to achieve wavelength selection. They can also be wavelength shifted by OPO, but in that case output power is limited by optical damage on the nonlinear crystal surfaces and shifter resonator optics. QCLs can be wavelength shifted by thermal means, but such lasers operating in Fabry-Perot resonators with angle tuned gratings can offer broader band coverage at high speed. Solid state lasers have proven to be most effective in the MWIR, although attempts have been made to extend their reach to the LWIR. In both these bands, angle tuned OPO shifters have been effective. In all these cases, one of the critical elements of the wavelength shifter is the precision angle tuning mechanism which must satisfy the combined requirements of speed, position accuracy and repeatability, compactness, and robustness. One example is the CO2 TEA laser now incorporated in the FAL (Frequency Agile Laser) which operates at a pulse repetition frequency (PRF) of 200 Hz. The FAL grating angle tuner requires a 10 rad angular resolution over a 5 degree angle with a settling time of 5 msec and an angular repeatability of 10 rad over temperature ranges of at least 0-40oC. The present FAL tuner achieves only a 2.5 degree of angle in 5 msec. Therefore, a two-fold increase in speed is required to solve the present requirement; and a speed increase of three to four times over the present device will be required to satisfy the advanced requirement for a higher data rate FAL system. Proposed improvements to the FAL laser transmitter to make more laser lines available by using isotope gas mixtures would require a two-fold improvement in the angular resolution and repeatability due to the increased selectivity required. The CO2 waveguide laser typically operates at tens of kHz PRF; however in that case, high number multiple pulse averaging is typical, and broadband wavelength shift rates on the order of 200-500 Hz are still applicable. The QCL type offers the advantage of small size even after the necessary thermal controllers and power supplies are added to the transmitter volume. In order to realize the small size potential of these relatively compact transmitters, an equivalently small tuner would be very desirable. Importantly, a small tuner would allow for efficient close coupling to the external Fabry-Perot resonator. Present tuners have volumes typically on the order of 600 cc, not including power supplies and ancillary electronics. What is needed is a reduction in tuner volume by at least 50% while achieving the speed and position accuracy required for an external resonator QCL. It is also very desirable to develop a tuner that is lightweight and electrically efficient so that the overall package size and weight can be kept below 2 liters and 1 kg, respectively. Wavelength tuning speed and precision are key to acquiring high fidelity target data upon which advanced detection algorithms can operate. For example, in the case of LWIR standoff detection, atmospheric and target evolution effects can induce significant data noise which can be alleviated to some extent by high laser PRF and wavelength tuning speed. High data speeds provide for the possibility of fast and effective pulse averaging leading to fast algorithm throughputs and reduced time to alarm. PHASE I: Perform analysis and feasibility studies. Develop conceptual designs for the tuner including a means to test and verify the performance. Provide a detailed development plan for design, fabrication, and testing of the wavelength tuner to be carried out in the Phase II program. PHASE II: Use the results of Phase I to design, fabricate, test and deliver a tuner prototype for demonstration with a government-furnished laser. Provide a roadmap for the integration of the laser and tuner combination with a government-furnished sensor. PHASE III DUAL USE APPLICATIONS: The result of Phase II will be demonstration of a tuner that can be used for rapidly interrogating chem-bio agents. In addition to immediate military applications, the tuner will find widespread use in important civilian applications, including WMD (weapons of mass destruction) detection, pollution monitoring, commercial manufacturing process monitoring, and commercial equipment that is necessary for scientific and aerospace corporations. REFERENCES: (1.) D. Cohn, W. Griffin, L. Klaras, E. Griffin, H. Marciniak, J. Fox, C. Swim,"WILDCAT sensor", SPIE Proceedings 4036, 210, Orlando, Florida, 24-25 (April 2000); (2.) D. Cohn, L. Klaras, J. Fox, C. Swim,"WILDCAT sensor design", Proceedings Fourth Joint Workshop on Standoff Detection for Chemical and Biological Defense, Williamsburg, VA, 305, 26-30 (Oct 1998); (3.) D. Cohn, J. Fox and C. Swim,"Frequency agile CO2 laser for chemical sensing", SPIE Proceedings, Los Angeles, California, vol. 2118, p 72, (Jan 1994).ARMY201101272011022820110330-1Closed67012http://www.sbir.gov/node/67012OBJECTIVE: To develop an alternative to the existing hexachloroethane (HC) and terephthalic (TA) smoke compositions that will produce a very low flame while maintaining a high smoke output. This composition should be similar in high performance as the M8 HC Smoke Grenade but with much less toxic materials and less incendiary hazards. New formulations should avoid hazardous materials to address toxicological concerns. HC smoke grenades produces toxic products such as zinc chloride. Some flame reductions could be achieved through hardware design, but improved chemical compositions are desirable. These devices intended for hand held devices to protect personnel, specifically the M8, but can also find use in the vehicle launched M83 grenade as well. Desirable specifications of the M8: provide a screen 3 meters high by 10 meters long; build up a cloud within 6 seconds,; having a duration of at least 90 seconds. Current TA smoke is a much less toxic and less incendiary smoke but is much lower in performance than the M8 HC smoke. DESCRIPTION: Currently visible obscurant grenades employ high explosives configured as a center burster to disseminate spherical powders. These devices offer very short dissemination periods, making it difficult to maintain protection for the soldier and equipment. Pyrotechnic smokes are composed of active fillers that typically consist of HC smoke mixtures (hexachloroethane/zinc) or TA smoke mixtures (terephthalic acid). In addition, Red Phosphorus is widely used to generate long duration visible obscuration. For all pyrotechnic or burning devices, there are many flame hazards associated with them that restrict their use. These items are avoided because they start brush fires in outdoor applications. They are very difficult to use for indoor applications and create hazards for personnel. The following is a list of performance metrics of various visible smoke grenades. 1. Red Phosphorous (RP) Yield factor of 4.8 at 10 degrees C, 50% RH. Extinction () is 3.5m2/g, Pack Density 2.0, FOM=21 2. Hexachloroethane (HC) Yield factor is 2.1 at 10 degrees C, 50% RH. Extinction () is 3.9m2/g, Pack Density 1.9, FOM=7.4 3. Terephthalic (TA) Yield factor is 0.28 at 10 degrees C, 50% RH. Extinction () is 4.9m2/g, Pack Density 1.3, FOM=3.4 PHASE I: Develop alternative formulations that when reacted, produce a yield factor of at least 2.0. Yield factor is the amount of grams airborne divided by the total amount of grams disseminate. New formulations should also have material extinctions of at least 3.5m2/g in the visible wavelength region. Flame fronts reduction should be at least 50% the HC M8 grenade, which is generally around 1ft at initiation. Ideally, no flame fronts are desired. Demonstrate a concept that can produce a similar amount of smoke as the M8 without using HC that can give Grenade Figure of Merit (FOM) of about 4.0. The FOM for a grenade would be the product of the extinction value, fill fraction, packing density and yield. One possible solution would be to produce hydroscopic species that can increase yield factors(FY). Improving the YF of the current TA smoke grenades (M83 and M90) from approximately 0.28 (or 28%) to something closer to the HC grenades will increase the Grenade Figure of Merit (FOM). Improvement in the how to fill and pack devices will improve the fill fraction and packing densities. New formulations should have higher than 4.0 extinction coefficients (with a high scattering component) in the visible region and be less toxic than the current M8 HC Smoke Grenade. Edgewood Chemical Biological Command (ECBC) has already focused on the ability to obtain a suitable reactions from the embedded chlorine with environmentally friendly oxidizers, as well as looked at finding other suitable fuels to replace the zinc in the old HC smoke composition. Tests can be performed at ECBC obscurant chamber to determine dissemination efficiency, extinction values, temperature and burn rates. At least 5 devices with different formulations should be delivered to ECBC for testing at the end of Phase I Toxicology is a complex and expensive field to evaluate. For Phase 1, a literature search should be provided to compare any new formulation to the existing HC formulation. In reference 6, the 15 minute exposure for HC smoke is given as 10mg/m3. PHASE II: Down select from the Phase I effort at least two formulations that show improvements in the grenade figure of merit and reductions in flame fronts on the M8 size device. Refine the design into two fully-functioning grenades. These must have the overall dimensions of the M106 or M8 handheld grenade. The second part of the Phase II effort is to design and produce using the previous formulations a larger size device with the overall dimensions of the M90 vehicle launched grenade. Scale up includes both hardware design and generation of material. An analysis of how the increase container size and material fills will effect the smoke production and dispersion. Finally, scale up production of the fill material and grenade hardware to be able to field test 60 (30 of each M8 and M90 size) devices at ECBC outdoor field testing areas to demonstrate improvements in smoke production (FOM) and flame reduction. PHASE III DUAL USE APPLICATIONS: The grenades developed in this program can be integrated into current military obscurant applications. Improved visual devices are needed to reduce current logistics burden in needing to carry countermeasures to protect the soldier and his equipment. Other dual use applications include markers for emergency rescue, signaling operations and aeronautic stunt planes. Improved dissemination techniques can be beneficial for all powdered materials in the metallurgy, ceramic, pharmaceutical and fuel industries. Industrial applications include electronics, fuel cells/ batteries, and solar energy. REFERENCES: 1. Bohren, C.F.; Huffman, D.R. Absorption and Scattering of Light by Small Particles; Wiley-Interscience: New York, 1983. 2. Embury, Janon; Maximizing Infrared Extinction Coefficients for Metal Discs, Rods, and Spheres, ECBC-TR-226, Feb 2002, ADA400404, 77 Page(s) 3. Clyens, S.; Johnson, W., The Dynamic Compaction of Powdered Materials, Materials Science and Engineering, 30 (1977), 121-139. 4. Schwarz, R. B., Kasiraj, P., Vreeland T., Ahrens, T. J., A Theory for the Shock-wave Consolidation of Powders, Acta Metall., Vol. 32, pp. 1243-1252. 5. Pyrotechnic Smoke Analysis Vol I, ERDEC-TR-129, N. Sordoni, W.Heard, W. Rouse, Dec 1993 6. Toxicity of Military Smokes and Obscurants, Vol 1, Committee on Toxicology, Commission on Life Sciences, National Research Council., ISBN 0-3090-56 166-3ARMY201101272011022820110330-1Closed67012http://www.sbir.gov/node/67012OBJECTIVE: Traumatic Brain Injury (TBI) is one of the hallmark injuries of the current conflicts in Iraq and Afghanistan. The primary source of these injuries is exposure to blast from Improvised Explosive Devices (IEDs). TBIs have a wide spectrum of sequelae associated with them. While severe TBIs are rapidly identifiable (many are skull penetrating), mild and moderate TBIs are much more difficult to detect and diagnose. Indeed, much of military medical research is devoted towards understanding these subtle injuries. Mild and moderate and TBIs are suspected in Post Traumatic Stress Disorder, seizures and even in Alzheimer"s disease and Parkinsonism. Diffusion Tensor Imaging is a subset of Magnetic Resonance Imaging (MRI) technology, which many Radiologists, Medical Physicists and Clinicians hypothesize could be a key tool towards unraveling the pathological nature of mild and moderate TBIs. One of the major challenges precluding this technique from wider acceptance as a tool for TBI detection and diagnosis is the lack of data acquisition and instrumentation standards between manufacturers and researchers. Standards or tools that could be used to calibrate measurements between operators and instrumentation would greatly increase our knowledge of TBIs. It would enable more direct comparisons between datasets acquired at differing medical institutions. It would also help to standardize long-term instrument performance at a given institution. This would reduce the amount of noise within single datasets and empower their standalone statistical significance. This topic seeks Research, Development, Test and Evaluation funds to develop MRI phantoms for DTI in order to provide a means of calibrating MRI scanner performance across multiple research facilities. This would greatly enable the meaningful analysis and sharing of complex TBI patient datasets. As a result, it would great help move the field towards imaging biomarkers for these injuries. DESCRIPTION: The human brain is perhaps the most complex information management and processing system ever created. It is also arguably one of the most fragile. Despite centuries of study, our understanding of how the structure of the brain is altered in response to the pathologies of disease and injury is still in its infancy. Traumatic Brain Injury (TBI) research is a high priority for today"s military since these injuries are often seen currently seen in theater. Many of these are the result of exposure to Improvised Explosive Devices (IEDs). High performance medical imaging techniques have enabled our understanding of diseases and pathologies such as stroke, multiple sclerosis and Parkinsonism (1-3). Techniques such as Computed Tomography (CT) and MRI also have been used to understand severe TBIs (4); however it has become clear that these conventional anatomical imaging methods in their current forms offer little towards understanding the full nature of mild and moderate TBIs. One novel technique currently under evaluation for its potential to evaluate mild and moderate TBIs is Diffusion Tensor Imaging (DTI), a subset of MRI. In DTI, the alterations in the microenvironments in brain, such as in neuronal fibers can be detected by changes in the diffusion properties of water. While Levin et al. (6) present evidence that DTI could be of limited use for mild and moderate TBIs, several other reports show that DTI offers the potential to identify imaging biomarkers of these injuries (7-8). A recently hosted DTI workshop identified some of the major bottlenecks towards improving the sensitivity and specificity of DTI (9). Improving the sensitivity and specificity was identified as a key component towards addressing the efficacy of this technique to identify injuries associated with mild and moderate TBIs. One strategy towards boosting the sensitivity and specificity of this technique is to acquire DTI-specific phantoms, which would be used to standardized instrumentation and acquisition parameters. This standardization is envisioned not only to be used across institutions; but as an internal standard across large patient cohorts acquired at a single site. The latter point is very important since dataset homogeneity is required to enhance any potential signal associated with very subtle differences in brain anatomy that may be attributable to mild or moderate TBI. MR scanner performance is well known to require occasional calibration. Secondly, standardization across multiple instruments and facilities will allow for sharing of datasets. This, in turn, would greatly increase the statistical power of these measurements. This topic therefore seeks the development of DTI phantoms for performance standardization of MR scanners. The ability to calibrate the performance of MR scanners to specifically perform DTI undoubtedly will reduce systematic errors associated with the acquisition of DTI datasets. PHASE I: The intent of this effort is to develop DTI phantoms that will mimic axonal integrity and water/dye diffusion through axons. Preliminary validation is expected at the end of Phase I. A validation plan should be presented as part of the proposal. The primary emphasis of the validation should pertain to the data acquisition chain in DTI rather than post processing. PHASE II: The selected proposal will outline a plan by which the prototype will be fully validated on a minimum of two different MRI scanners made by different manufacturers. The scanners used must be clinical scanners with data acquisition packages that are cleared for routine use by the FDA or local IRB. It is expected that as part of the validation process, the initial prototype will be refined. The validation plan should include a robust discussion of how improvements in data acquisition will be quantified. The end product of this development cycle is expected to generate a reproducible, complete phantom for DTI image acquisition standardization. The finished phantom prototype will be tested for a series of three reproductions of the prototype phantom. The selected proposal will outline a plan by which quality assurance for this low-scale initial production can be accomplished. It is expected that this plan will be similar to the original validation for the early prototype and will use multiple scanners of different manufacturer makes. PHASE III DUAL USE APPLICATIONS: In addition to improving our knowledge of combat-induced imaging biomarkers for mild and moderate TBI, other diseases such as Multiple Sclerosis and Parkinsonism would also benefit from the use of these phantoms. Standardizing the performance of MRI scanners for DTI could reveal subtle imaging-related clues regarding the onset of these diseases at their earliest stages. Phase III of this solicitation would therefore consider how these devices could advance our knowledge of imaging biomarkers for these diseases in a clinical setting. Other neuropathological diseases would be considered as well. The ultimate goal for this phase will be to validate a DTI imaging protocol for any proposed neurological or neuropathological insult that the offeror wishes to study outside of mild and moderate TBI. REFERENCES: (1) Ramli N, Rahmat K, Azmi K, Chong HT; The past, present and future of imaging in multiple sclerosis; J Clin Neurosci. 2010 Apr;17(4):422-7. Epub 2010 Feb 18. (2) Seppi K, Poewe W; Brain magnetic resonance imaging techniques in the diagnosis of parkinsonian syndromes. Neuroimaging Clin N Am. 2010 Feb;20(1):29-55. (3) Wardlaw JM; Neuroimaging in acute ischaemic stroke: insights into unanswered questions of pathophysiology; J Intern Med. 2010 Feb;267(2):172-90. (4) Jagoda AS, Bazarian JJ, Bruns JJ Jr, Cantrill SV, Gean AD, Howard PK, Ghajar J, Riggio S, Wright DW, Wears RL, Bakshy A, Burgess P, Wald MM, Whitson RR; Clinical policy: neuroimaging and decisionmaking in adult mild traumatic brain injury in the acute setting. J Emerg Nurs. 2009 Apr;35(2):e5-40. (5) Belanger HG, Vanderploeg RD, Curtiss G, Warden DL; Recent neuroimaging techniques in mild traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2007 Winter;19(1):5-20. (6) Levin HS, Wilde E, Troyanskaya M, Petersen NJ, Scheibel R, Newsome M, Radaideh M, Wu T, Yallampalli R, Chu Z, Li X; Diffusion tensor imaging of mild to moderate blast-related traumatic brain injury and its sequelae. J Neurotrauma. 2010 Apr;27(4):683-94. (7) Hartikainen KM, Waljas M, Isoviita T, Dastidar P, Liimatainen S, Solbakk AK, Ogawa KH, Soimakallio S, Ylinen A, Ohman J; Persistent symptoms in mild to moderate traumatic brain injury associated with executive dysfunction. J Clin Exp Neuropsychol. 2010 Mar 1:1-8. (8) Kumar R, Gupta RK, Husain M, Chaudhry C, Srivastava A, Saksena S, Rathore RK; Comparative evaluation of corpus callosum DTI metrics in acute mild and moderate traumatic brain injury: its correlation with neuropsychometric tests. Brain Inj. 2009 Jul;23(7):675-85. (9) Diffusion MRI for TBI Roadmap Development Workshop. June 2-3, 2010, Omni Hotel, Chicago.ARMY201101272011022820110330-1Closed66403http://www.sbir.gov/node/66403Paralytic shellfish poisoning (PSP) is an important public health threat and causes significant economic losses in New England and along the entire west coast of the US including Alaska. Paralytic shellfish poisoning is caused by consuming shellfish that have bioaccumulated saxitoxins which are produced by certain microalgae. The field detection kits used to monitor PSP detect only some of many forms of saxitoxins known as congeners. These kits currently fail to detect important saxitoxin congeners that are toxic to humans and marine mammals.NOAA201101012011012020110401-1Closed359037http://www.sbir.gov/node/359037 The primary mission of Federal Motor Carrier Safety Administration (FMCSA) of Department of Transportation (DOT) is to reduce crashes, injuries and fatalities involving large truck and buses. One of the strategies employed to accomplish this goal is to foster innovative research in new or augmenting safety enhancing technologies and to facilitate faster deployment of proven systems. In collaboration with our industry partners and stakeholders, we continuously identify new opportunities of emphasis that can serve our agency goals and objectives towards improving highway safety. The opportunity outlined in this solicitation refers to a challenge that, if addressed robustly and cost-effectively, has the high potential to further improve the efficacies of existing safety technologies. Background: In North America, the powered heavy trucks often haul a variety of towed units during their operation. As a reference, some of the common combination vehicle configurations can be found on page 26 (Figure 7) of the TRB publication "Trucking 101" [1].  In most cases, the combination vehicles are not "married couples", i.e., the tractor and the trailer(s) do not stay coupled through the life span of the vehicles. The common Commercial Motor Vehicle (CMV) operation involves a tractor to haul different trailers as often as in each trip. Furthermore, the typical lifecycle of a trailer is much longer than that for a tractor. There are operational and economic reasons leading to these market dynamics, but the important ramification of this fact is that tractors often have to haul a wide variety of old and new trailers with substantially differing characteristics. And there is little-to-no information available to the tractor as to what is being towed (that can be automatically detected without driver input). This solicitation calls for innovative solutions to automatically identify some trailer attributes from within the tractor (powered unit). These attributes of interest will be discussed in further details later on. Purpose: On-board safety systems on newer tractors are capable of providing enhanced safety margins for combination CMVs under a wide variety of operating conditions. Such systems include Electronic/Roll Stability Control, Adaptive Cruise Control and Crash Imminent Emergency Brake Assist, among others. They operate with nominal assumptions on the trailer characteristics. The need for these assumptions limits developers' ability to further optimize their safety systems' performances. Hence, there is substantial potential to improve efficacies of such on-board safety systems if there were a mechanism to automatically determine certain trailer characteristics from within the tractor in a robust manner without the reliance on the operator to be in the loop. Automatic detections need to be convertible into electrical signals that can be communicated via the vehicle database to these safety systems. Furthermore, the ability to know the vehicle combination type and the associated attributes of the trailer(s) at the tractor has the potential to simplify mobility applications such as Truck Parking initiatives (where parking reservation systems can be more optimally carried out if the combination vehicle characteristics are known) and to improve implementation efficacies of connected vehicle applications such as Vehicle-to-Vehicle (V2V) safety functions where one of the V's in the interaction is a combination vehicle with unique characteristics. Objectives: This solicitation calls for innovative solutions to identify some trailer attributes from within the tractor. Some trailer attributes of interest are the following and the proposed solution shall address at least a subset of the high priority attributes (as defined within the context of this solicitation) on this list: High priority attributes: The number of trailer units being towed, An accurate determination of whether the combination vehicle is a tractor-semi, tractor –double trailer or tractor-triple trailer (at a minimum, differentiate between semi and multi-trailer cases), The existence/nonexistence of (functioning) trailer ABS on (each of) the towed unit(s), An accurate determination of whether a functioning ABS system is existent on each of the hauled trailer units. Secondary attributes of interest are: The length of the trailer unit(s) (or the aggregated trailer train length), The number of axles and their potential locations (configurations of) on the trailer(s), Trailer height, Trailer type, and/or load type. The proposals can list capabilities of determining other trailer attributes for consideration as well. Such propositions need to explain why those factors would be important to vehicle and traffic safety. Proposers shall research and be aware of existing mechanisms to determine certain characteristics and identify the unique benefits of their propositions while keeping current means in perspective. For instance, using mass estimation algorithms and hard coded bobtail weight specifications of a tractor, it is possible to reliably determine if a trailer is connected to the tractor or not. That same mechanism also can help determine the total weight of the trailer but cannot tell what the weight difference is between the trailer and the load or how many trailers may be connected at any given time. Requirements for the Research: The vision for this solicitation is that the concept system will be fully decentralized and be resident on the tractor. It can be assumed that such a system will be installed on new tractors only (i.e. it will not be retrofitted on older tractors in the field). Since one of the primary objectives of this study is to improve efficacies of the listed commercially available technologies, the proposers can assume the existence of them on the tractor. The summary of the constraints associated with the Phase I work are the following. The proposed solution shall be hosted solely on the powered unit (tractor), i.e., the proposed solution shall not depend on the existence or non-existence of non-standard components on the Trailers and shall not require installation of anything new (on the Trailers). While the above requirement is ultimately desired, practical solutions requiring very rudimentary modifications to the trailer units may also be considered, however, they should be very easy to install and very cost effective. Furthermore, if a modification to the trailer is proposed as part of the solution, a section should be dedicated in the technical approach section describing why high volume costs (component, installation and maintenance costs) would be considered cost-effective and feasible keeping the pool of existing Trailers in the field in perspective. There should be no additional connections required to the trailers except for the common connections such as the 7-pin electrical connector and the pneumatic connections between the powered and towed units (via the gladhands ), The solution shall work with all new and legacy trailers without a priori knowledge on the trailer attributes, The solution shall not rely on the operator's action or inaction, The solution shall not rely on the existence of or communication to a road-side equipment or require for new infrastructural changes, The determination accuracy shall be documented and be better than 2-sigma level (95.5%) in correctly identifying each subgroup within a given characteristics, The solution could depend on a reasonable learning period where estimation logic may need to take its course. However, the system shall provide a confidence metric and converge to a highly reliable determination within a reasonable amount of time. An example "reasonable time" would be from the vehicle power-up event to the vehicle reaching 20mph speed for the first time. This is not a golden rule but an example that can be used as guidance. Proposals that depend on a "learning period" shall discuss the reasonableness of the convergence requirements. Research Plan: The proposers should outline a sound technical approach that can address at least a subset of the trailer attributes classified as "high priority" within the context of this solicitation. Phase I work should result in a proof of concept for the proposed trailer attribute determination system.  During Phase II, the system will be developed to demonstrate the capability at the desired accuracy levels on real vehicles and a risk assessment plan will be carried out to address the potential failure modes and the corresponding ramifications for the intended uses of this solution. Targeted Technology Readiness Level (TRL) for Phase I is "Basic Technology Research" (TRL 1 & 2) and "Research to Prove Feasibility" (TRL 2 & 3). Notes: Roadside based solutions are NOT part of this solicitation. There is other research being carried out where trailer attributes can be measured via external devices and wirelessly communicated to the vehicle. Such proposals to this solicitation will not be considered. Examples of such work are TDS Model 110 [3] and TDS Model 230 [4], as well as another SBIR 11.1 FH3 (closed). [5] The accuracy desired for the determination of the number of connected trailer units is 6-sigma level (99.9997%). However, projected accuracies of 2-sigma (95.5%) or better would be considered for Phase I evaluations [accuracy is implied for each subgroup characterization]. Camera based solutions are often not well suited for this kind of research. While such technologies are not excluded from consideration, a proposer leveraging camera-based technologies shall address the common shortcomings of such technology such as their impairment by inclement weather, surface reflections, lens contamination, background interference, among others. Since existing connectivity between the tractor and the trailer(s) take place over the power line and the pneumatic line, the prospective proposers are encouraged to attempt to further leverage these mechanisms in conjunction with recent advances in electronics, computing, acoustics and nano-technology among others. An example technology that leverages power-line connectivity is power line carrier (PLC) for trucks [2]. If the proposed technology is susceptible to vibration, the proposal should address how the technical approach will handle cab suspension. The proposers are responsible to investigate and disclose all trademarks, licensing needs and intellectual property rights that may be in place in relation to their proposals. DOT201104042011040420110613-1Closed67059http://www.sbir.gov/node/67059NIAAA supports research on the causes, prevention, control, and treatment of the major health problems associated with alcohol use. Through its extramural research programs, NIAAA funds a wide range of basic and applied research to develop new and/or improved technologies and approaches for increasing the effectiveness of diagnosis, treatment, and prevention. NIAAA also is concerned with strengthening research dissemination, scientific communications, public education, and data collection activities in the areas of its research programs. For additional information about areas of interest to the NIAAA, you are invited to visit our home page at http://www.niaaa.nih.gov. Phase IIB Competing Renewal Awards NIAAA will accept SBIR/STTR Phase IIB Competing Renewal grant applications from Phase II SBIR/STTR awardees to continue the process of developing products that require approval of a Federal regulatory agency (e.g., FDA, FCC). Such products include, but are not limited to, medical implants, drugs, vaccines, and new treatment or diagnostic tools that require FDA approval. This renewal grant should allow small businesses to get to a stage where interest and investment by third parties is more likely. Please contact Dr. Max Guo (contact information provided below) before beginning the process of putting an application together. Prospective applicants are strongly encouraged to contact NIH staff prior to submission of a Competing Renewal application. Prospective applicants are strongly encouraged to submit to the program contact a letter of intent that includes the following information: •Descriptive title of the proposed research •Name, address, and telephone number of the Principal Investigator •Names of other key personnel •Participating institutions •Funding Opportunity Announcement Number (e.g., PA-10-XXX) Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NIH staff to estimate the potential review workload and plan the review. It is expected that only a portion of NIAAA SBIR/STTR Phase II awards will be eligible for a Phase IIB Competing Renewal grant. The following examples would make appropriate topics for proposed SBIR or STTR Phase IIB Competing Renewal projects. These examples are meant for illustrative purposes and are not exclusive of other appropriate activities: •Preclinical studies, including pharmacology and toxicology, beyond those conducted under the Phase I (R43) and initial Phase II (R44) grants. Some in vivo or in vitro studies would be expected to have been carried out in Phase I or the initial Phase II grant. •Completion of studies as required by the Food and Drug Administration (FDA) for Investigational New Drug (IND) or Radioactive Drug Research Committee (RDRC) application •Development and clinical evaluation of new alcohol-sensitive biomarkers •Assessment of devices with regard to performance standards related to the FDA approval process •Safety and effectiveness studies of novel medical devices •Biocompatibility studies of surface materials of putative medical implants •Evaluation of novel imaging approaches for diagnostic purposes •Clinical studies in support of New Drug Application approval by the FDA •Clinical studies in support of Pre-Market Approval for biomarkers/medical devices by the FDA Direct your questions about scientific/research issues to: Q. Max Guo, Ph.D. Phone: 301-443-0639 Email: Max.Guo@nih.gov Pharmaceutical Development for Alcoholism Treatment The topic focuses on applied and, where appropriate, clinical research on pharmacologic agents for use in the treatment or medical management of alcoholism, disorders resulting from alcoholism, the improvement and refinement of drugs currently available for therapeutic purposes, or drugs suitable for use in basic research studies on alcohol addiction. Areas that may be of interest to small businesses include, but are not limited to: A.Development of agents to attenuate drinking behavior, e.g., drugs to curb craving B.Development of aversive agents such as disulfiram that can attenuate drinking behavior C.Development of agents to treat acute alcohol withdrawal D.Development of drugs that are capable of improving or reversing alcohol-induced cognitive impairments E.Development of agents to induce sobriety in intoxicated individuals (i.e., amethystic agents) F.Development of agents to treat associated psychiatric disorders and/or drug abuse, and to diminish drinking G.Development of improved methods of drug delivery for the treatment of alcoholism. The systems developed must be capable of maintaining therapeutic drug levels for extended periods of time to alleviate compliance problems. H.Development of drugs for the treatment of alcoholic hepatitis, cirrhosis, pancreatitis, cardiomyopathy, or other alcohol-induced tissue damage I.Research on the pharmacodynamics and pharmacokinetics of concurrent ethanol and other drug use. For clinical questions, contact: Joanne B. Fertig, Ph.D. 301-443-0635 Email: Joanne.Fertig@nih.gov For pre-clinical questions, contact: Mark Egli, Ph.D. (Neuroscience and behavior) 301-594-6382 Email: Mark.Egli@nih.gov Svetlana Radaeva, Ph.D. (Organ damage) 301-433-1189 Email: sr252a@nih.gov Diagnostic Assessment of Alcohol Use Disorders and Comorbidity Innovative self-report and biochemical approaches to the early identification of alcohol use problems and diagnosis of alcohol use disorders and comorbidity are needed. The research design should include measurements of reliability and validity in appropriate population samples. Areas that may be of interest to small businesses include, but are not limited to: A.Development or adaptation of diagnostic instruments measuring alcohol use disorders and related comorbid conditions in general population and treated samples, including youth, the elderly, pregnant women, ethnic minorities, the handicapped, and persons with low-level reading skills). B.Development and testing of computer algorithms necessary to derive diagnoses of alcohol use disorders and associated comorbidity. C.Development of innovative methods for diagnostic assessment in clinical settings. Development and testing of detailed audio, visual, or printed training modules to accompany diagnostic instruments. Cherry Lowman, Ph.D. 301-443-0637 Email: Cherry.Lowman@nih.gov Treatment of Alcoholism A.Development and evaluation of innovative therapeutic approaches across the continuum of alcoholism care. B.Development and validation of tools to aid in the clinical management of patients, including selection of appropriate interventions, process evaluation, assessment of outcome, aftercare, and patient tracking, in various treatment settings. Cherry Lowman, Ph.D. 301-443-0637 Email: Cherry.Lowman@nih.gov Alcohol Biosensors and Data Analysis Systems It is anticipated that innovative and improved alcohol sensors would be useful in a variety of situations including, but not limited to, clinical monitoring, forensics and human or animal research. Specific sensor characteristics would complement their intended use. This applies to characteristics such as sampling frequency, degree of accuracy, data storage capacity and data transmission frequency. Depending on their intended purpose and use, alcohol sensors may be augmented with additional information such as other physiological measurements or geospatial determinations. Devices need to be compatible with human comfort, and devices to be worn for weeks or months may present particular challenges. Since alcohol readings are likely to be baseline most of the time, these sensing devices generally require ways to monitor contact and readiness to record. Moreover, where necessary, measurement fidelity should be robust to subject's activities including active efforts at tampering. The mode of data storage will need to conform to power limitations and strategies for data transmission which may require telemetry. In addition to alcohol monitoring and data transmission this program also includes the opportunity to develop appropriate data analysis systems. Examples include: estimating blood alcohol concentrations, reconstructing patterns of alcohol consumption, and monitoring large numbers of devices to identify significant, but infrequent, events while minimizing false positives. R. Thomas Gentry, Ph.D. 301-443-6009 Email: Tom.Gentry@nih.gov Promoting Adherence to Medical, Pharmacologic, and Behavioral Treatments for Alcohol Use Disorders Several recent reports and literature reviews point to the continuing need for improving adherence to therapeutic regimens. Adherence rates vary considerably across diseases and treatments, measuring instruments, and populations, with rates ranging from 30% to 60% in many instances. The reasons for non-adherence are multifaceted. Health-care providers, organizational systems, and patient factors all play a role in adherence to therapeutic regimens. Thus, to understand and eventually improve adherence, conceptual frameworks and interventions need to take into account institutional, system, situational, interpersonal, and personal factors as well as the characteristics of the illness or condition and of the treatment regimen. While extensive research exists and successful techniques have been identified, greater efforts are needed to develop and implement programs based upon these findings. Applications are sought to develop: A.Programs to implement effective interventions and to evaluate their implementation. B.Professional education courses or web-based training modules on interventions and to monitor their effectiveness. In both cases, the emphasis is on how to encourage health practitioners to utilize interventions that will improve their patients’ adherence to medical, pharmacologic, and behavioral regimens for alcohol abuse and dependence. Margaret E. Mattson, Ph.D. 301-443-0638 Email: Margaret.Mattson@nih.gov Prevention This area of interest focuses on the development and evaluation of innovative prevention and intervention programs, or specific materials for integration into existing programs, which utilize state-of-the-art technology and are based on currently accepted clinical and behavioral strategies. Applicants are strongly encouraged to consult with research methodologists and statisticians to ensure that state-of-the-art approaches to design, analysis, and interpretation of studies under this topic are used. Areas that may be of interest to small businesses include, but are not limited to: A.Development and evaluation of innovative prevention/intervention programs, or specific materials for integration into existing programs, which utilize state-of-the-art technology and are based on currently accepted clinical and behavioral strategies. Special emphasis should be placed on the needs of high-risk groups, ethnic and minority populations, youth, children of alcoholics, women, the handicapped, and the elderly. Examples of such materials include school-based curricula, interactive videos, computer-based multimedia programs, training manuals for teachers or parents, and community-based programs. B.Development and evaluation of educational materials designed to intervene with the elderly around specific age-related risks for alcohol problems. Particular attention should be given to age-related reductions in alcohol tolerance, interactions between alcohol and prescription and over-the-counter medications, possible exacerbation of some medical conditions common among the elderly, potential biomedical and behavioral consequences of excessive alcohol use, and the role of alcohol in falls, fires, burns, pedestrian and traffic injuries, and other unintentional injuries. C.Development and evaluation of statistical analysis programs tailored to the design and analysis of alcohol prevention-relevant research. Programs could focus on a variety of areas including: imputation of missing data under varying design assumptions; simulation of distributions of outcomes based on varying mixtures of sample populations; application of chronic or infectious disease models to targeted communities; and models of the potential effect of various policy-based interventions, such as increased taxation or reduction of outlet density by license revocation and control. Robert C. Freeman, Ph.D. 301-443-8820 Email: Robert.Freeman@nih.gov Health Services Research on Alcohol-Related Problems Research projects are sought that will expand knowledge and improve delivery of alcohol treatment and prevention services. The research objectives include, but are not limited to, the effects of organizational structures and financing mechanisms on the availability, accessibility, utilization, delivery, content, quality, outcomes, and costs of alcohol treatment services. Objectives also include studying the effectiveness and cost-effectiveness of alcohol prevention services in reducing the demand for health care services and improving the methodological tools useful for conducting health services research. Areas that may be of interest to small businesses include, but are not limited to: A.Development and assessment of protocols to assist in the identification, recruitment, and selection of treatment personnel to enhance the matching of staff to program needs. B.Development and assessment of computer software or other protocols to assist in the management of treatment delivery. Software should be useful for assessment, diagnosis, patient placement criteria, monitoring of services received, tracking patient progress, and billing. C.Development and assessment of software to assist clinicians in scoring and assessment of score norms for commonly used assessment instruments. These packages should include protocols for guiding client feedback in a clinic or office-based setting. D.Development and assessment of software or other protocols to assist treatment programs and service agencies in measuring, assessing, or otherwise documenting clinically relevant performance indicators or improvements in quality of service provision. E.Development and assessment of protocols to facilitate the selection, implementation, adoption, and maintenance of evidence-based services consistent with target population need, staffing and program resources, and expected outcomes. These protocols should be flexible enough to work across a variety of settings and modalities. F.Development and assessment of software or other protocols to facilitate the incorporation of screening and identification tools into routine usage in primary care, emergency, obstetric, mental health, and other health care settings. Research projects should facilitate both the provisions of brief interventions, medical management, effective referral to specialized alcohol treatment, and follow-up. G.Development and assessment of software or other protocols for monitoring service costs of alcohol treatment services including core, ancillary, out-sourced services. These tools should provide a user-friendly system of monitoring costs that could be implemented without additional accounting expertise by the staff at a typical treatment setting. At the same time, such tools should be defensible as measures of the true opportunity costs of providing alcohol treatment services. Such software might be bundled with billing software. Robert Huebner, Ph.D. 301-443-4344 Email: Bob.Huebner@nih.gov Fetal Alcohol Spectrum Disorder (FASD) and Alcohol-Related Birth Defects FASD is the collective term for the broad array of documented adverse effects resulting from in utero alcohol exposure. The most serious of these is fetal alcohol syndrome (FAS), a devastating developmental disorder characterized by craniofacial abnormalities, growth retardation, and nervous system impairments that may include mental retardation. Other diagnostic categories include partial FAS, alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBD). Children and adults with FASD may exhibit multiple cognitive, behavioral, and emotional deficits that impair daily functioning in many domains. The NIAAA supports research leading to improved diagnosis and assessment of impairment and disability, as well as the development of tools to enhance academic and daily living skills. Areas that may be of interest to small businesses include, but are not limited to: A.Development and assessment of diagnostic and/or screening methods that can be used prenatally to identify fetuses affected by ethanol. B.Development and validation of biomarkers that can be used to verify prenatal alcohol exposure in neonates. C.Development and validation of assessment methods to provide more accurate clinical diagnosis of FASD at all life stages. D.Development and testing of skill-building, therapeutic, and education program products that enhance the social, cognitive, adaptive and motor abilities of individuals with FASD. E.Development of neurobehavioral tools or instruments to assess responsiveness of individuals with FASD to medications and/or cognitive/behavioral therapies. F.Development of accurate measures of the responsiveness of children affected by prenatal exposure to alcohol to stress and predictors of vulnerability to alcohol-drinking or other psychopathology during adolescence and adulthood. G.Development and evaluation of educational and training programs designed to enhance the skills of non-professional caregivers in dealing with the problems associated with FAS. H.Development and validation of innovative approaches to prevent harmful drinking during pregnancy. For basic research questions, contact: Dale Hereld, MD, Ph.D. 301-443-0912 Email: Dale.Hereld@nih.gov William C. Dunty, Ph.D. 301-443-7351 Email: William.Dunty@nih.gov For prevention research questions, contact: Marcia Scott, Ph.D. 301-402-6328 Email: Marcia.Scott@nih.gov Alcohol Use and HIV, HBV, or HCV Infection Alcohol use, including hazardous drinking, by persons infected with HIV, HBV, and HCV, is quite common in the United States. Alcohol consumption is widely acknowledged as a co-factor in the sexual transmission, susceptibility to infection, and progression of the infectious diseases. However, detailed relationships between alcohol use and viral infections, diseases progression, antiretroviral therapy and adverse outcomes, notably in liver disease progression, are less recognized or understood. Recent research indicates that inflammatory pathways predominate in alcoholic hepatitis whereas adaptive immunity plays a primary role in viral hepatitis, offering multiple targets for novel preventive and therapeutic interventions. Comprehensive studies to improve understanding of the factors underlying alcohol and viral etiologies in liver disease and the impact of antiretroviral drugs on liver disease progression are needed. A better understanding of alcohol’s effects on liver disease in patients with HIV/HBV/HCV infection may improve diagnosis and treatment outcomes. NIAAA supports research leading to improved diagnosis and treatment of alcohol-induced disorders in people infected with HIV, HBV, or HCV. Areas that may be of interest to small businesses include, but are not limited to: A.New preventive and therapeutic approaches designed to protect the liver from alcohol and antiretroviral drug-induced liver injury in patients infected with HIV, HBV, or HCV. B.Development of therapies aimed at molecular targets that play a role in the development of alcoholic and viral liver diseases. C.Develop and evaluate drugs that mitigate the effects of oxidative stress on mitochondrial function thereby preventing liver disease progression. D.Development of biomarkers for individuals who are most prone to alcohol-induced damage in those patients infected with HIV, HBV, or HCV. For HBV/HCV and basic research questions on HIV, contact: H. Joe Wang, Ph.D. 301-451-0747 Email: He.Wang@nih.gov For clinical or epidemiological questions on HIV, contact: Kendall J. Bryant, Ph.D. 301-402-9389 Email: Kendall.Bryant@nih.gov Research Tools The NIAAA supports the development of new or improved tools to enhance the ability to conduct alcohol-related laboratory studies on humans and animals and to more effectively analyze data from large databases. Examples include transgenic animal models, cell lines, new ligands for neuroimaging, and simulators of alcohol impairment. Areas that may be of interest to small businesses include, but are not limited to: A.Development of novel animal models, including transgenic animals, possessing specific traits of significance for the study of alcoholism, or for the study of specific pathologic disease states which arise from excessive alcohol consumption. B.Development of a hepatocyte cell line capable of maintaining viability and metabolic functions in culture systems for an indefinite period. C.Development of new methods of ethanol administration to animals that produce precise dose control or that closely mimic types of alcohol exposure occurring in humans, including, but not limited to, binge drinking, acute consumption, moderate consumption and chronic consumption. D.Development of specialized cell culture chambers to provide controlled administration of ethanol to in vitro cell systems. E.Development of ligands which will enhance the potential usefulness of PET and SPECT imaging technologies for the study of the etiology of alcoholism and related brain pathology. F.Development of genetic, epigenetic, genomic, proteomic, metabolomic, lipidomic, glycomic or other systems-wide methods for assessment, prognosis, diagnosis or treatment of alcohol-induced disorders. G.Development of computational, statistical or bioinformatics tools to organize and manage high throughput data obtained by genomic, functional genomic or other ‘omic strategies. H.Development of databases, methods for integration of databases, or data analysis systems for alcohol research. Kathy Jung, Ph.D. 301-443-8744 Email: Mary.Jung@nih.gov Development of Biomolecular Signatures of Alcohol Exposure and Alcohol-induced Tissue Injury Acute and chronic alcohol consumption leads to health-related complications and ultimately to significant societal costs. Quantitative and qualitative markers of high-risk drinking behavior and alcohol-induced tissue damage would greatly improve medical efforts to recognize and treat alcohol-related disorders. Traditional biomarkers currently in clinical use lack specificity, sensitivity, and accuracy, and fail to provide long-term information. Biomarkers of sufficient reliability, sensitivity and specificity are likely to be comprised of a panel of physiological parameters, rather than a single molecular entity. Thus, NIAAA seeks to support the discovery and development of pattern-based molecular fingerprints or signatures of alcohol consumption and of alcohol-induced tissue injury. High throughput approaches using genomics, epigenomics, transcriptomics, proteomics, metabolomics, lipomics, or glycomics are encouraged. Biomarker signatures may be composed of multiple genes, RNAs, microRNAs, proteins, or metabolites, or combinations thereof. Furthermore, alterations in lipid, lipoprotein, or glycoprotein profiles may reflect the metabolic effects of alcohol exposure and may be considered as potentially predictive. Biomarker signatures that address multiple aspects of alcohol consumption and alcohol damage are needed. These include, but are not limited to: A.Biomarkers of long-term alcohol consumption. A biomarker panel reflecting the cumulative intake of alcohol over a period of months or more would be of great diagnostic use, both in terms of recognizing problem drinking and in terms of the potential for organ damage. B.Biomarkers that distinguish between binge, acute, moderate and chronic drinking. Each of these modes of alcohol intake has different physiological effects. The ability to distinguish dose and timing of drinking would enhance clinicians’ ability to design appropriate treatment and intervention protocols. C.Biomarkers of compliance after withdrawal. Biomarker signatures in this class would be comprised of metabolic products that decrease rapidly upon abstinence, in contrast to the characteristics of biomarkers that reflect cumulative alcohol. The ability to detect relapse accurately will support successful behavioral interventions. D.Biomarker signatures of alcohol-induced organ damage. The damage due to alcohol consumption is likely to be organ-specific, with signatures reflecting alcohol-induced damage likely to be different for heart damage, liver damage, encephalopathy, a dysregulated immune system, or other alcohol target. E.Biomarker signatures of familial risk factors for alcoholism. Early identification of subjects predisposed to alcoholism will allow for early intervention, and allow the subject to make informed decisions. Kathy Jung, Ph.D. 301-443-8744 Email: Mary.Jung@nih.gov Clinical Testing of Biochemical Markers The development of effective biochemical markers represents a powerful means for early diagnosis and treatment of alcohol dependent/abuse patients and for the identification of individuals who have a predisposition for alcoholism. There are two different types of biochemical markers: trait markers and state markers. Trait biomarkers have the ability to detect inborn characteristics of individuals who are vulnerable for alcoholism. This type of marker would be invaluable for screening of high-risk individuals (e.g., children of alcoholics) and targeting them with preventive or early treatment interventions. In addition, trait markers might assist practitioners in identifying subpopulations of alcoholics who may need different treatment strategies. An ideal trait marker should have several features. First, it should display validity in detecting people susceptible to alcoholism, particularly before the onset of alcoholism or during periods of stable abstinence. Second, it should be easily and reliably measured. Third, it should be specific for alcoholism only and not affected by other medical or psychiatric disorders or drugs. Since alcoholism is a complex disease, it is likely that more than one type of gene and protein exist as trait marker. State markers or markers of alcohol consumption serve several important purposes. First, they can assist physicians in diagnosing individuals with chronic drinking problems, particularly patients who deny excessive drinking. Moreover, they may also identify individuals in early stages of heavy drinking, thus avoiding the long-term medical, psychological, and social consequences of chronic alcoholism. Second, state biomarkers can aid in the diagnosis and treatment of other diseases (liver diseases, pancreatitis, and cardiovascular diseases) that were, at least, caused by excessive drinking. Third, they are useful in alcohol treatment and prevention programs. Since the goal of many of programs is abstinence, monitoring relapse is important in gauging success. Last, state biomarkers are important in clinical alcohol trials. Although self-reports have become more sophisticated and valid (e.g., Timeline Followback), they still rely on accurate reporting. These new and reliable biomarkers could then be used to confirm the self-report. Several biomarkers with certain limitations are currently in use including carbohydrate-deficient transferrin (CDT), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and mean corpuscular volume (MCV). New state markers need to be developed that incorporate the following attributes: validity, reliability, stability, cost, practicability, acceptability, and transportability. Areas that may be of interest to small businesses include, but are not limited to: A.Develop and evaluate clinically alcohol-sensitive biomarkers to identify individuals who are predisposed to alcoholism; determine relapse; measure levels of drinking; and determine alcohol-induced tissue damage. B.Identify genes, and proteins that are expressed during the development of alcohol dependence for biomarker development. C.Develop methodologies for high throughput identification of alcohol metabolites and other signaling molecules that are expressed during alcohol intake. D.Use knowledge of genetic and molecular mechanisms underlying alcohol-induced organ damage (including alcohol-related liver, pancreas, heart disease and FAS) to develop new biomarkers of tissue and cell damage. E.Evaluate clinically innovative alcohol-sensitive biomarkers (trait, relapse, organ damage) for sensitivity and specificity. Raye Z. Litten, Ph.D. 301-443-0636 Email: Raye.Litten@nih.gov Stem Cell Research for Alcohol-induced Disorders Stem cells are master cells in the body and they have the remarkable potential to develop into many different cell types. Stem cells may become a renewable source of replacement cells to treat alcohol related diseases. They can also be used to study disease processes, and to develop new and more effective drugs. Recent research progress on stem cells has offered great opportunities to study conditions and diseases related to alcohol abuse and alcoholism. Stem cells can come from embryos or adult tissues. They are generally categorized into 1) Embryonic stem cells; 2) Induced pluripotent stem cells (iPS cells); and 3) Adult stem cells. The NIAAA supports SBIR/STTR research using any of these 3 types of stem cell, which can lead to improved understanding of alcohol related diseases and conditions, and better treatment. Areas that may be of interest to small businesses include, but are not limited to: A.Generate and disseminate induced pluripotent stem cells (iPS) from mature human cells to resemble diverse individual variations regarding alcohol metabolism. Use these genetic variant models to study alcohol dependence and pharmacotherapy development. Examples of these genetic variations include Alcohol Dehydrogenase (ADH), Aldehyde Dehydrogenase (ALDH), cytochrome P450 isozyme CYP2E1, and Glutathione S transferase (GST). B.Generate and disseminate disease-specific iPS cell lines for studies on the biology and signaling pathways that contribute to the alcohol-related disease pathology. C.Study the potential of using patient-specific iPS cells for cell replacement therapies to treat alcohol-caused tissue damages. Peter Gao, M.D. 301-443-6106 Email: Peter.Gao@nih.gov Real-time Detection of Neurochemical Changes in Response to Alcohol Drinking Many pharmacological mechanisms of ethanol action in the brain are mediated by time-dependent neurochemical events in multiple brain regions. Despite great progress in identifying ethanol’s neurochemical actions, we do not fully know how neurochemicals change in real time following ethanol administration and drinking (acute and chronic). Multidimensional measurement of neurochemical change (i.e., concentration, time, region) are needed to reveal kinetics underlying alcohol effects to guide future medication development and promote mechanistic understanding of alcohol drinking. With this SBIR/STTR grant solicitation, NIAAA seeks development of biosensors enabling monitoring of regional neurochemical changes in the brains of rats and/or mice in real time as they drink alcohol. Recent studies report the plausibility of using microsensors coupled with wireless detection methods to instantaneously monitor multiple neurochemical changes in animals. NIAAA seeks development of microsensors with sufficient resolution to provide neuroanatomical regional specificity. In addition to brain ethanol concentration, neurochemicals of interest include, but are not limited to, glutamate, dopamine, GABA, acetylcholine, and signaling molecules. Work under this solicitation should be directed toward the development of commercial strategies for the real-time measurement of extracellular neurochemical and brain ethanol concentrations in behaving animals. Changhai Cui, Ph.D. 301-443-1678 Email: Changhai.Cui@nih.gov Mark Egli, Ph.D. 301-594-6382 Email: Mark.Egli@nih.gov Other Research Topic(s) Within the Mission of the Institute For additional information on research topics, contact: Q. Max Guo, Ph.D. National Institute on Alcohol Abuse and Alcoholism 5635 Fishers Lane, Room 2037 Bethesda, MD 20892-9304 For Federal Express delivery, use: Rockville, MD 20852-1705 Phone: 301-443-0639 Email: Max.Guo@nih.gov For administrative and business management questions, contact: Ms. Judy Fox Grants Management Officer National Institute on Alcohol Abuse and Alcoholism Phone: 301-443-4704, Fax: 301-443-3891 Email: Judy.Fox@nih.govHHS201104262011042620110626-1Closed67059http://www.sbir.gov/node/67059The NIAID's Division of AIDS, Division of Allergy, Immunology, and Transplantation, and Division of Microbiology and Infectious Diseases fund SBIR/STTR grants on topics related to their mission and activities as described below. Questions on specific research areas may be addressed to the NIAID Program Officials listed below. General questions on the NIAID SBIR and STTR programs and on administrative and business management may be addressed to contacts listed for the NIAID section. When possible, applicants are encouraged to use email for communication. For information about NIAID's Small Business Programs, please visit http://funding.niaid.nih.gov/researchfunding/sb/pages/default.aspx. Limited Amount of Award (Total not Annual) For budgetary or programmatic reasons, NIAID may decrease the requested length of an award or the requested amount of an award. Applicants considering requesting a Phase I grant greater than $300,000 total cost or a Phase II grant greater than $2 million total cost are strongly encouraged to contact Gregory Milman (below) before submitting an application. Phase IIB SBIR Competing Renewal Awards The NIAID will accept Phase IIB SBIR Competing Renewal grant applications to continue the process of developing products that require approval of a regulatory agency (e.g., FDA). Projects that are particularly encouraged include those in the NIAID Small Business High Priority Areas of Interest (http://funding.niaid.nih.gov/researchfunding/sb/pages/sbirareas.aspx). NIAID will not accept Phase IIB STTR Competing Renewal applications. NIAID will accept Phase IIB SBIR Competing Renewal applications for a project period of up to three years and a budget not to exceed a total cost of $1 million per year (including direct cost, F&A, and fee/profit) provided the time period and amount are well justified. The total amount of all consultant costs and contractual costs normally may not exceed 50% of the total costs requested for initial SBIR Phase II applications. NIAID SBIR Phase IIB Competing Renewal grant applications may exceed this guideline, however, when well justified and when those costs are necessary to support preclinical studies and related expenses. Examples of well founded reasons for exceeding this guideline include, but are not limited to, subcontracts for safety, toxicity, or efficacy testing in animals, and subcontracts to assure compliance with Good Manufacturing Practices expectations of the FDA. Human clinical trials may not be a component of proposed SBIR or STTR research. See Notice of NIAID Policy on investigator initiated clinical trials at http://grants.nih.gov/grants/guide/notice-files/NOT-AI-10-024.html. Small business applicants are encouraged to contact Gregory Milman (below) to discuss NIAID funding for human clinical trials. NIAID does NOT request a letter of intent for Phase IIB Competing Renewal Applications. However, prior to submission, applicants are strongly encouraged to contact: Gregory Milman, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Room 2130, MSC-7610 6700-B Rockledge Drive Bethesda, MD 20892-7610 (US Mail) Rockville, MD 20817-7610 (Delivery Services) Telephone 301-496-8666 Fax: 301-402-0369 Email: gm16s@nih.gov Division of AIDS The Division of AIDS (DAIDS) supports research on the pathogenesis, natural history, and transmission of HIV and HIV disease, and promotes progress in its detection, treatment, and prevention. Director: Dr. Carl Dieffenbach 301-496-0545 Email: cd17u@nih.gov BASIC SCIENCES PROGRAM Supports basic and applied research on the causes, diagnosis, treatment and prevention of HIV and AIDS. Director: Dr. Susan Plaeger 301-402-9444 Email: splaeger@niaid.nih.gov A.Epidemiology Branch. Population-based research and modeling studies of HIV transmission and associated biological and behavioral factors. Also, the treated and natural history of HIV, including research on immunology, virology, therapy and other issues surrounding care, and other co-morbidities, their interactions and impact on clinical outcome. Contact: Joana Roe 301-435-3759 Email: jr108r@nih.gov B.Pathogenesis Branch. Molecular and cellular biology, virology, and immunology of virus-host interactions and mechanisms of immunopathogenesis and HIV transmission. Identification and characterization of host and viral factors that impact viral transmission, host restriction, pathogenesis and latency. Characterization of potential targets for discovery or design of novel therapeutic strategies. Innovative approaches for monitoring or studying viral infection, pathogenesis and latency. Contact: Dr. Karl Salzwedel 301-496-5332 Email: salzwedelkd@niaid.nih.gov C.Targeted Interventions Branch. Research areas: (1) targeted therapeutics emphasizing under-explored viral and cellular targets; (2) innovative therapeutic strategies including immune-based and gene-based therapies and therapeutic vaccines; (3) translational research for effective therapeutics spanning preclinical discovery through IND-enabling studies; (4) animal models for evaluating new therapeutic entities, regimens, and strategies; and (5) therapeutic approaches using nanotechnology. Contact: Dr. Roger Miller 301-496-6430 Email: rm42i@nih.gov VACCINE RESEARCH PROGRAM Supports the development of vaccines to prevent AIDS. Director: Dr. Margaret (Peggy) Johnston 301-402-0846 Email: pj7p@nih.gov A.Vaccine Clinical Research and Development Branch. Research areas: (1) coordination of phase I, II, and III domestic and international clinical trials of candidate AIDS vaccines; (2) coordination of the characterization of immune responses in HIV-infected and uninfected immunized volunteers, using micro and macro assays; and (3) coordination of studies to identify, validate, and standardize immunologic and virologic markers for monitoring response of participants in vaccine clinical trials. Contact: Dr. Jim Lane 301-451-2758 Email: laneji@mail.nih.gov B.Preclinical Research and Development Branch. Support of applied preclinical development of candidate AIDS vaccines, delivery methods and novel vaccine vectors, and adjuvants for the prevention of AIDS; promotion and evaluation of safety and efficacy of the prevention modalities, especially novel vaccine concepts identified in preclinical models including trials in non-human primates; genetic and immunologic variation; and mucosal immunity in SIV, HIV, and SHIV models. Contact: Dr. Yen Li 301-496-3816 Email: yli@niaid.nih.gov C.Vaccine Discovery Branch. Research on: 1) identification of optimal antigens for HIV vaccine design (e.g., epitope mapping, epitope dominance, etc.); 2) identification of cellular components or novel antigens created by env-host interactions as vaccine targets; 3) development of innovative small animal models and in vitro systems to assess immune responses to vaccines; and 4) novel innate and mucosal immune pathways, adjuvants and immunomodulators to improve vaccine responses. Contact: Dr. Geetha Bansal 301-496-5042 Email: gbansal@niaid.nih.gov THERAPEUTICS RESEARCH PROGRAM Develops and oversees research and development of therapies for HIV disease, including complications, co-infections, co-morbidities and cancers, in adults, infants, children, and adolescents. Acting Director: Dr. Carla Pettinelli 301-402-5582 Email: pettinelli@niaid.nih.gov A.Drug Development and Clinical Sciences Branch. Discovery and preclinical development of experimental therapies for HIV, TB and other infectious diseases; maintenance of a database of potential anti-HIV and anti-opportunistic infection compounds; immunologic, virologic, and pharmacologic research related to the design and conduct of clinical trials. Chief: Dr. Mike Ussery 301-402-0134 Email: mussery@niaid.nih.gov B.HIV Research Branch. Clinical research of strategies to treat adult primary HIV infection and complications; strategies to augment HIV immune responses and general host immunity. Contact: Daniella Livnat 301-435-3775 Email: dlivnat@niaid.nih.gov C.Complications & Co-Infections Research Branch. Preclinical and clinical research to develop new or improved therapies for the treatment and prophylaxis of Pneumocystis carinii pneumonia, Mycobacterium avium disease, and cryptococcosis. Evaluation of diagnostics of or agents for treatment or prevention of hepatitis B or hepatitis C secondary to HIV infection in adults. Contact : Dr. Chris Lambros 301-435-3769 Email: clambros@niaid.nih.gov D.International Maternal, Adolescent and Pediatric Medicine Branch. HIV therapies in children and adolescents. Strategies to reduce transmission from mother to infant or fetus. Chief: Dr. Ed Handelsman 301-402-3221 Email: handelsmane@niaid.nih.gov E.Prevention Sciences Program. Conduct basic research on mechanisms of HIV transmission supportive of new biomedical strategies for interrupting transmission. Conduct of domestic and international phase I, II, and III clinical trials to evaluate HIV/AIDS prevention strategies, including microbicides, chemoprophylactic agents, and other biomedical and behavioral risk reduction interventions. Acting Director: Sheryl Zwerski, MSN, CRNP 301-402-4032 Email: szwerski@niaid.nih.gov F.Microbicide Research Branch. Basic research on mechanisms of HIV transmission leading to new biomedical strategies for interrupting transmission. Translational research on microbicides, spanning discovery and preclinical through pilot human clinical research. Pilot clinical studies of the performance of microbicide vehicles with regard to coverage of and persistence on mucosal surfaces, potential biomarkers of safety, behavioral acceptability, and new technology to evaluate safety. Dr. Roberta Black Chief Topical Microbicide Research Branch 301-496-8199 Email: rblack@niaid.nih.gov Division of Allergy, Immunology, and Transplantation The Division of Allergy, Immunology, and Transplantation (DAIT) supports studies of the immune system in health and the cause, pathogenesis, diagnosis, prevention, and treatment of disease caused by immune dysfunction. Director: Daniel Rotrosen, M.D. 301-496-1886 Email: drotrosen@niaid.nih.gov A.Asthma, Allergy, and Inflammation Branch. Asthma, atopic dermatitis, hypersensitivity reactions, rhinitis, sepsis, sinusitis, urticaria, basic studies of asthma and allergy mechanisms, new therapies to prevent or treat asthma and allergic diseases, food allergies, epidemiology and prevention, phagocyte biology, eosinophilic gastroenteritis, and mechanisms of host defense. Methodologies to design, manage, and analyze clinical and epidemiologic research of the etiology, prevention, and treatment of asthma, allergy, and inflammatory diseases. Chief: Dr. Matthew Fenton 301-451-0144 Email: fentonm@niaid.nih.gov B.Basic Immunology Branch. Origin, maturation, and interactions of immune cells, immune cell receptors, ligands, cytokine biology, molecular basis of activation, antigen recognition, immune tolerance, immune response regulation, hematopoiesis and stem cell biology, enhancement of vaccine effectiveness in neonates and adults, and basic immunology of vaccines and immunotherapeutics as medical countermeasures for biodefense. Chief: Dr. Helen Quill 301-496-7551, Fax: 301-480-2381 Email: hquill@niaid.nih.gov C.Clinical Immunology Branch. Preclinical and clinical research to develop and improve therapies for the treatment of autoimmune diseases, primary immune deficiencies (not HIV), basic research of disease mechanisms, and biomarkers, immunotherapy of disease processes, disorders mediated by lymphocyte products, and mucosal immunity. Chief: Dr. James McNamara 301-451-3121, Fax: 301-480-1450 Email: jmcnamara@niaid.nih.gov D.Transplantation Immunobiology Branch. Acute and chronic graft rejection, allogeneic and xenogeneic transplantation, development of immunomodulatory agents to prevent and treat graft rejection, genomics of the alloimmune response, hematopoietic stem cell transplantation, major histocompatibility complex, minor histocompatibility antigens, infectious and malignant complications of immunosuppression in transplantation, and technologies for MHC typing. Chief: Dr. Nancy Bridges 301-496-5598 Email: nbridges@niaid.nih.gov E.Radiation Countermeasures Program. Radioprotectants, mitigators and therapeutics for acute radiation syndrome or the delayed effects of acute radiation exposure; radionuclide-specific therapies, including chelating agents, blocking agents, and other novel decorporation agents; improved methods of radiation biodosimetry and bioassay for radionuclide contamination; biomarkers of organ-specific radiation injury; therapeutics for radiation combined injury; therapeutics for radiation-induced immunosenescence. Chief: Dr. Richard Hatchett 301-451-3109 Email: hatchettr@niaid.nih.gov Division of Microbiology and Infectious Diseases The Division of Microbiology and Infectious Diseases (DMID) supports research to better understand, treat, and ultimately prevent infectious diseases caused by virtually all infectious agents, except HIV. DMID supports a broad spectrum of research from basic molecular structure, microbial physiology and pathogenesis, to the development of new and improved vaccines and therapeutics. DMID also supports medical diagnostics research, which is defined as research to improve the quality of patient assessment and care that would result in the implementation of appropriate therapeutic or preventive measures. DMID does not support research directed at decontamination or the development of environmentally oriented detectors, whose primary purpose is the identification of specific agents in the environment. Note that some of the organisms and toxins listed below are considered NIAID priority pathogens or toxins for biodefense and emerging infectious disease research. Director: Dr. Carole Heilman 301-496-1884 Email: ch25v@nih.gov A.Bacteriology and Mycology Branch. The branch oversees research on medical mycology, hospital infections (including Acinetobacter, Klebsiella, Serratia, Legionella, Pseudomonas, Aeromonas, Enterobacter, Proteus, non-enteric E. coli, actinomycetes and others), staphylococci, enterococci, bacterial zoonoses (plague, anthrax, tularemia, glanders, melioidosis, Lyme disease, rickettsial diseases, anaplasmosis, ehrlichiosis and Q fever), and leptospirosis. Research is encouraged in the following general areas: (1) product vaccines, adjuvants, therapeutics and diagnostics (including target identification and characterization, device or apparatus development, novel delivery, and preclinical evaluation); (2) products to combat antibacterial and antifungal drug resistance; (3) applied proteomics and genomics; (4) host-pathogen interactions, including pathogenesis and host response; (5) genetics, molecular, and cell biology; (6) microbial structure and function; and (7) vector-pathogen interactions or disease transmission to humans via arthropod vectors. Research in the following areas is of particular interest to the branch, but research on all of the above is welcome: •Vaccines, therapeutics, and medical diagnostics for hospital infections •Adjunctive therapies to combat antimicrobial resistance •Diagnostics for aspergillosis •Novel approaches for the diagnosis of Lyme disease Contact: Dr. Alec Ritchie 301-402-8643, Fax: 301-402-2508 Email: aritchie@niaid.nih.gov B.Enteric and Hepatic Diseases Branch. Special emphasis areas include vaccines against hepatitis C virus; antimicrobials and antivirals that focus on novel targets such as host-pathogen interactions to combat the development of resistance; vaccines and therapies for botulinum neurotoxins, especially therapies that that target toxins once they enter cells; therapies and diagnostics for Clostridium difficile that include recurrent disease issues; development of a simple, rapid point-of-care diagnostic tool for the simultaneous identification of multiple diarrheal pathogens that includes their antibiotic resistance profiles; pediatric vaccines to prevent the major worldwide causes of diarrhea; more stable vaccines and improved formulation methods; and novel therapeutics for chronic hepatitis B and C. Research areas of the Branch include the following organisms and diseases: astrovirus, Bacteroides spp., Campylobacter spp., enteric Clostridia spp. including botulinum neurotoxins, commensals and normal flora, pathogenic Escherichia coli, gastroduodenal disease, gastroenteritis, Helicobacter spp., Listeria spp., Noroviruses including Norwalk, ricin toxin, rotaviruses, Salmonella serovars, Shigella spp., Staphylococcus enterotoxin B, Vibrio spp. enteric Yersinia spp., hepatitis viruses A, B, C, D, and E, as well as cholera, diarrhea, enterotoxins, gastroenteritis, gastroduodenal disease and ulcers, and Guillain-Barre syndrome. Program Contact: Dr. Marian Wachtel 301-451-3754, Fax: 301-402-1456 Email: wachtelm@niaid.nih.gov C.Parasitology and International Programs Branch. Research areas: (1) protozoan infections, including amebiasis, cryptosporidiosis, cyclosporiasis, giardiasis, leishmaniasis, malaria, trypanosomiasis, toxoplasmosis; helminth infections, including cysticercosis, echinococcosis, lymphatic filariasis, schistosomiasis, onchocerciasis, others (e.g., roundworms, tapeworms, and flukes); invertebrate vectors/ectoparasites, black flies, sandflies, tsetse flies, mosquitoes, ticks, snails, mites; (2) parasite biology (genetics, genomics, physiology, molecular biology, and biochemistry); (3) protective immunity, immunopathogenesis, evasion of host responses; (4) clinical, epidemiologic, and natural history studies of parasitic diseases; (5) research and development of vaccines, drugs, immunotherapeutics, and medical diagnostics, and (6) vector biology and management; mechanisms of pathogen transmission. Chief: Dr. Lee Hall 301-496-2544, Fax: 301-402-0659 Email: lhall@niaid.nih.gov D.Respiratory Diseases Branch. Research areas: (1) viral respiratory diseases, including those caused by: human coronaviruses (including SARS), influenza viruses, and paramyxoviruses (including parainfluenza viruses and respiratory syncytial virus); (2) bacterial respiratory infections, including those caused by Moraxella catarrhalis (chronic obstructive pulmonary disease), Pseudomonas aeruginosa and Burkholderia cepacia (associated with cystic fibrosis), Corynebacterium diphtheriae (diphtheria), groups A and B streptococci, Haemophilus influenzae, Neisseria meningitidis, Bordetella pertussis (pertussis), Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Klebsiella pneumoniae and community acquired pneumonia; (3) acute otitis media; (4) mycobacterial diseases, including those caused by: M. tuberculosis (tuberculosis), extensively- and multi-drug resistant M. tuberculosis, M. leprae (leprosy), and M. ulcerans (Buruli ulcer) and other non-tuberculous mycobacterial diseases. Areas of emphasis include: development of new antibiotics with novel mechanisms of action, improved therapeutics for viral and bacterial respiratory diseases including immunotherapeutics, new or improved vaccines (with and without adjuvants), improved and more rapid multiplex point-of-care diagnostic tests or other screening tools that can detect infection prior to active disease and identify drug resistance. Contact: Dr. Gail Jacobs 301-496-5305, Fax: 301-496-8030 Email: ggjacobs@niaid.nih.gov E.Sexually Transmitted Infections Branch. Areas of emphasis include the development of medical diagnostics including better and more rapid multiplex point of care tests and other screening or novel delivery systems for diagnostic tools, topical microbicides, vaccines and drugs for sexually transmitted infections (STIs) and other reproductive tract syndromes, such as bacterial vaginosis; molecular immunology; vaginal ecology and immunology; epidemiologic and behavioral research including strategies to reduce transmission of STIs; genomics and proteomics of sexually transmitted pathogens; adolescents and STIs; STIs and medically underserved populations and minority groups; STIs and infertility and adverse outcomes of pregnancy; role of STIs in HIV transmission; role of HIV in altering the natural history of STIs; and other sequellae of STIs. Contact: Elizabeth Rogers 301-451-3742, Fax: 301-480-3617 Email: erogers@niaid.nih.gov F.Virology Branch. Areas of emphasis for SBIR/STTR applications include:1) vaccine development; 2) viral vectors; 3) structure and function of viruses and viral proteins as targets for therapeutic interventions or diagnostics; 4) the development and validations of assays for disease diagnosis and to measure response to therapy; 5) the development and preclinical testing of immunotherapeutic and antiviral drugs for acute and chronic viral illnesses; 6) approaches to identify antiviral targets and agents; 7) chemical design and synthesis of novel antiviral agents; 8) preclinical antiviral evaluations including in vitro screening and prophylactic or therapeutic antiviral evaluations of human viral infections in animal models; 9) the development of rapid medical diagnostic systems. The Virology Branch focuses on the following: acute viral infections (including Nipah and Hendra viruses), arthropod-borne and rodent-borne viral diseases (including Dengue, West Nile, Japanese encephalitis, Chikungunya, yellow fever, hantavirus, etc.), viral hemorrhagic fevers (Ebola, Lassa fever, etc.), measles, polio, coxsackie virus, enterovirus 71 and other enteroviruses, poxviruses, rabies, and rubella. The Virology Branch also focuses on the following persistent viral diseases and viruses: adenoviruses, BK virus, bornaviruses, coronaviruses, herpesviruses, human T-lymphotrophic virus, JC virus, human papillomaviruses, parvoviruses, and prion diseases. Applications targeting the development of therapies, immunotherapies, vaccines and diagnostics for any of these infections are sought. The Virology Branch does not support applications covering environmental detection and decontamination. Contact: Dr. Ramya Natarajan 301-594-1586, Fax: 301-402-0659 Email: ramya.natarajan@nih.gov Other Research Topic(s) Within the Mission of the Institute For additional information on research topics, contact: Dr. Gregory Milman National Institute of Allergy and Infectious Diseases 301-496-8666, Fax: 301-402-0369 Email: gmilman@niaid.nih.gov For administrative and business management questions, contact: Mr. Michael Wright Grants Management Specialist National Institute of Allergy and Infectious Diseases 301-451-2688, Fax: 301-493-0597 Email: mawright@mail.nih.govHHS201104262011042620110626-1Closed67059http://www.sbir.gov/node/67059The goal of the NCI is to eliminate the suffering and death due to cancer. The Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Programs are NCI's engine of innovation for developing and commercializing novel technologies and products to prevent, diagnose, and treat cancer. NCI’s SBIR and STTR Programs offer funding in nanotechnology, anti-cancer agents, biomarkers, proteomics, diagnostics, imaging technologies, pharmacodynamics, and many more areas of interest to the NCI. NCI’s SBIR and STTR programs focus on research, development and delivery and are critical to achieving the institute’s goals. Research opportunities cited below are not all inclusive; those listed are “open-ended” to encourage submission of innovative projects that fit NCI’s mission. For additional information, access the NCI SBIR homepage: http://sbir.cancer.gov/. In addition, please see the contact list at the end of the NCI section to identify the Program Director within the NCI SBIR Development Center who specializes in your technology area. Phase IIB SBIR Competing Renewal Awards NCI offers Phase IIB opportunities that focus on the commercialization of SBIR-developed technologies. Contact the NCI SBIR Development Center at 301-594-7709, NCISBIR@mail.nih.gov for additional information. Center to Reduce Cancer Health Disparities Established in March 2001, CRCHD is the cornerstone of the Institute’s efforts to reduce the unequal burden of cancer in our society. A central goal of the Center is to translate research discoveries into policies and/or services aimed at reducing cancer-related health disparities in racial, ethnic, elderly and medically underserved communities. To learn more about the Center, please visit our website: http://crchd.cancer.gov. The Center is interested in the following SBIR/STTR applications: A.Communication. Training tools to help health professionals deal with issues concerning health literacy and cultural competency. B.Health Care and Epidemiology. Computer software and hardware for hand-held data input and analysis devices; databases and other tools to study patterns of cancer care in underserved communities. C.New Technology. Instrumentation to facilitate early detection and screening, including telemedicine and remote medical imaging, and bioengineering technology (including nanotechnology) applied to cancer detection and diagnosis in underserved communities. D.Geographic Information Systems. Simple, low-cost mapping software to overlay cancer patterns with socioeconomic data, health system infrastructure, healthcare, personal behaviors, ethnicity, risk factors, and consumer profiling among underserved communities. E.Human Genomics. Tools and technology for health care providers using cancer research developments from genomics, pharmaco-genetics and proteonomics for underserved populations. Division of Cancer Biology The Division of Cancer Biology (DCB) plans and directs, coordinates, and evaluates a grant- and contract-supported program of extramural basic research on cancer cell biology and cancer immunology, and cancer etiology, including the effects of biological, chemical and physical agents, in the promotion of cancer; maintains surveillance over developments in its program and assesses the national need for research in cancer biology, immunology and etiology; evaluates mechanisms of biological, chemical and physical carcinogenesis and subsequent tumor growth and progression to metastasis; tests for carcinogenic potential of environmental agents; and serves as the focal point for the Federal Government on the synthesis of epidemiological and experimental data concerning biological agents relating to cancer. For additional information, please visit our home page at http://www.nci.nih.gov/dcb/dcbhom.htm. A.Cancer Cell Biology. The Cancer Cell Biology Branch (CCBB) seeks to understand the biological basis of cancer at the cellular and molecular level. This research utilizes lower eukaryote and animal models, and animal and human tumor cells and tissues to analyze the mechanisms responsible for the growth and progression of cancer. Specific research and technologies supported by CCBB include but are not limited to the following: 1.Development of novel methods and tools to study key aspects of programmed cell death including its regulation and modulation. 2.Development of methods to identify and isolate tissue-specific stem cells. 3.Development of markers associated with specific cellular processes or differentiation. 4.Development of novel techniques, tools, and vectors to transfer functional genes, proteins, antibodies, etc. into intact cells or organisms. 5.New or improved technologies for the efficient microdissection of tumor tissue sections to isolate and preserve human cancer cells appropriate for research. 6.Generation of new inbred genetic animal models that transmit defective or altered cancer-related genes. 7.Development of novel technologies, methodologies, tools, or basic instrumentation to facilitate basic cancer research (research tools). 8.Development of methods and tools to study processes of protein trafficking, post-translational modification, and degradation. 9.Development of novel methods and tools for the analysis of intracellular organelles. 10.Development of novel methods and tools to determine intracellular gradient status. 11.Improved extraction methodologies and tools for tumor specimens for the subsequent analysis of DNA, RNA, and proteins. 12.Development of new or improved methods to isolate intact cellular regulatory complexes for functional studies. 13.Development of novel methods and tools to examine key cellular communication pathways. 14.Improved extraction methodologies and tools for tumor specimens for the subsequent analysis of DNA, RNA, and proteins. 15.Development of new or improved methods to isolate intact cellular regulatory complexes for functional studies. 16.Development of novel methods and tools to examine key cellular communication pathways. B.Cancer Etiology. The Cancer Etiology Branch (CEB) supports research that seeks to determine the role of chemical, physical and biological agents as factors or cofactors in the etiology of human and animal cancer. The biological agents of primary interest are DNA viruses, RNA viruses, AIDS and AIDS-associated viruses, although the research may encompass all forms of life including bacteria and other microbial agents associated with cancer and use animal models of cancer and cancer vaccines. Chemical Carcinogenesis studies are concerned with cancers initiated or promoted by chemical or physical agents. A wide range of approaches are supported, including studies of the genetics of cell transformation, mutagenesis, tumor promotion and DNA damage, as well as studies of basic biochemistry and molecular biology of oncogenic and suspected oncogenic agents, viral oncogenes and associated tumor suppressor genes, pathogenesis and natural history studies, animal models, and preventive vaccine research. Mechanistic studies are encouraged in areas such as metabolism, toxicity and physiological distribution of carcinogens, genetics and regulation of enzymes, biochemical and molecular markers, and organ and cell culture systems and animal models. Also of interest are studies on cancer etiology by environmental chemicals, tobacco consumption and exposure, nutritional hazards, alcohol, asbestos, silica, and man-made fibers. CEB supports studies on endogenous exposure to steroid hormones and the generation of oxygen radicals during normal metabolism, studies on phytoestrogens and xenoestrogens and their impact on the metabolism of endogenous estrogens. In addition, CEB supports the development of analytical technologies to facilitate studies relating to carcinogenesis and mutagenesis. Specific research and technologies supported by CEB include but are not limited to the following: 1.Development of reagents, probes, and methodologies to evaluate the etiologic role of oncogenic viruses and other microbial agents (such as bacteria) in human cancer. 2.Development of novel in vitro culture techniques for oncogenic viruses or other microbial agents associated with or suspected of causing human cancer. 3.Development of sensitive, simplified diagnostic kits or reagents for the detection of oncogenic viruses or other microbial agents. 4.Development and characterization of animal models for studies of the mechanism of cancer induction by viruses or other microbial agents. The animals should faithfully mimic the human diseases associated with the virus or other microbial agent. 5.Development of methods (e.g., new-anti-microbial compounds, new vaccine approaches) to avert the induction of neoplasia in humans and animals by oncogenic viruses or bacteria. 6.Development of other novel technologies, methodologies or instrumentation to determine the role of biological agents, especially viruses, in the etiology of cancer. 7.Development and validation of methods for food treatment, preparation, or processing that will reduce or eliminate carcinogen/mutagen content. 8.Development of rapid analytical techniques for the qualitative and quantitative detection and screening of xenobiotics, chemical contaminants, and carcinogens/mutagens in human foods and biological and physiological specimens. 9.Development of in vitro and in vivo models for basic studies of carcinogenesis in specific organ systems, such as the pancreas, prostate, ovary, central nervous system, kidney, endometrium, stomach, and upper aerodigestive tract. 10.Development of methods for the production of carcinogens, anticarcinogens, metabolites, biomarkers of exposure, oxidative damage markers, and DNA adducts, both labeled and unlabeled, which are neither currently available commercially nor offered in the NCI Chemical Carcinogen Reference Standard Repository. The production of these compounds, in gram quantities, is desired for sale/distribution to the research community. 11.Development of methods for detection, separation, and quantitation of enantiomeric carcinogens, metabolites, adducts, and biomarkers of carcinogen exposure. 12.Development of monoclonal antibodies that are specific for different carcinogen-nucleoside adducts and demonstration of their usefulness in immunoassays. Of particular interest are antibodies to alpha-beta unsaturated carbonyl compounds (such as acrolein and crotonaldehyde) which can form exocyclic nucleoside adducts with DNA, and immunoassays for carcinogen/protein adducts as potential biomarkers of exposure. 13.Development of immunoassays using monoclonal antibodies that are specific for different polymorphs of Phase I and II carcinogen-metabolizing enzymes and repair enzymes. Included, but not limited to, are antibodies to the cytochrome P450 isozymes, glutathione S-transferases, and N-acetyl transferases. 14.Development of rapid, sensitive, and quantitative assays for the identification and measurement of androgens, estrogens, phytoestrogens, and xenoestrogens in complex biological matrices. 15.Development of rapid analytical techniques for the direct measurement of ligand-protein receptor interactions and determination of binding coefficients. 16.Development of analytical instrumentation for the detection and quantitation of extremely low levels of Tritium (3H) or 3H and Carbon-14 (14C) from biological samples. Of particular interest is the development of small-sized, accelerator-based mass spectrometry equipment capable of measuring down to, or below, contemporary background levels of 3H and 14C that would make this sensitive technique more widely available to research groups. The design and development of technologically improved and miniaturized individual components, including ion source, sample preparation (autosampling apparatus), accelerator, and mass spectrometric detectors, are also solicited. 17.Synthesis of selective suicide inhibitors of cytochrome P450 isoforms and selective arachidonic acid pathway inhibitors/ enhancers for basic biochemical studies and anticarcinogenic potential. 18.Development of invertebrate animal models (such as Drosophila, C. elegans, clam, and sea urchin) for the study of environmental chemicals and/or hormonal carcinogenesis. 19.Development of more efficient and reliable methods of preserving valuable animal model gene stocks by innovative in vitro techniques. 20.Development of a defined diet for support and maintenance of aquatic and marine fish models of cancer including but not limited to swordtail, zebrafish, medaka, mummichog, guppy, Fugu, and Damselfish. 21.Development of serum free tissue culture media for aquatic and marine fish models of cancer. C.Cancer Immunology and Hematology. The Cancer Immunology and Hematology Branch (CIHB) supports a broad spectrum of basic research focused on the earliest stages of hematopoiesis and tracing the molecular events that lead to the development of all the functional elements of the immune system and, when errors occur, to the development of leukemias and lymphomas. Most research of interest falls into three major areas. The first is the immune response to tumors to include studies of all of the cells (T, B, NK, antigen-presenting, and other myeloid cells) and secreted molecules (antibodies and cytokines) of the immune system that can recognize and affect tumor growth. Emphasis is placed on the alteration in the mechanisms responsible for the failure of immune response to eradicate most tumors under normal conditions, and the development of strategies to circumvent these mechanisms. A second major area of interest examines the biology of hematopoietic malignancies to describe the molecular biology reasons underlying the cell's failure to respond to normal growth controls and to develop novel approaches to prevention or therapy. The third distinct area supported is the basic biology of bone-marrow transplantation, including studies of host cell engraftment, graft-versus-host disease, and the basis of the graft-versus-leukemia effect. Specific research and technologies supported by CIHB include but are not limited to the following: 1.Development of improved or novel monoclonal antibody technologies including improvements of methodologies for fusion, production of novel cells as fusion partners, selection and assay of antibody producing clones, and production of new and improved monoclonal antibodies. 2.Synthesis, structure and function of antibodies capable of reacting with tumor cells, agents that induce tumors and agents used in the treatment of tumors. 3.Development of in vivo animal models systems that can be used to study the immune response to tumors and the mechanisms of immunotherapy. 4.Synthesis, structure and function of soluble factors that participate in, activate and/or regulate hematopoietic cell growth and the immune response to tumors, including interferons, other lymphokines and cytokines (interleukins), hematopoietic growth factors, helper factors, suppressor factors and cytotoxic factors. 5.Application of biochemical, molecular biological and immunological techniques for identifying tumor antigens that are good targets for the development of vaccine-type strategies of cancer immunotherapy. 6.Development of techniques to enhance the immune response to tumors, including modification of tumor cells and/or antitumor lymphocytes to facilitate cancer vaccine strategies. 7.Development of improved methodology for manipulating bone marrow inoculum to decrease the incidence of graft-versus-host disease without increasing the risk of graft failure or leukemic relapse. 8.Development of improved methodology for increasing the number of peripheral blood stem cells available for harvest for use in transplantation, including improved methods of identifying and removing residual leukemic cells in the autologous transplant setting. 9.Development of methods to identify and define human minor histocompatability antigens. 10.Development of novel culture systems to improve the expansion of lymphocytes and dendritic cells. 11.Development of the combination of cell culture and other research tools to better expand human hematopoietic stem cells. 12.Development of improved techniques for computational simulation/modeling of biological processes involved in immunologic defenses against tumor cells such as signal transduction, cell cycle progression, and intracellular translocation. 13.Development of other novel technologies, methodologies or instrumentation to facilitate basic research in either tumor immunology or cancer hematology. 14.Development of molecular, cellular or biochemical techniques to isolate and/or characterize tumor stem cells from hematologic malignancies. D.DNA and Chromosome Aberrations. The DNA and Chromosome Aberrations Branch (DCAB) seeks to study the genome at the DNA and chromosome level, including discovery of genes at sites of chromosome breaks, deletions, and translocations; DNA repair; structure and mechanisms of chromosome alterations; epigenetic changes; radiation- and chemical-induced changes in DNA replication and other alterations; and analytical technologies. Specific research and technologies supported by DCAB include but are not limited to the following: 1.Development of new, improved technologies for characterization of chromosomal aberrations in cancer. 2.Development of new, improved, or high throughput technologies for whole genome scanning for chromosome aberrations in cancer. 3.New or improved technologies to increase accuracy of karyotypic analyses of tumor specimens. 4.New or improved methods to mutate or replace genes at specific sites in intact cells. 5.Development of new, sensitive methods to assess the methylation status of genes. 6.Development and distribution of genomic resources suitable for genomic manipulation or cytogenetic studies. 7.Technologies for assaying for mammalian genes relevant to repair of damage induced by exposure of mammalian cells to ionizing and non-ionizing radiations, with special emphasis on human cells. 8.Methods/approaches to study the repair of DNA lesions induced by exposure of mammalian cells to ionizing radiations (both high- and low-LET). 9.Development and characterization of human cell lines with specific DNA-repair deficiencies. 10.Development of genetic constructs that utilize radiation-responsive regulatory genes to control the expression of targeted structural genes in mammalian cells. 11.Development of new methods/technologies to assay transcription factor binding sites across whole genomes. 12.Use of RNAi and siRNA in the development of novel methods and tools for the study of gene expression, gene silencing, gene regulation, and genome-wide screening in cells and tissues. 13.Development and integration of nanotechnology and microfluidics in the analysis of DNA and chromosomal aberrations and the identification, mapping, and cloning of cancer susceptibility and resistance genes. 14.Development of human tumor cDNA library banks to study gene expression in cancer. 15.Generation of new or improved animal models or non-mammalian models (e.g. flies, worms) as research tools to study human cancers. E.Mouse Models of Human Cancers Consortium. The Mouse Models of Human Cancer Consortium is a program based in the Office of the Director, DCB. The Consortium has the important goal of providing mouse cancer model-related resources and infrastructure to the research community, in part through various outreach activities. The outreach requirement generates the need for innovative educational or informational materials that convey the content of Consortium meetings and symposia, or document hands-on workshops in which models or techniques that are pertinent to mouse modeling are demonstrated. The instructional materials may be CD-ROMs, videotapes, Web-based interactive programs, or other media. F.Structural Biology and Molecular Applications. The Structural Biology and Molecular Applications Branch (SBMAB) focuses on structural and molecular studies to explore the processes of carcinogenesis and tumorigenesis. Areas of interest include structural biology, genomics, proteomics, molecular and cellular imaging, enzymology, bio-related and combinatorial chemistry, bioinformatics, systems biology and integrative biology as they apply to cancer biology. Interests also include modeling and theoretical approaches to cellular and molecular dimensions of cancer biology. Specific research and technologies supported by SBMAB include but are not limited to: 1.Development of new, improved, or high throughput technologies for whole genome scanning for gene identification. 2.Development of systems that will automate the technology of culturing or assaying single cells. 3.New or improved technologies for efficient microdissection of tumor tissue sections for the development of tissue arrays. 4.Improved extraction techniques for tumor specimens for subsequent DNA, RNA, and protein analyses. 5.Rapid methods to isolate intact complexes of regulatory proteins and to separate and identify the proteins for biophysical studies. 6.New or improved technologies for the preservation of small amounts of DNA/RNA/protein samples 7.Development of new techniques and vectors for transfer of genes, proteins, and antisense molecules into cells. 8.Generation of software and computer models for the prediction of macromolecular structure and function. 9.Development of bioinformatic tools for the study of cancer biology including facilitating genome data, gene “mining,” cluster analysis, and data base management. 10.Development of novel gene technology (e.g., microarray, differential display technology) for measurement of differential gene expression levels and functional genomics studies. 11.Development of novel proteomic tools for the analysis of protein expression in cancer biology. 12.Computer-based methodologies to assist in the understanding of signal transduction and cancer biology. 13.Methodologies and techniques for the imaging of macromolecules in vitro and in vivo. 14.Development of other novel technologies, methodologies or instrumentation to facilitate basic research (research tools) in cancer biology. 15.Develop new approaches and technologies for the structural determination of large biomolecular complexes. 16.Development and integration of nanotechnology approaches and tools in basic cancer biology research. 17.Application and development of novel approaches for in vivo and in vitro modifications of protein expression in cells and tissues, e.g. RNAi, microRNA, other small molecules. 18.Mathematical and theoretical models for the understanding of cancer biology. 19.Development of new software and lab analysis tools that will improve the recording and collection of data and experimental protocols in order to facilitate cancer biology research. 20.Technology and software for elucidating molecular interactions and networks. 21.Develop new, improved or high-throughput technologies for analyzing epigenomic changes. 22.Improved software for the integration of heterogeneous data sources. 23.Development of new, improved or high-throughput technologies for understanding the cancer metabolome. G.Tumor Biology and Metastasis. This branch supports research that seeks to understand the interactions of cancer cells with the tumor and/or host microenvironment in order to delineate the molecular mechanisms and signaling pathways of tumor angiogenesis and lymphangiogenesis, cell migration and invasion, tumor progression, and metastasis. This includes examination of cell-cell and cell-matrix interactions, and the roles played by cell growth factors and cytokines, adhesion molecules, cytoskeleton and the nuclear matrix, and matrix-degrading enzymes, as well as studies on the pathology and biology of solid tumors and tumor bearing animals, and the development of technology to facilitate these studies. Emerging areas of emphasis are the microenvironment created by inflammation and the inflammatory signaling molecules in tumor initiation and progression and the role of somatic stem cells in determining tumor progression and metastatic behavior. Stem cell motility, positional information cues from surrounding tissue and adhesion properties together with issues of epithelial-mesenchymal transitions related to cancer progression are supported. Emphasis is also placed on the role of the extracellular matrix and tissue microenvironment during development and tissue morphogenesis, and on the role of glycoproteins in tumor growth, invasion, and metastasis. The branch also focuses on the function of steroid hormones, their receptors and coregulators during tumor growth and progression. Models utilized in these studies may include animal models, tumor tissues/cells, their components, or their products. The development of organotypic models that closely mimic in vivo models is encouraged. Specific research and technologies supported by TBMB include but are not limited to: 1.New technical strategies to identify and assess the function of components of the extracellular matrix. 2.Development of new in vitro cancer models to study the pathology and biology of solid tumors and tumor bearing animals. 3.New in vivo models of angiogenesis, lymphangiogenesis, cancer progression and metastasis. 4.Development of technologies to identify novel factors that modulate angiogenesis and lymphangiogenesis. 5.Identification of genes and/or enzymes associated with glycosylation in tumor cells. 6.Identification of novel coregulators of nuclear steroid receptor superfamily. 7.Development of improved techniques for computational simulation/modeling of biological processes involved in malignant transformation, persistence, or invasion, such as signal transduction, cell cycle progression, and intracellular translocation. 8.Development of new assays or methods to evaluate tumor cell invasiveness. 9.Development of new assays or methods to study molecules and pathways involved in cell-to-cell signaling or communication. 10.Development of appropriate new animal, cellular or organotypic models to study tumor stroma interactions, 3-D models that closely mimic in-vivo conditions. 11.Study roles of cytokines/growth factors released by host cells during inflammation, invasion, tumor progression and metastasis. Division of Cancer Control and Population Sciences The Division of Cancer Control and Population Sciences conducts basic and applied research in the behavioral, social, and population sciences, including epidemiology, biostatistics, and genetics that, independently or in combination with biomedical approaches, reduces cancer risk, incidence, morbidity, and mortality. Laboratory, clinical and population-based research, and health care are translated into cancer prevention, detection, treatment, and rehabilitation activities that cross the life span and the entire process of carcinogenesis, from primary behavioral prevention in youth, to screening, treatment, and survivorship. For additional information, please visit our home page at http://dccps.nci.nih.gov. A.Epidemiology and Genetics. The Epidemiology and Genetics Research Program supports research in epidemiology, biometry, genetic epidemiology, molecular epidemiology, nutritional epidemiology, infectious epidemiology, environmental epidemiology, computing methodology, and multidisciplinary activities related to human cancers. The topics of interest to the Epidemiology and Genetics Research Program (EGRP) are: •Tools for assessment of exposures and biomarkers: oDevelopment of methods for measuring biomarkers of human exposure or susceptibility, and of nutritional status, and methods for monitoring changes in biomarkers for use in cancer epidemiologic studies. oDevelopment of new or improved devices for quantitative measurement of human exposure to environmental carcinogens for epidemiologic studies. oDevelopment of methods to evaluate potential cancer clusters for epidemiologic studies. •Tools for cancer epidemiology studies: oDevelopment of tools to model cancer risks from environmental and occupational agents. oDevelopment of software for electronic capture of risk factor data for cancer epidemiologic studies. oBuild consumer-friendly risk prediction models from epidemiologic data. oDevelopment of software for tracking biological specimens for cancer epidemiologic studies. oDevelopment of software for electronic identification, screening, and recruitment of participants, especially minorities, into epidemiologic studies. oDevelopment of Web-based data collection or applicable bioinformatics tools for cancer epidemiology. oDevelopment of software or methods for rapid case ascertainment of cancers. oDevelopment of geographic information systems with special visualization techniques for the simultaneous assessment of environmental exposures and health outcomes. oDevelopment of tools using publicly available data to identify population-based controls for epidemiologic studies. oDevelopment of software for analysis of DNA methylation biomarkers for early detection of prostate or breast cancers with use of specimens from biorepositories. oMicroRNA Profiling in Epidemiologic studies. oDetection of mitochondrial DNA alterations for Cancer Epidemiologic studies. For more information on this program please go to http://epi.grants.cancer.gov. B.Multimedia Technology and Health Communication in Cancer Control. Over the past few decades, advances in technology have played a key role in enhancing the quality of cancer care through improvements in the prevention, diagnosis, and treatment of cancer. A driving force fostering the utilization of media technology to develop cancer communication products and their dissemination is NCI’s Multimedia Technology and Health Communication SBIR/STTR Program. The Program serves as an ‘engine of innovation’ translating cancer research into commercially viable products for primary care professionals, researchers, patients and their families, and the general public. The objectives of this program are to (1) fund science-based, theory-driven, user-centered grants and contracts to translate cancer research into programs, interventions, systems, networks, or products needed by professionals or the public to reduce cancer risk or improve the quality of life of cancer survivors; (2) promote the use of innovative media technology and/or communication approaches in cancer prevention and control applications used in medical and community settings; (3) improve communication behaviors of primary care professions, patients, and care-givers in cancer-related matters; (4) promote organizational infrastructures changes that promote the use of products developed in the program; (5) promote the development of system models; and (6) expand the methods for evaluating ehealth research and developed products. Investigators interested in applying for grants in this SBIR program should access: http://cancercontrol.cancer.gov/hcirb/sbir/ for a list of topics that address current gaps in ehealth research and that are updated during the fiscal year. This site also provides important program requirements and other SBIR information. Division of Cancer Treatment and Diagnosis The Division of Cancer Treatment and Diagnosis funds research into the development of tools, methodologies and therapeutic agents that will better diagnose, assess, cure and effectively treat cancer. We support a spectrum of research projects from preclinical exploratory research and development through clinical trials. A.Cancer Diagnosis. The Cancer Diagnosis Program (CDP) supports the development of technologies, reagents, instrumentation, and methodologies to improve cancer diagnosis or prognosis or to predict or assess response to therapy. This does not include technologies for imaging of patients. CDP also supports the adaptation or improvement of basic research technologies for use as clinical tools. Technologies supported by CDP may be designed to work with tissues, blood, serum, urine, or other biological fluids. Technologies supported by CDP include but are not limited to the following: 1.Technologies for comprehensive and/or high throughput analysis of molecular alterations at the level of DNA, RNA, or protein. Includes for example, mutation detection systems, gene expression arrays, systems for monitoring epigenetic changes (alternative splicing or methylation), high throughput proteomics (including post-translational modification and protein-protein interactions and methods for protein quantitation). 2.Micro-electro mechanical systems (MEMs) and other nanotechnologies for the analysis of DNA, RNA, or protein (e.g., micro-capillary systems, lab on a chip applications, micro-separation technologies). 3.Mass spectrometry for the analysis of nucleic acids or proteins. 4.Discovery and development of new or improved diagnostic markers or probes targeting changes in DNA, RNA, or proteins, including the generation of molecular diversity libraries by phage display and other combinatorial techniques, and affinity-based screening methods. 5.cDNA library technologies, including improved methods for generating high quality cDNA clones and libraries and methods for generating high quality cDNA from tissues (including archived specimens). 6.Resources for clinical research. a.Instruments, technologies or reagents for improved collection, preparation, and storage of human tissue specimens and biological fluids. b.Improved methods for isolation and storage of DNA, RNA, or proteins. c.Tissue and reagent standards: development of standard reagents such as representational DNA, RNA, and proteins and standard tissue preparations to improve the quality of or facilitate the validation of clinical laboratory assays. d.Methodologies for directed micro-sampling of human tissue specimens, including for example, new or improved methodologies for tissue microarrays. 7.Tissue preservation: fixatives and embedding materials or stabilizers that preserves tissue integrity and cellular architecture and simultaneously allows molecular analysis of DNA, RNA, or proteins. 8.Bioinformatics. a.Methods for acquisition and analysis of data associated with molecular profiling and other comprehensive molecular analysis technologies, including for example, analysis of microarray images and data as well as methods to combine, store and analyze molecular data produced by different techniques (e.g., combined analysis of proteomics and gene expression data). b.Methods for collecting, categorizing or analyzing large data sets containing pathology data or histological images and associated clinical or experimental data, including for example, tumor marker measurements, tissue microarray data, and other relevant biological information. c.Software/algorithms to interpret and analyze clinical and pathology data including methods that relate data from clinical databases to external data sources. Includes for example, neural networks, artificial intelligence, data-mining, data-trend analysis, patient record encryption protocols, and automatic diagnostic coding using standard nomeclatures. d.Informatics tools to support tissue procurement and tissue banking activities. 9.Statistical methods and packages designed for data analysis including correlation of clinical and experimental data. 10.Automated Cytology. a.High resolution image analysis for use with specimens (e.g., blood, tissues, cells) and tissue microarrays. b.Instrumentation including microscopy and flow cytometry. c.CGH, FISH, immunohistochemical staining and other hybridization assays using probes with fluorescent or other novel tags. d.Methods for single cell isolation and sorting. e.Methods for single cell classification and analysis. 11.Instrumentation for the detection and diagnosis of tumors, including endoscopy and magnetic resonance spectroscopy (MRS). 12.Immunoassays using monoclonal, polyclonal, or modified antibodies. Affinity-based binding assays using libraries of aptamers including chemical ligands, small peptides or modified antibodies. For additional information about areas of interest to the CDP Technology Development Branch, visit our home page at: http://cancerdiagnosis.nci.nih.gov. B.Biochemistry and Pharmacology. Preclinical and Exploratory Investigational New Drug (IND) studies designed to improve cancer treatment. General areas of interest: Discovery of new drugs or drug combinations and treatment strategies, selective targeting, development of clinically relevant preclinical models, pharmaceutical development, ADME (absorption, distribution, metabolism and excretion) studies and toxicologic evaluations, understanding mechanisms of drug actions (responses to therapies), and preventing and overcoming drug resistance. Areas of current emphasis: Molecular targeted approaches, including application of safety and efficacy biomarkers to the discovery and development of drugs; application of advanced technologies, such as nanotechnology and imaging technologies, to improved assays for quantitation of safety and efficacy biomarkers; approaches that reduce costs and increase speed of preclinical drug development; and approaches that will lead to “personalized medicine,” including better predictions of drug response and adverse reactions, drug-drug interactions, and drug efficacy monitoring. For additional information, please visit our home page at http://dtp.nci.nih.gov and select “Grants/Contracts.” 1.Drug Discovery. a.Design and synthesize novel compounds for evaluation as potential anticancer agents. Synthesize simpler analogs of complex antitumor structures that retain antitumor activity. b.Develop computer modeling and biophysical techniques such as x-ray crystallography and NMR spectroscopy. c.Design prodrugs of anticancer agents that are selectively activated in cancer cells. d.Discover new anticancer agents that exploit unique properties of tumors, that induce or modulate apoptosis, or that induce or modulate differentiation. e.Design and synthesize anticancer prodrugs, latent drugs, or modifiers of cancer drug metabolism or excretion. f.Develop ways to produce adequate quantities of promising natural products or natural product derivatives through total synthesis. g.Develop scale-up and manufacturing technology for the synthesis of materials with promising anticancer potential. h.Develop chemical libraries for anticancer drug screening programs. The generation of small molecular weight libraries (HHS201104262011042620110626-1Closed67059http://www.sbir.gov/node/67059The mission of the NlDA is to lead the nation in bringing the power of science to bear on drug abuse and addiction, through support and conduct of research across a broad range of disciplines and by ensuring rapid and effective dissemination and use of research results to improve prevention, treatment, and policy. For additional information about areas of interest to the NIDA, please visit our home page at http://www.nida.nih.gov/. Phase IIB Competing Renewal Awards NIDA will accept SBIR/STTR Phase IIB Competing Renewal grant applications from Phase II SBIR/STTR awardees to continue the process of developing products that require approval of a Federal regulatory agency. Such products include, but are not limited to: medical implants, drugs, vaccines, and new treatment or diagnostic tools that require FDA approval. This renewal grant should allow small businesses to get to a stage where interest and investment by third parties is more likely. Transitioning a new molecular entity from preclinical to the clinical phase of development, requires large-scale production of the new molecular entity and toxicity testing, activities which are both costly and time consuming. The cost and time constraints imposed by advanced stage development of a new molecular entity pose significant obstacles for small businesses. Although Phase I and Phase II SBIR support is sufficient for initial discovery efforts (e.g., compound synthesis and some in vitro and in vivo preclinical pharmacological testing), it is not adequate to support either the kind of developmental work needed for compliance with the FDA’s requirement for an investigational new drug (IND), or for clinical trials. This announcement adds another three years of support to SBCs for drug development by providing a second stage of Phase II SBIR funding through the mechanism of a Phase IIB SBIR Competing Renewal grant. It is recognized that an award of this type may not support the entire medications development timeline for any given drug. The Competing Renewal grant will however, allow small businesses to carry a medication from the preclinical to the clinical stage, which will aid in attracting interest and investment by third, parties, and provide an important resource for new pharmaceuticals for the treatment of substance abuse. Please contact Kris Bough (contact information provided below) before beginning the process of putting an application together. Prospective applicants are strongly encouraged to contact NIH staff prior to submission of a Phase IIB Competing Renewal application. Prospective applicants are strongly encouraged to submit to the program contact a letter of intent that includes the following information: •Descriptive title of the proposed research •Name, address, and telephone number of the Principal Investigator •Names of other key personnel •Participating institutions Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NIH staff to estimate the potential review workload and plan the review. It is expected that only a portion of NIDA SBIR/STTR Phase II awards will be eligible for a Phase IIB Competing Renewal grant. The following examples would make appropriate topics for proposed SBIR or STTR Phase IIB Competing Renewal projects. These are meant for illustrative purposes only and are not exclusive of other appropriate activities. Research and development efforts can be focused on medications for the treatment of cocaine, methamphetamine, and other stimulant abuse, as well as towards opiate, cannabis, PCP and club drugs. The medications under development should be targeted towards attainment of abstinence, maintenance, and/or relapse prevention. •Preclinical studies, including pharmacology and toxicology, beyond those conducted under the initial SBIR Phase I and Phase II grants. The studies conducted under the previous grants should be sufficient to provide a sound rationale for continued development of the entity or entities. •Completion of studies as required by the FDA for an IND application. •Human laboratory clinical trials to determine a medication's safety profile, metabolism, cardiovascular effects, interaction with drugs of abuse, etc. •Clinical studies to assess the efficacy of the medication under development. Kristopher Bough, Ph.D. Program Officer, Medications Research Grants Branch (MRGB) Div. of Pharmacotherapies and Medical Consequences of Drug Abuse NIH - National Institute on Drug Abuse (NIDA) 6001 Executive Boulevard Room 4153, MSC 9551 Bethesda, MD 20892 Express mail/courier use: Rockville, MD 20852 Tel: 301-443-9800, Fax: 301-443-9649 Email: boughk@mail.nih.gov Division of Basic Neuroscience and Behavioral Research (DBNBR) DBNBR’s basic neuroscience and behavioral research focuses on understanding the mechanisms, characteristics, and processes of drug abuse both in adult and developing organisms. Basic behavioral, cognitive, neurobiological, cellular, molecular, chemical, and genetics research aims at characterizing and understanding drug seeking, compulsive behavior, and addictive processes. These research areas necessarily include studies of normal processes. Using both animal and human studies, basic behavioral research focuses on behavioral and cognitive processes that may or do lead to drug initiation, and the behavioral and cognitive consequences of drug abuse. Neurobiology research focuses on the neural mechanisms and substrates underlying behavioral and cognitive processes and vulnerability factors associated with drug abuse, addiction, sensitization, tolerance, and relapse. DBNBR also supports basic chemistry and pharmacological studies focusing on structure/activity relationships, definition, and characterization of systems involved in drug actions, chemical synthesis of new ligands, pharmacokinetics, analytical methods, understanding basic mechanisms of drug action and drug testing. The focus of maternal and paternal drug use is to ascertain the consequences of drug exposure on brain development as well as on other physiological systems. Computational and theoretical modeling of biological systems and behavioral processes, biomedical computing and/or information science and technology development is supported by DBNBR. 1.Metabolomics in Drug Abuse Research. Metabolomics is the study of all molecules of a cell or organism and their identification and quantification that helps to understand the cellular regulation, metabolic pathways and activity and response under normal and other conditions. This technique thus could be used to develop metabolic profiling of normal or healthy subjects and subjects under the influence of substances of abuse or those undergoing drug rehabilitation programs. NIDA is looking for applications on development of novel metabolomics technologies toward practical application in pathway and network investigation in biological systems particularly in understanding the mechanisms of drug addiction and discovering biomarkers for developing treatment for drug addiction. Phase I application should demonstrate the feasibility of developing new metabolomics technology and phase II should focus on the application of this technology in drug abuse research. Hari H. Singh, Ph.D. 301-443-1887 E-mail: hs87j@nih.gov 2.Development of Alternate Drug Delivery Dosage Forms for Drugs Abuse Studies. SBIR applications are solicited to design and develop alternate dosage forms for drugs that are not orally administered such as nicotine, marijuana, heroin, etc. Phase I should demonstrate the feasibility of the proposed innovation and Phase II, the development and testing of the innovation. Hari H. Singh, Ph.D. 301-443-1887 E-mail: hs87j@nih.gov 3.Discovery of New Chemical Probes. SBIR applications are solicited to discover new chemical compounds as biological probes either by synthesis or isolation from natural resources in studying the mechanisms of action of drugs of abuse. Such substances could be new chemical compounds, drug products, or peptides. Currently there are several ligands available through the NIDA drug supply system such as SR 141716A, SR144528, CP 55,840, anandamide, epibatidine, Kaffiralin 1 and 2, etc. All probes for cannabinoids, neuropeptides, nicotinic acetylcholinergic receptors and related probes for drug abuse study are encouraged. In addition applications on biological screening of such new compounds as potential ligands for drug abuse research will also be considered. Phase I should demonstrate the feasibility of the proposed innovation and Phase II, the development, characterization, testing, and screening of innovation. It should also be demonstrated that the new or modified chemical compounds are suitable for drug abuse research. Rao S. Rapaka, Ph.D. 301-443-1887 Email: rr82u@nih.gov 4.Discovery and Study of Psychoactive Components of Botanicals. NIDA is looking for applications to develop methods for the isolation, purification, identification and characterization of active and inactive ingredients of herbal plants (stimulants, hallucinogenic, analgesics, and/or narcotics) and evaluation of their biological properties. Such studies may include chemistry, toxicology, pharmacodynamics, pharmacokinetics and the mechanisms of action of active and inactive ingredients to understand their efficacy, usefulness, adverse effects and abuse potential. Phase I should demonstrate the feasibility of the proposed innovation and Phase II, the development, characterization, testing, and screening of innovation. Rao S. Rapaka, Ph.D. 301-443-1887 Email: rr82u@nih.gov 5.Virtual Reality for Treatment of Pain. Virtual Reality (VR) exposure can reduce reported pain during wound care. Grant applications are sought to examine the utility of VR technologies in the treatment of various types of pain. Development of treatments for both acute and chronic pain is sought. These treatments can be based in clinical settings or the patients’ homes. Phase I testing should establish the feasibility of the use of this technology in the particular population to be tested. Phase I should also produce data that demonstrates that this methodology is effective for the particular type of pain being treated. Phase II should involve larger-scale testing (e.g., more subjects and treatment trials) examining various treatment parameters (e.g., timing of treatment, types of VR environments). The focus of Phase II testing should be the refinement of this treatment for use in pain patients. David Thomas, Ph.D. 301-435-1313 Email: dt78k@nih.gov 6.Virtual Reality for the Treatment of Drug Abuse. Virtual Reality (VR) can be a useful clinical tool. In this particular study, VR exposure was used to allow patients to selectively not attend to an otherwise painful procedure. Drug abuse, like pain, is a problem that is strongly impacted by stimuli in the abuser’s environment and psychological factors. Thus, it is reasonable to assume that VR may be useful in allowing individuals to ignore drugs cravings, withdrawal symptoms or environmental cues that promote drug abuse. Grant applications are sought to examine the utility of VR technologies in the treatment of various types of drug abuse. These treatments can be based in clinical settings or the patients' homes. These treatments can be developed to address drug withdrawal, drug craving or on-going drug related behaviors. The development of VR technologies to address abuse of all types of drugs (e.g., cocaine, marijuana, nicotine, alcohol, inhalants) is sought. Phase I testing should establish the feasibility of the use of this technology for the particular drug problem addressed (e.g., cocaine craving, opioid withdrawal) and should also produce data that demonstrates that this methodology is effective for the particular drug problem. Phase II should involve larger-scale testing (e.g., more subjects and treatment trials) examining various treatment parameters (e.g., timing of treatment, types of VR environments). The focus of Phase II testing should be the refinement of this treatment for use in the treatment of drug abusers. David Thomas, Ph.D. 301-435-1313 Email: dt78k@nih.gov 7.Development of a Virtual Reality Environment for Teaching about the Impact of Drug Abuse on the Brain. Virtual reality (VR) is emerging as a technology with a multitude of uses within the medical sciences. In terms of the science of drug abuse, it is being developed as a treatment tool. The current solicitation seeks the development of a virtual reality environment that can be used in educational settings to teach about how drugs of abuse (both illicit and licit) affect the brain and behavior. The cost of portable hardware needed to present a VR environment is relatively inexpensive. If education programs like the one sought in this solicitation were available, it is likely that VR would be used as a teaching tool in many settings, including classrooms and museums. The particular program sought here is to present an interactive three-dimensional virtual brain that shows normal brain functions and, in contrast, brain function after exposure to drugs of abuse. This technology could illustrate the neurotoxic and long-term effects of drug abuse on the brain. This VR may include other features that are not described above, provided that it will be useful in educating individuals about the medical, behavioral and social effects of drug abuse. The phase I application should develop a beta version of the program. Further, the phase I application should include a preliminary demonstration of “usability,” where it is shown that the types of people being educated with this program (e.g. teachers) can effectively operate this system without extensive training. Further, it should be demonstrated that the hardware is easily worn by subjects, and that the subjects can rapidly understand how to effectively interact in the VR environment. David Thomas, Ph.D. 301-435-1313 Email: dt78k@nih.gov 8.Nanoscience-based Design of Therapies for Substance Abuse Treatment. Nanoscience and nanotechnology, by manipulating matter at the atomic or molecular levels, are emerging research areas that have the potential to fundamentally transform the study of biological systems and lead to the development of new methods for detection, prevention, and treatment of substance abuse and related disease states. NIDA invites nanotechnology-based applications in the following areas: a.Methods to enhance the efficacy of FDA-approved compounds by reducing their size to the nanoscale range to alter absorption, distribution, metabolism, or excretion. b.Development of new compounds, through manipulation of matter at the atomic or molecular levels that could more readily pass the blood-brain-barrier or cell membranes. c.Development of nanoscale particles for controlled targeted delivery of therapeutics, genes, or antibodies. d.Methods to enhance existing imaging technologies using magnetic properties at the nanoscale. e.Application of nanostructures (e.g. noble metal nanoparticles, quantum dots, and nanolithographic structures that show promise for diagnostic development) for identification and analysis of genes, proteins, and other biological molecules implicated in the actions of drugs of abuse. Applications are invited from any of the above areas. Phase I should demonstrate convincingly the viability of the proposed innovation, whereas Phase II should carry out the development, characterization, testing, and screening of the innovation. Thomas G. Aigner, Ph.D. 301-435-1314 Email: ta17r@nih.gov 9.Functional Genomics Resources and Strategies. In the post-genomic era, an explosion of gene discovery studies utilizing strategies such as genome-wide association scans, microarrays, and proteomics have identified a host of genes/gene variants associated with susceptibility to, or protection from, diseases of addiction. A critical next step is to validate these candidate genes/variants to determine which ones play an authentic functional role in mediating addiction. Functional validation could occur at many different phenotypic levels ranging from the molecular to the behavioral. Studies could investigate a few high priority genes/variants or could test several hundred genes/variants rapidly. The development of resources and strategies that would facilitate functional validation of genes/gene variants include (but are not limited to) the following areas: a.Gene/variant effects on subcellular localization, stability, or function of mRNAs/proteins relevant to drug addiction. b.The development of imaging and other strategies to identify gene/variant effects on neuronal or brain functions relevant to addiction. c.Strategies to identify gene/variant effects on behavior, such as response to addictive stimuli, stress, or changes in social situations. d.RNA interference-mediated depletion of candidate genes in cells or whole organisms to look for phenotypic alterations such as changes in synapse, dendritic spine, or cell morphology, gene expression, or behavioral responses to drugs of abuse. e.Strategies exploiting the growing collection of genetic mutants in candidate genes (particularly utilizing model organisms such as mouse, zebrafish, Drosophila, C. elegans or yeast) to functionally validate genes/variants. f.Approaches enabling comparison of wild type protein function to the function of allelic variants using in vivo transgenes or in vitro biochemical assays, especially if these approaches reveal whether a variation increases or decreases gene function. g.Systems-based approaches investigating whether a set of candidate genes is co-expressed in a particular brain region or cell type, physically interacts with one another, or functions together in a signal transduction cascade are also of great interest. h.Approaches to ascribe drug abuse-related function to genes/variants in non-coding RNAs, microRNAs, gene regulatory elements, gene copy number, or other putative non-protein coding regions of the genome. i.Methods of translating functional studies in model systems to validate gene/variant function in humans. John Satterlee, Ph. D. (301)-435-1020 Email: satterleej@nida.nih.gov 10.Genetic Studies. The National Institute on Drug Abuse is interested in applications that would facilitate the identification of genetic loci that confer vulnerability to substance abuse and addiction. Areas of interest include but are not limited to: a.Collection and genotyping of human pedigrees and sib-pairs for vulnerability or resistance to drug abuse. b.Isolation and identification of mutant strains in genetic model systems such as Zebra fish, Drosophila, C. elegans, mice, and rats that are more vulnerable or resistant to drugs of abuse. c.Throughput screens for identifying genetic vulnerability to addiction in genetic model systems. d.Development of transgenic models for drug abuse using bacterial artificial or yeast artificial chromosomes. e.Development of software and databases for candidate genes for drug abuse. f.Identification and mapping of functional polymorphisms of candidate genes for drug abuse. g.Placement of candidate genes for drug abuse on biochips. h.Marker-assisted breeding of congenic mouse and rat strains for mapping quantitative trait loci associated with addiction and drug abuse. i.Vectors for gene transfer into neurons. Jonathan Pollock, Ph.D. 301-443-1887 Email: jp183r@nih.gov 11.Effects of Drugs at the Cellular Level. Development of new imaging techniques, reagents and related hardware and software for dynamic investigations of the effects of drugs of abuse on cellular activities and communications. For example, these techniques might include, but are not limited to, development and utilization of reagents for magnetic resonance microscopy and other MRI methods; development of methodologies applying functional MRI to drug abuse studies; the use of dyes, intrinsic signals, and other optical indicators for studying signal transduction mechanisms, the regulatory control of protein entities (such as phosphorylation), and neuronal excitatory and inhibitory pathways. Areas of interest may include but are not limited to: a.Studies using molecular biological techniques to scale-up protein production for investigations aimed at enhancing understanding of the structure, function and regulation of molecular entities involved in the cellular mechanisms through which abused drugs act. b.Validated in vitro test systems can reduce the use of animals in screening new compounds that may be of potential benefit in treating drug abuse. Test systems are needed to evaluate activity at receptors or other sites of action, explore mechanism(s) of action, and assess potential toxicity. c.With the recent success in molecular cloning of various drug abuse relevant receptors, enzymes, and other proteins, researchers will elucidate the molecular mechanism of action of these drugs. Studies to generate strains of transgenic animals carrying a gene of interest are solicited. Of special interest are knockout and tissue-specific knockout animals. These animals can be used to identify gene function, and to study the pharmacological, physiological, and behavioral role of a single gene. Jonathan Pollock, Ph.D. 301-443-1887 Email: jp183r@nih.gov 12.Research Resources. The National Institute on Drug Abuse is interested in applications that would generate the following resources for drug abuse research: a.Resources for the application of genetic engineering to dynamically monitor neuronal function. b.C57BL6 Mouse embryonic stem cells and spermatogonial stem cells. c.Turnkey technology for proteomics such as the development of protein and peptide chips to study drug effects on neuronal mechanisms. d.Antibodies, aptamers, ligands, etc. relevant to drug abuse research. Jonathan Pollock, Ph.D. 301-443-1887 Email: jp183r@nih.gov 13.Computation, Modeling and Data Integration in Drug Abuse Research. a.Development of software or other tools, which enable data integration, and the development of computational models related to addiction and other medical consequences of substance abuse, e.g. tools that enable the integration of proteomics, genomics, transcriptomics, metabolomics and other data into applications leading to systems understanding of drug effects upon biological systems, or developing innovative approaches for managing knowledge and integrating information from text, data, image, and other sources or files generated in addiction research. b.Tools, which enable multilevel and multiscale modeling of biological and behavioral systems relevant to substance abuse research, such as those relevant to evaluations of expected utility. c.Development of software tools and interactive technologies (such as applications of grid technologies and networked appliances) which enable the prevention, treatment and study of substance abuse as well as the evaluation of prevention and treatment strategies. Karen Skinner, Ph.D. 301-435-0886 Email: Ks79x@nih.gov Division of Epidemiology, Services and Prevention Research (DESPR) A.Prevention Research Branch (PRB). The Prevention Research Branch (PRB) supports a program of research in drug abuse and drug related HIV prevention to (1) examine the efficacy and effectiveness of new and innovative theory-based prevention approaches for drug abuse, drug-related HIV/AIDS and other associated health risks, (2) determine the cognitive, social, emotional, biological and behavioral processes that account for effectiveness of approaches, (3) clarify factors related to the effective and efficient provision of prevention services, and (4) develop and test methodologies appropriate for studying these complex aspects of prevention science. Prevention Research. Rigorous scientific prevention research is encouraged to study novel approaches to substance abuse prevention for use at multiple levels of the social environment including: the family, schools, peer groups, community and faith-based organizations, the workplace, health care systems, etc. The purpose of this research is to determine the efficacy and effectiveness of novel program materials, training strategies, and technologies developed to prevent the onset and progression of drug abuse and drug-related HIV/AIDS infection. Materials and technologies may target a single risk-level or may take a comprehensive approach encompassing audiences at the universal, selective, and/or indicated levels. Universal interventions target the general population; selective target subgroups of the population with defined risk factors for substance abuse; indicated interventions target individuals who have detectable signs or symptoms foreshadowing drug abuse and addiction, but who have not met diagnostic criteria. NIDA encourages the development and testing of innovative prevention intervention technologies that are sensitive and relevant to cultural and gender differences. 1.Laboratory studies of the underlying mechanisms and effects of various prevention approaches such as persuasive communication (e.g., mass media and print media) as they are affected by and effect drug related cognition, emotion, motivation and behaviors. 2.Decomposition of prevention programs, practices and strategies to understand components that account for program effectiveness. 3.Research on features of prevention curricula, materials, implementation, approaches, training, technical assistance, and systems integration that contribute to positive outcomes. 4.Training modules and ongoing technical assistance for program implementers of research based substance abuse prevention programming strategies. 5.Prevention intervention dissemination technologies and mechanisms that integrate research with practice; specifically the transfer of drug abuse prevention information to decision-makers, funders, and practitioners. 6.Prevention services research on the organization, financing, management, delivery, and utilization of drug abuse prevention programs. 7.State-of-the-art and practical strategies for the integration of evidence-based prevention approaches into existing prevention service delivery systems. 8.Studies that develop and assess reliability and validity of developmentally appropriate self-report, physiological, and biochemical measures for use in prevention trials in a variety of settings and a variety of audiences. 9.Development of and testing of environmental change strategies for schools, neighborhoods, communities, etc. to use in reducing substance use initiation and/or progression. 10.Development of practical and affordable community tools for: needs and resource assessment, selection of appropriate evidence-based programs and strategies, high-quality implementation of identified programs and strategies, evaluation at community, organization and individual levels, and sustainability. 11.Drug abuse prevention methodological research on promising data collection, data storage, data dissemination, and reporting techniques. 12.Promoting wider and more effective (e.g. with enhanced fidelity) use of evidence-based prevention interventions for substance abuse and related HIV prevention, including interventions made available thru CDC and other federal agencies. 13.Studies applying technologies and strategies that have been developed for use in other disciplines in order to examine the utility of their application for drug abuse prevention, such as virtual reality technologies being used for some clinical conditions (e.g. phobias, eating disorders), and serious video games are being used for some clinical conditions (e.g., cancer patients), but not for drug abuse prevention. 14.Development and testing of innovative drug abuse prevention intervention products, using discoveries from the basic biological (e.g. neurobiological), psychological (e.g. emotional, behavioral, cognitive, and developmental) and social (e.g. social learning, peer network, and communications) sciences. 15.Development and testing of adaptations for efficacious prevention research approaches to make these more appropriate for special populations including racial and ethnic minorities, non-English speaking populations, immigrant populations, rural and migrant populations, low literacy populations, or persons with disabilities. 16.Development of methods, state-of-the-art tools and systems for community coalition-building. 17.Development and testing of tools to measure intervention costs, cost effectiveness, and net economic benefits. 18.Development and testing of rapid assessment tools of sexual and drug use risk behaviors for use in health care and public health environments, including STI clinics and AIDS research centers. 19.Development and testing of tools to promote security and appropriate prescribing of scheduled prescription drugs. Technologies can be developed to assist medical professionals, schools, service providers and others in making prescribing decisions, educating patients and their caretakers, or dispensing and monitoring of medications. 20.Development of new technologies to support drug abuse prevention interventions with military personnel, veterans and their families. Tools can include adaptations of efficacious and effective drug abuse prevention interventions to maximize health care efficiencies and to address negative life stress resulting from sustained combat operations, a major contributor to both the onset and exacerbation of substance abuse and mental health problems. 21.Development of new technologies for delivery and implementation of efficacious drug abuse prevention interventions for rural and frontier communities. Augie Diana, Ph.D. 301-443-1942 Email: dianaa@nida.nih.gov B.Epidemiology Research Branch (ERB). The ERB supports a research program on drug abuse epidemiology that includes (1) studies of trends and patterns of drug abuse and related conditions such as HIV/AIDS in the general population and among subpopulations, (2) studies of causal mechanisms leading to onset, escalation, maintenance, and cessation of drug abuse across stages of human development, (3) studies of person–environment interactions, (4) studies of behavioral and social consequences of drug abuse, (5) bio-epidemiologic studies including genetic epidemiology studies, (6) methodological studies to improve the design of epidemiologic studies and to develop innovative statistical approaches, including modeling techniques. 1.Improvement of Reliability and Validity of Reporting of Sensitive Data. The reliability and validity of self-report of drug use and related behaviors (e.g., HIV risk behavior) is a matter of great concern. Use of new technologies for real time data collection in ecological settings is of great interest because these technologies enable collection of drug consumption data in context. Studies to improve methodologies based on variations of standard survey protocols or computer-assisted self-interview (CASI) and personal interview (CAPI) are also encouraged. 2.Instrument Development. Easy-to-use assessment instruments are needed to enhance epidemiology research. Areas of interest include but are not limited to: a.Community Assessment. The development of community diagnostic instruments for psychometrically sound assessment of community characteristics is essential to improve our understanding of how community factors affect drug abuse and ensuing behavioral and social consequences. Standardized assessments of community characteristics are needed to better understand the full impact of drug use and to develop targeted interventions to specific community needs. b.Assessment of Psychiatric Comorbidity in Community Settings. Easy to use, reliable, and valid instruments are needed to assess psychiatric comorbidity in different populations of drug abusers, including adolescents and those in community drug abuse treatment settings. c.Assessment Instruments to Measure CNS Function Related to Drug Abuse. The development of age-appropriate assessment instruments to measure behavioral and cognitive function over the course of development will contribute to our understanding of vulnerability to drug abuse and functional impairment due to drug use. 3.Development of State-of-the-Art Mechanisms for Epidemiological Research. The development of state-of-the-art mechanisms to facilitate the use of Geographical Information Systems (GIS) in community epidemiology studies (for example Community Epidemiology Work Groups) and other drug abuse research is if great interest. There is a need for enhanced software and hardware for GIS interfaces, database management, visualization, and innovative spatial analysis capabilities. The role of GIS in public health management and practice continues to evolve. Application of this technology is an important step towards better understanding drug abuse issues and their inherent complexities. The ability to evaluate geospatial information provides a unique perspective of public health issues such as emerging and shifting epidemics, the utilization of treatment services, and rapid assessment of the impact of incidents ranging from natural disasters to bioterrorism. When used alongside more traditional epidemiological techniques, GIS provides epidemiologists the ability to address new questions, refine, or enhance existing analyses. Bethany Deeds, Ph.D. 301-402-1935 Email: deedsb@nida.nih.gov 4.Improving Measures of Addiction Risk. Individual differences in risk for drug addiction are often expressed in degree rather than kind, that is, as gradations along an underlying continuum that stretches from unobservable variations in risk for addiction to extreme and fully debilitating addiction severity. Assessment instruments in use today for measuring drug addiction (i.e., compulsivity in seeking and using drugs despite harmful consequences) have proven reliability and validity, but are of limited use for evaluating individual differences in risk for drug addiction. Advances in computerized adaptive testing methods, computer-assisted technologies, and psychometrics, including item response theory, suggest that the capabilities now exist for the development of the next generation in addiction assessment. New assessment instruments are needed to detect meaningful variation between, within, and across individuals over time that is scalable along the dimension of risk for addiction; these instruments should allow for efficient assessment of the risk construct with minimal burden for administration, training, and cost to the researcher, clinician, research participant, or patient; and they should ultimately provide valid and reliable scores corresponding to established diagnostic criteria for substance use disorders. Elizabeth Lambert, M.Sc. 301-402-1933 Email: elambert@nida.nih.gov 5.Developing, Validating, Refining Tools for Ecologic Momentary Assessment. Ecologic Momentary Assessment (EMA) includes the measurement of exposures and events in real time as they occur, and in the natural environment where they occur, such as the home, neighborhood, or workplace. EMA tools include portable technologies for longitudinal data collection in the field, such as mobile phone electronic diaries and PDAs, geopositioning devices, motion sensors, biosensors, environmental sensors, and audiovisual devices. In addiction and behavioral research, new EMA tools may enhance the contextual and temporal resolution of exposures, and the biological or behavioral processes presumed to occur in response. Specific challenges to address in the implementation of EMA include optimizing the timing of measurement and data quality, establishing sensor validity and reliability in different populations, reducing intensely longitudinal data for statistical analysis, achieving user acceptability, and safeguarding user privacy. Studies are encouraged that address these and other challenges to improve the validity and acceptability of EMA tools. Louise Eideroff, Ph.D. 301-451-8663 Email: wideroffl@nida.nih.gov C.Services Research Branch (SRB). The SRB supports a program of research on the effectiveness of drug abuse treatment with a focus on the quality, cost, access to, and cost-effectiveness of care for drug abuse dependence disorders. Primary research foci include: (a) the effectiveness and cost-benefits and cost-effectiveness of drug abuse treatment, (b) factors affecting treatment access, utilization, and health and behavioral outcomes for defined populations, (c) the effects of organization, financing, and management of services on treatment outcomes, (d) drug abuse service delivery systems and models, such as continuity of care, stages of change, or service linkage and integration models, and (e) drug abuse treatment services for HIV seropositive patients and for those at risk of infection. 1.Drug Abuse Treatment Economic Research. This initiative will support research to design and develop data systems for financial management and economic analysis of treatment programs and larger systems in new healthcare settings and managed care networks. Managerial decision-making requires the implementation of sophisticated data systems to facilitate routine budgeting processes, allocation of resources, performance measurement, and pricing decisions. The focus is on the needs of managers within the organization and managers outside of the organization. Data system development must be based on standard cost behavior and profit analysis. Data systems must be designed with correct cost concepts (accounting and economic) in order to permit cost and pricing decisions to be developed for new treatment technologies and management of ongoing systems. In research settings, such an initiative is vital for the assessment of new technologies developed for transfer to practice. 2.Determining the Costs of Implementing Evidence-Based Practices (EBPs) and Other Technologies in Drug Abuse Treatment. Research shows that new technologies or evidence-based practices (EBPs) can improve drug treatment outcomes, and it has been asserted that large-scale drug abuse treatment improvement requires systematic implementation of proven practices, processes, and technologies. Often, however, new drug treatment approaches are not adopted or sustained in usual practice, even in programs that served as settings for research showing their effectiveness. This may be due in part to a poor understanding of the initial or ongoing costs entailed by new practices, processes, or technologies (hereafter referred to as technologies). Methods and tools need to be developed and tested to help drug abuse treatment service providers and payers arrive at realistic estimates of the costs of implementing and sustaining new technologies in usual practice settings. With regard to new technologies, implementing is defined as an ongoing process of selecting, adopting, and adapting these new technologies into ongoing treatment, particularly with consideration for the local setting, population and available resources. Sustaining is defined as an ongoing process of providing needed resources (such as staffing, training, and equipment), maintaining the quality of the new technology through evaluation, monitoring, and improvement, and determining its ongoing utility compared to alternatives. The tools and methodologies should be able to identify and estimate costs separately for implementing and for sustaining new technologies, and should consider both clinical and administrative technology. At a minimum, domains in which costs should be estimated include assessment of programmatic need, appropriateness, and value; staffing qualifications (salary and competencies); training, support, equipment, and other infrastructure requirements; information / data requirements; quality monitoring and improvement; and evaluation of outcomes. Sarah Duffy, Ph.D. 301-443-6504 Email: sduffy@nida.nih.gov 3.Personnel Selection Technology Research for Drug Abuse Treatment Clinics. Research is showing that employee turnover is a substantial problem among substance abuse treatment services providers. Applications supporting innovative research that develops and validates generic staff selection systems which could be adopted and tailored for use by drug abuse treatment clinics are welcome. Like many small businesses, drug abuse treatment clinics have problems attracting and retaining qualified personnel. Also like many small businesses, treatment clinics have limited resources to apply to the recruiting, screening, and hiring of new and replacement personnel. Research has shown that the application of standardized screening and selection methods designed to maximize person-job fit can cost-effectively reduce staff turnover. Systematic methods such as background inventories, protocol-driven interviews, aptitude tests, and credit checks have demonstrated validity for improving person-job fit. Examples of possible projects might include development of easy-to-understand guidance about legal considerations in hiring practices, software that transform job task analysis into selection criteria, interview protocols to standardize applicant screening, tolls to help improve recruitment, and/or self-paced training for hiring officials or interview panels to improve screening reliability. 4.Customer Retention Technology. Premature disengagement from drug abuse treatment participation is a common problem and ranges from approximately 30 to 60% based upon the clinic and modality studied. Past research has very frequently attributed dropping out of treatment to participant characteristics (e.g., motivation, addiction severity, comorbidity) and/or environmental factors (e.g., social pressures, unemployment, homelessness). Seldom has the dropout problem been studied in the context of customer satisfaction. That is, there is little research looking at the causes of dropping out of treatment attributable to organizational factors (e.g., policies, practices, context) that influence participant withdrawal decisions. Needed are tools and systems for assessing and surveying drug abuse treatment program participant perceptions and satisfaction levels, summarizing and report participant assessments, interpreting results, and adjusting policies and practices to improve satisfaction and participant retention in treatment. 5.Effective Management and Operation of Drug Abuse Treatment Services Delivery. The bulk of drug abuse treatment is conducted in small clinical settings with therapeutic staffs of less than a dozen people. Small clinics lack resources to help improve efficiency and effectiveness in both business and therapeutic practices. Areas that may be of interest to small businesses include, but are not limited to: a.Computer-based leader/manager self assessment tools: On-line and other types of tools to help those supervising the delivery of drug abuse treatment services to gain insights about personal strengths and weaknesses, and to help guide them to improved leadership and management practices. b.Organizational change tools: Handbooks describing step-by-step way to introduce more efficient business practices such as quality management/monitoring, creating empowered work teams, formalized goal setting, improved customer relations, forming organization linkages, and adopting new fiscal and resource management techniques. c.Organizational change tools: Handbooks describing step-by-step ways to introduce more efficient or effective therapeutic practices such as, adding pharmacotherapy in a previously drug-free clinic, adopting new medical/pharmacotherapy or behavioral interventions, and adopting new approaches to clinical collaboration and/or case management. 6.Assessment Tools for Quantifying and Organizational Culture that Promotes and Sustains a Drug-Free Workforce. Though drug-free workplace programs are ubiquitous in large businesses, small businesses often lack the staff and resources to create effective drug-free programs because they may involve in-house or contract experts to educate, train, monitor, and enforce policies and practices that will sustain a healthy workforce and a safe and healthy workplace. Though there are numerous model drug-free workplace policies and programs provided free by federal, state, and local governments as well as nongovernmental organizations, many fail to provide management with affordable or free, easy-to-use tools to assess the baseline of their organizations’ culture for drug abuse intolerance, and to monitor progress in building a drug-free organizational culture. Research shows that individual employees and organizations vary in their support for a drug-free workplace. Surveys indicate that coworker tolerance for illicit drug use varies by the type of drug, the type of industry, and the work role of the respondents. A drug-free culture creates commonly-held attitudes, beliefs and practices among employees that are socially reinforced. Once established, the need for costly external incentives and other measures abates as coworkers socialize new incumbents and enforce behavior promoting abstinence. Tools and methodologies need to be developed to a) assess an organization’s baseline culture for drug abuse intolerance both on and off the job, b) identify policies and practices that undermine a drug-free culture, c) enable the identification of programs, policies, and practices capable of helping the workforce develop/strengthen an organizational culture of intolerance for drug use, and d) estimate the impact on the organization’s quality of work-life, job safety, individual and group performance and productivity, and the profitability of the organization itself. Included would be inexpensive and easy to use tools for monitoring workforce behavior change, and changes in the impact on the organization (as outlined in “d”). Thomas F. Hilton, Ph.D. 301-443-6504 Email: Tom.Hilton@nih.gov 7.Web-Based Technologies: Transporting Services Research to Practice. This initiative will support the development and testing of the effectiveness of web-based technologies that facilitate the translation of drug abuse prevention and treatment services research into practice. The ultimate goal is the delivery of efficacious, low-cost interventions to the greatest number of individuals in community settings. Delivery of evidence-based services in community settings often is hampered by lack of state-of-the-art information about the contents of efficacious interventions, the organizational structures and processes that make effective implementation possible, and available training and technical assistance. Applications may include, but are not limited to, the development and testing of new and innovative Internet-based systems that provide practitioners with (a) current information on evidence-based treatments with the greatest promise for defined populations of drug abusers; (b) assistance in translating clinical trials data into clinically useful information; (c) information and training on how to effectively organize, manage, and deliver evidence-based prevention and treatment services; (d) strategies for organizational change and capacity building; and (e) access to training and technical assistance on the adoption of new prevention and treatment interventions. 8.New Technologies for Screening, Assessing, and Preventing Problem Drug Use and HIV, Matching Patients with Appropriate Treatment Services. Increased understanding of the complexities of problem drug use and HIV risk behaviors has sparked growing interest in and increased need for new user-friendly technologies to assist in the screening, assessment, and prevention of drug abuse and HIV, and in the matching of patients with appropriate treatment services. New technologies, including CD-ROM, hand-held, Internet, videotape, videodisc, and other electronic means have great potential for helping treatment providers in specialty and non-specialty care settings including primary care contexts to (a) screen for problem drug use and associated health problems and risk behaviors, including HIV, (b) assess the nature and degree of drug use and HIV risk behaviors, (c) embed items for screening or assessing problem drug use within existing clinical tools, (d) deliver appropriate prevention interventions, and (e) identify appropriate types and levels of treatment services for patients based on their individual treatment needs. These new technologies potentially can provide a more cost effective way of identifying problem drug use, HIV risk behaviors and infection, and associated health problems in a variety of health care settings, speeding the assessment and treatment process, and improving treatment placement decisions. Dionne Jones, Ph.D. 301-443-6504 Email: djones@nida.nih.gov 9.Reintegration of Criminal Offenders into the Community. Many offenders enter the criminal justice system with drug abuse problems and related health issues. In addition to addressing these health care issues within the prison walls, treatment programs are increasingly called upon to help offenders successfully reintegrate into the community following incarceration. This often means helping offenders to manage their recovery through monitoring, linkage with continuing care services, development of social support networks, and education of friends and family members about the nature of drug abuse and the challenges facing the offender upon release from prison. It is estimated that over the next several years, more than 600,000 criminal justice offenders, many of whom have drug abuse problems, per year will be released to return to their communities. New technologies are needed to help treatment providers in the criminal justice system and in the community coordinate efforts to effectively (a) monitor offenders’ recovery once they have been released into the community, (b) prevent relapse, (c) identify relapse early and efficiently re-engage released offenders in appropriate treatment, (d) link released offenders with continuing care services in the community, (e) develop social support networks for recently released offenders in recovery, and (e) educate offenders’ family members so that they can more effectively support offenders in recovery once they have been released from prison. Dionne Jones, Ph.D. 301-443-6504 Email: djones@nida.nih.gov 10.Technologies to Support Quality Improvement in Addiction Treatment Systems. New technologies to support quality improvement in community-based, addiction treatment provider systems are needed. Quality improvement methods, although well established in business and healthcare management, are underutilized in addiction treatment. Addiction treatment systems have limited resources for initiating, developing, implementing, and sustaining quality improvement practices. Most community-based provider systems have limited capacity to capture and integrate information about (a) the nature and extent of community needs and resources; (b) organizational and management processes to facilitate adoption, adaptation, implementation, and sustained use of science-based innovations; (c) implementation costs for new service innovations; (d) client satisfaction; and (e) quality of care. Centralized, automated and cost-efficient technological tools for these purposes could help provider systems improve the quality and efficiency of their treatment services, meet accreditation requirements, and reduce operating costs. Bennett Fletcher, Ph.D. 301-443-6504 Email: bfletche@nida.nih.gov 11.Electronic Drug Abuse Treatment Referral Systems for Physicians. Research shows that primary care physicians often do not screen for drug abuse disorders. While this may be related to stigma attached to illicit drug use or to a lack of adequate health insurance, it may also be due to the lack of an adequate referral system that primary care physicians can use for the patients they identify as having a potential drug problem. The lack of a referral system places a greater burden on the physician to secure treatment resources for the patient, and also places the physician at greater risk if no appropriate treatment can be found. A practical and usable electronic drug abuse treatment referral system needs to be developed and tested for use by physicians in primary care settings, including doctor’s offices. To be effective and useful, the system needs to be targeted at local needs, for example by taking into account local private insurance coverage and the types of insurance accepted by local treatment providers. It should also include an actively-maintained database of local providers, with information on insurance carrier, geographic “catchment” area of treatment providers, types of substance disorders treated, types of co-occurring disorders (mental disorders, etc.) treated, gender, age, other pertinent treatment factors needed by primary care physicians to make appropriate referrals. The system should be designed to be reliable and efficient, allowing for appointment scheduling or other needed arrangements to ensure a successful referral. Feasibility and cost-efficiency should be carefully considered. Richard Denisco, M.D. 301-443-6504 Email: deniscor@nida.nih.gov Center for the Clinical Trials Network The mission of the Clinical Trials Network (CTN) is to improve the quality of drug abuse treatment throughout the country using science as the vehicle. The CTN provides an enterprise in which the National Institute on Drug Abuse, treatment researchers, and community-based service providers cooperatively develop, validate, refine, and deliver new treatment options to patients in community-level clinical practice. This unique partnership between community treatment providers and academic research leaders aims to achieve the following objectives: •Conducting studies of behavioral, pharmacological, and integrated behavioral and pharmacological treatment interventions of therapeutic effect in rigorous, multi-site clinical trials to determine effectiveness across a broad range of community-based treatment settings and diversified patient populations; and •Ensuring the transfer of research results to physicians, clinicians, providers, and patients. Materials and processes that facilitate clinical trials in community practice settings are particularly needed in this program. Areas of research include but are not limited to: •Projects that would simplify, automate, standardize, or reduce the cost of administration of clinical research instruments used in CTN trials •Projects that would reduce error rates in completing assessment or clinical instruments and in transmitting data to data management entities •Projects to develop instruments that measure factors relevant and important to the conduct of addictions research, such as: the extent of craving and/or of withdrawal, the risk of addiction to a particular substance, the therapeutic alliance between patient and therapist, perceived satisfaction with health care, probabilities of a pain management patient developing dependence/abuse on pain medications, and probability of successfully completing detoxification •Projects to develop instruments that measure and predict HIV risk behaviors •Projects that develop and evaluate innovative diagnostic drug screening tests for drug abuse, such as oral swabs •Projects that develop and evaluate the use of gene chip technology for drug abuse risk factors With all questions regarding CTN-sponsored SBIR research, please contact: Quandra Scudder 301-443-6697 Email: scudderq@nida.nih.gov Specific projects could include: 1.Development of Combination Medication for Emergency Treatment of Opioid Overdose in the Presence of Benzodiazepines. Suspected opioid overdose—coma, apnea and pin point pupil—is treated by the administration of naloxone, which, while effective, is short-lived. Patients often leave the Emergency Room, return immediately to opioid use, and suffer dire consequences as a result. There is sufficient preclinical and clinical evidence that buprenorphine may be a more effective medication for treatment of opioid overdose in such patients. However, the clinical development of this treatment strategy has been hampered by concerns that many opioid abusers also abuse benzodiazepine, and in such patients the administration of buprenorphine may be hazardous. Fumazinil, a specific benzodiazepine antagonist used to treat benzodiazepine overdose, can be co-administered with buprenorphine and may protect such patients from the ill effects of buprenorphine in cases of overdose involving both opioids and benzodiazepine. The goal is to develop and test the buprenorphine-fumazinil combination medication formulation for the treatment of opioid overdose with suspected concurrent benzodiazepine abuse. 2.Screening and Development of Partial Agonists at the Human CB1 Receptor for Treatment of Marijuana Dependence or Withdrawal. NIDA seeks applications to screen and/or develop CB1-receptor partial agonists for application in the pharmacotherapeutic treatment of marijuana dependence or withdrawal. The potential benefits of CB1-receptor partial agonists in the treatment of dependence may parallel those of safe and effective nicotine or opiate partial-agonist replacement therapies, where buprenorphine and varenicline have demonstrated effectiveness in enhancing abstinence from opioid use and cigarette smoking, respectively. As implied by the designations of partial-agonist replacement or substitution therapy, a partial-agonist medication has core biological effects similar to those of the abused drug. Importantly however, there is a ceiling-effect dose with the administration of partial agonists not present with full agonists such that at high doses, partial agonists are less likely to precipitate adverse behavioral or biological events and to have abuse liability compared to full agonists. The phase I project should identify compounds that bind to human CB1-receptors as partial agonists and, in the phase II, the grantee should develop and evaluate selected partial agonists. 3.Improved Device to Capture and Measure Drug Use in Oral Fluid. Oral fluid (OF) testing is a promising method to monitor for drugs of abuse. The main advantages of OF is the simplicity and noninvasiveness of sample collection. Aside of patient’s/ study participant’s comfort and preference compared to urine drug screen, the oral fluid sample collection can be easily observed, obviating the need for special restroom facilities and same-sex collectors and making adulteration of the specimen more difficult. Furthermore, infection risk is lower than for drawing blood. For clinical toxicology applications, including use in clinical trials, drug treatment programs, physician office and emergency room testing, onsite OF testing would offer rapid availability of results for diagnostic or research purposes. At this point, however, Substance Abuse and Mental Health Services Administration approval of OF testing has been delayed because of questions about drug device performance, disposition of drugs in OF, and need for improvement of assays. The greatest current limitation for OF testing is the small number of controlled drug administration studies available to inform interpretation of OF tests. (Bosker, Huestis, 2009) Applications should address current limitations and present methods to remove obstacles for wider usage of OF testing in clinical practice and research. Reference: Bosker WM, Huestis MA. Oral Fluid Testing for Drugs of Abuse. Clinical Chemistry.2009; 55:11 1910-1931 4.Improved Technology of Testing Devices to Remotely Capture and Measure Drug Use in Biological Specimens. There is an ongoing need for more accurate, practical and convenient point-of-collection testing devices for monitoring drugs of abuse. Current devices that test for illicit drugs in urine, oral fluid (saliva), sweat and hair have strengths and limitations. The goal of this solicitation is to develop new technologies/devices that will increase strengths (e.g. accuracy, practicality, and convenience) and decrease limitations (e.g. minimum frequency, contamination, and adulteration) of testing methodologies. New technology might permit testing from remote locations (e.g. patient’s or subject’s home) while ensuring real time data collection and transfer into medical records/study databases. Risk of adulteration should be minimized to a level comparable with tests provided in drug treatment centers or study sites. The phase I application should explore all tests currently available, especially new technologies allowing for remote collection of the data. In phase II, the grantee should develop and test a prototype. 5.New Technologies: Integrating Data from Prescription Monitoring Program(s) to Current Clinical Practice. In some states the prescription monitoring program collects prescription data for controlled substances into a central database that can then be used by a limited number of authorized users to assist in deterring the illegitimate use of prescription drugs. Prescribers and dispensers in some states may query the database to assist in determining treatment history and to rule out the possibility that a patient is "doctor shopping" or "scamming" to obtain controlled substances. Limited time/resources of busy medical offices are a barrier to obtaining and utilizing this information to improve quality of treatment for each individual patient. This initiative will support development and testing of the effectiveness of new technologies that facilitate utilization of data collected by Prescription Monitoring Program(s) in clinical practice. Applications may include, but are not limited to, the development and testing of new and innovative Internet-based systems that provide a) practitioners with current information of their patients’ treatment/medication compliance; and b) transfers data automatically to patients chart, etc. The goal is to minimize barriers faced by clinical staff to obtain, record and utilize the data while maintaining strict security requirements (i.e., confidentiality, integrity, and availability). These new technologies should provide a more cost effective way of identifying treatment non-compliance and help adjust a treatment plan according to the needs of individual patients as well as decrease potential diversion of controlled substances. The phase I application will explore and describe current Prescription Monitoring Programs and new technologies allowing development and testing of the application in phase II. Division of Pharmacotherapies & Medical Consequences of Drug Abuse The NIDA Division of Pharmacotherapies & Medical Consequences of Drug Abuse (DPMCDA) supports research aimed at the development and testing of pharmacological and behavioral treatments for drug abuse and addiction. This includes the identification, evaluation, development, approvability, and efficacy testing of new and improved pharmacotherapeutic agents, as well as the testing of marketed medications, and of behavioral treatments used alone or integrated with medications. A.Chemistry and Pharmaceutics Branch (CPB). 1.Synthesis (either using traditional or combinatorial techniques) or discovery (natural products) of new chemical compounds that would have potential as treatment agents for the medical management of stimulant (e.g., cocaine, methamphetamine, or nicotine) addiction. Consideration should be given to the design of partial agonists or pure antagonists that diminish the reinforcing effects of stimulants, as well as full agonists that could function to normalize physiological activity following discontinuation of stimulant use. The CPB supports research in the design (including molecular modeling and structure-activity relationship studies) and synthesis of novel compounds, formulation development, bioanalytical methods development, and pharmacokinetics/ pharmacodynamics aimed at the discovery and development of new medications for treating drug addiction. Areas that may be of interest to small businesses include, but are not limited to research related to the design and development of new compounds and improved drug products (drug delivery) for the treatment of drug addiction. 2.Compounds of interest include those that are designed to affect dopaminergic (i.e., D1 agonists, D3 agonists and D3 antagonists) activity, CRF antagonists, compounds affecting glutamate activity, GABAergic activity, small molecule neuropeptide antagonists and compounds acting through other mechanisms for which justification has been supplied. 3.Synthesis (either using traditional or combinatorial techniques) of new chemical compounds that would have potential as treatment agents for the medical management of cannabinoid abuse. 4.Development of new immunotherapeutic treatments that would have the potential as treatment agents for stimulant or cannabinoid abuse. 5.Development of heroin/morphine-protein conjugates (heroin/morphine conjugate vaccines) for the treatment of heroin/opiate addiction. Richard Kline, Ph.D. 301-443-8293 Email: rk108@nih.gov 6.Development of new approaches for the administration of potential addiction treatment drugs (including small molecules, natural products, peptides, proteins, antibodies, etc.) with poor bioavailability. 7.Development of controlled release dosage forms for addiction treatment medications in order to maintain therapeutic drug levels for extended periods of time to alleviate compliance problems associated with addiction treatment. 8.Development of novel dosage forms or chemical/pharmaceutical approaches that eliminate or significantly reduce the abuse potential of prescription drugs/drug products. 9.Development of novel technologies and strategies to deliver potential therapeutic agents (including small molecules and peptides) across blood brain barrier for the treatment of drug addiction. Moo Park, Ph.D. 301-443-5280 Email: mp264a@nih.gov B.Medications Discovery and Toxicology Branch (MDTB). The MDTB supports research on the development of preclinical behavioral models (e.g., of craving, drug-seeking behavior, dependence, or relapse), biochemical assays, gene expressional assays and electrophysiological methods to identify and characterize new medications to treat substance abuse, as well as pharmacological screening of novel compounds to identify potential drug abuse medications. The Branch also supports research on toxicity studies of potential medications for the treatment of substance abuse, and interactions of potential treatment medications with abused substances. Areas that may be of interest to small businesses include, but are not limited to development of new methods for discovery of medications useful in treating drug addiction. Of special interest would be the development of new animal models of addiction, incorporating established drug self-administration techniques that show increased relevance to the clinical setting. Development of relevant biochemical or electrophysiological screening methods is also encouraged. Jane B. Acri, Ph.D. 301-443-8489 Email: ja96v@nih.gov C.Medications Research Grants Branch (MRGB). 1.Develop Novel Treatments for SRDs. The MRGB seeks to support the development of novel pharmacotherapeutic- and immunological treatments for persons with substance-related disorders (SRDs). The Branch also supports projects aimed at incorporating technological advances that could be used to more effectively treat SRDs. This solicitation aims to support small business development of compounds that have completed (or are nearing completion of) successful preclinical evaluation. Treatments should aim to help subjects reduce drug use, become drug free, prolong abstinence/reduce craving, or facilitate survival from drug overdose. Therapies that small businesses might consider evaluating include, but are not limited to: •A novel (e.g., new chemical entity, novel drug formulation) that could be used to treat SRDs •A marketed compound (e.g., SSRIs, anti-epileptic drugs) that could be used to treat SRDs •Vaccines for substances of abuse (e.g., cocaine, nicotine) •Monoclonal antibodies for substances of abuse (e.g., methamphetamine, PCP) •Naturally-occurring compounds (e.g., dietary supplements) that could be used to treat SRDs •Or, a rationalized poly-therapeutic combination of pharmacotherapies designed to more comprehensively treat SRDs Treatments that concurrently help alleviate associated psychiatric co-morbidities (e.g., depression, schizophrenia, PTSD, anxiety, etc.) and/or are focused upon underserved/vulnerable populations (e.g., pregnant women and their fetuses, adolescents, racial or ethnic minorities, women/gender issues, subjects within the criminal justice system) are especially encouraged. 2.Development of a Test/Device to More Effectively Diagnose/Manage Patients with SRDs. This solicitation aims to support the identification and development of an innovative test/device that can be used to help more effectively diagnose and/or manage patients with SRDs. The use of this novel diagnostic tool might help to: (1) expedite the development of-, and/or (2) enhance existing treatments for patients with SRDs. Possible diagnostic tests/devices that a small business might consider, but are not limited to, include: • An assay/device (e.g., skin sensors, oral swabs) that detects a substance of abuse more reliably than oft-used urinalysis. Optimally, the analytical test/device would be non-invasive and easy-to-use, such that it could be used on an outpatient basis. •Discovery/development of a diagnostic test/screen that could help physicians more effectively manage treatments for patients with SRDs. 3.Discovery / Development of Biomarkers Related to SRD Treatment Outcomes. Because drug addiction is a brain disease which can change the structure and function of the brain, there is a unique opportunity to develop biomarkers that could reliably predict/assess SRD treatment outcome. To date, evaluations of SRDs often utilize subjective measures (e.g., patient-reported questionnaires) to assess disease progression and primary treatment outcomes. Biomarkers represent a more objective measure of physiological functioning that can be used to predict, diagnose, evaluate the progression of, and/or more accurately assess overall treatment safety and effectiveness. The goal of this initiative is to support the small business discovery/development of reproducible, quantitative biomarkers related to SRD treatment outcomes. Potential biomarkers might be derived from underlying variations in DNA, gene expression, proteins, metabolism, and/or neuroimages, among others. 4.Creation of a Data Repository/Software Tool for SRD-related Clinical Research Data. Clinical data management is currently heterogeneous. Different investigators use different nomenclatures, definitions, timeframes, data-collection instruments, data analysis and reporting methods. This varied (and often inadequate) data management system severely limits the interpretation of results from clinical trials and complicates the ability to make data-based decisions concerning the overall effectiveness of a therapeutic intervention. Appropriate collection and standardization of clinical trial data should permit, for example, more statistically-valid comparisons of treatment outcomes and data integration, meta-analysis, and aid in the development of more effective, individualized clinical treatments for patients with SRDs. The purpose of this initiative is to support small business development of repository/software tool that can be used to more efficiently capture and manage (i.e., facilitate/standardize collection, storage, screen/analyze, report) data obtained from NIDA-funded clinical trials. Collection/storage of these data should follow HIPAA guidelines (http://www.hhs.gov/ocr/privacy/index.html) to guarantee the privacy and confidentiality of all study participants. Kristopher Bough, Ph.D. 301-443-9800 Email: boughk@mail.nih.gov Division of Clinical Neuroscience and Behavioral Research (DCNBR) A.Behavioral and Integrative Treatment Branch. The Behavioral and Integrative Treatment Branch is interested in research on behavioral and integrative treatments for drug abuse and addiction. The term "behavioral treatments" is used in a broad sense and includes various forms of psychotherapy, behavior therapy, cognitive therapy, family therapy, couples and marital therapy, group therapy, skills training, meditation, guided imagery, counseling, and rehabilitative therapies. The term, “Integrative treatments” refers to treatments that combine behavioral interventions with other treatments, including other behavioral therapies, medications, and/or complementary/alternative therapies. Behavioral and integrative treatment research has been conceptualized to consist of three stages. Stage I, or early treatment development, involves research on the development, refinement, and pilot testing of behavioral and integrative interventions. Stage I may include translational research that incorporates concepts, methods or findings from other disciplines (e.g., neuroscience, cognitive science, etc.) into the development of behavioral and integrative treatments. Stage I may also include research to develop or adapt treatments to become more “community-friendly.” Stage II includes testing treatments that show promise and testing the “dose-response” of treatments. Stage III is research aimed at determining if and how efficacious behavioral treatments may be transported to community settings. Stage III may include studies that test treatments in community settings, with community therapists. Stage III may also include studies that develop or test methods of training treatment providers to administer treatments. Determination of mechanism of action of treatment is relevant to all three stages. Specific areas of interest include: 1.Translation from Basic Behavioral or Cognitive Science. “Stage I” research on the development of behavioral therapies or components of such therapies that are based on developments and findings from the basic behavioral or cognitive sciences. 2.Translation of Cognitive, Affective and Social Neuroscience Findings Towards Development of Behavioral Treatments. “Stage I” research on the development of behavioral treatments or components of such therapies that are based on developments and findings from cognitive, affective, or social neuroscience. For example, one may wish to apply findings on the neural underpinnings of adolescent risk-taking behaviors to target the developmental needs of substance using youth, or apply findings on the link between early adversity and the impairment of emotion regulatory abilities to address the needs of substance using victims of childhood abuse. 3.Treatment of Sleep Disorders for Individuals in Drug Abuse Treatment. Recent research on sleep has shed new light on its importance to psychological and physical health. Sleep deprivation has been linked with impaired cognitive performance, negative mood, and even decreased immune function. Drug abusers often cite insomnia as reason for relapse, and may use drugs to modulate their sleep/waking cycles. However, the treatment of sleep disorders has not been a primary focus of drug abuse treatment research. The development and testing of sleep hygiene interventions, alone or in combination with behavioral interventions, for use in conjunction with drug abuse treatment, as a means of improving treatment for drug abuse is needed. Developmentally and age appropriate, as well as gender sensitive treatment of sleep disorders could impact on the development of more effective treatment interventions. Lisa Onken, Ph.D. 301-443-2235 Email: l010n@nih.gov 4.Modifying Efficacious Behavioral Treatments to be Community Friendly. Several behavioral interventions have been found to be efficacious for the treatment of drug addiction. However, there are barriers to implementation of behavioral treatments in community-based settings. Community settings that treat drug addicted individuals are reluctant or unwilling to adopt these interventions for a variety of reasons. Reasons that scientifically-based behavioral treatments are not accepted by community providers could include the excessive cost of implementation, the length of time for administration of treatment, inadequate training available for therapists and counselors, treatments not shown to be generalizable for different patient populations or for polydrug abusing populations, etc. Research aimed at modifying efficacious behavioral treatments to make them more acceptable to community settings is needed. Settings might include, drug abuse treatment facilities, primary care, managed care, after-school or classroom settings, colleges, and the criminal and juvenile justice system. Examples of possible studies are those that are designed to reduce the cost of treatments, reduce the time of administration of treatments, aid in training of therapists, counselors and nurses, adapt individual therapies for group situations, etc. 5.Treatments to Prevent Escalation from Abuse to Dependence. Therapies for drug abusers who are not yet dependent on drugs to reduce risk of escalation to dependence and therapies for drug abusers who have not considered or claim little interest in seeking treatment for their drug problems are needed. Treatments for participants in their natural environment, such as treatments delivered over the Internet, cell phone, or in neighborhood settings such as churches and recreation centers are desired. A particular focus on treatments which incorporate engagement strategies for hard to interest groups are requested. Educational games, interactive video content, fluency based learning approaches and other methods to help maintain involvement are encouraged. 6.Virtual Reality Applications for Drug Abuse. Development and improvement of treatments using Virtual Reality and other new simulation technologies is needed. New technology may help to make existing treatments more effective, or may make novel treatments possible. Behavioral treatment research to develop, modify, adapt, and test treatments for drug abuse and for co-morbid psychiatric conditions (such as anxiety disorders) using new technologies is of interest. Recently virtual reality simulations have been used to train medical personnel in demanding medical procedures such as microsurgery techniques. Virtual training allows trainees to gain familiarity with both the environment in which services are delivered as well as the intervention techniques without the danger of mistakes impacting live patients. Virtual reality interfaces can assess skill acquisition and provide detailed feedback during procedures to help trainees correct mistakes or avoid making them altogether. In the drug abuse field, training and dissemination efforts have been hampered by a dearth of knowledge about ways to conduct dissemination. Although trainees often practice on actual clients, this approach has drawbacks including its reliance on the client or participant’s schedule and willingness to participate in training sessions and potential danger to the client or if the intervention is delivered incorrectly. Libraries of virtual reality simulations of drug users in treatment or “virtual patients” are needed to provide experiential training for treatment providers without relying on existing patients. This will help facilitate the rapid and effective dissemination of proven treatment strategies. 7.Virtual Clinical Trials Settings for Conducting Behavioral Treatment Trials and Addictions Treatment Provider Education Trials in Cyberspace. Virtual communities such as Second Life as well as private web forums offer a unique opportunity for behavioral therapy researchers and providers to establish and conduct online psychotherapy and behavioral therapy development research as well as a forum to develop provider “university’s” at which various training techniques may be tested for discovering the most efficacious way to deliver continuing education and other training in the latest methods of treating addiction. Applications are encouraged to develop such a forum and test either a provider training or behavioral therapy method in an online trial. As part of this research platform, methods for obtaining consent, maintaining confidentiality, collecting data and where needed, assessing provider adherence and competence are expected. 8.Remote and/or Mobile Abstinence and Identity Verification. Methods are needed for at home or mobile abstinence verification which include identity verification. Drug abuse treatment researchers are in the process of developing web-based and mobile phone based treatments which can extend treatment beyond the clinic walls. Additionally, there is growing recognition by providers that drug addiction is a chronic disease which may require multiple bouts of treatment. However, currently there are no means of monitoring abstinence once patients leave formal treatment or validating progress of patients undergoing treatment located outside a clinic which provides onsite testing. Monitoring onsite testing poses barriers to patient privacy but unobserved sample donation may be subject to switching and adulterants. Products are needed which both test for the presence of illicit substances and which accurately identify the donor of the sample and the time of its submission so patients can participate in monitoring outside of formal treatment settings. Blood sampling similar in invasiveness to a skin prick for diabetes testing or other low risk sampling of other tissues and specimens may be acceptable. Scalability and automation of methods are particularly desirable. Cecelia Spitznas, Ph.D. 301-443-0107, Fax: 301-443-6814 Email: cmcnamar@mail.nih.gov 9.Improving Adherence to Medications and Treatment for Drug Abusers with HIV/AIDS. The introduction of highly active antiretroviral therapy (HAART) has significantly changed HIV/AIDS clinical care. There is a need for research related to the development and testing of new and improved behavioral interventions(alone, and in combination with pharmacological treatments for drug addiction), in order to facilitate better adherence to antiviral regimens among drug abusers with HIV infection, including HIV positive drug abusers with comorbid medical illnesses and/or psychiatric disorders. There is also a need to develop and test adherence interventions administered or assisted by technological devices such as computers, the internet, expert system models, telephone pagers, or hand-held computers. 10.Treatment for Emerging or Specific Populations. Therapies designed to intervene with understudied populations including users of drugs such as methamphetamine, MDMA and other club drugs, marijuana, inhalants, and prescription opioids and psychostimulants, as well as children of substance abusers in need of treatment, and drug abusers with comorbid psychiatric disorders and/or medical illnesses such as HIV/AIDS, hepatitis, etc. 11.Development of HIV Risk Reduction Interventions. Research to develop and evaluate behavioral strategies to reduce HIV risk behaviors in HIV-positive and HIV-negative substance abusing treatment populations. Where appropriate, risk reduction interventions should be adapted to patients’ age, gender, cultural background and potential cognitive impairments, and should address compliance with medical regimens. The product of such research might be training, supervision, or educational materials, such as manuals or videotapes that describe the intervention and its implementation by treatment staff. 12.Woman and Gender Differences in the Provision of Behavioral Treatments, and HIV/AIDS Risk Reduction Approaches. Develop and evaluate specific behavioral treatment approaches targeting drug-addicted women. This may include behavioral therapies, skills training techniques, counseling strategies, and HIV and other infectious disease behavioral risk reduction strategies. This may also include development and testing of training materials that specifically address women and gender differences in drug addiction treatment to promote effective use of research-based treatment approaches. Training materials may involve treatment manuals, training videos, CD ROM or DVD technologies, Internet or computer based programs to manage aspects of treatment administration, or other innovative educational strategies for health professionals using new technologies. 13.Behavioral Treatments Drawing from Stress Research or Stress-Management Interventions. Projects are encouraged that apply concepts from stress research (such as appraisal, coping, and social support) to drug abuse in innovative ways, or that test the extent to which stress-management interventions can be applied to the treatment of drug abuse and interventions to reduce risk of HIV and other infectious diseases. Examples of stress-management techniques that may have novel application to drug abuse and HIV risk include techniques that teach problem-solving and affect-management, restore one’s sense of purpose and meaning, prevent burnout in the face of chronic stressors, increase self-efficacy for managing stress, inoculate against stressors, train relaxation and meditation, intervene during crises, enlist social support and system support, and others. 14.Behavioral Strategies for Increasing Medication Adherence. Research to develop and to evaluate strategies to induce recovering addicts to take medication for a prolonged time, especially opioid antagonist naltrexone; partial opioid-agonist buprenorphine, etc. to encourage HIV infected drug users to comply with medical treatments (HAART) in drug abuse treatment settings; or to adapt existing behavioral strategies to increase patient compliance and cooperation in long-term treatment for drug abuse or for diseases associated with drug abuse such as tuberculosis or hepatitis. An important consideration should be cost and practicality of use in actual clinical practice or in an aftercare program. The product of such research might be a manual, which describes the behavioral strategy, and its implementation by treatment staff or scientific data regarding evaluation. Shoshana Kahana, Ph.D. 301-443-2261, Fax: 301-443-6814 Email: kahanas@mail.nih.gov 15.Integration of Behavioral Treatments and Pharmacotherapies. Development of integrated behavioral treatments and pharmacotherapies may enhance the efficacy of both types of therapeutic interventions. For instance, the maintenance and detoxification of heroin addicts could perhaps be optimized by the integration of distinctive behavioral treatments devised specifically for opioid agonists, antagonists or partial agonists determined by the heterogeneity of the subgroup of addicts and the pharmacological differences of the medications. Integration of medications and behavioral treatments could possibly enhance compliance with medication regimens, increase retention allowing pharmacological effects to occur and prevent relapse to drug abuse and addiction. 16.Behavioral Treatment Research for Drug Abuse and Addiction in Primary Care. Recent research has shown that physicians and other clinicians often fail to recognize drug abuse or addiction among their primary care patients. In addition, a significant number of these clinicians reported that they did not know how to intervene with their patients if drug abuse or addiction was suspected. Drug abuse related illnesses and morbidity often occur in adults and may have begun in adolescence. However, very little research has been done to develop or test behavioral treatment approaches or combined pharmacological and behavioral treatments for drug abuse and addiction in primary care settings. The objectives of this initiative are to encourage research on the development and testing of innovative behavioral treatment approaches e.g. screening and brief interventions, use of web-based or mobile technologies used alone or in combination with pharmacological treatments. Other goals of this research initiative are to encourage additional research on the development and validation of culturally sensitive screening and assessment instruments for use with youth and adults in primary care; and to encourage research on the transportability of efficacious behavioral treatments to primary care settings, as well as research on science-based training approaches for changing primary care clinicians' behaviors regarding their recognition and intervention with drug abusing or addicted patients. While motivational enhancement approaches for some drug abusing populations have been found to be effective, this behavioral approach has not been widely used in primary care. 17.Using Telemedicine to Deliver Efficacious Treatment to Underserved Populations in Specialty Addictions Treatment and/or General Medical Settings. Telemedicine programs are being used in urban medical centers to rapidly disseminate science-based information on new medical treatments. In addition, approximately one-third of the rural hospitals are now using telemedicine to improve patient care Studies are needed to modify existing treatments developed by NIDA researchers for deployment and testing as telemedicine treatments at remote locations to underserved populations. These may be delivered in any patient care context including primary care or specialty addiction treatment. Modification of the treatment content to apply to the remote patient population and provider training materials to orient the onsite staff who may not be experienced at delivering the new treatment may be needed. 18.Youth Smoking Cessation. Smoking related illnesses usually occur in adults. However, tobacco use and nicotine addiction generally begin in childhood or adolescence. Despite health warnings, adolescents continue to initiate smoking at alarming rates and the majority will continue to smoke as adults. Adolescents who begin to smoke, develop nicotine dependence very quickly and exhibit withdrawal symptoms during quit attempts in a similar fashion to adults. Most adolescents who smoke, express a desire to quite. To date, research on smoking cessation for teen and young adult smokers has not been particularly fruitful. This initiative requests research aimed at the development and testing of smoking cessation treatments tailored to the specific needs of adolescents and young adults. Consideration should also be given to gender and ethnicity. 19.Complementary and Alternative Medicine Therapies (CAM) for Drug Abuse Treatment. Research is encouraged on complementary and alternative interventions for drug abuse treatment either as the sole treatment or as an adjunct to enhance the therapeutic potency of existing drug abuse treatments. Any of the five CAM categories: Whole medical systems, mind-body interventions, biologically-based therapies, Manipulative/body-based therapies and energy therapies would be considered for this initiative (for more information, see http://nccam.nih.gov/). CAM therapies are interventions that are commonly used in “real world” settings, but whose therapeutic efficacy has not been scientifically demonstrated. The product of this research might also be a manual or video, which illustrates the intervention and how it is implemented by treatment staff. Geetha Subramaniam, M.D. 301-435-0974 Email: geetha.subramaniam@nih.gov 20.Developing, Evaluating, and Transporting Culturally Sensitive Behavioral Treatments for Racial and Ethnic Minorities. Minority populations are disproportionately affected by the consequences of drug abuse. Research to develop and evaluate behavioral treatments that are culturally sensitive and relevant for diverse racial and ethnic minority populations is encouraged. This may include studies of behavioral treatments, alone or in combination with pharmacological treatment, or studies of behavioral strategies for increasing adherence to taking medications. In the development and evaluation of the behavioral treatment, attention needs to be directed at examining medical, social, and cultural factors that may influence adherence to the behavioral treatment approach and treatment outcome. Also, little is known about the transportability of efficacious behavioral treatments for minority populations. Research is needed on how to transport science-based treatments to various racial/ethnic populations. 21.Incorporating Smoking Cessation in Drug Abuse Treatment. Research is encouraged to develop and test behavioral and combined behavioral and pharmacological treatments for nicotine-addicted individuals who also are addicted to other substances, such as heroin, cocaine, methamphetamines and alcohol. Prevalence of cigarette smoking is extremely high among drug dependent individuals attending drug treatment. Many treatment providers are reluctant to address smoking cessation with clients either because they believe that substance abusers are not interested in quitting or because they fear smoking treatment will have a negative impact on drug abuse treatment outcome. However, studies have shown that many drug abuse clients are interested in quitting smoking and that the concurrent treatment of tobacco dependence and other drug dependencies does not threaten abstinence and might even assist in maintaining it. Research is needed to develop and test smoking cessation treatments that can be incorporated into treatments for illicit drugs of abuse. 22.Developing Treatments for Smokers with Comorbid Disorders. Research is encouraged that focuses on the development, refinement, and testing of behavioral treatments for smokers with psychiatric comorbidity, such as depression, schizophrenia, or anxiety disorders. Smoking prevalence is very high in individuals with psychiatric disorders. These populations generally respond poorly to traditional smoking cessation treatments. Similarly, medical comorbidities are widely prevalent and are in need of additional research in adults and in special populations such as youth, LGBT and homeless persons. Research is needed to develop and test innovative behavioral and combined behavioral and pharmacological treatments that address the unique needs of these individuals. 23.Tobacco Cessation for Pregnant and Post-Partum Women. Smoking among pregnant women remains an ongoing public health concern. It is estimated that approximately 20-30% of pregnant women smoke. Maternal smoking during pregnancy has been linked to infant mortality, impaired fetal brain and nervous system development, premature and complicated births, and low birth-weight babies. For women who do quit during pregnancy, relapse rates vary, but are reported as approximately 25% before delivery, 50% within four months postpartum, and 70-90% by one year postpartum. Children of smokers continue to be at risk for respiratory illness, middle ear infections, impaired lung function, and Sudden Infant Death Syndrome. Sustained tobacco cessation during pregnancy and the postpartum period reduces health risks to both mothers and their babies. Research focused on the development of innovative behavioral and combined behavioral and pharmacological interventions for nicotine-addicted pregnant and postpartum women is encouraged. Interventions may be tailored to sub-populations of pregnant smokers, such as teenage girls, heavy smokers, ethnic minorities, or low SES populations. Examples of other potential studies may include the development of smoking cessation interventions that address co-occurring issues, such as depression or weight-gain, interventions that include partners or support persons, Internet-based interventions or interventions that can be delivered by primary care physicians. 24Behavioral Treatments for Groups. This includes the development of new psychotherapy approaches, the modification or testing of existing behavioral treatments, and the design and/or testing of innovative clinical training and supervision methods for dissemination of efficacious treatments to community settings. Examples of relevant projects are: traditional group therapies, such as 12-step and therapeutic community approaches, and newer group therapies such as cognitive-behavioral and acceptance-oriented approaches; groups for various populations, such as adolescents, adults, couple and family groups, gender-specific groups, and groups tailored for racial or ethnic minority populations. Of particular interest are projects that address the recent reports suggesting possible contraindications of group treatments for some populations (e.g., delinquent adolescents), or in some formats (e.g., less-structured, client-led groups). Debra Grossman, M.A. 301-443-2249 Email: dg79a@nih.gov 25.Developing Behavioral Treatments for Cognitively Impaired Drug Abusers. While there are currently many efficacious interventions available for drug addicted individuals in treatment, more can potentially be done to enhance treatments by addressing cognitive impairments that may accompany chronic drug use and HIV infection. Many commonly utilized drug addiction and HIV-risk reduction interventions assume certain basic cognitive capacities and abilities that may be absent, or impaired, in chronic drug abusers who may also be HIV-positive. For substance abusers to benefit from psychological treatment, they must be capable of attending to and receiving new information, integrating it with existing information stores, and translating this input into more concrete behavioral change. Substance abusers with cognitive limitations, who may not comprehend the interventions, are more likely to drop out of treatment, relapse faster, and have poorer long-term outcomes in comparison to cognitively intact substance abusers. Research is needed to develop, modify, and test “cognitive-friendly” drug dependence treatments that could lead to improved treatment response and outcome. 26.Interventions to Improve Engagement and Retention in Treatment. Therapies designed specifically to engage and retain individuals in treatment, especially those at high risk for HIV. An example could be a therapy that is: (1) sensitive to the age and motivational level of the client; (2) is specifically designed to respond to the needs of the individual, whatever his or her developmental and motivational level might be; and (3) actively works to increase an individual's desire to remain in treatment. 27.Development of New or Improved Addiction Assessment Measures and Procedures. Research directed at the improvement of a currently available measure or the design of a new psychosocial, social or environmental measure appropriate for use in the clinical assessment of youth and adult substance abusing populations. Special consideration should be given to a specific screening or diagnostic tool, or to a specific measure of treatment readiness, treatment compliance, service utilization, therapeutic process or drug treatment outcome. 28.Marijuana Treatment. Marijuana is the most commonly used illicit substance in the U.S. However, relative to other drugs of abuse, little research has focused on the treatment of marijuana dependence. Trends in the literature suggest that the types of treatments effective with other substances of abuse are likely to be effective with marijuana dependence. Initial studies also suggest that many patients do not show a positive treatment response, indicating that marijuana dependence is not easily treated. Research is needed toward developing and testing effective interventions for marijuana dependent individuals. 29.Transporting Behavioral Treatments to Community Practitioners. There is a need for effective methods of transferring behavioral treatments found to be effective in Stage I clinical trials to clinical practice. Cognitive-behavioral therapy, operant behavioral therapy, group therapy, and family therapy are among the therapies that have been shown to be efficacious in a highly controlled setting and may be helpful treatment approaches in community treatment programs as well. However, community practitioners may have been trained using other approaches and may not have been exposed to these scientifically based approaches. Emphasis should be placed on examining mechanisms to transfer effective research-based drug abuse treatment information and skills-based techniques to practitioners in the community. This may involve the development and testing of innovative training materials and procedures to use in the training of community practitioners to skillfully administer these treatments, including the development of highly innovative technology transfer and communication approaches. Research testing the transportability of empirically supported therapies to the community is an important component of the Behavioral and Integrative Treatment Development Program. There is also a need for the development of educational methods to train non-drug abuse health care workers in relating to drug abusers; eliciting medical histories regarding past or present drug abuse; recognition of the signs and symptoms of drug abuse; identification of those at high-risk for HIV and other drug abuse related medical problems such as tuberculosis or hepatitis. Development and validation of a drug abuse screening instrument which can be administered by primary health care providers, and training in administering such an instrument is also needed. Will Aklin, Ph.D. 301-443-3207 Email: aklinwm@mail.nih.gov 30.Treatment Modules for Specific Problems or Populations. Discrete therapy components that address specific problems common among drug addicted individuals and that can be implemented in conjunction with other therapeutic services. For example, an investigator may wish to develop a four session, highly focused, job seeking skills module that can be easily implemented by a wide range of practitioners to effectively increase appropriate job seeking behavior. Other examples include, but are not limited to, modules to engage ambivalent drug dependent individuals in treatment, modules to increase assertiveness in female drug addicts who feel pressured by others to use drugs, modules to improve study skills and pro-social interactions among withdrawn substance abusing adolescents, or to incorporate effective HIV risk reduction techniques. 31.Behavioral Treatments for Pre-Adolescents and Adolescents. Developmentally appropriate behavioral treatments for pre-adolescents and adolescents that incorporate HIV risk reduction counseling as an integral component of the treatment. This includes the development of new, or refinement of existing psychotherapies, behavioral therapies, and counseling (group and/or individual). This also includes the development and testing of manuals as well as other creative, interactive approaches for therapy delivery that may consider different settings for delivery, such as primary care, school-based health programs, juvenile justice settings, etc. Also the behavioral treatments should be culturally and gender sensitive. 32.Behavioral Treatments for Couples and Families. This includes the development of new psychotherapy approaches, the modification or testing of existing behavioral treatments, and the design and/or testing of innovative clinical training and supervision methods for dissemination of efficacious treatments to community settings, for youth and adult substance users. Treatments that target domestic violence or other forms of interpersonal abuse along with substance abuse are encouraged. 33.Innovative Technologies for Drug Abuse Treatment, HIV Risk Reduction, and Training Clinicians. Relevant research would be directed at the development and evaluation of innovative technologies to treat substance abuse, enhance adherence to medications, and/or reduce risk for HIV infection or transmission. Approaches should be capable of being readily incorporated at reasonable cost into various treatment settings. Areas of interest include Internet-based treatment or training programs, CD-ROM technology, audio delivery devices, photo therapeutic instruments, and hand-held computers. Also of interest are creative approaches for disseminating science-based behavioral treatments and for training therapists to use scientifically based treatments for drug abuse and addiction. Such approaches might include Internet-based education, interactive computer programs, telemedicine, etc. Finally, approaches which apply therapies with evidence of efficacy through new media such as web-based platforms, over email, or through chat rooms and bullet boards are also desirable. Jessica Chambers, Ph.D. 301-443-2237 Email: jcampbel@nida.nih.gov B. Clinical Neuroscience Research. The Clinical Neuroscience Branch (CNB) supports research on the biological etiology (determining the biological basis for vulnerability to drug abuse and progression to addiction, including studies on individual differences and genetics) and clinical neurobiology of addiction (exploring alterations of the structure and/or function of the human central nervous system following acute or chronic exposure of drugs of abuse), and the neurobiology of development (neurobiological effects of drugs of abuse and addiction during various stages of development and maturation, effects of drug exposure on neurobiological processes, development of methodologies and refinement of techniques used in pediatric neuroimaging). The Branch also supports investigations on the cognitive neuroscience of drug abuse and addiction, the neurobiology of treatment, neuroAIDS, and human pain and analgesia. Areas that may be of interest to small businesses include, but are not limited to: 1.Innovative Technology and Tools for Human Substance Abuse Research. There is a continuing need for the development of methods, tools, and technology that can be used as markers of or interventions for brain, genetic or behavioral (including cognitive and affective) alterations in humans related to the risk, or reliance (etiology) of, effects of, or recovery from substance abuse. NIDA has a strong interest in facilitating the identification and use of cross-disciplinary research tools and materials that can be applied to human research that will advance our understanding drug abuse. NIDA also has a strong interest in promoting the commercial adaptation and widespread availability of discoveries (“tools”) made in the course of interdisciplinary research to better serve its mission. The term research “tool" is being used in its broadest sense to embrace the full range of resources that scientists use in the laboratory and clinicians use as therapeutics; therefore, one investigator’s tool may be another's end product. The value of research tools is difficult to assess and varies greatly from one tool to the next and from one situation to the next. Providers and users are likely to differ in their assessments of the value of research tools. Many research and clinical tools are costly to develop and have significant competitive value to the firms that own them. Of particular interest are methods that could be used to determine the effects of drug abuse/ addiction treatments on neurobiological systems in an attempt to understand the neurobiological processes underlying risk and recovery. Also of interest are methods and tools that can be integrated or expend with brain imaging techniques or other brain-related measures that can be used in human subjects. Examples include, but are not limited to; Development of stimulus-generating hardware and/or software for use in substance abuse studies, including neurocognitive tasks, presentation of drug-related images for the induction of craving or to probe attentional or affective processes, and “virtual reality” types of dynamic stimuli important in studies of drug abuse and addiction; Remote and mobile based technologies such as PDA’s, “smart phones”, or web-based applications for measuring cognitive and affective function in real world environments; Development or implementation of interventions such as trans-cranial or direct current brain stimulation, real-time neurofeedback, or cognitive training; New infomatic tools for primary data analysis or secondary data analysis would also be appropriate; Another example would be methods or technology related to development of the human central nervous system and how drugs of abuse perturb this process. Developmental studies of these populations presents unique challenges when using neuroimaging technology. The development of novel techniques, or the refinement of existing methods, to provide direct noninvasive measures of brain structure and/or function that are adapted specifically for use in pediatric and adolescent populations is strongly encouraged. Also, neurocognitive and other neurobehavioral tasks for use in these populations, especially where they can be designed to probe underlying neurobiological processes, need to be developed (for developmental issues, contact Cheryl Boyce, Ph.D.). Steven Grant, Ph.D. 301-443-4877 Email: sgrant@nida.nih.gov or Cheryl Boyce, Ph.D. 301-443-4877 Email: cboyce@nida.nih.gov 2.Human Brain Neurochemical and Molecular Imaging. Measurement of brain neurochemistry, neuropharmacology (receptors) and gene expression in humans using non-invasive imaging has lagged behind advances in these areas in pre-clinical research as well as in functional and anatomical neuroimaging in humans. There is a continuing need for development of new ways to measure molecular targets in the human brain. Examples include, but are not limited to novel radioligands for PET and SPECT imaging in human brain for molecular targets (e.g., receptors, intracellular messengers, disease-related proteins), as well as novel methods that use magnetic resonance imaging or other emerging technologies such as optical imaging.. The primary application of these methods will be in basic human research. Ultimately, these measures may also be used as potential biological markers and surrogate endpoints for translational and clinical research, drug discovery and development, and clinical trials. The scope of the projects may encompass pilot or clinical feasibility evaluation in pre-clinical studies, model development, or clinical studies. Alternatively, the focus may be on research and development of new technologies for molecular, neurochemical or neuropharmacological development. Steven Grant, Ph.D. 301-443-4877 Email: sgrant@nida.nih.gov 3.Neuro-Rehabilitation of Drug-Induced Cognitive Deficiencies. The increased awareness that the brain is capable of substantial plasticity throughout the lifespan has opened the possibility that intervention can be developed alter brain or cognitive function so as to accelerate recovery of brain and cognitive dysfunction. Such interventions encompass both direct interventions of brain function as well as indirect interventions based on cognitive or behavioral principles. Direct interventions include trans-cranial or direct current brain stimulation, real-time neurofeedback, and deep brain stimulation. Another complementary approach is based on game technology for “serious (health-related) rather than purely recreational purposes. Serious games can provide a completely controlled, noninvasive, safe and alternative methodology for a variety of important studies of drug abuse and addiction. By involving a person in an interactive computerized situation, designed to be both entertaining yet directive (i.e., in the sense of covertly shaping desired behaviors via highly flexible and programmable sets of scenarios), altered behaviors can be introduced by pre-programming consequences to counteract and potentially reset undesirable neurobiological and neurobehavioral deficits associated with chronic drug abuse. Areas of cognitive impairment related to substance abuse that could be enhanced through the use of either direct brain interventions, or “serious” games include diminished decision-making ability, attention/concentration deficits, attentional biases, lack of cognitive flexibility and problem solving abilities, inability to use feedback to monitor/change behavior, memory impairments,. Steven Grant, Ph.D. 301-402-1746 Email: sgrant@nida.nih.gov 4.Measurement of Psychosocial Stress in Relation to Substance Abuse. There is the need for development, improvement and/or adaptation of precise and reliable field deployable measurement technologies can detect and quantify an individual’s exposure to psychosocial stress and/or one or more drugs. Ideally, the technology could be scalable from selected samples to full population studies. Comprehensive assessment includes measuring acute/chronic/cumulative exposures to psychosocial stress and/or addictive substances with a high degree of temporal and spatial resolution (i.e., as a person moves through environments), and with a high degree of accuracy and sensitivity to detect meaningful variations in extent of and response to exposure across developmental periods (ranging from prenatal to senescence) and among various population groups. Such technologies may include use of emerging remote and mobile technologies such as PDA’s, “smart phones”, or web-based applications. Harold Gordon, Ph.D. 301-443-4877 Email: hr23r@nih.gov C.Human Development Research. The Behavioral and Brain Development Branch (BBDB) supports a broad research, research training and career development programs directed toward: (1) an increased understanding of how developmental processes and developmental outcomes are affected by drug exposure and related factors; (2) an increased understanding of developmental processes that are relevant to: (a) drug use, abuse, addiction, treatment and relapse, and (b) risk behaviors related to drug abuse and other health conditions that often accompany drug use (e.g., HIV infection, STDs); (3) the use of translational approaches to increase understanding of these developmental processes; and (4) an increase in effective interventions aimed at preventing or ameliorating negative developmental outcomes resulting from exposure to drugs and related factors across diverse populations (e.g. racial/ethnic minority; rural/urban, etc.). 1.Develop Improved Technology for Assessment of Prenatal Drug Exposure and Passive Postnatal Drug Exposure. a.Develop and refine methods for the detection and quantification of infant exposure to drugs of abuse during pregnancy, including nicotine cocaine, marijuana, opiates, and methamphetamines. b.Develop and refine methods for the detection and quantification of passive exposure to illicit drugs during infancy and childhood including second and third hand exposure to nicotine, marijuana, or other drugs of abuse. c.Develop technologies for us in diverse settings (e.g. primary care, emergency rooms, obstetrics/gynecology, etc.) of the assessment of prenatal drug exposure and passive postnatal drug exposure. Nicolette Borek, Ph.D., 301-402-0866 Email: nborek@nida.nih.gov 2.Develop Interactive Database Systems on Human Subjects Issues for Use by Drug Abuse Researchers Studying School-Age Children and Adolescents Drug Use. Develop systems to assist investigators in obtaining technical and legal information relevant to involvement of children and adolescents in research on drug abuse. Examples of pertinent situations include tracking long-term health and development of children exposed to drugs during pregnancy, and investigating vulnerability and possible pathways to drug abuse including children in primary care and child care settings, and school-age children and adolescents. Human subject issues addressing family environments, child abuse and domestic violence, and secondary data sources are also of interest. These database systems should address issues such as assent and consent, should provide information on variation in laws and guidelines across jurisdictions, should include the capacity for interactive communication on numerous situations potentially facing clinical research and health care professionals, and should serve as sources of referral for additional assistance. Nicolette Borek, Ph.D. 301-402-0866 Email: nborek@nida.nih.gov 3.Develop Improved Methods of Neuroimaging to Assess Structural and Functional Status of the Brains of Children and Adolescents Exposed to Drugs. Document the feasibility and accuracy of appropriate and acceptable methods for assessing brain structure and function of children and adolescents, with special attention to any or all of the following groups: those exposed to drugs during pregnancy, those passively exposed during infancy and childhood, This could also include products to improve the tolerability, safety and validity of neuroimaging in children and adolescents, e.g. tools or techniques to reduce head-motion artifacts and image those actively using illicit substances. Documentation should include attention to such matters as technological difficulties and risks, and standardization issues relevant to testing conditions and image analysis. Karen Sirocco, Ph.D. 301-443-4877 Email: ksirocco@nidal.nih.gov or James Bjork, Ph.D. 301-443-3209 Email: jbjork@nida.nih.gov 4.Develop and Refine Methodologies and Clinical Tools for Measurement and Effective Interventions of Developmental Factors and Drug Use Among Children and Adolescents. a.Research to develop and refine methodologies for drug use detection and quantification which may address issues of acceptability, reliability, and validity of one or more methods for clinical research and practice (e.g., interviews, computerized questionnaires, and biological indicators such as saliva or sweat). Development of web, hardware and software technology tools to enable refined physiological and behavioral assessment of normal and atypical infant and child development which may inform risk and interventions for drug use are also of interest. Nicolette Borek, Ph.D. 301-402-0866 Email: nborek@nida.nih.gov b.Research and development of novel, or the enhancement of existing tools to be used in effective preventive or treatment interventions, and information dissemination to or understand drug use and its developmental effects for children, adolescents and their families. These tools might be used by researchers, health professionals and other health care providers, as well as by those in the broader community, including educators, day care providers, family members, etc. These tools must take into account cultural and developmental factor to assure their effectiveness and validity. Cheryl Anne Boyce, Ph.D. 301-443-4877 Email: cboyce@mail.nih.gov. Office of Science Policy and Communications (OSPC) Science Education. In order to improve science education in the area of drug abuse research (e.g., disciplines such as neuroscience, psychology, epidemiology), efforts are needed to develop innovative methods for improving knowledge of and generating interest in science among school children, the general public, health care providers, and others. These might include but are not limited to: •Development of innovative curricula using state of the art technology. •Development of media programs on the science of drug abuse and addiction. These may include television, radio, motion pictures (including CD, and DVD), newspaper articles, magazine articles, books, experiments, computer software, CD-ROMs, web sites, social media or electronic communications instruments or channels, or other written, electronic, or audiovisual presentations designed to educate about the biology of drug abuse and addiction. •Development of methodologies to present drug abuse and science information to particular groups, such as kindergarten and elementary school students, African Americans, Hispanics, persons with disabilities and health care providers. •Development of computer based learning systems that allow students to experience the scientific process. •Development of virtual reality or serious gaming to present neuroscience/drug abuse information for children and others. •Development of specific materials, activities, or programs that promote science education related to drug abuse, such as exhibits, curriculum materials, coloring books, videos, teacher education workshops, partnership programs with scientists and educators, or workshops for health care providers. •Development of specific materials, activities or programs that promote the teaching of scientific and research ethics to middle and high school students. Cathrine Sasek, Ph.D. 301-443-6071 Email: csasek@nih.gov International Program NIDA’s International Program develops and disseminates important new information on the causes, consequences, prevention and treatment of drug abuse and addiction that will help address the growing problems related to illegal drug use and addiction around the world. NIDA’s International Program is currently interested in supporting US-based small businesses to develop products and services in the following areas: 1.Development of standardized behavioral, physiological, and/or toxicological measures of drug use and drug impairment for use in international comparative studies of drugged driving. 2.Development of a mechanism to enhance international drug abuse researchers’ ability to conduct secondary data analyses. While the strategies to address the international phenomenon of drug addiction need to be empirically driven, there are limited funds to support original international drug abuse research which subsequently increases the importance of secondary analyses of existing data sources particularly in low- and middle-income countries. The mechanism to expand the use of existing data sources that can inform policy is likely be multifaceted and may include: identification of existing data sources, provision of training in secondary data analyses, and interpretation of data analyses for making policy-based decisions. The focus of the research can address any component of drug use, abuse and addiction that is within NIDA’s research portfolio. Steve Gust, Ph.D. 301-443-6480 Email: sgust@nida.nih.govHHS201104262011042620110626-1Closed67059http://www.sbir.gov/node/67059The NIDCR conducts and fosters research on the etiology, pathogenesis, prevention, diagnosis, and treatment of oral, craniofacial and dental diseases and conditions. For more specific information about areas of interest to the NIDCR, please visit our home page at http://www.nidcr.nih.gov. NIDCR’s small business programs are highly focused on maximizing translational opportunities – moving rapidly and intentionally toward pushing innovation in basic orofacial biology into useful products. The following are areas of particular interest. Developmental Biology and Mammalian Genetics Emphasis is on the understanding of the development of tooth and bone, and on the identification of the genetic and environmental contributions to craniofacial disorders. The objective of this scientific program is to elucidate the underlying causes of craniofacial disorders, thereby advancing the fields of diagnosis, treatment, and prevention. Small business opportunities in this area include but are not limited to: A.Develop early pregnancy genetic tests to screen fetal cells in maternal blood for genetic mutations involved in inherited syndrome and non-syndrome craniofacial defects. B.Develop instrumentation to improve the diagnosis and treatment of inherited and acquired craniofacial defects. C.Develop improved appliances to aid suckling by newborn infants with cleft palate and cleft lip. Infectious Diseases and Immunity Research relating to the etiology, pathogenesis, prevention, diagnosis and treatment of infectious diseases of the oral cavity is supported by the NIDCR. This includes research on practical ways to effectively use the host immune system to prevent or treat oral infectious diseases and microbial-induced inflammation. Infectious diseases of the oral cavity include caries, periodontitis, candidiasis, peri-implantitis, pulpitis, and various viral, bacterial, and fungal infections of the oral mucosa and research on the diagnosis and prevention of oral manifestations and malignancies of HIV infection and AIDS. Specific examples of technology development needs include but are not limited to: A.Develop ways to overcome or eliminate the risk of oral infections in persons who smoke or chew tobacco, drink alcohol, or are immunosuppressed, have diabetes, are malnourished, or are psychologically stressed. B.Explore novel methods or agents to eradicate oral biofilms (dental plaque) on teeth, oral soft tissues, and dental implants without adversely effecting the normal oral flora. C.Isolate, synthesize or prepare new antibiotics and antimicrobial agents that can overcome bacterial and fungal resistance to current compounds. Formulate combinatorial drug regimens to attack microbes growing in oral biofilms (dental plaque). D.Develop controlled release systems for local delivery of synthetic peptides, recombinant proteins, or other chemical or immunotherapeutic agents to prevent, control, and/or treat oral infectious diseases, or the oral manifestations of HIV infection. E.Develop biological response modifiers or other immunological approaches to reduce or eliminate microbial-induced chronic inflammation or the tissue destruction associated with chronic inflammation in the oral cavity. F.Develop ways to interfere with microbial colonization and growth through the use of antimicrobial agents and chemotherapy. G.Identify and exploit the structural features of oral biofilms for increased therapeutics delivery. H.Develop computer programs to model biologically active peptide regions of oral components that have anti-fungal, anti-bacterial and anti-viral activities. Challenges appropriate for small business applications could include: I.Develop substitutes of naturally occurring chemicals (phytochemicals) known to have a role in controlling opportunistic infections induced by HIV. J.Develop synthetic peptides and recombinant proteins of oral components with anti-fungal, anti-bacterial and anti-viral activities including those against HIV. K.Develop oral topical formulations with combined microbicidal, analgesic, and anti-inflammatory activities to enhance oral mucosal defenses and prevent and/or control oral infections and lesions in HIV-infected and/or immunosuppressed subjects. Epithelial Cell Regulation and Transformation Emphasis is on the molecular mechanisms of oral epithelial cell regulation and aberrations of these mechanisms. Research related to early diagnosis, prevention, and treatment of oral neoplasias is particularly relevant for the NIDCR small business program. Some examples include but are not limited to the following areas: A.Develop imaging techniques for the early detection, diagnosis and prognosis of pre-malignant head and neck lesions including oral salivary gland carcinomas. B.Develop immunotherapies (e.g. vaccines, gene therapies) effective against viruses suspected to be etiologic agents in the induction of pre-malignant and malignant head and neck lesions. C.Develop effective pharmacological, immunological and radiological modalities for treatment of pre-malignant and malignant head and neck lesions. D.Develop novel technologies for the genetic and molecular-targeted therapy of head and neck carcinomas. E.Develop novel micro and nano-sensor technologies that can release therapeutic agents in tumor cells. F.Develop regimens for the alleviation of the oral complications of cancer therapy. G.Develop novel technologies for using stem cells as therapeutics for head and neck cancers. Mineralized Tissue and Salivary Gland Physiology, Pharmacogenetics and Injury Emphasis is on the physiology of bones, teeth and salivary glands, craniofacial tissue damage and repair, and pharmacogenetics of agents used for the treatment of craniofacial and oral diseases and disorders. Such technologies that could speed translational research might include but are not limited to: A.Develop standardized, high-sensitivity, high-accuracy methods, instrumentation, and/or devices to detect oral bone loss, assess alveolar bone quality, and to monitor for bone repair. B.Develop novel agents and vehicles for local inhibition of bone loss and/or augmentation of bone growth for the treatment of periodontal diseases or craniofacial reconstruction. C.Develop novel methods and instrumentation to detect and/or treat the earliest signs of demineralized enamel that may develop into carious lesions. D.Develop systems that effectively remove or neutralize dental caries using non-mechanical means to minimize iatrogenic pulp death. E.Develop non-invasive devices to assess pulpal health prior to and during treatment; develop means to neutralize necrotic pulps non-mechanically to reduce or eliminate the need for root canal therapy. F.Develop novel methods and agents to promote scarless repair of cleft lip and scarless cutaneous healing following craniofacial surgery. G.Develop viral and non-viral vectors for salivary gene therapy and gene therapeutics. H.Develop non-invasive methods for the determination of efficacy and safety of artificial saliva, sialogogues and of their delivery vehicles used in addressing the diminution or lack of saliva (xerostomia) due to Sjögren’s syndrome or head and neck irradiation cancer therapy. I.Develop apparatus for craniofacial bone distraction for building bone for craniofacial reconstruction or orthodontic procedures. J.Develop more efficient methods, materials, and devices for prevention of injuries to the teeth, mouth, and face during athletic activities. K.Develop genetic standards, databases, and diagnostics to predict oral responses to drugs used for the treatment of craniofacial, oral and dental diseases. L.Develop standardized methodologies for the detection of fluoride load in the body from saliva, serum, urine, nail clippings, and hair. Molecular and Cellular Neuroscience Emphasis is on research on chronic disabling diseases of the oral-craniofacial-dental areas including chronic pain, neuropathies and neurodegenerative disorders, diseases of the temporomandibular joint. NIDCR encourages small business applications to: A.Develop improved techniques for measuring nociceptive, chemosensory, tactile, kinesthetic, or proprioceptive function involving craniofacial structures. Such measures may be useful in screening for deficits, improving diagnosis, or for evaluating responses to dental treatments or interventions. B.Develop improved measures for assessing oral-motor coordination or oral behaviors (e.g., swallowing, masticatory efficiency). C.Develop improved biomarkers or treatments for neuropathic conditions or neurodegenerative conditions affecting oral-craniofacial tissues or structures. D.Develop assays facilitating reliable evaluations of relationships between hormonal or chronobiological variations and other risk factors as these relate to onset or exacerbation of pain symptoms. E.Discover and develop non-narcotic medications with particular emphasis on chronic orofacial pain disorders. Biotechnology and Biomaterials Emphasis is on the development of novel biomaterials and technologies for promoting repair, regeneration, restoration and reconstruction of diseased and injured oral and craniofacial tissues. This includes development of natural and synthetic biomaterials for dental repair and for manufacturing of craniofacial tissue replacement constructs, quantitative methods for evaluating the quality and performance of biomaterials and tissue constructs, as well as their interactions with host tissues. Specific examples of relevant small business applications could include but are not limited to: A.Develop technologies for design and fabrication of biocompatible biomaterials and tissue constructs to be used for reconstruction and regeneration of oral and craniofacial tissues. B.Develop non-destructive in vitro and in vivo methods for imaging of cells, tissue constructs and biomaterials. C.Develop methods for curtailing disease-associated inflammation and promoting wound healing and endogenous regeneration of oral and craniofacial tissues. D.Develop synthetic analogues of oral and craniofacial tissues and organs for use in high throughput biological assays of tissue function and physiology. E.Develop sensitive methods for measuring and quantification of biomaterial-tissue biocompatibility and biotoxicity including restorative materials interacting with secondary decay. F.Develop mathematical and computer algorithms for modeling oral and craniofacial tissue function and physiology. G.Develop technologies for ensuring sterility of biomaterials and tissue engineered constructs prior to implantation. H.Develop efficient and non-immunogenic viral and non-viral gene delivery systems to oral and craniofacial tissues. I.Develop nanotechnology-based implantable biomaterials for dental, oral and craniofacial tissue restoration. J.Develop improved surgical techniques for replacement of dental, oral and craniofacial tissues and organs. K.Develop safe and effective technologies for the diagnosis and treatment of temporomandibular joint disorders (TMJDs). L.Develop safe and effective biomaterials and construct fabrication technologies for repairing TMJDs. M.Develop new or improved composite biomaterials and adhesive sealants (possibly replacing Bis-GMA resin-based systems) suitable for restoring crowns of posterior teeth and exposed roots of teeth. N.Develop new effective orthodontic and other prosthetic appliances and constructs. O.Develop approaches for generating complex tissue/organ structures, such as teeth, periodontal ligament, TMJ, and vascularized and innervated bone and muscle. P.Develop methods for standardization and comparison of different stem and progenitor cell populations for use in dental and craniofacial tissue engineering. Q.Develop methods for targeted delivery and release of therapeutic biomolecules to oral and craniofacial tissues. R.Development of instrumentation for early caries detection and comparison studies on specificity and selectivity with respect to current clinical practice. Clinical and Behavioral Research Provides support for the development of evidence-based products related to behavioral and social aspects of oral health, oral health prevention or treatment interventions, and other patient-oriented aspects of oral health. This includes support for clinical trials and patient-oriented research to establish safety and initial efficacy of products. NIDCR is especially interested in applications that significantly improve oral health by: 1) being broadly applicable to many populations, 2) contributing to meaningful oral health improvements for a specific population, 3) expediting translation of research findings into oral health improvements, and/or 4) equipping oral health care providers, educators or researchers with tools to improve public oral health. Examples of studies of interest include, but are not limited to, the following: A.Develop and test devices or methods to improve time-sampled monitoring of behavioral adherence with preventive or therapeutic regimens specifically relevant to oral diseases/conditions. Such devices or methods could be utilized in a variety of settings, including naturalistic settings, within clinical trials, within oral health care delivery systems, etc. B.Develop and test novel compliance and survey measures or tools to identify the underlying causes of insufficient preventive dentistry for specific underserved populations. C.Develop, or adapt for use in a new population or setting, novel measures or methods for identifying individual, family, group, or other processes that explain oral health behavior. D.Develop and test for safety, efficacy, and/or effectiveness of measures or materials for diagnosing, preventing, or treating oral, dental, and craniofacial conditions and disorders. E.Develop, or adapt for use in a new population or setting, oral health interventions utilizing technology to improve efficiency of delivery (e.g., management of chronic pain related to temporomandibular joint disorders, etc.). F.Develop, or adapt for use in a new population or setting, interventions addressing health behaviors highly associated with oral health (e.g., tobacco, alcohol, and other drug use; management of diabetes, HIV infection, or other chronic illnesses; etc.). G.Develop technologies or modules that utilize existing web-based platforms to improve preventive oral health hygiene for children and adolescents (e.g., social marketing via web-based interaction, virtual reality “worlds”, “massively multiplayer online games”, etc.). H.Develop and test innovative methods for facilitating collaborations, referrals, and/or ongoing follow-ups between oral health professionals and other health care professionals. I.Develop and test web-based training or other innovative approaches for oral health care professionals to accelerate accurate translation of new knowledge regarding oral diseases and their effective prevention or treatment into clinical or public health practice. J.Develop and test the effectiveness of innovative teaching tools to inform oral health professionals or the public regarding oral cancer prevention and early detection. Other Research Topic(s) Within the Mission of the Institute For additional information on research topics, contact: R. Dwayne Lunsford, Ph.D. Coordinator, SBIR/STTR Program Director, Microbiology Program Integrative Biology and Infectious Disease Branch Division of Extramural Research National Institute of Dental and Craniofacial Research-NIH 6701 Democracy Blvd., Rm. 626 Bethesda, MD 20892-4878 301-594-2421, Fax: 301-480-8319 Email: lunsfordr@nidcr.nih.gov For administrative and business management questions, contact: Ms. Mary Greenwood Chief Grants Management Officer National Institute of Dental and Craniofacial Research 6701 Democracy Blvd., Rm. 658 Bethesda, MD 20892-4878 301-594-4808, Fax: 301-480-3562 Email: md74u@nih.govHHS201104262011042620110626-1Closed67059http://www.sbir.gov/node/67059The NEI supports research with respect to blinding eye diseases, visual disorders, mechanisms of normal visual function, preservation of sight, and the special health problems and requirements of individuals with impaired vision. Applications for all areas of vision research are encouraged. Examples that may be of interest to small businesses are provided below, but this list is not meant to be exhaustive. Phase IIB Competing Renewal Awards The NEI will accept Phase IIB SBIR Competing Renewal grant applications from NEI-supported Phase II SBIR awardees to continue the process of developing technologies that ultimately require federal regulatory approval or require extraordinary time and effort in the Research and Development phase. Such technologies include, but are not limited to, pharmacologic agents, biological products, and devices related to the mission of the NEI. This renewal grant should allow small businesses to reach a stage where interest and investment by third parties is more likely. The Competing Renewal application must be a logical extension of a previously completed NEI-supported Phase II (R44) SBIR grant. NEI grantees seeking SBIR Phase IIB Competing Renewal funding must submit an application within a period no later than the first six receipt dates following expiration of the previous Phase II budget period. Budgets up to $750,000 total costs per year and time periods up to two (2) years may be requested for this Phase IIB Competing Renewal opportunity. Potential applicants are strongly advised to contact Dr. Jerome Wujek (contact information provided below) before beginning the process of putting an application together. The following examples would make appropriate topics for proposed NEI SBIR Phase IIB Competing Renewal projects. These are meant for illustrative purposes only and are not exclusive of other appropriate activities: •Preclinical studies, including pharmacology and toxicology, beyond those conducted under the Phase I (R43) and initial Phase II (R44) grants. Some in vivo or in vitro studies would be expected to have been carried out in Phase I or the initial Phase II grant. •Completion of studies as required by the Food and Drug Administration (FDA) for Investigational New Drug (IND) or New Drug Application (NDA). •FDA-required pre-clinical and clinical safety and effectiveness studies of medical devices and tissue engineered products for an Investigational Device Exemption (IDE) or Pre-market Approval (PMA). •FDA-required evaluation of novel imaging approaches for diagnostic purposes. General Research Topics NEI is interested in providing support for the development of new technologies, strategies, research tools, reagents and methods that can be applied to basic and translational research which will benefit vision health. This encompasses research and development of innovative enabling technologies in areas of genomics, proteomics and nanotechnology. More specific topics include drug discovery, high throughput assays, drug delivery systems, gene therapy and cell-based therapies, development of in vitro and in vivo disease models, surgical devices and materials, telemedicine and teaching tools, and design and fabrication of new or improved ophthalmic instruments for diagnosis and treatment of eye disorders. Retinal Diseases Program Research and development of new therapeutic approaches for inflammatory and degenerative diseases and for inhibition of abnormal angiogenesis in the retina and choroid; development of better methods of diagnosing and treating diabetic retinopathy and other vascular diseases; development of non-invasive techniques for early diagnosis of macular degeneration and other retinal degenerative diseases; development of instruments and procedures for improved surgical management of retinal detachments; development of retinal prostheses to help restore visual function; development of methods for cell or tissue transplantation. Corneal Diseases Program Research and development of new therapeutic agents and drug delivery methods for the treatment of corneal injury, infection, dry eye and other ocular surface disorders; development of new biomaterials for corneal prostheses and corneal transplants; development of instruments and procedures for correcting the refractive power of the cornea and/or measuring the cornea's optical properties or other physiological properties. Lens and Cataract Program Research and development of new approaches in the post-operative management of cataract surgery; development of new surgical instruments for cataract extraction and new biomaterials for replacement of the natural lens; development of accommodative intraocular lenses. Glaucoma and Optic Neuropathies Program Research and development of new therapeutic agents, instruments, and procedures for the diagnosis and treatment of glaucoma; development of non-invasive methods to measure changes in the optic nerve head and retinal fiber layer. Strabismus, Amblyopia, and Visual Processing Program Research and development of new approaches to detect and treat strabismus and abmlyopia; development of new tools and techniques for vision screening; development of innovative techniques to study factors that facilitate regeneration and guidance of nerve fibers. Visual Impairment and Blindness Program Research and development of instruments and methods to better specify, measure, and categorize residual visual function; development and evaluation of optical, electronic, and other devices that meet the rehabilitative and everyday living needs of blind or visually-impaired persons. Myopia and Refractive Error Research and development of instruments and procedures for diagnosing or treating myopia; development of new or improved methods and materials for correcting the refractive power of the eye and/or measuring the eye's optical properties or other physiological properties; new materials and manufacturing processes for eyeglasses and contact lenses. Additional Information The NEI's programs are described in more extensive detail in documents which are available from the Institute. For additional information about the research programs of the NEI, please visit our home page at http://www.nei.nih.gov. For more information on research topics, contact: Jerome Wujek, Ph.D. Research Resources Officer Division of Extramural Research National Eye Institute Suite 1300, 5635 Fishers Lane Bethesda, MD 20892 National Eye Institute 301-451-2020, Fax: 301-496-2297 Email: wujekjer@nei.nih.gov For administrative and business management questions, contact: Mr. William Darby Grants Management Officer Division of Extramural Research National Eye Institute Suite 1300, 5635 Fishers Lane Bethesda, MD 20892 National Eye Institute 301-451-2020, Fax: 301-496-9997 Email: wwd@nei.nih.govHHS201104262011042620110626-1Closed67059http://www.sbir.gov/node/67059The NIGMS supports research and research training in the basic medical sciences and related natural and behavioral sciences and in specific clinical areas (i.e., clinical pharmacology, trauma and burn injury, sepsis and anesthesiology). The NIGMS also supports health-related research that is otherwise not assigned to another of the PHS components. The three divisions and one center that support research of potential interest to small businesses and their collaborators include: Division of Cell Biology and Biophysics Division of Genetics and Developmental Biology Division of Pharmacology, Physiology, and Biological Chemistry Center for Bioinformatics and Computational Biology For additional information about areas of interest to the NIGMS, please visit our home page at http://www.nigms.nih.gov. This site includes staff contact information by program area (http://www.nigms.nih.gov/About/ContactByArea.htm). It also includes links to program announcements that highlight NIGMS areas of special emphasis (http://www.nigms.nih.gov/Research). In some cases, these announcements specifically mention the SBIR and STTR grant mechanisms, in most cases they do not. However, it is clear that small businesses could make contributions to the research objectives described in these announcements. Phase IIB Competing Renewal Awards NIGMS will accept Phase IIB SBIR-only Competing Renewal grant applications to continue the process of developing products that ultimately require 1) clinical evaluation, 2) approval by a Federal regulatory agency, and 3) continuing refinements to durable medical equipment (DME) designs such as cost reduction, testing for safety, durability, and reliability, and meeting or establishing standards. This renewal grant should allow small businesses to get to reach a stage where interest and investment by third parties is more likely. Such products include, but are not limited to biological products, devices, drugs, medical implants, etc. related to the mission of the NIGMS. The previously funded Phase II SBIR grant need not have been submitted in response to a particular solicitation, as long as the research is appropriate to the purpose of this solicitation. Budgets up to $750,000 total costs per year and time periods up to 2 years may be requested for this Phase IIB Competing Renewal opportunity. These awards are intended to support completion of research needed to obtain an IND or IDE. Applicants must provide evidence that they have consulted formally with the FDA concerning the research needed for the development of a drug, biologic or medical device and that the proposed research will address these regulatory requirements. Such evidence should include FDA correspondence from a pre-IND meeting for an IND application or a pre-IDE meeting for an IDE application, and the status of the project in a timeline related to Federal regulatory approval processes. Prospective applicants are strongly encouraged to contact NIH staff listed at the end of this NIGMS topics announcement prior to submission of a Phase IIB Competing Renewal application. Prospective applicants are strongly encouraged to submit to the program contact a letter of intent that includes the following information: •Descriptive title of the proposed research •Name, address, and telephone number of the Principal Investigator •Names of other key personnel •Participating institutions •Funding Opportunity Announcement Number (e.g., PA-10-XXX) Division of Cell Biology and Biophysics Research on membrane synthesis, structure, and function; membrane models; membrane transport; cell division; cell organization; cell motility; and biophysics of proteins, nucleic acids, and biological assemblies, including viral entry, packaging, maturation, and release, as well as the development of instrumentation, components, and methods for the analysis of cellular components and macromolecules by imaging, spectroscopy, and diffraction analysis. SBIR and STTR applications on the application of cell biology, biophysics, biochemistry, physics, mathematics, and chemistry to biomedical problems, and the development of instrumentation to facilitate research in cell biology and biophysics, such as, but not limited to, the topics listed below are welcome. A.Development and improvement of methods for the expression, solubilization, and purification of milligram quantities of regulatory, cellular, and membrane associated proteins, as well as for the preparation of specifically labeled macromolecules and the recovery of proteins from inclusion bodies. B.Development of novel ligands, inhibitors, and other probes for spectroscopic and microscopic analysis of cellular assemblies and viral structures, macromolecules and components, their localization and function in vivo and at a single molecule level. C.Development of instrumentation, devices, and methods for detecting in real time, analyzing, and separating biologically important compounds, macromolecules, and their interactions. D.Development of new methods and materials directed toward the solution of biological macromolecule structures by, but not limited to, x-ray diffraction, electron diffraction, and NMR spectroscopy. 1.New methods for the determination of the structures of membrane associated proteins. 2.New methods for the determination of macromolecular structures in a high throughput mode, including improved detectors, data collection, automated data analysis, and faster software for structure calculations and comparisons. 3.New methods designed to improve the efficiency of beam line use at synchrotrons. 4.New methods and technology which enhance the efficiency and reduce the costs of structural genomics protein structure determination pipelines. 5.New methods to facilitate the structure determination of large macromolecular assemblies. E.Development of technology for the imaging of molecules and cells, including but not limited to: 1.Reagents, methods, instrumentation and software for existing and potential kinds of microscopy of molecules and cells (including light, electron, X-ray, scanning probe, and others). Improved probes and supporting technologies for dynamic (real-time) imaging of molecules and molecular events in living cells by light microscopy. 2.Reagents, methods, and software for conventional and cryo-electron microscopy, including automated apparatus for controlled and reproducible specimen preparation. 3.Instrumentation, methods and technologies for analysis and manipulation of cells, subcellular components, and single molecules, including atomic force microscopy, atomic forceps and tweezers, and solid state microscopy. 4.Development of analytical systems and tools such as imaging systems and probes, to be used at the nanoscale. 5.Methods, probes, and data analysis for spectroscopy, including magnetic resonance, fluorescence spectroscopy, and EPR. F.Theoretical methods for, but not limited to: 1.Analysis of macromolecular structures. 2.Prediction of the three dimensional structures of biological macromolecules. 3.Improved methods for structure-based drug design. 4.Improved methods for the simulation and prediction of the dynamics of biological macromolecules. G.Development of computerized tools that might be used in the presentation of the concepts of cell and structural biology to audiences at a variety of levels. Division of Genetics and Developmental Biology Research on developing a better understanding of fundamental processes and mechanisms of development and inheritance in health and disease. Support of basic topics in genetics and developmental biology, including nucleic acid chemistry, the structure of genetic material, the mechanisms of transmission and expression of genetic information, cellular regulation of growth and differentiation, and population genetics. Areas that may be of interest to small businesses include, but are not limited to: A.Development of computer software for the analysis of the primary and secondary structures of nucleic acids as these relate to genetic problems. B.Improvement in procedures for the separation and analysis of nucleic acids and proteins as these relate to genetic problems. C.Improvement of methodology (technology) for genetic analysis (e.g., gene expression, probes). D.Development of probes for detection of human genetic polymorphisms, including disease genes. E.Development of improved procedures for cytogenetics and diagnostic array technology. F.Improvement in procedures (statistical, computational, laboratory) for the analysis of gene flow and gene dynamics in human populations. G.Development of improved vectors for gene transfer. H.Development of valid animal models for genetic diseases and birth defects. I.Development of quantitative approaches to the analysis of complex biological systems. J.Development of tools and technologies to detect and monitor complex human phenotypes or traits. K.Development of technology to derive and expand pluripotent cell populations from non-embryonic sources, for example, induced pluripotent stem cells (iPS). L.Development of improved technology to scale up the growth of induced pluripotent stem cells in culture and to regulate their differentiation state M.Development of markers, reagents and tools to characterize the unique properties of iPS cell lines and to distinguish them from adult stem cells and more differentiated cells. N.Development of existing human embryonic stem cell lines and new or existing iPS cells as a model system for drug discovery. O.Development or improvement of methodology for generation of antibodies or other affinity reagents for proteins and other small molecules in non-mammalian genetic model systems. P.Development of methods for chemical modifications that improve the properties of nucleic acids for gene silencing. Q.Improvement in procedures (statistical, computational, laboratory) for the high- and medium-throughput analysis of gene expression patterns and regulatory networks. R.Development or improvement of methods for high throughput detection of epigenomic changes. S.Development or improvement of methods for characterizing the metabolic interactions of complex communities of microorganisms particularly those involved in host-microbe interactions. T.Development of improved or novel methodology for structure/function analysis of very large macromolecular complexes involved in transmission or expression of genetic material. Division of Pharmacology, Physiology, and Biological Chemistry Research related to the actions of therapeutics, including anesthetics, and the development of biotechnological methods for their production and investigation. Research on cell signaling molecules and signaling intermediates, particularly those related to G-protein coupled receptors. Research in the field of glycomics, especially tool and methods development for this emerging field. Research on pain management as it relates to anesthesia and the perioperative period. Research on responses to traumatic injury, including burn injury, and methods to mitigate these responses. Research on wound healing and tissue repair. Research on the causes and treatments for common complications of critically ill patients (sepsis, systemic inflammatory response syndrome, multiple organ failure), especially directed towards the role of the inflammatory and innate immune responses. Research leading to new knowledge of physiological functions at the molecular, cellular, and organ systems levels. Research on the structure, function, and biosynthesis of cellular components and cellular metabolism, bioenergetics, and mechanisms of enzyme action, regulation, and inhibition. Research leading to the synthesis of new chemical entities or development of new chemical methods to probe biological phenomena or to alter the behavior of biological systems. Examples include, but are not limited to: A.Methods for isolation, characterization, and production of natural and bio-engineered products. 1.Metabolic engineering for the production of biochemicals through genetic and bioengineering manipulation of biosynthetic pathways. 2.Biosensors for use both in vivo and in vitro in process engineering. 3.Methods for rapid purification of natural products. 4.Methods for rapid determination of natural product structures. 5.Methods for efficient production of natural products. 6.Universal expression systems for heterologous production of natural products. B.Development of innovative synthetic chemistry. 1.Catalytic asymmetric methods and methods for large-scale synthesis. 2.New methods applicable to combinatorial library construction, design, analysis, and/or handling. 3.Improved methods for preparation of isotopically labeled amino acids, peptides, proteins, and prosthetic groups, and therapeutic agents. C.Development of enzymes, catalytic antibodies, ribozymes, artificial enzymes, and host molecules as drugs or synthetic tools. 1.Synthesis of suicide substrates, affinity labeling agents, and transition state analogs as potential therapeutic agents. 2.New enzyme assays to reduce the reliance on radio-isotopes. 3.General approaches for high throughput screening. D.Isolation, characterization, and development of factors involved in tissue repair and wound healing, i.e., growth factors. Tissue engineering. Development of artificial skin and skin replacements. E.Development of strategies, methods, or molecular based treatments to improve the speed and outcome of wound healing or to induce regeneration as a substitute to normal wound healing. F.Metabolomics/metabonomics of injury and/or critical illness. G.Improved systems for collection, processing, and analysis of real time physiological data from injured or critically ill patients. Application of systems biology or complexity theory approaches towards understanding the physiology of injured and critically ill organisms. H.Development of tools, software, algorithms, etc. needed to link clinical, demographic, physiological, genomic, proteomic or other datasets of injured or critically ill organisms. I.Development of strategies, methods, or new technologies to improve the delivery, monitoring, safety and efficacy of anesthesia. J.Research to improve drug design. 1.Methods for understanding of structure-activity relationships. 2.Mechanisms of drug-receptor interactions. 3.Development of molecular diversity libraries. K.Research to improve drug bioavailability by improved understanding of factors that influence absorption, metabolism, transport, or clearance of therapeutics and underlying mechanisms. 1.Determination of structure-activity relationships for drug metabolizing enzymes. 2.Determination of structure-transport relationships for active and passive transport of drugs and metabolites. 3.Research on drug transporter structure, function, and regulation. 4.Development and validation of models for prediction of drug bioavailability and metabolism in humans. 5.Research on inter- and intra-individual differences in bioavailability. 6.Methods to improve sensitivity, accuracy, speed, and simplicity for measurements of drugs and their metabolites in complex biological matrices. L.Application of pharmacokinetic and pharmaceutical principles to the study of large biomolecules, such as proteins, polypeptides, and oligonucleotides. M.Development of novel targeted delivery systems for both conventional drugs and large molecules. N.Research to discover, detect, and understand the genetic basis of individual differences in drug responses. 1.Identification of polymorphisms in human drug receptor and drug metabolizing enzymes. 2.Development of laboratory-based and computational approaches for pharmacogenetic and pharmacogenomic mechanistic studies. 3.Development of statistical analysis methods related to research in pharmacogenomics. 4.Development of genotyping and phenotyping tests to support research in pharmacogenomics. 5.Development of proteomic and metabolomic methodologies related to research in pharmacogenomics. 6.Creation of appropriate databases, specimen, and cell culture collections to support research in this area. O.Development of novel in vivo and in vitro methods to predict toxicities of pharmacologic agents. P.Development of differentiated hepatic cell lines from human stem cells that are equivalent to adult hepatocytes to characterize metabolic profiles of pharmacological candidates by phase 1 and 2 enzymes. Q.Development of bioinformatic, mathematical, and/or computational approaches/resources and/or pharmacokinetic modeling programs which utilize ADME parameters of drugs and pharmacogenomic information of individual patients or patient populations to reduce adverse drug reactions in individual patients. R.Development of ontologies and modules useful for combining and mining databases containing genotype and phenotype information in order to discover correlations for drug effects, either therapeutic or adverse. S.Development of methods and tools for the field of glycomics including but not limited to: 1.Development of carbohydrate specific databases as well as informatics tools to mine carbohydrate data bases. 2.Development of new facile methodologies to rapidly synthesize and expand defined carbohydrate libraries, especially those applicable for screening for glycomic biomarkers, assessing carbohydrate protein interactions, and development of glycan arrays. 3.Development of linker methods for carbohydrates. 4.Development of methods for exploring glycan-protein, glycan-lipid, and glycan-glycan interactions. 5.Development of well characterized commercial sources of glycosyltransferases and glycosidases that can be used as research tools by the scientific community. 6.Development of methods for high throughput structural analysis of the glycoconjugates of proteins and lipids. 7.Development of defined antibodies as tools for the field of glycomics. T.Development and application of methods and materials for the elucidation of membrane protein structures at or near atomic resolution. 1.Novel vector and host cell systems for over-expression of membrane proteins, in both unlabeled and isotopically labeled forms. 2.Novel and high purity detergents and non-detergent solubilization agents for the purification and crystallization of membrane proteins. 3.Apparatus to facilitate crystallization and manipulation of fragile crystals for data collection. 4.Reagents for heavy atom derivatization of membrane protein crystals. U.Development of high-throughput methods for sequencing and resequencing of mitochondrial genes and relevant nuclear genes and for proteomic and/or functional profiling of mitochondria in diagnosis of mitochondrial diseases. V.Development of methods to create site-directed and knock-out mutations of mitochondrially-encoded genes in higher eukaryotic cells and experimental animals. W.Development of new metal ion chelators and other tools to probe and/or alter the localization and concentration of metal ions in cells and in whole organisms. Research to exploit metal metabolism and metal-regulated cellular control and cell-cell signaling processes to probe and/or alter cell function. Research to develop investigational and therapeutic applications of metal-complexes and to understand the factors governing their pharmacology and toxicology. X.Development of high-throughput methods and strategies to characterize the function of proteins and enzymes and/or define the functional interrelationships of proteins and enzymes. Y.Development of research tools to promote scientific collaboration in any of the above areas of research. For example, applications software for secure peer-to-peer networking to facilitate the exchange of scientific data and research materials or to construct a searchable distributed database. Z.Development of tools to characterize oxidative stress and oxidative stress related molecules (NO, peroxynitrite, hydrogen peroxide, lipoxidation products modified proteins, DNA modifications, etc.) including the extent and/or localization (by organ/tissue/cell/organelle) of oxidative stress. Center for Bioinformatics and Computational Biology A.Development of tools and methods to model complex biological systems that fall within the mission of NIGMS. B.Development of tools and methods for behavioral and social modeling. C.Development and enhancement of databases and data formats for activities that fall within the mission of NIGMS. D.Development of tools and methods for scientific visualization, data mining, and integration and interoperability of different databases and varying modalities of data. E.Design and development of software and hardware for improving the effectiveness of computational approaches in biomedical research. Other Research Topic(s) Within the Mission of the Institute For additional information on research topics, contact: Cell Biology and Biophysics Charles Edmonds, Ph.D. National Institute of General Medical Sciences 301-594-0828, Fax: 301-480-2004 Email: edmondsc@nigms.nih.gov Genetics and Developmental Biology Stefan Maas, Ph.D. National Institute of General Medical Sciences 301-594-0943, Fax: 301-480-2228 Email: maassw@nigms.nih.gov Pharmacology, Physiology, and Biological Chemistry Scott Somers, Ph.D. National institute of General Medical Sciences 301-594-3827, Fax: 301-480-2802 Email: somerss@nigms.nih.gov Center for Bioinformatics and Computational Biology Peter Lyster, Ph.D. National Institute of General Medical Sciences 301-451-6446, Fax: 301-480-2802 Email: lysterp@nigms.nih.gov For administrative and business management questions, contact: Ms. Patrice Molnar National Institute of General Medical Sciences 301-594-5136, Fax: 301-480-2554 Email: molnarp@nigms.nih.govHHS201104262011042620110626-1Closed67059http://www.sbir.gov/node/67059The successful completion of the HGP in 2003 set the stage for making use of the immense potential inherent in knowledge of the complete DNA sequence of the human genome to be applied for the improvement of human health and well-being. In an effort to outline a path forward, the Vision Document (Nature 422,835-847 (2003)) broadly outlined three areas that need to be addressed: (1) elucidating the structure and function of genomes; (2) translating genome-based knowledge into health benefits; and (3) promoting the use of genomics to maximize benefits and minimize harms. The latter area relates closely to NHGRI’s Ethical, Legal and Social Implications (ELSI) Program. The research topics encompassed by this area have traditionally been included in a separate program announcement. However, given the growing interrelatedness of genomics to research in humans and to applications in health care and other settings, it has become increasingly clear that the investigation of ELSI issues cannot be separated from the genomic research that generates these issues. As a result, the ELSI research agenda is described in this NHGRI-wide announcement, as well as in a separate ELSI-specific Program Announcement http://grants.nih.gov/grants/guide/pa-files/PA-08-012.html). The purpose of this document is to provide information to investigators about the breadth of NHGRI’s research interests and is very similar the Institute’s general funding opportunity announcements (http://grants.nih.gov/grants/ guide/pa-files/PA-07-458.html and http://grants.nih.gov/grants/guide/pa-files/PA-07-459.html). When appropriate, NHGRI will publish Requests for Applications that will be used to stimulate research in specific areas, to fill gaps in research knowledge, or to generate community resources that will further the mission of genomics or ELSI research. The following are areas of high interest for investigator-initiated applications; they are not listed in priority order. Technology and Methods Development Technology development in DNA sequencing and genotyping are examples of activities that have changed the nature of what scientific research questions are practical to address, have enabled new approaches, and have potentiated the development of new community resource data sets. Many areas of critical importance to the realization of the genomics-based vision for biomedical research require continued technological and methodological developments before pilots and then large-scale approaches can be attempted. Accordingly, the NHGRI will continue to support the development of new, fundamental technologies in all areas of genomics. Other important areas in which technology development applications would be responsive to this Program Announcement include (but are not limited to) analyses of gene expression, discovery and characterization of genetic variation; identification of the genetic contributions to health, disease, and drug response; statistical analytic methods for understanding human genomic variation and its relationship to health and disease; and chemical genomics. There is also continued interest in supporting technology development for the comprehensive discovery of functional elements in the human and model organism genomes, and new DNA sequencing technology. Many of these assays would benefit from the ability to work with very small amounts of starting material, to the limit of single cells. The Institute is also interested in contributing selectively to the development of new and needed technology in related areas, such as proteomics and systems biology research, when NHGRI funding can be used to further a truly unique development that will have a significant impact on the field. Bioinformatics Genome databases are essential resources for the biological and biomedical research communities. The creation and maintenance of effective databases are as important a component of research funding as data generation. The NHGRI has been a primary source of support for several major genetics/genomics-oriented databases and will continue to foster technology improvements to develop effective methods for integrating, displaying, and providing access to genomic information. Projects addressing new database technologies to improve the utility of genome databases would be appropriate as applications. Computational Biology The NHGRI has supported the generation of many large-scale genomic data sets such as genome sequence, haplotype maps, transcriptome measurements, protein interactions, and functional elements. NHGRI encourages the development of new computational methods and tools to analyze these and other large datasets, and to extract useful biological information from them. Where possible, existing community data standards and methods for data exchange should be used in the development of these new methods and tools. Further information on programs related to genomic databases and computational biology is available at this website: http://www.genome.gov/10001735. The development of new sequencing technologies has dramatically increased the amount of data produced for genomics. NHGRI is interested in supporting new computational applications for the production and analysis of data from these new sequencing platforms. These applications would include better computational methods for storage, compression and transfer of large datasets by biomedical researchers along with better analysis methods to interpret these data and integrate with other data types. Some genomic data analysis and display tools have been developed that already are used in the community that would benefit from additional work to support broader dissemination, for example making them efficient, reliable, robust, well-documented, and well-supported. NHGRI will support projects to extend the support for these informatics tools to make them readily adopted by any biomedical research laboratory that wishes to use genomic technologies to address biological questions. Population Genomics This is an emerging discipline that applies genomic technologies, such as genome-wide association testing and sequencing, to population studies to identify gene regions, genes, or variants affecting common etiologically complex conditions and predict individual risk. It also investigates the value of applying genomic methods in clinical care for the diagnosis, treatment, and prevention of complex diseases. The research scope of Population Genomics at NHGRI includes: developing resources and statistical methods for observational studies and clinical trials incorporating advanced genomic technologies; conducting proof-of-principle studies that apply genomic technologies to particular conditions that can be generalized to a broader range of conditions (e.g., translating genomic information to clinical care); and developing research methods and infrastructure needed for future epidemiologic studies of genetic and environmental contribution to disease in the United States, including a large, prospective cohort study of genes and environment. For additional information about Population Genomics within NHGRI, please visit this website: http://www.genome.gov/19518660. Ethical, Legal and Social Implications NHGRI supports studies that examine issues and, where appropriate, develop policy options in the following areas: 1) the translation of genomic information to improved human health; 2) the conduct of genomic research—particularly genome-wide association studies, medical sequencing and clinical studies; 3) intellectual property issues surrounding access to and use of genomic information; 4) the use of genomic information and technologies in non-health care settings; 5) the impact of genomics on concepts of race, ethnicity, kinship and individual and group identity; 6) the implications, for both individuals and society, of uncovering genetic contributions not only to disease but also to 'normal' human traits and behaviors; and 7) how different individuals, cultures, and religious traditions view the ethical boundaries for the uses of genetics and genomics. Several of these topics are closely integrated with genomic research, which is why they are described here. Other Research Topic(s) Within the Mission of the Institute Individuals interested in any of the above listed areas are encouraged to contact the NHGRI staff listed below. For more specific information about areas of interest to the NHGRI, please visit our home page at http://www.genome.gov/Grants/. For additional information on research topics, contact: All Research Topics Except ELSI Bettie J. Graham, Ph.D. National Human Genome Research Institute 301-496-7531, Fax: 301-480-2770 Email: bg30t@nih.gov ELSI Research Topics Jean E. McEwen, J.D., Ph.D. National Human Genome Research Institute 301-402-4997, Fax: 301-402-1950 Email: jm522n@nih.gov For administrative and business management questions, contact: Ms. Cheryl Chick Chief, Grants Management Officer National Human Genome Research Institute 301-435-7858, Fax: 301-402-1951 Email: ChickC@mail.nih.govHHS201104262011042620110626-1Closed67059http://www.sbir.gov/node/67059The mission of the National Institute of Mental Health (NIMH) is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. Mental disorders constitute an immense burden on the U.S. population, with major depression now the leading cause of disability in the U.S., and schizophrenia, bipolar disorder, and obsessive-compulsive disorder ranked among the ten leading causes of disability. NIMH also takes a leading role in understanding the impact of behavior on HIV transmission and pathogenesis, and in developing effective behavioral preventive interventions. The NIMH conducts a wide range of research, research training, research capacity development, as well as public information outreach and dissemination to fulfill its mission. For additional information about areas of interest to the NIMH, please visit our home page at http://www.nimh.nih.gov. NIMH-Supported Program Announcements: (if the program announcement has expired, please contact Dr. Margaret Grabb for information on new opportunities, and also see: http://www.nimh.nih.gov/research-funding/small-business/small-business-program-announcements-issued-by-nimh.shtml) 1.Lab to Marketplace: Tools for Brain and Behavioral Research (SBIR) http://grants.nih.gov/grants/guide/pa-files/PA-08-071.html 2.Competing Renewal Awards of SBIR Phase II Grants for Brain and Behavior Tools (SBIR) http://grants.nih.gov/grants/guide/pa-files/PA-08-056.html 3.Innovations in Biomedical Computational Science and Technology (SBIR) http://grants.nih.gov/grants/guide/pa-files/PAR-09-220.html 4.Development of PET and SPECT ligands for brain imaging (SBIR) http://grants.nih.gov/grants/guide/pa-files/PA-08-137.html 5.Pharmacologic Agents and Drugs for Mental Disorders (SBIR) http://grants.nih.gov/grants/guide/pa-files/PA-08-142.html Also see: http://grants.nih.gov/grants/guide/notice-files/NOT-MH-09-008.html. 6.Development of Biomarkers for Mental Health Research and Clinical Use (SBIR) http://grants.nih.gov/grants/guide/pa-files/PA-09-045.html 7.Probes for Microimaging the Nervous System (SBIR) http://grants.nih.gov/grants/guide/pa-files/PA-09-062.html. 8.High Throughput Tools for Brain and Behavior http://grants.nih.gov/grants/guide/pa-files/PA-08-001.html (SBIR) http://grants.nih.gov/grants/guide/pa-files/PA-08-002.html (STTR). 9.Bioengineering Nanotechnology Initiative (SBIR) http://grants.nih.gov/grants/guide/pa-files/PA-09-267.html 10.Novel Tools for Investigating Brain-derived GPCRs in Mental Health Research (SBIR) http://grants.nih.gov/grants/guide/pa-files/PA-10-081.html 11.Tools to Mitigate and Understand the Mental Health Effects of National Disasters (SBIR) http://grants.nih.gov/grants/guide/pa-files/PA-09-117.html 12.Manufacturing Processes of Medical, Dental, and Biological Technologies (SBIR) http://grants.nih.gov/grants/guide/pa-files/PA-09-113.html 13.Computational Tools for Research in Neuroscience, Behavioral Science and Mental Health http://grants.nih.gov/grants/guide/pa-files/PA-07-424.html (SBIR) http://grants.nih.gov/grants/guide/pa-files/PA-07-423.html (STTR) 14.Probes and Instrumentation for Monitoring and Manipulating Nervous System Plasticity (SBIR) http://grants.nih.gov/grants/guide/pa-files/PA-08-146.html 15.Robotics Technology Development and Deployment [RTD2] (SBIR) http://grants.nih.gov/grants/guide/pa-files/PAR-10-279.html Phase IIB Competing Renewal Awards See http://grants.nih.gov/grants/guide/notice-files/NOT-MH-09-008.html and http://grants.nih.gov/grants/guide/pa-files/PA-08-056.html. The NIMH will accept Phase IIB SBIR Competing Renewal grant applications in two categories: 1) to continue research and development of technologies that ultimately require federal regulatory approval (see below and see http://grants.nih.gov/grants/guide/notice-files/NOT-MH-09-008.html, and 2) to continue research and development of complex instrumentation, clinical research tools, or behavioral interventions and treatments (see below and see funding opportunity announcement PA-08-056, entitled “Competing Renewal Awards of SBIR Phase II Grants for Brain and Behavior Tools (R44)” http://grants.nih.gov/grants/guide/pa-files/PA-08-056.html. Technologies in the former category (those that ultimately require federal regulatory approval) include, but are not limited to: pharmacologic agents and drugs, biological products, medical devices, vaccines, etc., related to the mission of the NIMH. Phase IIB SBIR Competing Renewal grants for such technologies should allow small businesses to get research and development to a stage where interest and investment by third parties is more likely. Companies engaging in drug development for the treatment of mental health disorders may be eligible to submit Competing Renewal applications through the specific funding opportunity announcement PA-08-142 entitled “Pharmacologic Agents and Drugs for Mental Disorders (SBIR [R43/R44])” http://grants.nih.gov/grants/guide/pa-files/PA-08-142.html. For this specific opportunity, budgets up to $1.0 million total costs per year and time periods up to three years may be requested. Companies that are developing technologies that do not focus on drug development, but that require federal regulatory approval prior to commercialization, may be eligible to submit a Phase IIB Competing Renewal application through the standard SBIR funding opportunity announcement. For this opportunity, budget limits of up to $800,000 total costs per year and time periods up to 3 years may be requested. Please contact your Program Director or Dr. Margaret Grabb (contact information provided below) before beginning the process of putting an application together. In addition, prospective applicants are strongly encouraged to submit to the program contact a letter of intent that includes the following information: •Descriptive title of the proposed research •Name, address, and telephone number of the Principal Investigator •Names of other key personnel •Participating institutions •Funding Opportunity Announcement Number (e.g., PA-10-XXX) Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NIH staff to estimate the potential review workload and plan the review. It is expected that only a portion of NIMH SBIR Phase II awards will be eligible for a Phase IIB Competing Renewal grant. The following examples would make appropriate topics for proposed NIMH SBIR Phase IIB Competing Renewal projects. These are meant for illustrative purposes only and are not exclusive of other appropriate activities: •Preclinical studies, including pharmacology and toxicology, beyond those conducted under the Phase I (R43) and initial Phase II (R44) grants. Some in vivo or in vitro studies would be expected to have been carried out in Phase I or the initial Phase II grant. •Completion of studies as required by the Food and Drug Administration (FDA) for Investigational New Drug (IND) or Radioactive Drug Research Committee (RDRC) application. •Studies in normal healthy volunteers to determine a drug’s safety profile, metabolism, etc. •Clinical studies in patient/disease population to assess the drug’s effectiveness. •Assessment of devices with regard to performance standards related to the FDA approval process. •Safety and effectiveness studies of novel medical devices. •Evaluation of novel imaging approaches for diagnostic purposes. •Clinical studies in support of Pre-Market Approval for biomarkers/medical devices by the FDA. Although technologies in the latter category (complex instrumentation, clinical research tools, or behavioral interventions/treatments) may not require federal regulatory approval, extraordinary time and effort is needed for their research and development. Therefore, NIMH supports Phase IIB Competing Renewal awards of existing Phase II grants for such technologies. The Phase IIB Competing Renewal award for these would provide up to an additional three years of support at total cost funding levels of up to $800,000 per year. Applicants should apply through the funding opportunity announcement PA-08-056, entitled “Competing Renewal Awards of SBIR Phase II Grants for Brain and Behavior Tools (R44)” http://grants.nih.gov/grants/guide/pa-files/PA-08-056.html. Direct your questions about scientific/research issues to: Margaret Grabb, Ph.D. National Institute of Mental Health 6001 Executive Boulevard, Room 7201, MSC 9645 Bethesda, MD 20892-9645 Rockville, MD 20852 (for express/courier service) Telephone: 301-443-3563 FAX: 301-443-1731 Email: mgrabb@mail.nih.gov Division of Neuroscience and Basic Behavioral Science Through research in neuroscience and basic behavioral science we can gain an understanding of the fundamental mechanisms underlying thought, emotion, and behavior and an understanding of what goes wrong in the brain in mental illness. Research sponsored by the Division of Neuroscience and Basic Behavioral Science covers a broad range of neuroscience topics: from both experimental and theoretical approaches, from molecules to whole brains to populations of individuals, from single cell organisms to humans, from across the entire lifespan, and from states of health and disease. This division also supports research on the basic behavioral, psychological, and social processes that underlie normal behavioral functioning. The topics listed below reflect the NIMH interest in technologies related to this broad range, but should not be considered a complete list. Prospective applicants are strongly encouraged to contact Dr. Margaret Grabb (listed below) with questions about the relevance of their interests to the mission of this division. A.Cutting-Edge Technologies for Neuroscience Research. Most of the research topics listed after this one are posed from the Division's neuroscience and basic behavioral science mission-oriented perspective, however, the technologies that might be developed to address those mission goals might be quite fundamental. Prospective applicants familiar with such technologies, but not familiar with the mission-related use of these technologies, are strongly encouraged to contact Dr. Margaret Grabb (listed below) for assistance in bridging this gap between their technical knowledge and knowledge of the neuroscience-related mission of NIMH. Technologies and approaches that might be used in products relevant to this mission include, but are not limited to: 1.Caged Molecules. These chemical entities could be activated, or could release an active agent, when specified bonds are broken by chemical, biochemical, photic, or other means. Among other uses, such molecules could be used to indicate biochemical or physiological processes or to deliver pharmacologic substances to highly localized brain regions. 2.Genetically Engineered Proteins. Such proteins could be put to any number of uses, including to express a fluorophore or chromophore at the occurrence of specific biochemical processes to report the time and location of such processes in brain tissue. 3.Inducible Gene Expression. Methods to turn on or off expression of particular genes in animals on the basis of time in the lifespan, location in the brain, or other factors. Such a capability would significantly advance basic brain research, and would have important implications for treatment and therapy of mental illness. 4.Combinatorial Approaches. These are high-through-put approaches that can be used to screen and synthesize molecules that affect brain cells. 5.Biocompatible Biomaterials. Such research and development relates to the chronic use of electrodes and other probes used in brain research, as well as implanted drug delivery devices. 6.Nanotechnologies. This emerging area of technology presents a wide range of opportunities for brain research, from the fabrication of probes to monitor brain physiology to novel means of delivering drugs and other substances. 7.Informatics Tools. Such technologies allow brain scientists, clinicians and theorists to make better sense and use of their data. These tools and approaches include those to acquire, store, visualize, analyze, integrate, synthesize and share data, including those for electronic collaboration. 8.Simulation Technologies. Computer-based, biologically realistic simulations of parts of neurons, neurons, and circuits. 9.Mathematical, Statistical and Computer Algorithms. Such algorithms could be used to analyze large and/or complex data sets. Examples of these data sets include those derived from multiple, single-unit recording studies and functional imaging studies. Among other applications, these could be used to segment images (obtained from electron or light microscopes, or from volumetric imaging instruments such as confocal microscopes and magnetic resonance imagers), filter noise, visualize data or search vast data sets for specified patterns or data (e.g., use of pattern recognition algorithms to search time series data sets obtained from electrophysiological recording of neural activity, or video data obtained from behavioral analysis of genetically altered animals). In addition, digital reconstruction of dendritic and axonal arbors would be of interest. 10.Telemetry. Transferring data from one point to another is important for neuroscientists monitoring the physiological signals from the brain. Telemetry, even over relatively short distances (from a few millimeters to a few meters), could, for example, provide a means to obtain data from awake, behaving animals without interfering with the behavior of interest. Examples include telemetry that can be easily implanted/attached to awake behaving animals for measuring peripheral/autonomic responses (this approach could be used to inform stress/emotion research), miniaturized telemetry for use in smaller animals with increased numbers of recording devices/electrodes implanted per animal. Alternatives to telemetry would be considered as well. 11.Biosensors. Neurons communicate with each other through thousands of different chemical substances; internally, molecular pathways direct the function of the neuron. Sensors of high specificity and sensitivity for such substances would provide neuroscientists with important new ways to study the brain. B.Instrumentation for Basic Neuroscience Research. Modern equipment that uses the most recent technological advances is needed in neuroscience research so that neural substrates of mental illness can be identified and localized. The NIMH is interested in supporting research and development of new or improved approaches relevant to, but not limited to, the following: 1.Neurophysiology. Microelectrodes for stimulation and/or recording, smart nanoscaffolds, macroelectrodes, biocompatible coatings, interfaces to electronics, software for data analysis, visualization, etc. Systems with better/easier MR compatibility would also be of interest. 2.Cell Sorting. Based on cell size, type, function, morphology, abnormal features, specific membrane proteins, etc. 3.In Vivo Electrochemical Voltammetry. More sensitive and selective electrodes, software for data analysis, etc. 4.High Performance Liquid Chromatography. Improved reliability, specificity, sensitivity, etc. 5.Technology to support Multiple Unit Recording Electrode Arrays. Recording techniques, analysis techniques and raw data storage. 6.Physiological and Behavioral Monitoring. Temperature, activity, sleep duration, neuronal activity, EEG activity, EKG, pulse rate, recording, capture and analysis of multiple single unit activity from microelectrodes, automated SWS analysis and coherence of EEG rhythms, and further refinement of High density EEGs. 7.Development of novel technologies for stimulating specific cells or signaling pathways in awake behaving animals. 8.Development of more sensitive fluorescent probes for simultaneous and real time measures of multiple neurotransmitter release and intracellular signaling pathway activities. 9.Associated Software. C.Macroscopic Neuroimaging. Modern technologies allow for the observation of the structure and function of the intact brain. This capability has the potential to greatly advance understanding of the brain in both health and disease, and across the lifespan. NIMH is interested in advancing this area of technology through enhancing current tools and approaches, as well as developing entirely new ways to image the brain. All modalities are of interest, including, but not limited to: magnetic resonance imaging (MRI) or spectroscopy, positron emission tomography (PET), optical imaging or spectroscopy, single photon emission computed tomography, magnetoencephalography (MEG), diffusion tensor imaging (DTI), etc. While not an imaging technique itself, transcranial magnetic stimulation (TMS) is an associated, important technology. TMS can be used in combination with fMRI as means to further assess physiology and integrity of neural systems both in health and in mental disorders. Due to its greatly increased use in recent years, technologies specifically focused on improving the utility and specificity of fMRI techniques are of particular interest. 1.Innovative agents and/or technologies to visualize brain connectivity, activity, and neural plasticity in situ with minimal invasion. 2.Improvement in the techniques, the design and construction of devices for non-invasive imaging for any modality, for example, improving spatial resolution, quantitative accuracy, signal-to-noise ratio, and electronics. 3.Development and enhancement of non-invasive imaging techniques for evaluating alterations in brain physiology produced by drugs. These would include techniques for monitoring changes in regional blood flow; concentrations of drug and/or tissue metabolites; and the distribution and activity of receptors. 4.Synthesis, or isolation from natural products, of highly selective receptor ligands or indicators of neurochemical processes, which would be labeled for imaging by one or more particular modality. 5.Development of selective hormone receptor ligands for brain imaging. 6.Development of imaging agents to examine the integrity of the blood brain barrier following infection and other environmental challenges. 7.New approaches in radiochemistry that will permit more exact identification of the chemical changes associated with behavioral states (e.g., sleep or arousal) or mental illness as observed with any particular neuroimaging modality. 8.Synthesis of molecules containing stable, rarely occurring isotopes designed to be detected by non-invasive imaging techniques (e.g., fluorine-containing molecules, carbon-13 labeled substrates). 9.Methods and associated products for quantification of imaging data including new statistical approaches for evaluating the data. 10.Methods to integrate routines for greater and more precise computer enhancement of the images, and for combining or overlaying images obtained from multiple modalities. 11.Software needed for the precise quantification of data obtained from these imaging techniques with emphasis on the reliable definition of discrete, anatomically distinct areas within the brain. 12.Novel agents or other tools to increase the ability to correlate features of MR images with histological features (e.g., cytoarchitecture or chemoarchitecture) both identified and those yet to be identified. 13.Generation of physiologic measurements from images of regional radioactivity generated during PET, especially for the study of brain neurotransmitter/neuroreceptor systems. 14.Novel approaches to visualizing data obtained in neuroimaging, such as the computational “unfolding” of three-dimensional images of cerebral cortex. 15.Improved methods for pediatric brain imaging. These would include: software and database products, equipment for creating a “child-friendly” environment and for the behavioral training of children and impaired subjects for cooperation and motion reduction during neuroimaging procedures. 16.Combining of different imaging technologies (e.g., ERPs and fMRI; MEG and fMRI; MEG and EEG, optogenetic methods and fMRI, etc.). The latter example, optfMRI, can be used as means of improving tools for further understanding of neural bases of fMRI signals and to produce connectivity a map of neural cells that can be defined both genetically and topographically with a combination of these two techniques. 17.New tools and devices to simultaneously record hemodynamic signals (BOLD, rCBF, etc.) and neural activity (EEG, LFP, spiking, etc.) to better understand the direct relationship between blood flow variables and neural activity within the brain. 18.Development of equipment, software and other tools for recording and quantifying eye movements, motion, and autonomic reactivity during scanning, applicable to all ages (including young children) particularly in the MRI environment. 19.Methods for relating changes in brain morphology and metabolism associated with age, particularly infancy through adolescence, to changes in hemodynamic responses to neural activity and fMRI signals. 20.Improvements in TMS techniques that will allow for greater specificity in the sites of stimulation and greater control over the effects of the stimulation. In particular, improvements in stimulators that would allow much smaller effective fields of stimulation with more reliable and repeatable stimulator placement would be a significant benefit to the field. 21.Real time fMRI is becoming a research tool of interest with potential clinical/therapeutic neurofeedback applications. Products are needed that would enhance the ability of scientists to use this technology for those neurofeedback applications in an off-the-shelf manner. 22.Development of methods to improve efficiency, specificity and controllability of viruses used in primate tract tracing studies. 23.Development of more sophisticated imaging strategies in rodents. 24.Development of a user-friendly interface to serial reconstruction software capable of generating stackable, 3D images of axonal and dendritic arborizations at the light and electron microscopic level. D.Microscopic Neuroimaging. The morphology of individual neurons and the distribution of subcellular components within them, are key to understanding the manner in which these cells function. Advances in the development of agents indicating neuronal structure and function that can be visualized microscopically are important to the NIMH's interest in brain research. This includes enhancements of current agents and ligands to be imaged (agents indicating specific biochemical processes or structures, etc.); development of novel agents and ligands; software to assist interaction with the data; and other related technologies and methods. Examples would include, but not be limited to: 1.Software and hardware for analyzing image data obtained by microscopes, including tools to automatically or semi-automatically. Identify particular profiles (e.g., labeled cell bodies), segment images, reconstruct images into three dimensional representations, perform unbiased counting and measuring, etc. 2.Synthesis and testing of novel or improved probes for microimaging the nervous system. E.Molecular and Cellular Neurobiology and Neurochemistry. Manipulating and studying basic molecular, cellular and chemical processes has led to insight to understanding brain function, and has provided the foundation on which pharmacological interventions have been developed for the treatment of mental illness. NIMH is interested in supporting a wide range of new techniques and tools related to this area. These include, but are not limited to: 1.New low-cost techniques for hybridoma production of monoclonal antibodies specific for “neural antigens” (e.g., neurotransmitters, small peptides, neurotransmitter receptors). 2.Innovative methods for establishing a “monoclonal bank” (frozen cells) for each of the cell lines as a permanent, widely available, reliable, and low cost source of monoclonal antibodies for research on the nervous system. 3.Labeled antibodies or other agents that will readily identify receptors for which there are no ligands (orphan receptors) and which have low densities in the brain. 4.Automated methods for quantifying the low levels of bound ligands for quantifying receptors that are sparsely scattered in the brain. 5.New cell lines that express each of the known neurotransmitter receptors so that each cell line will be homogeneous for one receptor. 6.New cell lines that express each of the above receptors linked to some metabolic function and/or second messenger so that the functional consequences of receptor occupancy can be detected. 7.High volume, inexpensive assay methods for measuring both receptor occupancy and cellular response for each of the receptor types. 8.Develop cell culture models for neurons, including methods of purifying homogeneous populations of non-transformed cells by, for example, developing markers to identify neuronal cell types for use in characterizing cell-type-specific signaling pathways which may be useful in tracking the effects of various drugs. 9.Develop techniques for either activating or deactivating specific ion channels, receptors and signal transduction pathways. 10.Develop dynamic biochemical and imaging assays that allow measurement of variables now obtained only through electrophysiological techniques. 11.Develop tools to facilitate proteomic analysis of CNS neurons. 12.Develop tools to facilitate in vivo studies of protein-protein interaction, folding and aggregation. These technologies could impact our understanding of the basic neurotransmitter receptors chemistry and on developing of more selective small chemical entities with high affinities for CNS targets. 13.New approaches to study the multiple functions of particular proteins. 14.Tools to study post-translational changes in proteins (expression levels, post-translational modifications, etc.) in specified tissue compartments and subcellular domains. 15.Technologies to study functional entities within cells (e.g., green fluorescent protein approaches) and subcellular compartments. 16.Tools and approaches to study coordinate changes in genes and their functional relationship to phenotypes, including phenotypes associated with specific brain disorders. 17.Novel tools and approaches to study protein-protein interactions, especially those with phosphoproteins. Further develop methods and reagents for studying the structures of membrane proteins at atomic resolution. Membrane protein systems that are of particular interest to NIMH include proteins involved in normal function and pathology of cells (neurons and glia) in the central and peripheral nervous system. 18.Develop novel techniques for isolating and identifying the structure of brain-derived membrane proteins. 19.New methods to identify peptide receptors for which traditional biochemical approaches (e.g.: radiolabeling techniques) failed to produce results. This would be relevant for the development of small molecular probes that would target peptide systems that might be altered in mental disorders. 20.Development of new and optimization of the existing methods for non-invasive quantitative detection of hormones and hormone action in awake behaving animals. 21.Development of novel technologies to adapt human induced pluripotent stem cells (iPSCs) to identify molecular and cellular dysfunction underlying mental illness and for high throughput screening assays for candidate therapeutics. 22.Continuing to improve optogenetic techniques (combining optical and genetic techniques to probe neural circuits within intact animals). F.Genetic and Transgenic Technology. Advances in genetic and transgenic technologies offer many opportunities to probe fundamental questions about the brain, behavior and pathology. NIMH is broadly interested in these areas; some examples of topics relevant to the mission of this Institute include, but are not limited to: 1.Methods to perform site-directed mutagenesis in cell lines for the study of membrane proteins such as ion channels and neurotransmitter receptors. 2.Development of gene “knockout” or “knockin” animals using such approaches as homologous recombination targeting genes important in neurotransmission, development, and tropic interactions as well as models relevant to psychiatric disease. 3.New methods to delete or alter targeted genes in the preparation of transgenic animals including methods that increase or decrease gene expression. 4.Development of new techniques and apparatus for delivery of synthetic nucleic acids to manipulate endogenous gene expression in specific cell populations and/or brain regions. 5.Develop and validate standardized behavioral tests and apparatuses to assess the gene knockouts and/or gene “knockins” affecting neurotransmission. 6.New approaches for spatially and/or temporally restricted gene activation and/or inactivation. 7.Develop novel markers for elucidating how signaling cascades impact DNA transcription. 8.New ways to assess quantitatively transcription of genes in real time in a manner that is minimally injurious to cells (e.g., non-permeabilizing approaches). 9.Develop new technologies to study gene function and expression, including approaches to studying gene and protein expression at single cell resolution. 10.Develop novel approaches to study the expression characteristics of non-coding (nc) RNA molecules as well as developing methodologies using nc-RNAs to manipulate gene expression in cells and tissues of the nervous system. 11.Development of embryonic stem (ES) cell lines from rodent strains (rats and mice) of relevance to behavioral research. 12.Development of technologies and approaches to facilitate the collection and distribution of ES cell lines containing mutations of potential relevance to behavioral and neural processes relevant to neuropsychiatric disorders. 13.Develop methods for long-term storage of transgenic germ cell lines. 14.Develop technologies and approaches to aid in the renewal of founder colonies of transgenic mice from repositories of transgenic germ cell lines. 15.Develop databases on neurobiological transgenic animals produced to date, including information such as the origin of the transgenic animal, key features of the biological and behavioral mutant, availability and location of germ cell lines, and existence of breeding colonies. 16.Develop gene transfer technologies such as viral vectors and non-viral (e.g. polymer-based) systems to produce long-term, stable gene expression in the brain. 17.Develop methods to analyze and manipulate DNA structure to study epigenetic modifications and chromatin remodeling in brain tissue and neuronal populations. 18.Development of selective gene silencing strategies to ablate neurons in one circuitry in order to examine its specific behavioral consequences. 19.Technology development in epigenetics: a) development of novel and highly accurate tools to analyze proteomics of histones b) development of antibodies for immunochemical studies of histone modifications that selectively target a specific DNA modification site c) develop and apply tools for epigenetic research to determine how, when, and where experience affects gene expression. 20.Technology development in Microbiome research: a) development of tools for high throughput genomic analysis of human microbiome; b) development of informatics tools to study the huge amount data that will result from these studies; and c) development of methods to determine the interaction between microbial community genes and host genetics as a potential contributing factor for mental disorders. G.Neuroimmunology. Research on the interplay between the brain, neuroendocrine system, and, immune system has revealed important links between these major homeostatic system components. Examples of NIMH-relevant topics in this area include, but are not limited to: 1.Development of new tools to explore the specific properties of the blood-brain barrier responsible for the selective delivery or retention of cytokines, immune cells, and drugs affecting immune activity in the brain. 2.Development of assays for identifying potential autoimmune components of psychiatric disorders. 3.Identification of critical molecules, processes, and pathways mediating signals from the peripheral immune system to the brain. 4.Development of novel cytokine ligands and antagonists, and neuroimaging agents. H.Pharmacology. Pharmacological intervention represents a major force in the treatment of mental illness, and NIMH is interested in supporting research and development in this area. However, pharmacologic agents that primarily act on molecular targets which replicate those of currently-marketed pharmaceuticals used in the treatment of mental disorders would not be of interest for this program. Relevant pharmacology topics include, but are not limited to: 1.New chemical entities with high, selective affinities for CNS targets. Examples include, but are not limited to, receptors, transporters, ion channels, enzymes, kinases, or second or third messenger systems. 2.Methods to evaluate old and new chemical entities (including complex mixtures of crude extracts from natural products) for possible therapeutic usefulness using “in vitro” and “in vivo” assays and model systems. 3.Methods for extraction, fractionalization, and isolation of active compounds from natural products. Water-soluble compounds are of particular interest due to the difficulty of the procedures. 4.Computer algorithms that model receptors to evaluate theoretical permutations of known molecules to find the molecule with the maximum probability of having the highest affinity for a specific receptor as well as those that have the potential for the most desirable “on” and “off” rates. 5.Computer models of the blood brain barrier and evaluate potential and actual drug molecules for their ability to cross or penetrate this barrier. 6.Strategies for evaluating pharmacological agents (e.g., animal behavioral testing, computer simulation) within specific domains of cognitive function. 7.Behavioral “models” similar in animals and humans; behavioral pharmacological effects that may serve as “surrogate” markers in humans. 8.Development of models for evaluating drug effects within functional brain circuits relevant to mental disorders. 9.Development of novel drug delivery systems. 10.Tools for Drug Development including neuroimaging (e.g., radiolabeled compounds) and development of animal models. 11.Pharmacological profiling (in vitro and in vivo) for potential therapeutic drugs. 12.Methods for evaluation of long-term effects of psychotropic drug administration in animal models or human subjects. If clinical populations are being tested, the technology would be appropriate for either the Division of Developmental Translational Research (DDTR) or the Division of Adult Translation Research (DATR) at NIMH. 13.Improving existing, and developing new, vectors for delivery of genes to the brain. 14.Development of novel therapeutic approaches targeting gene expression through effects on promoter activity or epigenetic mechanisms. 15.Development of novel high throughput screening (HTS) assays for drug development. Examples include, but are not limited to, in vitro functional assays, toxicology screens, blood-brain barrier permeability assays, and circuit based or behavioral assays. 16.Development of novel molecular targets for drug development to treat mental illnesses. I.Tract Tracing Methods and Tools. Little is known about the details of the connectivity of the human nervous system, because the best tract tracing techniques are invasive and require the deposit of substances in vivo. Methods that would be applicable to post-mortem tissue would allow significant progress in connectional studies of human tissue, as well as non-human tissue, particularly with regard to the development of c, quantu onnections and the connections of structures not easily accessed in vivo. Examples include the development of improved physical, chemical and/or biological markers for neuroanatomical tract-tracing (e.g. m dots, caged molecules, viral delivery agents, etc.). J.Educational Tools. Neuroscience, basic behavioral science and human genetics are compelling areas of science that not only touch upon a diverse array of disciplines, but also provide insights to the essence of what it is to be human. Products aimed at teaching the substance of these fields to students of all ages would be useful in disseminating this information and these insights. Examples include, but are not limited to: software and other interactive media used to convey fundamental concepts about the brain to children; computer simulations of neuroscience experiments; updateable media that presents state-of-the-art information on particular topics for use by experts; website or other online, interactive electronic vehicle to allow for sharing of information about the brain and its functions, including technologies for holding interactive research conferences related to basic behavioral sciences, basic neuroscience, or clinical neuroscience. K.Neuroinformatics. Data generated by brain research are diverse, vast, and complex. The diversity of data is due to the fact that neuroscience data are obtained from: theoretical, experimental and clinical approaches; from levels of biological organization that span molecules to populations of individuals and from single-cell organisms to humans; and from states of health, disease, and models of disease. The quantity of data in brain research is the result of tens of thousands of neuroscience laboratories working around the world. The complexity of data reflects the high level of interconnectedness of the data, and their high dimensionality. Neuroinformatics is a new area of science that draws upon neuroscience, information science, computer science, statistics, applied mathematics, and a variety of engineering fields to develop tools that will let neuroscientists make better sense and use of their data. These tools include software and hardware for digital data acquisition, visualization, analysis, integration, and sharing (e.g., through tools for electronic scientific collaboration). Such tools can address data of any type or from any area of neuroscience; examples include, but are not limited to: 1.Databases, querying approaches, and information retrieval tools for neuroscience and neuroscience-related data. An example would be the development of a web-based database for sharing, analyzing and comparing the pharmacological responses of a variety of CNS active compounds in preclinical studies relevant to mental health. 2.Tools for neuroscience data visualization (and other forms of presentation) and manipulation (probabilistic atlases of brain structure or function, new statistical approaches for analyzing data, etc.). 3.Software for integration and synthesis of neuroscience data (computational models of neurons to integrate data about structure and function, environments to merge data from multiple imaging modalities, etc.). 4.Tools for electronic collaboration to allow neuroscientists to interact with colleagues, data, and instruments at a distance (this could include novel types of “groupware”, etc.). 5.Tools that bridge existing neuroscience and biology information tools and resources, such as databases and informatics tools associated with genome mapping efforts. For further information on basic neuroscience or basic behavioral science research topics, contact: Margaret Grabb, Ph.D. National Institute of Mental Health 6001 Executive Blvd. Room 7201 Mail Stop Code 9645 Bethesda, MD 20892 301-443-3563, Fax: 301-443-1731 Email: mgrabb@mail.nih.gov The Division of Developmental Translational Research The Division of Developmental Translational Research directs, plans, and supports programs of research and research training leading to the prevention and cure of childhood psychopathology. This long-term goal will be accomplished through an integrated program of research across behavioral/psychological processes, brain development, environment and genetics. The topics listed below reflect the NIMH interest in technologies related to this research area, but should not be considered a complete list. Prospective applicants are strongly encouraged to contact Dr. Margaret Grabb (listed below) with questions about the relevance of their interests to the mission of this division. A.Technologies for Clinical Pediatric Research. It is important to develop reliable methods that can correctly identify the normal and abnormal components of cognitive, emotional, and psychosocial behavior, as well as normal and abnormal physiological and biochemical functions, in human development. Computer-based methods of accomplishing this are also needed to increase the accessibility and reliability of information made available to the research community. Examples include: 1.Measurements of Alterations in Pediatric Development in Patients with Mental Health Disorders Using Physiological and Behavioral Measures. Research studies indicate that some mental health disorders, such as autism, may begin to develop as early as infancy. Therefore non-invasive modern equipment that use the most recent technological advances are needed to isolate specific physiological and behavioral changes during development, to identify potential diagnostic markers of mental health disorders. A priority for this program is to support research and development of hardware and software tools to measure pediatric development. Examples of technologies needed include: a.Psychophysiological measures to evaluate infants, children or adolescents. b.Miniaturized non-invasive instruments to record psychophysiological data (e.g., heart and respiration rate, galvanic skin response, and defensive motor behavior). c.Telemetry capability for non-invasive devices so that children can be monitored for prolonged periods without interfering with their behavior. d.Computer programs and inexpensive computers that will collect, analyze and identify recurring patterns in the psychophysiological measure(s) of interest. 2.Pediatric Assessment Tool. Diagnosis of mental health disorders in children and adolescents is vital to providing early interventions to treat the disorder. In addition, a better understanding of the concept of functioning in psychopathology, and its appropriate measurement, is needed in pediatric populations. In the future, diagnostic tools may even help detect the initial onset of illness in children at risk, before symptoms occur. A priority for this program is to develop novel diagnostic tools to detect mental health disorders in children and adolescents. Of particular interest to this division are methods that can be used with children and adolescents with limited verbal communication (i.e., very young or developmentally disabled). Biochemical, genetic, physiological and psychological tool development is welcomed. a.Technologies to assess CNS effects of psychosocial or pharmacological interventions. b.Development of reliable and stable biomarkers/biosignatures that can identify at-risk individuals prior to disease onset, biological and behavioral indicators or predictors of treatment response, measures of disease progression, measures to identify dose ranges prior to clinical studies, preclinical or clinical efficacy testing, toxicity measures for drug development, defining patients to enroll in the clinical study, identifying CNS abnormalities, etc. c.Assessment tools for pediatric mental health disorders that are sensitive to developmental change, gender and cultural diversity, variation in cognitive and behavioral functioning, hearing and/or speech impairment, and co-morbid disorders. d.Innovative approaches to assessing mental disorders using new statistical and psychometric techniques such as Item Response Theory. e.Computerized methodologies for assessing various mental disorders suitable for use in primary care settings, e.g. they would need to function rapidly and reliably. f.Biological and behavioral measures to define and assess specific impairment-related components of psychiatric disorders, e.g., cognitive dysfunctions in schizophrenia. g.Development of valid and reliable measures that operationalize functioning within and across developmental periods, and that can be used in a variety of service settings. Such measures can lead to more accurate diagnoses, a better understanding of the impact of psychiatric disorders, and better tracking of treatment effectiveness. 3.Behavior Monitoring and Analysis of Pediatric Mental Health Disorders. a.Improve or create new video devices to monitor human behavior and ease analysis of behavior. b.Computer software to ease analysis of behavior monitored by video or telemetry systems. c.Automated methods to detect specific emotional states using behavioral and autonomic indicators: This Division is specifically interested in technologies that can identify children with heightened or dampened emotional states that could be associated with particular mental health disorders, including children with limited verbal skills (i.e., very young or developmentally disabled). If the technology will primarily be used to investigate basic mechanisms of behavior, the Division of Neuroscience and Basic Behavioral Science at NIMH would be the most appropriate division to contact. 4.Intervention Development for Childhood-Onset Mental Disorders. a.Strategies (e.g., animal behavioral testing, computer simulation) for evaluating, in early developmental periods, the effects of pharmacological agents on specific functional domains and brain circuits associated with mental disorders. b.Strategies (e.g., animal behavioral testing, computer simulation) for evaluating, in early developmental periods, the effects of cognitive or behavioral interventions (e.g., cognitive rehabilitation, attention training) or device-based protocols (e.g., transcranial magnetic stimulation or direct current stimulation) on specific functional domains and brain circuits associated with mental disorders. c.Methods for evaluation of long-term effects of psychotherapeutic drug administration or brain stimulation protocols in developmental animal models. 5.Methodological Research and Development. There is a need to devise new ways of data collection, analysis, management and dissemination. Examples include: a.Technologies that use the most recent technological advances to identify aberrations in the CNS during development, associated with mental disorders. Once these aberrations are identified and localized, rational therapies can be developed and evaluated. b.Innovative, computer-based methods to monitor preventive and treatment intervention efforts and correlate them with outcome measures are needed. Results should be accessible to other interested parties without compromising the privacy of the individual. c.Development of innovative software for addressing the integration of distributed cross-disciplinary data sources into coherent knowledge bases. The data should focus on pediatric mental health disorders. d.Computer-based intervention development for parents or for school settings. e.Development of databases containing detailed genetic and behavioral information on pediatric populations and their families, as resources for the field in investigations of gene x environment interactions. f.Mathematical, statistical and computer algorithms that could be used to analyze large and/or complex data sets. Examples of these data sets include those derived from functional imaging studies. Among other applications, these could be used to segment images such as those obtained from magnetic resonance imagers, filter noise, visualize data or search vast data sets for specified patterns or data (e.g., use of pattern recognition algorithms to search time series data sets obtained from electrophysiological recording of neural activity, or video data obtained from behavioral analysis of genetically altered animals). Improved techniques for path analysis when examining functional imaging datasets would also be of interest. B.Child and Adolescent Treatment and Preventive Intervention Research. An estimated one in ten children and adolescents in the United States suffers from mental illness severe enough to cause some level of impairment. Yet, it remains unclear what treatments are the best and safest for these developing age groups. A priority for this program is to support research and development of novel psychopharmacological or psychosocial approaches for the treatment and prevention of mental illness in childhood and adolescence, in subjects aged 18 and below. The goal of this research is broad and inclusive with respect to the heterogeneity of patients, the severity and chronicity of disorders, and the range of outcomes measured. Disorders studied include all mental and behavioral disorders. Interventions studied include pharmacologic approaches (individual and combination medications), somatic approaches, behavioral and psychotherapeutic approaches. Research is supported on individual and combined approaches. Research that translates findings on basic physiological or behavioral processes into novel preventive or treatment interventions is especially encouraged. Effectiveness studies that focus on interventions of known efficacy are assigned to the Division of Services and Intervention Research. Human subjects include child and adolescent age groups covering the full range of mental disorders individually and in complex patterns of comorbidity with other mental disorders and behavioral problems (e.g., anxiety and depression) and substance abuse (e.g., depression and alcohol abuse). 1.Pharmacologic Treatment Intervention. Clinical testing of novel mechanism therapeutics is the principle aim of this technology development section. This includes Phase IIa and proof of concept studies in pediatric subjects. It is expected the pharmacologic agents selected for these studies be IND-ready and based on novel molecular targets identified through basic and clinical research, preclinical research and animal model research relevant to understanding developmental aspects of mental illness. 2.Combined Intervention. Areas include all research that combines different treatment modalities in a single combined or comparative protocol (e.g., pharmacologic plus psychosocial intervention). 3.Psychosocial Intervention. Areas include development and application of new psychotherapeutic, behavioral, and psychosocial treatments, based on the latest advances in development neuroscience. 4.Preventive Intervention Program. Areas include preventive intervention studies in which efficacy has not been demonstrated, including those designed to reduce the risk of onset or delay onset of mental disorders, dysfunctions and related problems within asymptomatic and subclinical populations and those related to treatment (e.g., prevention of relapse, recurrence) or side effects (prevention/ minimization of tardive dyskinesia, etc.). Prevention studies that focus on behavioral problems, without a focus on a specific mental health disorder or a specific domain of function that significantly impacts a mental health disorder (e.g. cognitive function) should contact NICHD. 5. Development and Maintenance of Clinical Trial Networks. Areas include the development of hardware/software to facilitate research collaborations in conducting clinical trials, technologies to facilitate data sharing, merging of multiple data sets, and the development and maintenance of common protocols across research sites working on a common pediatric preventive or treatment intervention. C.Science Education in Mental Disorders. There is a critical need for improvement in science education, particularly in areas specifically related to brain, behavior and mental illness. Examples include: 1.Research on the best ways to present neuroscience and behavioral science information, in the context of mental health disorders, to particular groups of students (e.g., kindergarten through sixth grade). 2.Computer-based systems to teach students how to observe scientific phenomena related to the brain, behavior and mental illness, and to report them clearly in writing. 3.Research on better ways to communicate new knowledge and directions of scientific growth in the area of neuroscience and mental illness to teachers and curriculum developers. For further information on Developmental Translational Research-related topics, contact: Margaret Grabb, Ph.D. National Institute of Mental Health 6001 Executive Blvd. Room 7201 Mail Stop Code 9645 Bethesda, MD 20892 301-443-3563, Fax: 301-443-1731 Email: mgrabb@mail.nih.gov Division of Adult Translational Research and Treatment Development (DATR) The DATR is responsible for planning, directing and supporting programs of research, research training, research dissemination and resource development aimed at understanding the pathophysiology of mental illness and hastening the translation of behavioral science and neuroscience advances into innovations in clinical care. The Division supports a broad portfolio of pre-clinical and human clinical studies that focus on the phenotypic characterization and risk factors for major psychiatric disorders. In addition , the Division studies psychiatric disorders of late life. The division is comprised of four branches. These branches are: The Adult Psychopathology and Psychosocial Intervention Research Branch, The Clinical Neuroscience Research Branch, the Geriatrics Research Branch and the Experimental Therapeutics Branch. This division also includes a program on Traumatic Stress Disorders Research. Their respective functions are as follows: Adult Psychopathology and Psychosocial Intervention Research Branch. This branch promotes the integration of basic behavioral and neuroscience findings into translational research on the foundations of psychopathology and functional disability. The branch targets new science based assessment, prevention, treatment and rehabilitation practices including research on causal risk and protective factors for mental disorders, mechanisms that convert vulnerability into psychiatric symptoms and disability and use of modern psychometric and statistical theories to advance nosology and assessment. Other specific areas of emphasis include mood, eating disorders, anxiety disorders and schizophrenia. Clinical Neuroscience Branch. The focus of this branch is on the understanding of the neural basis of mental disorders. Human and animal studies are supported on the molecular, cellular and systems level of brain function designed to elucidate the pathophysiology of mental disease and to translate these findings to clinical diagnosis, treatment and prevention. These approaches are applied to the spectrum of mental disorders including schizophrenia, depression, bipolar disorder, anxiety disorder and other brain disorders. Areas of emphasis include: identification of valid and unique neurophysiological markers or complexes of markers for the major mental disorders and development of animal and or computational models that accurately mimic complex neurophysiology or behaviors characteristic of mental illness. Geriatrics Research Branch. This branch focuses on research and resource development in the etiology, pathophysiology and course of mental disorders of late life as well as in the treatment and rehabilitation of persons with these disorders. Disorders studied include mood, anxiety and personality disorders, psychotic disorders and schizophrenia, psychiatric syndromes and behavioral disorders in Alzheimer’s Disease and related dementias, suicide, and eating disorders. Selected areas of emphasis include: development of more reliable and valid phenotypes, assessments and biological and behavioral markers for late-life mental disorders; development of improved treatment and preventive intervention techniques for use in geriatric care settings; and identification of genetic, brain imaging and other predictors of variability in older adults’ treatment response. Experimental Therapeutics Branch. This branch supports multidisciplinary research on novel pharmacological approaches to the treatment of mental disorders, evaluation of existing treatments of mental disorders, development and assessment of putative biomarkers of psychiatric disease and treatment response and development and testing of novel treatments. Studies supported include early phase clinical studies of new medications, studies to predict treatment response and studies to validate biomarkers or predictors of therapeutic response to pharmacological intervention. Side effects of therapeutic agents are also given emphasis. Traumatic Stress Disorders Research Program. This program supports integrating basic behavioral and neuroscience findings into translational research on psychopathology associated with trauma exposure. Areas of emphasis include developing disorder and risk assessment tools based on individual differences, the development of treatment and preventive interventions for posttraumatic disorders, and identifying mechanisms of therapies and mechanisms of disorder that are impacted by therapies. This program also supports a broader continuum of research (basic science, clinical practice, and health care system factors) focused on the mental health consequences of mass trauma and violence (e.g. war, terrorism, natural and technological disaster), including interventions and service delivery in children, adolescents, and adults impacted by mass trauma. All applications relevant to the mission of the Division of Adult translational Research and Treatment Development will receive full consideration. Possible areas for future research include: A.Instrumentation for Clinical Research. Up-to-date hardware/software systems that use the most recent technological advances are needed to identify CNS dysfunction(s) related to mental disease. Once these dysfunctions are identified and localized, rational therapies can be developed and evaluated. 1.Physiological and Behavioral Monitoring: Technologies are needed to continuously monitoring physiological data (e.g., temperature, activity, sleep duration, EEG activity, ECG, pulse rate) with behavior, noninvasively and without impacting behavior. These monitoring devices should be designed for use with subjects that have a mental illness. 2.Data Analysis from Complex Data Sets: Computational tools are needed to record, catalog, categorize and identify interrelationships between several of the above measures. 3.Deep Brain Stimulation Technologies: Improvements in deep brain stimulation technology in human subjects/patients is increasingly important as this technique becomes more common as a potential treatment option for Obsessive Compulsive Disorder, depression, and other disorders. B.Technologies for Adult Clinical Research. It is important to develop reliable methods that can correctly identify the normal and abnormal components of cognitive, emotional, and psychosocial behavior in human development. Computer-based methods of accomplishing this aim are needed to increase the accessibility and reliability of information made available to the research community. 1.Assessment Tools. a.Technologies to assess CNS effects of psychosocial variables and interventions. b.Innovative approaches to assessing mental disorders using new statistical and psychometric techniques such as Item Response Theory. c.Computerized methodologies for assessing various mental disorders suitable for use in primary care settings. d.Inexpensive methodologies or techniques for assessing adherence to medication regimens. e.Innovative technologies for identifying and directing clinical attention to potentially adverse psychotropic drug interactions, particularly in vulnerable patients with complex regimens involving multiple medications. f.Simple-to-use tools for assessing individual risk profiles for the development of various mental disorders. 2.Methodological Research and Development. There is a need to devise new ways of data collection, analysis, management and dissemination. a.New relatively culture-free taxonomies and/or measures of basic behavioral and social phenomena that can be employed in research across socio-cultural contexts. b.Innovative computer-based observation techniques, and computer software and hardware that allow on-line methods for characterization of interpersonal interactions in groups. c.Low cost microcomputer software for the recording and analysis of patterns and sequences in observed social interactions. d.Causal modeling methodology as applied to correlational longitudinal data sets. e.A data translation and communication package for collecting, archiving, and making available existing longitudinal behavioral sets to the scientific community for secondary or meta-analyses. f.Flexible user-friendly software for control of timed, multi-modal stimulus presentation and response collection for experiments on perception and cognition. g.Development of improved standardized instruments and methods for assessing assets, deficits, and disorders in adult and late life. C.Adult Treatment and Preventive Intervention Research. 1.Development of novel methods to enhance efficiency of early phase clinical trials. 2.Development of novel assessments of psychopathology suitable for use in clinical research. 3.Identification of causal risk and protective factors for mental disorders. 4.Development of standardized assessments of psychiatric and comorbid disorders. 5.Develop psychometrically sound methods for assessing the cognitive, affective and behavioral response systems believed to underpin clinical symptoms and functional impairments. 6.Identify valid markers of illness onset. 7.Develop new definitions and measures to assess functioning in people with psychiatric disorders including self-reports, tests that simulate real-world tasks and new approaches to ratings by observers. 8.Creation and validation of new measures of functional capacity. 9.New approaches to assess the functional effects of drug or psychosocial interventions to treat mental disorders. 10.Identify valid and unique neuropsychological markers for the major mental and personality disorders. 11.Identify more reliable and valid phenotypes, assessments and behavioral markers for late-life mental disorders. 12.Development of techniques for maintaining or restoring mental capacities in older adults who experience declining learning and memory abilities due to age-related brain disorders. D.Experimental Therapeutics Research. 1.Early phase clinical studies of new medications targeting major mental illnesses or symptom domains now lacking adequate treatments. 2.Development of novel somatic treatments or medical devices for the treatment of mental illness. 3.Development of reliable and stable biomarkers/biosignatures that can identify at-risk individuals prior to disease onset, biological and behavioral indicators or predictors of treatment response, measures of disease progression, measures to identify dose ranges prior to clinical studies, preclinical or clinical efficacy testing, toxicity measures for drug development, defining patients to enroll in the clinical study, identifying CNS abnormalities, etc. Examples of side effect issues include: a)Development of new approaches to understand and predict the types, rates and pathophysiology of adverse effects of psychotropic medications. b)Development of new techniques to predict emergence of later abnormalities in body weight and disorders of glucose and lipid metabolism during treatment with psychotropic drugs. c)New methods to predict and assess the effects of psychotropic medication on cerebrovascular and cardiovascular function. 4.New approaches to understand age-related changes on the emergence of adverse effects from psychotropic medications. 5.New approaches, including pharmacological to prevent or reduce the negative metabolic, vascular and other side effects of psychotropic medications. For further information on these topics, contact: Margaret Grabb, Ph.D. National Institute of Mental Health 6001 Executive Blvd. Room 7201 Mail Stop Code 9645 Bethesda, MD 20892 301-443-3563, Fax: 301-443-1731 Email: mgrabb@mail.nih.gov Division of AIDS Research (DAR) The DAR supports research to develop and disseminate behavioral interventions that prevent HIV/AIDS transmission, support HIV/AIDS treatment and care, and understand and alleviate the neuropsychiatric consequences to HIV/AIDS infection. Specific topics related to these research areas are listed below. Inquiries are encouraged. THE CENTER FOR MENTAL HEALTH RESEARCH ON AIDS: A.Technologies to Facilitate Research in HIV/AIDS Prevention and Care 1.Innovative approaches for assessing HIV sexual risk behavior among research participants and at-risk populations, including biomarkers of risk behavior. 2.Development of electronic, on-line archives of validated HIV/AIDS research instruments. 3.Development and validation of novel self-report, computer-assisted, and virtual reality HIV/AIDS research instruments and assessments. 4.Development of methods to assess functioning in families in which there is an HIV infection in order to develop improved treatment modalities. 5.New tools and methods that physicians and researchers could use to monitor patient adherence to prescribed HIV/AIDS antiretroviral medication regimens in real time. 6.Computational systems that physicians and researchers can use to model the development of drug resistance based on degree and pattern of patient adherence to HIV/AIDS antiretroviral medications. 7.Technologies to assist the merging of multiple forms of HIV/AIDS data sets (e.g., community- or clinic-level data, pharmacy claims, patient self-reports, etc.) and to facilitate innovative and complex analytic strategies. 8.Causal modeling methodology as applied to correlational longitudinal data sets collected in HIV/AIDS research. 9.The development and advancement of innovative research trial designs (e.g., fixed adaptive, encouragement, partially randomized preference) for HIV/AIDS prevention and care research. 10.Technology and electronic systems that will facilitate participant scheduling, tracking, and retention in HIV/AIDS clinical trials and longitudinal studies. 11.The application of modern technology to enhance the science, operation, and management of multi-site HIV/AIDS clinical trials and behavioral research. 12.A data translation and communication package for collecting, archiving, and making available existing HIV/AIDS behavioral data sets to the scientific community for secondary or meta-analyses. B.HIV Prevention Interventions. CMHRA seeks innovative technologies and strategies that will help reduce HIV transmission risk behavior, especially among populations at high risk for HIV infection (such as ethnic minority populations and young men-who-have-sex with men), as well as among individuals who are infected with HIV. 1.Development of methods to reduce, prevent and/or change HIV-associated and STD risk behaviors. 2.Development of school-based HIV prevention curricula, including innovative uses of emerging technologies. 3.Curricula, computer software and virtual reality programs that provide communication skills, training and role-play exercises for HIV risk reduction. 4.Methods to increase use of HIV testing and that facilitate effective test result obtainment, confirmation and counseling. 5.Novel approaches to address the issue of relapse prevention of HIV-associated risk behaviors. 6.Development of new behavioral strategies to reduce high-risk HIV transmission behavior among persons recently infected. C.HIV/AIDS Educational Tools, Curricula, and Scientific Training 1.Development of computer-based or online HIV/AIDS prevention curricula and interventions for parents, foster parents and guardians, schools, or community settings. 2.Research on the best ways to present HIV/AIDS science and prevention information in an age-appropriate manner to particular groups of students. 3.Development of print and/or computer based materials to assist primary care practitioners in informing their patients about HIV risk and prevention. 4.Innovative approaches to the development of curricula for training in multicultural issues and development of cultural competence in HIV risk assessment. 5.Develop and test technologies designed to modify the practice behaviors and decision-making process of health care providers to improve the quality of screening, counseling, prevention, and treatment services for HIV positive persons or individuals at-risk for HIV. 6.Video and computer-assisted methods to train health and mental health care providers in the psychosocial and neuropsychiatric aspects of HIV infection and AIDS. 7.Development of materials and programs to assist health care practitioners in improving patient adherence to HIV/AIDS medical regimens. 8.Development of training materials to increase awareness regarding the neurodevelopmental consequences of HIV infection in children in developing countries. 9.Development of strategies and systems to encourage entry and retention of individuals with non-HIV/AIDS science backgrounds (engineers, computer scientists, medical anthropologists, law, business) or perspectives (individuals from under-represented communities) into the HIV/AIDS research field. 10.Development of systems to keep established researchers and practitioners up-to-date on the findings and implementation of HIV research. D.Systems to Advance the Dissemination and Implementation of HIV/AIDS Interventions 1.Web-based networks and software for the dissemination, identification, and tailoring of efficacious HIV/AIDS behavioral interventions targeting at-risk populations. 2.Development of technological approaches to increase the sustainable uptake of scientifically based HIV/AIDS prevention interventions across diverse community settings. 3.Development of strategies or application of technology to assist organizations in identifying and implementing proven HIV prevention strategies and in addressing health disparities. 4.Novel methods of disseminating HIV prevention materials to be used in community based outreach programs for special populations (school dropouts, homeless, street youth, incarcerated youth). 5.Development of innovative approaches to link researchers with community providers in the implementation of research-based HIV prevention efforts at the community level. 6.Systems that build the capacity of HIV/AIDS community-based organizations to conduct program evaluations and document intervention outcomes for the purposes of maintaining and enhancing ongoing intervention programs. E.Technologies to Support HIV/AIDS Mental Health Services 1.Use of technology to develop and disseminate curricula for training clinicians and other health care practitioners in the prevention and treatment of HIV-related mental disorders. 2.Development of novel programs to help people recognize and access treatment of mental health problems arising from living with HIV/AIDS as a long-term chronic condition. 3.Develop rehabilitative approaches to alleviate HIV-associated neurodevelopmental abnormalities that may restrict children’s academic achievements and quality of life. 4.Development of innovative approaches to reduce stigma often expressed toward individuals with HIV/AIDS. 5.Develop and test interventions for appropriate HIV status disclosure to relationship partners, family members, and health care providers, in an effort to optimizes the likelihood of positive outcomes. F.Tools to Monitor and Improve Patient Adherence to HIV/AIDS Treatment 1.Development of novel methods to expedite and enhance linkage to primary medical care for individuals who receive HIV-seropositive test results in community-based settings. 2.Technologies that will electronically monitor HIV/AIDS patient adherence to antiretroviral medications and that will use wireless technology to radio this data back to providers and/or researchers for real-time monitoring of adherence. 3.Clinic-based systems that will screen HIV/AIDS patients for medication adherence while they await medical appointments and that will immediately integrate these patient reports into the electronic medical record so this information is routinely available to physicians during their appointments with patients. 4.Development of novel tools or methodologies designed to improve patient adherence to HIV/AIDS drug therapies. 5.Systems that improve adherence to HIV/AIDS medical care by enhancing the ability of patients to monitor and manage scheduled medical appointments, routine prescription refills, and daily medication doses. 6.Novel systems for distributing, dispensing, or administering antiretroviral drugs that are designed to enhance patient adherence to these regimens. 7.Biologically-based technologies that will aid medical doctors in determining how a particular individual may respond to a particular HIV/AIDS medication, i.e. “individualized medicine.” For example, genomic and phenotypic information combined could be used in determining whether a drug will be an effective treatment for an individual. Likewise, genomic and phenotypic information may help to identify which patients are at risk for drug-induced side effects. G.Research Tools and Treatments for Neuro-AIDS: HIV-1 Infection and the Nervous System 1.Development of novel non-invasive (e.g., neuroimaging) approaches to assess and study mechanisms of neurologic and neurocognitive dysfunction associated with HIV infection. 2.Development of in-vivo and in-vitro models to assess mechanisms of HIV-1 trafficking into and out of the CNS, mechanisms of neuropathogenesis and therapeutic strategies for eradicating HIV-1 in the CNS. 3.Development of novel molecular markers for NeuroAIDS using proteomics, microarrays and neuroimaging. 4.Development of novel molecular approaches to study compartmentalized viral evolution in the CNS. 5.Development of improved anti-retroviral therapeutic strategies for targeting CNS infections including: nanotechnologies, facilitated entry of anti-retroviral therapeutic agents through the blood-brain barrier by manipulation of transporter systems and development of novel anti-retroviral therapeutic agents that readily pass through the blood-brain barrier. 6.Development of novel therapeutic approaches to block or reverse CNS dysfunction associated with HIV infection. 7.Discovery and development of novel tools and cost effective methods for detecting the efficacy and neurological and neuropsychiatric side effects of anti-retroviral medications. 8.New approaches to reduce transmission risk or neuro-cognitive impairment in persons with recent HIV infection (0-6 months post exposure). 9.Novel therapeutic and diagnostic instrumentation development for the detection and treatment of neurological manifestations of HIV co-infections such as tuberculosis, hepatitis C, toxoplasmosis, that can be used in developing countries. 10.Development of novel or refinement of existing cell-based assays designed to screen compounds (small molecule, large molecule, bioproduct, etc.) targeted to treat neurologic and psychiatric disorders that are associated with HIV/AIDS. 11.Development of novel or refinement of existing animal models to test the efficacy and toxicity of new agents targeted specifically towards eliminating/eradicating HIV or its sequelae in the brain. 12.Discovery and development of small molecular inhibitors or enhancers targeted to mechanisms that play critical roles in viral replication pathways especially in the CNS. 13.Improvement/validation/characterization of the existing in vitro and animal models that are used for screening compounds that have therapeutic potential for NeuroAIDS and its associated complications. 14.Novel compounds or adjunctive therapies that have the potential to protect/ameliorate/treat the long-term neurologic and psychiatric side effects of ARVs in the presence or absence of psychotropic medications. 15.Novel models or methods for the pharmacokinetic/pharmacodynamic studies to detect long-term neuropsychological adverse effects of ARVs. 16.Applications that assess the neuroprotective potential or inhibition of HIV replication in the brain with FDA-approved drugs that are currently registered for other indications (off-label validation studies). 17.Development/improvement of cost effective methods, assays, or instruments that detect currently approved ARVs plasma concentrations in relationship with disease progression. 18.Discovery and development of biomarkers designed to detect drug efficacy, measure viral load, or provide evidence that agents are directed against the targets in the CNS or peripheral nervous system (PNS). 19.Development of technology (IT or other) to optimally study/analyze/report on adverse effects of ARVs in the presence of other medications, especially psychotropic medications, drugs of abuse, or medications to treat drug abuse. 20.Develop or adapt neurological/ neuropsychological/neurobehavioral assessments to evaluate HIV associated abnormalities in adults/children in resource poor environments that are adaptable to different cultures and languages. For information related to programs supported by the Center for Mental Health Research on AIDS please contact: Michael J. Stirratt, Ph.D. Program Officer, Adherence Program and SBIR/STTR Programs Center for Mental Health Research on AIDS Division of AIDS and Health Research National Institute of Mental Health 6001 Executive Blvd., Room 6199 Bethesda, MD 20892 (Postal mail) Rockville, MD 20852 (FedEx, UPS) Telephone: 301-443-6802 Fax: 301-443-9719 E-mail: stirrattm@mail.nih.gov Division of Services and Intervention Research The Division of Services and Interventions Research supports research, research demonstrations, research training, resource development, and research dissemination in prevention and treatment interventions, services research, clinical epidemiology, and diagnostic and disability assessment. The division is composed of three branches: Services Research and Clinical Epidemiology Branch, Adult Treatment and Preventive Intervention Research Branch, and Child and Adolescent Treatment and Preventive Intervention Research Branch. The Division supports two critical areas of research: •Intervention research to evaluate the effectiveness of pharmacologic, psychosocial (psychotherapeutic and behavioral), somatic, rehabilitative and combination interventions on mental and behavior disorders-including acute and longer-term therapeutic effects on functioning across domains (such as school, family, peer functioning) for children, adolescents and adults. •Mental health services research The interventions focus is broad and inclusive with respect to the heterogeneity of patients, the severity and chronicity of disorders, and the variety of community and institutional settings in which treatment is provided. It includes clinical trials evaluating the effectiveness of known efficacious interventions, as well as studies evaluating modified or adapted forms of interventions for use with additional populations (such as women, ethnic and racial groups), new settings (public sector, pediatric primary care, schools, other non-academic settings, communities at large) and people with co-occurring disorders. Other foci include: identifying subgroups who may be more likely to benefit from treatment, evaluating the combined or sequential use of interventions (such as to extend effect among refractory subgroups), determining the optimal length of intervention, establishing the utility of continuation or maintenance treatment (that is, for prevention of relapse or recurrence), and evaluating the long-term impact of efficacious interventions on symptoms and functioning. Services research covers all mental health services research issues, across the lifespan and disorders, including, but not limited to: •Services organization, delivery (process and receipt of care), and related health economics at the individual, clinical, program, community and systems levels in specialty mental health, general health, and other delivery settings (such as the workplace). •Interventions to improve the quality and outcomes of care (including diagnostic, treatment, preventive, and rehabilitation services. •Enhanced capacity for conducting services research •The clinical epidemiology of mental disorders across all clinical and service settings. The Division also provides biostatistical analysis and clinical trials operations expertise for research studies; analyzes and evaluates national mental health needs and community research partnership opportunities; and supports research on health disparities. The priorities for 2011 should focus on technologies that advance the scientific opportunities and recommendations of “The Road Ahead: Research Partnerships to Transform Services, A Report by the National Advisory Mental Health Council’s Workgroups on Services and Clinical Epidemiology Research.” “The Road Ahead: Research Partnerships to Transform Services, A Report by the National Advisory Mental Health Council’s Workgroups on Services and Clinical Epidemiology Research,” and the NIMH Strategic Plan. Examples are listed below: 1.Clinical Trials Methodologies: The development, testing and refinement of methodologies, instruments and statistical approaches to facilitate collaborative clinical trials for the prevention, treatment and rehabilitation of individuals with mental disorders; the development of innovative trials design (e.g., fixed adaptive, encouragement, partially randomized preference) the application of modern technology to enhance the science, operation, and management of multi-site mental health clinical trials; and the development of mental health clinical trial archives. The development of portable clinical trial management systems such as serious adverse event (SAE) oversight and monitoring software. Adaptation of existing clinical trial methodologies to study mental health disorders. Development of common data elements to enhance uniformity across clinical trials with and amongst disorders. 2.Science Training and Education: SBIR applications must focus on DSIR’s research priorities. Develop, modify and test new and existing technologies, strategies and approaches to: (1) enhance science and research training across the educational/ career pipeline; (2) improve scientific literacy for clinicians and service/ organizational providers; (3) encourage entry and retention of individuals with non-mental health science backgrounds (engineers, computer scientists, medical anthropologists, law, business) or perspectives (individuals from under-represented communities) into the mental health services and interventions field; (4) keep established researchers and practitioners up-to-date on the findings, implementation, and methods of services and interventions research; and (5) facilitate participatory research with individuals, families and communities. This can include the development of science/ research education materials, curriculum, methodologies and web-based programs relevant to the mission of the division; the development of networking and collaborative approaches to research training in mental health interventions and services research; and the development of multi-media approaches (combined with traditional strategies) to improve the level of scientific and career mentoring that mental health services and interventions researchers receive. 3.Public Health Oriented Pharmacoeconomics: Develop and test simulation models for estimating the amount of total out-of-pocket expenditures (co-payments) for the most frequently prescribed psychotropic drugs under different insurance benefit scenarios and/or under different pharmacy benefit management scenarios. Models should also be developed to accommodate common combined pharmaceutical approaches. 4.Dissemination: Development of technological approaches to increase the sustainable uptake of scientifically based treatments and services across diverse community settings. This could include web-based interactive tools for state/county mental health or related (e.g., schools) agencies around implementation of evidence-based practices. Development of innovative ways (e.g., new technology, use of multi-media) of disseminating information to stakeholders. Development of new approaches to the dissemination and implementation of evidence based mental health interventions to underserved populations (e.g., rural/frontier, aging individuals with neuropsychiatric disorders). Development of technology to enhance conduct of clinical trials and the dissemination of their results. 5.Implementation: Application of new technologies, approaches and strategies to identify and utilize active therapeutic ingredients in complex community-based services and programs that optimize functioning and sustain community reintegration of people with mental disorders. Use of technologies and strategies to assist service systems to more adequately plan for transitions (e.g., child to adult system, prison to community) and seamlessly integrate mentally ill individuals moving between these sectors. 6.Merging Multiple Data Sets: Merging multiple data sets (e.g., claims, trials, pharmacy etc.) for innovative and complex analytic strategies. 7.Community Outreach to Diverse and Underserved Populations: Application of new technologies and strategies to develop, test, and refine culturally appropriate materials and approaches to: foster help-seeking and engagement of diverse and underserved populations in research-based mental health treatment and prevention; to foster participation in community based research by diverse and underserved populations; and to inform diverse provider groups about state-of-the-art mental health treatments and services in order to facilitate their implementation of these interventions. 8.Computerized Methodologies for Mental Health Services Research: Applications need to focus on computerized methods to assess mental disorders in primary care settings including screening devices for identifying mental disorders across the life-span; development of computer software and hardware that allow conducting computer assisted interviews with severely mentally ill people for research purposes to obtain information on their quality of care; design work to move assessment as rapidly as possible to computerized adaptive testing (CAT); apply audio and video technologies to assess patient’s treatment preferences. A.Services Research and Clinical Epidemiology Branch. The branch supports research on the organization, financing, delivery, effectiveness, and appropriateness of mental health care in everyday settings in order to find ways to improve the effectiveness, efficiency, and equity of mental health services (including preventive services) in community and other settings. Also supported are studies on pharmacoeconomics, pharmaco-epidemiology, and the distribution, determinants, and course of mental illness in the context of various clinical settings. Mental health services include mental health care provided in specialty mental health and general health care settings, including primary care, hospitals, nursing homes, and other residential care settings, as well as in educational settings and various legal system settings, such as jails, juvenile detention and correctional facilities, prisons, and probation and parole programs. Other services often needed by mentally ill persons include social services, vocational and rehabilitation services, welfare, and housing. Relevant services include those provided to children and adolescents with emotional disorders, adults and elderly adults with mental disorders, and persons with mental illness that co-occurs with physical illness and with alcohol and/or drug abuse disorder. Research methodologies include ethnographic studies, surveys, and analyses of secondary data, randomized controlled trials, quasi-experimental designs, cohort, and case-control studies. Advances in clinical epidemiology, mental health treatment and services research fields have made it imperative that intensive work continue in the areas of assessment/screening technologies, outcome assessment measurement and measurement packages, dissemination technologies, data analysis techniques, and the training of clinicians and providers. The translation of efficacious and effective treatments into primary care, community mental health centers, and managed care settings is both a major challenge and opportunity to develop technologies and systems that will improve the care and rehabilitation of patients and enable them to profit from the research advances that have been made. Research is needed on the dissemination of empirically supported treatments or services. 1.Methodological Research Program. Supports studies that involve development, testing, and refinement of methodologies and instruments to facilitate research on services for mentally ill persons, including measures of severity of illness, family burden, social support, quality of care, effectiveness of care, direct and indirect cost of mental disorders, and short-term and long-term outcome measures; studies submitted by statisticians, psychometricians, and other experts in research methodology and scientific data analysis for work on the design, measurement, and statistical challenges inherent in conducting mental health services research. 2.Outcomes and Quality of Care Research. This program is concerned with strengthening the theoretical and empirical base for mental health services research by including approaches that derive from sociology, anthropology, and the behavioral sciences in general. The program supports research relating to issues of culture, social systems, and social networks as they relate to help seeking, use, and provision of services, effectiveness, quality, and outcomes of services. 3.Systems Research Program. Supports studies on organization, coordination, and collaboration of mental health and related services both within and across care settings in order to improve mental health outcomes and prevent or treat co-occurring substance abuse, physical problems, and other behavioral health disorders. Service sectors of interest include: the criminal justice system, housing and other social services, community support, post-trauma services, and adult autism services. Also relevant are studies to establish the effectiveness of legal mechanisms relevant to persons with mental illness, such as outpatient commitment, community monitoring, and guardianship; and the development of the role and expertise of social workers in mental health research activities. 4.Disparities in Mental Health Services Program. Plans, stimulates, disseminates, and supports research on the complex factors that influence disparities in mental health services, particularly across special population groups such as racial and ethnic groups, as well as women and children, and persons living in rural and frontier areas. The program addresses care delivered in a variety of settings such as the specialty mental health sector, the general medical sector, and community settings (such as schools). Also, it supports research that examines innovative services interventions (such as community-based participatory methods, faith-based) to overcome mental health disparities related to mental health service delivery and use. 5.Sociocultural Research Program. Is concerned with strengthening the theoretical and empirical base for mental health services research by including approaches that derive from sociology, anthropology, and the behavioral sciences in general. The program supports research relating to issues of culture, social systems, and social networks as they relate to help seeking, use, and provision of services, effectiveness, quality, and outcomes of services. 6.Child and Adolescent Services Research Program. Includes research on the quality, organization, and content of services for children with mental disorders and their families. The program focuses on child mental health services provided in multiple sectors and settings, such as schools, primary care, child welfare, juvenile justice, and mental health. Program emphases include practice research within child service systems, research testing the outcomes of innovative child service delivery models, and studies that examine the adaptability or sustainability of child mental health services. 7.Financing and Managed Care Research. Supports research on economic factors affecting the delivery of mental health services including the economic burden of mental illness; financing and reimbursement of public and private mental health services; impact of various forms of managed care and physician payment methods on the cost of mental health care; pharmaco-economics; evaluation of the impact of insurance coverage including mandated coverage and mental health insurance parity on access, cost, and quality; cost-benefit, cost-effectiveness and cost-utility analysis of mental health service interventions; and economic analysis of practice patterns of different mental health providers. The goal of the program is to expand understanding of the role of economic factors in the delivery and use of mental health services and assist in the development of improved mental health financing methods promoting high quality, cost-effective care for people suffering from mental disorders. 8.Primary Care Research. Includes studies on the delivery and effectiveness of mental health services within the general health care sector; recognition, diagnosis, management, and treatment of mental and emotional problems by primary care providers; coordination of general medical care with and referrals to mental health specialists; provision of psychiatric emergency services, consultation/liaison psychiatry, and other psychiatry, psychology, and social work services within the general medical care sector; studies that improve understanding of how best to improve care for people with mental disorders and co-occurring physical conditions. 9.Clinical Epidemiology Research. Includes epidemiologic studies of mental disorders in clinical settings, that is, the distribution of treatments and services in a population; studies to determine usual or best practices and the relationship to patient, provider, and system factors, as well as to outcomes; pharmaco-epidemiology studies; research to identify factors for the development of mental disorders in clinical settings, factors important in the natural history of mental disorders, including comorbid conditions, and the rates of occurrence of mental disorders in clinical and services populations. 10.Disablement and Functioning Research Program. Supports studies on the development of methodologies for assessing disablements and functional status, and the development of global and specific measures of disablements and functional status; the identification and assessment of disablements/functional status in clinical investigations and in clinical epidemiological surveys. In addition, it supports studies of the relationship of rehabilitative and traditional mental health services and service systems; impact of disability benefits and insurance; factors affecting impairments and disabilities during and as an outcome of rehabilitation and other treatments; rehabilitative services focused on specific domains of disabilities, such as work and social relationships; and, factors that influence and sustain community reintegration. 11.Dissemination and Implementation Research Program. Includes studies that will contribute to the development of a sound knowledge base on the effective transmission of mental health information to multiple stakeholders and of the process by which efficacious interventions can be adopted within clinical settings. Research on dissemination will address how information about mental health care interventions is created, packaged, transmitted, and interpreted among a variety of important stakeholder groups. Research on implementation will address the level to which mental health interventions can fit within real-world service systems. Related topics include multilevel decision-making perspectives about services and interventions in community settings, with special focus on translating behavioral science into applied research in these areas. B.Adult Treatment and Preventive Interventions Research Branch. This Branch supports research evaluating the therapeutic (acute, maintenance, and preventive) and adverse effects of psychosocial, psychopharmacologic, and somatic interventions of proven efficacy in the treatment of mental disorders in adults. It includes trials evaluating and comparing the effectiveness of known efficacious interventions, as well as studies evaluating modified or adapted forms of interventions for use with specialized populations (such as women, or specific ethnic or racial groups), new settings (public sector, or computer based), new methods of treatment delivery (e.g., web or computer –based), and people with comorbid physical or mental disorders. 1.Somatic Treatments Program. Areas include electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (RTMS), bright light, physical exercise, and similar nonpharmacologic approaches for which efficacy has been demonstrated. 2.Adult Psychotherapy Intervention Program. Areas of program responsibility include evaluation of the effectiveness of psychotherapeutic, behavioral, and pspychosocial treatments, assessment of standardized approaches to treatment (based on treatment manuals), and applications of psychotherapy treatments. 3.Adult Psychopharmacology Intervention Program. Areas of program responsibility include research involving psychotropic medications of demonstrated efficacy. Examples include evaluation of long-term effectiveness of pharmacotherapy and treatment of subpopulations of recognized diagnostic groups. 4.Adult Integrated Treatment Program. Areas of program responsibility include the use of combined or sequential treatment approaches to improve long-term outcome. A major focus is improvement of efficacious psychopharmacological interventions to maximize symptomatic relief while minimizing adverse reactions. For example, medications may be combined with the full range of therapies in individual, conjoint, or group settings. 5.Preventive Interventions Program. Areas of program responsibility include studies evaluating the effectiveness of preventive interventions, including those designed to reduce the occurrence of mental disorders, dysfunctions and related problems within asymptomatic and subclinical populations and those related to treatment (such as prevention of relapse, recurrence, inappropriate resource use) or side effects. A specially designated programmatic focus is the area of suicide prevention. 6.Rehabilitative Interventions. Areas of program responsibility include evaluation of the effectiveness of psychotherapeutic, behavioral, and psychosocial treatments, assessment of standardized approaches to treatment (based on treatment manuals), and applications of psychotherapy. C.Child and Adolescent Treatment and Preventive Intervention Research Branch. The branch supports research to evaluate the effectiveness of mental health preventive, treatment and rehabilitative interventions- alone or in combination-for children and adolescents (including those co-occurring with other conditions). The Branch also supports research addressing the long-term effectiveness of known efficacious interventions, including their role in the prevention of relapse and recurrence of mental disorders. Areas of emphasis include: Research on the effectiveness of treatment interventions for childhood and adolescent mental and behavioral disorders in practice and community settings to determine the real life therapeutic benefit short-and-long term; Research to prevent mental and behavioral disorders in children and adolescents; Research to build new methodologies that can be effectively used to evaluate the safety of interventions in community settings; Research to determine whether treatment of mental and behavioral disorders in children results in improved outcomes as adolescents and young adults and prevents the negative functional outcomes associated with those disorders (such as substance abuse, academic failure, higher medical costs, co-occurring mental disorders). juvenile justice facilities. 1.Pharmacologic Treatment Intervention Program. Areas of program responsibility include evaluation and comparison of efficacious pharmacological and other somatic treatments for children and adolescents with mental disorders. 2.Combined Intervention Program. Child and Adolescent Combined Intervention Program. Areas of program responsibility include all research that combines different treatment modalities in which efficacy has been demonstrated in a single combined or comparative protocol. 3.Psychosocial Intervention Program. Supports research evaluating the effectiveness of psychosocial interventions on children’s and adolescents mental and behavior disorders, including acute and longer-term therapeutic effects on functioning across domains. It includes trials evaluating the effectiveness of known efficacious interventions, as well as studies evaluating modified or adapted forms of interventions for use with additional populations, new settings, and people with comorbid disorders. 4.Preventive Intervention Program. Areas of program responsibility include research examining the effectiveness of preventive intervention studies, including those designed to reduce the occurrence of mental disorders, dysfunctions and related problems with asymptomatic subclinical populations. D.Clinical Trials Operations and Biostatistics Unit. This Unit serves as the operations focal point for collaborative clinical trials on mental disorders in adults and children. The Unit has responsibility for operations and oversight of both contract-supported and cooperative agreement-supported multisite clinical trial protocols, as well as operations focus on special clinical trial research projects that may be undertaken by the Institute. In addition, the Unit has general leadership responsibility for over-arching matters related to clinical trials operations, such as the coordination of the ancillary protocols across the large trials, development of long-term strategies for clinical trials research (such as clinical trials research networks), improvement of the quality of clinical trials by development and monitoring of operations guidelines, and implementing the NIMH policy for dissemination of public access datasets. Unit staff serves as primary liaison with the Data and Safety Monitoring Boards for all matters related to the operation and conduct of the clinical trials. The Unit provides consultation to Institute staff and grantee/contractor staff on biostatistical matters related to appropriateness of study design, determination of power and sample size, and approaches to statistical analysis of data from clinical trials supported by NIMH. For further information on Services and Intervention Research contact: Adam Haim Division of Services and Intervention Research 6001 Executive Boulevard Room 7160, MSC 9649 Bethesda, MD 20892-9635 301-445-3593 Email: haima@mail.nih.govHHS201104262011042620110626-1Closed67059http://www.sbir.gov/node/67059The mission of NINDS is to reduce the burden of neurological disease—a burden borne by every age group, by every segment of society, by people all over the world. To this end, the Institute supports and conducts research on the healthy and diseased brain, spinal cord, and peripheral nerves. Hundreds of disorders afflict the nervous system. Common disorders such as stroke, epilepsy, Parkinson’s disease, and autism are well-known. Many other neurological disorders are rare and known only to the individuals and families affected, their doctors, and scientists. The NINDS SBIR/STTR program funds small business concerns to conduct innovative neuroscience research or neuroscience research and development (R/R&D) that has both the potential for commercialization and public benefit. NINDS is committed to helping small business concerns commercialize their technologies through its grant funding, technical assistance program participation, and outreach at meetings. NINDS encourages all Phase II applicants to apply to the NIH Commercialization Assistance Program (CAP) to gain assistance in transferring their products to the marketplace. The CAP program is open to all Phase II grants that were active in the past six years. NINDS is increasingly tracking the progress of its funded small business concerns and the products they develop. Funding priority will be given to those small business concerns that show not only their ability to develop products but their growth as a small business concern towards independence from the SBIR/STTR program. LIMITED AMOUNT OF AWARD For budgetary, administrative, or programmatic reasons, NINDS may decrease the length of an award and/or the budget recommended by a review committee, or not fund an application. Generally, NINDS does not fund Phase I applications greater than $350,000 total cost per year for up to 2 years or Phase II applications greater than $1,000,000 total cost per year for up to 3 years. Applicants considering a requested budget greater than these limits are strongly encouraged to contact program staff before submitting an application. Phase IIB Competing Renewal Awards In addition to the traditional Phase I and II applications, NINDS will accept Phase IIB SBIR/STTR Competing Renewal grant applications to continue the process of developing products that require approval of a federal regulatory agency. Such products include, but are not limited to: medical implants, drugs, biologics, and new treatment or diagnostic tools that require FDA approval. NINDS will accept applications for up to three years that do not exceed $1,000,000 per year in total costs. The following examples would make appropriate topics for proposed SBIR or STTR Phase IIB Competing Renewal projects. This list is not meant to be all-inclusive, and applications for other appropriate activities will be accepted. 1.Studies for preclinical discovery and development of drugs to treat neurological disorders. Appropriate areas of effort may include the following (but are not limited to): medicinal chemistry structure-activity relationship (SAR) studies to develop drug candidates, pharmacology studies aimed at evaluating the potential therapeutic activity and side effect profile of drug candidates, medicinal chemistry and pharmacology studies aimed at synthesizing and evaluating compounds as potential drug leads and as preclinical drug candidates, and studies aimed at evaluating drug metabolism and pharmacokinetic behavior in rodents. These efforts should extend beyond those conducted under the initial SBIR Phase I and Phase II grants. The studies conducted under the previous grants should be sufficient to provide a sound rationale for continued development. 2.Completion of studies as required by the FDA for an IND application. 3.Safety and effectiveness studies of novel medical devices. 4.Human clinical trials/studies to determine the safety profile, metabolism, and/or efficacy of a drug. Please contact Ms. Stephanie Fertig (contact information provided below) before beginning the process of preparing an application. Prospective applicants are strongly encouraged to submit a letter of intent that includes the following information: •Descriptive title of the proposed research •Name, address, and telephone number of the Principal Investigator •Names of other key personnel •Participating institutions •Funding Opportunity Announcement Number (e.g., PA-10-XXX) Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NIH staff to estimate the potential review workload and plan the review. It is expected that only a portion of NINDS SBIR/STTR Phase II awards will be eligible for a Competing Renewal grant. Any Phase IIB Competing Renewal applications that do not propose to develop products that require regulatory approval, or that exceed the total cost budget cap, will be withdrawn from consideration prior to peer review. For more information on Competing Renewal Awards of SBIR Phase II grants for Brain and Behavior Tools: http://grants.nih.gov/grants/guide/pa-files/PA-08-056.html. Ms. Stephanie Fertig, M.B.A. Project Manager, Small Business Programs 301-496-1447; Fax: 301-480-1080 Email: fertigs@ninds.nih.gov For general questions related to the small business program, email: nindssmallbusiness@mail.nih.gov. RESEARCH TOPICS OF INTEREST TO NINDS General Areas of Interest The NINDS accepts a broad range of small business applications that are significant, innovative, and relevant to its mission. Examples of research topics within the mission of NINDS that may be of interest to small businesses are shown below. This list is not all inclusive and some research areas fall into multiple categories. 1.Therapeutics and Diagnostics Development for Neurological Disorders, including biomarker and diagnostic assays, therapeutics (drugs, biologics, and/or devices) for treatment of neurological disorders, and technologies/methodologies to deliver therapeutics to the central nervous system. 2.Clinical and Rehabilitation Tools, including intraoperative technologies for neurosurgeons, rehabilitation devices and programs for neurological disorders, and brain monitoring systems 3.Technology and Tools, including imaging technologies to image the nervous system, neural interfaces technologies, and tools for neuroscience research and drug development. In addition to the research topics listed, NINDS also solicits applications in specific program areas. For additional information about NINDS program announcements, please visit our small business home page at: http://www.ninds.nih.gov/funding/small-business/. Clinical Trials The NINDS is committed to identifying effective treatments for neurological disorders by supporting well-executed clinical trials. NINDS may decline funding of a clinical trial application for programmatic or administrative reasons. SBIR applicants are strongly encouraged to contact Joanne Odenkirchen (contact information provided below) within the NINDS Office of Clinical Research for advice about potential clinical trial applications prior to submission in order to determine the relevance of the proposed research to NINDS and its potential for translating discoveries to clinical interventions for neurological disorders. For more information about what is generally required before trials are funded, applicants are encouraged to review the NINDS Office of Clinical Research webpage (http://www.ninds.nih.gov/research/clinical_research/index.htm). Joanne Odenkirchen, M.P.H. Clinical Research Project Manager, Office of Clinical Research 301-496-3104 Email: jo21x@nih.gov NINDS Cooperative Program in Translational Research Although translational research is supported through the general SBIR/STTR program announcement, the NINDS also has a Cooperative Program in Translational research (PAR-08-235). The NINDS Cooperative Program encourages Phase II and Fast-Track applications that directly address the identification and pre-clinical testing of new therapeutics for neurological disorders. The program will facilitate solicitation, development, and review of therapy-directed projects to accelerate the translation of basic research discoveries into therapeutic candidates for clinical testing. This program is specifically directed at projects that include therapeutic leads with demonstrated activity against the intended disease target. The program supports pre-clinical optimization and testing of these leads and projects must be sufficiently advanced that an IND or IDE application to the FDA can be submitted by the end of the project period. The program does not support early-stage therapeutic discovery activities such as high throughput screening. The program also excludes clinical research, basic research, and studies of disease mechanism. This is a milestone-driven cooperative agreement program involving participation of NINDS staff in the development of the project plan and monitoring of research progress. For more information on the NINDS Cooperative Program in Translational Research-Small Business Awards (SBIR[U44]): http://grants.nih.gov/grants/guide/pa-files/PAR-08-235.html. Due to the unique requirements of the NINDS Cooperative Program in Translational Research, applicants are strongly encouraged to consult with Dr. Tom Miller at least three months prior to the next receipt date. Dr. Tom Miller, Ph.D., M.B.A. Program Director, Office of Translational Research 301-496-1447 Email: millert@ninds.nih.gov Countermeasures Against Chemical Threats NINDS manages the NIH Countermeasures Against Chemical Threats (CounterACT) program. CounterACT supports research and development on new and improved therapeutics or diagnostic technologies to prevent or mitigate the toxic effects from exposure to chemical threats, defined as toxic chemical agents that could be used in a terrorist attack against civilians, or those that could be released at toxic levels by accident or natural disaster. This includes the development of new (or support of existing) partnerships between small business and not-for-profit laboratories engaged in this research. The scope of research supported includes early screening for compounds with the desired biological activity, advanced preclinical and efficacy testing, through clinical research with promising candidate therapeutics. For more information on this program, including specific program announcements, please see: www.ninds.nih.gov/counteract. Applicants are strongly encouraged to consult with Dr. David Jett to determine the programmatic relevance of their proposed research. David A. Jett, Ph.D. Program Director, NIH CounterACT Research 301-496-6035 Email: jettd@ninds.nih.gov For additional information on research topics, contact: Ms. Stephanie Fertig, M.B.A. Research Project Manager, Small Business Programs 301-496-1447, Fax: 301-480-1080 Email: fertigs@ninds.nih.gov or for general questions related to the small business program, email: nindssmallbusiness@mail.nih.gov For administrative and business management questions, contact: Ms. Tijuanna Decoster Chief, Grants Management Branch 301-496-9231, Fax: 301-402-4370 Email: decostert@mail.nih.govHHS201104262011042620110626-1Closed358893http://www.sbir.gov/node/358893The U.S. Customs and Border Protection (CBP) use UGS units to detect personnel, vehicles, and aircraft engaged in illegal activity at the U.S. border. The UGS units consist of: sensor(s) for detecting activity; a buried housing that contains a processing unit that interprets the received signals from the sensor(s) and performs administrative and control tasks; a radio for communicating alarms back to a CBP Command Center; and a power supply. An UGS unit normally employs a microphone to detect acoustic energy generated by the target. Processing of the received acoustic signal can provide information on the time the target passed the UGS, and the targets’s speed and range. Line-of-bearing and track information in near real time is desirable for the Border Patrol (BP) to determine where a target engaged in illegal activity may be headed. With the current deployment of single channel microphone UGS units, tracking information would have to be realized from the use of multiple UGS units and correlation of the individual information from them. Deploying multiple UGS units entails an operational impact and it is desirable to be able to develop a track solution from a single UGS. A low cost, low power, acoustic sensor that can provide directional information in both heading and altitude (for aircraft) and which can be integrated with existing UGS units is desired. It should be noted that the acoustic signature of some types of targets is narrowband in nature such that correlation processing of multiple acoustic sensors at the UGS site is not deemed viable (i.e., Army’s Boomerang sensor unit). A tri-axial acoustic sensor would provide the desired functionality for operating near the border. In order for a tri-axial acoustic sensor to be reasonable for employment, the cost of the sensor can’t greatly increase the overall cost of a deployed UGS units. Commercially available UGS units may range in cost from $2K-$10K depending upon the vendor. A tri-axial acoustic sensor also should not increase the power consumption of the UGS markedly either. Sensor power consumption should be on the order of three times that of a microphone sensor (ignoring increased processing requirements) when all three channels are used. The bandwidth of the directional acoustic sensor should be great enough to capture the acoustic signature of the different types of targets. Directional acoustic sensors proposed for this solicitation need to show that their sensitivity or self noise does not markedly decrease the detection range of a target in comparison to a single channel microphone. Directional acoustic sensors proposed for this solicitation also need to address the sensitivity of the sensor to wind noise and/or the ability to shield the sensor from wind noise. Directional acoustic sensors proposed for this solicitation also will require an alignment capability or an alignment procedure such that heading measurements can be related to absolute coordinates. It should be noted that UGS are often deployed at night in a covert fashion and an alignment process that compromises the covertness of the deployment would not be acceptable. PHASE I: Provide detailed analysis on sensitivity, self noise, wind noise abatement, directional capability, power, packaging, alignment, and cost for the proposed sensor. Consider/analyze methods for reducing power consumption (i.e., initially detecting and classifying a target on a single axis and using multiple axes only for tracking). Verify the analysis with measured data obtained both from laboratory testing and from field testing. PHASE II: Work with an UGS manufacturer (approved by DHS S&T) for interfacing the directional acoustic sensor to their UGS units. The interface will involve both hardware and software modifications that will need to be performed by the UGS manufacturer. Laboratory test the prototype unit for self noise, directional accuracy, power draw, overall UGS power change from a single channel microphone configuration, and alignment accuracy. Field test the prototype unit with the directional acoustic sensor against targets of interest and verify detection range and tracking capability. PHASE III: COMMERCIAL APPLICATIONS: Refine sensor packaging from the Phase II field trials. Market and transition the directional sensor capability to UGS vendors used by DHS and also UGS vendors used by the U.S. Army and Marine Corps.S&T201104292011051220110628-1Closed358893http://www.sbir.gov/node/358893Within the area of mobile device forensics, the Department of Homeland Security (DHS) Science and Technology (S&T) Directorate is currently interested in three distinct facets of this complex problem area. Proposers can respond to any of the three sub-topics listed below (i.e., proposers may submit up to three different sub-topic proposals in response to this mobile device forensics topic). Sub-topic 1. NAND/NOR Chip Forensics – Flash memory is now present in a variety of devices including: mobile phones, iPads, eReaders, thumb drives, picture frames, and laptops. Investigators require technology to effectively obtain information from flash memory (both NAND and NOR) chips in a forensically sound manner. There are three issues for law enforcement in this area: 1. Reading the data stored on the chip 2. Reverse engineering of the wear-leveling algorithm 3. Mounting the file system The developed capability is envisioned to be a lab tool that addresses all three of the above issues. This is not intended to be extended for field use at this time. Sub-topic 2. Bypassing PIN/PUK Codes – GSM, iDen, World Phones, and satellite phones use removable Subscriber Identity Module (SIM) and Micro-SIM cards to communicate on a cellular network. Without a PIN, an investigator cannot directly access data stored on a locked SIM card. Data on the SIM typically includes: contact lists, call history, SMS messages, and subscriber information. SIM cards can be locked with a 4-digit Personal Identity Number (PIN) and an 8- digit Personal Unlocking Key (PUK) that disables direct access to, and examination of, data stored on the SIM. Law enforcement investigators require a tool to extract PIN and PUK codes from locked SIM cards. Sub-topic 3. Disposable Cell Phone Analysis – Disposable phones (“throw-away”, “burner”, or “fast” phones) are frequently used by criminals because they are inexpensive and do not require a contract, credit card or personal information. Most disposable phones are GSM based, but CDMA phones are also available and these handsets either do not have external port access to retrieve information or access is prohibited in some other fashion. Law enforcement requires a tool to extract information from disposable phones. This sub-topic will focus on the demonstration and development of methods and tools that will allow an investigator to acquire all: call logs, contacts, pictures, videos, and text messages stored within all disposable cell phones. The goals of this effort are: 1. Demonstrate and implement the capability to acquire the full physical memory of the devices in a designated population of disposable cell phones in a forensically sound manner. 2. Demonstrate and implement the capability to efficiently examine (parse) acquired data from a designated population of disposable cell phones in a forensically sound manner. PHASE I: Sub-topic 1. NAND/NOR Chip Forensics – Design a method for comprehensive chip reader and memory parser for NAND and NOR flash memory chips. Sub-topic 2. Bypassing PIN/PUK Codes – Design a method for a forensically sound tool that will successfully decrypt SIM cards by acquiring PIN and PUK codes from locked SIM cards. Sub-topic 3. Disposable Cell Phone Analysis - Design a method to acquire physical memory from a designated population of disposable cell phones in a forensically sound manner. PHASE II: Sub-topic 1. NAND/NOR Chip Forensics – Demonstrate and implement hardware and software applications for development of a comprehensive chip reading and memory parsing tool for NAND and NOR flash memory chips. The tool should be developed for law enforcement and forensic examiner use and, where possible, should be delivered as open source technology. Sub-topic 2. Bypassing PIN/PUK Codes – Demonstrate and implement hardware and software applications for development of a forensically sound tool that will successfully decrypt SIM cards by acquiring PIN and PUK codes from locked SIM cards. The tool should be developed for law enforcement and forensic examiner use and, where possible, should be delivered as open source technology. Sub-topic 3. Disposable Cell Phone Analysis – Demonstrate and implement hardware and software tools required to acquire and efficiently examine physical memory data from a designated population of disposable cell phones in a forensically sound manner. The tool should be developed for law enforcement and forensic examiner use and, where possible, should be delivered as open source technology. PHASE III: COMMERCIAL APPLICATIONS: All sub-topics - The final developed tools will be marketable to a wide variety of Federal, State, and local law enforcement agencies. It is anticipated that those tools delivered as open source technology will require support, custom extensions, and additional applications as new mobile device technologies are commercially introduced.S&T201104292011051220110628-1Closed360216http://www.sbir.gov/node/360216 The NIGMS supports research and research training in the basic medical sciences and related natural and behavioral sciences and in specific clinical areas (i.e., clinical pharmacology, trauma and burn injury, sepsis and anesthesiology). The NIGMS also supports health-related research that is otherwise not assigned to another of the PHS components. The three divisions and one center that support research of potential interest to small businesses and their collaborators include: Division of Cell Biology and Biophysics Division of Genetics and Developmental Biology Division of Pharmacology, Physiology, and Biological Chemistry Center for Bioinformatics and Computational Biology For additional information about areas of interest to the NIGMS, please visit our home page at http://www.nigms.nih.gov. This site includes staff contact information by program area ( http://www.nigms.nih.gov/About/ContactByArea.htm). It also includes links to program announcements that highlight NIGMS areas of special emphasis ( http://www.nigms.nih.gov/Research). In some cases, these announcements specifically mention the SBIR and STTR grant mechanisms, in most cases they do not. However, it is clear that small businesses could make contributions to the research objectives described in these announcements. HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 The NIGMS supports research and research training in the basic medical sciences and related natural and behavioral sciences and in specific clinical areas (i.e., clinical pharmacology, trauma and burn injury, sepsis and anesthesiology). The NIGMS also supports health-related research that is otherwise not assigned to another of the PHS components. The three divisions and one center that support research of potential interest to small businesses and their collaborators include: Division of Cell Biology and Biophysics Division of Genetics and Developmental Biology Division of Pharmacology, Physiology, and Biological Chemistry Center for Bioinformatics and Computational Biology For additional information about areas of interest to the NIGMS, please visit our home page at http://www.nigms.nih.gov. This site includes staff contact information by program area ( http://www.nigms.nih.gov/About/ContactByArea.htm). It also includes links to program announcements that highlight NIGMS areas of special emphasis ( http://www.nigms.nih.gov/Research). In some cases, these announcements specifically mention the SBIR and STTR grant mechanisms, in most cases they do not. However, it is clear that small businesses could make contributions to the research objectives described in these announcements. HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 The NIGMS supports research and research training in the basic medical sciences and related natural and behavioral sciences and in specific clinical areas (i.e., clinical pharmacology, trauma and burn injury, sepsis and anesthesiology). The NIGMS also supports health-related research that is otherwise not assigned to another of the PHS components. The three divisions and one center that support research of potential interest to small businesses and their collaborators include: Division of Cell Biology and Biophysics Division of Genetics and Developmental Biology Division of Pharmacology, Physiology, and Biological Chemistry Center for Bioinformatics and Computational Biology For additional information about areas of interest to the NIGMS, please visit our home page at http://www.nigms.nih.gov. This site includes staff contact information by program area ( http://www.nigms.nih.gov/About/ContactByArea.htm). It also includes links to program announcements that highlight NIGMS areas of special emphasis ( http://www.nigms.nih.gov/Research). In some cases, these announcements specifically mention the SBIR and STTR grant mechanisms, in most cases they do not. However, it is clear that small businesses could make contributions to the research objectives described in these announcements. HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 This area of interest focuses on the development and evaluation of innovative prevention and intervention programs, or specific materials for integration into existing programs, which utilize state-of-the-art technology and are based on currently accepted clinical and behavioral strategies. Applicants are strongly encouraged to consult with research methodologists and statisticians to ensure that state-of-the-art approaches to design, analysis, and interpretation of studies under this topic are used. Areas that may be of interest to small businesses include, but are not limited to: A. Development and evaluation of innovative prevention/intervention programs, or specific materials for integration into existing programs, which utilize state-of-the-art technology and are based on currently accepted clinical and behavioral strategies. Special emphasis should be placed on the needs of high-risk groups, ethnic and minority populations, youth, children of alcoholics, women, the handicapped, and the elderly. Examples of such materials include school-based curricula, interactive videos, computer-based multimedia programs, training manuals for teachers or parents, and community-based programs. B. Development and evaluation of educational materials designed to intervene with the elderly around specific age-related risks for alcohol problems. Particular attention should be given to age-related reductions in alcohol tolerance, interactions between alcohol and prescription and over-the-counter medications, possible exacerbation of some medical conditions common among the elderly, potential biomedical and behavioral consequences of excessive alcohol use, and the role of alcohol in falls, fires, burns, pedestrian and traffic injuries, and other unintentional injuries. C. Development and evaluation of statistical analysis programs tailored to the design and analysis of alcohol prevention-relevant research. Programs could focus on a variety of areas including: imputation of missing data under varying design assumptions; simulation of distributions of outcomes based on varying mixtures of sample populations; application of chronic or infectious disease models to targeted communities; and models of the potential effect of various policy-based interventions, such as increased taxation or reduction of outlet density by license revocation and control. Robert C. Freeman, Ph.D. 301-443-8820 Email: Robert.Freeman@nih.gov HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 The Division of Microbiology and Infectious Diseases (DMID) supports research to better understand, treat, and ultimately prevent infectious diseases caused by virtually all infectious agents, except HIV. DMID supports a broad spectrum of research from basic molecular structure, microbial physiology and pathogenesis, to the development of new and improved vaccines and therapeutics. DMID also supports medical diagnostics research, which is defined as research to improve the quality of patient assessment and care that would result in the implementation of appropriate therapeutic or preventive measures. DMID does not support research directed at decontamination or the development of environmentally oriented detectors, whose primary purpose is the identification of specific agents in the environment. Note that some of the organisms and toxins listed below are considered NIAID priority pathogens or toxins for biodefense and emerging infectious disease research. Director: Dr. Carole Heilman 301-496-1884 Email: ch25v@nih.gov A. Bacteriology and Mycology Branch. The branch oversees research on medical mycology, hospital infections (including Acinetobacter, Klebsiella, Serratia, Legionella, Pseudomonas, Aeromonas, Enterobacter, Proteus, non-enteric E. coli, actinomycetes and others), staphylococci, enterococci, bacterial zoonoses (plague, anthrax, tularemia, glanders, melioidosis, Lyme disease, rickettsial diseases, anaplasmosis, ehrlichiosis and Q fever), and leptospirosis. Research is encouraged in the following general areas: (1) product vaccines, adjuvants, therapeutics and diagnostics (including target identification and characterization, device or apparatus development, novel delivery, and preclinical evaluation); (2) products to combat antibacterial and antifungal drug resistance; (3) applied proteomics and genomics; (4) host-pathogen interactions, including pathogenesis and host response; (5) genetics, molecular, and cell biology; (6) microbial structure and function; and (7) vector-pathogen interactions or disease transmission to humans via arthropod vectors. Research in the following areas is of particular interest to the branch, but research on all of the above is welcome: · Vaccines, therapeutics, and medical diagnostics for hospital infections · Adjunctive therapies to combat antimicrobial resistance Diagnostics for aspergillosis · Novel approaches for the diagnosis of Lyme disease Contact: Dr. Alec Ritchie 301-402-8643, Fax: 301-402-2508 Email: aritchie@niaid.nih.gov B. Enteric and Hepatic Diseases Branch. Special emphasis areas include vaccines against hepatitis C virus; antimicrobials and antivirals that focus on novel targets such as host-pathogen interactions to combat the development of resistance; vaccines and therapies for botulinum neurotoxins, especially therapies that that target toxins once they enter cells; therapies and diagnostics for Clostridium difficile that include recurrent disease issues; development of a simple, rapid point-of-care diagnostic tool for the simultaneous identification of multiple diarrheal pathogens that includes their antibiotic resistance profiles; pediatric vaccines to prevent the major worldwide causes of diarrhea; more stable vaccines and improved formulation methods; and novel therapeutics for chronic hepatitis B and C. Research areas of the Branch include the following organisms and diseases: astrovirus, Bacteroides spp., Campylobacter spp., enteric Clostridia spp. including botulinum neurotoxins, commensals and normal flora, pathogenic Escherichia coli, gastroduodenal disease, gastroenteritis, Helicobacter spp., Listeria spp., Noroviruses including Norwalk, ricin toxin, rotaviruses, Salmonella serovars, Shigella spp., Staphylococcus enterotoxin B, Vibrio spp. enteric Yersinia spp., hepatitis viruses A, B, C, D, and E, as well as cholera, diarrhea, enterotoxins, gastroenteritis, gastroduodenal disease and ulcers, and Guillain-Barre syndrome. Program Contact: Dr. Marian Wachtel 301-451-3754, Fax: 301-402-1456 Email: wachtelm@niaid.nih.gov C. Parasitology and International Programs Branch. Research areas: (1) protozoan infections, including amebiasis, cryptosporidiosis, cyclosporiasis, giardiasis, leishmaniasis, malaria, trypanosomiasis, toxoplasmosis; helminth infections, including cysticercosis, echinococcosis, lymphatic filariasis, schistosomiasis, onchocerciasis, others (e.g., roundworms, tapeworms, and flukes); invertebrate vectors/ectoparasites, black flies, sandflies, tsetse flies, mosquitoes, ticks, snails, mites; (2) parasite biology (genetics, genomics, physiology, molecular biology, and biochemistry); (3) protective immunity, immunopathogenesis, evasion of host responses; (4) clinical, epidemiologic, and natural history studies of parasitic diseases; (5) research and development of vaccines, drugs, immunotherapeutics, and medical diagnostics, and (6) vector biology and management; mechanisms of pathogen transmission. Chief: Dr. Lee Hall 301-496-2544, Fax: 301-402-0659 Email: lhall@niaid.nih.gov D. Respiratory Diseases Branch. Research areas: (1) viral respiratory diseases, including those caused by: human coronaviruses (including SARS), influenza viruses, and paramyxoviruses (including parainfluenza viruses and respiratory syncytial virus); (2) bacterial respiratory infections, including those caused by Moraxella catarrhalis (chronic obstructive pulmonary disease), Pseudomonas aeruginosa andBurkholderia cepacia (associated with cystic fibrosis), Corynebacterium diphtheriae (diphtheria), groups A and B streptococci,Haemophilus influenzae, Neisseria meningitidis, Bordetella pertussis (pertussis), Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Klebsiella pneumoniae and community acquired pneumonia; (3) acute otitis media; (4) mycobacterial diseases, including those caused by: M. tuberculosis (tuberculosis), extensively- and multi-drug resistant M. tuberculosis, M. leprae (leprosy), and M. ulcerans (Buruli ulcer) and other non-tuberculous mycobacterial diseases. Areas of emphasis include: development of new antibiotics with novel mechanisms of action, improved therapeutics for viral and bacterial respiratory diseases including immunotherapeutics, new or improved vaccines (with and without adjuvants), improved and more rapid multiplex point-of-care diagnostic tests or other screening tools that can detect infection prior to active disease and identify drug resistance. Contact: Dr. Gail Jacobs 301-496-5305, Fax: 301-496-8030 Email: ggjacobs@niaid.nih.gov E. Sexually Transmitted Infections Branch. Areas of emphasis include the development of medical diagnostics including better and more rapid multiplex point of care tests and other screening or novel delivery systems for diagnostic tools, topical microbicides, vaccines and drugs for sexually transmitted infections (STIs) and other reproductive tract syndromes, such as bacterial vaginosis; molecular immunology; vaginal ecology and immunology; epidemiologic and behavioral research including strategies to reduce transmission of STIs; genomics and proteomics of sexually transmitted pathogens; adolescents and STIs; STIs and medically underserved populations and minority groups; STIs and infertility and adverse outcomes of pregnancy; role of STIs in HIV transmission; role of HIV in altering the natural history of STIs; and other sequellae of STIs. Contact: Elizabeth Rogers 301-451-3742, Fax: 301-480-3617 Email: erogers@niaid.nih.gov F. Virology Branch. Areas of emphasis for SBIR/STTR applications include:1) vaccine development; 2) viral vectors; 3) structure and function of viruses and viral proteins as targets for therapeutic interventions or diagnostics; 4) the development and validations of assays for disease diagnosis and to measure response to therapy; 5) the development and preclinical testing of immunotherapeutic and antiviral drugs for acute and chronic viral illnesses; 6) approaches to identify antiviral targets and agents; 7) chemical design and synthesis of novel antiviral agents; 8) preclinical antiviral evaluations including in vitro screening and prophylactic or therapeutic antiviral evaluations of human viral infections in animal models; 9) the development of rapid medical diagnostic systems. The Virology Branch focuses on the following: acute viral infections (including Nipah and Hendra viruses), arthropod-borne and rodent-borne viral diseases (including Dengue, West Nile, Japanese encephalitis, Chikungunya, yellow fever, hantavirus, etc.), viral hemorrhagic fevers (Ebola, Lassa fever, etc.), measles, polio, coxsackie virus, enterovirus 71 and other enteroviruses, poxviruses, rabies, and rubella. The Virology Branch also focuses on the following persistent viral diseases and viruses: adenoviruses, BK virus, bornaviruses, coronaviruses, herpesviruses, human T-lymphotrophic virus, JC virus, human papillomaviruses, parvoviruses, and prion diseases. Applications targeting the development of therapies, immunotherapies, vaccines and diagnostics for any of these infections are sought. The Virology Branch does not support applications covering environmental detection and decontamination. Contact: Dr. Ramya Natarajan 301-594-1586, Fax: 301-402-0659 Email: ramya.natarajan@nih.gov HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 The Division of Cancer Treatment and Diagnosis funds research into the development of tools, methodologies and therapeutic agents that will better diagnose, assess, cure and effectively treat cancer. We support a spectrum of research projects from preclinical exploratory research and development through clinical trials. A. Cancer Diagnosis. The Cancer Diagnosis Program (CDP) supports the development of technologies, reagents, instrumentation, and methodologies to improve cancer diagnosis or prognosis or to predict or assess response to therapy. This does not include technologies for imaging of patients. CDP also supports the adaptation or improvement of basic research technologies for use as clinical tools. Technologies supported by CDP may be designed to work with tissues, blood, serum, urine, or other biological fluids. Technologies supported by CDP include but are not limited to the following: 1. Technologies for comprehensive and/or high throughput analysis of molecular alterations at the level of DNA, RNA, or protein. Includes for example, mutation detection systems, gene expression arrays, systems for monitoring epigenetic changes (alternative splicing or methylation), high throughput proteomics (including post-translational modification and protein-protein interactions and methods for protein quantitation). 2. Micro-electro mechanical systems (MEMs) and other nanotechnologies for the analysis of DNA, RNA, or protein (e.g., micro-capillary systems, lab on a chip applications, micro-separation technologies). 3. Mass spectrometry for the analysis of nucleic acids or proteins. 4. Discovery and development of new or improved diagnostic markers or probes targeting changes in DNA, RNA, or proteins, including the generation of molecular diversity libraries by phage display and other combinatorial techniques, and affinity-based screening methods. 5. cDNA library technologies, including improved methods for generating high quality cDNA clones and libraries and methods for generating high quality cDNA from tissues (including archived specimens). 6. Resources for clinical research. a. Instruments, technologies or reagents for improved collection, preparation, and storage of human tissue specimens and biological fluids. b. Improved methods for isolation and storage of DNA, RNA, or proteins. c. Tissue and reagent standards: development of standard reagents such as representational DNA, RNA, and proteins and standard tissue preparations to improve the quality of or facilitate the validation of clinical laboratory assays. d. Methodologies for directed micro-sampling of human tissue specimens, including for example, new or improved methodologies for tissue microarrays. 7. Tissue preservation: fixatives and embedding materials or stabilizers that preserves tissue integrity and cellular architecture and simultaneously allows molecular analysis of DNA, RNA, or proteins. 8. Bioinformatics. a. Methods for acquisition and analysis of data associated with molecular profiling and other comprehensive molecular analysis technologies, including for example, analysis of microarray images and data as well as methods to combine, store and analyze molecular data produced by different techniques (e.g., combined analysis of proteomics and gene expression data). b. Methods for collecting, categorizing or analyzing large data sets containing pathology data or histological images and associated clinical or experimental data, including for example, tumor marker measurements, tissue microarray data, and other relevant biological information. c. Software/algorithms to interpret and analyze clinical and pathology data including methods that relate data from clinical databases to external data sources. Includes for example, neural networks, artificial intelligence, data-mining, data-trend analysis, patient record encryption protocols, and automatic diagnostic coding using standard nomeclatures. d. Informatics tools to support tissue procurement and tissue banking activities. 9. Statistical methods and packages designed for data analysis including correlation of clinical and experimental data. 10. Automated Cytology. a. High resolution image analysis for use with specimens (e.g., blood, tissues, cells) and tissue microarrays. b. Instrumentation including microscopy and flow cytometry. c. CGH, FISH, immunohistochemical staining and other hybridization assays using probes with fluorescent or other novel tags. d. Methods for single cell isolation and sorting. e. Methods for single cell classification and analysis. 11. Instrumentation for the detection and diagnosis of tumors, including endoscopy and magnetic resonance spectroscopy (MRS). 12. Immunoassays using monoclonal, polyclonal, or modified antibodies. Affinity-based binding assays using libraries of aptamers including chemical ligands, small peptides or modified antibodies. For additional information about areas of interest to the CDP Technology Development Branch, visit our home page at: http://cancerdiagnosis.nci.nih.gov. B. Biochemistry and Pharmacology. Preclinical and Exploratory Investigational New Drug (IND) studies designed to improve cancer treatment. General areas of interest: Discovery of new drugs or drug combinations and treatment strategies, selective targeting, development of clinically relevant preclinical models, pharmaceutical development, ADME (absorption, distribution, metabolism and excretion) studies and toxicologic evaluations, understanding mechanisms of drug actions (responses to therapies), and preventing and overcoming drug resistance. Areas of current emphasis: Molecular targeted approaches, including application of safety and efficacy biomarkers to the discovery and development of drugs; application of advanced technologies, such as nanotechnology and imaging technologies, to improved assays for quantitation of safety and efficacy biomarkers; approaches that reduce costs and increase speed of preclinical drug development; and approaches that will lead to “personalized medicine,” including better predictions of drug response and adverse reactions, drug-drug interactions, and drug efficacy monitoring. For additional information, please visit our home page at http://dtp.nci.nih.gov and select “Grants/Contracts.” 1. Drug Discovery. a. Design and synthesize novel compounds for evaluation as potential anticancer agents. Synthesize simpler analogs of complex antitumor structures that retain antitumor activity. b. Develop computer modeling and biophysical techniques such as x-ray crystallography and NMR spectroscopy. c. Design prodrugs of anticancer agents that are selectively activated in cancer cells. d. Discover new anticancer agents that exploit unique properties of tumors, that induce or modulate apoptosis, or that induce or modulate differentiation. e. Design and synthesize anticancer prodrugs, latent drugs, or modifiers of cancer drug metabolism or excretion. f. Develop ways to produce adequate quantities of promising natural products or natural product derivatives through total synthesis. g. Develop scale-up and manufacturing technology for the synthesis of materials with promising anticancer potential. h. Develop chemical libraries for anticancer drug screening programs. The generation of small molecular weight libraries (<700 MW, e.g., non-polymeric organic molecules, transition-state analogs, cyclic peptides, peptidomimetics) is encouraged. i. Develop and apply technologies in genetics, genomics, proteomics, glycomics, lipidomics, metabolomics, and systems biology to the discovery of potential drug targets associated with multiple pathways or networks. Design and optimize agents that block or activate targets/pathways that are likely to control, re-program, retard or kill cancer cells, especially cancer initiating cells (often called cancer stem cells). 2. Drug Evaluation. a. Develop and evaluate anti-metastatic and/or anti-angiogenesis agents or strategies, including combination therapies, in appropriate model systems. b. Develop and evaluate anticancer gene therapy in appropriate model systems. The development of new gene delivery approaches is encouraged. c. Develop novel or improved in vitro and in vivo test systems. There is a special need for new types of in vivo tumor models, such as orthotopic tumor models, models using transgenic or gene knockout animals, and models to evaluate agents that induce differentiation or apoptosis or that target cancer initiating cells (often called cancer stem cells). d. Develop strategies to detect, prevent, or overcome drug resistance. e. Develop novel treatment strategies such as extra corporeal treatment. f. Develop new assays based on molecular targets, especially those that may be amplified or altered in cancer cells. For example, develop assays for agents that interact with oncogenes, suppressor genes, signal transduction pathways, transcription factors, or promoters. Assays based on molecular targets that can be adapted for high volume screening of chemical libraries are especially encouraged as well as in vivo models, which can be used for “proof of concept” (i.e., validating selectivity of the agent for the target and confirming that modulation of the target results in antitumor activity). g. Develop cost-effective and useful techniques to improve in vitro cell culture methodology, such as the development of automated systems, serum-free media, or carbon dioxide-free buffering systems to stabilize cell culture performance. h. Identify and employ novel targets for antitumor drug discovery utilizing non-mammalian genetically defined organisms, such as fruit flies, worms, zebrafish and yeast. i. Develop and apply technologies such as microarrays, proteomics or RNAi to improve the efficiency of drug discovery. j. Develop cell lines that contain bioluminescent reporter genes, such as luciferase, that can be controlled by activating specific promoters. 3. Pharmaceutical Development. a. Develop new methods to improve drug solubility for administration of promising antitumor compounds, such as water miscible nontoxic water solubility enhancing agents. b. Develop bioavailable alternatives to the intravenous delivery of cytotoxic chemotherapy. For example, develop new excipients to enhance oral bioavailability of anticancer agents. c. Develop biocompatible additives and excipients for highly concentrated proteins and peptide formulations to enhance bioavailability and stability suitable for subcutaneous delivery of agents. d. Develop improved methods to reduce thrombophlebitis and other related side effects observed following intravenous injection of some anticancer drugs. e. Develop new and innovative techniques for sterilization of parenteral dosage forms. f. Develop in vitro and in vivo models to predict human oral bioavailability of anticancer drugs. g. Develop practical delivery systems involving nanotechnology (dendrimers, nanoparticles, nanoshells, etc.) or other strategies to deliver anticancer drugs to specific target sites. h. Develop new technology to manufacture liposomal and intravenous emulsions in an environmentally friendly manner and in accordance with OSHA standards. i. Develop additives and/or processes to eliminate cold chain storage of biotherapeutic agents, especially vaccines. 4. Toxicology and Pharmacology. a. Develop biochemical or molecular (genomic, proteomic, or metabolomic) response profiles of specific target organs (e.g., bone marrow, gastrointestinal tract, liver, kidney, heart, lung) to permit rapid identification of toxic effects resulting from anticancer drug administration. b. Develop clinically relevant in vitro and/or in vivo tests for estimation and prediction of gastrointestinal toxicity, neurotoxicity (central and peripheral), cardiotoxicity, hepatotoxicity, nephrotoxicity and pulmonary toxicity. c. Correlate in vivo and in vitro models for organ toxicity as described above in 4b. Validate for various anticancer drugs. d. Develop drug metabolism (Phase I and Phase II) profiles for anticancer agents in human, mouse, rat and dog liver S-9, microsomes and slices. e. Develop systems to identify toxic effects of drugs by characterizing reactions with biomolecules or receptors. f. Develop in vitro tests to detect, qualify and quantify toxic effects of antineoplastic drugs. Develop techniques for determining individual variations in drug responses due to genetic polymorphisms or other factors. Develop pharmacodynamic endpoints and surrogate endpoints using appropriate biomarkers to aid in the selection of doses and schedules and the monitoring of responses and toxicity. g. Develop personal computer programs for pharmacokinetics models capable of predicting drug behavior in humans from preclinical pharmacokinetics data in mice, rats, dogs, and non-human primates. h. Investigate and develop techniques for relating specific enzyme activities (both catabolic and anabolic) to body sizes of different species. i. Investigate techniques that would allow parameters, e.g., Km and Vmax for enzymes, to be scaled from preclinical to clinical models. j. Develop analytical strategies applicable to the quantitation of potent anticancer drugs in biological fluids at the pg/ml level, e.g., Bryostatin. k. Develop non-invasive techniques to determine drug distribution in various animal models. l. Evaluate interspecies transporter distribution and its impact on pharmacokinetic parameters, e.g., the impact of pharmacogenetic variation in biodistribution. m. Determine optimal pharmacokinetic sampling schedules for use in dose titration/pharmacodynamic assessment by integrating information such as pre-clinical pharmacokinetic data, physico-chemical drug properties and mechanism of action. n. Develop an in vitro/in situ system for high throughput drug screens for oral bioavailability. o. Develop and deliver organ specific chemo-protective agents. p. Develop and evaluate rapid, cost-effective methods, including biochemical, functional multiplexed, imaging, nanotechnology-based, and microfluidics-based assays, to quantitate surrogate endpoints for determination of doses, dosing schedules, safety, and efficacy of drugs. q. Identify and develop biomarkers to evaluate drug activities and toxicities. r. Develop assays in support of Exploratory Investigational New Drug Studies using biomarkers or other appropriate endpoints. s. Develop, standardize, and validate cost-effective tools for obtaining comprehensive ADME and toxicology profiles that may better predict the performance of drugs in humans. t. Develop and analytically validate assays or tools for measuring safety, efficacy, and dosing biomarkers. 5. Animal Production and Genetics. a. Investigate alternatives to expensive barrier systems for exclusion of pathogens from rodent colonies, e.g., by use of micro-isolator cages, and evaluate their performance. b. Develop and evaluate specialized shipping containers for pathogen-free animals. 6. Natural Product Discoveries. Note that execution of projects in most of these topic areas will require collaboration and signed agreements with countries where the source organism was originally collected. a. Develop techniques for the study of non-culturable organisms in order to identify antitumor agents. b. Develop techniques for the genetic and biochemical characterization and the manipulation of biosynthetic pathways to create leads. Use combinatorial biosynthesis to generate libraries of un-natural natural products as drug leads. c. Use genetic techniques for the identification of microbial consortia, and for the identification and isolation of genes controlling the biosynthetic pathways producing potential antitumor agents. d. Express biosynthetic pathways from microbes or microbial consortia that are known to produce antitumor agents, but in organisms amenable to standard fermentation techniques. e. Investigate new biological methods, such as tissue culture, aquaculture, hydroponics, etc., for the production of natural products as potential anticancer agents. f. Develop new systems of large-scale production using biotransformation, tissue or cell culture, biotechnology, modification of the chemical ecology of producing organisms, etc., in order to produce the large quantities of anticancer drugs needed for preclinical or clinical development. g. Develop methods for the isolation, purification, identification, cultivation, and extraction of microorganisms from unusual marine or terrestrial habitats for antitumor screening. Examples are gliding bacteria, barophilic, endophytic, thermophilic, and tropical canopy organisms. h. Investigate newer methods of isolation and purification, such as super-critical fluid extraction and chromatography, centrifugal countercurrent chromatography or affinity-based separations, in the isolation and purification of natural products with anticancer activity. i. Develop simple immunoassays that can be used to monitor the levels of natural products of interest in simple extracts of the relevant raw material. These assays should be capable of being developed for use “in the field” and also in developing countries. j. Develop analytical and biological methods for isolation, purification and validation of active constituents identified from alternative medicine and complementary studies; use of these purified constituents alone or in combination with conventional anticancer agents. 7. Data Management Systems. a. Develop data support systems for chemical library programs. b. Develop bioinformatics tools to accelerate the identification, functional understanding and validation of drug targets. c. Develop bioinformatics tools to predict ADME and toxicology characteristics of drug candidates. d. Develop “data mining” strategies such as neural networks. e. Develop algorithms for determining optimal drug combinations and for prediction of optimal effectiveness of individual agents. f. Develop bioinformatics tools to support a systems biology approach to drug discovery and development. g. Develop bioinformatics tools to support genomic/proteomic and other "omics" profiling experiments in support of drug discovery and development. C. Cancer and Nutrition. Research to improve the methodology of nutritional assessment in a cancer population. Innovative approaches to evaluate the contribution of nutritional status to response to cancer treatment. 1. Research to improve the methodology of nutritional assessment in a cancer population. 2. Develop means to evaluate the contribution of nutritional status to response to cancer treatment. D. Clinical Treatment Research. Clinical research studies designed to improve cancer treatment. Emphasis is on clinical trials for the evaluation of new therapeutic agents, development of assay systems to measure patient response to chemotherapy, development of prognostic assays, and development of methods of analysis and management of clinical trials data. Studies designed to improve human subject protections for patient access to clinical cancer trials. 1. Evaluation of New Cancer Therapies. a. Conduct clinical trials for the evaluation of new therapeutic agents or modalities of treatment employing drugs, biologics or surgery. b. Clinical trials using “unconventional therapies,” including, but not limited to, behavioral and psychological approaches, dietary, herbal, pharmacologic and biologic treatments, and immuno-augmentative therapies. c. Development and evaluation of new clinical approaches using gene transfer or gene therapy technologies. d. Development and evaluation of new clinical approaches using tumor associated antigens or vaccines in order to enhance immunogenicity. e. Develop and characterize novel chemical compounds that may be useful anticancer agents, either alone or in combination with other modalities such as radiotherapy. f. Develop techniques to lessen the toxicity of existing anticancer treatments. g. Develop new techniques for the delivery of anticancer agents that will maximize therapeutic effects and minimize toxicity. h. Develop new surgical techniques or tools or improve existing techniques that are/may be utilized in cancer treatment. i. Characterize and produce clinical grade monoclonal antibodies to detect and treat malignancies. 2. Development of Prognostic Assays to Monitor Patient Response to Therapies. a. Develop assay systems to measure the response of human tumors to chemotherapy or biologics. b. Characterize drug resistance mechanisms and design methods to overcome clinical drug resistance. c. Develop assays for prognostic factors to identify patient subsets who may benefit from specific cancer treatment therapies. d. Development of assays to assess effects of agents on specific molecular targets in clinical studies. e. Develop new techniques for relating past preclinical information to past clinical results for prediction of future useful clinical agents from future preclinical data (both in vitro and in vivo). 3. Clinical Trials Informatics. a. Develop new tools and methodologies for the analysis of clinical trials results. b. Develop new informatics tools to facilitate clinical trials data entry from the bedside and coordination of data entry and transmission throughout the institution and to other collaborating institutions or organizations. c. Development of novel web-based approaches to clinical trials informatics for transmission of data to NCI or other organizations. Topics include point of treatment data capture and reporting, electronic protocols, OLAP (On-line Analytical Processing), support for the Common Toxicity Criteria, and drug accountability support. d. Develop new interchange standards, based on technologies such as XML, for sharing data among heterogeneous systems. Specific applications areas include, Adverse Even Reporting, Case Report Forms. e. Develop new tools for support of Common Data Elements. f. Develop new approaches for interface with electronic medical records, with intent to streamline data reporting, registration, and toxicity reporting of Clinical Trial information. E. Cancer Imaging Program. The mission of this program is to promote and support: Cancer-related basic, translational and clinical research in imaging sciences and technology, and integration and application of these imaging discoveries and developments to the understanding of cancer biology and to the clinical management of cancer and cancer risk. Toward this effort, CIP 1) funds research in the development of tools, methodologies and imaging agents/probes that will better diagnose, assess, and effectively treat cancer, and 2) supports a spectrum of research projects from preclinical exploratory research and development through clinical trials. Areas of interest include but are not limited to: 1. Development of medical imaging systems for early cancer detection, screening, response to therapy and interventions including image-guided therapy. 2. Development of preclinical and clinical in vivo imaging systems, methods, imaging probes and contrast agents and related image reconstruction, image processing, image display and image-based information as required to detect, classify, monitor and guide therapeutics to cancer and precancerous conditions. 3. Development of methods to assess the value of imaging procedures for the above goals. 4. Development of systems and methods for improved production and distribution of radioactive materials for cancer imaging and/or treatment. 5. Development of systems, methods and their optimization for studying the adverse reactions/effects of image-guided and other diagnostic and therapeutic interventions. 6. Any other investigator-initiated research idea that is relevant to cancer biomedical imaging. 7. Development of systems, methods and their optimization to advance the role of imaging in assessment of response to therapy through increased application of quantitative anatomic, functional, and molecular imaging endpoints in clinical therapeutic trials and dissemination of these systems and methods with appropriate scientific communities. F. Radiation Research. The Radiation Research Program (RRP) supports basic, developmental and applied research (including clinical) related to cancer treatment utilizing ionizing and non-ionizing radiations. Therapeutic modalities include photon therapy, particle therapy, photodynamic therapy (PDT), hyperthermia, radioimmunotherapy (RIT), systemic targeted radionuclide therapy (STaRT), and boron neutron capture therapy (BNCT). Radiation research encompasses a range of scientific disciplines including basic biology, chemistry, physics and clinical radiation oncology. Topics of interest include, but are not limited to, the following areas: 1. Development of devices for planning, measuring, and delivering radiation therapy or related therapies, including devices for patient positioning and quality assurance for the following: (a) ionizing radiation, particularly 3-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT); (b) PDT; (c) hyperthermia; (d) RIT; (e) STaRT; and (f) particle therapy. 2. Development of devices for dosimetry for (a) ionizing radiation; (b) PDT, particularly those capable of measuring light doses at depth in tissues; (c) thermometry for hyperthermia, particularly non-invasive thermometry; and (d) RIT. Devices may include chemical, solid state, film, biological or ionization systems to detect or read out exposures. Accuracy, precision and linear response are essential over the range of doses and temperatures employed in the research laboratory and/or in the clinic, depending on their intended use. Devices for thermometry during hyperthermia treatment must give accurate readings with the heating device(s) with which they are to be used. 3. Development and evaluation of computer hardware and software for radiation therapy, such as computation algorithms, computer workstations, image guidance techniques, and informatics methods for treatment planning, delivery and outcomes analysis. 4. Development of novel drugs to increase the effectiveness of radiation therapy or related therapies: (a) chemical modifiers of radiation response, particularly small molecules directed at molecular targets involved in tumor radioresistance; (b) photosensitizers for PDT; (c) sensitizers for use with hyperthermia; and (d) prodrugs that are selectively activated within the tumor. 5. Development of drugs to prevent, reduce or reverse normal tissue response, especially the late effects that develop months or years after therapy. Compounds that are based on a rationale for achieving a therapeutic gain (an improved differential response between tumor and normal tissue) are of greatest interest. Enhancement of response must be achieved at radiation doses and treatment schedules employed clinically. 6. Development of predictive assays and monitors of response to radiotherapy, PDT, hyperthermia, STaRT, or RIT. Tools are needed to identify patients that would benefit from specific therapeutic approaches. G. Biological Response Modifiers (BRM). Research on agents or approaches that alter the relationship between tumor and host by modifying the host's biological response to tumor cells with resultant therapeutic benefits. Both preclinical and clinical investigations are conducted on the utility of a wide variety of natural and synthetic agents and on biological manipulations of immunological and non-immunological host mediated, tumor-growth controlling mechanisms in cancer therapy. Studies are encouraged which utilize in vitro assays and/or animal model systems to investigate mechanisms of BRMs. Examples of innovative research include but are not limited to: 1. Evaluation of molecular genetic approaches to discovery of new therapeutic agents, delivery of BRMs or development of gene therapy. 2. Development of improved techniques to synthesize, screen and develop new oligonucleotides including iRNA sequences for therapeutic purposes, such as signal modulation, anti-oncogene or anti-viral effects. 3. Improvement in cell-culturing techniques, e.g., by developing automated cell culture systems, specialized media, or improved methods to induce activation, proliferation or differentiation. 4. Development of new procedures or reagents for the modulation of the suppressor arm of the immune system in experimental models, directed towards successful immunotherapy. 5. Improvement of tumor-associated antigens or vaccines in an attempt to enhance immunogenicity. 6. Evaluating autoimmunity in the context of anti-tumor response in vivo to vaccines. 7. Development of novel in vitro assays for the primary screening of BRMs. 8. Application of observations describing shared receptors and mediators between the neuroendocrine and immune systems in studying immunobiology and immunotherapy of cancer. 9. Development and optimization of viral oncolytic agents. 10. Development of novel or improved methods for process development and manufacture of biotherapeutics, including but not limited to antibodies, recombinant proteins, peptides, oligonucleotides, and products based on viral or bacterial vectors, per executive order (E.O. 13329) mandating federal agencies assist the private sector in manufacturing innovation efforts. 11. Development of innovative methods for monitoring the manufacturing process for biotherapeutics using in-line or on-line process analyzers to improve the efficiency of process controls and determination of production end-points (see Guidance for Industry, PAT-A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance, www.FDA.gov). 12. Development of methods to more efficiently assess factors related to the ultimate product quality, safety and efficacy of biologics. HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 A. Prevention Research Branch (PRB). The Prevention Research Branch (PRB) supports a program of research in drug abuse and drug related HIV prevention to (1) examine the efficacy and effectiveness of new and innovative theory-based prevention approaches for drug abuse, drug-related HIV/AIDS and other associated health risks, (2) determine the cognitive, social, emotional, biological and behavioral processes that account for effectiveness of approaches, (3) clarify factors related to the effective and efficient provision of prevention services, and (4) develop and test methodologies appropriate for studying these complex aspects of prevention science. Prevention Research. Rigorous scientific prevention research is encouraged to study novel approaches to substance abuse prevention for use at multiple levels of the social environment including: the family, schools, peer groups, community and faith-based organizations, the workplace, health care systems, etc. The purpose of this research is to determine the efficacy and effectiveness of novel program materials, training strategies, and technologies developed to prevent the onset and progression of drug abuse and drug-related HIV/AIDS infection. Materials and technologies may target a single risk-level or may take a comprehensive approach encompassing audiences at the universal, selective, and/or indicated levels. Universal interventions target the general population; selective target subgroups of the population with defined risk factors for substance abuse; indicated interventions target individuals who have detectable signs or symptoms foreshadowing drug abuse and addiction, but who have not met diagnostic criteria. NIDA encourages the development and testing of innovative prevention intervention technologies that are sensitive and relevant to cultural and gender differences. 1. Laboratory studies of the underlying mechanisms and effects of various prevention approaches such as persuasive communication (e.g., mass media and print media) as they are affected by and effect drug related cognition, emotion, motivation and behaviors. 2. Decomposition of prevention programs, practices and strategies to understand components that account for program effectiveness. 3. Research on features of prevention curricula, materials, implementation, approaches, training, technical assistance, and systems integration that contribute to positive outcomes. 4. Training modules and ongoing technical assistance for program implementers of research based substance abuse prevention programming strategies. 5. Prevention intervention dissemination technologies and mechanisms that integrate research with practice; specifically the transfer of drug abuse prevention information to decision-makers, funders, and practitioners. 6. Prevention services research on the organization, financing, management, delivery, and utilization of drug abuse prevention programs. 7. State-of-the-art and practical strategies for the integration of evidence-based prevention approaches into existing prevention service delivery systems. 8. Studies that develop and assess reliability and validity of developmentally appropriate self-report, physiological, and biochemical measures for use in prevention trials in a variety of settings and a variety of audiences. 9. Development of and testing of environmental change strategies for schools, neighborhoods, communities, etc. to use in reducing substance use initiation and/or progression. 10. Development of practical and affordable community tools for: needs and resource assessment, selection of appropriate evidence-based programs and strategies, high-quality implementation of identified programs and strategies, evaluation at community, organization and individual levels, and sustainability. 11. Drug abuse prevention methodological research on promising data collection, data storage, data dissemination, and reporting techniques. 12. Promoting wider and more effective (e.g. with enhanced fidelity) use of evidence-based prevention interventions for substance abuse and related HIV prevention, including interventions made available thru CDC and other federal agencies. 13. Studies applying technologies and strategies that have been developed for use in other disciplines in order to examine the utility of their application for drug abuse prevention, such as virtual reality technologies being used for some clinical conditions (e.g. phobias, eating disorders), and serious video games are being used for some clinical conditions (e.g., cancer patients), but not for drug abuse prevention. 14. Development and testing of innovative drug abuse prevention intervention products, using discoveries from the basic biological (e.g. neurobiological), psychological (e.g. emotional, behavioral, cognitive, and developmental) and social (e.g. social learning, peer network, and communications) sciences. 15. Development and testing of adaptations for efficacious prevention research approaches to make these more appropriate for special populations including racial and ethnic minorities, non-English speaking populations, immigrant populations, rural and migrant populations, low literacy populations, or persons with disabilities. 16. Development of methods, state-of-the-art tools and systems for community coalition-building. 17. Development and testing of tools to measure intervention costs, cost effectiveness, and net economic benefits. 18. Development and testing of rapid assessment tools of sexual and drug use risk behaviors for use in health care and public health environments, including STI clinics and AIDS research centers. 19. Development and testing of tools to promote security and appropriate prescribing of scheduled prescription drugs. Technologies can be developed to assist medical professionals, schools, service providers and others in making prescribing decisions, educating patients and their caretakers, or dispensing and monitoring of medications. 20. Development of new technologies to support drug abuse prevention interventions with military personnel, veterans and their families. Tools can include adaptations of efficacious and effective drug abuse prevention interventions to maximize health care efficiencies and to address negative life stress resulting from sustained combat operations, a major contributor to both the onset and exacerbation of substance abuse and mental health problems. 21. Development of new technologies for delivery and implementation of efficacious drug abuse prevention interventions for rural and frontier communities. Augie Diana, Ph.D. 301-443-1942 Email: dianaa@nida.nih.gov B. Epidemiology Research Branch (ERB). The ERB supports a research program on drug abuse epidemiology that includes (1) studies of trends and patterns of drug abuse and related conditions such as HIV/AIDS in the general population and among subpopulations, (2) studies of causal mechanisms leading to onset, escalation, maintenance, and cessation of drug abuse across stages of human development, (3) studies of person–environment interactions, (4) studies of behavioral and social consequences of drug abuse, (5) bio-epidemiologic studies including genetic epidemiology studies, (6) methodological studies to improve the design of epidemiologic studies and to develop innovative statistical approaches, including modeling techniques. 1. Improvement of Reliability and Validity of Reporting of Sensitive Data. The reliability and validity of self-report of drug use and related behaviors (e.g., HIV risk behavior) is a matter of great concern. Use of new technologies for real time data collection in ecological settings is of great interest because these technologies enable collection of drug consumption data in context. Studies to improve methodologies based on variations of standard survey protocols or computer-assisted self-interview (CASI) and personal interview (CAPI) are also encouraged. 2. Instrument Development. Easy-to-use assessment instruments are needed to enhance epidemiology research. Areas of interest include but are not limited to: a. Community Assessment. The development of community diagnostic instruments for psychometrically sound assessment of community characteristics is essential to improve our understanding of how community factors affect drug abuse and ensuing behavioral and social consequences. Standardized assessments of community characteristics are needed to better understand the full impact of drug use and to develop targeted interventions to specific community needs. b. Assessment of Psychiatric Comorbidity in Community Settings. Easy to use, reliable, and valid instruments are needed to assess psychiatric comorbidity in different populations of drug abusers, including adolescents and those in community drug abuse treatment settings. c. Assessment Instruments to Measure CNS Function Related to Drug Abuse. The development of age-appropriate assessment instruments to measure behavioral and cognitive function over the course of development will contribute to our understanding of vulnerability to drug abuse and functional impairment due to drug use. 3. Development of State-of-the-Art Mechanisms for Epidemiological Research. The development of state-of-the-art mechanisms to facilitate the use of Geographical Information Systems (GIS) in community epidemiology studies (for example Community Epidemiology Work Groups) and other drug abuse research is if great interest. There is a need for enhanced software and hardware for GIS interfaces, database management, visualization, and innovative spatial analysis capabilities. The role of GIS in public health management and practice continues to evolve. Application of this technology is an important step towards better understanding drug abuse issues and their inherent complexities. The ability to evaluate geospatial information provides a unique perspective of public health issues such as emerging and shifting epidemics, the utilization of treatment services, and rapid assessment of the impact of incidents ranging from natural disasters to bioterrorism. When used alongside more traditional epidemiological techniques, GIS provides epidemiologists the ability to address new questions, refine, or enhance existing analyses. Bethany Deeds, Ph.D. 301-402-1935 Email: deedsb@nida.nih.gov 4. Improving Measures of Addiction Risk. Individual differences in risk for drug addiction are often expressed in degree rather than kind, that is, as gradations along an underlying continuum that stretches from unobservable variations in risk for addiction to extreme and fully debilitating addiction severity. Assessment instruments in use today for measuring drug addiction (i.e., compulsivity in seeking and using drugs despite harmful consequences) have proven reliability and validity, but are of limited use for evaluating individual differences in risk for drug addiction. Advances in computerized adaptive testing methods, computer-assisted technologies, and psychometrics, including item response theory, suggest that the capabilities now exist for the development of the next generation in addiction assessment. New assessment instruments are needed to detect meaningful variation between, within, and across individuals over time that is scalable along the dimension of risk for addiction; these instruments should allow for efficient assessment of the risk construct with minimal burden for administration, training, and cost to the researcher, clinician, research participant, or patient; and they should ultimately provide valid and reliable scores corresponding to established diagnostic criteria for substance use disorders. Elizabeth Lambert, M.Sc. 301-402-1933 Email: elambert@nida.nih.gov 5. Developing, Validating, Refining Tools for Ecologic Momentary Assessment. Ecologic Momentary Assessment (EMA) includes the measurement of exposures and events in real time as they occur, and in the natural environment where they occur, such as the home, neighborhood, or workplace. EMA tools include portable technologies for longitudinal data collection in the field, such as mobile phone electronic diaries and PDAs, geopositioning devices, motion sensors, biosensors, environmental sensors, and audiovisual devices. In addiction and behavioral research, new EMA tools may enhance the contextual and temporal resolution of exposures, and the biological or behavioral processes presumed to occur in response. Specific challenges to address in the implementation of EMA include optimizing the timing of measurement and data quality, establishing sensor validity and reliability in different populations, reducing intensely longitudinal data for statistical analysis, achieving user acceptability, and safeguarding user privacy. Studies are encouraged that address these and other challenges to improve the validity and acceptability of EMA tools. Louise Eideroff, Ph.D. 301-451-8663 Email: wideroffl@nida.nih.gov C. Services Research Branch (SRB). The SRB supports a program of research on the effectiveness of drug abuse treatment with a focus on the quality, cost, access to, and cost-effectiveness of care for drug abuse dependence disorders. Primary research foci include: (a) the effectiveness and cost-benefits and cost-effectiveness of drug abuse treatment, (b) factors affecting treatment access, utilization, and health and behavioral outcomes for defined populations, (c) the effects of organization, financing, and management of services on treatment outcomes, (d) drug abuse service delivery systems and models, such as continuity of care, stages of change, or service linkage and integration models, and (e) drug abuse treatment services for HIV seropositive patients and for those at risk of infection. 1. Drug Abuse Treatment Economic Research. This initiative will support research to design and develop data systems for financial management and economic analysis of treatment programs and larger systems in new healthcare settings and managed care networks. Managerial decision-making requires the implementation of sophisticated data systems to facilitate routine budgeting processes, allocation of resources, performance measurement, and pricing decisions. The focus is on the needs of managers within the organization and managers outside of the organization. Data system development must be based on standard cost behavior and profit analysis. Data systems must be designed with correct cost concepts (accounting and economic) in order to permit cost and pricing decisions to be developed for new treatment technologies and management of ongoing systems. In research settings, such an initiative is vital for the assessment of new technologies developed for transfer to practice. 2. Determining the Costs of Implementing Evidence-Based Practices (EBPs) and Other Technologies in Drug Abuse Treatment. Research shows that new technologies or evidence-based practices (EBPs) can improve drug treatment outcomes, and it has been asserted that large-scale drug abuse treatment improvement requires systematic implementation of proven practices, processes, and technologies. Often, however, new drug treatment approaches are not adopted or sustained in usual practice, even in programs that served as settings for research showing their effectiveness. This may be due in part to a poor understanding of the initial or ongoing costs entailed by new practices, processes, or technologies (hereafter referred to as technologies). Methods and tools need to be developed and tested to help drug abuse treatment service providers and payers arrive at realistic estimates of the costs of implementing and sustaining new technologies in usual practice settings. With regard to new technologies, implementing is defined as an ongoing process of selecting, adopting, and adapting these new technologies into ongoing treatment, particularly with consideration for the local setting, population and available resources. Sustaining is defined as an ongoing process of providing needed resources (such as staffing, training, and equipment), maintaining the quality of the new technology through evaluation, monitoring, and improvement, and determining its ongoing utility compared to alternatives. The tools and methodologies should be able to identify and estimate costs separately for implementing and for sustaining new technologies, and should consider both clinical and administrative technology. At a minimum, domains in which costs should be estimated include assessment of programmatic need, appropriateness, and value; staffing qualifications (salary and competencies); training, support, equipment, and other infrastructure requirements; information / data requirements; quality monitoring and improvement; and evaluation of outcomes. Sarah Duffy, Ph.D. 301-443-6504 Email: sduffy@nida.nih.gov 3. Personnel Selection Technology Research for Drug Abuse Treatment Clinics. Research is showing that employee turnover is a substantial problem among substance abuse treatment services providers. Applications supporting innovative research that develops and validates generic staff selection systems which could be adopted and tailored for use by drug abuse treatment clinics are welcome. Like many small businesses, drug abuse treatment clinics have problems attracting and retaining qualified personnel. Also like many small businesses, treatment clinics have limited resources to apply to the recruiting, screening, and hiring of new and replacement personnel. Research has shown that the application of standardized screening and selection methods designed to maximize person-job fit can cost-effectively reduce staff turnover. Systematic methods such as background inventories, protocol-driven interviews, aptitude tests, and credit checks have demonstrated validity for improving person-job fit. Examples of possible projects might include development of easy-to-understand guidance about legal considerations in hiring practices, software that transform job task analysis into selection criteria, interview protocols to standardize applicant screening, tolls to help improve recruitment, and/or self-paced training for hiring officials or interview panels to improve screening reliability. 4. Customer Retention Technology. Premature disengagement from drug abuse treatment participation is a common problem and ranges from approximately 30 to 60% based upon the clinic and modality studied. Past research has very frequently attributed dropping out of treatment to participant characteristics (e.g., motivation, addiction severity, comorbidity) and/or environmental factors (e.g., social pressures, unemployment, homelessness). Seldom has the dropout problem been studied in the context of customer satisfaction. That is, there is little research looking at the causes of dropping out of treatment attributable to organizational factors (e.g., policies, practices, context) that influence participant withdrawal decisions. Needed are tools and systems for assessing and surveying drug abuse treatment program participant perceptions and satisfaction levels, summarizing and report participant assessments, interpreting results, and adjusting policies and practices to improve satisfaction and participant retention in treatment. 5. Effective Management and Operation of Drug Abuse Treatment Services Delivery. The bulk of drug abuse treatment is conducted in small clinical settings with therapeutic staffs of less than a dozen people. Small clinics lack resources to help improve efficiency and effectiveness in both business and therapeutic practices. Areas that may be of interest to small businesses include, but are not limited to: a. Computer-based leader/manager self assessment tools: On-line and other types of tools to help those supervising the delivery of drug abuse treatment services to gain insights about personal strengths and weaknesses, and to help guide them to improved leadership and management practices. b. Organizational change tools: Handbooks describing step-by-step way to introduce more efficient business practices such as quality management/monitoring, creating empowered work teams, formalized goal setting, improved customer relations, forming organization linkages, and adopting new fiscal and resource management techniques. c. Organizational change tools: Handbooks describing step-by-step ways to introduce more efficient or effective therapeutic practices such as, adding pharmacotherapy in a previously drug-free clinic, adopting new medical/pharmacotherapy or behavioral interventions, and adopting new approaches to clinical collaboration and/or case management. 6. Assessment Tools for Quantifying and Organizational Culture that Promotes and Sustains a Drug-Free Workforce. Though drug-free workplace programs are ubiquitous in large businesses, small businesses often lack the staff and resources to create effective drug-free programs because they may involve in-house or contract experts to educate, train, monitor, and enforce policies and practices that will sustain a healthy workforce and a safe and healthy workplace. Though there are numerous model drug-free workplace policies and programs provided free by federal, state, and local governments as well as nongovernmental organizations, many fail to provide management with affordable or free, easy-to-use tools to assess the baseline of their organizations’ culture for drug abuse intolerance, and to monitor progress in building a drug-free organizational culture. Research shows that individual employees and organizations vary in their support for a drug-free workplace. Surveys indicate that coworker tolerance for illicit drug use varies by the type of drug, the type of industry, and the work role of the respondents. A drug-free culture creates commonly-held attitudes, beliefs and practices among employees that are socially reinforced. Once established, the need for costly external incentives and other measures abates as coworkers socialize new incumbents and enforce behavior promoting abstinence. Tools and methodologies need to be developed to a) assess an organization’s baseline culture for drug abuse intolerance both on and off the job, b) identify policies and practices that undermine a drug-free culture, c) enable the identification of programs, policies, and practices capable of helping the workforce develop/strengthen an organizational culture of intolerance for drug use, and d) estimate the impact on the organization’s quality of work-life, job safety, individual and group performance and productivity, and the profitability of the organization itself. Included would be inexpensive and easy to use tools for monitoring workforce behavior change, and changes in the impact on the organization (as outlined in “d”). Thomas F. Hilton, Ph.D. 301-443-6504 Email: Tom.Hilton@nih.gov 7. Web-Based Technologies: Transporting Services Research to Practice. This initiative will support the development and testing of the effectiveness of web-based technologies that facilitate the translation of drug abuse prevention and treatment services research into practice. The ultimate goal is the delivery of efficacious, low-cost interventions to the greatest number of individuals in community settings. Delivery of evidence-based services in community settings often is hampered by lack of state-of-the-art information about the contents of efficacious interventions, the organizational structures and processes that make effective implementation possible, and available training and technical assistance. Applications may include, but are not limited to, the development and testing of new and innovative Internet-based systems that provide practitioners with (a) current information on evidence-based treatments with the greatest promise for defined populations of drug abusers; (b) assistance in translating clinical trials data into clinically useful information; (c) information and training on how to effectively organize, manage, and deliver evidence-based prevention and treatment services; (d) strategies for organizational change and capacity building; and (e) access to training and technical assistance on the adoption of new prevention and treatment interventions. 8. New Technologies for Screening, Assessing, and Preventing Problem Drug Use and HIV, Matching Patients with Appropriate Treatment Services. Increased understanding of the complexities of problem drug use and HIV risk behaviors has sparked growing interest in and increased need for new user-friendly technologies to assist in the screening, assessment, and prevention of drug abuse and HIV, and in the matching of patients with appropriate treatment services. New technologies, including CD-ROM, hand-held, Internet, videotape, videodisc, and other electronic means have great potential for helping treatment providers in specialty and non-specialty care settings including primary care contexts to (a) screen for problem drug use and associated health problems and risk behaviors, including HIV, (b) assess the nature and degree of drug use and HIV risk behaviors, (c) embed items for screening or assessing problem drug use within existing clinical tools, (d) deliver appropriate prevention interventions, and (e) identify appropriate types and levels of treatment services for patients based on their individual treatment needs. These new technologies potentially can provide a more cost effective way of identifying problem drug use, HIV risk behaviors and infection, and associated health problems in a variety of health care settings, speeding the assessment and treatment process, and improving treatment placement decisions. Dionne Jones, Ph.D. 301-443-6504 Email: djones@nida.nih.gov 9. Reintegration of Criminal Offenders into the Community. Many offenders enter the criminal justice system with drug abuse problems and related health issues. In addition to addressing these health care issues within the prison walls, treatment programs are increasingly called upon to help offenders successfully reintegrate into the community following incarceration. This often means helping offenders to manage their recovery through monitoring, linkage with continuing care services, development of social support networks, and education of friends and family members about the nature of drug abuse and the challenges facing the offender upon release from prison. It is estimated that over the next several years, more than 600,000 criminal justice offenders, many of whom have drug abuse problems, per year will be released to return to their communities. New technologies are needed to help treatment providers in the criminal justice system and in the community coordinate efforts to effectively (a) monitor offenders’ recovery once they have been released into the community, (b) prevent relapse, (c) identify relapse early and efficiently re-engage released offenders in appropriate treatment, (d) link released offenders with continuing care services in the community, (e) develop social support networks for recently released offenders in recovery, and (e) educate offenders’ family members so that they can more effectively support offenders in recovery once they have been released from prison. Dionne Jones, Ph.D. 301-443-6504 Email: djones@nida.nih.gov 10. Technologies to Support Quality Improvement in Addiction Treatment Systems. New technologies to support quality improvement in community-based, addiction treatment provider systems are needed. Quality improvement methods, although well established in business and healthcare management, are underutilized in addiction treatment. Addiction treatment systems have limited resources for initiating, developing, implementing, and sustaining quality improvement practices. Most community-based provider systems have limited capacity to capture and integrate information about (a) the nature and extent of community needs and resources; (b) organizational and management processes to facilitate adoption, adaptation, implementation, and sustained use of science-based innovations; (c) implementation costs for new service innovations; (d) client satisfaction; and (e) quality of care. Centralized, automated and cost-efficient technological tools for these purposes could help provider systems improve the quality and efficiency of their treatment services, meet accreditation requirements, and reduce operating costs. Bennett Fletcher, Ph.D. 301-443-6504 Email: bfletche@nida.nih.gov 11. Electronic Drug Abuse Treatment Referral Systems for Physicians. Research shows that primary care physicians often do not screen for drug abuse disorders. While this may be related to stigma attached to illicit drug use or to a lack of adequate health insurance, it may also be due to the lack of an adequate referral system that primary care physicians can use for the patients they identify as having a potential drug problem. The lack of a referral system places a greater burden on the physician to secure treatment resources for the patient, and also places the physician at greater risk if no appropriate treatment can be found. A practical and usable electronic drug abuse treatment referral system needs to be developed and tested for use by physicians in primary care settings, including doctor’s offices. To be effective and useful, the system needs to be targeted at local needs, for example by taking into account local private insurance coverage and the types of insurance accepted by local treatment providers. It should also include an actively-maintained database of local providers, with information on insurance carrier, geographic “catchment” area of treatment providers, types of substance disorders treated, types of co-occurring disorders (mental disorders, etc.) treated, gender, age, other pertinent treatment factors needed by primary care physicians to make appropriate referrals. The system should be designed to be reliable and efficient, allowing for appointment scheduling or other needed arrangements to ensure a successful referral. Feasibility and cost-efficiency should be carefully considered. Richard Denisco, M.D. 301-443-6504 Email: deniscor@nida.nih.gov Center for the Clinical Trials Network The mission of the Clinical Trials Network (CTN) is to improve the quality of drug abuse treatment throughout the country using science as the vehicle. The CTN provides an enterprise in which the National Institute on Drug Abuse, treatment researchers, and community-based service providers cooperatively develop, validate, refine, and deliver new treatment options to patients in community-level clinical practice. This unique partnership between community treatment providers and academic research leaders aims to achieve the following objectives: · Conducting studies of behavioral, pharmacological, and integrated behavioral and pharmacological treatment interventions of therapeutic effect in rigorous, multi-site clinical trials to determine effectiveness across a broad range of community-based treatment settings and diversified patient populations; and · Ensuring the transfer of research results to physicians, clinicians, providers, and patients. Materials and processes that facilitate clinical trials in community practice settings are particularly needed in this program. Areas of research include but are not limited to: · Projects that would simplify, automate, standardize, or reduce the cost of administration of clinical research instruments used in CTN trials · Projects that would reduce error rates in completing assessment or clinical instruments and in transmitting data to data management entities · Projects to develop instruments that measure factors relevant and important to the conduct of addictions research, such as: the extent of craving and/or of withdrawal, the risk of addiction to a particular substance, the therapeutic alliance between patient and therapist, perceived satisfaction with health care, probabilities of a pain management patient developing dependence/abuse on pain medications, and probability of successfully completing detoxification · Projects to develop instruments that measure and predict HIV risk behaviors · Projects that develop and evaluate innovative diagnostic drug screening tests for drug abuse, such as oral swabs · Projects that develop and evaluate the use of gene chip technology for drug abuse risk factors With all questions regarding CTN-sponsored SBIR research, please contact: Quandra Scudder 301-443-6697 Email: scudderq@nida.nih.gov Specific projects could include: 1. Development of Combination Medication for Emergency Treatment of Opioid Overdose in the Presence of Benzodiazepines. Suspected opioid overdose—coma, apnea and pin point pupil—is treated by the administration of naloxone, which, while effective, is short-lived. Patients often leave the Emergency Room, return immediately to opioid use, and suffer dire consequences as a result. There is sufficient preclinical and clinical evidence that buprenorphine may be a more effective medication for treatment of opioid overdose in such patients. However, the clinical development of this treatment strategy has been hampered by concerns that many opioid abusers also abuse benzodiazepine, and in such patients the administration of buprenorphine may be hazardous. Fumazinil, a specific benzodiazepine antagonist used to treat benzodiazepine overdose, can be co-administered with buprenorphine and may protect such patients from the ill effects of buprenorphine in cases of overdose involving both opioids and benzodiazepine. The goal is to develop and test the buprenorphine-fumazinil combination medication formulation for the treatment of opioid overdose with suspected concurrent benzodiazepine abuse. 2. Screening and Development of Partial Agonists at the Human CB1 Receptor for Treatment of Marijuana Dependence or Withdrawal. NIDA seeks applications to screen and/or develop CB1-receptor partial agonists for application in the pharmacotherapeutic treatment of marijuana dependence or withdrawal. The potential benefits of CB1-receptor partial agonists in the treatment of dependence may parallel those of safe and effective nicotine or opiate partial-agonist replacement therapies, where buprenorphine and varenicline have demonstrated effectiveness in enhancing abstinence from opioid use and cigarette smoking, respectively. As implied by the designations of partial-agonist replacement or substitution therapy, a partial-agonist medication has core biological effects similar to those of the abused drug. Importantly however, there is a ceiling-effect dose with the administration of partial agonists not present with full agonists such that at high doses, partial agonists are less likely to precipitate adverse behavioral or biological events and to have abuse liability compared to full agonists. The phase I project should identify compounds that bind to human CB1-receptors as partial agonists and, in the phase II, the grantee should develop and evaluate selected partial agonists. 3. Improved Device to Capture and Measure Drug Use in Oral Fluid. Oral fluid (OF) testing is a promising method to monitor for drugs of abuse. The main advantages of OF is the simplicity and noninvasiveness of sample collection. Aside of patient’s/ study participant’s comfort and preference compared to urine drug screen, the oral fluid sample collection can be easily observed, obviating the need for special restroom facilities and same-sex collectors and making adulteration of the specimen more difficult. Furthermore, infection risk is lower than for drawing blood. For clinical toxicology applications, including use in clinical trials, drug treatment programs, physician office and emergency room testing, onsite OF testing would offer rapid availability of results for diagnostic or research purposes. At this point, however, Substance Abuse and Mental Health Services Administration approval of OF testing has been delayed because of questions about drug device performance, disposition of drugs in OF, and need for improvement of assays. The greatest current limitation for OF testing is the small number of controlled drug administration studies available to inform interpretation of OF tests. (Bosker, Huestis, 2009) Applications should address current limitations and present methods to remove obstacles for wider usage of OF testing in clinical practice and research. Reference: Bosker WM, Huestis MA. Oral Fluid Testing for Drugs of Abuse. Clinical Chemistry.2009; 55:11 1910-1931 4. Improved Technology of Testing Devices to Remotely Capture and Measure Drug Use in Biological Specimens. There is an ongoing need for more accurate, practical and convenient point-of-collection testing devices for monitoring drugs of abuse. Current devices that test for illicit drugs in urine, oral fluid (saliva), sweat and hair have strengths and limitations. The goal of this solicitation is to develop new technologies/devices that will increase strengths (e.g. accuracy, practicality, and convenience) and decrease limitations (e.g. minimum frequency, contamination, and adulteration) of testing methodologies. New technology might permit testing from remote locations (e.g. patient’s or subject’s home) while ensuring real time data collection and transfer into medical records/study databases. Risk of adulteration should be minimized to a level comparable with tests provided in drug treatment centers or study sites. The phase I application should explore all tests currently available, especially new technologies allowing for remote collection of the data. In phase II, the grantee should develop and test a prototype. 5. New Technologies: Integrating Data from Prescription Monitoring Program(s) to Current Clinical Practice. In some states the prescription monitoring program collects prescription data for controlled substances into a central database that can then be used by a limited number of authorized users to assist in deterring the illegitimate use of prescription drugs. Prescribers and dispensers in some states may query the database to assist in determining treatment history and to rule out the possibility that a patient is "doctor shopping" or "scamming" to obtain controlled substances. Limited time/resources of busy medical offices are a barrier to obtaining and utilizing this information to improve quality of treatment for each individual patient. This initiative will support development and testing of the effectiveness of new technologies that facilitate utilization of data collected by Prescription Monitoring Program(s) in clinical practice. Applications may include, but are not limited to, the development and testing of new and innovative Internet-based systems that provide a) practitioners with current information of their patients’ treatment/medication compliance; and b) transfers data automatically to patients chart, etc. The goal is to minimize barriers faced by clinical staff to obtain, record and utilize the data while maintaining strict security requirements (i.e., confidentiality, integrity, and availability). These new technologies should provide a more cost effective way of identifying treatment non-compliance and help adjust a treatment plan according to the needs of individual patients as well as decrease potential diversion of controlled substances. The phase I application will explore and describe current Prescription Monitoring Programs and new technologies allowing development and testing of the application in phase II. HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 A. Behavioral and Integrative Treatment Branch. The Behavioral and Integrative Treatment Branch is interested in research on behavioral and integrative treatments for drug abuse and addiction. The term "behavioral treatments" is used in a broad sense and includes various forms of psychotherapy, behavior therapy, cognitive therapy, family therapy, couples and marital therapy, group therapy, skills training, meditation, guided imagery, counseling, and rehabilitative therapies. The term, “Integrative treatments” refers to treatments that combine behavioral interventions with other treatments, including other behavioral therapies, medications, and/or complementary/alternative therapies. Behavioral and integrative treatment research has been conceptualized to consist of three stages. Stage I, or early treatment development, involves research on the development, refinement, and pilot testing of behavioral and integrative interventions. Stage I may include translational research that incorporates concepts, methods or findings from other disciplines (e.g., neuroscience, cognitive science, etc.) into the development of behavioral and integrative treatments. Stage I may also include research to develop or adapt treatments to become more “community-friendly.” Stage II includes testing treatments that show promise and testing the “dose-response” of treatments. Stage III is research aimed at determining if and how efficacious behavioral treatments may be transported to community settings. Stage III may include studies that test treatments in community settings, with community therapists. Stage III may also include studies that develop or test methods of training treatment providers to administer treatments. Determination of mechanism of action of treatment is relevant to all three stages. Specific areas of interest include: 1. Translation from Basic Behavioral or Cognitive Science. “Stage I” research on the development of behavioral therapies or components of such therapies that are based on developments and findings from the basic behavioral or cognitive sciences. 2. Translation of Cognitive, Affective and Social Neuroscience Findings Towards Development of Behavioral Treatments. “Stage I” research on the development of behavioral treatments or components of such therapies that are based on developments and findings from cognitive, affective, or social neuroscience. For example, one may wish to apply findings on the neural underpinnings of adolescent risk-taking behaviors to target the developmental needs of substance using youth, or apply findings on the link between early adversity and the impairment of emotion regulatory abilities to address the needs of substance using victims of childhood abuse. 3. Treatment of Sleep Disorders for Individuals in Drug Abuse Treatment. Recent research on sleep has shed new light on its importance to psychological and physical health. Sleep deprivation has been linked with impaired cognitive performance, negative mood, and even decreased immune function. Drug abusers often cite insomnia as reason for relapse, and may use drugs to modulate their sleep/waking cycles. However, the treatment of sleep disorders has not been a primary focus of drug abuse treatment research. The development and testing of sleep hygiene interventions, alone or in combination with behavioral interventions, for use in conjunction with drug abuse treatment, as a means of improving treatment for drug abuse is needed. Developmentally and age appropriate, as well as gender sensitive treatment of sleep disorders could impact on the development of more effective treatment interventions. Lisa Onken, Ph.D. 301-443-2235 Email: l010n@nih.gov 4. Modifying Efficacious Behavioral Treatments to be Community Friendly. Several behavioral interventions have been found to be efficacious for the treatment of drug addiction. However, there are barriers to implementation of behavioral treatments in community-based settings. Community settings that treat drug addicted individuals are reluctant or unwilling to adopt these interventions for a variety of reasons. Reasons that scientifically-based behavioral treatments are not accepted by community providers could include the excessive cost of implementation, the length of time for administration of treatment, inadequate training available for therapists and counselors, treatments not shown to be generalizable for different patient populations or for polydrug abusing populations, etc. Research aimed at modifying efficacious behavioral treatments to make them more acceptable to community settings is needed. Settings might include, drug abuse treatment facilities, primary care, managed care, after-school or classroom settings, colleges, and the criminal and juvenile justice system. Examples of possible studies are those that are designed to reduce the cost of treatments, reduce the time of administration of treatments, aid in training of therapists, counselors and nurses, adapt individual therapies for group situations, etc. 5. Treatments to Prevent Escalation from Abuse to Dependence. Therapies for drug abusers who are not yet dependent on drugs to reduce risk of escalation to dependence and therapies for drug abusers who have not considered or claim little interest in seeking treatment for their drug problems are needed. Treatments for participants in their natural environment, such as treatments delivered over the Internet, cell phone, or in neighborhood settings such as churches and recreation centers are desired. A particular focus on treatments which incorporate engagement strategies for hard to interest groups are requested. Educational games, interactive video content, fluency based learning approaches and other methods to help maintain involvement are encouraged. 6. Virtual Reality Applications for Drug Abuse. Development and improvement of treatments using Virtual Reality and other new simulation technologies is needed. New technology may help to make existing treatments more effective, or may make novel treatments possible. Behavioral treatment research to develop, modify, adapt, and test treatments for drug abuse and for co-morbid psychiatric conditions (such as anxiety disorders) using new technologies is of interest. Recently virtual reality simulations have been used to train medical personnel in demanding medical procedures such as microsurgery techniques. Virtual training allows trainees to gain familiarity with both the environment in which services are delivered as well as the intervention techniques without the danger of mistakes impacting live patients. Virtual reality interfaces can assess skill acquisition and provide detailed feedback during procedures to help trainees correct mistakes or avoid making them altogether. In the drug abuse field, training and dissemination efforts have been hampered by a dearth of knowledge about ways to conduct dissemination. Although trainees often practice on actual clients, this approach has drawbacks including its reliance on the client or participant’s schedule and willingness to participate in training sessions and potential danger to the client or if the intervention is delivered incorrectly. Libraries of virtual reality simulations of drug users in treatment or “virtual patients” are needed to provide experiential training for treatment providers without relying on existing patients. This will help facilitate the rapid and effective dissemination of proven treatment strategies. 7. Virtual Clinical Trials Settings for Conducting Behavioral Treatment Trials and Addictions Treatment Provider Education Trials in Cyberspace. Virtual communities such as Second Life as well as private web forums offer a unique opportunity for behavioral therapy researchers and providers to establish and conduct online psychotherapy and behavioral therapy development research as well as a forum to develop provider “university’s” at which various training techniques may be tested for discovering the most efficacious way to deliver continuing education and other training in the latest methods of treating addiction. Applications are encouraged to develop such a forum and test either a provider training or behavioral therapy method in an online trial. As part of this research platform, methods for obtaining consent, maintaining confidentiality, collecting data and where needed, assessing provider adherence and competence are expected. 8. Remote and/or Mobile Abstinence and Identity Verification. Methods are needed for at home or mobile abstinence verification which include identity verification. Drug abuse treatment researchers are in the process of developing web-based and mobile phone based treatments which can extend treatment beyond the clinic walls. Additionally, there is growing recognition by providers that drug addiction is a chronic disease which may require multiple bouts of treatment. However, currently there are no means of monitoring abstinence once patients leave formal treatment or validating progress of patients undergoing treatment located outside a clinic which provides onsite testing. Monitoring onsite testing poses barriers to patient privacy but unobserved sample donation may be subject to switching and adulterants. Products are needed which both test for the presence of illicit substances and which accurately identify the donor of the sample and the time of its submission so patients can participate in monitoring outside of formal treatment settings. Blood sampling similar in invasiveness to a skin prick for diabetes testing or other low risk sampling of other tissues and specimens may be acceptable. Scalability and automation of methods are particularly desirable. Cecelia Spitznas, Ph.D. 301-443-0107, Fax: 301-443-6814 Email: cmcnamar@mail.nih.gov 9. Improving Adherence to Medications and Treatment for Drug Abusers with HIV/AIDS. The introduction of highly active antiretroviral therapy (HAART) has significantly changed HIV/AIDS clinical care. There is a need for research related to the development and testing of new and improved behavioral interventions(alone, and in combination with pharmacological treatments for drug addiction), in order to facilitate better adherence to antiviral regimens among drug abusers with HIV infection, including HIV positive drug abusers with comorbid medical illnesses and/or psychiatric disorders. There is also a need to develop and test adherence interventions administered or assisted by technological devices such as computers, the internet, expert system models, telephone pagers, or hand-held computers. 10. Treatment for Emerging or Specific Populations. Therapies designed to intervene with understudied populations including users of drugs such as methamphetamine, MDMA and other club drugs, marijuana, inhalants, and prescription opioids and psychostimulants, as well as children of substance abusers in need of treatment, and drug abusers with comorbid psychiatric disorders and/or medical illnesses such as HIV/AIDS, hepatitis, etc. 11. Development of HIV Risk Reduction Interventions. Research to develop and evaluate behavioral strategies to reduce HIV risk behaviors in HIV-positive and HIV-negative substance abusing treatment populations. Where appropriate, risk reduction interventions should be adapted to patients’ age, gender, cultural background and potential cognitive impairments, and should address compliance with medical regimens. The product of such research might be training, supervision, or educational materials, such as manuals or videotapes that describe the intervention and its implementation by treatment staff. 12. Woman and Gender Differences in the Provision of Behavioral Treatments, and HIV/AIDS Risk Reduction Approaches. Develop and evaluate specific behavioral treatment approaches targeting drug-addicted women. This may include behavioral therapies, skills training techniques, counseling strategies, and HIV and other infectious disease behavioral risk reduction strategies. This may also include development and testing of training materials that specifically address women and gender differences in drug addiction treatment to promote effective use of research-based treatment approaches. Training materials may involve treatment manuals, training videos, CD ROM or DVD technologies, Internet or computer based programs to manage aspects of treatment administration, or other innovative educational strategies for health professionals using new technologies. 13. Behavioral Treatments Drawing from Stress Research or Stress-Management Interventions. Projects are encouraged that apply concepts from stress research (such as appraisal, coping, and social support) to drug abuse in innovative ways, or that test the extent to which stress-management interventions can be applied to the treatment of drug abuse and interventions to reduce risk of HIV and other infectious diseases. Examples of stress-management techniques that may have novel application to drug abuse and HIV risk include techniques that teach problem-solving and affect-management, restore one’s sense of purpose and meaning, prevent burnout in the face of chronic stressors, increase self-efficacy for managing stress, inoculate against stressors, train relaxation and meditation, intervene during crises, enlist social support and system support, and others. 14. Behavioral Strategies for Increasing Medication Adherence. Research to develop and to evaluate strategies to induce recovering addicts to take medication for a prolonged time, especially opioid antagonist naltrexone; partial opioid-agonist buprenorphine, etc. to encourage HIV infected drug users to comply with medical treatments (HAART) in drug abuse treatment settings; or to adapt existing behavioral strategies to increase patient compliance and cooperation in long-term treatment for drug abuse or for diseases associated with drug abuse such as tuberculosis or hepatitis. An important consideration should be cost and practicality of use in actual clinical practice or in an aftercare program. The product of such research might be a manual, which describes the behavioral strategy, and its implementation by treatment staff or scientific data regarding evaluation. Shoshana Kahana, Ph.D. 301-443-2261, Fax: 301-443-6814 Email: kahanas@mail.nih.gov 15. Integration of Behavioral Treatments and Pharmacotherapies. Development of integrated behavioral treatments and pharmacotherapies may enhance the efficacy of both types of therapeutic interventions. For instance, the maintenance and detoxification of heroin addicts could perhaps be optimized by the integration of distinctive behavioral treatments devised specifically for opioid agonists, antagonists or partial agonists determined by the heterogeneity of the subgroup of addicts and the pharmacological differences of the medications. Integration of medications and behavioral treatments could possibly enhance compliance with medication regimens, increase retention allowing pharmacological effects to occur and prevent relapse to drug abuse and addiction. 16. Behavioral Treatment Research for Drug Abuse and Addiction in Primary Care. Recent research has shown that physicians and other clinicians often fail to recognize drug abuse or addiction among their primary care patients. In addition, a significant number of these clinicians reported that they did not know how to intervene with their patients if drug abuse or addiction was suspected. Drug abuse related illnesses and morbidity often occur in adults and may have begun in adolescence. However, very little research has been done to develop or test behavioral treatment approaches or combined pharmacological and behavioral treatments for drug abuse and addiction in primary care settings. The objectives of this initiative are to encourage research on the development and testing of innovative behavioral treatment approaches e.g. screening and brief interventions, use of web-based or mobile technologies used alone or in combination with pharmacological treatments. Other goals of this research initiative are to encourage additional research on the development and validation of culturally sensitive screening and assessment instruments for use with youth and adults in primary care; and to encourage research on the transportability of efficacious behavioral treatments to primary care settings, as well as research on science-based training approaches for changing primary care clinicians' behaviors regarding their recognition and intervention with drug abusing or addicted patients. While motivational enhancement approaches for some drug abusing populations have been found to be effective, this behavioral approach has not been widely used in primary care. 17. Using Telemedicine to Deliver Efficacious Treatment to Underserved Populations in Specialty Addictions Treatment and/or General Medical Settings . Telemedicine programs are being used in urban medical centers to rapidly disseminate science-based information on new medical treatments. In addition, approximately one-third of the rural hospitals are now using telemedicine to improve patient care Studies are needed to modify existing treatments developed by NIDA researchers for deployment and testing as telemedicine treatments at remote locations to underserved populations. These may be delivered in any patient care context including primary care or specialty addiction treatment. Modification of the treatment content to apply to the remote patient population and provider training materials to orient the onsite staff who may not be experienced at delivering the new treatment may be needed. 18. Youth Smoking Cessation. Smoking related illnesses usually occur in adults. However, tobacco use and nicotine addiction generally begin in childhood or adolescence. Despite health warnings, adolescents continue to initiate smoking at alarming rates and the majority will continue to smoke as adults. Adolescents who begin to smoke, develop nicotine dependence very quickly and exhibit withdrawal symptoms during quit attempts in a similar fashion to adults. Most adolescents who smoke, express a desire to quite. To date, research on smoking cessation for teen and young adult smokers has not been particularly fruitful. This initiative requests research aimed at the development and testing of smoking cessation treatments tailored to the specific needs of adolescents and young adults. Consideration should also be given to gender and ethnicity. 19. Complementary and Alternative Medicine Therapies (CAM) for Drug Abuse Treatment. Research is encouraged on complementary and alternative interventions for drug abuse treatment either as the sole treatment or as an adjunct to enhance the therapeutic potency of existing drug abuse treatments. Any of the five CAM categories: Whole medical systems, mind-body interventions, biologically-based therapies, Manipulative/body-based therapies and energy therapies would be considered for this initiative (for more information, see http://nccam.nih.gov/). CAM therapies are interventions that are commonly used in “real world” settings, but whose therapeutic efficacy has not been scientifically demonstrated. The product of this research might also be a manual or video, which illustrates the intervention and how it is implemented by treatment staff. Geetha Subramaniam, M.D. 301-435-0974 Email: geetha.subramaniam@nih.gov 20. Developing, Evaluating, and Transporting Culturally Sensitive Behavioral Treatments for Racial and Ethnic Minorities. Minority populations are disproportionately affected by the consequences of drug abuse. Research to develop and evaluate behavioral treatments that are culturally sensitive and relevant for diverse racial and ethnic minority populations is encouraged. This may include studies of behavioral treatments, alone or in combination with pharmacological treatment, or studies of behavioral strategies for increasing adherence to taking medications. In the development and evaluation of the behavioral treatment, attention needs to be directed at examining medical, social, and cultural factors that may influence adherence to the behavioral treatment approach and treatment outcome. Also, little is known about the transportability of efficacious behavioral treatments for minority populations. Research is needed on how to transport science-based treatments to various racial/ethnic populations. 21. Incorporating Smoking Cessation in Drug Abuse Treatment. Research is encouraged to develop and test behavioral and combined behavioral and pharmacological treatments for nicotine-addicted individuals who also are addicted to other substances, such as heroin, cocaine, methamphetamines and alcohol. Prevalence of cigarette smoking is extremely high among drug dependent individuals attending drug treatment. Many treatment providers are reluctant to address smoking cessation with clients either because they believe that substance abusers are not interested in quitting or because they fear smoking treatment will have a negative impact on drug abuse treatment outcome. However, studies have shown that many drug abuse clients are interested in quitting smoking and that the concurrent treatment of tobacco dependence and other drug dependencies does not threaten abstinence and might even assist in maintaining it. Research is needed to develop and test smoking cessation treatments that can be incorporated into treatments for illicit drugs of abuse. 22. Developing Treatments for Smokers with Comorbid Disorders. Research is encouraged that focuses on the development, refinement, and testing of behavioral treatments for smokers with psychiatric comorbidity, such as depression, schizophrenia, or anxiety disorders. Smoking prevalence is very high in individuals with psychiatric disorders. These populations generally respond poorly to traditional smoking cessation treatments. Similarly, medical comorbidities are widely prevalent and are in need of additional research in adults and in special populations such as youth, LGBT and homeless persons. Research is needed to develop and test innovative behavioral and combined behavioral and pharmacological treatments that address the unique needs of these individuals. 23. Tobacco Cessation for Pregnant and Post-Partum Women. Smoking among pregnant women remains an ongoing public health concern. It is estimated that approximately 20-30% of pregnant women smoke. Maternal smoking during pregnancy has been linked to infant mortality, impaired fetal brain and nervous system development, premature and complicated births, and low birth-weight babies. For women who do quit during pregnancy, relapse rates vary, but are reported as approximately 25% before delivery, 50% within four months postpartum, and 70-90% by one year postpartum. Children of smokers continue to be at risk for respiratory illness, middle ear infections, impaired lung function, and Sudden Infant Death Syndrome. Sustained tobacco cessation during pregnancy and the postpartum period reduces health risks to both mothers and their babies. Research focused on the development of innovative behavioral and combined behavioral and pharmacological interventions for nicotine-addicted pregnant and postpartum women is encouraged. Interventions may be tailored to sub-populations of pregnant smokers, such as teenage girls, heavy smokers, ethnic minorities, or low SES populations. Examples of other potential studies may include the development of smoking cessation interventions that address co-occurring issues, such as depression or weight-gain, interventions that include partners or support persons, Internet-based interventions or interventions that can be delivered by primary care physicians. 24 Behavioral Treatments for Groups. This includes the development of new psychotherapy approaches, the modification or testing of existing behavioral treatments, and the design and/or testing of innovative clinical training and supervision methods for dissemination of efficacious treatments to community settings. Examples of relevant projects are: traditional group therapies, such as 12-step and therapeutic community approaches, and newer group therapies such as cognitive-behavioral and acceptance-oriented approaches; groups for various populations, such as adolescents, adults, couple and family groups, gender-specific groups, and groups tailored for racial or ethnic minority populations. Of particular interest are projects that address the recent reports suggesting possible contraindications of group treatments for some populations (e.g., delinquent adolescents), or in some formats (e.g., less-structured, client-led groups). Debra Grossman, M.A. 301-443-2249 Email: dg79a@nih.gov 25. Developing Behavioral Treatments for Cognitively Impaired Drug Abusers. While there are currently many efficacious interventions available for drug addicted individuals in treatment, more can potentially be done to enhance treatments by addressing cognitive impairments that may accompany chronic drug use and HIV infection. Many commonly utilized drug addiction and HIV-risk reduction interventions assume certain basic cognitive capacities and abilities that may be absent, or impaired, in chronic drug abusers who may also be HIV-positive. For substance abusers to benefit from psychological treatment, they must be capable of attending to and receiving new information, integrating it with existing information stores, and translating this input into more concrete behavioral change. Substance abusers with cognitive limitations, who may not comprehend the interventions, are more likely to drop out of treatment, relapse faster, and have poorer long-term outcomes in comparison to cognitively intact substance abusers. Research is needed to develop, modify, and test “cognitive-friendly” drug dependence treatments that could lead to improved treatment response and outcome. 26. Interventions to Improve Engagement and Retention in Treatment. Therapies designed specifically to engage and retain individuals in treatment, especially those at high risk for HIV. An example could be a therapy that is: (1) sensitive to the age and motivational level of the client; (2) is specifically designed to respond to the needs of the individual, whatever his or her developmental and motivational level might be; and (3) actively works to increase an individual's desire to remain in treatment. 27. Development of New or Improved Addiction Assessment Measures and Procedures. Research directed at the improvement of a currently available measure or the design of a new psychosocial, social or environmental measure appropriate for use in the clinical assessment of youth and adult substance abusing populations. Special consideration should be given to a specific screening or diagnostic tool, or to a specific measure of treatment readiness, treatment compliance, service utilization, therapeutic process or drug treatment outcome. 28. Marijuana Treatment. Marijuana is the most commonly used illicit substance in the U.S. However, relative to other drugs of abuse, little research has focused on the treatment of marijuana dependence. Trends in the literature suggest that the types of treatments effective with other substances of abuse are likely to be effective with marijuana dependence. Initial studies also suggest that many patients do not show a positive treatment response, indicating that marijuana dependence is not easily treated. Research is needed toward developing and testing effective interventions for marijuana dependent individuals. 29. Transporting Behavioral Treatments to Community Practitioners. There is a need for effective methods of transferring behavioral treatments found to be effective in Stage I clinical trials to clinical practice. Cognitive-behavioral therapy, operant behavioral therapy, group therapy, and family therapy are among the therapies that have been shown to be efficacious in a highly controlled setting and may be helpful treatment approaches in community treatment programs as well. However, community practitioners may have been trained using other approaches and may not have been exposed to these scientifically based approaches. Emphasis should be placed on examining mechanisms to transfer effective research-based drug abuse treatment information and skills-based techniques to practitioners in the community. This may involve the development and testing of innovative training materials and procedures to use in the training of community practitioners to skillfully administer these treatments, including the development of highly innovative technology transfer and communication approaches. Research testing the transportability of empirically supported therapies to the community is an important component of the Behavioral and Integrative Treatment Development Program. There is also a need for the development of educational methods to train non-drug abuse health care workers in relating to drug abusers; eliciting medical histories regarding past or present drug abuse; recognition of the signs and symptoms of drug abuse; identification of those at high-risk for HIV and other drug abuse related medical problems such as tuberculosis or hepatitis. Development and validation of a drug abuse screening instrument which can be administered by primary health care providers, and training in administering such an instrument is also needed. Will Aklin, Ph.D. 301-443-3207 Email: aklinwm@mail.nih.gov 30. Treatment Modules for Specific Problems or Populations. Discrete therapy components that address specific problems common among drug addicted individuals and that can be implemented in conjunction with other therapeutic services. For example, an investigator may wish to develop a four session, highly focused, job seeking skills module that can be easily implemented by a wide range of practitioners to effectively increase appropriate job seeking behavior. Other examples include, but are not limited to, modules to engage ambivalent drug dependent individuals in treatment, modules to increase assertiveness in female drug addicts who feel pressured by others to use drugs, modules to improve study skills and pro-social interactions among withdrawn substance abusing adolescents, or to incorporate effective HIV risk reduction techniques. 31. Behavioral Treatments for Pre-Adolescents and Adolescents. Developmentally appropriate behavioral treatments for pre-adolescents and adolescents that incorporate HIV risk reduction counseling as an integral component of the treatment. This includes the development of new, or refinement of existing psychotherapies, behavioral therapies, and counseling (group and/or individual). This also includes the development and testing of manuals as well as other creative, interactive approaches for therapy delivery that may consider different settings for delivery, such as primary care, school-based health programs, juvenile justice settings, etc. Also the behavioral treatments should be culturally and gender sensitive. 32. Behavioral Treatments for Couples and Families. This includes the development of new psychotherapy approaches, the modification or testing of existing behavioral treatments, and the design and/or testing of innovative clinical training and supervision methods for dissemination of efficacious treatments to community settings, for youth and adult substance users. Treatments that target domestic violence or other forms of interpersonal abuse along with substance abuse are encouraged. 33. Innovative Technologies for Drug Abuse Treatment, HIV Risk Reduction, and Training Clinicians. Relevant research would be directed at the development and evaluation of innovative technologies to treat substance abuse, enhance adherence to medications, and/or reduce risk for HIV infection or transmission. Approaches should be capable of being readily incorporated at reasonable cost into various treatment settings. Areas of interest include Internet-based treatment or training programs, CD-ROM technology, audio delivery devices, photo therapeutic instruments, and hand-held computers. Also of interest are creative approaches for disseminating science-based behavioral treatments and for training therapists to use scientifically based treatments for drug abuse and addiction. Such approaches might include Internet-based education, interactive computer programs, telemedicine, etc. Finally, approaches which apply therapies with evidence of efficacy through new media such as web-based platforms, over email, or through chat rooms and bullet boards are also desirable. Jessica Chambers, Ph.D. 301-443-2237 Email: jcampbel@nida.nih.gov B. Clinical Neuroscience Research. The Clinical Neuroscience Branch (CNB) supports research on the biological etiology (determining the biological basis for vulnerability to drug abuse and progression to addiction, including studies on individual differences and genetics) and clinical neurobiology of addiction (exploring alterations of the structure and/or function of the human central nervous system following acute or chronic exposure of drugs of abuse), and the neurobiology of development (neurobiological effects of drugs of abuse and addiction during various stages of development and maturation, effects of drug exposure on neurobiological processes, development of methodologies and refinement of techniques used in pediatric neuroimaging). The Branch also supports investigations on the cognitive neuroscience of drug abuse and addiction, the neurobiology of treatment, neuroAIDS, and human pain and analgesia. Areas that may be of interest to small businesses include, but are not limited to: 1. Innovative Technology and Tools for Human Substance Abuse Research. There is a continuing need for the development of methods, tools, and technology that can be used as markers of or interventions for brain, genetic or behavioral (including cognitive and affective) alterations in humans related to the risk, or reliance (etiology) of, effects of, or recovery from substance abuse. NIDA has a strong interest in facilitating the identification and use of cross-disciplinary research tools and materials that can be applied to human research that will advance our understanding drug abuse. NIDA also has a strong interest in promoting the commercial adaptation and widespread availability of discoveries (“tools”) made in the course of interdisciplinary research to better serve its mission. The term research “tool" is being used in its broadest sense to embrace the full range of resources that scientists use in the laboratory and clinicians use as therapeutics; therefore, one investigator’s tool may be another's end product. The value of research tools is difficult to assess and varies greatly from one tool to the next and from one situation to the next. Providers and users are likely to differ in their assessments of the value of research tools. Many research and clinical tools are costly to develop and have significant competitive value to the firms that own them. Of particular interest are methods that could be used to determine the effects of drug abuse/ addiction treatments on neurobiological systems in an attempt to understand the neurobiological processes underlying risk and recovery. Also of interest are methods and tools that can be integrated or expend with brain imaging techniques or other brain-related measures that can be used in human subjects. Examples include, but are not limited to; Development of stimulus-generating hardware and/or software for use in substance abuse studies, including neurocognitive tasks, presentation of drug-related images for the induction of craving or to probe attentional or affective processes, and “virtual reality” types of dynamic stimuli important in studies of drug abuse and addiction; Remote and mobile based technologies such as PDA’s, “smart phones”, or web-based applications for measuring cognitive and affective function in real world environments; Development or implementation of interventions such as trans-cranial or direct current brain stimulation, real-time neurofeedback, or cognitive training; New infomatic tools for primary data analysis or secondary data analysis would also be appropriate; Another example would be methods or technology related to development of the human central nervous system and how drugs of abuse perturb this process. Developmental studies of these populations presents unique challenges when using neuroimaging technology. The development of novel techniques, or the refinement of existing methods, to provide direct noninvasive measures of brain structure and/or function that are adapted specifically for use in pediatric and adolescent populations is strongly encouraged. Also, neurocognitive and other neurobehavioral tasks for use in these populations, especially where they can be designed to probe underlying neurobiological processes, need to be developed (for developmental issues, contact Cheryl Boyce, Ph.D.). Steven Grant, Ph.D. 301-443-4877 Email: sgrant@nida.nih.gov or Cheryl Boyce, Ph.D. 301-443-4877 Email: cboyce@nida.nih.gov 2. Human Brain Neurochemical and Molecular Imaging. Measurement of brain neurochemistry, neuropharmacology (receptors) and gene expression in humans using non-invasive imaging has lagged behind advances in these areas in pre-clinical research as well as in functional and anatomical neuroimaging in humans. There is a continuing need for development of new ways to measure molecular targets in the human brain. Examples include, but are not limited to novel radioligands for PET and SPECT imaging in human brain for molecular targets (e.g., receptors, intracellular messengers, disease-related proteins), as well as novel methods that use magnetic resonance imaging or other emerging technologies such as optical imaging.. The primary application of these methods will be in basic human research. Ultimately, these measures may also be used as potential biological markers and surrogate endpoints for translational and clinical research, drug discovery and development, and clinical trials. The scope of the projects may encompass pilot or clinical feasibility evaluation in pre-clinical studies, model development, or clinical studies. Alternatively, the focus may be on research and development of new technologies for molecular, neurochemical or neuropharmacological development. Steven Grant, Ph.D. 301-443-4877 Email: sgrant@nida.nih.gov 3. Neuro-Rehabilitation of Drug-Induced Cognitive Deficiencies. The increased awareness that the brain is capable of substantial plasticity throughout the lifespan has opened the possibility that intervention can be developed alter brain or cognitive function so as to accelerate recovery of brain and cognitive dysfunction. Such interventions encompass both direct interventions of brain function as well as indirect interventions based on cognitive or behavioral principles. Direct interventions include trans-cranial or direct current brain stimulation, real-time neurofeedback, and deep brain stimulation. Another complementary approach is based on game technology for “serious (health-related) rather than purely recreational purposes. Serious games can provide a completely controlled, noninvasive, safe and alternative methodology for a variety of important studies of drug abuse and addiction. By involving a person in an interactive computerized situation, designed to be both entertaining yet directive (i.e., in the sense of covertly shaping desired behaviors via highly flexible and programmable sets of scenarios), altered behaviors can be introduced by pre-programming consequences to counteract and potentially reset undesirable neurobiological and neurobehavioral deficits associated with chronic drug abuse. Areas of cognitive impairment related to substance abuse that could be enhanced through the use of either direct brain interventions, or “serious” games include diminished decision-making ability, attention/concentration deficits, attentional biases, lack of cognitive flexibility and problem solving abilities, inability to use feedback to monitor/change behavior, memory impairments,. Steven Grant, Ph.D. 301-402-1746 Email: sgrant@nida.nih.gov 4. Measurement of Psychosocial Stress in Relation to Substance Abuse. There is the need for development, improvement and/or adaptation of precise and reliable field deployable measurement technologies can detect and quantify an individual’s exposure to psychosocial stress and/or one or more drugs. Ideally, the technology could be scalable from selected samples to full population studies. Comprehensive assessment includes measuring acute/chronic/cumulative exposures to psychosocial stress and/or addictive substances with a high degree of temporal and spatial resolution (i.e., as a person moves through environments), and with a high degree of accuracy and sensitivity to detect meaningful variations in extent of and response to exposure across developmental periods (ranging from prenatal to senescence) and among various population groups. Such technologies may include use of emerging remote and mobile technologies such as PDA’s, “smart phones”, or web-based applications. Harold Gordon, Ph.D. 301-443-4877 Email: hr23r@nih.gov C. Human Development Research. The Behavioral and Brain Development Branch (BBDB) supports a broad research, research training and career development programs directed toward: (1) an increased understanding of how developmental processes and developmental outcomes are affected by drug exposure and related factors; (2) an increased understanding of developmental processes that are relevant to: (a) drug use, abuse, addiction, treatment and relapse, and (b) risk behaviors related to drug abuse and other health conditions that often accompany drug use (e.g., HIV infection, STDs); (3) the use of translational approaches to increase understanding of these developmental processes; and (4) an increase in effective interventions aimed at preventing or ameliorating negative developmental outcomes resulting from exposure to drugs and related factors across diverse populations (e.g. racial/ethnic minority; rural/urban, etc.). 1. Develop Improved Technology for Assessment of Prenatal Drug Exposure and Passive Postnatal Drug Exposure. a. Develop and refine methods for the detection and quantification of infant exposure to drugs of abuse during pregnancy, including nicotine cocaine, marijuana, opiates, and methamphetamines. b. Develop and refine methods for the detection and quantification of passive exposure to illicit drugs during infancy and childhood including second and third hand exposure to nicotine, marijuana, or other drugs of abuse. c. Develop technologies for us in diverse settings (e.g. primary care, emergency rooms, obstetrics/gynecology, etc.) of the assessment of prenatal drug exposure and passive postnatal drug exposure. Nicolette Borek, Ph.D., 301-402-0866 Email: nborek@nida.nih.gov 2. Develop Interactive Database Systems on Human Subjects Issues for Use by Drug Abuse Researchers Studying School-Age Children and Adolescents Drug Use. Develop systems to assist investigators in obtaining technical and legal information relevant to involvement of children and adolescents in research on drug abuse. Examples of pertinent situations include tracking long-term health and development of children exposed to drugs during pregnancy, and investigating vulnerability and possible pathways to drug abuse including children in primary care and child care settings, and school-age children and adolescents. Human subject issues addressing family environments, child abuse and domestic violence, and secondary data sources are also of interest. These database systems should address issues such as assent and consent, should provide information on variation in laws and guidelines across jurisdictions, should include the capacity for interactive communication on numerous situations potentially facing clinical research and health care professionals, and should serve as sources of referral for additional assistance. Nicolette Borek, Ph.D. 301-402-0866 Email: nborek@nida.nih.gov 3. Develop Improved Methods of Neuroimaging to Assess Structural and Functional Status of the Brains of Children and Adolescents Exposed to Drugs. Document the feasibility and accuracy of appropriate and acceptable methods for assessing brain structure and function of children and adolescents, with special attention to any or all of the following groups: those exposed to drugs during pregnancy, those passively exposed during infancy and childhood, This could also include products to improve the tolerability, safety and validity of neuroimaging in children and adolescents, e.g. tools or techniques to reduce head-motion artifacts and image those actively using illicit substances. Documentation should include attention to such matters as technological difficulties and risks, and standardization issues relevant to testing conditions and image analysis. Karen Sirocco, Ph.D. 301-443-4877 Email: ksirocco@nidal.nih.gov or James Bjork, Ph.D. 301-443-3209 Email: jbjork@nida.nih.gov 4. Develop and Refine Methodologies and Clinical Tools for Measurement and Effective Interventions of Developmental Factors and Drug Use Among Children and Adolescents. a. Research to develop and refine methodologies for drug use detection and quantification which may address issues of acceptability, reliability, and validity of one or more methods for clinical research and practice (e.g., interviews, computerized questionnaires, and biological indicators such as saliva or sweat). Development of web, hardware and software technology tools to enable refined physiological and behavioral assessment of normal and atypical infant and child development which may inform risk and interventions for drug use are also of interest. Nicolette Borek, Ph.D. 301-402-0866 Email: nborek@nida.nih.gov b. Research and development of novel, or the enhancement of existing tools to be used in effective preventive or treatment interventions, and information dissemination to or understand drug use and its developmental effects for children, adolescents and their families. These tools might be used by researchers, health professionals and other health care providers, as well as by those in the broader community, including educators, day care providers, family members, etc. These tools must take into account cultural and developmental factor to assure their effectiveness and validity. Cheryl Anne Boyce, Ph.D. 301-443-4877 Email: cboyce@mail.nih.gov HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 Emphasis is on the molecular mechanisms of oral epithelial cell regulation and aberrations of these mechanisms. Research related to early diagnosis, prevention, and treatment of oral neoplasias is particularly relevant for the NIDCR small business program. Some examples include but are not limited to the following areas: A. Develop imaging techniques for the early detection, diagnosis and prognosis of pre-malignant head and neck lesions including oral salivary gland carcinomas. B. Develop immunotherapies (e.g. vaccines, gene therapies) effective against viruses suspected to be etiologic agents in the induction of pre-malignant and malignant head and neck lesions. C. Develop effective pharmacological, immunological and radiological modalities for treatment of pre-malignant and malignant head and neck lesions. D. Develop novel technologies for the genetic and molecular-targeted therapy of head and neck carcinomas. E. Develop novel micro and nano-sensor technologies that can release therapeutic agents in tumor cells. F. Develop regimens for the alleviation of the oral complications of cancer therapy. G. Develop novel technologies for using stem cells as therapeutics for head and neck cancers HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 The NHGRI has supported the generation of many large-scale genomic data sets such as genome sequence, haplotype maps, transcriptome measurements, protein interactions, and functional elements. NHGRI encourages the development of new computational methods and tools to analyze these and other large datasets, and to extract useful biological information from them. Where possible, existing community data standards and methods for data exchange should be used in the development of these new methods and tools. Further information on programs related to genomic databases and computational biology is available at this website: http://www.genome.gov/10001735. The development of new sequencing technologies has dramatically increased the amount of data produced for genomics. NHGRI is interested in supporting new computational applications for the production and analysis of data from these new sequencing platforms. These applications would include better computational methods for storage, compression and transfer of large datasets by biomedical researchers along with better analysis methods to interpret these data and integrate with other data types. Some genomic data analysis and display tools have been developed that already are used in the community that would benefit from additional work to support broader dissemination, for example making them efficient, reliable, robust, well-documented, and well-supported. NHGRI will support projects to extend the support for these informatics tools to make them readily adopted by any biomedical research laboratory that wishes to use genomic technologies to address biological questions. HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 Through research in neuroscience and basic behavioral science we can gain an understanding of the fundamental mechanisms underlying thought, emotion, and behavior and an understanding of what goes wrong in the brain in mental illness. Research sponsored by the Division of Neuroscience and Basic Behavioral Science covers a broad range of neuroscience topics: from both experimental and theoretical approaches, from molecules to whole brains to populations of individuals, from single cell organisms to humans, from across the entire lifespan, and from states of health and disease. This division also supports research on the basic behavioral, psychological, and social processes that underlie normal behavioral functioning. The topics listed below reflect the NIMH interest in technologies related to this broad range, but should not be considered a complete list. Prospective applicants are strongly encouraged to contact Dr. Margaret Grabb (listed below) with questions about the relevance of their interests to the mission of this division. A. Cutting-Edge Technologies for Neuroscience Research. Most of the research topics listed after this one are posed from the Division's neuroscience and basic behavioral science mission-oriented perspective, however, the technologies that might be developed to address those mission goals might be quite fundamental. Prospective applicants familiar with such technologies, but not familiar with the mission-related use of these technologies, are strongly encouraged to contact Dr. Margaret Grabb (listed below) for assistance in bridging this gap between their technical knowledge and knowledge of the neuroscience-related mission of NIMH. Technologies and approaches that might be used in products relevant to this mission include, but are not limited to: 1. Caged Molecules. These chemical entities could be activated, or could release an active agent, when specified bonds are broken by chemical, biochemical, photic, or other means. Among other uses, such molecules could be used to indicate biochemical or physiological processes or to deliver pharmacologic substances to highly localized brain regions. 2. Genetically Engineered Proteins. Such proteins could be put to any number of uses, including to express a fluorophore or chromophore at the occurrence of specific biochemical processes to report the time and location of such processes in brain tissue. 3. Inducible Gene Expression. Methods to turn on or off expression of particular genes in animals on the basis of time in the lifespan, location in the brain, or other factors. Such a capability would significantly advance basic brain research, and would have important implications for treatment and therapy of mental illness. 4. Combinatorial Approaches. These are high-through-put approaches that can be used to screen and synthesize molecules that affect brain cells. 5. Biocompatible Biomaterials. Such research and development relates to the chronic use of electrodes and other probes used in brain research, as well as implanted drug delivery devices. 6. Nanotechnologies. This emerging area of technology presents a wide range of opportunities for brain research, from the fabrication of probes to monitor brain physiology to novel means of delivering drugs and other substances. 7. Informatics Tools. Such technologies allow brain scientists, clinicians and theorists to make better sense and use of their data. These tools and approaches include those to acquire, store, visualize, analyze, integrate, synthesize and share data, including those for electronic collaboration. 8. Simulation Technologies. Computer-based, biologically realistic simulations of parts of neurons, neurons, and circuits. 9. Mathematical, Statistical and Computer Algorithms. Such algorithms could be used to analyze large and/or complex data sets. Examples of these data sets include those derived from multiple, single-unit recording studies and functional imaging studies. Among other applications, these could be used to segment images (obtained from electron or light microscopes, or from volumetric imaging instruments such as confocal microscopes and magnetic resonance imagers), filter noise, visualize data or search vast data sets for specified patterns or data (e.g., use of pattern recognition algorithms to search time series data sets obtained from electrophysiological recording of neural activity, or video data obtained from behavioral analysis of genetically altered animals). In addition, digital reconstruction of dendritic and axonal arbors would be of interest. 10. Telemetry. Transferring data from one point to another is important for neuroscientists monitoring the physiological signals from the brain. Telemetry, even over relatively short distances (from a few millimeters to a few meters), could, for example, provide a means to obtain data from awake, behaving animals without interfering with the behavior of interest. Examples include telemetry that can be easily implanted/attached to awake behaving animals for measuring peripheral/autonomic responses (this approach could be used to inform stress/emotion research), miniaturized telemetry for use in smaller animals with increased numbers of recording devices/electrodes implanted per animal. Alternatives to telemetry would be considered as well. 11. Biosensors. Neurons communicate with each other through thousands of different chemical substances; internally, molecular pathways direct the function of the neuron. Sensors of high specificity and sensitivity for such substances would provide neuroscientists with important new ways to study the brain. B. Instrumentation for Basic Neuroscience Research. Modern equipment that uses the most recent technological advances is needed in neuroscience research so that neural substrates of mental illness can be identified and localized. The NIMH is interested in supporting research and development of new or improved approaches relevant to, but not limited to, the following: 1. Neurophysiology. Microelectrodes for stimulation and/or recording, smart nanoscaffolds, macroelectrodes, biocompatible coatings, interfaces to electronics, software for data analysis, visualization, etc. Systems with better/easier MR compatibility would also be of interest. 2. Cell Sorting. Based on cell size, type, function, morphology, abnormal features, specific membrane proteins, etc. 3. In Vivo Electrochemical Voltammetry. More sensitive and selective electrodes, software for data analysis, etc. 4. High Performance Liquid Chromatography. Improved reliability, specificity, sensitivity, etc. 5. Technology to support Multiple Unit Recording Electrode Arrays. Recording techniques, analysis techniques and raw data storage. 6. Physiological and Behavioral Monitoring. Temperature, activity, sleep duration, neuronal activity, EEG activity, EKG, pulse rate, recording, capture and analysis of multiple single unit activity from microelectrodes, automated SWS analysis and coherence of EEG rhythms, and further refinement of High density EEGs. 7. Development of novel technologies for stimulating specific cells or signaling pathways in awake behaving animals. 8. Development of more sensitive fluorescent probes for simultaneous and real time measures of multiple neurotransmitter release and intracellular signaling pathway activities. 9. Associated Software. C. Macroscopic Neuroimaging. Modern technologies allow for the observation of the structure and function of the intact brain. This capability has the potential to greatly advance understanding of the brain in both health and disease, and across the lifespan. NIMH is interested in advancing this area of technology through enhancing current tools and approaches, as well as developing entirely new ways to image the brain. All modalities are of interest, including, but not limited to: magnetic resonance imaging (MRI) or spectroscopy, positron emission tomography (PET), optical imaging or spectroscopy, single photon emission computed tomography, magnetoencephalography (MEG), diffusion tensor imaging (DTI), etc. While not an imaging technique itself, transcranial magnetic stimulation (TMS) is an associated, important technology. TMS can be used in combination with fMRI as means to further assess physiology and integrity of neural systems both in health and in mental disorders. Due to its greatly increased use in recent years, technologies specifically focused on improving the utility and specificity of fMRI techniques are of particular interest. 1. Innovative agents and/or technologies to visualize brain connectivity, activity, and neural plasticity in situ with minimal invasion. 2. Improvement in the techniques, the design and construction of devices for non-invasive imaging for any modality, for example, improving spatial resolution, quantitative accuracy, signal-to-noise ratio, and electronics. 3. Development and enhancement of non-invasive imaging techniques for evaluating alterations in brain physiology produced by drugs. These would include techniques for monitoring changes in regional blood flow; concentrations of drug and/or tissue metabolites; and the distribution and activity of receptors. 4. Synthesis, or isolation from natural products, of highly selective receptor ligands or indicators of neurochemical processes, which would be labeled for imaging by one or more particular modality. 5. Development of selective hormone receptor ligands for brain imaging. 6. Development of imaging agents to examine the integrity of the blood brain barrier following infection and other environmental challenges. 7. New approaches in radiochemistry that will permit more exact identification of the chemical changes associated with behavioral states (e.g., sleep or arousal) or mental illness as observed with any particular neuroimaging modality. 8. Synthesis of molecules containing stable, rarely occurring isotopes designed to be detected by non-invasive imaging techniques (e.g., fluorine-containing molecules, carbon-13 labeled substrates). 9. Methods and associated products for quantification of imaging data including new statistical approaches for evaluating the data. 10. Methods to integrate routines for greater and more precise computer enhancement of the images, and for combining or overlaying images obtained from multiple modalities. 11. Software needed for the precise quantification of data obtained from these imaging techniques with emphasis on the reliable definition of discrete, anatomically distinct areas within the brain. 12. Novel agents or other tools to increase the ability to correlate features of MR images with histological features (e.g., cytoarchitecture or chemoarchitecture) both identified and those yet to be identified. 13. Generation of physiologic measurements from images of regional radioactivity generated during PET, especially for the study of brain neurotransmitter/neuroreceptor systems. 14. Novel approaches to visualizing data obtained in neuroimaging, such as the computational “unfolding” of three-dimensional images of cerebral cortex. 15. Improved methods for pediatric brain imaging. These would include: software and database products, equipment for creating a “child-friendly” environment and for the behavioral training of children and impaired subjects for cooperation and motion reduction during neuroimaging procedures. 16. Combining of different imaging technologies (e.g., ERPs and fMRI; MEG and fMRI; MEG and EEG, optogenetic methods and fMRI, etc.). The latter example, optfMRI, can be used as means of improving tools for further understanding of neural bases of fMRI signals and to produce connectivity a map of neural cells that can be defined both genetically and topographically with a combination of these two techniques. 17. New tools and devices to simultaneously record hemodynamic signals (BOLD, rCBF, etc.) and neural activity (EEG, LFP, spiking, etc.) to better understand the direct relationship between blood flow variables and neural activity within the brain. 18. Development of equipment, software and other tools for recording and quantifying eye movements, motion, and autonomic reactivity during scanning, applicable to all ages (including young children) particularly in the MRI environment. 19. Methods for relating changes in brain morphology and metabolism associated with age, particularly infancy through adolescence, to changes in hemodynamic responses to neural activity and fMRI signals. 20. Improvements in TMS techniques that will allow for greater specificity in the sites of stimulation and greater control over the effects of the stimulation. In particular, improvements in stimulators that would allow much smaller effective fields of stimulation with more reliable and repeatable stimulator placement would be a significant benefit to the field. 21. Real time fMRI is becoming a research tool of interest with potential clinical/therapeutic neurofeedback applications. Products are needed that would enhance the ability of scientists to use this technology for those neurofeedback applications in an off-the-shelf manner. 22. Development of methods to improve efficiency, specificity and controllability of viruses used in primate tract tracing studies. 23. Development of more sophisticated imaging strategies in rodents. 24. Development of a user-friendly interface to serial reconstruction software capable of generating stackable, 3D images of axonal and dendritic arborizations at the light and electron microscopic level. D. Microscopic Neuroimaging. The morphology of individual neurons and the distribution of subcellular components within them, are key to understanding the manner in which these cells function. Advances in the development of agents indicating neuronal structure and function that can be visualized microscopically are important to the NIMH's interest in brain research. This includes enhancements of current agents and ligands to be imaged (agents indicating specific biochemical processes or structures, etc.); development of novel agents and ligands; software to assist interaction with the data; and other related technologies and methods. Examples would include, but not be limited to: 1. Software and hardware for analyzing image data obtained by microscopes, including tools to automatically or semi-automatically. Identify particular profiles (e.g., labeled cell bodies), segment images, reconstruct images into three dimensional representations, perform unbiased counting and measuring, etc. 2. Synthesis and testing of novel or improved probes for microimaging the nervous system. E. Molecular and Cellular Neurobiology and Neurochemistry. Manipulating and studying basic molecular, cellular and chemical processes has led to insight to understanding brain function, and has provided the foundation on which pharmacological interventions have been developed for the treatment of mental illness. NIMH is interested in supporting a wide range of new techniques and tools related to this area. These include, but are not limited to: 1. New low-cost techniques for hybridoma production of monoclonal antibodies specific for “neural antigens” (e.g., neurotransmitters, small peptides, neurotransmitter receptors). 2. Innovative methods for establishing a “monoclonal bank” (frozen cells) for each of the cell lines as a permanent, widely available, reliable, and low cost source of monoclonal antibodies for research on the nervous system. 3. Labeled antibodies or other agents that will readily identify receptors for which there are no ligands (orphan receptors) and which have low densities in the brain. 4. Automated methods for quantifying the low levels of bound ligands for quantifying receptors that are sparsely scattered in the brain. 5. New cell lines that express each of the known neurotransmitter receptors so that each cell line will be homogeneous for one receptor. 6. New cell lines that express each of the above receptors linked to some metabolic function and/or second messenger so that the functional consequences of receptor occupancy can be detected. 7. High volume, inexpensive assay methods for measuring both receptor occupancy and cellular response for each of the receptor types. 8. Develop cell culture models for neurons, including methods of purifying homogeneous populations of non-transformed cells by, for example, developing markers to identify neuronal cell types for use in characterizing cell-type-specific signaling pathways which may be useful in tracking the effects of various drugs. 9. Develop techniques for either activating or deactivating specific ion channels, receptors and signal transduction pathways. 10. Develop dynamic biochemical and imaging assays that allow measurement of variables now obtained only through electrophysiological techniques. 11. Develop tools to facilitate proteomic analysis of CNS neurons. 12. Develop tools to facilitate in vivo studies of protein-protein interaction, folding and aggregation. These technologies could impact our understanding of the basic neurotransmitter receptors chemistry and on developing of more selective small chemical entities with high affinities for CNS targets. 13. New approaches to study the multiple functions of particular proteins. 14. Tools to study post-translational changes in proteins (expression levels, post-translational modifications, etc.) in specified tissue compartments and subcellular domains. 15. Technologies to study functional entities within cells (e.g., green fluorescent protein approaches) and subcellular compartments. 16. Tools and approaches to study coordinate changes in genes and their functional relationship to phenotypes, including phenotypes associated with specific brain disorders. 17. Novel tools and approaches to study protein-protein interactions, especially those with phosphoproteins. Further develop methods and reagents for studying the structures of membrane proteins at atomic resolution. Membrane protein systems that are of particular interest to NIMH include proteins involved in normal function and pathology of cells (neurons and glia) in the central and peripheral nervous system. 18. Develop novel techniques for isolating and identifying the structure of brain-derived membrane proteins. 19. New methods to identify peptide receptors for which traditional biochemical approaches (e.g.: radiolabeling techniques) failed to produce results. This would be relevant for the development of small molecular probes that would target peptide systems that might be altered in mental disorders. 20. Development of new and optimization of the existing methods for non-invasive quantitative detection of hormones and hormone action in awake behaving animals. 21. Development of novel technologies to adapt human induced pluripotent stem cells (iPSCs) to identify molecular and cellular dysfunction underlying mental illness and for high throughput screening assays for candidate therapeutics. 22. Continuing to improve optogenetic techniques (combining optical and genetic techniques to probe neural circuits within intact animals). F. Genetic and Transgenic Technology. Advances in genetic and transgenic technologies offer many opportunities to probe fundamental questions about the brain, behavior and pathology. NIMH is broadly interested in these areas; some examples of topics relevant to the mission of this Institute include, but are not limited to: 1. Methods to perform site-directed mutagenesis in cell lines for the study of membrane proteins such as ion channels and neurotransmitter receptors. 2. Development of gene “knockout” or “knockin” animals using such approaches as homologous recombination targeting genes important in neurotransmission, development, and tropic interactions as well as models relevant to psychiatric disease. 3. New methods to delete or alter targeted genes in the preparation of transgenic animals including methods that increase or decrease gene expression. 4. Development of new techniques and apparatus for delivery of synthetic nucleic acids to manipulate endogenous gene expression in specific cell populations and/or brain regions. 5. Develop and validate standardized behavioral tests and apparatuses to assess the gene knockouts and/or gene “knockins” affecting neurotransmission. 6. New approaches for spatially and/or temporally restricted gene activation and/or inactivation. 7. Develop novel markers for elucidating how signaling cascades impact DNA transcription. 8. New ways to assess quantitatively transcription of genes in real time in a manner that is minimally injurious to cells (e.g., non-permeabilizing approaches). 9. Develop new technologies to study gene function and expression, including approaches to studying gene and protein expression at single cell resolution. 10. Develop novel approaches to study the expression characteristics of non-coding (nc) RNA molecules as well as developing methodologies using nc-RNAs to manipulate gene expression in cells and tissues of the nervous system. 11. Development of embryonic stem (ES) cell lines from rodent strains (rats and mice) of relevance to behavioral research. 12. Development of technologies and approaches to facilitate the collection and distribution of ES cell lines containing mutations of potential relevance to behavioral and neural processes relevant to neuropsychiatric disorders. 13. Develop methods for long-term storage of transgenic germ cell lines. 14. Develop technologies and approaches to aid in the renewal of founder colonies of transgenic mice from repositories of transgenic germ cell lines. 15. Develop databases on neurobiological transgenic animals produced to date, including information such as the origin of the transgenic animal, key features of the biological and behavioral mutant, availability and location of germ cell lines, and existence of breeding colonies. 16. Develop gene transfer technologies such as viral vectors and non-viral (e.g. polymer-based) systems to produce long-term, stable gene expression in the brain. 17. Develop methods to analyze and manipulate DNA structure to study epigenetic modifications and chromatin remodeling in brain tissue and neuronal populations. 18. Development of selective gene silencing strategies to ablate neurons in one circuitry in order to examine its specific behavioral consequences. 19. Technology development in epigenetics: a) development of novel and highly accurate tools to analyze proteomics of histones b) development of antibodies for immunochemical studies of histone modifications that selectively target a specific DNA modification site c) develop and apply tools for epigenetic research to determine how, when, and where experience affects gene expression. 20. Technology development in Microbiome research: a) development of tools for high throughput genomic analysis of human microbiome; b) development of informatics tools to study the huge amount data that will result from these studies; and c) development of methods to determine the interaction between microbial community genes and host genetics as a potential contributing factor for mental disorders. G. Neuroimmunology. Research on the interplay between the brain, neuroendocrine system, and, immune system has revealed important links between these major homeostatic system components. Examples of NIMH-relevant topics in this area include, but are not limited to: 1. Development of new tools to explore the specific properties of the blood-brain barrier responsible for the selective delivery or retention of cytokines, immune cells, and drugs affecting immune activity in the brain. 2. Development of assays for identifying potential autoimmune components of psychiatric disorders. 3. Identification of critical molecules, processes, and pathways mediating signals from the peripheral immune system to the brain. 4. Development of novel cytokine ligands and antagonists, and neuroimaging agents. H. Pharmacology. Pharmacological intervention represents a major force in the treatment of mental illness, and NIMH is interested in supporting research and development in this area. However, pharmacologic agents that primarily act on molecular targets which replicate those of currently-marketed pharmaceuticals used in the treatment of mental disorders would not be of interest for this program. Relevant pharmacology topics include, but are not limited to: 1. New chemical entities with high, selective affinities for CNS targets. Examples include, but are not limited to, receptors, transporters, ion channels, enzymes, kinases, or second or third messenger systems. 2. Methods to evaluate old and new chemical entities (including complex mixtures of crude extracts from natural products) for possible therapeutic usefulness using “in vitro” and “in vivo” assays and model systems. 3. Methods for extraction, fractionalization, and isolation of active compounds from natural products. Water-soluble compounds are of particular interest due to the difficulty of the procedures. 4. Computer algorithms that model receptors to evaluate theoretical permutations of known molecules to find the molecule with the maximum probability of having the highest affinity for a specific receptor as well as those that have the potential for the most desirable “on” and “off” rates. 5. Computer models of the blood brain barrier and evaluate potential and actual drug molecules for their ability to cross or penetrate this barrier. 6. Strategies for evaluating pharmacological agents (e.g., animal behavioral testing, computer simulation) within specific domains of cognitive function. 7. Behavioral “models” similar in animals and humans; behavioral pharmacological effects that may serve as “surrogate” markers in humans. 8. Development of models for evaluating drug effects within functional brain circuits relevant to mental disorders. 9. Development of novel drug delivery systems. 10. Tools for Drug Development including neuroimaging (e.g., radiolabeled compounds) and development of animal models. 11. Pharmacological profiling (in vitro and in vivo) for potential therapeutic drugs. 12. Methods for evaluation of long-term effects of psychotropic drug administration in animal models or human subjects. If clinical populations are being tested, the technology would be appropriate for either the Division of Developmental Translational Research (DDTR) or the Division of Adult Translation Research (DATR) at NIMH. 13. Improving existing, and developing new, vectors for delivery of genes to the brain. 14. Development of novel therapeutic approaches targeting gene expression through effects on promoter activity or epigenetic mechanisms. 15. Development of novel high throughput screening (HTS) assays for drug development. Examples include, but are not limited to, in vitro functional assays, toxicology screens, blood-brain barrier permeability assays, and circuit based or behavioral assays. 16. Development of novel molecular targets for drug development to treat mental illnesses. I. Tract Tracing Methods and Tools. Little is known about the details of the connectivity of the human nervous system, because the best tract tracing techniques are invasive and require the deposit of substances in vivo. Methods that would be applicable to post-mortem tissue would allow significant progress in connectional studies of human tissue, as well as non-human tissue, particularly with regard to the development of c, quantu onnections and the connections of structures not easily accessed in vivo. Examples include the development of improved physical, chemical and/or biological markers for neuroanatomical tract-tracing (e.g. m dots, caged molecules, viral delivery agents, etc.). J. Educational Tools. Neuroscience, basic behavioral science and human genetics are compelling areas of science that not only touch upon a diverse array of disciplines, but also provide insights to the essence of what it is to be human. Products aimed at teaching the substance of these fields to students of all ages would be useful in disseminating this information and these insights. Examples include, but are not limited to: software and other interactive media used to convey fundamental concepts about the brain to children; computer simulations of neuroscience experiments; updateable media that presents state-of-the-art information on particular topics for use by experts; website or other online, interactive electronic vehicle to allow for sharing of information about the brain and its functions, including technologies for holding interactive research conferences related to basic behavioral sciences, basic neuroscience, or clinical neuroscience. K. Neuroinformatics. Data generated by brain research are diverse, vast, and complex. The diversity of data is due to the fact that neuroscience data are obtained from: theoretical, experimental and clinical approaches; from levels of biological organization that span molecules to populations of individuals and from single-cell organisms to humans; and from states of health, disease, and models of disease. The quantity of data in brain research is the result of tens of thousands of neuroscience laboratories working around the world. The complexity of data reflects the high level of interconnectedness of the data, and their high dimensionality. Neuroinformatics is a new area of science that draws upon neuroscience, information science, computer science, statistics, applied mathematics, and a variety of engineering fields to develop tools that will let neuroscientists make better sense and use of their data. These tools include software and hardware for digital data acquisition, visualization, analysis, integration, and sharing (e.g., through tools for electronic scientific collaboration). Such tools can address data of any type or from any area of neuroscience; examples include, but are not limited to: 1. Databases, querying approaches, and information retrieval tools for neuroscience and neuroscience-related data. An example would be the development of a web-based database for sharing, analyzing and comparing the pharmacological responses of a variety of CNS active compounds in preclinical studies relevant to mental health. 2. Tools for neuroscience data visualization (and other forms of presentation) and manipulation (probabilistic atlases of brain structure or function, new statistical approaches for analyzing data, etc.). 3. Software for integration and synthesis of neuroscience data (computational models of neurons to integrate data about structure and function, environments to merge data from multiple imaging modalities, etc.). 4. Tools for electronic collaboration to allow neuroscientists to interact with colleagues, data, and instruments at a distance (this could include novel types of “groupware”, etc.). 5. Tools that bridge existing neuroscience and biology information tools and resources, such as databases and informatics tools associated with genome mapping efforts. For further information on basic neuroscience or basic behavioral science research topics, contact: Margaret Grabb, Ph.D. National Institute of Mental Health 6001 Executive Blvd. Room 7201 Mail Stop Code 9645 Bethesda, MD 20892 301-443-3563, Fax: 301-443-1731 Email: mgrabb@mail.nih.gov HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 The Division of Developmental Translational Research directs, plans, and supports programs of research and research training leading to the prevention and cure of childhood psychopathology. This long-term goal will be accomplished through an integrated program of research across behavioral/psychological processes, brain development, environment and genetics. The topics listed below reflect the NIMH interest in technologies related to this research area, but should not be considered a complete list. Prospective applicants are strongly encouraged to contact Dr. Margaret Grabb (listed below) with questions about the relevance of their interests to the mission of this division. A. Technologies for Clinical Pediatric Research. It is important to develop reliable methods that can correctly identify the normal and abnormal components of cognitive, emotional, and psychosocial behavior, as well as normal and abnormal physiological and biochemical functions, in human development. Computer-based methods of accomplishing this are also needed to increase the accessibility and reliability of information made available to the research community. Examples include: 1. Measurements of Alterations in Pediatric Development in Patients with Mental Health Disorders Using Physiological and Behavioral Measures. Research studies indicate that some mental health disorders, such as autism, may begin to develop as early as infancy. Therefore non-invasive modern equipment that use the most recent technological advances are needed to isolate specific physiological and behavioral changes during development, to identify potential diagnostic markers of mental health disorders. A priority for this program is to support research and development of hardware and software tools to measure pediatric development. Examples of technologies needed include: a. Psychophysiological measures to evaluate infants, children or adolescents. b. Miniaturized non-invasive instruments to record psychophysiological data (e.g., heart and respiration rate, galvanic skin response, and defensive motor behavior). c. Telemetry capability for non-invasive devices so that children can be monitored for prolonged periods without interfering with their behavior. d. Computer programs and inexpensive computers that will collect, analyze and identify recurring patterns in the psychophysiological measure(s) of interest. 2. Pediatric Assessment Tool. Diagnosis of mental health disorders in children and adolescents is vital to providing early interventions to treat the disorder. In addition, a better understanding of the concept of functioning in psychopathology, and its appropriate measurement, is needed in pediatric populations. In the future, diagnostic tools may even help detect the initial onset of illness in children at risk, before symptoms occur. A priority for this program is to develop novel diagnostic tools to detect mental health disorders in children and adolescents. Of particular interest to this division are methods that can be used with children and adolescents with limited verbal communication (i.e., very young or developmentally disabled). Biochemical, genetic, physiological and psychological tool development is welcomed. a. Technologies to assess CNS effects of psychosocial or pharmacological interventions. b. Development of reliable and stable biomarkers/biosignatures that can identify at-risk individuals prior to disease onset, biological and behavioral indicators or predictors of treatment response, measures of disease progression, measures to identify dose ranges prior to clinical studies, preclinical or clinical efficacy testing, toxicity measures for drug development, defining patients to enroll in the clinical study, identifying CNS abnormalities, etc. c. Assessment tools for pediatric mental health disorders that are sensitive to developmental change, gender and cultural diversity, variation in cognitive and behavioral functioning, hearing and/or speech impairment, and co-morbid disorders. d. Innovative approaches to assessing mental disorders using new statistical and psychometric techniques such as Item Response Theory. e. Computerized methodologies for assessing various mental disorders suitable for use in primary care settings, e.g. they would need to function rapidly and reliably. f. Biological and behavioral measures to define and assess specific impairment-related components of psychiatric disorders, e.g., cognitive dysfunctions in schizophrenia. g. Development of valid and reliable measures that operationalize functioning within and across developmental periods, and that can be used in a variety of service settings. Such measures can lead to more accurate diagnoses, a better understanding of the impact of psychiatric disorders, and better tracking of treatment effectiveness. 3. Behavior Monitoring and Analysis of Pediatric Mental Health Disorders. a. Improve or create new video devices to monitor human behavior and ease analysis of behavior. b. Computer software to ease analysis of behavior monitored by video or telemetry systems. c. Automated methods to detect specific emotional states using behavioral and autonomic indicators: This Division is specifically interested in technologies that can identify children with heightened or dampened emotional states that could be associated with particular mental health disorders, including children with limited verbal skills (i.e., very young or developmentally disabled). If the technology will primarily be used to investigate basic mechanisms of behavior, the Division of Neuroscience and Basic Behavioral Science at NIMH would be the most appropriate division to contact. 4. Intervention Development for Childhood-Onset Mental Disorders. a. Strategies (e.g., animal behavioral testing, computer simulation) for evaluating, in early developmental periods, the effects of pharmacological agents on specific functional domains and brain circuits associated with mental disorders. b. Strategies (e.g., animal behavioral testing, computer simulation) for evaluating, in early developmental periods, the effects of cognitive or behavioral interventions (e.g., cognitive rehabilitation, attention training) or device-based protocols (e.g., transcranial magnetic stimulation or direct current stimulation) on specific functional domains and brain circuits associated with mental disorders. c. Methods for evaluation of long-term effects of psychotherapeutic drug administration or brain stimulation protocols in developmental animal models. 5. Methodological Research and Development. There is a need to devise new ways of data collection, analysis, management and dissemination. Examples include: a. Technologies that use the most recent technological advances to identify aberrations in the CNS during development, associated with mental disorders. Once these aberrations are identified and localized, rational therapies can be developed and evaluated. b. Innovative, computer-based methods to monitor preventive and treatment intervention efforts and correlate them with outcome measures are needed. Results should be accessible to other interested parties without compromising the privacy of the individual. c. Development of innovative software for addressing the integration of distributed cross-disciplinary data sources into coherent knowledge bases. The data should focus on pediatric mental health disorders. d. Computer-based intervention development for parents or for school settings. e. Development of databases containing detailed genetic and behavioral information on pediatric populations and their families, as resources for the field in investigations of gene x environment interactions. f. Mathematical, statistical and computer algorithms that could be used to analyze large and/or complex data sets. Examples of these data sets include those derived from functional imaging studies. Among other applications, these could be used to segment images such as those obtained from magnetic resonance imagers, filter noise, visualize data or search vast data sets for specified patterns or data (e.g., use of pattern recognition algorithms to search time series data sets obtained from electrophysiological recording of neural activity, or video data obtained from behavioral analysis of genetically altered animals). Improved techniques for path analysis when examining functional imaging datasets would also be of interest. B. Child and Adolescent Treatment and Preventive Intervention Research. An estimated one in ten children and adolescents in the United States suffers from mental illness severe enough to cause some level of impairment. Yet, it remains unclear what treatments are the best and safest for these developing age groups. A priority for this program is to support research and development of novel psychopharmacological or psychosocial approaches for the treatment and prevention of mental illness in childhood and adolescence, in subjects aged 18 and below. The goal of this research is broad and inclusive with respect to the heterogeneity of patients, the severity and chronicity of disorders, and the range of outcomes measured. Disorders studied include all mental and behavioral disorders. Interventions studied include pharmacologic approaches (individual and combination medications), somatic approaches, behavioral and psychotherapeutic approaches. Research is supported on individual and combined approaches. Research that translates findings on basic physiological or behavioral processes into novel preventive or treatment interventions is especially encouraged. Effectiveness studies that focus on interventions of known efficacy are assigned to the Division of Services and Intervention Research. Human subjects include child and adolescent age groups covering the full range of mental disorders individually and in complex patterns of comorbidity with other mental disorders and behavioral problems (e.g., anxiety and depression) and substance abuse (e.g., depression and alcohol abuse). 1. Pharmacologic Treatment Intervention. Clinical testing of novel mechanism therapeutics is the principle aim of this technology development section. This includes Phase IIa and proof of concept studies in pediatric subjects. It is expected the pharmacologic agents selected for these studies be IND-ready and based on novel molecular targets identified through basic and clinical research, preclinical research and animal model research relevant to understanding developmental aspects of mental illness. 2. Combined Intervention. Areas include all research that combines different treatment modalities in a single combined or comparative protocol (e.g., pharmacologic plus psychosocial intervention). 3. Psychosocial Intervention. Areas include development and application of new psychotherapeutic, behavioral, and psychosocial treatments, based on the latest advances in development neuroscience. 4. Preventive Intervention Program. Areas include preventive intervention studies in which efficacy has not been demonstrated, including those designed to reduce the risk of onset or delay onset of mental disorders, dysfunctions and related problems within asymptomatic and subclinical populations and those related to treatment (e.g., prevention of relapse, recurrence) or side effects (prevention/ minimization of tardive dyskinesia, etc.). Prevention studies that focus on behavioral problems, without a focus on a specific mental health disorder or a specific domain of function that significantly impacts a mental health disorder (e.g. cognitive function) should contact NICHD. 5. Development and Maintenance of Clinical Trial Networks. Areas include the development of hardware/software to facilitate research collaborations in conducting clinical trials, technologies to facilitate data sharing, merging of multiple data sets, and the development and maintenance of common protocols across research sites working on a common pediatric preventive or treatment intervention. C. Science Education in Mental Disorders. There is a critical need for improvement in science education, particularly in areas specifically related to brain, behavior and mental illness. Examples include: 1. Research on the best ways to present neuroscience and behavioral science information, in the context of mental health disorders, to particular groups of students (e.g., kindergarten through sixth grade). 2. Computer-based systems to teach students how to observe scientific phenomena related to the brain, behavior and mental illness, and to report them clearly in writing. 3. Research on better ways to communicate new knowledge and directions of scientific growth in the area of neuroscience and mental illness to teachers and curriculum developers. For further information on Developmental Translational Research-related topics, contact: Margaret Grabb, Ph.D. National Institute of Mental Health 6001 Executive Blvd. Room 7201 Mail Stop Code 9645 Bethesda, MD 20892 301-443-3563, Fax: 301-443-1731 Email: mgrabb@mail.nih.gov HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 General Areas of Interest The NINDS accepts a broad range of small business applications that are significant, innovative, and relevant to its mission. Examples of research topics within the mission of NINDS that may be of interest to small businesses are shown below. This list is not all inclusive and some research areas fall into multiple categories. 1. Therapeutics and Diagnostics Development for Neurological Disorders, including biomarker and diagnostic assays, therapeutics (drugs, biologics, and/or devices) for treatment of neurological disorders, and technologies/methodologies to deliver therapeutics to the central nervous system. 2. Clinical and Rehabilitation Tools, including intraoperative technologies for neurosurgeons, rehabilitation devices and programs for neurological disorders, and brain monitoring systems 3. Technology and Tools, including imaging technologies to image the nervous system, neural interfaces technologies, and tools for neuroscience research and drug development. In addition to the research topics listed, NINDS also solicits applications in specific program areas. For additional information about NINDS program announcements, please visit our small business home page at: http://www.ninds.nih.gov/funding/small-business/. Clinical Trials The NINDS is committed to identifying effective treatments for neurological disorders by supporting well-executed clinical trials. NINDS may decline funding of a clinical trial application for programmatic or administrative reasons. SBIR applicants are strongly encouraged to contact Joanne Odenkirchen (contact information provided below) within the NINDS Office of Clinical Research for advice about potential clinical trial applications prior to submission in order to determine the relevance of the proposed research to NINDS and its potential for translating discoveries to clinical interventions for neurological disorders. For more information about what is generally required before trials are funded, applicants are encouraged to review the NINDS Office of Clinical Research webpage ( http://www.ninds.nih.gov/research/clinical_research/index.htm ). Joanne Odenkirchen, M.P.H. Clinical Research Project Manager, Office of Clinical Research 301-496-3104 Email: jo21x@nih.gov NINDS Cooperative Program in Translational Research Although translational research is supported through the general SBIR/STTR program announcement, the NINDS also has a Cooperative Program in Translational research (PAR-08-235). The NINDS Cooperative Program encourages Phase II and Fast-Track applications that directly address the identification and pre-clinical testing of new therapeutics for neurological disorders. The program will facilitate solicitation, development, and review of therapy-directed projects to accelerate the translation of basic research discoveries into therapeutic candidates for clinical testing. This program is specifically directed at projects that include therapeutic leads with demonstrated activity against the intended disease target. The program supports pre-clinical optimization and testing of these leads and projects must be sufficiently advanced that an IND or IDE application to the FDA can be submitted by the end of the project period. The program does not support early-stage therapeutic discovery activities such as high throughput screening. The program also excludes clinical research, basic research, and studies of disease mechanism. This is a milestone-driven cooperative agreement program involving participation of NINDS staff in the development of the project plan and monitoring of research progress. For more information on the NINDS Cooperative Program in Translational Research-Small Business Awards (SBIR[U44]): http://grants.nih.gov/grants/guide/pa-files/PAR-08-235.html. Due to the unique requirements of the NINDS Cooperative Program in Translational Research, applicants are strongly encouraged to consult with Dr. Tom Miller at least three months prior to the next receipt date. Dr. Tom Miller, Ph.D., M.B.A. Program Director, Office of Translational Research 301-496-1447 Email: millert@ninds.nih.gov Countermeasures Against Chemical Threats NINDS manages the NIH Countermeasures Against Chemical Threats (CounterACT) program. CounterACT supports research and development on new and improved therapeutics or diagnostic technologies to prevent or mitigate the toxic effects from exposure to chemical threats, defined as toxic chemical agents that could be used in a terrorist attack against civilians, or those that could be released at toxic levels by accident or natural disaster. This includes the development of new (or support of existing) partnerships between small business and not-for-profit laboratories engaged in this research. The scope of research supported includes early screening for compounds with the desired biological activity, advanced preclinical and efficacy testing, through clinical research with promising candidate therapeutics. For more information on this program, including specific program announcements, please see: www.ninds.nih.gov/counteract. Applicants are strongly encouraged to consult with Dr. David Jett to determine the programmatic relevance of their proposed research. David A. Jett, Ph.D. Program Director, NIH CounterACT Research 301-496-6035 Email: jettd@ninds.nih.gov For additional information on research topics, contact: Ms. Stephanie Fertig, M.B.A. Research Project Manager, Small Business Programs 301-496-1447, Fax: 301-480-1080 Email: fertigs@ninds.nih.gov or for general questions related to the small business program, email: nindssmallbusiness@mail.nih.gov For administrative and business management questions, contact: Ms. Tijuanna Decoster Chief, Grants Management Branch 301-496-9231, Fax: 301-402-4370 Email: decostert@mail.nih.gov HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 This area of interest focuses on the development and evaluation of innovative prevention and intervention programs, or specific materials for integration into existing programs, which utilize state-of-the-art technology and are based on currently accepted clinical and behavioral strategies. Applicants are strongly encouraged to consult with research methodologists and statisticians to ensure that state-of-the-art approaches to design, analysis, and interpretation of studies under this topic are used. Areas that may be of interest to small businesses include, but are not limited to: A. Development and evaluation of innovative prevention/intervention programs, or specific materials for integration into existing programs, which utilize state-of-the-art technology and are based on currently accepted clinical and behavioral strategies. Special emphasis should be placed on the needs of high-risk groups, ethnic and minority populations, youth, children of alcoholics, women, the handicapped, and the elderly. Examples of such materials include school-based curricula, interactive videos, computer-based multimedia programs, training manuals for teachers or parents, and community-based programs. B. Development and evaluation of educational materials designed to intervene with the elderly around specific age-related risks for alcohol problems. Particular attention should be given to age-related reductions in alcohol tolerance, interactions between alcohol and prescription and over-the-counter medications, possible exacerbation of some medical conditions common among the elderly, potential biomedical and behavioral consequences of excessive alcohol use, and the role of alcohol in falls, fires, burns, pedestrian and traffic injuries, and other unintentional injuries. C. Development and evaluation of statistical analysis programs tailored to the design and analysis of alcohol prevention-relevant research. Programs could focus on a variety of areas including: imputation of missing data under varying design assumptions; simulation of distributions of outcomes based on varying mixtures of sample populations; application of chronic or infectious disease models to targeted communities; and models of the potential effect of various policy-based interventions, such as increased taxation or reduction of outlet density by license revocation and control. Robert C. Freeman, Ph.D. 301-443-8820 Email: Robert.Freeman@nih.gov HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 The Division of Microbiology and Infectious Diseases (DMID) supports research to better understand, treat, and ultimately prevent infectious diseases caused by virtually all infectious agents, except HIV. DMID supports a broad spectrum of research from basic molecular structure, microbial physiology and pathogenesis, to the development of new and improved vaccines and therapeutics. DMID also supports medical diagnostics research, which is defined as research to improve the quality of patient assessment and care that would result in the implementation of appropriate therapeutic or preventive measures. DMID does not support research directed at decontamination or the development of environmentally oriented detectors, whose primary purpose is the identification of specific agents in the environment. Note that some of the organisms and toxins listed below are considered NIAID priority pathogens or toxins for biodefense and emerging infectious disease research. Director: Dr. Carole Heilman 301-496-1884 Email: ch25v@nih.gov A. Bacteriology and Mycology Branch. The branch oversees research on medical mycology, hospital infections (including Acinetobacter, Klebsiella, Serratia, Legionella, Pseudomonas, Aeromonas, Enterobacter, Proteus, non-enteric E. coli, actinomycetes and others), staphylococci, enterococci, bacterial zoonoses (plague, anthrax, tularemia, glanders, melioidosis, Lyme disease, rickettsial diseases, anaplasmosis, ehrlichiosis and Q fever), and leptospirosis. Research is encouraged in the following general areas: (1) product vaccines, adjuvants, therapeutics and diagnostics (including target identification and characterization, device or apparatus development, novel delivery, and preclinical evaluation); (2) products to combat antibacterial and antifungal drug resistance; (3) applied proteomics and genomics; (4) host-pathogen interactions, including pathogenesis and host response; (5) genetics, molecular, and cell biology; (6) microbial structure and function; and (7) vector-pathogen interactions or disease transmission to humans via arthropod vectors. Research in the following areas is of particular interest to the branch, but research on all of the above is welcome: · Vaccines, therapeutics, and medical diagnostics for hospital infections · Adjunctive therapies to combat antimicrobial resistance Diagnostics for aspergillosis · Novel approaches for the diagnosis of Lyme disease Contact: Dr. Alec Ritchie 301-402-8643, Fax: 301-402-2508 Email: aritchie@niaid.nih.gov B. Enteric and Hepatic Diseases Branch. Special emphasis areas include vaccines against hepatitis C virus; antimicrobials and antivirals that focus on novel targets such as host-pathogen interactions to combat the development of resistance; vaccines and therapies for botulinum neurotoxins, especially therapies that that target toxins once they enter cells; therapies and diagnostics for Clostridium difficile that include recurrent disease issues; development of a simple, rapid point-of-care diagnostic tool for the simultaneous identification of multiple diarrheal pathogens that includes their antibiotic resistance profiles; pediatric vaccines to prevent the major worldwide causes of diarrhea; more stable vaccines and improved formulation methods; and novel therapeutics for chronic hepatitis B and C. Research areas of the Branch include the following organisms and diseases: astrovirus, Bacteroides spp., Campylobacter spp., enteric Clostridia spp. including botulinum neurotoxins, commensals and normal flora, pathogenic Escherichia coli, gastroduodenal disease, gastroenteritis, Helicobacter spp., Listeria spp., Noroviruses including Norwalk, ricin toxin, rotaviruses, Salmonella serovars, Shigella spp., Staphylococcus enterotoxin B, Vibrio spp. enteric Yersinia spp., hepatitis viruses A, B, C, D, and E, as well as cholera, diarrhea, enterotoxins, gastroenteritis, gastroduodenal disease and ulcers, and Guillain-Barre syndrome. Program Contact: Dr. Marian Wachtel 301-451-3754, Fax: 301-402-1456 Email: wachtelm@niaid.nih.gov C. Parasitology and International Programs Branch. Research areas: (1) protozoan infections, including amebiasis, cryptosporidiosis, cyclosporiasis, giardiasis, leishmaniasis, malaria, trypanosomiasis, toxoplasmosis; helminth infections, including cysticercosis, echinococcosis, lymphatic filariasis, schistosomiasis, onchocerciasis, others (e.g., roundworms, tapeworms, and flukes); invertebrate vectors/ectoparasites, black flies, sandflies, tsetse flies, mosquitoes, ticks, snails, mites; (2) parasite biology (genetics, genomics, physiology, molecular biology, and biochemistry); (3) protective immunity, immunopathogenesis, evasion of host responses; (4) clinical, epidemiologic, and natural history studies of parasitic diseases; (5) research and development of vaccines, drugs, immunotherapeutics, and medical diagnostics, and (6) vector biology and management; mechanisms of pathogen transmission. Chief: Dr. Lee Hall 301-496-2544, Fax: 301-402-0659 Email: lhall@niaid.nih.gov D. Respiratory Diseases Branch. Research areas: (1) viral respiratory diseases, including those caused by: human coronaviruses (including SARS), influenza viruses, and paramyxoviruses (including parainfluenza viruses and respiratory syncytial virus); (2) bacterial respiratory infections, including those caused by Moraxella catarrhalis (chronic obstructive pulmonary disease), Pseudomonas aeruginosa andBurkholderia cepacia (associated with cystic fibrosis), Corynebacterium diphtheriae (diphtheria), groups A and B streptococci,Haemophilus influenzae, Neisseria meningitidis, Bordetella pertussis (pertussis), Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Klebsiella pneumoniae and community acquired pneumonia; (3) acute otitis media; (4) mycobacterial diseases, including those caused by: M. tuberculosis (tuberculosis), extensively- and multi-drug resistant M. tuberculosis, M. leprae (leprosy), and M. ulcerans (Buruli ulcer) and other non-tuberculous mycobacterial diseases. Areas of emphasis include: development of new antibiotics with novel mechanisms of action, improved therapeutics for viral and bacterial respiratory diseases including immunotherapeutics, new or improved vaccines (with and without adjuvants), improved and more rapid multiplex point-of-care diagnostic tests or other screening tools that can detect infection prior to active disease and identify drug resistance. Contact: Dr. Gail Jacobs 301-496-5305, Fax: 301-496-8030 Email: ggjacobs@niaid.nih.gov E. Sexually Transmitted Infections Branch. Areas of emphasis include the development of medical diagnostics including better and more rapid multiplex point of care tests and other screening or novel delivery systems for diagnostic tools, topical microbicides, vaccines and drugs for sexually transmitted infections (STIs) and other reproductive tract syndromes, such as bacterial vaginosis; molecular immunology; vaginal ecology and immunology; epidemiologic and behavioral research including strategies to reduce transmission of STIs; genomics and proteomics of sexually transmitted pathogens; adolescents and STIs; STIs and medically underserved populations and minority groups; STIs and infertility and adverse outcomes of pregnancy; role of STIs in HIV transmission; role of HIV in altering the natural history of STIs; and other sequellae of STIs. Contact: Elizabeth Rogers 301-451-3742, Fax: 301-480-3617 Email: erogers@niaid.nih.gov F. Virology Branch. Areas of emphasis for SBIR/STTR applications include:1) vaccine development; 2) viral vectors; 3) structure and function of viruses and viral proteins as targets for therapeutic interventions or diagnostics; 4) the development and validations of assays for disease diagnosis and to measure response to therapy; 5) the development and preclinical testing of immunotherapeutic and antiviral drugs for acute and chronic viral illnesses; 6) approaches to identify antiviral targets and agents; 7) chemical design and synthesis of novel antiviral agents; 8) preclinical antiviral evaluations including in vitro screening and prophylactic or therapeutic antiviral evaluations of human viral infections in animal models; 9) the development of rapid medical diagnostic systems. The Virology Branch focuses on the following: acute viral infections (including Nipah and Hendra viruses), arthropod-borne and rodent-borne viral diseases (including Dengue, West Nile, Japanese encephalitis, Chikungunya, yellow fever, hantavirus, etc.), viral hemorrhagic fevers (Ebola, Lassa fever, etc.), measles, polio, coxsackie virus, enterovirus 71 and other enteroviruses, poxviruses, rabies, and rubella. The Virology Branch also focuses on the following persistent viral diseases and viruses: adenoviruses, BK virus, bornaviruses, coronaviruses, herpesviruses, human T-lymphotrophic virus, JC virus, human papillomaviruses, parvoviruses, and prion diseases. Applications targeting the development of therapies, immunotherapies, vaccines and diagnostics for any of these infections are sought. The Virology Branch does not support applications covering environmental detection and decontamination. Contact: Dr. Ramya Natarajan 301-594-1586, Fax: 301-402-0659 Email: ramya.natarajan@nih.gov HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 The Division of Cancer Treatment and Diagnosis funds research into the development of tools, methodologies and therapeutic agents that will better diagnose, assess, cure and effectively treat cancer. We support a spectrum of research projects from preclinical exploratory research and development through clinical trials. A. Cancer Diagnosis. The Cancer Diagnosis Program (CDP) supports the development of technologies, reagents, instrumentation, and methodologies to improve cancer diagnosis or prognosis or to predict or assess response to therapy. This does not include technologies for imaging of patients. CDP also supports the adaptation or improvement of basic research technologies for use as clinical tools. Technologies supported by CDP may be designed to work with tissues, blood, serum, urine, or other biological fluids. Technologies supported by CDP include but are not limited to the following: 1. Technologies for comprehensive and/or high throughput analysis of molecular alterations at the level of DNA, RNA, or protein. Includes for example, mutation detection systems, gene expression arrays, systems for monitoring epigenetic changes (alternative splicing or methylation), high throughput proteomics (including post-translational modification and protein-protein interactions and methods for protein quantitation). 2. Micro-electro mechanical systems (MEMs) and other nanotechnologies for the analysis of DNA, RNA, or protein (e.g., micro-capillary systems, lab on a chip applications, micro-separation technologies). 3. Mass spectrometry for the analysis of nucleic acids or proteins. 4. Discovery and development of new or improved diagnostic markers or probes targeting changes in DNA, RNA, or proteins, including the generation of molecular diversity libraries by phage display and other combinatorial techniques, and affinity-based screening methods. 5. cDNA library technologies, including improved methods for generating high quality cDNA clones and libraries and methods for generating high quality cDNA from tissues (including archived specimens). 6. Resources for clinical research. a. Instruments, technologies or reagents for improved collection, preparation, and storage of human tissue specimens and biological fluids. b. Improved methods for isolation and storage of DNA, RNA, or proteins. c. Tissue and reagent standards: development of standard reagents such as representational DNA, RNA, and proteins and standard tissue preparations to improve the quality of or facilitate the validation of clinical laboratory assays. d. Methodologies for directed micro-sampling of human tissue specimens, including for example, new or improved methodologies for tissue microarrays. 7. Tissue preservation: fixatives and embedding materials or stabilizers that preserves tissue integrity and cellular architecture and simultaneously allows molecular analysis of DNA, RNA, or proteins. 8. Bioinformatics. a. Methods for acquisition and analysis of data associated with molecular profiling and other comprehensive molecular analysis technologies, including for example, analysis of microarray images and data as well as methods to combine, store and analyze molecular data produced by different techniques (e.g., combined analysis of proteomics and gene expression data). b. Methods for collecting, categorizing or analyzing large data sets containing pathology data or histological images and associated clinical or experimental data, including for example, tumor marker measurements, tissue microarray data, and other relevant biological information. c. Software/algorithms to interpret and analyze clinical and pathology data including methods that relate data from clinical databases to external data sources. Includes for example, neural networks, artificial intelligence, data-mining, data-trend analysis, patient record encryption protocols, and automatic diagnostic coding using standard nomeclatures. d. Informatics tools to support tissue procurement and tissue banking activities. 9. Statistical methods and packages designed for data analysis including correlation of clinical and experimental data. 10. Automated Cytology. a. High resolution image analysis for use with specimens (e.g., blood, tissues, cells) and tissue microarrays. b. Instrumentation including microscopy and flow cytometry. c. CGH, FISH, immunohistochemical staining and other hybridization assays using probes with fluorescent or other novel tags. d. Methods for single cell isolation and sorting. e. Methods for single cell classification and analysis. 11. Instrumentation for the detection and diagnosis of tumors, including endoscopy and magnetic resonance spectroscopy (MRS). 12. Immunoassays using monoclonal, polyclonal, or modified antibodies. Affinity-based binding assays using libraries of aptamers including chemical ligands, small peptides or modified antibodies. For additional information about areas of interest to the CDP Technology Development Branch, visit our home page at: http://cancerdiagnosis.nci.nih.gov. B. Biochemistry and Pharmacology. Preclinical and Exploratory Investigational New Drug (IND) studies designed to improve cancer treatment. General areas of interest: Discovery of new drugs or drug combinations and treatment strategies, selective targeting, development of clinically relevant preclinical models, pharmaceutical development, ADME (absorption, distribution, metabolism and excretion) studies and toxicologic evaluations, understanding mechanisms of drug actions (responses to therapies), and preventing and overcoming drug resistance. Areas of current emphasis: Molecular targeted approaches, including application of safety and efficacy biomarkers to the discovery and development of drugs; application of advanced technologies, such as nanotechnology and imaging technologies, to improved assays for quantitation of safety and efficacy biomarkers; approaches that reduce costs and increase speed of preclinical drug development; and approaches that will lead to “personalized medicine,” including better predictions of drug response and adverse reactions, drug-drug interactions, and drug efficacy monitoring. For additional information, please visit our home page at http://dtp.nci.nih.gov and select “Grants/Contracts.” 1. Drug Discovery. a. Design and synthesize novel compounds for evaluation as potential anticancer agents. Synthesize simpler analogs of complex antitumor structures that retain antitumor activity. b. Develop computer modeling and biophysical techniques such as x-ray crystallography and NMR spectroscopy. c. Design prodrugs of anticancer agents that are selectively activated in cancer cells. d. Discover new anticancer agents that exploit unique properties of tumors, that induce or modulate apoptosis, or that induce or modulate differentiation. e. Design and synthesize anticancer prodrugs, latent drugs, or modifiers of cancer drug metabolism or excretion. f. Develop ways to produce adequate quantities of promising natural products or natural product derivatives through total synthesis. g. Develop scale-up and manufacturing technology for the synthesis of materials with promising anticancer potential. h. Develop chemical libraries for anticancer drug screening programs. The generation of small molecular weight libraries (<700 MW, e.g., non-polymeric organic molecules, transition-state analogs, cyclic peptides, peptidomimetics) is encouraged. i. Develop and apply technologies in genetics, genomics, proteomics, glycomics, lipidomics, metabolomics, and systems biology to the discovery of potential drug targets associated with multiple pathways or networks. Design and optimize agents that block or activate targets/pathways that are likely to control, re-program, retard or kill cancer cells, especially cancer initiating cells (often called cancer stem cells). 2. Drug Evaluation. a. Develop and evaluate anti-metastatic and/or anti-angiogenesis agents or strategies, including combination therapies, in appropriate model systems. b. Develop and evaluate anticancer gene therapy in appropriate model systems. The development of new gene delivery approaches is encouraged. c. Develop novel or improved in vitro and in vivo test systems. There is a special need for new types of in vivo tumor models, such as orthotopic tumor models, models using transgenic or gene knockout animals, and models to evaluate agents that induce differentiation or apoptosis or that target cancer initiating cells (often called cancer stem cells). d. Develop strategies to detect, prevent, or overcome drug resistance. e. Develop novel treatment strategies such as extra corporeal treatment. f. Develop new assays based on molecular targets, especially those that may be amplified or altered in cancer cells. For example, develop assays for agents that interact with oncogenes, suppressor genes, signal transduction pathways, transcription factors, or promoters. Assays based on molecular targets that can be adapted for high volume screening of chemical libraries are especially encouraged as well as in vivo models, which can be used for “proof of concept” (i.e., validating selectivity of the agent for the target and confirming that modulation of the target results in antitumor activity). g. Develop cost-effective and useful techniques to improve in vitro cell culture methodology, such as the development of automated systems, serum-free media, or carbon dioxide-free buffering systems to stabilize cell culture performance. h. Identify and employ novel targets for antitumor drug discovery utilizing non-mammalian genetically defined organisms, such as fruit flies, worms, zebrafish and yeast. i. Develop and apply technologies such as microarrays, proteomics or RNAi to improve the efficiency of drug discovery. j. Develop cell lines that contain bioluminescent reporter genes, such as luciferase, that can be controlled by activating specific promoters. 3. Pharmaceutical Development. a. Develop new methods to improve drug solubility for administration of promising antitumor compounds, such as water miscible nontoxic water solubility enhancing agents. b. Develop bioavailable alternatives to the intravenous delivery of cytotoxic chemotherapy. For example, develop new excipients to enhance oral bioavailability of anticancer agents. c. Develop biocompatible additives and excipients for highly concentrated proteins and peptide formulations to enhance bioavailability and stability suitable for subcutaneous delivery of agents. d. Develop improved methods to reduce thrombophlebitis and other related side effects observed following intravenous injection of some anticancer drugs. e. Develop new and innovative techniques for sterilization of parenteral dosage forms. f. Develop in vitro and in vivo models to predict human oral bioavailability of anticancer drugs. g. Develop practical delivery systems involving nanotechnology (dendrimers, nanoparticles, nanoshells, etc.) or other strategies to deliver anticancer drugs to specific target sites. h. Develop new technology to manufacture liposomal and intravenous emulsions in an environmentally friendly manner and in accordance with OSHA standards. i. Develop additives and/or processes to eliminate cold chain storage of biotherapeutic agents, especially vaccines. 4. Toxicology and Pharmacology. a. Develop biochemical or molecular (genomic, proteomic, or metabolomic) response profiles of specific target organs (e.g., bone marrow, gastrointestinal tract, liver, kidney, heart, lung) to permit rapid identification of toxic effects resulting from anticancer drug administration. b. Develop clinically relevant in vitro and/or in vivo tests for estimation and prediction of gastrointestinal toxicity, neurotoxicity (central and peripheral), cardiotoxicity, hepatotoxicity, nephrotoxicity and pulmonary toxicity. c. Correlate in vivo and in vitro models for organ toxicity as described above in 4b. Validate for various anticancer drugs. d. Develop drug metabolism (Phase I and Phase II) profiles for anticancer agents in human, mouse, rat and dog liver S-9, microsomes and slices. e. Develop systems to identify toxic effects of drugs by characterizing reactions with biomolecules or receptors. f. Develop in vitro tests to detect, qualify and quantify toxic effects of antineoplastic drugs. Develop techniques for determining individual variations in drug responses due to genetic polymorphisms or other factors. Develop pharmacodynamic endpoints and surrogate endpoints using appropriate biomarkers to aid in the selection of doses and schedules and the monitoring of responses and toxicity. g. Develop personal computer programs for pharmacokinetics models capable of predicting drug behavior in humans from preclinical pharmacokinetics data in mice, rats, dogs, and non-human primates. h. Investigate and develop techniques for relating specific enzyme activities (both catabolic and anabolic) to body sizes of different species. i. Investigate techniques that would allow parameters, e.g., Km and Vmax for enzymes, to be scaled from preclinical to clinical models. j. Develop analytical strategies applicable to the quantitation of potent anticancer drugs in biological fluids at the pg/ml level, e.g., Bryostatin. k. Develop non-invasive techniques to determine drug distribution in various animal models. l. Evaluate interspecies transporter distribution and its impact on pharmacokinetic parameters, e.g., the impact of pharmacogenetic variation in biodistribution. m. Determine optimal pharmacokinetic sampling schedules for use in dose titration/pharmacodynamic assessment by integrating information such as pre-clinical pharmacokinetic data, physico-chemical drug properties and mechanism of action. n. Develop an in vitro/in situ system for high throughput drug screens for oral bioavailability. o. Develop and deliver organ specific chemo-protective agents. p. Develop and evaluate rapid, cost-effective methods, including biochemical, functional multiplexed, imaging, nanotechnology-based, and microfluidics-based assays, to quantitate surrogate endpoints for determination of doses, dosing schedules, safety, and efficacy of drugs. q. Identify and develop biomarkers to evaluate drug activities and toxicities. r. Develop assays in support of Exploratory Investigational New Drug Studies using biomarkers or other appropriate endpoints. s. Develop, standardize, and validate cost-effective tools for obtaining comprehensive ADME and toxicology profiles that may better predict the performance of drugs in humans. t. Develop and analytically validate assays or tools for measuring safety, efficacy, and dosing biomarkers. 5. Animal Production and Genetics. a. Investigate alternatives to expensive barrier systems for exclusion of pathogens from rodent colonies, e.g., by use of micro-isolator cages, and evaluate their performance. b. Develop and evaluate specialized shipping containers for pathogen-free animals. 6. Natural Product Discoveries. Note that execution of projects in most of these topic areas will require collaboration and signed agreements with countries where the source organism was originally collected. a. Develop techniques for the study of non-culturable organisms in order to identify antitumor agents. b. Develop techniques for the genetic and biochemical characterization and the manipulation of biosynthetic pathways to create leads. Use combinatorial biosynthesis to generate libraries of un-natural natural products as drug leads. c. Use genetic techniques for the identification of microbial consortia, and for the identification and isolation of genes controlling the biosynthetic pathways producing potential antitumor agents. d. Express biosynthetic pathways from microbes or microbial consortia that are known to produce antitumor agents, but in organisms amenable to standard fermentation techniques. e. Investigate new biological methods, such as tissue culture, aquaculture, hydroponics, etc., for the production of natural products as potential anticancer agents. f. Develop new systems of large-scale production using biotransformation, tissue or cell culture, biotechnology, modification of the chemical ecology of producing organisms, etc., in order to produce the large quantities of anticancer drugs needed for preclinical or clinical development. g. Develop methods for the isolation, purification, identification, cultivation, and extraction of microorganisms from unusual marine or terrestrial habitats for antitumor screening. Examples are gliding bacteria, barophilic, endophytic, thermophilic, and tropical canopy organisms. h. Investigate newer methods of isolation and purification, such as super-critical fluid extraction and chromatography, centrifugal countercurrent chromatography or affinity-based separations, in the isolation and purification of natural products with anticancer activity. i. Develop simple immunoassays that can be used to monitor the levels of natural products of interest in simple extracts of the relevant raw material. These assays should be capable of being developed for use “in the field” and also in developing countries. j. Develop analytical and biological methods for isolation, purification and validation of active constituents identified from alternative medicine and complementary studies; use of these purified constituents alone or in combination with conventional anticancer agents. 7. Data Management Systems. a. Develop data support systems for chemical library programs. b. Develop bioinformatics tools to accelerate the identification, functional understanding and validation of drug targets. c. Develop bioinformatics tools to predict ADME and toxicology characteristics of drug candidates. d. Develop “data mining” strategies such as neural networks. e. Develop algorithms for determining optimal drug combinations and for prediction of optimal effectiveness of individual agents. f. Develop bioinformatics tools to support a systems biology approach to drug discovery and development. g. Develop bioinformatics tools to support genomic/proteomic and other "omics" profiling experiments in support of drug discovery and development. C. Cancer and Nutrition. Research to improve the methodology of nutritional assessment in a cancer population. Innovative approaches to evaluate the contribution of nutritional status to response to cancer treatment. 1. Research to improve the methodology of nutritional assessment in a cancer population. 2. Develop means to evaluate the contribution of nutritional status to response to cancer treatment. D. Clinical Treatment Research. Clinical research studies designed to improve cancer treatment. Emphasis is on clinical trials for the evaluation of new therapeutic agents, development of assay systems to measure patient response to chemotherapy, development of prognostic assays, and development of methods of analysis and management of clinical trials data. Studies designed to improve human subject protections for patient access to clinical cancer trials. 1. Evaluation of New Cancer Therapies. a. Conduct clinical trials for the evaluation of new therapeutic agents or modalities of treatment employing drugs, biologics or surgery. b. Clinical trials using “unconventional therapies,” including, but not limited to, behavioral and psychological approaches, dietary, herbal, pharmacologic and biologic treatments, and immuno-augmentative therapies. c. Development and evaluation of new clinical approaches using gene transfer or gene therapy technologies. d. Development and evaluation of new clinical approaches using tumor associated antigens or vaccines in order to enhance immunogenicity. e. Develop and characterize novel chemical compounds that may be useful anticancer agents, either alone or in combination with other modalities such as radiotherapy. f. Develop techniques to lessen the toxicity of existing anticancer treatments. g. Develop new techniques for the delivery of anticancer agents that will maximize therapeutic effects and minimize toxicity. h. Develop new surgical techniques or tools or improve existing techniques that are/may be utilized in cancer treatment. i. Characterize and produce clinical grade monoclonal antibodies to detect and treat malignancies. 2. Development of Prognostic Assays to Monitor Patient Response to Therapies. a. Develop assay systems to measure the response of human tumors to chemotherapy or biologics. b. Characterize drug resistance mechanisms and design methods to overcome clinical drug resistance. c. Develop assays for prognostic factors to identify patient subsets who may benefit from specific cancer treatment therapies. d. Development of assays to assess effects of agents on specific molecular targets in clinical studies. e. Develop new techniques for relating past preclinical information to past clinical results for prediction of future useful clinical agents from future preclinical data (both in vitro and in vivo). 3. Clinical Trials Informatics. a. Develop new tools and methodologies for the analysis of clinical trials results. b. Develop new informatics tools to facilitate clinical trials data entry from the bedside and coordination of data entry and transmission throughout the institution and to other collaborating institutions or organizations. c. Development of novel web-based approaches to clinical trials informatics for transmission of data to NCI or other organizations. Topics include point of treatment data capture and reporting, electronic protocols, OLAP (On-line Analytical Processing), support for the Common Toxicity Criteria, and drug accountability support. d. Develop new interchange standards, based on technologies such as XML, for sharing data among heterogeneous systems. Specific applications areas include, Adverse Even Reporting, Case Report Forms. e. Develop new tools for support of Common Data Elements. f. Develop new approaches for interface with electronic medical records, with intent to streamline data reporting, registration, and toxicity reporting of Clinical Trial information. E. Cancer Imaging Program. The mission of this program is to promote and support: Cancer-related basic, translational and clinical research in imaging sciences and technology, and integration and application of these imaging discoveries and developments to the understanding of cancer biology and to the clinical management of cancer and cancer risk. Toward this effort, CIP 1) funds research in the development of tools, methodologies and imaging agents/probes that will better diagnose, assess, and effectively treat cancer, and 2) supports a spectrum of research projects from preclinical exploratory research and development through clinical trials. Areas of interest include but are not limited to: 1. Development of medical imaging systems for early cancer detection, screening, response to therapy and interventions including image-guided therapy. 2. Development of preclinical and clinical in vivo imaging systems, methods, imaging probes and contrast agents and related image reconstruction, image processing, image display and image-based information as required to detect, classify, monitor and guide therapeutics to cancer and precancerous conditions. 3. Development of methods to assess the value of imaging procedures for the above goals. 4. Development of systems and methods for improved production and distribution of radioactive materials for cancer imaging and/or treatment. 5. Development of systems, methods and their optimization for studying the adverse reactions/effects of image-guided and other diagnostic and therapeutic interventions. 6. Any other investigator-initiated research idea that is relevant to cancer biomedical imaging. 7. Development of systems, methods and their optimization to advance the role of imaging in assessment of response to therapy through increased application of quantitative anatomic, functional, and molecular imaging endpoints in clinical therapeutic trials and dissemination of these systems and methods with appropriate scientific communities. F. Radiation Research. The Radiation Research Program (RRP) supports basic, developmental and applied research (including clinical) related to cancer treatment utilizing ionizing and non-ionizing radiations. Therapeutic modalities include photon therapy, particle therapy, photodynamic therapy (PDT), hyperthermia, radioimmunotherapy (RIT), systemic targeted radionuclide therapy (STaRT), and boron neutron capture therapy (BNCT). Radiation research encompasses a range of scientific disciplines including basic biology, chemistry, physics and clinical radiation oncology. Topics of interest include, but are not limited to, the following areas: 1. Development of devices for planning, measuring, and delivering radiation therapy or related therapies, including devices for patient positioning and quality assurance for the following: (a) ionizing radiation, particularly 3-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT); (b) PDT; (c) hyperthermia; (d) RIT; (e) STaRT; and (f) particle therapy. 2. Development of devices for dosimetry for (a) ionizing radiation; (b) PDT, particularly those capable of measuring light doses at depth in tissues; (c) thermometry for hyperthermia, particularly non-invasive thermometry; and (d) RIT. Devices may include chemical, solid state, film, biological or ionization systems to detect or read out exposures. Accuracy, precision and linear response are essential over the range of doses and temperatures employed in the research laboratory and/or in the clinic, depending on their intended use. Devices for thermometry during hyperthermia treatment must give accurate readings with the heating device(s) with which they are to be used. 3. Development and evaluation of computer hardware and software for radiation therapy, such as computation algorithms, computer workstations, image guidance techniques, and informatics methods for treatment planning, delivery and outcomes analysis. 4. Development of novel drugs to increase the effectiveness of radiation therapy or related therapies: (a) chemical modifiers of radiation response, particularly small molecules directed at molecular targets involved in tumor radioresistance; (b) photosensitizers for PDT; (c) sensitizers for use with hyperthermia; and (d) prodrugs that are selectively activated within the tumor. 5. Development of drugs to prevent, reduce or reverse normal tissue response, especially the late effects that develop months or years after therapy. Compounds that are based on a rationale for achieving a therapeutic gain (an improved differential response between tumor and normal tissue) are of greatest interest. Enhancement of response must be achieved at radiation doses and treatment schedules employed clinically. 6. Development of predictive assays and monitors of response to radiotherapy, PDT, hyperthermia, STaRT, or RIT. Tools are needed to identify patients that would benefit from specific therapeutic approaches. G. Biological Response Modifiers (BRM). Research on agents or approaches that alter the relationship between tumor and host by modifying the host's biological response to tumor cells with resultant therapeutic benefits. Both preclinical and clinical investigations are conducted on the utility of a wide variety of natural and synthetic agents and on biological manipulations of immunological and non-immunological host mediated, tumor-growth controlling mechanisms in cancer therapy. Studies are encouraged which utilize in vitro assays and/or animal model systems to investigate mechanisms of BRMs. Examples of innovative research include but are not limited to: 1. Evaluation of molecular genetic approaches to discovery of new therapeutic agents, delivery of BRMs or development of gene therapy. 2. Development of improved techniques to synthesize, screen and develop new oligonucleotides including iRNA sequences for therapeutic purposes, such as signal modulation, anti-oncogene or anti-viral effects. 3. Improvement in cell-culturing techniques, e.g., by developing automated cell culture systems, specialized media, or improved methods to induce activation, proliferation or differentiation. 4. Development of new procedures or reagents for the modulation of the suppressor arm of the immune system in experimental models, directed towards successful immunotherapy. 5. Improvement of tumor-associated antigens or vaccines in an attempt to enhance immunogenicity. 6. Evaluating autoimmunity in the context of anti-tumor response in vivo to vaccines. 7. Development of novel in vitro assays for the primary screening of BRMs. 8. Application of observations describing shared receptors and mediators between the neuroendocrine and immune systems in studying immunobiology and immunotherapy of cancer. 9. Development and optimization of viral oncolytic agents. 10. Development of novel or improved methods for process development and manufacture of biotherapeutics, including but not limited to antibodies, recombinant proteins, peptides, oligonucleotides, and products based on viral or bacterial vectors, per executive order (E.O. 13329) mandating federal agencies assist the private sector in manufacturing innovation efforts. 11. Development of innovative methods for monitoring the manufacturing process for biotherapeutics using in-line or on-line process analyzers to improve the efficiency of process controls and determination of production end-points (see Guidance for Industry, PAT-A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance, www.FDA.gov). 12. Development of methods to more efficiently assess factors related to the ultimate product quality, safety and efficacy of biologics. HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 A. Prevention Research Branch (PRB). The Prevention Research Branch (PRB) supports a program of research in drug abuse and drug related HIV prevention to (1) examine the efficacy and effectiveness of new and innovative theory-based prevention approaches for drug abuse, drug-related HIV/AIDS and other associated health risks, (2) determine the cognitive, social, emotional, biological and behavioral processes that account for effectiveness of approaches, (3) clarify factors related to the effective and efficient provision of prevention services, and (4) develop and test methodologies appropriate for studying these complex aspects of prevention science. Prevention Research. Rigorous scientific prevention research is encouraged to study novel approaches to substance abuse prevention for use at multiple levels of the social environment including: the family, schools, peer groups, community and faith-based organizations, the workplace, health care systems, etc. The purpose of this research is to determine the efficacy and effectiveness of novel program materials, training strategies, and technologies developed to prevent the onset and progression of drug abuse and drug-related HIV/AIDS infection. Materials and technologies may target a single risk-level or may take a comprehensive approach encompassing audiences at the universal, selective, and/or indicated levels. Universal interventions target the general population; selective target subgroups of the population with defined risk factors for substance abuse; indicated interventions target individuals who have detectable signs or symptoms foreshadowing drug abuse and addiction, but who have not met diagnostic criteria. NIDA encourages the development and testing of innovative prevention intervention technologies that are sensitive and relevant to cultural and gender differences. 1. Laboratory studies of the underlying mechanisms and effects of various prevention approaches such as persuasive communication (e.g., mass media and print media) as they are affected by and effect drug related cognition, emotion, motivation and behaviors. 2. Decomposition of prevention programs, practices and strategies to understand components that account for program effectiveness. 3. Research on features of prevention curricula, materials, implementation, approaches, training, technical assistance, and systems integration that contribute to positive outcomes. 4. Training modules and ongoing technical assistance for program implementers of research based substance abuse prevention programming strategies. 5. Prevention intervention dissemination technologies and mechanisms that integrate research with practice; specifically the transfer of drug abuse prevention information to decision-makers, funders, and practitioners. 6. Prevention services research on the organization, financing, management, delivery, and utilization of drug abuse prevention programs. 7. State-of-the-art and practical strategies for the integration of evidence-based prevention approaches into existing prevention service delivery systems. 8. Studies that develop and assess reliability and validity of developmentally appropriate self-report, physiological, and biochemical measures for use in prevention trials in a variety of settings and a variety of audiences. 9. Development of and testing of environmental change strategies for schools, neighborhoods, communities, etc. to use in reducing substance use initiation and/or progression. 10. Development of practical and affordable community tools for: needs and resource assessment, selection of appropriate evidence-based programs and strategies, high-quality implementation of identified programs and strategies, evaluation at community, organization and individual levels, and sustainability. 11. Drug abuse prevention methodological research on promising data collection, data storage, data dissemination, and reporting techniques. 12. Promoting wider and more effective (e.g. with enhanced fidelity) use of evidence-based prevention interventions for substance abuse and related HIV prevention, including interventions made available thru CDC and other federal agencies. 13. Studies applying technologies and strategies that have been developed for use in other disciplines in order to examine the utility of their application for drug abuse prevention, such as virtual reality technologies being used for some clinical conditions (e.g. phobias, eating disorders), and serious video games are being used for some clinical conditions (e.g., cancer patients), but not for drug abuse prevention. 14. Development and testing of innovative drug abuse prevention intervention products, using discoveries from the basic biological (e.g. neurobiological), psychological (e.g. emotional, behavioral, cognitive, and developmental) and social (e.g. social learning, peer network, and communications) sciences. 15. Development and testing of adaptations for efficacious prevention research approaches to make these more appropriate for special populations including racial and ethnic minorities, non-English speaking populations, immigrant populations, rural and migrant populations, low literacy populations, or persons with disabilities. 16. Development of methods, state-of-the-art tools and systems for community coalition-building. 17. Development and testing of tools to measure intervention costs, cost effectiveness, and net economic benefits. 18. Development and testing of rapid assessment tools of sexual and drug use risk behaviors for use in health care and public health environments, including STI clinics and AIDS research centers. 19. Development and testing of tools to promote security and appropriate prescribing of scheduled prescription drugs. Technologies can be developed to assist medical professionals, schools, service providers and others in making prescribing decisions, educating patients and their caretakers, or dispensing and monitoring of medications. 20. Development of new technologies to support drug abuse prevention interventions with military personnel, veterans and their families. Tools can include adaptations of efficacious and effective drug abuse prevention interventions to maximize health care efficiencies and to address negative life stress resulting from sustained combat operations, a major contributor to both the onset and exacerbation of substance abuse and mental health problems. 21. Development of new technologies for delivery and implementation of efficacious drug abuse prevention interventions for rural and frontier communities. Augie Diana, Ph.D. 301-443-1942 Email: dianaa@nida.nih.gov B. Epidemiology Research Branch (ERB). The ERB supports a research program on drug abuse epidemiology that includes (1) studies of trends and patterns of drug abuse and related conditions such as HIV/AIDS in the general population and among subpopulations, (2) studies of causal mechanisms leading to onset, escalation, maintenance, and cessation of drug abuse across stages of human development, (3) studies of person–environment interactions, (4) studies of behavioral and social consequences of drug abuse, (5) bio-epidemiologic studies including genetic epidemiology studies, (6) methodological studies to improve the design of epidemiologic studies and to develop innovative statistical approaches, including modeling techniques. 1. Improvement of Reliability and Validity of Reporting of Sensitive Data. The reliability and validity of self-report of drug use and related behaviors (e.g., HIV risk behavior) is a matter of great concern. Use of new technologies for real time data collection in ecological settings is of great interest because these technologies enable collection of drug consumption data in context. Studies to improve methodologies based on variations of standard survey protocols or computer-assisted self-interview (CASI) and personal interview (CAPI) are also encouraged. 2. Instrument Development. Easy-to-use assessment instruments are needed to enhance epidemiology research. Areas of interest include but are not limited to: a. Community Assessment. The development of community diagnostic instruments for psychometrically sound assessment of community characteristics is essential to improve our understanding of how community factors affect drug abuse and ensuing behavioral and social consequences. Standardized assessments of community characteristics are needed to better understand the full impact of drug use and to develop targeted interventions to specific community needs. b. Assessment of Psychiatric Comorbidity in Community Settings. Easy to use, reliable, and valid instruments are needed to assess psychiatric comorbidity in different populations of drug abusers, including adolescents and those in community drug abuse treatment settings. c. Assessment Instruments to Measure CNS Function Related to Drug Abuse. The development of age-appropriate assessment instruments to measure behavioral and cognitive function over the course of development will contribute to our understanding of vulnerability to drug abuse and functional impairment due to drug use. 3. Development of State-of-the-Art Mechanisms for Epidemiological Research. The development of state-of-the-art mechanisms to facilitate the use of Geographical Information Systems (GIS) in community epidemiology studies (for example Community Epidemiology Work Groups) and other drug abuse research is if great interest. There is a need for enhanced software and hardware for GIS interfaces, database management, visualization, and innovative spatial analysis capabilities. The role of GIS in public health management and practice continues to evolve. Application of this technology is an important step towards better understanding drug abuse issues and their inherent complexities. The ability to evaluate geospatial information provides a unique perspective of public health issues such as emerging and shifting epidemics, the utilization of treatment services, and rapid assessment of the impact of incidents ranging from natural disasters to bioterrorism. When used alongside more traditional epidemiological techniques, GIS provides epidemiologists the ability to address new questions, refine, or enhance existing analyses. Bethany Deeds, Ph.D. 301-402-1935 Email: deedsb@nida.nih.gov 4. Improving Measures of Addiction Risk. Individual differences in risk for drug addiction are often expressed in degree rather than kind, that is, as gradations along an underlying continuum that stretches from unobservable variations in risk for addiction to extreme and fully debilitating addiction severity. Assessment instruments in use today for measuring drug addiction (i.e., compulsivity in seeking and using drugs despite harmful consequences) have proven reliability and validity, but are of limited use for evaluating individual differences in risk for drug addiction. Advances in computerized adaptive testing methods, computer-assisted technologies, and psychometrics, including item response theory, suggest that the capabilities now exist for the development of the next generation in addiction assessment. New assessment instruments are needed to detect meaningful variation between, within, and across individuals over time that is scalable along the dimension of risk for addiction; these instruments should allow for efficient assessment of the risk construct with minimal burden for administration, training, and cost to the researcher, clinician, research participant, or patient; and they should ultimately provide valid and reliable scores corresponding to established diagnostic criteria for substance use disorders. Elizabeth Lambert, M.Sc. 301-402-1933 Email: elambert@nida.nih.gov 5. Developing, Validating, Refining Tools for Ecologic Momentary Assessment. Ecologic Momentary Assessment (EMA) includes the measurement of exposures and events in real time as they occur, and in the natural environment where they occur, such as the home, neighborhood, or workplace. EMA tools include portable technologies for longitudinal data collection in the field, such as mobile phone electronic diaries and PDAs, geopositioning devices, motion sensors, biosensors, environmental sensors, and audiovisual devices. In addiction and behavioral research, new EMA tools may enhance the contextual and temporal resolution of exposures, and the biological or behavioral processes presumed to occur in response. Specific challenges to address in the implementation of EMA include optimizing the timing of measurement and data quality, establishing sensor validity and reliability in different populations, reducing intensely longitudinal data for statistical analysis, achieving user acceptability, and safeguarding user privacy. Studies are encouraged that address these and other challenges to improve the validity and acceptability of EMA tools. Louise Eideroff, Ph.D. 301-451-8663 Email: wideroffl@nida.nih.gov C. Services Research Branch (SRB). The SRB supports a program of research on the effectiveness of drug abuse treatment with a focus on the quality, cost, access to, and cost-effectiveness of care for drug abuse dependence disorders. Primary research foci include: (a) the effectiveness and cost-benefits and cost-effectiveness of drug abuse treatment, (b) factors affecting treatment access, utilization, and health and behavioral outcomes for defined populations, (c) the effects of organization, financing, and management of services on treatment outcomes, (d) drug abuse service delivery systems and models, such as continuity of care, stages of change, or service linkage and integration models, and (e) drug abuse treatment services for HIV seropositive patients and for those at risk of infection. 1. Drug Abuse Treatment Economic Research. This initiative will support research to design and develop data systems for financial management and economic analysis of treatment programs and larger systems in new healthcare settings and managed care networks. Managerial decision-making requires the implementation of sophisticated data systems to facilitate routine budgeting processes, allocation of resources, performance measurement, and pricing decisions. The focus is on the needs of managers within the organization and managers outside of the organization. Data system development must be based on standard cost behavior and profit analysis. Data systems must be designed with correct cost concepts (accounting and economic) in order to permit cost and pricing decisions to be developed for new treatment technologies and management of ongoing systems. In research settings, such an initiative is vital for the assessment of new technologies developed for transfer to practice. 2. Determining the Costs of Implementing Evidence-Based Practices (EBPs) and Other Technologies in Drug Abuse Treatment. Research shows that new technologies or evidence-based practices (EBPs) can improve drug treatment outcomes, and it has been asserted that large-scale drug abuse treatment improvement requires systematic implementation of proven practices, processes, and technologies. Often, however, new drug treatment approaches are not adopted or sustained in usual practice, even in programs that served as settings for research showing their effectiveness. This may be due in part to a poor understanding of the initial or ongoing costs entailed by new practices, processes, or technologies (hereafter referred to as technologies). Methods and tools need to be developed and tested to help drug abuse treatment service providers and payers arrive at realistic estimates of the costs of implementing and sustaining new technologies in usual practice settings. With regard to new technologies, implementing is defined as an ongoing process of selecting, adopting, and adapting these new technologies into ongoing treatment, particularly with consideration for the local setting, population and available resources. Sustaining is defined as an ongoing process of providing needed resources (such as staffing, training, and equipment), maintaining the quality of the new technology through evaluation, monitoring, and improvement, and determining its ongoing utility compared to alternatives. The tools and methodologies should be able to identify and estimate costs separately for implementing and for sustaining new technologies, and should consider both clinical and administrative technology. At a minimum, domains in which costs should be estimated include assessment of programmatic need, appropriateness, and value; staffing qualifications (salary and competencies); training, support, equipment, and other infrastructure requirements; information / data requirements; quality monitoring and improvement; and evaluation of outcomes. Sarah Duffy, Ph.D. 301-443-6504 Email: sduffy@nida.nih.gov 3. Personnel Selection Technology Research for Drug Abuse Treatment Clinics. Research is showing that employee turnover is a substantial problem among substance abuse treatment services providers. Applications supporting innovative research that develops and validates generic staff selection systems which could be adopted and tailored for use by drug abuse treatment clinics are welcome. Like many small businesses, drug abuse treatment clinics have problems attracting and retaining qualified personnel. Also like many small businesses, treatment clinics have limited resources to apply to the recruiting, screening, and hiring of new and replacement personnel. Research has shown that the application of standardized screening and selection methods designed to maximize person-job fit can cost-effectively reduce staff turnover. Systematic methods such as background inventories, protocol-driven interviews, aptitude tests, and credit checks have demonstrated validity for improving person-job fit. Examples of possible projects might include development of easy-to-understand guidance about legal considerations in hiring practices, software that transform job task analysis into selection criteria, interview protocols to standardize applicant screening, tolls to help improve recruitment, and/or self-paced training for hiring officials or interview panels to improve screening reliability. 4. Customer Retention Technology. Premature disengagement from drug abuse treatment participation is a common problem and ranges from approximately 30 to 60% based upon the clinic and modality studied. Past research has very frequently attributed dropping out of treatment to participant characteristics (e.g., motivation, addiction severity, comorbidity) and/or environmental factors (e.g., social pressures, unemployment, homelessness). Seldom has the dropout problem been studied in the context of customer satisfaction. That is, there is little research looking at the causes of dropping out of treatment attributable to organizational factors (e.g., policies, practices, context) that influence participant withdrawal decisions. Needed are tools and systems for assessing and surveying drug abuse treatment program participant perceptions and satisfaction levels, summarizing and report participant assessments, interpreting results, and adjusting policies and practices to improve satisfaction and participant retention in treatment. 5. Effective Management and Operation of Drug Abuse Treatment Services Delivery. The bulk of drug abuse treatment is conducted in small clinical settings with therapeutic staffs of less than a dozen people. Small clinics lack resources to help improve efficiency and effectiveness in both business and therapeutic practices. Areas that may be of interest to small businesses include, but are not limited to: a. Computer-based leader/manager self assessment tools: On-line and other types of tools to help those supervising the delivery of drug abuse treatment services to gain insights about personal strengths and weaknesses, and to help guide them to improved leadership and management practices. b. Organizational change tools: Handbooks describing step-by-step way to introduce more efficient business practices such as quality management/monitoring, creating empowered work teams, formalized goal setting, improved customer relations, forming organization linkages, and adopting new fiscal and resource management techniques. c. Organizational change tools: Handbooks describing step-by-step ways to introduce more efficient or effective therapeutic practices such as, adding pharmacotherapy in a previously drug-free clinic, adopting new medical/pharmacotherapy or behavioral interventions, and adopting new approaches to clinical collaboration and/or case management. 6. Assessment Tools for Quantifying and Organizational Culture that Promotes and Sustains a Drug-Free Workforce. Though drug-free workplace programs are ubiquitous in large businesses, small businesses often lack the staff and resources to create effective drug-free programs because they may involve in-house or contract experts to educate, train, monitor, and enforce policies and practices that will sustain a healthy workforce and a safe and healthy workplace. Though there are numerous model drug-free workplace policies and programs provided free by federal, state, and local governments as well as nongovernmental organizations, many fail to provide management with affordable or free, easy-to-use tools to assess the baseline of their organizations’ culture for drug abuse intolerance, and to monitor progress in building a drug-free organizational culture. Research shows that individual employees and organizations vary in their support for a drug-free workplace. Surveys indicate that coworker tolerance for illicit drug use varies by the type of drug, the type of industry, and the work role of the respondents. A drug-free culture creates commonly-held attitudes, beliefs and practices among employees that are socially reinforced. Once established, the need for costly external incentives and other measures abates as coworkers socialize new incumbents and enforce behavior promoting abstinence. Tools and methodologies need to be developed to a) assess an organization’s baseline culture for drug abuse intolerance both on and off the job, b) identify policies and practices that undermine a drug-free culture, c) enable the identification of programs, policies, and practices capable of helping the workforce develop/strengthen an organizational culture of intolerance for drug use, and d) estimate the impact on the organization’s quality of work-life, job safety, individual and group performance and productivity, and the profitability of the organization itself. Included would be inexpensive and easy to use tools for monitoring workforce behavior change, and changes in the impact on the organization (as outlined in “d”). Thomas F. Hilton, Ph.D. 301-443-6504 Email: Tom.Hilton@nih.gov 7. Web-Based Technologies: Transporting Services Research to Practice. This initiative will support the development and testing of the effectiveness of web-based technologies that facilitate the translation of drug abuse prevention and treatment services research into practice. The ultimate goal is the delivery of efficacious, low-cost interventions to the greatest number of individuals in community settings. Delivery of evidence-based services in community settings often is hampered by lack of state-of-the-art information about the contents of efficacious interventions, the organizational structures and processes that make effective implementation possible, and available training and technical assistance. Applications may include, but are not limited to, the development and testing of new and innovative Internet-based systems that provide practitioners with (a) current information on evidence-based treatments with the greatest promise for defined populations of drug abusers; (b) assistance in translating clinical trials data into clinically useful information; (c) information and training on how to effectively organize, manage, and deliver evidence-based prevention and treatment services; (d) strategies for organizational change and capacity building; and (e) access to training and technical assistance on the adoption of new prevention and treatment interventions. 8. New Technologies for Screening, Assessing, and Preventing Problem Drug Use and HIV, Matching Patients with Appropriate Treatment Services. Increased understanding of the complexities of problem drug use and HIV risk behaviors has sparked growing interest in and increased need for new user-friendly technologies to assist in the screening, assessment, and prevention of drug abuse and HIV, and in the matching of patients with appropriate treatment services. New technologies, including CD-ROM, hand-held, Internet, videotape, videodisc, and other electronic means have great potential for helping treatment providers in specialty and non-specialty care settings including primary care contexts to (a) screen for problem drug use and associated health problems and risk behaviors, including HIV, (b) assess the nature and degree of drug use and HIV risk behaviors, (c) embed items for screening or assessing problem drug use within existing clinical tools, (d) deliver appropriate prevention interventions, and (e) identify appropriate types and levels of treatment services for patients based on their individual treatment needs. These new technologies potentially can provide a more cost effective way of identifying problem drug use, HIV risk behaviors and infection, and associated health problems in a variety of health care settings, speeding the assessment and treatment process, and improving treatment placement decisions. Dionne Jones, Ph.D. 301-443-6504 Email: djones@nida.nih.gov 9. Reintegration of Criminal Offenders into the Community. Many offenders enter the criminal justice system with drug abuse problems and related health issues. In addition to addressing these health care issues within the prison walls, treatment programs are increasingly called upon to help offenders successfully reintegrate into the community following incarceration. This often means helping offenders to manage their recovery through monitoring, linkage with continuing care services, development of social support networks, and education of friends and family members about the nature of drug abuse and the challenges facing the offender upon release from prison. It is estimated that over the next several years, more than 600,000 criminal justice offenders, many of whom have drug abuse problems, per year will be released to return to their communities. New technologies are needed to help treatment providers in the criminal justice system and in the community coordinate efforts to effectively (a) monitor offenders’ recovery once they have been released into the community, (b) prevent relapse, (c) identify relapse early and efficiently re-engage released offenders in appropriate treatment, (d) link released offenders with continuing care services in the community, (e) develop social support networks for recently released offenders in recovery, and (e) educate offenders’ family members so that they can more effectively support offenders in recovery once they have been released from prison. Dionne Jones, Ph.D. 301-443-6504 Email: djones@nida.nih.gov 10. Technologies to Support Quality Improvement in Addiction Treatment Systems. New technologies to support quality improvement in community-based, addiction treatment provider systems are needed. Quality improvement methods, although well established in business and healthcare management, are underutilized in addiction treatment. Addiction treatment systems have limited resources for initiating, developing, implementing, and sustaining quality improvement practices. Most community-based provider systems have limited capacity to capture and integrate information about (a) the nature and extent of community needs and resources; (b) organizational and management processes to facilitate adoption, adaptation, implementation, and sustained use of science-based innovations; (c) implementation costs for new service innovations; (d) client satisfaction; and (e) quality of care. Centralized, automated and cost-efficient technological tools for these purposes could help provider systems improve the quality and efficiency of their treatment services, meet accreditation requirements, and reduce operating costs. Bennett Fletcher, Ph.D. 301-443-6504 Email: bfletche@nida.nih.gov 11. Electronic Drug Abuse Treatment Referral Systems for Physicians. Research shows that primary care physicians often do not screen for drug abuse disorders. While this may be related to stigma attached to illicit drug use or to a lack of adequate health insurance, it may also be due to the lack of an adequate referral system that primary care physicians can use for the patients they identify as having a potential drug problem. The lack of a referral system places a greater burden on the physician to secure treatment resources for the patient, and also places the physician at greater risk if no appropriate treatment can be found. A practical and usable electronic drug abuse treatment referral system needs to be developed and tested for use by physicians in primary care settings, including doctor’s offices. To be effective and useful, the system needs to be targeted at local needs, for example by taking into account local private insurance coverage and the types of insurance accepted by local treatment providers. It should also include an actively-maintained database of local providers, with information on insurance carrier, geographic “catchment” area of treatment providers, types of substance disorders treated, types of co-occurring disorders (mental disorders, etc.) treated, gender, age, other pertinent treatment factors needed by primary care physicians to make appropriate referrals. The system should be designed to be reliable and efficient, allowing for appointment scheduling or other needed arrangements to ensure a successful referral. Feasibility and cost-efficiency should be carefully considered. Richard Denisco, M.D. 301-443-6504 Email: deniscor@nida.nih.gov Center for the Clinical Trials Network The mission of the Clinical Trials Network (CTN) is to improve the quality of drug abuse treatment throughout the country using science as the vehicle. The CTN provides an enterprise in which the National Institute on Drug Abuse, treatment researchers, and community-based service providers cooperatively develop, validate, refine, and deliver new treatment options to patients in community-level clinical practice. This unique partnership between community treatment providers and academic research leaders aims to achieve the following objectives: · Conducting studies of behavioral, pharmacological, and integrated behavioral and pharmacological treatment interventions of therapeutic effect in rigorous, multi-site clinical trials to determine effectiveness across a broad range of community-based treatment settings and diversified patient populations; and · Ensuring the transfer of research results to physicians, clinicians, providers, and patients. Materials and processes that facilitate clinical trials in community practice settings are particularly needed in this program. Areas of research include but are not limited to: · Projects that would simplify, automate, standardize, or reduce the cost of administration of clinical research instruments used in CTN trials · Projects that would reduce error rates in completing assessment or clinical instruments and in transmitting data to data management entities · Projects to develop instruments that measure factors relevant and important to the conduct of addictions research, such as: the extent of craving and/or of withdrawal, the risk of addiction to a particular substance, the therapeutic alliance between patient and therapist, perceived satisfaction with health care, probabilities of a pain management patient developing dependence/abuse on pain medications, and probability of successfully completing detoxification · Projects to develop instruments that measure and predict HIV risk behaviors · Projects that develop and evaluate innovative diagnostic drug screening tests for drug abuse, such as oral swabs · Projects that develop and evaluate the use of gene chip technology for drug abuse risk factors With all questions regarding CTN-sponsored SBIR research, please contact: Quandra Scudder 301-443-6697 Email: scudderq@nida.nih.gov Specific projects could include: 1. Development of Combination Medication for Emergency Treatment of Opioid Overdose in the Presence of Benzodiazepines. Suspected opioid overdose—coma, apnea and pin point pupil—is treated by the administration of naloxone, which, while effective, is short-lived. Patients often leave the Emergency Room, return immediately to opioid use, and suffer dire consequences as a result. There is sufficient preclinical and clinical evidence that buprenorphine may be a more effective medication for treatment of opioid overdose in such patients. However, the clinical development of this treatment strategy has been hampered by concerns that many opioid abusers also abuse benzodiazepine, and in such patients the administration of buprenorphine may be hazardous. Fumazinil, a specific benzodiazepine antagonist used to treat benzodiazepine overdose, can be co-administered with buprenorphine and may protect such patients from the ill effects of buprenorphine in cases of overdose involving both opioids and benzodiazepine. The goal is to develop and test the buprenorphine-fumazinil combination medication formulation for the treatment of opioid overdose with suspected concurrent benzodiazepine abuse. 2. Screening and Development of Partial Agonists at the Human CB1 Receptor for Treatment of Marijuana Dependence or Withdrawal. NIDA seeks applications to screen and/or develop CB1-receptor partial agonists for application in the pharmacotherapeutic treatment of marijuana dependence or withdrawal. The potential benefits of CB1-receptor partial agonists in the treatment of dependence may parallel those of safe and effective nicotine or opiate partial-agonist replacement therapies, where buprenorphine and varenicline have demonstrated effectiveness in enhancing abstinence from opioid use and cigarette smoking, respectively. As implied by the designations of partial-agonist replacement or substitution therapy, a partial-agonist medication has core biological effects similar to those of the abused drug. Importantly however, there is a ceiling-effect dose with the administration of partial agonists not present with full agonists such that at high doses, partial agonists are less likely to precipitate adverse behavioral or biological events and to have abuse liability compared to full agonists. The phase I project should identify compounds that bind to human CB1-receptors as partial agonists and, in the phase II, the grantee should develop and evaluate selected partial agonists. 3. Improved Device to Capture and Measure Drug Use in Oral Fluid. Oral fluid (OF) testing is a promising method to monitor for drugs of abuse. The main advantages of OF is the simplicity and noninvasiveness of sample collection. Aside of patient’s/ study participant’s comfort and preference compared to urine drug screen, the oral fluid sample collection can be easily observed, obviating the need for special restroom facilities and same-sex collectors and making adulteration of the specimen more difficult. Furthermore, infection risk is lower than for drawing blood. For clinical toxicology applications, including use in clinical trials, drug treatment programs, physician office and emergency room testing, onsite OF testing would offer rapid availability of results for diagnostic or research purposes. At this point, however, Substance Abuse and Mental Health Services Administration approval of OF testing has been delayed because of questions about drug device performance, disposition of drugs in OF, and need for improvement of assays. The greatest current limitation for OF testing is the small number of controlled drug administration studies available to inform interpretation of OF tests. (Bosker, Huestis, 2009) Applications should address current limitations and present methods to remove obstacles for wider usage of OF testing in clinical practice and research. Reference: Bosker WM, Huestis MA. Oral Fluid Testing for Drugs of Abuse. Clinical Chemistry.2009; 55:11 1910-1931 4. Improved Technology of Testing Devices to Remotely Capture and Measure Drug Use in Biological Specimens. There is an ongoing need for more accurate, practical and convenient point-of-collection testing devices for monitoring drugs of abuse. Current devices that test for illicit drugs in urine, oral fluid (saliva), sweat and hair have strengths and limitations. The goal of this solicitation is to develop new technologies/devices that will increase strengths (e.g. accuracy, practicality, and convenience) and decrease limitations (e.g. minimum frequency, contamination, and adulteration) of testing methodologies. New technology might permit testing from remote locations (e.g. patient’s or subject’s home) while ensuring real time data collection and transfer into medical records/study databases. Risk of adulteration should be minimized to a level comparable with tests provided in drug treatment centers or study sites. The phase I application should explore all tests currently available, especially new technologies allowing for remote collection of the data. In phase II, the grantee should develop and test a prototype. 5. New Technologies: Integrating Data from Prescription Monitoring Program(s) to Current Clinical Practice. In some states the prescription monitoring program collects prescription data for controlled substances into a central database that can then be used by a limited number of authorized users to assist in deterring the illegitimate use of prescription drugs. Prescribers and dispensers in some states may query the database to assist in determining treatment history and to rule out the possibility that a patient is "doctor shopping" or "scamming" to obtain controlled substances. Limited time/resources of busy medical offices are a barrier to obtaining and utilizing this information to improve quality of treatment for each individual patient. This initiative will support development and testing of the effectiveness of new technologies that facilitate utilization of data collected by Prescription Monitoring Program(s) in clinical practice. Applications may include, but are not limited to, the development and testing of new and innovative Internet-based systems that provide a) practitioners with current information of their patients’ treatment/medication compliance; and b) transfers data automatically to patients chart, etc. The goal is to minimize barriers faced by clinical staff to obtain, record and utilize the data while maintaining strict security requirements (i.e., confidentiality, integrity, and availability). These new technologies should provide a more cost effective way of identifying treatment non-compliance and help adjust a treatment plan according to the needs of individual patients as well as decrease potential diversion of controlled substances. The phase I application will explore and describe current Prescription Monitoring Programs and new technologies allowing development and testing of the application in phase II. HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 A. Behavioral and Integrative Treatment Branch. The Behavioral and Integrative Treatment Branch is interested in research on behavioral and integrative treatments for drug abuse and addiction. The term "behavioral treatments" is used in a broad sense and includes various forms of psychotherapy, behavior therapy, cognitive therapy, family therapy, couples and marital therapy, group therapy, skills training, meditation, guided imagery, counseling, and rehabilitative therapies. The term, “Integrative treatments” refers to treatments that combine behavioral interventions with other treatments, including other behavioral therapies, medications, and/or complementary/alternative therapies. Behavioral and integrative treatment research has been conceptualized to consist of three stages. Stage I, or early treatment development, involves research on the development, refinement, and pilot testing of behavioral and integrative interventions. Stage I may include translational research that incorporates concepts, methods or findings from other disciplines (e.g., neuroscience, cognitive science, etc.) into the development of behavioral and integrative treatments. Stage I may also include research to develop or adapt treatments to become more “community-friendly.” Stage II includes testing treatments that show promise and testing the “dose-response” of treatments. Stage III is research aimed at determining if and how efficacious behavioral treatments may be transported to community settings. Stage III may include studies that test treatments in community settings, with community therapists. Stage III may also include studies that develop or test methods of training treatment providers to administer treatments. Determination of mechanism of action of treatment is relevant to all three stages. Specific areas of interest include: 1. Translation from Basic Behavioral or Cognitive Science. “Stage I” research on the development of behavioral therapies or components of such therapies that are based on developments and findings from the basic behavioral or cognitive sciences. 2. Translation of Cognitive, Affective and Social Neuroscience Findings Towards Development of Behavioral Treatments. “Stage I” research on the development of behavioral treatments or components of such therapies that are based on developments and findings from cognitive, affective, or social neuroscience. For example, one may wish to apply findings on the neural underpinnings of adolescent risk-taking behaviors to target the developmental needs of substance using youth, or apply findings on the link between early adversity and the impairment of emotion regulatory abilities to address the needs of substance using victims of childhood abuse. 3. Treatment of Sleep Disorders for Individuals in Drug Abuse Treatment. Recent research on sleep has shed new light on its importance to psychological and physical health. Sleep deprivation has been linked with impaired cognitive performance, negative mood, and even decreased immune function. Drug abusers often cite insomnia as reason for relapse, and may use drugs to modulate their sleep/waking cycles. However, the treatment of sleep disorders has not been a primary focus of drug abuse treatment research. The development and testing of sleep hygiene interventions, alone or in combination with behavioral interventions, for use in conjunction with drug abuse treatment, as a means of improving treatment for drug abuse is needed. Developmentally and age appropriate, as well as gender sensitive treatment of sleep disorders could impact on the development of more effective treatment interventions. Lisa Onken, Ph.D. 301-443-2235 Email: l010n@nih.gov 4. Modifying Efficacious Behavioral Treatments to be Community Friendly. Several behavioral interventions have been found to be efficacious for the treatment of drug addiction. However, there are barriers to implementation of behavioral treatments in community-based settings. Community settings that treat drug addicted individuals are reluctant or unwilling to adopt these interventions for a variety of reasons. Reasons that scientifically-based behavioral treatments are not accepted by community providers could include the excessive cost of implementation, the length of time for administration of treatment, inadequate training available for therapists and counselors, treatments not shown to be generalizable for different patient populations or for polydrug abusing populations, etc. Research aimed at modifying efficacious behavioral treatments to make them more acceptable to community settings is needed. Settings might include, drug abuse treatment facilities, primary care, managed care, after-school or classroom settings, colleges, and the criminal and juvenile justice system. Examples of possible studies are those that are designed to reduce the cost of treatments, reduce the time of administration of treatments, aid in training of therapists, counselors and nurses, adapt individual therapies for group situations, etc. 5. Treatments to Prevent Escalation from Abuse to Dependence. Therapies for drug abusers who are not yet dependent on drugs to reduce risk of escalation to dependence and therapies for drug abusers who have not considered or claim little interest in seeking treatment for their drug problems are needed. Treatments for participants in their natural environment, such as treatments delivered over the Internet, cell phone, or in neighborhood settings such as churches and recreation centers are desired. A particular focus on treatments which incorporate engagement strategies for hard to interest groups are requested. Educational games, interactive video content, fluency based learning approaches and other methods to help maintain involvement are encouraged. 6. Virtual Reality Applications for Drug Abuse. Development and improvement of treatments using Virtual Reality and other new simulation technologies is needed. New technology may help to make existing treatments more effective, or may make novel treatments possible. Behavioral treatment research to develop, modify, adapt, and test treatments for drug abuse and for co-morbid psychiatric conditions (such as anxiety disorders) using new technologies is of interest. Recently virtual reality simulations have been used to train medical personnel in demanding medical procedures such as microsurgery techniques. Virtual training allows trainees to gain familiarity with both the environment in which services are delivered as well as the intervention techniques without the danger of mistakes impacting live patients. Virtual reality interfaces can assess skill acquisition and provide detailed feedback during procedures to help trainees correct mistakes or avoid making them altogether. In the drug abuse field, training and dissemination efforts have been hampered by a dearth of knowledge about ways to conduct dissemination. Although trainees often practice on actual clients, this approach has drawbacks including its reliance on the client or participant’s schedule and willingness to participate in training sessions and potential danger to the client or if the intervention is delivered incorrectly. Libraries of virtual reality simulations of drug users in treatment or “virtual patients” are needed to provide experiential training for treatment providers without relying on existing patients. This will help facilitate the rapid and effective dissemination of proven treatment strategies. 7. Virtual Clinical Trials Settings for Conducting Behavioral Treatment Trials and Addictions Treatment Provider Education Trials in Cyberspace. Virtual communities such as Second Life as well as private web forums offer a unique opportunity for behavioral therapy researchers and providers to establish and conduct online psychotherapy and behavioral therapy development research as well as a forum to develop provider “university’s” at which various training techniques may be tested for discovering the most efficacious way to deliver continuing education and other training in the latest methods of treating addiction. Applications are encouraged to develop such a forum and test either a provider training or behavioral therapy method in an online trial. As part of this research platform, methods for obtaining consent, maintaining confidentiality, collecting data and where needed, assessing provider adherence and competence are expected. 8. Remote and/or Mobile Abstinence and Identity Verification. Methods are needed for at home or mobile abstinence verification which include identity verification. Drug abuse treatment researchers are in the process of developing web-based and mobile phone based treatments which can extend treatment beyond the clinic walls. Additionally, there is growing recognition by providers that drug addiction is a chronic disease which may require multiple bouts of treatment. However, currently there are no means of monitoring abstinence once patients leave formal treatment or validating progress of patients undergoing treatment located outside a clinic which provides onsite testing. Monitoring onsite testing poses barriers to patient privacy but unobserved sample donation may be subject to switching and adulterants. Products are needed which both test for the presence of illicit substances and which accurately identify the donor of the sample and the time of its submission so patients can participate in monitoring outside of formal treatment settings. Blood sampling similar in invasiveness to a skin prick for diabetes testing or other low risk sampling of other tissues and specimens may be acceptable. Scalability and automation of methods are particularly desirable. Cecelia Spitznas, Ph.D. 301-443-0107, Fax: 301-443-6814 Email: cmcnamar@mail.nih.gov 9. Improving Adherence to Medications and Treatment for Drug Abusers with HIV/AIDS. The introduction of highly active antiretroviral therapy (HAART) has significantly changed HIV/AIDS clinical care. There is a need for research related to the development and testing of new and improved behavioral interventions(alone, and in combination with pharmacological treatments for drug addiction), in order to facilitate better adherence to antiviral regimens among drug abusers with HIV infection, including HIV positive drug abusers with comorbid medical illnesses and/or psychiatric disorders. There is also a need to develop and test adherence interventions administered or assisted by technological devices such as computers, the internet, expert system models, telephone pagers, or hand-held computers. 10. Treatment for Emerging or Specific Populations. Therapies designed to intervene with understudied populations including users of drugs such as methamphetamine, MDMA and other club drugs, marijuana, inhalants, and prescription opioids and psychostimulants, as well as children of substance abusers in need of treatment, and drug abusers with comorbid psychiatric disorders and/or medical illnesses such as HIV/AIDS, hepatitis, etc. 11. Development of HIV Risk Reduction Interventions. Research to develop and evaluate behavioral strategies to reduce HIV risk behaviors in HIV-positive and HIV-negative substance abusing treatment populations. Where appropriate, risk reduction interventions should be adapted to patients’ age, gender, cultural background and potential cognitive impairments, and should address compliance with medical regimens. The product of such research might be training, supervision, or educational materials, such as manuals or videotapes that describe the intervention and its implementation by treatment staff. 12. Woman and Gender Differences in the Provision of Behavioral Treatments, and HIV/AIDS Risk Reduction Approaches. Develop and evaluate specific behavioral treatment approaches targeting drug-addicted women. This may include behavioral therapies, skills training techniques, counseling strategies, and HIV and other infectious disease behavioral risk reduction strategies. This may also include development and testing of training materials that specifically address women and gender differences in drug addiction treatment to promote effective use of research-based treatment approaches. Training materials may involve treatment manuals, training videos, CD ROM or DVD technologies, Internet or computer based programs to manage aspects of treatment administration, or other innovative educational strategies for health professionals using new technologies. 13. Behavioral Treatments Drawing from Stress Research or Stress-Management Interventions. Projects are encouraged that apply concepts from stress research (such as appraisal, coping, and social support) to drug abuse in innovative ways, or that test the extent to which stress-management interventions can be applied to the treatment of drug abuse and interventions to reduce risk of HIV and other infectious diseases. Examples of stress-management techniques that may have novel application to drug abuse and HIV risk include techniques that teach problem-solving and affect-management, restore one’s sense of purpose and meaning, prevent burnout in the face of chronic stressors, increase self-efficacy for managing stress, inoculate against stressors, train relaxation and meditation, intervene during crises, enlist social support and system support, and others. 14. Behavioral Strategies for Increasing Medication Adherence. Research to develop and to evaluate strategies to induce recovering addicts to take medication for a prolonged time, especially opioid antagonist naltrexone; partial opioid-agonist buprenorphine, etc. to encourage HIV infected drug users to comply with medical treatments (HAART) in drug abuse treatment settings; or to adapt existing behavioral strategies to increase patient compliance and cooperation in long-term treatment for drug abuse or for diseases associated with drug abuse such as tuberculosis or hepatitis. An important consideration should be cost and practicality of use in actual clinical practice or in an aftercare program. The product of such research might be a manual, which describes the behavioral strategy, and its implementation by treatment staff or scientific data regarding evaluation. Shoshana Kahana, Ph.D. 301-443-2261, Fax: 301-443-6814 Email: kahanas@mail.nih.gov 15. Integration of Behavioral Treatments and Pharmacotherapies. Development of integrated behavioral treatments and pharmacotherapies may enhance the efficacy of both types of therapeutic interventions. For instance, the maintenance and detoxification of heroin addicts could perhaps be optimized by the integration of distinctive behavioral treatments devised specifically for opioid agonists, antagonists or partial agonists determined by the heterogeneity of the subgroup of addicts and the pharmacological differences of the medications. Integration of medications and behavioral treatments could possibly enhance compliance with medication regimens, increase retention allowing pharmacological effects to occur and prevent relapse to drug abuse and addiction. 16. Behavioral Treatment Research for Drug Abuse and Addiction in Primary Care. Recent research has shown that physicians and other clinicians often fail to recognize drug abuse or addiction among their primary care patients. In addition, a significant number of these clinicians reported that they did not know how to intervene with their patients if drug abuse or addiction was suspected. Drug abuse related illnesses and morbidity often occur in adults and may have begun in adolescence. However, very little research has been done to develop or test behavioral treatment approaches or combined pharmacological and behavioral treatments for drug abuse and addiction in primary care settings. The objectives of this initiative are to encourage research on the development and testing of innovative behavioral treatment approaches e.g. screening and brief interventions, use of web-based or mobile technologies used alone or in combination with pharmacological treatments. Other goals of this research initiative are to encourage additional research on the development and validation of culturally sensitive screening and assessment instruments for use with youth and adults in primary care; and to encourage research on the transportability of efficacious behavioral treatments to primary care settings, as well as research on science-based training approaches for changing primary care clinicians' behaviors regarding their recognition and intervention with drug abusing or addicted patients. While motivational enhancement approaches for some drug abusing populations have been found to be effective, this behavioral approach has not been widely used in primary care. 17. Using Telemedicine to Deliver Efficacious Treatment to Underserved Populations in Specialty Addictions Treatment and/or General Medical Settings . Telemedicine programs are being used in urban medical centers to rapidly disseminate science-based information on new medical treatments. In addition, approximately one-third of the rural hospitals are now using telemedicine to improve patient care Studies are needed to modify existing treatments developed by NIDA researchers for deployment and testing as telemedicine treatments at remote locations to underserved populations. These may be delivered in any patient care context including primary care or specialty addiction treatment. Modification of the treatment content to apply to the remote patient population and provider training materials to orient the onsite staff who may not be experienced at delivering the new treatment may be needed. 18. Youth Smoking Cessation. Smoking related illnesses usually occur in adults. However, tobacco use and nicotine addiction generally begin in childhood or adolescence. Despite health warnings, adolescents continue to initiate smoking at alarming rates and the majority will continue to smoke as adults. Adolescents who begin to smoke, develop nicotine dependence very quickly and exhibit withdrawal symptoms during quit attempts in a similar fashion to adults. Most adolescents who smoke, express a desire to quite. To date, research on smoking cessation for teen and young adult smokers has not been particularly fruitful. This initiative requests research aimed at the development and testing of smoking cessation treatments tailored to the specific needs of adolescents and young adults. Consideration should also be given to gender and ethnicity. 19. Complementary and Alternative Medicine Therapies (CAM) for Drug Abuse Treatment. Research is encouraged on complementary and alternative interventions for drug abuse treatment either as the sole treatment or as an adjunct to enhance the therapeutic potency of existing drug abuse treatments. Any of the five CAM categories: Whole medical systems, mind-body interventions, biologically-based therapies, Manipulative/body-based therapies and energy therapies would be considered for this initiative (for more information, see http://nccam.nih.gov/). CAM therapies are interventions that are commonly used in “real world” settings, but whose therapeutic efficacy has not been scientifically demonstrated. The product of this research might also be a manual or video, which illustrates the intervention and how it is implemented by treatment staff. Geetha Subramaniam, M.D. 301-435-0974 Email: geetha.subramaniam@nih.gov 20. Developing, Evaluating, and Transporting Culturally Sensitive Behavioral Treatments for Racial and Ethnic Minorities. Minority populations are disproportionately affected by the consequences of drug abuse. Research to develop and evaluate behavioral treatments that are culturally sensitive and relevant for diverse racial and ethnic minority populations is encouraged. This may include studies of behavioral treatments, alone or in combination with pharmacological treatment, or studies of behavioral strategies for increasing adherence to taking medications. In the development and evaluation of the behavioral treatment, attention needs to be directed at examining medical, social, and cultural factors that may influence adherence to the behavioral treatment approach and treatment outcome. Also, little is known about the transportability of efficacious behavioral treatments for minority populations. Research is needed on how to transport science-based treatments to various racial/ethnic populations. 21. Incorporating Smoking Cessation in Drug Abuse Treatment. Research is encouraged to develop and test behavioral and combined behavioral and pharmacological treatments for nicotine-addicted individuals who also are addicted to other substances, such as heroin, cocaine, methamphetamines and alcohol. Prevalence of cigarette smoking is extremely high among drug dependent individuals attending drug treatment. Many treatment providers are reluctant to address smoking cessation with clients either because they believe that substance abusers are not interested in quitting or because they fear smoking treatment will have a negative impact on drug abuse treatment outcome. However, studies have shown that many drug abuse clients are interested in quitting smoking and that the concurrent treatment of tobacco dependence and other drug dependencies does not threaten abstinence and might even assist in maintaining it. Research is needed to develop and test smoking cessation treatments that can be incorporated into treatments for illicit drugs of abuse. 22. Developing Treatments for Smokers with Comorbid Disorders. Research is encouraged that focuses on the development, refinement, and testing of behavioral treatments for smokers with psychiatric comorbidity, such as depression, schizophrenia, or anxiety disorders. Smoking prevalence is very high in individuals with psychiatric disorders. These populations generally respond poorly to traditional smoking cessation treatments. Similarly, medical comorbidities are widely prevalent and are in need of additional research in adults and in special populations such as youth, LGBT and homeless persons. Research is needed to develop and test innovative behavioral and combined behavioral and pharmacological treatments that address the unique needs of these individuals. 23. Tobacco Cessation for Pregnant and Post-Partum Women. Smoking among pregnant women remains an ongoing public health concern. It is estimated that approximately 20-30% of pregnant women smoke. Maternal smoking during pregnancy has been linked to infant mortality, impaired fetal brain and nervous system development, premature and complicated births, and low birth-weight babies. For women who do quit during pregnancy, relapse rates vary, but are reported as approximately 25% before delivery, 50% within four months postpartum, and 70-90% by one year postpartum. Children of smokers continue to be at risk for respiratory illness, middle ear infections, impaired lung function, and Sudden Infant Death Syndrome. Sustained tobacco cessation during pregnancy and the postpartum period reduces health risks to both mothers and their babies. Research focused on the development of innovative behavioral and combined behavioral and pharmacological interventions for nicotine-addicted pregnant and postpartum women is encouraged. Interventions may be tailored to sub-populations of pregnant smokers, such as teenage girls, heavy smokers, ethnic minorities, or low SES populations. Examples of other potential studies may include the development of smoking cessation interventions that address co-occurring issues, such as depression or weight-gain, interventions that include partners or support persons, Internet-based interventions or interventions that can be delivered by primary care physicians. 24 Behavioral Treatments for Groups. This includes the development of new psychotherapy approaches, the modification or testing of existing behavioral treatments, and the design and/or testing of innovative clinical training and supervision methods for dissemination of efficacious treatments to community settings. Examples of relevant projects are: traditional group therapies, such as 12-step and therapeutic community approaches, and newer group therapies such as cognitive-behavioral and acceptance-oriented approaches; groups for various populations, such as adolescents, adults, couple and family groups, gender-specific groups, and groups tailored for racial or ethnic minority populations. Of particular interest are projects that address the recent reports suggesting possible contraindications of group treatments for some populations (e.g., delinquent adolescents), or in some formats (e.g., less-structured, client-led groups). Debra Grossman, M.A. 301-443-2249 Email: dg79a@nih.gov 25. Developing Behavioral Treatments for Cognitively Impaired Drug Abusers. While there are currently many efficacious interventions available for drug addicted individuals in treatment, more can potentially be done to enhance treatments by addressing cognitive impairments that may accompany chronic drug use and HIV infection. Many commonly utilized drug addiction and HIV-risk reduction interventions assume certain basic cognitive capacities and abilities that may be absent, or impaired, in chronic drug abusers who may also be HIV-positive. For substance abusers to benefit from psychological treatment, they must be capable of attending to and receiving new information, integrating it with existing information stores, and translating this input into more concrete behavioral change. Substance abusers with cognitive limitations, who may not comprehend the interventions, are more likely to drop out of treatment, relapse faster, and have poorer long-term outcomes in comparison to cognitively intact substance abusers. Research is needed to develop, modify, and test “cognitive-friendly” drug dependence treatments that could lead to improved treatment response and outcome. 26. Interventions to Improve Engagement and Retention in Treatment. Therapies designed specifically to engage and retain individuals in treatment, especially those at high risk for HIV. An example could be a therapy that is: (1) sensitive to the age and motivational level of the client; (2) is specifically designed to respond to the needs of the individual, whatever his or her developmental and motivational level might be; and (3) actively works to increase an individual's desire to remain in treatment. 27. Development of New or Improved Addiction Assessment Measures and Procedures. Research directed at the improvement of a currently available measure or the design of a new psychosocial, social or environmental measure appropriate for use in the clinical assessment of youth and adult substance abusing populations. Special consideration should be given to a specific screening or diagnostic tool, or to a specific measure of treatment readiness, treatment compliance, service utilization, therapeutic process or drug treatment outcome. 28. Marijuana Treatment. Marijuana is the most commonly used illicit substance in the U.S. However, relative to other drugs of abuse, little research has focused on the treatment of marijuana dependence. Trends in the literature suggest that the types of treatments effective with other substances of abuse are likely to be effective with marijuana dependence. Initial studies also suggest that many patients do not show a positive treatment response, indicating that marijuana dependence is not easily treated. Research is needed toward developing and testing effective interventions for marijuana dependent individuals. 29. Transporting Behavioral Treatments to Community Practitioners. There is a need for effective methods of transferring behavioral treatments found to be effective in Stage I clinical trials to clinical practice. Cognitive-behavioral therapy, operant behavioral therapy, group therapy, and family therapy are among the therapies that have been shown to be efficacious in a highly controlled setting and may be helpful treatment approaches in community treatment programs as well. However, community practitioners may have been trained using other approaches and may not have been exposed to these scientifically based approaches. Emphasis should be placed on examining mechanisms to transfer effective research-based drug abuse treatment information and skills-based techniques to practitioners in the community. This may involve the development and testing of innovative training materials and procedures to use in the training of community practitioners to skillfully administer these treatments, including the development of highly innovative technology transfer and communication approaches. Research testing the transportability of empirically supported therapies to the community is an important component of the Behavioral and Integrative Treatment Development Program. There is also a need for the development of educational methods to train non-drug abuse health care workers in relating to drug abusers; eliciting medical histories regarding past or present drug abuse; recognition of the signs and symptoms of drug abuse; identification of those at high-risk for HIV and other drug abuse related medical problems such as tuberculosis or hepatitis. Development and validation of a drug abuse screening instrument which can be administered by primary health care providers, and training in administering such an instrument is also needed. Will Aklin, Ph.D. 301-443-3207 Email: aklinwm@mail.nih.gov 30. Treatment Modules for Specific Problems or Populations. Discrete therapy components that address specific problems common among drug addicted individuals and that can be implemented in conjunction with other therapeutic services. For example, an investigator may wish to develop a four session, highly focused, job seeking skills module that can be easily implemented by a wide range of practitioners to effectively increase appropriate job seeking behavior. Other examples include, but are not limited to, modules to engage ambivalent drug dependent individuals in treatment, modules to increase assertiveness in female drug addicts who feel pressured by others to use drugs, modules to improve study skills and pro-social interactions among withdrawn substance abusing adolescents, or to incorporate effective HIV risk reduction techniques. 31. Behavioral Treatments for Pre-Adolescents and Adolescents. Developmentally appropriate behavioral treatments for pre-adolescents and adolescents that incorporate HIV risk reduction counseling as an integral component of the treatment. This includes the development of new, or refinement of existing psychotherapies, behavioral therapies, and counseling (group and/or individual). This also includes the development and testing of manuals as well as other creative, interactive approaches for therapy delivery that may consider different settings for delivery, such as primary care, school-based health programs, juvenile justice settings, etc. Also the behavioral treatments should be culturally and gender sensitive. 32. Behavioral Treatments for Couples and Families. This includes the development of new psychotherapy approaches, the modification or testing of existing behavioral treatments, and the design and/or testing of innovative clinical training and supervision methods for dissemination of efficacious treatments to community settings, for youth and adult substance users. Treatments that target domestic violence or other forms of interpersonal abuse along with substance abuse are encouraged. 33. Innovative Technologies for Drug Abuse Treatment, HIV Risk Reduction, and Training Clinicians. Relevant research would be directed at the development and evaluation of innovative technologies to treat substance abuse, enhance adherence to medications, and/or reduce risk for HIV infection or transmission. Approaches should be capable of being readily incorporated at reasonable cost into various treatment settings. Areas of interest include Internet-based treatment or training programs, CD-ROM technology, audio delivery devices, photo therapeutic instruments, and hand-held computers. Also of interest are creative approaches for disseminating science-based behavioral treatments and for training therapists to use scientifically based treatments for drug abuse and addiction. Such approaches might include Internet-based education, interactive computer programs, telemedicine, etc. Finally, approaches which apply therapies with evidence of efficacy through new media such as web-based platforms, over email, or through chat rooms and bullet boards are also desirable. Jessica Chambers, Ph.D. 301-443-2237 Email: jcampbel@nida.nih.gov B. Clinical Neuroscience Research. The Clinical Neuroscience Branch (CNB) supports research on the biological etiology (determining the biological basis for vulnerability to drug abuse and progression to addiction, including studies on individual differences and genetics) and clinical neurobiology of addiction (exploring alterations of the structure and/or function of the human central nervous system following acute or chronic exposure of drugs of abuse), and the neurobiology of development (neurobiological effects of drugs of abuse and addiction during various stages of development and maturation, effects of drug exposure on neurobiological processes, development of methodologies and refinement of techniques used in pediatric neuroimaging). The Branch also supports investigations on the cognitive neuroscience of drug abuse and addiction, the neurobiology of treatment, neuroAIDS, and human pain and analgesia. Areas that may be of interest to small businesses include, but are not limited to: 1. Innovative Technology and Tools for Human Substance Abuse Research. There is a continuing need for the development of methods, tools, and technology that can be used as markers of or interventions for brain, genetic or behavioral (including cognitive and affective) alterations in humans related to the risk, or reliance (etiology) of, effects of, or recovery from substance abuse. NIDA has a strong interest in facilitating the identification and use of cross-disciplinary research tools and materials that can be applied to human research that will advance our understanding drug abuse. NIDA also has a strong interest in promoting the commercial adaptation and widespread availability of discoveries (“tools”) made in the course of interdisciplinary research to better serve its mission. The term research “tool" is being used in its broadest sense to embrace the full range of resources that scientists use in the laboratory and clinicians use as therapeutics; therefore, one investigator’s tool may be another's end product. The value of research tools is difficult to assess and varies greatly from one tool to the next and from one situation to the next. Providers and users are likely to differ in their assessments of the value of research tools. Many research and clinical tools are costly to develop and have significant competitive value to the firms that own them. Of particular interest are methods that could be used to determine the effects of drug abuse/ addiction treatments on neurobiological systems in an attempt to understand the neurobiological processes underlying risk and recovery. Also of interest are methods and tools that can be integrated or expend with brain imaging techniques or other brain-related measures that can be used in human subjects. Examples include, but are not limited to; Development of stimulus-generating hardware and/or software for use in substance abuse studies, including neurocognitive tasks, presentation of drug-related images for the induction of craving or to probe attentional or affective processes, and “virtual reality” types of dynamic stimuli important in studies of drug abuse and addiction; Remote and mobile based technologies such as PDA’s, “smart phones”, or web-based applications for measuring cognitive and affective function in real world environments; Development or implementation of interventions such as trans-cranial or direct current brain stimulation, real-time neurofeedback, or cognitive training; New infomatic tools for primary data analysis or secondary data analysis would also be appropriate; Another example would be methods or technology related to development of the human central nervous system and how drugs of abuse perturb this process. Developmental studies of these populations presents unique challenges when using neuroimaging technology. The development of novel techniques, or the refinement of existing methods, to provide direct noninvasive measures of brain structure and/or function that are adapted specifically for use in pediatric and adolescent populations is strongly encouraged. Also, neurocognitive and other neurobehavioral tasks for use in these populations, especially where they can be designed to probe underlying neurobiological processes, need to be developed (for developmental issues, contact Cheryl Boyce, Ph.D.). Steven Grant, Ph.D. 301-443-4877 Email: sgrant@nida.nih.gov or Cheryl Boyce, Ph.D. 301-443-4877 Email: cboyce@nida.nih.gov 2. Human Brain Neurochemical and Molecular Imaging. Measurement of brain neurochemistry, neuropharmacology (receptors) and gene expression in humans using non-invasive imaging has lagged behind advances in these areas in pre-clinical research as well as in functional and anatomical neuroimaging in humans. There is a continuing need for development of new ways to measure molecular targets in the human brain. Examples include, but are not limited to novel radioligands for PET and SPECT imaging in human brain for molecular targets (e.g., receptors, intracellular messengers, disease-related proteins), as well as novel methods that use magnetic resonance imaging or other emerging technologies such as optical imaging.. The primary application of these methods will be in basic human research. Ultimately, these measures may also be used as potential biological markers and surrogate endpoints for translational and clinical research, drug discovery and development, and clinical trials. The scope of the projects may encompass pilot or clinical feasibility evaluation in pre-clinical studies, model development, or clinical studies. Alternatively, the focus may be on research and development of new technologies for molecular, neurochemical or neuropharmacological development. Steven Grant, Ph.D. 301-443-4877 Email: sgrant@nida.nih.gov 3. Neuro-Rehabilitation of Drug-Induced Cognitive Deficiencies. The increased awareness that the brain is capable of substantial plasticity throughout the lifespan has opened the possibility that intervention can be developed alter brain or cognitive function so as to accelerate recovery of brain and cognitive dysfunction. Such interventions encompass both direct interventions of brain function as well as indirect interventions based on cognitive or behavioral principles. Direct interventions include trans-cranial or direct current brain stimulation, real-time neurofeedback, and deep brain stimulation. Another complementary approach is based on game technology for “serious (health-related) rather than purely recreational purposes. Serious games can provide a completely controlled, noninvasive, safe and alternative methodology for a variety of important studies of drug abuse and addiction. By involving a person in an interactive computerized situation, designed to be both entertaining yet directive (i.e., in the sense of covertly shaping desired behaviors via highly flexible and programmable sets of scenarios), altered behaviors can be introduced by pre-programming consequences to counteract and potentially reset undesirable neurobiological and neurobehavioral deficits associated with chronic drug abuse. Areas of cognitive impairment related to substance abuse that could be enhanced through the use of either direct brain interventions, or “serious” games include diminished decision-making ability, attention/concentration deficits, attentional biases, lack of cognitive flexibility and problem solving abilities, inability to use feedback to monitor/change behavior, memory impairments,. Steven Grant, Ph.D. 301-402-1746 Email: sgrant@nida.nih.gov 4. Measurement of Psychosocial Stress in Relation to Substance Abuse. There is the need for development, improvement and/or adaptation of precise and reliable field deployable measurement technologies can detect and quantify an individual’s exposure to psychosocial stress and/or one or more drugs. Ideally, the technology could be scalable from selected samples to full population studies. Comprehensive assessment includes measuring acute/chronic/cumulative exposures to psychosocial stress and/or addictive substances with a high degree of temporal and spatial resolution (i.e., as a person moves through environments), and with a high degree of accuracy and sensitivity to detect meaningful variations in extent of and response to exposure across developmental periods (ranging from prenatal to senescence) and among various population groups. Such technologies may include use of emerging remote and mobile technologies such as PDA’s, “smart phones”, or web-based applications. Harold Gordon, Ph.D. 301-443-4877 Email: hr23r@nih.gov C. Human Development Research. The Behavioral and Brain Development Branch (BBDB) supports a broad research, research training and career development programs directed toward: (1) an increased understanding of how developmental processes and developmental outcomes are affected by drug exposure and related factors; (2) an increased understanding of developmental processes that are relevant to: (a) drug use, abuse, addiction, treatment and relapse, and (b) risk behaviors related to drug abuse and other health conditions that often accompany drug use (e.g., HIV infection, STDs); (3) the use of translational approaches to increase understanding of these developmental processes; and (4) an increase in effective interventions aimed at preventing or ameliorating negative developmental outcomes resulting from exposure to drugs and related factors across diverse populations (e.g. racial/ethnic minority; rural/urban, etc.). 1. Develop Improved Technology for Assessment of Prenatal Drug Exposure and Passive Postnatal Drug Exposure. a. Develop and refine methods for the detection and quantification of infant exposure to drugs of abuse during pregnancy, including nicotine cocaine, marijuana, opiates, and methamphetamines. b. Develop and refine methods for the detection and quantification of passive exposure to illicit drugs during infancy and childhood including second and third hand exposure to nicotine, marijuana, or other drugs of abuse. c. Develop technologies for us in diverse settings (e.g. primary care, emergency rooms, obstetrics/gynecology, etc.) of the assessment of prenatal drug exposure and passive postnatal drug exposure. Nicolette Borek, Ph.D., 301-402-0866 Email: nborek@nida.nih.gov 2. Develop Interactive Database Systems on Human Subjects Issues for Use by Drug Abuse Researchers Studying School-Age Children and Adolescents Drug Use. Develop systems to assist investigators in obtaining technical and legal information relevant to involvement of children and adolescents in research on drug abuse. Examples of pertinent situations include tracking long-term health and development of children exposed to drugs during pregnancy, and investigating vulnerability and possible pathways to drug abuse including children in primary care and child care settings, and school-age children and adolescents. Human subject issues addressing family environments, child abuse and domestic violence, and secondary data sources are also of interest. These database systems should address issues such as assent and consent, should provide information on variation in laws and guidelines across jurisdictions, should include the capacity for interactive communication on numerous situations potentially facing clinical research and health care professionals, and should serve as sources of referral for additional assistance. Nicolette Borek, Ph.D. 301-402-0866 Email: nborek@nida.nih.gov 3. Develop Improved Methods of Neuroimaging to Assess Structural and Functional Status of the Brains of Children and Adolescents Exposed to Drugs. Document the feasibility and accuracy of appropriate and acceptable methods for assessing brain structure and function of children and adolescents, with special attention to any or all of the following groups: those exposed to drugs during pregnancy, those passively exposed during infancy and childhood, This could also include products to improve the tolerability, safety and validity of neuroimaging in children and adolescents, e.g. tools or techniques to reduce head-motion artifacts and image those actively using illicit substances. Documentation should include attention to such matters as technological difficulties and risks, and standardization issues relevant to testing conditions and image analysis. Karen Sirocco, Ph.D. 301-443-4877 Email: ksirocco@nidal.nih.gov or James Bjork, Ph.D. 301-443-3209 Email: jbjork@nida.nih.gov 4. Develop and Refine Methodologies and Clinical Tools for Measurement and Effective Interventions of Developmental Factors and Drug Use Among Children and Adolescents. a. Research to develop and refine methodologies for drug use detection and quantification which may address issues of acceptability, reliability, and validity of one or more methods for clinical research and practice (e.g., interviews, computerized questionnaires, and biological indicators such as saliva or sweat). Development of web, hardware and software technology tools to enable refined physiological and behavioral assessment of normal and atypical infant and child development which may inform risk and interventions for drug use are also of interest. Nicolette Borek, Ph.D. 301-402-0866 Email: nborek@nida.nih.gov b. Research and development of novel, or the enhancement of existing tools to be used in effective preventive or treatment interventions, and information dissemination to or understand drug use and its developmental effects for children, adolescents and their families. These tools might be used by researchers, health professionals and other health care providers, as well as by those in the broader community, including educators, day care providers, family members, etc. These tools must take into account cultural and developmental factor to assure their effectiveness and validity. Cheryl Anne Boyce, Ph.D. 301-443-4877 Email: cboyce@mail.nih.gov HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 Emphasis is on the molecular mechanisms of oral epithelial cell regulation and aberrations of these mechanisms. Research related to early diagnosis, prevention, and treatment of oral neoplasias is particularly relevant for the NIDCR small business program. Some examples include but are not limited to the following areas: A. Develop imaging techniques for the early detection, diagnosis and prognosis of pre-malignant head and neck lesions including oral salivary gland carcinomas. B. Develop immunotherapies (e.g. vaccines, gene therapies) effective against viruses suspected to be etiologic agents in the induction of pre-malignant and malignant head and neck lesions. C. Develop effective pharmacological, immunological and radiological modalities for treatment of pre-malignant and malignant head and neck lesions. D. Develop novel technologies for the genetic and molecular-targeted therapy of head and neck carcinomas. E. Develop novel micro and nano-sensor technologies that can release therapeutic agents in tumor cells. F. Develop regimens for the alleviation of the oral complications of cancer therapy. G. Develop novel technologies for using stem cells as therapeutics for head and neck cancers HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 The NHGRI has supported the generation of many large-scale genomic data sets such as genome sequence, haplotype maps, transcriptome measurements, protein interactions, and functional elements. NHGRI encourages the development of new computational methods and tools to analyze these and other large datasets, and to extract useful biological information from them. Where possible, existing community data standards and methods for data exchange should be used in the development of these new methods and tools. Further information on programs related to genomic databases and computational biology is available at this website: http://www.genome.gov/10001735. The development of new sequencing technologies has dramatically increased the amount of data produced for genomics. NHGRI is interested in supporting new computational applications for the production and analysis of data from these new sequencing platforms. These applications would include better computational methods for storage, compression and transfer of large datasets by biomedical researchers along with better analysis methods to interpret these data and integrate with other data types. Some genomic data analysis and display tools have been developed that already are used in the community that would benefit from additional work to support broader dissemination, for example making them efficient, reliable, robust, well-documented, and well-supported. NHGRI will support projects to extend the support for these informatics tools to make them readily adopted by any biomedical research laboratory that wishes to use genomic technologies to address biological questions. HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 Through research in neuroscience and basic behavioral science we can gain an understanding of the fundamental mechanisms underlying thought, emotion, and behavior and an understanding of what goes wrong in the brain in mental illness. Research sponsored by the Division of Neuroscience and Basic Behavioral Science covers a broad range of neuroscience topics: from both experimental and theoretical approaches, from molecules to whole brains to populations of individuals, from single cell organisms to humans, from across the entire lifespan, and from states of health and disease. This division also supports research on the basic behavioral, psychological, and social processes that underlie normal behavioral functioning. The topics listed below reflect the NIMH interest in technologies related to this broad range, but should not be considered a complete list. Prospective applicants are strongly encouraged to contact Dr. Margaret Grabb (listed below) with questions about the relevance of their interests to the mission of this division. A. Cutting-Edge Technologies for Neuroscience Research. Most of the research topics listed after this one are posed from the Division's neuroscience and basic behavioral science mission-oriented perspective, however, the technologies that might be developed to address those mission goals might be quite fundamental. Prospective applicants familiar with such technologies, but not familiar with the mission-related use of these technologies, are strongly encouraged to contact Dr. Margaret Grabb (listed below) for assistance in bridging this gap between their technical knowledge and knowledge of the neuroscience-related mission of NIMH. Technologies and approaches that might be used in products relevant to this mission include, but are not limited to: 1. Caged Molecules. These chemical entities could be activated, or could release an active agent, when specified bonds are broken by chemical, biochemical, photic, or other means. Among other uses, such molecules could be used to indicate biochemical or physiological processes or to deliver pharmacologic substances to highly localized brain regions. 2. Genetically Engineered Proteins. Such proteins could be put to any number of uses, including to express a fluorophore or chromophore at the occurrence of specific biochemical processes to report the time and location of such processes in brain tissue. 3. Inducible Gene Expression. Methods to turn on or off expression of particular genes in animals on the basis of time in the lifespan, location in the brain, or other factors. Such a capability would significantly advance basic brain research, and would have important implications for treatment and therapy of mental illness. 4. Combinatorial Approaches. These are high-through-put approaches that can be used to screen and synthesize molecules that affect brain cells. 5. Biocompatible Biomaterials. Such research and development relates to the chronic use of electrodes and other probes used in brain research, as well as implanted drug delivery devices. 6. Nanotechnologies. This emerging area of technology presents a wide range of opportunities for brain research, from the fabrication of probes to monitor brain physiology to novel means of delivering drugs and other substances. 7. Informatics Tools. Such technologies allow brain scientists, clinicians and theorists to make better sense and use of their data. These tools and approaches include those to acquire, store, visualize, analyze, integrate, synthesize and share data, including those for electronic collaboration. 8. Simulation Technologies. Computer-based, biologically realistic simulations of parts of neurons, neurons, and circuits. 9. Mathematical, Statistical and Computer Algorithms. Such algorithms could be used to analyze large and/or complex data sets. Examples of these data sets include those derived from multiple, single-unit recording studies and functional imaging studies. Among other applications, these could be used to segment images (obtained from electron or light microscopes, or from volumetric imaging instruments such as confocal microscopes and magnetic resonance imagers), filter noise, visualize data or search vast data sets for specified patterns or data (e.g., use of pattern recognition algorithms to search time series data sets obtained from electrophysiological recording of neural activity, or video data obtained from behavioral analysis of genetically altered animals). In addition, digital reconstruction of dendritic and axonal arbors would be of interest. 10. Telemetry. Transferring data from one point to another is important for neuroscientists monitoring the physiological signals from the brain. Telemetry, even over relatively short distances (from a few millimeters to a few meters), could, for example, provide a means to obtain data from awake, behaving animals without interfering with the behavior of interest. Examples include telemetry that can be easily implanted/attached to awake behaving animals for measuring peripheral/autonomic responses (this approach could be used to inform stress/emotion research), miniaturized telemetry for use in smaller animals with increased numbers of recording devices/electrodes implanted per animal. Alternatives to telemetry would be considered as well. 11. Biosensors. Neurons communicate with each other through thousands of different chemical substances; internally, molecular pathways direct the function of the neuron. Sensors of high specificity and sensitivity for such substances would provide neuroscientists with important new ways to study the brain. B. Instrumentation for Basic Neuroscience Research. Modern equipment that uses the most recent technological advances is needed in neuroscience research so that neural substrates of mental illness can be identified and localized. The NIMH is interested in supporting research and development of new or improved approaches relevant to, but not limited to, the following: 1. Neurophysiology. Microelectrodes for stimulation and/or recording, smart nanoscaffolds, macroelectrodes, biocompatible coatings, interfaces to electronics, software for data analysis, visualization, etc. Systems with better/easier MR compatibility would also be of interest. 2. Cell Sorting. Based on cell size, type, function, morphology, abnormal features, specific membrane proteins, etc. 3. In Vivo Electrochemical Voltammetry. More sensitive and selective electrodes, software for data analysis, etc. 4. High Performance Liquid Chromatography. Improved reliability, specificity, sensitivity, etc. 5. Technology to support Multiple Unit Recording Electrode Arrays. Recording techniques, analysis techniques and raw data storage. 6. Physiological and Behavioral Monitoring. Temperature, activity, sleep duration, neuronal activity, EEG activity, EKG, pulse rate, recording, capture and analysis of multiple single unit activity from microelectrodes, automated SWS analysis and coherence of EEG rhythms, and further refinement of High density EEGs. 7. Development of novel technologies for stimulating specific cells or signaling pathways in awake behaving animals. 8. Development of more sensitive fluorescent probes for simultaneous and real time measures of multiple neurotransmitter release and intracellular signaling pathway activities. 9. Associated Software. C. Macroscopic Neuroimaging. Modern technologies allow for the observation of the structure and function of the intact brain. This capability has the potential to greatly advance understanding of the brain in both health and disease, and across the lifespan. NIMH is interested in advancing this area of technology through enhancing current tools and approaches, as well as developing entirely new ways to image the brain. All modalities are of interest, including, but not limited to: magnetic resonance imaging (MRI) or spectroscopy, positron emission tomography (PET), optical imaging or spectroscopy, single photon emission computed tomography, magnetoencephalography (MEG), diffusion tensor imaging (DTI), etc. While not an imaging technique itself, transcranial magnetic stimulation (TMS) is an associated, important technology. TMS can be used in combination with fMRI as means to further assess physiology and integrity of neural systems both in health and in mental disorders. Due to its greatly increased use in recent years, technologies specifically focused on improving the utility and specificity of fMRI techniques are of particular interest. 1. Innovative agents and/or technologies to visualize brain connectivity, activity, and neural plasticity in situ with minimal invasion. 2. Improvement in the techniques, the design and construction of devices for non-invasive imaging for any modality, for example, improving spatial resolution, quantitative accuracy, signal-to-noise ratio, and electronics. 3. Development and enhancement of non-invasive imaging techniques for evaluating alterations in brain physiology produced by drugs. These would include techniques for monitoring changes in regional blood flow; concentrations of drug and/or tissue metabolites; and the distribution and activity of receptors. 4. Synthesis, or isolation from natural products, of highly selective receptor ligands or indicators of neurochemical processes, which would be labeled for imaging by one or more particular modality. 5. Development of selective hormone receptor ligands for brain imaging. 6. Development of imaging agents to examine the integrity of the blood brain barrier following infection and other environmental challenges. 7. New approaches in radiochemistry that will permit more exact identification of the chemical changes associated with behavioral states (e.g., sleep or arousal) or mental illness as observed with any particular neuroimaging modality. 8. Synthesis of molecules containing stable, rarely occurring isotopes designed to be detected by non-invasive imaging techniques (e.g., fluorine-containing molecules, carbon-13 labeled substrates). 9. Methods and associated products for quantification of imaging data including new statistical approaches for evaluating the data. 10. Methods to integrate routines for greater and more precise computer enhancement of the images, and for combining or overlaying images obtained from multiple modalities. 11. Software needed for the precise quantification of data obtained from these imaging techniques with emphasis on the reliable definition of discrete, anatomically distinct areas within the brain. 12. Novel agents or other tools to increase the ability to correlate features of MR images with histological features (e.g., cytoarchitecture or chemoarchitecture) both identified and those yet to be identified. 13. Generation of physiologic measurements from images of regional radioactivity generated during PET, especially for the study of brain neurotransmitter/neuroreceptor systems. 14. Novel approaches to visualizing data obtained in neuroimaging, such as the computational “unfolding” of three-dimensional images of cerebral cortex. 15. Improved methods for pediatric brain imaging. These would include: software and database products, equipment for creating a “child-friendly” environment and for the behavioral training of children and impaired subjects for cooperation and motion reduction during neuroimaging procedures. 16. Combining of different imaging technologies (e.g., ERPs and fMRI; MEG and fMRI; MEG and EEG, optogenetic methods and fMRI, etc.). The latter example, optfMRI, can be used as means of improving tools for further understanding of neural bases of fMRI signals and to produce connectivity a map of neural cells that can be defined both genetically and topographically with a combination of these two techniques. 17. New tools and devices to simultaneously record hemodynamic signals (BOLD, rCBF, etc.) and neural activity (EEG, LFP, spiking, etc.) to better understand the direct relationship between blood flow variables and neural activity within the brain. 18. Development of equipment, software and other tools for recording and quantifying eye movements, motion, and autonomic reactivity during scanning, applicable to all ages (including young children) particularly in the MRI environment. 19. Methods for relating changes in brain morphology and metabolism associated with age, particularly infancy through adolescence, to changes in hemodynamic responses to neural activity and fMRI signals. 20. Improvements in TMS techniques that will allow for greater specificity in the sites of stimulation and greater control over the effects of the stimulation. In particular, improvements in stimulators that would allow much smaller effective fields of stimulation with more reliable and repeatable stimulator placement would be a significant benefit to the field. 21. Real time fMRI is becoming a research tool of interest with potential clinical/therapeutic neurofeedback applications. Products are needed that would enhance the ability of scientists to use this technology for those neurofeedback applications in an off-the-shelf manner. 22. Development of methods to improve efficiency, specificity and controllability of viruses used in primate tract tracing studies. 23. Development of more sophisticated imaging strategies in rodents. 24. Development of a user-friendly interface to serial reconstruction software capable of generating stackable, 3D images of axonal and dendritic arborizations at the light and electron microscopic level. D. Microscopic Neuroimaging. The morphology of individual neurons and the distribution of subcellular components within them, are key to understanding the manner in which these cells function. Advances in the development of agents indicating neuronal structure and function that can be visualized microscopically are important to the NIMH's interest in brain research. This includes enhancements of current agents and ligands to be imaged (agents indicating specific biochemical processes or structures, etc.); development of novel agents and ligands; software to assist interaction with the data; and other related technologies and methods. Examples would include, but not be limited to: 1. Software and hardware for analyzing image data obtained by microscopes, including tools to automatically or semi-automatically. Identify particular profiles (e.g., labeled cell bodies), segment images, reconstruct images into three dimensional representations, perform unbiased counting and measuring, etc. 2. Synthesis and testing of novel or improved probes for microimaging the nervous system. E. Molecular and Cellular Neurobiology and Neurochemistry. Manipulating and studying basic molecular, cellular and chemical processes has led to insight to understanding brain function, and has provided the foundation on which pharmacological interventions have been developed for the treatment of mental illness. NIMH is interested in supporting a wide range of new techniques and tools related to this area. These include, but are not limited to: 1. New low-cost techniques for hybridoma production of monoclonal antibodies specific for “neural antigens” (e.g., neurotransmitters, small peptides, neurotransmitter receptors). 2. Innovative methods for establishing a “monoclonal bank” (frozen cells) for each of the cell lines as a permanent, widely available, reliable, and low cost source of monoclonal antibodies for research on the nervous system. 3. Labeled antibodies or other agents that will readily identify receptors for which there are no ligands (orphan receptors) and which have low densities in the brain. 4. Automated methods for quantifying the low levels of bound ligands for quantifying receptors that are sparsely scattered in the brain. 5. New cell lines that express each of the known neurotransmitter receptors so that each cell line will be homogeneous for one receptor. 6. New cell lines that express each of the above receptors linked to some metabolic function and/or second messenger so that the functional consequences of receptor occupancy can be detected. 7. High volume, inexpensive assay methods for measuring both receptor occupancy and cellular response for each of the receptor types. 8. Develop cell culture models for neurons, including methods of purifying homogeneous populations of non-transformed cells by, for example, developing markers to identify neuronal cell types for use in characterizing cell-type-specific signaling pathways which may be useful in tracking the effects of various drugs. 9. Develop techniques for either activating or deactivating specific ion channels, receptors and signal transduction pathways. 10. Develop dynamic biochemical and imaging assays that allow measurement of variables now obtained only through electrophysiological techniques. 11. Develop tools to facilitate proteomic analysis of CNS neurons. 12. Develop tools to facilitate in vivo studies of protein-protein interaction, folding and aggregation. These technologies could impact our understanding of the basic neurotransmitter receptors chemistry and on developing of more selective small chemical entities with high affinities for CNS targets. 13. New approaches to study the multiple functions of particular proteins. 14. Tools to study post-translational changes in proteins (expression levels, post-translational modifications, etc.) in specified tissue compartments and subcellular domains. 15. Technologies to study functional entities within cells (e.g., green fluorescent protein approaches) and subcellular compartments. 16. Tools and approaches to study coordinate changes in genes and their functional relationship to phenotypes, including phenotypes associated with specific brain disorders. 17. Novel tools and approaches to study protein-protein interactions, especially those with phosphoproteins. Further develop methods and reagents for studying the structures of membrane proteins at atomic resolution. Membrane protein systems that are of particular interest to NIMH include proteins involved in normal function and pathology of cells (neurons and glia) in the central and peripheral nervous system. 18. Develop novel techniques for isolating and identifying the structure of brain-derived membrane proteins. 19. New methods to identify peptide receptors for which traditional biochemical approaches (e.g.: radiolabeling techniques) failed to produce results. This would be relevant for the development of small molecular probes that would target peptide systems that might be altered in mental disorders. 20. Development of new and optimization of the existing methods for non-invasive quantitative detection of hormones and hormone action in awake behaving animals. 21. Development of novel technologies to adapt human induced pluripotent stem cells (iPSCs) to identify molecular and cellular dysfunction underlying mental illness and for high throughput screening assays for candidate therapeutics. 22. Continuing to improve optogenetic techniques (combining optical and genetic techniques to probe neural circuits within intact animals). F. Genetic and Transgenic Technology. Advances in genetic and transgenic technologies offer many opportunities to probe fundamental questions about the brain, behavior and pathology. NIMH is broadly interested in these areas; some examples of topics relevant to the mission of this Institute include, but are not limited to: 1. Methods to perform site-directed mutagenesis in cell lines for the study of membrane proteins such as ion channels and neurotransmitter receptors. 2. Development of gene “knockout” or “knockin” animals using such approaches as homologous recombination targeting genes important in neurotransmission, development, and tropic interactions as well as models relevant to psychiatric disease. 3. New methods to delete or alter targeted genes in the preparation of transgenic animals including methods that increase or decrease gene expression. 4. Development of new techniques and apparatus for delivery of synthetic nucleic acids to manipulate endogenous gene expression in specific cell populations and/or brain regions. 5. Develop and validate standardized behavioral tests and apparatuses to assess the gene knockouts and/or gene “knockins” affecting neurotransmission. 6. New approaches for spatially and/or temporally restricted gene activation and/or inactivation. 7. Develop novel markers for elucidating how signaling cascades impact DNA transcription. 8. New ways to assess quantitatively transcription of genes in real time in a manner that is minimally injurious to cells (e.g., non-permeabilizing approaches). 9. Develop new technologies to study gene function and expression, including approaches to studying gene and protein expression at single cell resolution. 10. Develop novel approaches to study the expression characteristics of non-coding (nc) RNA molecules as well as developing methodologies using nc-RNAs to manipulate gene expression in cells and tissues of the nervous system. 11. Development of embryonic stem (ES) cell lines from rodent strains (rats and mice) of relevance to behavioral research. 12. Development of technologies and approaches to facilitate the collection and distribution of ES cell lines containing mutations of potential relevance to behavioral and neural processes relevant to neuropsychiatric disorders. 13. Develop methods for long-term storage of transgenic germ cell lines. 14. Develop technologies and approaches to aid in the renewal of founder colonies of transgenic mice from repositories of transgenic germ cell lines. 15. Develop databases on neurobiological transgenic animals produced to date, including information such as the origin of the transgenic animal, key features of the biological and behavioral mutant, availability and location of germ cell lines, and existence of breeding colonies. 16. Develop gene transfer technologies such as viral vectors and non-viral (e.g. polymer-based) systems to produce long-term, stable gene expression in the brain. 17. Develop methods to analyze and manipulate DNA structure to study epigenetic modifications and chromatin remodeling in brain tissue and neuronal populations. 18. Development of selective gene silencing strategies to ablate neurons in one circuitry in order to examine its specific behavioral consequences. 19. Technology development in epigenetics: a) development of novel and highly accurate tools to analyze proteomics of histones b) development of antibodies for immunochemical studies of histone modifications that selectively target a specific DNA modification site c) develop and apply tools for epigenetic research to determine how, when, and where experience affects gene expression. 20. Technology development in Microbiome research: a) development of tools for high throughput genomic analysis of human microbiome; b) development of informatics tools to study the huge amount data that will result from these studies; and c) development of methods to determine the interaction between microbial community genes and host genetics as a potential contributing factor for mental disorders. G. Neuroimmunology. Research on the interplay between the brain, neuroendocrine system, and, immune system has revealed important links between these major homeostatic system components. Examples of NIMH-relevant topics in this area include, but are not limited to: 1. Development of new tools to explore the specific properties of the blood-brain barrier responsible for the selective delivery or retention of cytokines, immune cells, and drugs affecting immune activity in the brain. 2. Development of assays for identifying potential autoimmune components of psychiatric disorders. 3. Identification of critical molecules, processes, and pathways mediating signals from the peripheral immune system to the brain. 4. Development of novel cytokine ligands and antagonists, and neuroimaging agents. H. Pharmacology. Pharmacological intervention represents a major force in the treatment of mental illness, and NIMH is interested in supporting research and development in this area. However, pharmacologic agents that primarily act on molecular targets which replicate those of currently-marketed pharmaceuticals used in the treatment of mental disorders would not be of interest for this program. Relevant pharmacology topics include, but are not limited to: 1. New chemical entities with high, selective affinities for CNS targets. Examples include, but are not limited to, receptors, transporters, ion channels, enzymes, kinases, or second or third messenger systems. 2. Methods to evaluate old and new chemical entities (including complex mixtures of crude extracts from natural products) for possible therapeutic usefulness using “in vitro” and “in vivo” assays and model systems. 3. Methods for extraction, fractionalization, and isolation of active compounds from natural products. Water-soluble compounds are of particular interest due to the difficulty of the procedures. 4. Computer algorithms that model receptors to evaluate theoretical permutations of known molecules to find the molecule with the maximum probability of having the highest affinity for a specific receptor as well as those that have the potential for the most desirable “on” and “off” rates. 5. Computer models of the blood brain barrier and evaluate potential and actual drug molecules for their ability to cross or penetrate this barrier. 6. Strategies for evaluating pharmacological agents (e.g., animal behavioral testing, computer simulation) within specific domains of cognitive function. 7. Behavioral “models” similar in animals and humans; behavioral pharmacological effects that may serve as “surrogate” markers in humans. 8. Development of models for evaluating drug effects within functional brain circuits relevant to mental disorders. 9. Development of novel drug delivery systems. 10. Tools for Drug Development including neuroimaging (e.g., radiolabeled compounds) and development of animal models. 11. Pharmacological profiling (in vitro and in vivo) for potential therapeutic drugs. 12. Methods for evaluation of long-term effects of psychotropic drug administration in animal models or human subjects. If clinical populations are being tested, the technology would be appropriate for either the Division of Developmental Translational Research (DDTR) or the Division of Adult Translation Research (DATR) at NIMH. 13. Improving existing, and developing new, vectors for delivery of genes to the brain. 14. Development of novel therapeutic approaches targeting gene expression through effects on promoter activity or epigenetic mechanisms. 15. Development of novel high throughput screening (HTS) assays for drug development. Examples include, but are not limited to, in vitro functional assays, toxicology screens, blood-brain barrier permeability assays, and circuit based or behavioral assays. 16. Development of novel molecular targets for drug development to treat mental illnesses. I. Tract Tracing Methods and Tools. Little is known about the details of the connectivity of the human nervous system, because the best tract tracing techniques are invasive and require the deposit of substances in vivo. Methods that would be applicable to post-mortem tissue would allow significant progress in connectional studies of human tissue, as well as non-human tissue, particularly with regard to the development of c, quantu onnections and the connections of structures not easily accessed in vivo. Examples include the development of improved physical, chemical and/or biological markers for neuroanatomical tract-tracing (e.g. m dots, caged molecules, viral delivery agents, etc.). J. Educational Tools. Neuroscience, basic behavioral science and human genetics are compelling areas of science that not only touch upon a diverse array of disciplines, but also provide insights to the essence of what it is to be human. Products aimed at teaching the substance of these fields to students of all ages would be useful in disseminating this information and these insights. Examples include, but are not limited to: software and other interactive media used to convey fundamental concepts about the brain to children; computer simulations of neuroscience experiments; updateable media that presents state-of-the-art information on particular topics for use by experts; website or other online, interactive electronic vehicle to allow for sharing of information about the brain and its functions, including technologies for holding interactive research conferences related to basic behavioral sciences, basic neuroscience, or clinical neuroscience. K. Neuroinformatics. Data generated by brain research are diverse, vast, and complex. The diversity of data is due to the fact that neuroscience data are obtained from: theoretical, experimental and clinical approaches; from levels of biological organization that span molecules to populations of individuals and from single-cell organisms to humans; and from states of health, disease, and models of disease. The quantity of data in brain research is the result of tens of thousands of neuroscience laboratories working around the world. The complexity of data reflects the high level of interconnectedness of the data, and their high dimensionality. Neuroinformatics is a new area of science that draws upon neuroscience, information science, computer science, statistics, applied mathematics, and a variety of engineering fields to develop tools that will let neuroscientists make better sense and use of their data. These tools include software and hardware for digital data acquisition, visualization, analysis, integration, and sharing (e.g., through tools for electronic scientific collaboration). Such tools can address data of any type or from any area of neuroscience; examples include, but are not limited to: 1. Databases, querying approaches, and information retrieval tools for neuroscience and neuroscience-related data. An example would be the development of a web-based database for sharing, analyzing and comparing the pharmacological responses of a variety of CNS active compounds in preclinical studies relevant to mental health. 2. Tools for neuroscience data visualization (and other forms of presentation) and manipulation (probabilistic atlases of brain structure or function, new statistical approaches for analyzing data, etc.). 3. Software for integration and synthesis of neuroscience data (computational models of neurons to integrate data about structure and function, environments to merge data from multiple imaging modalities, etc.). 4. Tools for electronic collaboration to allow neuroscientists to interact with colleagues, data, and instruments at a distance (this could include novel types of “groupware”, etc.). 5. Tools that bridge existing neuroscience and biology information tools and resources, such as databases and informatics tools associated with genome mapping efforts. For further information on basic neuroscience or basic behavioral science research topics, contact: Margaret Grabb, Ph.D. National Institute of Mental Health 6001 Executive Blvd. Room 7201 Mail Stop Code 9645 Bethesda, MD 20892 301-443-3563, Fax: 301-443-1731 Email: mgrabb@mail.nih.gov HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 The Division of Developmental Translational Research directs, plans, and supports programs of research and research training leading to the prevention and cure of childhood psychopathology. This long-term goal will be accomplished through an integrated program of research across behavioral/psychological processes, brain development, environment and genetics. The topics listed below reflect the NIMH interest in technologies related to this research area, but should not be considered a complete list. Prospective applicants are strongly encouraged to contact Dr. Margaret Grabb (listed below) with questions about the relevance of their interests to the mission of this division. A. Technologies for Clinical Pediatric Research. It is important to develop reliable methods that can correctly identify the normal and abnormal components of cognitive, emotional, and psychosocial behavior, as well as normal and abnormal physiological and biochemical functions, in human development. Computer-based methods of accomplishing this are also needed to increase the accessibility and reliability of information made available to the research community. Examples include: 1. Measurements of Alterations in Pediatric Development in Patients with Mental Health Disorders Using Physiological and Behavioral Measures. Research studies indicate that some mental health disorders, such as autism, may begin to develop as early as infancy. Therefore non-invasive modern equipment that use the most recent technological advances are needed to isolate specific physiological and behavioral changes during development, to identify potential diagnostic markers of mental health disorders. A priority for this program is to support research and development of hardware and software tools to measure pediatric development. Examples of technologies needed include: a. Psychophysiological measures to evaluate infants, children or adolescents. b. Miniaturized non-invasive instruments to record psychophysiological data (e.g., heart and respiration rate, galvanic skin response, and defensive motor behavior). c. Telemetry capability for non-invasive devices so that children can be monitored for prolonged periods without interfering with their behavior. d. Computer programs and inexpensive computers that will collect, analyze and identify recurring patterns in the psychophysiological measure(s) of interest. 2. Pediatric Assessment Tool. Diagnosis of mental health disorders in children and adolescents is vital to providing early interventions to treat the disorder. In addition, a better understanding of the concept of functioning in psychopathology, and its appropriate measurement, is needed in pediatric populations. In the future, diagnostic tools may even help detect the initial onset of illness in children at risk, before symptoms occur. A priority for this program is to develop novel diagnostic tools to detect mental health disorders in children and adolescents. Of particular interest to this division are methods that can be used with children and adolescents with limited verbal communication (i.e., very young or developmentally disabled). Biochemical, genetic, physiological and psychological tool development is welcomed. a. Technologies to assess CNS effects of psychosocial or pharmacological interventions. b. Development of reliable and stable biomarkers/biosignatures that can identify at-risk individuals prior to disease onset, biological and behavioral indicators or predictors of treatment response, measures of disease progression, measures to identify dose ranges prior to clinical studies, preclinical or clinical efficacy testing, toxicity measures for drug development, defining patients to enroll in the clinical study, identifying CNS abnormalities, etc. c. Assessment tools for pediatric mental health disorders that are sensitive to developmental change, gender and cultural diversity, variation in cognitive and behavioral functioning, hearing and/or speech impairment, and co-morbid disorders. d. Innovative approaches to assessing mental disorders using new statistical and psychometric techniques such as Item Response Theory. e. Computerized methodologies for assessing various mental disorders suitable for use in primary care settings, e.g. they would need to function rapidly and reliably. f. Biological and behavioral measures to define and assess specific impairment-related components of psychiatric disorders, e.g., cognitive dysfunctions in schizophrenia. g. Development of valid and reliable measures that operationalize functioning within and across developmental periods, and that can be used in a variety of service settings. Such measures can lead to more accurate diagnoses, a better understanding of the impact of psychiatric disorders, and better tracking of treatment effectiveness. 3. Behavior Monitoring and Analysis of Pediatric Mental Health Disorders. a. Improve or create new video devices to monitor human behavior and ease analysis of behavior. b. Computer software to ease analysis of behavior monitored by video or telemetry systems. c. Automated methods to detect specific emotional states using behavioral and autonomic indicators: This Division is specifically interested in technologies that can identify children with heightened or dampened emotional states that could be associated with particular mental health disorders, including children with limited verbal skills (i.e., very young or developmentally disabled). If the technology will primarily be used to investigate basic mechanisms of behavior, the Division of Neuroscience and Basic Behavioral Science at NIMH would be the most appropriate division to contact. 4. Intervention Development for Childhood-Onset Mental Disorders. a. Strategies (e.g., animal behavioral testing, computer simulation) for evaluating, in early developmental periods, the effects of pharmacological agents on specific functional domains and brain circuits associated with mental disorders. b. Strategies (e.g., animal behavioral testing, computer simulation) for evaluating, in early developmental periods, the effects of cognitive or behavioral interventions (e.g., cognitive rehabilitation, attention training) or device-based protocols (e.g., transcranial magnetic stimulation or direct current stimulation) on specific functional domains and brain circuits associated with mental disorders. c. Methods for evaluation of long-term effects of psychotherapeutic drug administration or brain stimulation protocols in developmental animal models. 5. Methodological Research and Development. There is a need to devise new ways of data collection, analysis, management and dissemination. Examples include: a. Technologies that use the most recent technological advances to identify aberrations in the CNS during development, associated with mental disorders. Once these aberrations are identified and localized, rational therapies can be developed and evaluated. b. Innovative, computer-based methods to monitor preventive and treatment intervention efforts and correlate them with outcome measures are needed. Results should be accessible to other interested parties without compromising the privacy of the individual. c. Development of innovative software for addressing the integration of distributed cross-disciplinary data sources into coherent knowledge bases. The data should focus on pediatric mental health disorders. d. Computer-based intervention development for parents or for school settings. e. Development of databases containing detailed genetic and behavioral information on pediatric populations and their families, as resources for the field in investigations of gene x environment interactions. f. Mathematical, statistical and computer algorithms that could be used to analyze large and/or complex data sets. Examples of these data sets include those derived from functional imaging studies. Among other applications, these could be used to segment images such as those obtained from magnetic resonance imagers, filter noise, visualize data or search vast data sets for specified patterns or data (e.g., use of pattern recognition algorithms to search time series data sets obtained from electrophysiological recording of neural activity, or video data obtained from behavioral analysis of genetically altered animals). Improved techniques for path analysis when examining functional imaging datasets would also be of interest. B. Child and Adolescent Treatment and Preventive Intervention Research. An estimated one in ten children and adolescents in the United States suffers from mental illness severe enough to cause some level of impairment. Yet, it remains unclear what treatments are the best and safest for these developing age groups. A priority for this program is to support research and development of novel psychopharmacological or psychosocial approaches for the treatment and prevention of mental illness in childhood and adolescence, in subjects aged 18 and below. The goal of this research is broad and inclusive with respect to the heterogeneity of patients, the severity and chronicity of disorders, and the range of outcomes measured. Disorders studied include all mental and behavioral disorders. Interventions studied include pharmacologic approaches (individual and combination medications), somatic approaches, behavioral and psychotherapeutic approaches. Research is supported on individual and combined approaches. Research that translates findings on basic physiological or behavioral processes into novel preventive or treatment interventions is especially encouraged. Effectiveness studies that focus on interventions of known efficacy are assigned to the Division of Services and Intervention Research. Human subjects include child and adolescent age groups covering the full range of mental disorders individually and in complex patterns of comorbidity with other mental disorders and behavioral problems (e.g., anxiety and depression) and substance abuse (e.g., depression and alcohol abuse). 1. Pharmacologic Treatment Intervention. Clinical testing of novel mechanism therapeutics is the principle aim of this technology development section. This includes Phase IIa and proof of concept studies in pediatric subjects. It is expected the pharmacologic agents selected for these studies be IND-ready and based on novel molecular targets identified through basic and clinical research, preclinical research and animal model research relevant to understanding developmental aspects of mental illness. 2. Combined Intervention. Areas include all research that combines different treatment modalities in a single combined or comparative protocol (e.g., pharmacologic plus psychosocial intervention). 3. Psychosocial Intervention. Areas include development and application of new psychotherapeutic, behavioral, and psychosocial treatments, based on the latest advances in development neuroscience. 4. Preventive Intervention Program. Areas include preventive intervention studies in which efficacy has not been demonstrated, including those designed to reduce the risk of onset or delay onset of mental disorders, dysfunctions and related problems within asymptomatic and subclinical populations and those related to treatment (e.g., prevention of relapse, recurrence) or side effects (prevention/ minimization of tardive dyskinesia, etc.). Prevention studies that focus on behavioral problems, without a focus on a specific mental health disorder or a specific domain of function that significantly impacts a mental health disorder (e.g. cognitive function) should contact NICHD. 5. Development and Maintenance of Clinical Trial Networks. Areas include the development of hardware/software to facilitate research collaborations in conducting clinical trials, technologies to facilitate data sharing, merging of multiple data sets, and the development and maintenance of common protocols across research sites working on a common pediatric preventive or treatment intervention. C. Science Education in Mental Disorders. There is a critical need for improvement in science education, particularly in areas specifically related to brain, behavior and mental illness. Examples include: 1. Research on the best ways to present neuroscience and behavioral science information, in the context of mental health disorders, to particular groups of students (e.g., kindergarten through sixth grade). 2. Computer-based systems to teach students how to observe scientific phenomena related to the brain, behavior and mental illness, and to report them clearly in writing. 3. Research on better ways to communicate new knowledge and directions of scientific growth in the area of neuroscience and mental illness to teachers and curriculum developers. For further information on Developmental Translational Research-related topics, contact: Margaret Grabb, Ph.D. National Institute of Mental Health 6001 Executive Blvd. Room 7201 Mail Stop Code 9645 Bethesda, MD 20892 301-443-3563, Fax: 301-443-1731 Email: mgrabb@mail.nih.gov HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 General Areas of Interest The NINDS accepts a broad range of small business applications that are significant, innovative, and relevant to its mission. Examples of research topics within the mission of NINDS that may be of interest to small businesses are shown below. This list is not all inclusive and some research areas fall into multiple categories. 1. Therapeutics and Diagnostics Development for Neurological Disorders, including biomarker and diagnostic assays, therapeutics (drugs, biologics, and/or devices) for treatment of neurological disorders, and technologies/methodologies to deliver therapeutics to the central nervous system. 2. Clinical and Rehabilitation Tools, including intraoperative technologies for neurosurgeons, rehabilitation devices and programs for neurological disorders, and brain monitoring systems 3. Technology and Tools, including imaging technologies to image the nervous system, neural interfaces technologies, and tools for neuroscience research and drug development. In addition to the research topics listed, NINDS also solicits applications in specific program areas. For additional information about NINDS program announcements, please visit our small business home page at: http://www.ninds.nih.gov/funding/small-business/. Clinical Trials The NINDS is committed to identifying effective treatments for neurological disorders by supporting well-executed clinical trials. NINDS may decline funding of a clinical trial application for programmatic or administrative reasons. SBIR applicants are strongly encouraged to contact Joanne Odenkirchen (contact information provided below) within the NINDS Office of Clinical Research for advice about potential clinical trial applications prior to submission in order to determine the relevance of the proposed research to NINDS and its potential for translating discoveries to clinical interventions for neurological disorders. For more information about what is generally required before trials are funded, applicants are encouraged to review the NINDS Office of Clinical Research webpage ( http://www.ninds.nih.gov/research/clinical_research/index.htm ). Joanne Odenkirchen, M.P.H. Clinical Research Project Manager, Office of Clinical Research 301-496-3104 Email: jo21x@nih.gov NINDS Cooperative Program in Translational Research Although translational research is supported through the general SBIR/STTR program announcement, the NINDS also has a Cooperative Program in Translational research (PAR-08-235). The NINDS Cooperative Program encourages Phase II and Fast-Track applications that directly address the identification and pre-clinical testing of new therapeutics for neurological disorders. The program will facilitate solicitation, development, and review of therapy-directed projects to accelerate the translation of basic research discoveries into therapeutic candidates for clinical testing. This program is specifically directed at projects that include therapeutic leads with demonstrated activity against the intended disease target. The program supports pre-clinical optimization and testing of these leads and projects must be sufficiently advanced that an IND or IDE application to the FDA can be submitted by the end of the project period. The program does not support early-stage therapeutic discovery activities such as high throughput screening. The program also excludes clinical research, basic research, and studies of disease mechanism. This is a milestone-driven cooperative agreement program involving participation of NINDS staff in the development of the project plan and monitoring of research progress. For more information on the NINDS Cooperative Program in Translational Research-Small Business Awards (SBIR[U44]): http://grants.nih.gov/grants/guide/pa-files/PAR-08-235.html. Due to the unique requirements of the NINDS Cooperative Program in Translational Research, applicants are strongly encouraged to consult with Dr. Tom Miller at least three months prior to the next receipt date. Dr. Tom Miller, Ph.D., M.B.A. Program Director, Office of Translational Research 301-496-1447 Email: millert@ninds.nih.gov Countermeasures Against Chemical Threats NINDS manages the NIH Countermeasures Against Chemical Threats (CounterACT) program. CounterACT supports research and development on new and improved therapeutics or diagnostic technologies to prevent or mitigate the toxic effects from exposure to chemical threats, defined as toxic chemical agents that could be used in a terrorist attack against civilians, or those that could be released at toxic levels by accident or natural disaster. This includes the development of new (or support of existing) partnerships between small business and not-for-profit laboratories engaged in this research. The scope of research supported includes early screening for compounds with the desired biological activity, advanced preclinical and efficacy testing, through clinical research with promising candidate therapeutics. For more information on this program, including specific program announcements, please see: www.ninds.nih.gov/counteract. Applicants are strongly encouraged to consult with Dr. David Jett to determine the programmatic relevance of their proposed research. David A. Jett, Ph.D. Program Director, NIH CounterACT Research 301-496-6035 Email: jettd@ninds.nih.gov For additional information on research topics, contact: Ms. Stephanie Fertig, M.B.A. Research Project Manager, Small Business Programs 301-496-1447, Fax: 301-480-1080 Email: fertigs@ninds.nih.gov or for general questions related to the small business program, email: nindssmallbusiness@mail.nih.gov For administrative and business management questions, contact: Ms. Tijuanna Decoster Chief, Grants Management Branch 301-496-9231, Fax: 301-402-4370 Email: decostert@mail.nih.gov HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 This area of interest focuses on the development and evaluation of innovative prevention and intervention programs, or specific materials for integration into existing programs, which utilize state-of-the-art technology and are based on currently accepted clinical and behavioral strategies. Applicants are strongly encouraged to consult with research methodologists and statisticians to ensure that state-of-the-art approaches to design, analysis, and interpretation of studies under this topic are used. Areas that may be of interest to small businesses include, but are not limited to: A. Development and evaluation of innovative prevention/intervention programs, or specific materials for integration into existing programs, which utilize state-of-the-art technology and are based on currently accepted clinical and behavioral strategies. Special emphasis should be placed on the needs of high-risk groups, ethnic and minority populations, youth, children of alcoholics, women, the handicapped, and the elderly. Examples of such materials include school-based curricula, interactive videos, computer-based multimedia programs, training manuals for teachers or parents, and community-based programs. B. Development and evaluation of educational materials designed to intervene with the elderly around specific age-related risks for alcohol problems. Particular attention should be given to age-related reductions in alcohol tolerance, interactions between alcohol and prescription and over-the-counter medications, possible exacerbation of some medical conditions common among the elderly, potential biomedical and behavioral consequences of excessive alcohol use, and the role of alcohol in falls, fires, burns, pedestrian and traffic injuries, and other unintentional injuries. C. Development and evaluation of statistical analysis programs tailored to the design and analysis of alcohol prevention-relevant research. Programs could focus on a variety of areas including: imputation of missing data under varying design assumptions; simulation of distributions of outcomes based on varying mixtures of sample populations; application of chronic or infectious disease models to targeted communities; and models of the potential effect of various policy-based interventions, such as increased taxation or reduction of outlet density by license revocation and control. Robert C. Freeman, Ph.D. 301-443-8820 Email: Robert.Freeman@nih.gov HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 The Division of Microbiology and Infectious Diseases (DMID) supports research to better understand, treat, and ultimately prevent infectious diseases caused by virtually all infectious agents, except HIV. DMID supports a broad spectrum of research from basic molecular structure, microbial physiology and pathogenesis, to the development of new and improved vaccines and therapeutics. DMID also supports medical diagnostics research, which is defined as research to improve the quality of patient assessment and care that would result in the implementation of appropriate therapeutic or preventive measures. DMID does not support research directed at decontamination or the development of environmentally oriented detectors, whose primary purpose is the identification of specific agents in the environment. Note that some of the organisms and toxins listed below are considered NIAID priority pathogens or toxins for biodefense and emerging infectious disease research. Director: Dr. Carole Heilman 301-496-1884 Email: ch25v@nih.gov A. Bacteriology and Mycology Branch. The branch oversees research on medical mycology, hospital infections (including Acinetobacter, Klebsiella, Serratia, Legionella, Pseudomonas, Aeromonas, Enterobacter, Proteus, non-enteric E. coli, actinomycetes and others), staphylococci, enterococci, bacterial zoonoses (plague, anthrax, tularemia, glanders, melioidosis, Lyme disease, rickettsial diseases, anaplasmosis, ehrlichiosis and Q fever), and leptospirosis. Research is encouraged in the following general areas: (1) product vaccines, adjuvants, therapeutics and diagnostics (including target identification and characterization, device or apparatus development, novel delivery, and preclinical evaluation); (2) products to combat antibacterial and antifungal drug resistance; (3) applied proteomics and genomics; (4) host-pathogen interactions, including pathogenesis and host response; (5) genetics, molecular, and cell biology; (6) microbial structure and function; and (7) vector-pathogen interactions or disease transmission to humans via arthropod vectors. Research in the following areas is of particular interest to the branch, but research on all of the above is welcome: · Vaccines, therapeutics, and medical diagnostics for hospital infections · Adjunctive therapies to combat antimicrobial resistance Diagnostics for aspergillosis · Novel approaches for the diagnosis of Lyme disease Contact: Dr. Alec Ritchie 301-402-8643, Fax: 301-402-2508 Email: aritchie@niaid.nih.gov B. Enteric and Hepatic Diseases Branch. Special emphasis areas include vaccines against hepatitis C virus; antimicrobials and antivirals that focus on novel targets such as host-pathogen interactions to combat the development of resistance; vaccines and therapies for botulinum neurotoxins, especially therapies that that target toxins once they enter cells; therapies and diagnostics for Clostridium difficile that include recurrent disease issues; development of a simple, rapid point-of-care diagnostic tool for the simultaneous identification of multiple diarrheal pathogens that includes their antibiotic resistance profiles; pediatric vaccines to prevent the major worldwide causes of diarrhea; more stable vaccines and improved formulation methods; and novel therapeutics for chronic hepatitis B and C. Research areas of the Branch include the following organisms and diseases: astrovirus, Bacteroides spp., Campylobacter spp., enteric Clostridia spp. including botulinum neurotoxins, commensals and normal flora, pathogenic Escherichia coli, gastroduodenal disease, gastroenteritis, Helicobacter spp., Listeria spp., Noroviruses including Norwalk, ricin toxin, rotaviruses, Salmonella serovars, Shigella spp., Staphylococcus enterotoxin B, Vibrio spp. enteric Yersinia spp., hepatitis viruses A, B, C, D, and E, as well as cholera, diarrhea, enterotoxins, gastroenteritis, gastroduodenal disease and ulcers, and Guillain-Barre syndrome. Program Contact: Dr. Marian Wachtel 301-451-3754, Fax: 301-402-1456 Email: wachtelm@niaid.nih.gov C. Parasitology and International Programs Branch. Research areas: (1) protozoan infections, including amebiasis, cryptosporidiosis, cyclosporiasis, giardiasis, leishmaniasis, malaria, trypanosomiasis, toxoplasmosis; helminth infections, including cysticercosis, echinococcosis, lymphatic filariasis, schistosomiasis, onchocerciasis, others (e.g., roundworms, tapeworms, and flukes); invertebrate vectors/ectoparasites, black flies, sandflies, tsetse flies, mosquitoes, ticks, snails, mites; (2) parasite biology (genetics, genomics, physiology, molecular biology, and biochemistry); (3) protective immunity, immunopathogenesis, evasion of host responses; (4) clinical, epidemiologic, and natural history studies of parasitic diseases; (5) research and development of vaccines, drugs, immunotherapeutics, and medical diagnostics, and (6) vector biology and management; mechanisms of pathogen transmission. Chief: Dr. Lee Hall 301-496-2544, Fax: 301-402-0659 Email: lhall@niaid.nih.gov D. Respiratory Diseases Branch. Research areas: (1) viral respiratory diseases, including those caused by: human coronaviruses (including SARS), influenza viruses, and paramyxoviruses (including parainfluenza viruses and respiratory syncytial virus); (2) bacterial respiratory infections, including those caused by Moraxella catarrhalis (chronic obstructive pulmonary disease), Pseudomonas aeruginosa andBurkholderia cepacia (associated with cystic fibrosis), Corynebacterium diphtheriae (diphtheria), groups A and B streptococci,Haemophilus influenzae, Neisseria meningitidis, Bordetella pertussis (pertussis), Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Klebsiella pneumoniae and community acquired pneumonia; (3) acute otitis media; (4) mycobacterial diseases, including those caused by: M. tuberculosis (tuberculosis), extensively- and multi-drug resistant M. tuberculosis, M. leprae (leprosy), and M. ulcerans (Buruli ulcer) and other non-tuberculous mycobacterial diseases. Areas of emphasis include: development of new antibiotics with novel mechanisms of action, improved therapeutics for viral and bacterial respiratory diseases including immunotherapeutics, new or improved vaccines (with and without adjuvants), improved and more rapid multiplex point-of-care diagnostic tests or other screening tools that can detect infection prior to active disease and identify drug resistance. Contact: Dr. Gail Jacobs 301-496-5305, Fax: 301-496-8030 Email: ggjacobs@niaid.nih.gov E. Sexually Transmitted Infections Branch. Areas of emphasis include the development of medical diagnostics including better and more rapid multiplex point of care tests and other screening or novel delivery systems for diagnostic tools, topical microbicides, vaccines and drugs for sexually transmitted infections (STIs) and other reproductive tract syndromes, such as bacterial vaginosis; molecular immunology; vaginal ecology and immunology; epidemiologic and behavioral research including strategies to reduce transmission of STIs; genomics and proteomics of sexually transmitted pathogens; adolescents and STIs; STIs and medically underserved populations and minority groups; STIs and infertility and adverse outcomes of pregnancy; role of STIs in HIV transmission; role of HIV in altering the natural history of STIs; and other sequellae of STIs. Contact: Elizabeth Rogers 301-451-3742, Fax: 301-480-3617 Email: erogers@niaid.nih.gov F. Virology Branch. Areas of emphasis for SBIR/STTR applications include:1) vaccine development; 2) viral vectors; 3) structure and function of viruses and viral proteins as targets for therapeutic interventions or diagnostics; 4) the development and validations of assays for disease diagnosis and to measure response to therapy; 5) the development and preclinical testing of immunotherapeutic and antiviral drugs for acute and chronic viral illnesses; 6) approaches to identify antiviral targets and agents; 7) chemical design and synthesis of novel antiviral agents; 8) preclinical antiviral evaluations including in vitro screening and prophylactic or therapeutic antiviral evaluations of human viral infections in animal models; 9) the development of rapid medical diagnostic systems. The Virology Branch focuses on the following: acute viral infections (including Nipah and Hendra viruses), arthropod-borne and rodent-borne viral diseases (including Dengue, West Nile, Japanese encephalitis, Chikungunya, yellow fever, hantavirus, etc.), viral hemorrhagic fevers (Ebola, Lassa fever, etc.), measles, polio, coxsackie virus, enterovirus 71 and other enteroviruses, poxviruses, rabies, and rubella. The Virology Branch also focuses on the following persistent viral diseases and viruses: adenoviruses, BK virus, bornaviruses, coronaviruses, herpesviruses, human T-lymphotrophic virus, JC virus, human papillomaviruses, parvoviruses, and prion diseases. Applications targeting the development of therapies, immunotherapies, vaccines and diagnostics for any of these infections are sought. The Virology Branch does not support applications covering environmental detection and decontamination. Contact: Dr. Ramya Natarajan 301-594-1586, Fax: 301-402-0659 Email: ramya.natarajan@nih.gov HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 The Division of Cancer Treatment and Diagnosis funds research into the development of tools, methodologies and therapeutic agents that will better diagnose, assess, cure and effectively treat cancer. We support a spectrum of research projects from preclinical exploratory research and development through clinical trials. A. Cancer Diagnosis. The Cancer Diagnosis Program (CDP) supports the development of technologies, reagents, instrumentation, and methodologies to improve cancer diagnosis or prognosis or to predict or assess response to therapy. This does not include technologies for imaging of patients. CDP also supports the adaptation or improvement of basic research technologies for use as clinical tools. Technologies supported by CDP may be designed to work with tissues, blood, serum, urine, or other biological fluids. Technologies supported by CDP include but are not limited to the following: 1. Technologies for comprehensive and/or high throughput analysis of molecular alterations at the level of DNA, RNA, or protein. Includes for example, mutation detection systems, gene expression arrays, systems for monitoring epigenetic changes (alternative splicing or methylation), high throughput proteomics (including post-translational modification and protein-protein interactions and methods for protein quantitation). 2. Micro-electro mechanical systems (MEMs) and other nanotechnologies for the analysis of DNA, RNA, or protein (e.g., micro-capillary systems, lab on a chip applications, micro-separation technologies). 3. Mass spectrometry for the analysis of nucleic acids or proteins. 4. Discovery and development of new or improved diagnostic markers or probes targeting changes in DNA, RNA, or proteins, including the generation of molecular diversity libraries by phage display and other combinatorial techniques, and affinity-based screening methods. 5. cDNA library technologies, including improved methods for generating high quality cDNA clones and libraries and methods for generating high quality cDNA from tissues (including archived specimens). 6. Resources for clinical research. a. Instruments, technologies or reagents for improved collection, preparation, and storage of human tissue specimens and biological fluids. b. Improved methods for isolation and storage of DNA, RNA, or proteins. c. Tissue and reagent standards: development of standard reagents such as representational DNA, RNA, and proteins and standard tissue preparations to improve the quality of or facilitate the validation of clinical laboratory assays. d. Methodologies for directed micro-sampling of human tissue specimens, including for example, new or improved methodologies for tissue microarrays. 7. Tissue preservation: fixatives and embedding materials or stabilizers that preserves tissue integrity and cellular architecture and simultaneously allows molecular analysis of DNA, RNA, or proteins. 8. Bioinformatics. a. Methods for acquisition and analysis of data associated with molecular profiling and other comprehensive molecular analysis technologies, including for example, analysis of microarray images and data as well as methods to combine, store and analyze molecular data produced by different techniques (e.g., combined analysis of proteomics and gene expression data). b. Methods for collecting, categorizing or analyzing large data sets containing pathology data or histological images and associated clinical or experimental data, including for example, tumor marker measurements, tissue microarray data, and other relevant biological information. c. Software/algorithms to interpret and analyze clinical and pathology data including methods that relate data from clinical databases to external data sources. Includes for example, neural networks, artificial intelligence, data-mining, data-trend analysis, patient record encryption protocols, and automatic diagnostic coding using standard nomeclatures. d. Informatics tools to support tissue procurement and tissue banking activities. 9. Statistical methods and packages designed for data analysis including correlation of clinical and experimental data. 10. Automated Cytology. a. High resolution image analysis for use with specimens (e.g., blood, tissues, cells) and tissue microarrays. b. Instrumentation including microscopy and flow cytometry. c. CGH, FISH, immunohistochemical staining and other hybridization assays using probes with fluorescent or other novel tags. d. Methods for single cell isolation and sorting. e. Methods for single cell classification and analysis. 11. Instrumentation for the detection and diagnosis of tumors, including endoscopy and magnetic resonance spectroscopy (MRS). 12. Immunoassays using monoclonal, polyclonal, or modified antibodies. Affinity-based binding assays using libraries of aptamers including chemical ligands, small peptides or modified antibodies. For additional information about areas of interest to the CDP Technology Development Branch, visit our home page at: http://cancerdiagnosis.nci.nih.gov. B. Biochemistry and Pharmacology. Preclinical and Exploratory Investigational New Drug (IND) studies designed to improve cancer treatment. General areas of interest: Discovery of new drugs or drug combinations and treatment strategies, selective targeting, development of clinically relevant preclinical models, pharmaceutical development, ADME (absorption, distribution, metabolism and excretion) studies and toxicologic evaluations, understanding mechanisms of drug actions (responses to therapies), and preventing and overcoming drug resistance. Areas of current emphasis: Molecular targeted approaches, including application of safety and efficacy biomarkers to the discovery and development of drugs; application of advanced technologies, such as nanotechnology and imaging technologies, to improved assays for quantitation of safety and efficacy biomarkers; approaches that reduce costs and increase speed of preclinical drug development; and approaches that will lead to “personalized medicine,” including better predictions of drug response and adverse reactions, drug-drug interactions, and drug efficacy monitoring. For additional information, please visit our home page at http://dtp.nci.nih.gov and select “Grants/Contracts.” 1. Drug Discovery. a. Design and synthesize novel compounds for evaluation as potential anticancer agents. Synthesize simpler analogs of complex antitumor structures that retain antitumor activity. b. Develop computer modeling and biophysical techniques such as x-ray crystallography and NMR spectroscopy. c. Design prodrugs of anticancer agents that are selectively activated in cancer cells. d. Discover new anticancer agents that exploit unique properties of tumors, that induce or modulate apoptosis, or that induce or modulate differentiation. e. Design and synthesize anticancer prodrugs, latent drugs, or modifiers of cancer drug metabolism or excretion. f. Develop ways to produce adequate quantities of promising natural products or natural product derivatives through total synthesis. g. Develop scale-up and manufacturing technology for the synthesis of materials with promising anticancer potential. h. Develop chemical libraries for anticancer drug screening programs. The generation of small molecular weight libraries (<700 MW, e.g., non-polymeric organic molecules, transition-state analogs, cyclic peptides, peptidomimetics) is encouraged. i. Develop and apply technologies in genetics, genomics, proteomics, glycomics, lipidomics, metabolomics, and systems biology to the discovery of potential drug targets associated with multiple pathways or networks. Design and optimize agents that block or activate targets/pathways that are likely to control, re-program, retard or kill cancer cells, especially cancer initiating cells (often called cancer stem cells). 2. Drug Evaluation. a. Develop and evaluate anti-metastatic and/or anti-angiogenesis agents or strategies, including combination therapies, in appropriate model systems. b. Develop and evaluate anticancer gene therapy in appropriate model systems. The development of new gene delivery approaches is encouraged. c. Develop novel or improved in vitro and in vivo test systems. There is a special need for new types of in vivo tumor models, such as orthotopic tumor models, models using transgenic or gene knockout animals, and models to evaluate agents that induce differentiation or apoptosis or that target cancer initiating cells (often called cancer stem cells). d. Develop strategies to detect, prevent, or overcome drug resistance. e. Develop novel treatment strategies such as extra corporeal treatment. f. Develop new assays based on molecular targets, especially those that may be amplified or altered in cancer cells. For example, develop assays for agents that interact with oncogenes, suppressor genes, signal transduction pathways, transcription factors, or promoters. Assays based on molecular targets that can be adapted for high volume screening of chemical libraries are especially encouraged as well as in vivo models, which can be used for “proof of concept” (i.e., validating selectivity of the agent for the target and confirming that modulation of the target results in antitumor activity). g. Develop cost-effective and useful techniques to improve in vitro cell culture methodology, such as the development of automated systems, serum-free media, or carbon dioxide-free buffering systems to stabilize cell culture performance. h. Identify and employ novel targets for antitumor drug discovery utilizing non-mammalian genetically defined organisms, such as fruit flies, worms, zebrafish and yeast. i. Develop and apply technologies such as microarrays, proteomics or RNAi to improve the efficiency of drug discovery. j. Develop cell lines that contain bioluminescent reporter genes, such as luciferase, that can be controlled by activating specific promoters. 3. Pharmaceutical Development. a. Develop new methods to improve drug solubility for administration of promising antitumor compounds, such as water miscible nontoxic water solubility enhancing agents. b. Develop bioavailable alternatives to the intravenous delivery of cytotoxic chemotherapy. For example, develop new excipients to enhance oral bioavailability of anticancer agents. c. Develop biocompatible additives and excipients for highly concentrated proteins and peptide formulations to enhance bioavailability and stability suitable for subcutaneous delivery of agents. d. Develop improved methods to reduce thrombophlebitis and other related side effects observed following intravenous injection of some anticancer drugs. e. Develop new and innovative techniques for sterilization of parenteral dosage forms. f. Develop in vitro and in vivo models to predict human oral bioavailability of anticancer drugs. g. Develop practical delivery systems involving nanotechnology (dendrimers, nanoparticles, nanoshells, etc.) or other strategies to deliver anticancer drugs to specific target sites. h. Develop new technology to manufacture liposomal and intravenous emulsions in an environmentally friendly manner and in accordance with OSHA standards. i. Develop additives and/or processes to eliminate cold chain storage of biotherapeutic agents, especially vaccines. 4. Toxicology and Pharmacology. a. Develop biochemical or molecular (genomic, proteomic, or metabolomic) response profiles of specific target organs (e.g., bone marrow, gastrointestinal tract, liver, kidney, heart, lung) to permit rapid identification of toxic effects resulting from anticancer drug administration. b. Develop clinically relevant in vitro and/or in vivo tests for estimation and prediction of gastrointestinal toxicity, neurotoxicity (central and peripheral), cardiotoxicity, hepatotoxicity, nephrotoxicity and pulmonary toxicity. c. Correlate in vivo and in vitro models for organ toxicity as described above in 4b. Validate for various anticancer drugs. d. Develop drug metabolism (Phase I and Phase II) profiles for anticancer agents in human, mouse, rat and dog liver S-9, microsomes and slices. e. Develop systems to identify toxic effects of drugs by characterizing reactions with biomolecules or receptors. f. Develop in vitro tests to detect, qualify and quantify toxic effects of antineoplastic drugs. Develop techniques for determining individual variations in drug responses due to genetic polymorphisms or other factors. Develop pharmacodynamic endpoints and surrogate endpoints using appropriate biomarkers to aid in the selection of doses and schedules and the monitoring of responses and toxicity. g. Develop personal computer programs for pharmacokinetics models capable of predicting drug behavior in humans from preclinical pharmacokinetics data in mice, rats, dogs, and non-human primates. h. Investigate and develop techniques for relating specific enzyme activities (both catabolic and anabolic) to body sizes of different species. i. Investigate techniques that would allow parameters, e.g., Km and Vmax for enzymes, to be scaled from preclinical to clinical models. j. Develop analytical strategies applicable to the quantitation of potent anticancer drugs in biological fluids at the pg/ml level, e.g., Bryostatin. k. Develop non-invasive techniques to determine drug distribution in various animal models. l. Evaluate interspecies transporter distribution and its impact on pharmacokinetic parameters, e.g., the impact of pharmacogenetic variation in biodistribution. m. Determine optimal pharmacokinetic sampling schedules for use in dose titration/pharmacodynamic assessment by integrating information such as pre-clinical pharmacokinetic data, physico-chemical drug properties and mechanism of action. n. Develop an in vitro/in situ system for high throughput drug screens for oral bioavailability. o. Develop and deliver organ specific chemo-protective agents. p. Develop and evaluate rapid, cost-effective methods, including biochemical, functional multiplexed, imaging, nanotechnology-based, and microfluidics-based assays, to quantitate surrogate endpoints for determination of doses, dosing schedules, safety, and efficacy of drugs. q. Identify and develop biomarkers to evaluate drug activities and toxicities. r. Develop assays in support of Exploratory Investigational New Drug Studies using biomarkers or other appropriate endpoints. s. Develop, standardize, and validate cost-effective tools for obtaining comprehensive ADME and toxicology profiles that may better predict the performance of drugs in humans. t. Develop and analytically validate assays or tools for measuring safety, efficacy, and dosing biomarkers. 5. Animal Production and Genetics. a. Investigate alternatives to expensive barrier systems for exclusion of pathogens from rodent colonies, e.g., by use of micro-isolator cages, and evaluate their performance. b. Develop and evaluate specialized shipping containers for pathogen-free animals. 6. Natural Product Discoveries. Note that execution of projects in most of these topic areas will require collaboration and signed agreements with countries where the source organism was originally collected. a. Develop techniques for the study of non-culturable organisms in order to identify antitumor agents. b. Develop techniques for the genetic and biochemical characterization and the manipulation of biosynthetic pathways to create leads. Use combinatorial biosynthesis to generate libraries of un-natural natural products as drug leads. c. Use genetic techniques for the identification of microbial consortia, and for the identification and isolation of genes controlling the biosynthetic pathways producing potential antitumor agents. d. Express biosynthetic pathways from microbes or microbial consortia that are known to produce antitumor agents, but in organisms amenable to standard fermentation techniques. e. Investigate new biological methods, such as tissue culture, aquaculture, hydroponics, etc., for the production of natural products as potential anticancer agents. f. Develop new systems of large-scale production using biotransformation, tissue or cell culture, biotechnology, modification of the chemical ecology of producing organisms, etc., in order to produce the large quantities of anticancer drugs needed for preclinical or clinical development. g. Develop methods for the isolation, purification, identification, cultivation, and extraction of microorganisms from unusual marine or terrestrial habitats for antitumor screening. Examples are gliding bacteria, barophilic, endophytic, thermophilic, and tropical canopy organisms. h. Investigate newer methods of isolation and purification, such as super-critical fluid extraction and chromatography, centrifugal countercurrent chromatography or affinity-based separations, in the isolation and purification of natural products with anticancer activity. i. Develop simple immunoassays that can be used to monitor the levels of natural products of interest in simple extracts of the relevant raw material. These assays should be capable of being developed for use “in the field” and also in developing countries. j. Develop analytical and biological methods for isolation, purification and validation of active constituents identified from alternative medicine and complementary studies; use of these purified constituents alone or in combination with conventional anticancer agents. 7. Data Management Systems. a. Develop data support systems for chemical library programs. b. Develop bioinformatics tools to accelerate the identification, functional understanding and validation of drug targets. c. Develop bioinformatics tools to predict ADME and toxicology characteristics of drug candidates. d. Develop “data mining” strategies such as neural networks. e. Develop algorithms for determining optimal drug combinations and for prediction of optimal effectiveness of individual agents. f. Develop bioinformatics tools to support a systems biology approach to drug discovery and development. g. Develop bioinformatics tools to support genomic/proteomic and other "omics" profiling experiments in support of drug discovery and development. C. Cancer and Nutrition. Research to improve the methodology of nutritional assessment in a cancer population. Innovative approaches to evaluate the contribution of nutritional status to response to cancer treatment. 1. Research to improve the methodology of nutritional assessment in a cancer population. 2. Develop means to evaluate the contribution of nutritional status to response to cancer treatment. D. Clinical Treatment Research. Clinical research studies designed to improve cancer treatment. Emphasis is on clinical trials for the evaluation of new therapeutic agents, development of assay systems to measure patient response to chemotherapy, development of prognostic assays, and development of methods of analysis and management of clinical trials data. Studies designed to improve human subject protections for patient access to clinical cancer trials. 1. Evaluation of New Cancer Therapies. a. Conduct clinical trials for the evaluation of new therapeutic agents or modalities of treatment employing drugs, biologics or surgery. b. Clinical trials using “unconventional therapies,” including, but not limited to, behavioral and psychological approaches, dietary, herbal, pharmacologic and biologic treatments, and immuno-augmentative therapies. c. Development and evaluation of new clinical approaches using gene transfer or gene therapy technologies. d. Development and evaluation of new clinical approaches using tumor associated antigens or vaccines in order to enhance immunogenicity. e. Develop and characterize novel chemical compounds that may be useful anticancer agents, either alone or in combination with other modalities such as radiotherapy. f. Develop techniques to lessen the toxicity of existing anticancer treatments. g. Develop new techniques for the delivery of anticancer agents that will maximize therapeutic effects and minimize toxicity. h. Develop new surgical techniques or tools or improve existing techniques that are/may be utilized in cancer treatment. i. Characterize and produce clinical grade monoclonal antibodies to detect and treat malignancies. 2. Development of Prognostic Assays to Monitor Patient Response to Therapies. a. Develop assay systems to measure the response of human tumors to chemotherapy or biologics. b. Characterize drug resistance mechanisms and design methods to overcome clinical drug resistance. c. Develop assays for prognostic factors to identify patient subsets who may benefit from specific cancer treatment therapies. d. Development of assays to assess effects of agents on specific molecular targets in clinical studies. e. Develop new techniques for relating past preclinical information to past clinical results for prediction of future useful clinical agents from future preclinical data (both in vitro and in vivo). 3. Clinical Trials Informatics. a. Develop new tools and methodologies for the analysis of clinical trials results. b. Develop new informatics tools to facilitate clinical trials data entry from the bedside and coordination of data entry and transmission throughout the institution and to other collaborating institutions or organizations. c. Development of novel web-based approaches to clinical trials informatics for transmission of data to NCI or other organizations. Topics include point of treatment data capture and reporting, electronic protocols, OLAP (On-line Analytical Processing), support for the Common Toxicity Criteria, and drug accountability support. d. Develop new interchange standards, based on technologies such as XML, for sharing data among heterogeneous systems. Specific applications areas include, Adverse Even Reporting, Case Report Forms. e. Develop new tools for support of Common Data Elements. f. Develop new approaches for interface with electronic medical records, with intent to streamline data reporting, registration, and toxicity reporting of Clinical Trial information. E. Cancer Imaging Program. The mission of this program is to promote and support: Cancer-related basic, translational and clinical research in imaging sciences and technology, and integration and application of these imaging discoveries and developments to the understanding of cancer biology and to the clinical management of cancer and cancer risk. Toward this effort, CIP 1) funds research in the development of tools, methodologies and imaging agents/probes that will better diagnose, assess, and effectively treat cancer, and 2) supports a spectrum of research projects from preclinical exploratory research and development through clinical trials. Areas of interest include but are not limited to: 1. Development of medical imaging systems for early cancer detection, screening, response to therapy and interventions including image-guided therapy. 2. Development of preclinical and clinical in vivo imaging systems, methods, imaging probes and contrast agents and related image reconstruction, image processing, image display and image-based information as required to detect, classify, monitor and guide therapeutics to cancer and precancerous conditions. 3. Development of methods to assess the value of imaging procedures for the above goals. 4. Development of systems and methods for improved production and distribution of radioactive materials for cancer imaging and/or treatment. 5. Development of systems, methods and their optimization for studying the adverse reactions/effects of image-guided and other diagnostic and therapeutic interventions. 6. Any other investigator-initiated research idea that is relevant to cancer biomedical imaging. 7. Development of systems, methods and their optimization to advance the role of imaging in assessment of response to therapy through increased application of quantitative anatomic, functional, and molecular imaging endpoints in clinical therapeutic trials and dissemination of these systems and methods with appropriate scientific communities. F. Radiation Research. The Radiation Research Program (RRP) supports basic, developmental and applied research (including clinical) related to cancer treatment utilizing ionizing and non-ionizing radiations. Therapeutic modalities include photon therapy, particle therapy, photodynamic therapy (PDT), hyperthermia, radioimmunotherapy (RIT), systemic targeted radionuclide therapy (STaRT), and boron neutron capture therapy (BNCT). Radiation research encompasses a range of scientific disciplines including basic biology, chemistry, physics and clinical radiation oncology. Topics of interest include, but are not limited to, the following areas: 1. Development of devices for planning, measuring, and delivering radiation therapy or related therapies, including devices for patient positioning and quality assurance for the following: (a) ionizing radiation, particularly 3-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT); (b) PDT; (c) hyperthermia; (d) RIT; (e) STaRT; and (f) particle therapy. 2. Development of devices for dosimetry for (a) ionizing radiation; (b) PDT, particularly those capable of measuring light doses at depth in tissues; (c) thermometry for hyperthermia, particularly non-invasive thermometry; and (d) RIT. Devices may include chemical, solid state, film, biological or ionization systems to detect or read out exposures. Accuracy, precision and linear response are essential over the range of doses and temperatures employed in the research laboratory and/or in the clinic, depending on their intended use. Devices for thermometry during hyperthermia treatment must give accurate readings with the heating device(s) with which they are to be used. 3. Development and evaluation of computer hardware and software for radiation therapy, such as computation algorithms, computer workstations, image guidance techniques, and informatics methods for treatment planning, delivery and outcomes analysis. 4. Development of novel drugs to increase the effectiveness of radiation therapy or related therapies: (a) chemical modifiers of radiation response, particularly small molecules directed at molecular targets involved in tumor radioresistance; (b) photosensitizers for PDT; (c) sensitizers for use with hyperthermia; and (d) prodrugs that are selectively activated within the tumor. 5. Development of drugs to prevent, reduce or reverse normal tissue response, especially the late effects that develop months or years after therapy. Compounds that are based on a rationale for achieving a therapeutic gain (an improved differential response between tumor and normal tissue) are of greatest interest. Enhancement of response must be achieved at radiation doses and treatment schedules employed clinically. 6. Development of predictive assays and monitors of response to radiotherapy, PDT, hyperthermia, STaRT, or RIT. Tools are needed to identify patients that would benefit from specific therapeutic approaches. G. Biological Response Modifiers (BRM). Research on agents or approaches that alter the relationship between tumor and host by modifying the host's biological response to tumor cells with resultant therapeutic benefits. Both preclinical and clinical investigations are conducted on the utility of a wide variety of natural and synthetic agents and on biological manipulations of immunological and non-immunological host mediated, tumor-growth controlling mechanisms in cancer therapy. Studies are encouraged which utilize in vitro assays and/or animal model systems to investigate mechanisms of BRMs. Examples of innovative research include but are not limited to: 1. Evaluation of molecular genetic approaches to discovery of new therapeutic agents, delivery of BRMs or development of gene therapy. 2. Development of improved techniques to synthesize, screen and develop new oligonucleotides including iRNA sequences for therapeutic purposes, such as signal modulation, anti-oncogene or anti-viral effects. 3. Improvement in cell-culturing techniques, e.g., by developing automated cell culture systems, specialized media, or improved methods to induce activation, proliferation or differentiation. 4. Development of new procedures or reagents for the modulation of the suppressor arm of the immune system in experimental models, directed towards successful immunotherapy. 5. Improvement of tumor-associated antigens or vaccines in an attempt to enhance immunogenicity. 6. Evaluating autoimmunity in the context of anti-tumor response in vivo to vaccines. 7. Development of novel in vitro assays for the primary screening of BRMs. 8. Application of observations describing shared receptors and mediators between the neuroendocrine and immune systems in studying immunobiology and immunotherapy of cancer. 9. Development and optimization of viral oncolytic agents. 10. Development of novel or improved methods for process development and manufacture of biotherapeutics, including but not limited to antibodies, recombinant proteins, peptides, oligonucleotides, and products based on viral or bacterial vectors, per executive order (E.O. 13329) mandating federal agencies assist the private sector in manufacturing innovation efforts. 11. Development of innovative methods for monitoring the manufacturing process for biotherapeutics using in-line or on-line process analyzers to improve the efficiency of process controls and determination of production end-points (see Guidance for Industry, PAT-A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance, www.FDA.gov). 12. Development of methods to more efficiently assess factors related to the ultimate product quality, safety and efficacy of biologics. HHS201101242011030520110805-1Closed360216http://www.sbir.gov/node/360216 A. Prevention Research Branch (PRB). The Prevention Research Branch (PRB) supports a program of research in drug abuse and drug related HIV prevention to (1) examine the efficacy and effectiveness of new and innovative theory-based prevention approaches for drug abuse, drug-related HIV/AIDS and other associated health risks, (2) determine the cognitive, social, emotional, biological and behavioral processes that account for effectiveness of approaches, (3) clarify factors related to the effective and efficient provision of prevention services, and (4) develop and test methodologies appropriate for studying these complex aspects of prevention science. Prevention Research. Rigorous scientific prevention research is encouraged to study novel approaches to substance abuse prevention for use at multiple levels of the social environment including: the family, schools, peer groups, community and faith-based organizations, the workplace, health care systems, etc. The purpose of this research is to determine the efficacy and effectiveness of novel program materials, training strategies, and technologies developed to prevent the onset and progression of drug abuse and drug-related HIV/AIDS infection. Materials and technologies may target a single risk-level or may take a comprehensive approach encompassing audiences at the universal, selective, and/or indicated levels. Universal interventions target the general population; selective target subgroups of the population with defined risk factors for substance abuse; indicated interventions target individuals who have detectable signs or symptoms foreshadowing drug abuse and addiction, but who have not met diagnostic criteria. NIDA encourages the development and testing of innovative prevention intervention technologies that are sensitive and relevant to cultural and gender differences. 1. Laboratory studies of the underlying mechanisms and effects of various prevention approaches such as persuasive communication (e.g., mass media and print media) as they are affected by and effect drug related cognition, emotion, motivation and behaviors. 2. Decomposition of prevention programs, practices and strategies to understand components that account for program effectiveness. 3. Research on features of prevention curricula, materials, implementation, approaches, training, technical assistance, and systems integration that contribute to positive outcomes. 4. Training modules and ongoing technical assistance for program implementers of research based substance abuse prevention programming strategies. 5. Prevention intervention dissemination technologies and mechanisms that integrate research with practice; specifically the transfer of drug abuse prevention information to decision-makers, funders, and practitioners. 6. Prevention services research on the organization, financing, management, delivery, and utilization of drug abuse prevention programs. 7. State-of-the-art and practical strategies for the integration of evidence-based prevention approaches into existing prevention service delivery systems. 8. Studies that develop and assess reliability and validity of developmentally appropriate self-report, physiological, and biochemical measures for use in prevention trials in a variety of settings and a variety of audiences. 9. Development of and testing of environmental change strategies for schools, neighborhoods, communities, etc. to use in reducing substance use initiation and/or progression. 10. Development of practical and affordable community tools for: needs and resource assessment, selection of appropriate evidence-based programs and strategies, high-quality implementation of identified programs and strategies, evaluation at community, organization and individual levels, and sustainability. 11. Drug abuse prevention methodological research on promising data collection, data storage, data dissemination, and reporting techniques. 12. Promoting wider and more effective (e.g. with enhanced fidelity) use of evidence-based prevention interventions for substance abuse and related HIV prevention, including interventions made available thru CDC and other federal agencies. 13. Studies applying technologies and strategies that have been developed for use in other disciplines in order to examine the utility of their application for drug abuse prevention, such as virtual reality technologies being used for some clinical conditions (e.g. phobias, eating disorders), and serious video games are being used for some clinical conditions (e.g., cancer patients), but not for drug abuse prevention. 14. Development and testing of innovative drug abuse prevention intervention products, using discoveries from the basic biological (e.g. neurobiological), psychological (e.g. emotional, behavioral, cognitive, and developmental) and social (e.g. social learning, peer network, and communications) sciences. 15. Development and testing of adaptations for efficacious prevention research approaches to make these more appropriate for special populations including racial and ethnic minorities, non-English speaking populations, immigrant populations, rural and migrant populations, low literacy populations, or persons with disabilities. 16. Development of methods, state-of-the-art tools and systems for community coalition-building. 17. Development and testing of tools to measure intervention costs, cost effectiveness, and net economic benefits. 18. Development and testing of rapid assessment tools of sexual and drug use risk behaviors for use in health care and public health environments, including STI clinics and AIDS research centers. 19. Development and testing of tools to promote security and appropriate prescribing of scheduled prescription drugs. Technologies can be developed to assist medical professionals, schools, service providers and others in making prescribing decisions, educating patients and their caretakers, or dispensing and monitoring of medications. 20. Development of new technologies to support drug abuse prevention interventions with military personnel, veterans and their families. Tools can include adaptations of efficacious and effective drug abuse prevention interventions to maximize health care efficiencies and to address negative life stress resulting from sustained combat operations, a major contributor to both the onset and exacerbation of substance abuse and mental health problems. 21. Development of new technologies for delivery and implementation of efficacious drug abuse prevention interventions for rural and frontier communities. Augie Diana, Ph.D. 301-443-1942 Email: dianaa@nida.nih.gov B. Epidemiology Research Branch (ERB). The ERB supports a research program on drug abuse epidemiology that includes (1) studies of trends and patterns of drug abuse and related conditions such as HIV/AIDS in the general population and among subpopulations, (2) studies of causal mechanisms leading to onset, escalation, maintenance, and cessation of drug abuse across stages of human development, (3) studies of person–environment interactions, (4) studies of behavioral and social consequences of drug abuse, (5) bio-epidemiologic studies including genetic epidemiology studies, (6) methodological studies to improve the design of epidemiologic studies and to develop innovative statistical approaches, including modeling techniques. 1. Improvement of Reliability and Validity of Reporting of Sensitive Data. The reliability and validity of self-report of drug use and related behaviors (e.g., HIV risk behavior) is a matter of great concern. Use of new technologies for real time data collection in ecological settings is of great interest because these technologies enable collection of drug consumption data in context. Studies to improve methodologies based on variations of standard survey protocols or computer-assisted self-interview (CASI) and personal interview (CAPI) are also encouraged. 2. Instrument Development. Easy-to-use assessment instruments are needed to enhance epidemiology research. Areas of interest include but are not limited to: a. Community Assessment. The development of community diagnostic instruments for psychometrically sound assessment of community characteristics is essential to improve our understanding of how community factors affect drug abuse and ensuing behavioral and social consequences. Standardized assessments of community characteristics are needed to better understand the full impact of drug use and to develop targeted interventions to specific community needs. b. Assessment of Psychiatric Comorbidity in Community Settings. Easy to use, reliable, and valid instruments are needed to assess psychiatric comorbidity in different populations of drug abusers, including adolescents and those in community drug abuse treatment settings. c. Assessment Instruments to Measure CNS Function Related to Drug Abuse. The development of age-appropriate assessment instruments to measure behavioral and cognitive function over the course of development will contribute to our understanding of vulnerability to drug abuse and functional impairment due to drug use. 3. Development of State-of-the-Art Mechanisms for Epidemiological Research. The development of state-of-the-art mechanisms to facilitate the use of Geographical Information Systems (GIS) in community epidemiology studies (for example Community Epidemiology Work Groups) and other drug abuse research is if great interest. There is a need for enhanced software and hardware for GIS interfaces, database management, visualization, and innovative spatial analysis capabilities. The role of GIS in public health management and practice continues to evolve. Application of this technology is an important step towards better understanding drug abuse issues and their inherent complexities. The ability to evaluate geospatial information provides a unique perspective of public health issues such as emerging and shifting epidemics, the utilization of treatment services, and rapid assessment of the impact of incidents ranging from natural disasters to bioterrorism. When used alongside more traditional epidemiological techniques, GIS provides epidemiologists the ability to address new questions, refine, or enhance existing analyses. Bethany Deeds, Ph.D. 301-402-1935 Email: deedsb@nida.nih.gov 4. Improving Measures of Addiction Risk. Individual differences in risk for drug addiction are often expressed in degree rather than kind, that is, as gradations along an underlying continuum that stretches from unobservable variations in risk for addiction to extreme and fully debilitating addiction severity. Assessment instruments in use today for measuring drug addiction (i.e., compulsivity in seeking and using drugs despite harmful consequences) have proven reliability and validity, but are of limited use for evaluating individual differences in risk for drug addiction. Advances in computerized adaptive testing methods, computer-assisted technologies, and psychometrics, including item response theory, suggest that the capabilities now exist for the development of the next generation in addiction assessment. New assessment instruments are needed to detect meaningful variation between, within, and across individuals over time that is scalable along the dimension of risk for addiction; these instruments should allow for efficient assessment of the risk construct with minimal burden for administration, training, and cost to the researcher, clinician, research participant, or patient; and they should ultimately provide valid and reliable scores corresponding to established diagnostic criteria for substance use disorders. Elizabeth Lambert, M.Sc. 301-402-1933 Email: elambert@nida.nih.gov 5. Developing, Validating, Refining Tools for Ecologic Momentary Assessment. Ecologic Momentary Assessment (EMA) includes the measurement of exposures and events in real time as they occur, and in the natural environment where they occur, such as the home, neighborhood, or workplace. EMA tools include portable technologies for longitudinal data collection in the field, such as mobile phone electronic diaries and PDAs, geopositioning devices, motion sensors, biosensors, environmental sensors, and audiovisual devices. In addiction and behavioral research, new EMA tools may enhance the contextual and temporal resolution of exposures, and the biological or behavioral processes presumed to occur in response. Specific challenges to address in the implementation of EMA include optimizing the timing of measurement and data quality, establishing sensor validity and reliability in different populations, reducing intensely longitudinal data for statistical analysis, achieving user acceptability, and safeguarding user privacy. Studies are encouraged that address these and other challenges to improve the validity and acceptability of EMA tools. Louise Eideroff, Ph.D. 301-451-8663 Email: wideroffl@nida.nih.gov C. Services Research Branch (SRB). The SRB supports a program of research on the effectiveness of drug abuse treatment with a focus on the quality, cost, access to, and cost-effectiveness of care for drug abuse dependence disorders. Primary research foci include: (a) the effectiveness and cost-benefits and cost-effectiveness of drug abuse treatment, (b) factors affecting treatment access, utilization, and health and behavioral outcomes for defined populations, (c) the effects of organization, financing, and management of services on treatment outcomes, (d) drug abuse service delivery systems and models, such as continuity of care, stages of change, or service linkage and integration models, and (e) drug abuse treatment services for HIV seropositive patients and for those at risk of infection. 1. Drug Abuse Treatment Economic Research. This initiative will support research to design and develop data systems for financial management and economic analysis of treatment programs and larger systems in new healthcare settings and managed care networks. Managerial decision-making requires the implementation of sophisticated data systems to facilitate routine budgeting processes, allocation of resources, performance measurement, and pricing decisions. The focus is on the needs of managers within the organization and managers outside of the organization. Data system development must be based on standard cost behavior and profit analysis. Data systems must be designed with correct cost concepts (accounting and economic) in order to permit cost and pricing decisions to be developed for new treatment technologies and management of ongoing systems. In research settings, such an initiative is vital for the assessment of new technologies developed for transfer to practice. 2. Determining the Costs of Implementing Evidence-Based Practices (EBPs) and Other Technologies in Drug Abuse Treatment. Research shows that new technologies or evidence-based practices (EBPs) can improve drug treatment outcomes, and it has been asserted that large-scale drug abuse treatment improvement requires systematic implementation of proven practices, processes, and technologies. Often, however, new drug treatment approaches are not adopted or sustained in usual practice, even in programs that served as settings for research showing their effectiveness. This may be due in part to a poor understanding of the initial or ongoing costs entailed by new practices, processes, or technologies (hereafter referred to as technologies). Methods and tools need to be developed and tested to help drug abuse treatment service providers and payers arrive at realistic estimates of the costs of implementing and sustaining new technologies in usual practice settings. With regard to new technologies, implementing is defined as an ongoing process of selecting, adopting, and adapting these new technologies into ongoing treatment, particularly with consideration for the local setting, population and available resources. Sustaining is defined as an ongoing process of providing needed resources (such as staffing, training, and equipment), maintaining the quality of the new technology through evaluation, monitoring, and improvement, and determining its ongoing utility compared to alternatives. The tools and methodologies should be able to identify and estimate costs separately for implementing and for sustaining new technologies, and should consider both clinical and administrative technology. At a minimum, domains in which costs should be estimated include assessment of programmatic need, appropriateness, and value; staffing qualifications (salary and competencies); training, support, equipment, and other infrastructure requirements; information / data requirements; quality monitoring and improvement; and evaluation of outcomes. Sarah Duffy, Ph.D. 301-443-6504 Email: sduffy@nida.nih.gov 3. Personnel Selection Technology Research for Drug Abuse Treatment Clinics. Research is showing that employee turnover is a substantial problem among substance abuse treatment services providers. Applications supporting innovative research that develops and validates generic staff selection systems which could be adopted and tailored for use by drug abuse treatment clinics are welcome. Like many small businesses, drug abuse treatment clinics have problems attracting and retaining qualified personnel. Also like many small businesses, treatment clinics have limited resources to apply to the recruiting, screening, and hiring of new and replacement personnel. Research has shown that the application of standardized screening and selection methods designed to maximize person-job fit can cost-effectively reduce staff turnover. Systematic methods such as background inventories, protocol-driven interviews, aptitude tests, and credit checks have demonstrated validity for improving person-job fit. Examples of possible projects might include development of easy-to-understand guidance about legal considerations in hiring practices, software that transform job task analysis into selection criteria, interview protocols to standardize applicant screening, tolls to help improve recruitment, and/or self-paced training for hiring officials or interview panels to improve screening reliability. 4. Customer Retention Technology. Premature disengagement from drug abuse treatment participation is a common problem and ranges from approximately 30 to 60% based upon the clinic and modality studied. Past research has very frequently attributed dropping out of treatment to participant characteristics (e.g., motivation, addiction severity, comorbidity) and/or environmental factors (e.g., social pressures, unemployment, homelessness). Seldom has the dropout problem been studied in the context of customer satisfaction. That is, there is little research looking at the causes of dropping out of treatment attributable to organizational factors (e.g., policies, practices, context) that influence participant withdrawal decisions. Needed are tools and systems for assessing and surveying drug abuse treatment program participant perceptions and satisfaction levels, summarizing and report participant assessments, interpreting results, and adjusting policies and practices to improve satisfaction and participant retention in treatment. 5. Effective Management and Operation of Drug Abuse Treatment Services Delivery. The bulk of drug abuse treatment is conducted in small clinical settings with therapeutic staffs of less than a dozen people. Small clinics lack resources to help improve efficiency and effectiveness in both business and therapeutic practices. Areas that may be of interest to small businesses include, but are not limited to: a. Computer-based leader/manager self assessment tools: On-line and other types of tools to help those supervising the delivery of drug abuse treatment services to gain insights about personal strengths and weaknesses, and to help guide them to improved leadership and management practices. b. Organizational change tools: Handbooks describing step-by-step way to introduce more efficient business practices such as quality management/monitoring, creating empowered work teams, formalized goal setting, improved customer relations, forming organization linkages, and adopting new fiscal and resource management techniques. c. Organizational change tools: Handbooks describing step-by-step ways to introduce more efficient or effective therapeutic practices such as, adding pharmacotherapy in a previously drug-free clinic, adopting new medical/pharmacotherapy or behavioral interventions, and adopting new approaches to clinical collaboration and/or case management. 6. Assessment Tools for Quantifying and Organizational Culture that Promotes and Sustains a Drug-Free Workforce. Though drug-free workplace programs are ubiquitous in large businesses, small businesses often lack the staff and resources to create effective drug-free programs because they may involve in-house or contract experts to educate, train, monitor, and enforce policies and practices that will sustain a healthy workforce and a safe and healthy workplace. Though there are numerous model drug-free workplace policies and programs provided free by federal, state, and local governments as well as nongovernmental organizations, many fail to provide management with affordable or free, easy-to-use tools to assess the baseline of their organizations’ culture for drug abuse intolerance, and to monitor progress in building a drug-free organizational culture. Research shows that individual employees and organizations vary in their support for a drug-free workplace. Surveys indicate that coworker tolerance for illicit drug use varies by the type of drug, the