DOD/DHP SBIR 2012.2 3

OBJECTIVE: To develop a simulation-based training system to assist in teaching and training junctional and non-compressible hemorrhage control. The primary target is existing US Army / DOD military medical special operations training programs, but a secondary target could be other government agencies upon coordination with the government topic manager. The system could also have application to medical training programs in the academic and private sectors. The training audience is"soon-to-be-deployed"medics. The field of point of injury care is dynamic, but the simulation technologies applied to improve trauma training are nascent. So, we seek the development of an innovative, adaptable, and expandable trauma training system. DESCRIPTION: Deployed military medics and non-medic soldiers, especially those with non- medical functions, are driven on the battlefield to manage significant junctional and non-compressible hemorrhage that, until recently, have not been treatable. New adjuncts have been developed, e.g., Combat Ready Clamp (CROC) and Abdominal Aortic Tourniquet, but suitable training systems have not. As a result, both medics and non-medic soldiers may be unprepared to use them proficiently. Also, medical skills are prone to deteriorate during deployment. Thus, both the US Army and other DOD medical training programs have a need to rapidly refresh skills of soldiers and soldier medics who are going to, and returning from, forward based assignments. Junctional and non-compressible hemorrhage control is a prime example of traumatic injuries that (1) are rarely seen in non-combat situations and, therefore, (2) difficult to train for. This opportunity focuses on developing and assessing this junctional and non-compressible hemorrhage control training system to determine its effectiveness for training and use in demanding military medical training environment(s). The training system must support and respond to non-specific mechanical pressure. This training has a direct impact on the care of our military personnel, and the criteria for success are weighted toward systems demonstrating the ability to assist the staff to accomplish their mission. We seek a system that: - is based on established educational objectives - includes metrics upon which to judge proficiency performance - supports practice of both cognitive and psycho-motor skills required of medics - presents multiple trauma cases / scenarios - tests the cognitive and psychomotor skills of trainees at the beginning of training - identifies deficiencies in cognitive and psychomotor capability - tests the cognitive and psychomotor skills of trainees at the conclusion of training - develops a training program to correct them prior to deployment - assesses the training effectiveness of the system - results in minimal negative impact, e.g., time, disruption, resources, of the training staff - improves the quality of cognitive and psychomotor training, to teachers and/or students - improves the efficiency of cognitive and psychomotor training, to teachers and/or students - equals or reduces the cost of cognitive and psychomotor training, to teachers and/or students - addresses virtual mentoring capability with potential to reduce time required by instructors and students - is SCORM-compliant - employs open architecture principles Required: Final product must address junctional and non-compressible hemorrhage control at inguinal injury sites, pelvic injuries, e.g., groin injuries, and axillary injury sites. Optional: 1. Hemorrhage control including target abdominal target application points, e.g., umbilicus. 2. Team training system that includes training for all members of a maneuver element, soldiers and medics. PHASE I: Perform a feasibility study and analysis and develop a concept including discussion of how the system could be implemented. Identify the innovative technologies and approach proposed, technical risks of the approach, as well as the costs, benefits and schedule associated with development and demonstration of the prototype. Identify minimum system requirements and development tools. Demonstrate the foundational technology for simulation based junctional and non-compressible hemorrhage control training. PHASE II: Demonstrate the prototype system"s capability to train for multiple junctional and non-compressible hemorrhage control scenarios. Validation of the proposed Junctional and non-compressible and Non-Compressible Hemorrhage Control Training System is mandatory. Data from these studies will need to be provided, analyzed, and presented in the final report. Report data obtained as a result of the training assessment. In the marketing plan section of the Phase II proposal, include recommendations for effective implementation and estimates of resources required to operate, maintain and sustain the system into the future. PHASE III: This capability is expected to result in a system with military and civilian wide application to train to proficiency both the cognitive and psychomotor skills necessary to treat junctional and non-compressible hemorrhage.

OBJECTIVE: To accelerate the integration of advanced sensor technology into synthetic mannequins to facilitate objective measurement of user metrics during both training and education activities. At the end of Phase I, a proof of concept must be demonstrated and at the end of Phase II an integrated prototype (Beta) must be developed and demonstrated. DESCRIPTION: Mannequins are currently a common tool for medical training and education. Many of these have a hard exterior cover and lack adequate and/or appropriate modeled internal anatomy and thus may not even be considered for open surgical procedural training and/or laparoscopic / endoscopic procedural training. Although these existing mannequins are functionally capable of objectively measuring a user"s actions, this functionality is not adequate for tracking the performance of open procedures. In some cases, the space requirements for the sensor and communication apparatus prevent the user from performing other procedures entirely. Anatomically appropriate synthetic models have been developed and some of these have different tissue properties and may possibly serve the open and laparoscopic surgery community. The structure of these synthetic models allows trainees to dissect, cut, suture, and potentially perform a broader-range of tasks than are currently available on most commercially available mannequin(s). Mannequins which incorporate synthetic models representing a variety of tissues and/or tissue planes that are currently under development require further functional testing and validation and most still need an expert to review the novices actions subjectively. One effort that could accelerate this validation process would be the integration of advanced sensor technology to track and report on user manipulation of the specific tissues and connected with the overall systemic model. Existing advanced sensor technology is sophisticated enough to allow for the integration of embedded sensors into these mannequins/models to facilitate the measurement and reporting of targeted metrics. The integrated model as a whole must be reusable and have a high degree of repeatability of measurement. The sensors employed must provide for economical use in repeated training exercises either through high quality, durable components or low cost replaceable ones. The overall design must support repeatability of measurement in either case. The integration of the sensors with the tissues must detect dissection of tissue planes, incisions into/through tissues, and suturing (approximation) of the modeled anatomy to name a few. In addition, the advanced synthetic mannequin should replicate as much of the systemic human physiological response system as possible (i.e. changes at the tissue level have systemic affects that should be represented. Sensors implemented at the tissue level need to be integrated with other sensors and communicate data to and from other systemic sensors to measure and communicate data and information such as blood pressure, pulse, respiratory rate, stroke volume, tidal volume, pCO2, renal output, and glomerular filtration rate to name a few to the end user. The goal is to provide as realistic of a human response to interventional procedures on the synthetic mannequin as possible while also providing objective measurement of user metrics during both training and education activities. PHASE I: Deliverable at the end of Phase I: a proof of concept for integrating advanced sensor technology with the synthetic tissues/organs demonstrating the ability to detect several different parameters including (no particular order) 1) force(s) exerted on the tissue, 2) direction(s) the force(s) applied, 3) cutting or tearing of tissue(s), and 4) forces for approximation of tissue. Must provide preliminary data relevant to the robustness and repeatability of measurement of the sensor systems and the synthetic tissue. In addition to the monthly reports and final reporting requirements, an initial concept design for an integrated system must be delivered as well. A Review will be held around the 5th or 6th month at the government site Fort Detrick, Maryland to present and demonstrate the proof of concept developed and results obtained to date. Suggested alternates to sensors used during Phase I as well as suggested alternate bio-materials used for synthetic tissues need to be considered as a part of the research. The Phase I proposal must include projected concept and develop key component technological milestones, have a preliminary methodology on how analysis of the predicted performance of both the sensors and the synthetic tissue in addition to items such as working hypothesis, clinical impact, military impact, technical tasks, research methodologies supporting the hypothesis, and statement of work. No trials/studies needing Institutional Review Board (IRB) during Phase I will be accepted. PHASE II: At the end of Phase II, it is expected that a fully integrated prototype system (i.e. integration of sensors, synthetic material with properties mimicking tissue, and software) be demonstrated and the demonstration is included as a final project deliverable (i.e. presentation at the government site Fort Detrick, Maryland). This integrated prototype system must provide sensing capabilities at both the tissue and system levels and provide the end user with objective data regarding the performance of the trainee. Examples of sensing capabilities are, but not limited to (and in no particular order), 1) force(s) exerted on the tissue, 2) direction(s) the force(s) applied, 3) cutting or tearing of tissue(s), 4) approximation of tissue, 5) occlusion and the release of occlusion of tissue, 6) application of energy onto the tissue, 7) multiple tools (hands / fingers can be included as"tools"applied to the tissue (such as the concept of retraction) to name just a few, and 8) measurement of"fluids"within the vasculature to name a few. Preliminary validation of the tissue level sensor and synthetic model is mandatory: this would include items, but not necessarily limited to, detection of stretch and how much tension and distance is used on the tissue, detection of tissue cut and percentage cut (note, need to detect partial tissue cuts), tissue approximation and how much tension was placed on the tissue during approximation, and if tissue has been occluded (including partial occlusion) and release of occlusion. Validation at the systemic level (refers to something that is spread throughout, system-wide, affecting a group or system such as a body) is optional. Data from these studies are an anticipated outcome of Phase II and data should be analyzed, summarized, and presented in the final report. At the end of Phase II it is also expected that preliminary specifications on synthetic tissue model are provided, and sensor specifications are outlined. Preliminary data regarding robustness, reliability, accuracy, and repeatability is optional as a delivery at the end of Phase II. Estimated cost for production of prototype based on costs of sensors, synthetic tissues, other materials and supplies, labor, and overhead required to produce the prototype be provided as a deliverable. Descriptions of preliminary estimated product life and robustness of synthetic tissues and sensors should be provided, and a concept of the overview of maintenance should be included in the final report. Phase II should also include a preliminary evaluation by Subject Matter Experts (SMEs). These SMEs should not have been a part of the requirements and development and should serve only in the evaluation portion. These SMEs are not required to be military and/or government, but need to be in good standing with their respective organization and professional society. Evaluation should include clinical relevance as well and may include content and/or construct methodologies. Summary and analysis of data needs to be included as a deliverable. The Phase II proposal should include a commercialization plan/strategy, including letters of support or agreements if applicable. This commercialization plan should include analyses of customers (types and size), market opportunities and value, cost estimate of the unit for production and for sale, and projected company"s sales, revenues or operating loss. PHASE III: A fully robust, ergonomic, cost-effective, manufactured commercialize product should be developed. Manufacturing capabilities and scale up plans provided. Test results on robustness, shipping, electrical safety testing, accuracy, consistency, and repeatability should be included. Specifications of manufactured product as well as manufacturing process need to be prepared and finalized. Materials, material properties, and conditions under which product may be shipped and stored are needed.

OBJECTIVE: Create a multi-substrate 3D printer with the ability to render high-fidelity anatomically accurate synthetic physical tissue models that can be used for anatomy, trauma and surgical training purposes. It is desired that such simulated tissue consist of multiple substances with varying physical properties, so that bone, muscle, vessels, skin and adipose or organ tissue can be simulated. DESCRIPTION: As part of a strategy to lower costs and reduce the use of animal and human cadaveric tissue, this SBIR intends to develop 3D printing technology so that anatomically accurate, multi-substance human tissue analogues can be produced for training purposes. The printer should be able to produce several simulated types of tissue and deposit them in mixed format; i.e., a sample of printed tissue could include hard bone as well as compliant muscle, skin and major blood vessels and perhaps empty spaces within that substrate. If such technology were possible, a wide variety of human anatomy sections could be printed on demand. These simulated anatomy sections could be used for surgery rehearsal, visualization, procedural training and other uses. The actual printed substrates should ideally not be actual biological tissues, but rather materials that simulate their physical properties. PHASE I: At the end of Phase I it is expected that a proof of concept of a 3D printer be demonstrated for multi-substrate deposition, including detailed data on performance of the concept and identify anticipated performance of a more sophisticated working prototype. It is expected that appropriate stimulants be created and tested for bone, muscle, adipose tissue, integument (vessels or tissue planes), skin and possibly organs. Plans for software to be used in the Phase II effort, if the company is selected, should be elucidated. The Phase I proposal must include proposed concept and identify key component technological milestones, have a preliminary methodology on the predicted performance of the printer and printing substrates in addition to a working hypothesis, research methodologies supporting the hypothesis, technical tasks, clinical impact, military impact, and statement of work. The Phase I proposal must also include a target end-consumer cost for the printer if it were to be successfully developed. Similar cost estimates, with practical examples, must be provided for consumables needed to produce anatomical sections. Anticipated resolution must be specified. PHASE II: At the end of Phase II it is expected that a working prototype system will be demonstrated. The working prototype must work with multiple substrates and effectively produce printing outputs that contain at least three types of tissue and empty space areas. The task of creating effective tissue planes (including major vessels) must be definitively addressed. Description of plans, if any, to colorize tissue stimulant materials during printing need to be included in the deliverable Phase II must contain a validation study that examines simulated anatomy output for use in a medical training setting. In addition, the Phase II system must include software tools and anatomy data to allow users to produce a variety of simulated tissue sections. The ability to produce printed tissue output from data of CT and MRI scans is desired. A robust prototype, including 3D anatomy data and consumables, must be delivered for independent testing. Testing of the prototype needs to be performed by an organization that has not participated in the requirements or development. Summary and analysis of data needs to be provided as a Phase II deliverable. PHASE III: Fully robust, ergonomic, cost-effective, manufactured commercialized product. Manufacturing capabilities and scale up plans shall be provided. Test results on robustness, shipping, electrical safety testing, accuracy, consistency, and comparability to current existing methodologies are required. Detailed product cost and consumable cost information is necessary. Specifications of manufactured product as well as manufacturing process need to be prepared and finalized. Materials, material properties, conditions under which product may be shipped and stored are needed.

OBJECTIVE: Prototype architecture to execute an open source, universal health exchange language, as described in a recent President"s Council Of Advisors On Science And Technology (PCAST) Report. DESCRIPTION: Most DOD, VHA, and civilian healthcare systems encounter significant challenges in exchanging health information due to the lack of a universal health exchange language. Without effective health information exchange, continuity of patient care is less than optimal, healthcare access and availability are hampered, and healthcare costs increase. This topic is of particular importance to DOD, which is a provider and payer of care for 9.6M beneficiaries. Two thirds of military healthcare is delivered in the civilian sector. As a matter of background, the PCAST Report On"Realizing The Full Potential Of Health Information Technology To Improve Healthcare For Americans: The Path Forward", sets forth general recommendations regarding how healthcare information technology can be used to improve healthcare access, availability, acceptability, continuity, cost-effectiveness, and quality. The report cites the beneficial work of the HHS Office of the National Coordinator (ONC) for Healthcare Information Technology in developing standards and an initial nationwide healthcare information exchange to share data to improve healthcare delivery and support research for the public good. The report points out that"national decisions can and should be made soon to establish a"universal exchange language"that enables health IT data to be shared across institutions; and also to create the infrastructure that allows physicians and patients to assemble a patient"s data across institutional boundaries, subject to strong, persistent, privacy safeguards and consistent with applicable patient privacy preferences."The PCAST report further states that,"creating the required capabilities is technically feasible, as demonstrated by technology frameworks with demonstrated success in other sectors of the economy. The best way to manage and store data for advanced health informatics is to break data down into the smallest individual pieces that make sense to exchange or aggregate. These individual pieces are called"tagged data elements, because each unit of data is accompanied by a mandatory"metadata tag"that describes the attributes, provenance, and required security protections of the data."Current state: Some research surrounding use of healthcare metadata is underway and moving from academic labs into some early practical uses, such as demonstrated by Dr. Parsa Mirhaji for use in public health surveillance. Much of this research has been conducted using semantic web technologies employing the Resource Descriptive Framework (RDF), and Web Ontology Language (OWL), and query technologies such as SPARQL, which utilize the concept of"tuples", (subject, predicate, object), to relate data and achieve semantic interoperability. Other similar technologies exist, such as those from Metadata, Inc., although the semi-proprietary Metadata language, parts of which is available from Open Health Tools, is based on quintuplets vice tuples. Through their Health Data Dictionary (HDD) product, 3M has also supported some degree of semantic interoperability, using a knowledge representation scheme linked to a unique concept identifier, but it is not a true first-order predicate logic ontology. Language and Computing, now owned by Nuance, developed LinkBase, the world"s largest medical ontology, with limited commercial success. Adoption of these commercial technologies may have been limited by their proprietary, versus open nature, and associated licensing costs. It may be possible for some of these commercial technologies to be made open source, with companies then selling services around their technology, but this is a business decision that is up to the companies. Moving towards developing open source terminology mediation services may place these companies in a position wherein the Office of the National Coordinator for Healthcare IT could adopt those terminology mediation services for use in the Nationwide Health Information Network (NwHIN), and NwHIN Connect and Direct products (typically using a Berkeley Software Development License). In any event, the environment is ripe for continued academic and commercial collaboration under an STTR to advance the domain. Desired State: Research conducted under this topic will directly support the PCAST and ONC visions, but would be conducted primarily on behalf of the Military Health System, which provides an integrated healthcare delivery system for 9.6 million beneficiaries. This care is delivered through a combination of direct care Military Treatment Facilities and private healthcare delivery organizations under the TRICARE triple option health benefits program. Nearly two thirds of healthcare is delivered to military beneficiaries through the private sector. Given that military families are also highly mobile, moving on average every three years to new duty stations, finding a way to exchange data and create a longitudinal virtual electronic health record is an important objective of military medicine. Clearly the research would also be extensible to other national publically and privately funded healthcare delivery systems and information exchanges. The prototype to develop a universal exchange language for healthcare information and a digital infrastructure for locating patient records while strictly ensuring patient privacy may employ the U.S. Army Telemedicine and Advanced Technology Research Center"s (TATRC) Early Stage Platform (ESP) for Research and Development, which provides a fully replicate DOD Electronic Health Record and CHCS computerized physician order entry and results retrieval system for third party development, using virtual machine access. TATRC will coordinate this research closely with HHS, Office of the Nationwide Healthcare Information Coordinator, the Veterans Administration, and with the Center for Medicare Services (CMS). It is fully expected that the research will be extendable into the public good and will benefit the development of new electronic health records developed by the private sector that would utilize the universal exchange language. PHASE I: In Phase I, the awardee will outline a strategic, operational, and technical alternatives to creating a prototype, open source, universal health exchange language service that can operate as a service on the NwHIN, and support health exchange for military medicine. Phase I work should center on a limited number of use cases to be determined in conjunction with the government Contracting Officer Representative. Phase I will also provide opportunity for consultation with ONC for Healthcare IT and other subject matter experts. At the conclusion of Phase I, the awardee will recommend a technical reference implementation architecture, which will then be built as a prototype in Phase II of the SBIR. PHASE II: In Phase II, the awardee will build the universal health language prototype, as an open source service on the NwHIN Connect solution, and demonstrate the exchange of military, VA, and civilian health data with semantic interoperability in a laboratory setting, potentially using the TATRC early stage platform for research and development. At the conclusion of Phase II, the prototype will be demonstrated to U.S. Army TATRC, Military Health System, HHS ONC for Healthcare IT, HHS CMS, Veterans Administration, and other government officials. PHASE III: In Phase III, the universal health language service would be implemented on the NwHIN, or otherwise in local or regional health information exchanges to support scalable terminology mediation between electronic health records systems. Such work may also be commercialized and of interest to commercial electronic healthcare vendors. Ideally, the universal health language service would be an open source service, with the vendor choosing to sell services around the open technology.

OBJECTIVE: Explore the use of natural language and clinical language understanding technologies, combined with IBM Watson-like technologies, to predict provisional diagnosis, provide clinical decision support, predictive analytics, and improved outcomes for mild TBI and PTSD patients. Develop a mobile, cloud-based architecture that can integrate with existing or improved clinical workflow, and ties to the Electronic Health Record. DESCRIPTION: For more than 30 years, academic researchers have studied the use of computers to predict diagnoses and make recommendations for treatment. Such work has developed a number of standards and frameworks for developing and executing clinical decision support guidelines and algorithms, such as SAGE, EON, GLIF, and ATHENA. Several commercial products to couple knowledge with problems, and to predict diagnosis and recommend treatments, such as PKC Couplers, Agile Diagnosis, Isabel, TheraDoc, Zynx, and others, and have emerged on the marketplace but have not been widely adopted, perhaps because the clinical decision support guidelines are typically segregated to one disease domain, and do not cross domains. In addition, such clinical decision support systems have not been truly integrated into a clinician"s workflow and/or into the Electronic Health Record. Maintaining current medical knowledge within the algorithms has also posed considerable challenge. The TATRC Morningside Initiative, started in 2007, was an attempt at a private-public partnership to create an open source repository of clinical knowledge. Two recent developments may change adoption rates, however. First, Qualcomm has joined forces with X-Prize foundation to over a $10M prize to any individual or company that can develop a mobile computerized decision support tool that can diagnosis patients as good as a panel of board certified physicians. Second, using technology that has evolved out of the widely advertised Watson Jeopardy game challenge, IBM has announced a major collaboration with WellPoint to use Watson technologies to diagnosis and recommend treatments for oncology patients. Several key partnerships have formed between Nuance, IBM, and 3M to apply speech recognition, natural language processing, and medical ontologies towards development of improved clinical decision support tools to predict diagnoses and offer treatment options. A number of companies are also releasing products that use embedded sensors to collect patient physiological signs, and include them as input to the clinical decision support algorithms. Some of these products are smart-phoned based, although research in mobile, cloud-based technologies is just beginning and is 5 to 10 years from maturation. PHASE I: In Phase I, the awardee will develop alternative strategic, operational, and technical architectural views for a clinical decision support aid which can predict diagnosis from patient history, symptoms, and/or physiological signs, with a focus on using mobile, cloud-based speech recognition, natural language processing, and IBM Watson-like technologies to capture and analyze data. Initial use case will focus on improving outcomes for mild TBI and PTSD patients. The awardees will work with TATRC and its partners to incorporate existing, ongoing natural language processing and clinical decision support work as applicable, and produce a complete design document for a clinical decision support tool that will predict diagnoses based on patient history and symptoms. The government encourages evaluating the use of cloud-based algorithms which can be executed on mobile devices. The government also encourages the use of standards based, open source clinical practice guidelines for execution. To the extent that the specific pathways can be seen within the algorithm, and are not proprietary, they can also be used to support training of residents. PHASE II: In Phase II, one or more awardees from Phase I will build and test a prototype. TATRC can provide use of a virtualized Early Stage Development (ESP) platform that can be used in the project, although a vendor use fee will be negotiated under a CRADA. The ESP platform has access to a fully functional AHLTA and CHCS development and test environment. TATRC will also make available open source VISTA code that the awardees can consider using in the project. TATRC will attempt to supply sufficient military clinical subject matter expertise to test and evaluate the prototype as to clinical relevance, accuracy, and usability. The awardees should also provide their own clinical expertise in addition to what expertise the government may provide. PHASE III: It is anticipated that this research will yield improvements in application of mobile-based natural language processing, clinical language understanding, text analytics, computerized algorithms, and artificial and business intelligence, that may have applicability outside of the medical domain and may be applied in other domains, such as military intelligence. The government also expects that this research may yield new developments in computerized modeling and simulation to train personnel in a number of industries.

OBJECTIVE: Define and prototype architectural alternatives resulting in an easy-to use cohort builder for clinicians, nurses, and QA personnel. The cohort builder would be used for conducting quality assurance and comparative health effectiveness research; to recapitulate findings in the literature; and to remediate patient care issues for chronically ill patients. DESCRIPTION: The mantra of the Military Health System is to deliver available, accessible, acceptable, high quality, continuous, and cost effective healthcare to 9.6M beneficiaries. Each budget cycle the Military Health System is called upon to deliver continuously improving healthcare, yet has ever-increasing constraints placed on its resources. In order to do more with the same or less level of resources, and without adversely impacting health outcomes and patient safety, the Military Health System should engage in comparative health research studies to ascertain which treatments provide the best outcomes at equal or less cost than other therapies. Additional studies should be conducted to determine why one clinician may get better outcomes at equal or less cost than his/her peers, considering case mix (i.e. clinician profiling). Yet the Military Health System does not currently have the clinical analytical tools to conduct such analyses. Although the Military Health System (MHS) has a number of Automated Information Systems (AIS) in its inventory, including AHLTA, Clinicomp Essentris, CHCS, ICDB, MDR, M2, CDM, HSDW, AFCHIPS, Air Force Population Health Portal, Medical Home Clinical Data Mart, and others, there is no system that allows clinicians to build cohorts for quality assurance studies or comparative health effectiveness research, and compare those cohorts as to differences in health outcomes. In the current state, clinical quality assurance and comparative health effectiveness research studies cannot be easily conducted. Executing such studies requires extensive expertise in the form of data priests and statisticians, to identify appropriate data, pull it from the right sources, consolidate it, and analyze it. Conducting such studies can take months. Issues impacting the care of chronic care patients at the point of care cannot be easily identified or remediated at the point of care. Studies in the literature cannot be re-capitulated in a clinician"s panel in a matter of minutes. Of additional concern is the current rapid promulgation of domain-specific data marts and registries in the new Centers of Excellence, with no robust toolsets to conduct health outcomes on those registries. In the envisioned state, access to information would be democratized, with no need for data priests or statisticians. Clinicians, nurses, and QA personnel would access an easy-to-use cohort builder on their desks, that allows one to quickly build cohorts on any combination of parameters collected in base transaction systems; which supports different time events for different parameters; and provides for risk windows and blackout periods; for the primary purpose of remediating issues identified in chronic care patients. In addition, the cohort builder would be self-documenting in terms of identifying the basis for the cohorts, and produce analysis suitable for publication in research journals. The tool would incorporate a statistical service to make automated, on the-fly comparisons between cohorts as to differences in morbidity and mortality. All parameter lists, cohorts, and outcomes could be saved as objects and reused. The output of one study could become the input for another study. PHASE I: In Phase I, awardees will outline strategic, operational, and technical architecture alternatives for a prototype cohort builder to support health outcomes studies. The alternatives would include an analysis of existing GOTS and COTS products and their ability to be integrated into current clinical intelligence frameworks. The output of Phase I is a report that would provide details on the cohort builder would integrate with existing and planned MHS transactional, data marts, registries, and data warehouses, and which would serve as a complete design document to actually build a prototype cohort builder. PHASE II: In Phase II, the SBIR recipient(s) will build or buy a cohort builder, integrate it with various MHS data sources, and pilot the tool with approximately 20 clinicians at the Walter Reed Army Medical Center, USU, and Centers of Excellence. During the prototype, the Phase II recipient(s) would collect data on the usability of the cohort builder in conducting health outcomes studies, and conduct measurements on how the cohort builder improves the effectiveness and efficiency of outcomes studies over previously conducted manual efforts. Any particular studies conducted would require IRB approval in advance. PHASE III: Clinical intelligence and/or electronic health record vendors that support the analysis of healthcare delivery in traditional inpatient and outpatient settings could commercialize this research for use in new markets, including the life sciences. Those conducting comparative effectiveness of commercial products might even adopt the work outside the healthcare of life sciences arena.

OBJECTIVE: Develop a novel freestanding, lightweight, compact, portable sampling device to collect a broad spectrum of adult flying insect disease vectors. DESCRIPTION: Vector borne disease historically ranks among the leading causes of Disease and Injury (D&I) among U.S. service members deployed in support of military operations. Entomologists perform vector surveillance in order to mitigate the threat of vector borne disease among military populations. Vector surveillance provides information on density, abundance, distribution, and species composition of vectors as well as a way to evaluate results of control measures. In order to properly characterize the threat of vector borne diseases and develop effective control techniques, equipment used in vector surveillance operations needs to be highly effective, easily transported, and relatively maintenance free. Vector surveillance devices should ideally be able to target multiple groups of insect vectors and be self-contained, to eliminate the need for numerous devices and reliance on external power or fuel sources. The CDC light trap was developed in the mid-20th century and has been virtually unchanged since the 1960s. It is the primary piece of equipment used in vector surveillance for adult insect vectors, such as mosquitoes and sand flies, in military and civilian vector surveillance and control programs. Depending on availability, the CDC light trap is sometimes augmented with carbon dioxide from dry ice or another source. Unfortunately, even with carbon dioxide supplementation, this trap does not work well for many militarily important adult insect vectors, including the vectors of Dengue fever, malaria, and leishmaniasis. While the CDC light trap is recognized to have serious flaws in its ability to provide reliable, accurate vector surveillance for most adult flying insect vectors, it remains the standard trap used by military entomologists during deployments. As a component of the U.S. Army Medical Equipment Set (MES) Entomological Kit Field (UA 124A), it is fielded to all level II and III Army preventive medicine assets for operational use worldwide. Unfortunately, this trap has not kept up with the rapidly changing understanding of insect behavior and improving technology in recent years. Over the last two decades, newer adult flying insect traps have been developed in the commercial sector in an attempt to provide more effective means of surveying for important insect vectors. These newer devices rely on chemical cues, such as carbon dioxide or other chemicals that are present in human skin secretions, and/or different wavelengths of light. While some of these new traps, including the Mosquito Magnet, BG Sentinel, and Zumba traps, are more effective than the CDC light trap at collecting certain groups of host seeking mosquitoes, none of these traps are broadly effective against the variety of flying adult insect vectors (Bhalala and Arias 2009, Dusfour et al 2010). In addition, many of the new traps available are not as portable as the CDC light trap and still require reliance on external power or fuel sources, ranging from large batteries to propane tanks. The DoD Armed Forces Pest Management Board (AFPMB) has identified the need for new or improved vector surveillance systems as the most important research priority for military entomology (AFPMB 2011). Military vector surveillance varies from other governmental and non-governmental vector surveillance efforts in that military entomologists need the tools to conduct accurate surveillance in any environment or geographic region to which they may be deployed. Furthermore, military entomologists need tools that are easily transported in order to ensure that they can get them to any location, no matter how remote, where vector surveillance will be required. A vector surveillance tool that is broadly effective, reliable, and portable will fill a major gap in our ability to accurately characterize the threat of vector borne disease in military operations. The purpose of this project is to develop a novel device to perform surveillance on adult insect disease vectors. This device should be attractive to a variety of vector groups, including mosquitoes (Anopheles, Aedes, and Culex species) and sand flies (Phlebotomus and Lutzomyia species). Efficacy against black flies, biting midges, and tsetse flies would be desirable, but is not the primary focus of this effort. The trap should be freestanding, lightweight, compact, portable, and should not require an external power source. The internal power source should be DoD Green Energy compliant. The device may be either one standard piece of equipment that is effective against the broad range of vectors outlined above or it may consist of a modular design that can be tailored to the specific group of interest. PHASE I: This phase of the SBIR should focus on developing the initial concept and design for the surveillance trap. PHASE II: During the Phase II portion of this SBIR, the awardee should develop the prototype trap design. Once the initial prototype is developed, it should be tested in both laboratory and field environments for efficacy in collecting a variety of insect disease vectors, such as mosquito and sand fly vectors. Field testing should include operation in a variety of environments, including desert and tropical environments. At the conclusion of Phase II, the awardee should have developed a prototype that is effective in sampling for mosquitoes (Anopheles, Aedes, and Culex species) and sand flies (Phlebotomus and Lutzomyia species), is freestanding, lightweight, compact, portable, and operates without an external power source. PHASE III: The proposed SBIR has commercial applications outside of the military. This sort of novel vector collection device could be used in public health disease surveillance programs (both governmental and non-governmental) and by public health researchers. At the completion of a successful Phase II, the company should seek funding from either a private company for commercialization of the product or through advanced development funding. The product resulting from this SBIR should be considered for NSN assignment so that it may be readily purchased by military and other US governmental organizations. In addition, the product should be considered for inclusion in the MES Entomological Kit Field as a replacement for the CDC light trap. The product should also be commercially available for other vector borne disease surveillance applications.

OBJECTIVE: Develop and optimize integration of networked sensors located on torso and appendages of body to assess accurate center of-gravity and center-of-pressure in real time. DESCRIPTION: The most frequent and challenging symptom experienced by military personnel exposed to IED or concussive events is dizziness or loss of balance (Balaban 2009). Balance is also an issue for warfighters who require prostheses to compensate for loss of limbs. Biofeedback vibrotactile prostheses have recently been developed to assist patients during recovery while they are undergoing rehabilitation to achieve unsupported upright posture. (Atkins 2011, Rupert 2010). These sensory aids receive center-of-pressure (COP) and derived center-of-gravity (COG) information from static force plates. In order to provide assistive sensory information during the dynamic condition of walking without falling, it is necessary to provide real time COP/COG information to the assistive device. Recent advances in Micro-Electrical-Mechanical Systems (MEMS) have made accessible a variety of extremely small, rugged, reliable, low power consumption, and inexpensive sensors of acceleration and pressure. A collection of these devices should be capable of providing similar proprioceptive information that the distributed biological sensors of the human body provide the brain to carry out complex mobility tasks. What are the minimal number, location and type of sensors required to provide real-time balance information to an integrative device, which with an appropriate algorithm can provide assistive cueing to prevent falls? The technology achievements in MEMS, garments with built in electronics, and miniaturized short-range wireless transmission now create the opportunity to efficiently link multiple sensors (e.g. inertial, pressure, etc) that can provide the basis for"real-time"COG/COP information, which can be integrated with additional sensors and utilized to provide the patient tactile, visual and auditory cueing systems to enhance balance during dynamic conditions. This same technology has immediate and obvious applications to robotics. This topic seeks proposals addressing both hardware and software issues: the hardware must provide sufficient information to provide real-time COG/COP no matter how the extremities are being moved dynamically in space and the software should be able to predict falls during dynamic walking conditions. PHASE I: 1) Develop and demonstrate a prototype integration of distributed sensors capable of providing real-time COG and COP for ambulatory human or robot. 2) Outline plan for software development capable of predicting excursions outside the normal envelope of walking. PHASE II: 1) Building on the prototype from Phase I, test and demonstrate the system hardware and the software algorithm developed to predict falls. PHASE III: 1) Provide caretakers of wounded warriors with ambulatory device to replace current static force plate training and evaluation devices. 2) Incorporate balance technology into humanoid robotics.

OBJECTIVE: Develop a user-friendly, portable, universal hearing protection device (HPD) field attenuation estimation system (FAES) that deployed or garrison personnel can use to measure the effective noise protection provided by a hearing protection device or system that is fit and worn in the field. DESCRIPTION: It is generally understood that hearing protection devices typically fail to provide the protection that is measured in carefully controlled laboratory tests conducted in accordance with national testing standards (e.g., ANSI/ASA 12.6-2008). Berger (1993) conducted a meta-analysis of a number of field noise attenuation measurements and concluded (1) that the noise protection (as defined by the protectors"Noise Reduction Ratings [NRRs]) as seen in the field (i.e., real world) are appreciably lower than the NRRs calculated from carefully controlled standard-based laboratory studies and (2) that there is no clear relationship between the laboratory measurements and the real-world performance of the various hearing protectors. These two observations are valid for both insert (i.e., earplug) devices and circumaural (i.e., ear muff) devices. Berger (1980) summarizes various reasons why the field measurements do not meet the numbers obtained in the laboratory (comfort, utilization, fit, compatibility, readjustment, deterioration, and abuse). The point is, however, that only highly trained and motivated users of hearing protection devices can obtain consistent fits yielding noise protection that approaches that measured in the laboratory. Furthermore, hearing protection devices are not being employed sufficiently or properly in the military. Bjorn, Albery, Shilling and McKinley (2005) conducted a survey of hearing protector use by flight deck crews on six US Navy capital ships, four aircraft carriers and two amphibious ships. (Three ships were surveyed from the Second [Atlantic] and Third [Pacific] fleets.) They reported that only 53% of the flight deck crew that were surveyed (and who were required to wear double protection [i.e., earplugs and earmuffs]) wore earplugs and only 7% wore their earplugs in a manner to achieve the published 22 dB noise protection. Thus, the 46% of the Sailors that actually used earplugs wore them incorrectly. PHASE I: This topic seeks the development of a hearing protection validation system for use by medical or trained deployed personnel to evaluate the fit and protection of hearing protection devices. It will provide a single value Personal Attenuation Rating (PAR), calculate protected exposure levels in dBA, calculate protected exposure time limits, provide a percent dose estimate, conduct testing using a Field Microphone-In-Real-Ear (F-MIRE) technique that does not modify the hearing protection device, be capable of testing attenuation of any commercially available device including single, double, and triple (Active Noise Reduction) hearing protective devices, complete all measurements bilaterally in 15 minutes or less, be sold at a fixed single unit price ($2500 - $3500 range to include computer re: (2011 prices), use an iPad, tablet or portable hardware and operating system technology, have little to no consumables, have up-gradable software, be portable (less than 15 lbs), be ruggedized and durable for field or deployed use, be capable of data import and export from and to existing DoD systems, have computer interface capability, have database extraction and Excel file data transfer modality, be capable of testing multiple individuals concurrently (up to 8-10), be capable of DoD service or unit-self calibration, have a color screen display, produce a printable report, have an examiner testing menu, have a patient instructional display screen, provide individualized patient results and instructional materials, and be compliant with all current applicable ANSI standards. The Phase I deliverable will include an initial design concept that addresses solutions for at least 80% of the HPD FAES characteristics described in the previous paragraph. PHASE II: During Phase II, the awardee will implement the best approaches from Phase I into hardware and software and develop, test, and demonstrate all of the requirements of the HPD FAES noted above. At the end of Phase II, the company will deliver to the US Army Aeromedical Research Laboratory three (3) field-ready prototypes for laboratory and field testing. Laboratory testing will include, but not be limited to, comparisons with hearing protection performance measurement systems such as those that adhere to the requirements specified by ANSI/ASA S12.6"American National Standard Methods for Measuring the Real-Ear Attenuation of Hearing Protectors"(2008). Field testing will involve insertion of the device into an Army hearing conservation clinic and its use included as part of the Army Hearing Program (2008). PHASE III: The problem of HPD fit and fit verification is one faced by military, civilian governmental organizations (e.g., law enforcement agencies), and industry. The FAES developed as a result of this SBIR will be a valuable tool for all environments (including recreational environments) in which noise hazards exist and hearing protection is mandated or recommended. The Occupational Safety and Health Administration"s (OSHA) Alliance Program (2008) notes that individual HDP fit verification testing is an emerging"best practice"trend in hearing conservation programs. Phase III deliverables will be a validated, ruggedized FAES that is easily and reliably manufactured and can be utilized in harsh environments including military forward operating bases, shipboard, and on factory floors.

OBJECTIVE: Self-powered wearable biosensors will be developed to provide continuous health monitoring, in particular respiratory effort, and ECG monitoring. It will be demonstrated that wearable biosensors can be self-powered by harvesting ambient energy or monitored physiological signals. DESCRIPTION: Self-powered wearable biosensors could provide a powerful tool for continuous medical monitoring, and for monitoring personnel carrying heavy loads or in high-stress situations, such as monitoring Warfighters health, providing support for assessing Warfighter readiness and feedback mechanism for improving Warfighter performance, and reducing Warfighters"battery load. To enable wearable sensors, power on the order of mW must be available to enable continuous data sampling and processing, and wireless data transmission [1, 2]. Power that far exceeds those requirements, on the order of Watts, has been extracted from human gait using shoe, knee, and back-pack mounted generators [3-5]. Human energy sources may potentially provide not only a power source, but also physiological information [6-7]. In particular, respiratory effort and bioelectricity are always present energy sources that intrinsically carry rich physiological information. Respiratory effort available power has been estimated to be between in the mW range [3, 7]. Innovative solutions are being sought to provide and maintain continuous medical and health support for any operation requiring military service, through deployment of wearable biosensors. Minimum accomplishments include monitoring of at least one respiratory parameter, such as respiratory rate, and at least one cardiac parameter, such as heart rate. It is required that sensor will be battery-less, and derive electric energy from ambient sources or physiological signals. Ergonomic design embedded in clothing, continuous (24/7) operation, and wireless connectivity must be demonstrated. Use of a small, light, rechargeable battery is acceptable. PHASE I: During Phase I, technical feasibility of the proposed approach will be determined. Energy source will be identified for powering wearable biosensors. Required Phase I deliverables will include initial biosensor concept design, energy harvesting and consumption rate analysis, and plan for ergonomic deployment of the proposed concept. PHASE II: During Phase II, a commercially viable prototype will be fabricated and tested. Proposed self-powered, wearable biosensor concept will be validated, and component design, and system fabrication will be completed. The operation of the ergonomic prototype will be demonstrated. Required Phase II deliverables include wearable biosensor prototype, including ergonomic energy harvesting and physiological sensing hardware, robust software for physiological information extraction, and low-power wireless connectivity. PHASE III: There are clear commercial opportunities for continuous medical monitoring. The major military application are monitoring Warfighters health in training and deployment, providing support for assessing Warfighter readiness and feedback mechanism for improving Warfighter performance, and reducing Warfighters"battery load. The major civilian application is remote monitoring of patients with chronic disease, and human performance monitoring during athletic training.

OBJECTIVE: The objective of this research is to develop durable, scalable, robust and effective long-term antimicrobial textile finish. DESCRIPTION: There is a continuing need for antimicrobial textiles to provide a range of capabilities to the DOD. These include improved hygiene for soldiers via integration into uniforms to control odor; in medical textiles to control the transmission of pathogenic bacteria in field medical shelters and military hospitals. The goal of this topic is to identify light-weight, durable, antimicrobial finishes for textiles such that no degradation of other properties (e.g., porosity, mechanical properties) occurs. This is an important component in the overall strategy for improving soldier performance, and the development of Smart Textiles. Research will focus on developing and optimizing catalytic antimicrobial systems for direct integration into fabric for clothing, shelters, etc. The resulting technology should be easily integratable into fabric weaving and manufacture, and scalable to a high through-put process, allowing large volumes of fabrics to be treated. PHASE I: Initial research will focus on chemical functionalities that can be applied as a fabric finish to provide high antimicrobial activity. Key functional properties that need to be addressed include non-leaching behavior of the coating, and an assessment of antimicrobial activity against Gram positive and Gram negative bacteria. Application of the finish must not lead to significant degradation of other properties (i.e., porosity, dyeability, printability, durability, mechanical strength, flexibility). PHASE II: In this Phase, the process and characterization should be expanded to include cotton, polyester, and nylon and polyaramid textiles. Antimicrobial activity must be determined for coatings on all fiber types. Uniformity of the finish on each type should also be demonstrated. Textile properties should be determined using reliable metrology, and under typical conditions encountered by Soldiers and after multiple laundering cycles. The final coating and textile must be characterized to provide data on the extent of coating coverage, functional group density, coating adhesion, and antimicrobial activity and lifetime. PHASE III: This technology will have both DoD and civilian applications, including antimicrobial textiles, anti-infective wound dressings, hospital textiles, bedding, wipes, HVAC filters, and medical devices.

OBJECTIVE: Develop solution to enable closed loop anesthesia delivery system that can be used in far forward operations with regulatory plan for FDA approval, leading to commercialization of the product for use in the United States. DESCRIPTION: Total intravenous anesthesia (TIVA) technique through a target controlled infusion (TCI) approach is an accepted method of inducing and maintaining sedation and analgesia in Europe and other parts of the world, except the United States. Advantages of TIVA include improved postoperative outcomes and faster recovery with minimal side effects such as postoperative nausea and vomiting. Use of TCI anesthesia (TCIA) in the United States and in theater of operations for the United States Armed Forces could improve treatment of casualties including service members, but it is currently not possible because there is no FDA approved TCI devices on the market. One of the reasons for this absence of FDA approved TCI devices stems from a safety concern due to the fact that TCIA infusion rates are determined by population-based pharmacokinetic data and individual patient biometrics. Therefore, the exact targeted plasma or effect-site concentration selected by the anesthesiologist is more art than science (i.e. lacks precision). Current TCI devices with biofeedback for closed loop control of propofol infusion exists, using bispectral impedance brain monitoring as the biofeedback for example to guide anesthesiologist the level of consciousness in the patient. Although such method has been validated in clinical studies and can be used in feedback control paradigms, there are limitations to bispectral impedance brain monitoring for closed-loop propofol delivery. Chief concerns include that the level of consciousness is an indirect measure of the level of drug in the blood and as such is a delayed biomarker and that bispectral impedance brain monitoring does not provide information regarding the potentially lethal levels of the drug (i.e. acute toxicity). Hence, inclusion of a biosensor would be one approach that could provide for direct measured drug levels in the serum and development of an algorithm to control infusion rate of drugs in TCI devices would enable automated TCIA with minimal additional external devices and monitors that add more weight and volume, which need to be minimized in the far forward operations. The algorithm for correlating blood concentration to individual pharmacodynamics needs to be accurate and responsive (i.e. less than 1 second response time) to ensure the appropriate conscious state is reached without overdosing or under dosing the patient. The objective of this SBIR is to solicit for concepts that will enable automated TCIA system that could also be deployed for use in military theaters, to include far forward surgical teams and providers. Since existing TCI devices are already available, the solution should not include redesign of this component, but should focus on components that can be easily integrated into existing TCI devices to enable direct measurement of drug level and automation of the device, minimizing volume and weight for portability and taking into design considerations to fit within the environment. Due to the range of variance between individuals in the normal pharmacodynamics and kinetics of propofol, the functional physiologic end point is critical in assessing the patient"s conscious state. Therefore, innovation is also solicited for other biomonitoring concepts (other than bispectral impedance brain monitoring) that assess physiological parameters to guide anesthesiologist the depth of anesthesia whether the concept is used as an addition, separate, or alternative feedback control to direct measure of analgesia, but must address weight, volume, and ease of use to enable operations in the far forward. The proposed solution must account lags whether using physiologic state assessment and/or analytics associated with on-line propofol analysis, with less than 1 second response time. Partnership with TCI device maker is encouraged, but not required. Designs that can be easily integrated into all or most existing TCI devices are preferred. PHASE I: Conceptualize, design, and build a solution to enable closed loop TCIA and test the prototype. Required Phase I deliverables will include research design, prototype with limited testing in demonstrating proof-of-concept in vitro including performance metrics such as accuracy and sensitivity, research plans for preclinical testing, and commercialization strategy including regulatory plans. Literature and market review should be done as part of the proposal background information and not as a task to be executed during Phase I period. No animal or human use testing is to be proposed or executed during this 6-month Phase I period due to requirement of second level DoD review, which generally adds more time beyond the 6-month Phase I period. Travel should be budgeted to government site at Fort Detrick, Maryland for In Process Review at month 5 or 6 of Phase I, where results and deliverables obtained to date be presented before government subject matter experts, stakeholders, and program managers. PHASE II: Demonstrate the proposed closed loop system in preclinical studies (i.e. relevant large animal model). Required Phase II deliverables will include design improvements to the prototype based on Phase I testing, demonstration of the solution in relevant animal model, performance metrics of the system determined, and commercialization plans including regulatory pathway for FDA clearance. PHASE III: Phase III efforts should lead to FDA approval and be focused towards technology transition, preferably commercialization of STTR research and development. Efforts leading to FDA approval require execution of Phase II plans on commercialization and regulatory pathway, including identifying relevant patient population for clinical testing to evaluate safety and efficacy. The small business should have in plans to secure funding from non-SBIR government sources and /or the private sector to develop or transition the prototype into a viable product for sale in the military and/or private sector markets. Commercialization plans that include the private sector generally help lower cost through economy of scale.

OBJECTIVE: Develop a controlled, target-specific delivery system for topical treatment of peripheral neuropathy. DESCRIPTION: Peripheral neuropathy (PN) is a painful, debilitating, and often chronic condition associated with diabetes, cancer treated with various chemotherapies, and a wide variety of other diseases and conditions, such as infections, environmental/toxic exposures, alcoholism, and extremity injuries. PN is caused by damage to the small nerve fibers and may occur anywhere in the body, but is most common in the feet and lower legs. Pain symptoms may include sudden burning discomfort, electric shock-like sensation, tingling, numbness, and sensitivity to non-inducing stimuli (allodynia). The incidence of PN in diabetes is estimated as low as 20-25% and as high as 70%. The incidence of PN is about 30-40% in cancer patients treated with some of the commonly administered chemotherapeutic agents, including cisplatin and paclitaxel. In addition to the impact of PN on individuals with diabetes and cancer, the impact of PN on military and veteran populations is significant. Deployment-related conditions put military personnel at risk of peripheral nerve injuries and many other nerve injuries resulting from trauma, blasts, and exposure to agents or environmental factors. Pain management for neuropathies is a major medical concern for military and veteran healthcare. Taken together, the prevalence of PN-associated diseases like diabetes and cancer, combined with the significant relevance to military and veteran populations, underscore the need to develop novel treatments for PN. Currently, there is no established treatment for chemotherapy-induced PN, and only two agents (duloxetine and pregablin) are approved by the US FDA for treatment of diabetic PN. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is common, but is limited due to nonspecificity and long-term treatment toxicities. The analgesic efficacies of several other agents in treating PN are being tested in pre-clinical studies and clinical trials. While not all-inclusive, the major categories of systemically administered treatments for PN that have recently been investigated include: 1) tricyclic antidepressants; 2) selective serotonin-norepinephrine reuptake inhibitors (SSNRIs); 3) anticonvulsants; and 4) opioids. Considering the dose-limiting toxicities of several of these systemic treatments, topical treatment for PN is a promising, yet underdeveloped area of research and development. Topical capsaicin treatment has been investigated in diabetic patients and has shown some evidence of benefit. Topical lidocaine administered through a patch has also shown pain improvement in clinical trials done in diabetic patients. Topical treatments combining antidepressants and anticonvulsants have also recently emerged with promising findings in a clinical trial of patients with chemotherapy-induced PN. Some of the constraints and challenges of topical treatment development that need to be resolved include skin penetration and drug permeation, as well as optimum drug dosage for long periods to increase efficacy. This topic seeks to develop a drug delivery system for a novel topical treatment for PN. The innovative approach will deliver one or more drugs through the skin and into the affected area to relieve pain. The drug delivery system should optimize efficacy and bioavailability of the treatment by integrating a target-specific and a controlled drug-release mechanism. The delivery system is also expected have no, or minimal, toxicity. The choice of drug(s) to be tested should be based on current knowledge and recent studies on PN treatment. The system should include a topical formulation that would be easily applied by the patient or caregiver. PHASE I: Phase I work will design and develop the drug delivery system, and will use in vitro assays to test its feasibility in transporting the therapeutic through skin. Data will provide proof-of-concept that the system can be applied topically and penetrates through the skin barrier to transport and deliver the drug. An appropriate skin or skin-like model will be utilized. Parameters including optimal concentrations and topical formulation, nerve targeting capability, and controlled release will be defined. Appropriate controls will be used. PHASE II: Phase II work will test, optimize, and validate the delivery system in animal model(s) of PN to demonstrate the analgesic effects in reducing pain. The FDA approval pathway should be outlined and considered at each developmental stage. Parameters including optimal concentrations, biological activity, toxicity, nerve targeting specificity, and controlled release will be defined. In addition, tolerability of the topical formulation on the skin will be demonstrated. Validation of success will include the marked reduction or resolution of pain in the animal model(s). During Phase II, clinical experts with insight into relevant patient populations should be consulted as the system is being fully optimized. Potential commercial and clinical partners for Phase III and beyond should be identified. Phase II technical proposals should include a detailed explanation of how the small business will obtain a monetary return on investment within two years of completion of Phase II (e.g. through sales, licensing agreements, venture capital, non-SBIR grants). PHASE III: If successful, Phase II work will result in a novel nerve-targeted, controlled release drug delivery system to treat PN. During Phase III, additional experiments will be performed as necessary to prepare for FDA review of an IND application. A plan for protection of intellectual property should be created and executed. A detailed market analysis will be conducted, an initial clinical application for the therapeutic system will be selected, and a Phase I clinical trial will be initiated. Military application: The new therapeutic will be available to military personnel and veterans who suffer from PN caused by deployment-related conditions, including peripheral nerve trauma, infections, and environmental agents or toxins. In addition, healthcare and quality of life for veterans with diabetes and cancer could also benefit significantly. Commercial application: Health professionals around the world could utilize this therapeutic to treat PN caused by diabetes, cancer chemotherapy, and many other conditions that cause PN.

OBJECTIVE: Develop and validate a biometric model for use by the medical research community to address dismounted complex blast injury of the pelvis, abdomen, and genitals. DESCRIPTION: In Afghanistan, military medical healthcare providers have expressed an interest in providing protection to soldiers to mitigate dismounted complex blast injury (DCBI). Specifically, they would like to provide protection to the pelvic floor anatomical area, the abdomen, and the genitalia during a blast event such as that seen during the explosion of an improvised explosive device (IED). The problem was outlined in Report #8 from the OPERATION ENDURING FREEDOM (OEF) Field Assistance in Science&Technology Medical Team OEF FAST Team 04. Subject Matter Experts are in the process of collecting data to characterize the epidemiology of this event. Patient trauma data is being captured in the Joint Theater Registry (JTTR). A Pelvic Protection Working Group (PPWG) was formed, and an abbreviated analysis of JTTR shows six soldiers were recently wounded in action and sustained pelvic injuries. At least two commercial products were identified, and an evaluation was requested. In April, 2011, the Army Research Laboratory (ARL) conducted testing using a"sand cannon."These sorts of tests provide impact forces, but do not necessarily model what anatomical and physiological damage would result. Regional Command (South) (RC(S)) is a multi-national military group that is part of the International Security Assistance Force (ISAF) in Afghanistan. Its headquarters is located in Kandahar, Afghanistan. In May, 2011, A Joint Urgent Operational Needs Statement (JUONS) was presented to RC(S). The Project Manager, Soldier Protection and Individual Equipment (PM-SPIE) is pursuing the evaluation of potential products. The U.S. Army Research Institute of Environmental Medicine (USARIEM) Subject Matter Experts (SMEs) are planning to use a thermal manikin for an interim evaluation of commercial products. The ARL and USARIEM models are not ideal for identifying the anatomical and physiologic damage of DCBI to the pelvis, abdomen and genitalia that may occur. They will estimate the forces transmitted, etc. and can be used to provide input data for a biometric model of the anatomy and physiology of the targeted area. A biometric model of the anatomy and physiology of that pelvic area is needed. How well a possible protective solution performs will need to be determined using this biometric model. PHASE I: This phase would include investigation of the epidemiology of the problem. It would include the design of a concept for the model. This feasibility study would determine the scientific, technical, and commercial merit and feasibility of a biometric model for dismounted complex blast injury of the pelvis, abdomen and genitalia. The Phase I deliverables would include the results of the epidemiology study and the feasibility study as well as a validation plan for the model. The deliverables will be used to evaluate the readiness to move the effort to Phase II. PHASE II: This phase would include modeling and simulation of the three dimensional aspects of the anatomy and physiology of the area in question. The model would take force input (blast effect metrics), and provide some indicator of the resulting tissue disruption. The Phase II deliverables would include a demonstration of the prototype biometric model. PHASE III: Phase III includes the technology transition to an Acquisition Programs of Record and/or commercialization of the biometric model for pelvic injury. Funding will be from non-SBIR government sources and/or the private sector to develop or transition the biometric model into a viable product or service for sale in the military or private sector markets. The end-state of this research effort is a validated biometric model of the anatomy and physiology of pelvic floor injury. There is potential commercial application in the private sector with regard to blunt trauma resulting from sports injury, and the development and design of improved personal protective sports equipment.

OBJECTIVE: Develop an objective assay for the rapid and reliable detection/diagnosis of pain and its intensity for use with the traumatically injured including the severely cognitively impaired and sedated patients. The developed assay may include but is not limited to biomarker, imaging, electrophysiological, and other physiological and behavioral monitoring techniques. DESCRIPTION: A high percentage of evacuated soldiers reported experiencing severe acute pain. In a survey of 110 soldiers evacuated from Iraq to Landstuhl Regional Medical Center between July 2007 and February 2008, 60% of soldiers reported their worst pain to be severe (seven or greater on a zero to ten numeric rating scale; Buckenmaier III et al, 2009). Well managed pain in the battlefield is not only an immediate need to a suffering injured warrior but may reduce the probability of suffering from chronic pain (Perkins and Kehlet, 2000). For reasons not completely understood, many soldiers will be afflicted with chronic pain. Complicating the treatment of these patients is the high co-prevalence of chronic pain, posttraumatic stress disorder, and persistent post-concussive symptoms. Despite the numerous treatment options that have been developed for acute and chronic pain management, the treatment of pain often requires a multimodal approach that is individually tailored for the patient. The ability of health care workers to rapidly and reliably detect and measure the intensity of pain among patients that cannot reasonably"self-report"would provide a great advantage for managing pain and for the objective evaluation of treatment options. PHASE I: Required Phase I deliverables will include identifying the measures of pain and designing the plan for practical development of the proposed assay. PHASE II: Required Phase II deliverables will include the development, testing and demonstration of a prototype assay based on the finalized design from Phase I. PHASE III: The contractor should identify a market for the requested effort outside of the parameters of this initiative. A commercialization plan should be described including intended market, design and fabrication requirements, marketing plan, and distribution concept.

OBJECTIVE: The objective of this effort is to design a new innovative technology to intervene during the wound healing process (i.e. inflammatory, proliferative and/or remodeling stages) as to attenuate/control scar contracture and retain skin aesthetics following deep tissue burn injuries. DESCRIPTION: Here we recognize 450,000 burn injuries requiring medical occur in the U.S. each year. Approximately 55% of 45,000 of acute hospitalizations cases require admission to specialized burn units for treatment. Burn injuries also complicate approximately 5% to 10% of contemporary combat casualties not returned to duty within 72 hours. Military combat casualties may be complicated by burn injuries that comprise deep partial thickness, or second degree burns, to full thickness, third and forth degree burns. Re-epithelialization after injury often results in the formation of scars which may subsequently lead to contracture. A contracture scar is a permanent tightening of the skin where normal elastic connective tissue is replaced with inelastic fibrous tissue. Primary skin contractures are common and are the result of the destruction of skin, subdermal fat and fascia. Secondary contractures involve muscles and tendons and inhibit their mobility and may also result in nerve damage or degeneration. Current treatment options for scar contracture may involve over-the-counter treatments, steroid injection or even surgical intervention. The unmet needs lie in scar prevention or, in the case of scarring, the prevention of resultant scar contracture. It is envisioned that proposals will focus efforts on early intervention during the wound healing process, thereby preventing scar formation, or after scar formation has already occurred as a scar remodeling strategy. PHASE I: Conceptualize and design an innovative solution for inhibiting scar formation or subsequent contracture following burn injuries. The required Phase I deliverables will include: 1) a research design for engineering the proposed therapeutic and 2) A preliminary prototype with limited testing to demonstrate in vitro proof-of-concept evidence (to be executed at Phase I). Other supportive data such resulting from in vivo proof-of-feasibility studies may also be provided during this 6-month Phase I period. PHASE II: The researcher shall provide demonstration of solution in relevant animal model, performance metrics, and commercialization plans including regulatory pathway for FDA clearance design, develop, test, and demonstrate a prototype therapeutic that implements the Phase I methodology to prevent scar formation and facilitate wound healing at a burn injury site during this two year Phase II period. The researcher shall also describe in detail the plan for the Phase III effort. PHASE III: Plans on the commercialization/technology transition and regulatory pathway should be executed here and lead to FDA clearance/approval. They include: 1) identifying a relevant patient population for clinical testing to evaluate safety and efficacy and 2) GMP manufacturing sufficient materials for evaluation. The small business should also provide a strategy to secure additional funding from non-SBIR government sources and /or the private sector to support these efforts. Military application: The desired therapy will allow military practitioners to apply the therapy. Commercial application: Healthcare professionals world-wide could utilize this product as a therapy meant to improve the standard of care presently available to burn patients.