University Of Massachusetts

THE CENTER FOR ADVANCING POINT OF CARE IN HEART, LUNG, BLOOD AND SLEEP DISEASES

EDUCATION STABILIZATION FUND - PHASE 2

COOPERATIVE AGREEMENTS TO SUPPORT INNOVATIVE EXCHANGE INFORMATION TECHNOLOGY SYSTEMS

CARES ACT HIGHER EDUCATION EMERGENCY RELIEF FUND

EDUCATION STABILIZATION FUND - PHASE 2

NATIONAL CENTER ON PROGRAM MANAGEMENT AND FISCAL OPERATIONS

UNIVERSITY OF MASSACHUSETTS CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCE

TAS::89 0227::TAS RECOVERY; RECOVERY ACT - POLYMER-BASED MATERIALS FOR HARVESTING SOLAR ENERGY -- EFRC; PI - THOMAS RUSSELL

NATIONAL HEAD START CENTER ON PROGRAM MANAGEMENT AND FISCAL OPERATIONS

CARES ACT HIGHER EDUCATION EMERGENCY RELIEF FUND

UNIVERSITY OF MASSACHUSETTS LOWELL - INSTITUTIONAL FUNDING FROM THE HIGHER EDUCATION EMERGENCY RELIEF FUND

TRANSFORMING CLINICAL PRACTICES INITIATIVE - PTN

WORKER HEALTH AND SAFETY TRAINING COOPERATIVE AGREEMENT

MASSACHUSETTS AI AND TECHNOLOGY CENTER FOR CONNECTED CARE IN AGING AND ALZHEIMER'S DISEASE (MAITC) - PROJECT SUMMARY: OVERALL MORE THAN 90% OF OLDER AMERICANS WOULD PREFER TO STAY IN THEIR HOMES AS LONG AS POSSIBLE AS THEY AGE. HOWEVER, THE PREVALENCE OF CHRONIC ILLNESS INCLUDING ALZHEIMER'S DISEASE (AD) AND ALZHEIMER'S DISEASE RELATED DEMENTIAS (ADRD) CAN MAKE THE GOAL OF SUCCESSFUL AGING AT HOME OUT OF REACH WITHOUT SUBSTANTIAL SUPPORT. AT- HOME HEALTH CARE TECHNOLOGIES HOLD SIGNIFICANT PROMISE TO PROVIDE MANY NEEDED FORMS OF SUPPORT, BUT HAVE NOT BEEN SPECIFICALLY DEVELOPED FOR OLDER ADULTS, AD/ADRD PATIENTS, CAREGIVERS, AND THEIR CLINICIANS. MANY EXISTING HEALTH MONITORING TECHNOLOGIES ARE BURDENSOME TO USE FOR OLDER ADULTS, ARE NOT SUFFICIENTLY ACCURATE, HAVE SPECIFIC ALGORITHMIC BIASES, AND LACK ADEQUATE USABILITY, AND THE RESULTING DELUGE OF DATA OFTEN FAILS TO PROVIDE INFORMATION THAT CAN USEFULLY INFORM CAREGIVERS AND SUPPORT CLINICAL DECISIONS. FURTHER, MANY CURRENT TREATMENT AND INTERVENTION REGIMES ARE LIMITED IN TERMS OF THEIR ABILITY TO BE REMOTELY DELIVERED, MANAGED AND ADAPTED TO PATIENT NEEDS AND CAREGIVER ABILITIES OVER TIME. THE MASSACHUSETTS AI AND TECHNOLOGY CENTER FOR CONNECTED CARE IN AGING AND ALZHEIMER'S DISEASE (MAITC) IS A MULTIDISCIPLINARY CENTER SPANNING FIVE SITES – THE UNIVERSITY OF MASSACHUSETTS AMHERST, BRIGHAM AND WOMEN’S HOSPITAL, MASSACHUSETTS GENERAL HOSPITAL, BRANDEIS UNIVERSITY AND NORTHEASTERN UNIVERSITY – THAT AIMS TO FOSTER INTERDISCIPLINARY RESEARCH ON THE DEVELOPMENT, VALIDATION AND TRANSLATION OF EMERGING AI- ENHANCED TECHNOLOGIES TO ENHANCE CONNECTIONS BETWEEN OLDER ADULTS, CAREGIVERS, AND CLINICIANS IN ORDER TO MORE EFFECTIVELY SUPPORT HEALTHY AGING AS WELL AS THE CARE OF PATIENTS WITH AD/ADRD AT HOME. TO ACHIEVE THIS OBJECTIVE, MAITC WILL PURSUE THE FIVE AIMS. THE FIRST IS TO APPLY A RIGOROUS PROCESS WHICH INVOLVES ELICITING STAKEHOLDER NEEDS TO DRIVE THE FOCI OF PILOT STUDIES AND IDENTIFYING PROMISING TECHNOLOGIES SUITABLE FOR INCORPORATION INTO PILOT RESEARCH PROJECTS. THE SECOND IS TO FORM AND SUPPORT A MULTIDISCIPLINARY COMMUNITY OF ENGINEERS, COMPUTER SCIENTISTS, BEHAVIORAL SCIENTISTS, MEDICAL RESEARCHERS, NURSES AND CLINICIANS WORKING TO ADVANCE THE GOALS OF THE MAITC. THE THIRD IS TO PROVIDE ACCESS TO STATE-OF-ART VALIDATION FACILITIES, DIVERSE COHORTS ACROSS RURAL AND URBAN AREAS, AND TRANSLATION AND COMMERCIALIZATION SERVICES TO ENABLE RAPID, ROBUST AND MULTI-FACETED VALIDATION AND TRANSLATION OF AI-ENHANCED TECHNOLOGIES. THE FOURTH IS TO ADMINISTER A PILOT PROJECT GRANTING PROCESS AND ENSURE THAT THE PILOT PROJECTS ARE RESPONSIVE TO STAKEHOLDER NEEDS, USE EMERGING AI AND RELATED TECHNOLOGIES THAT HAVE SIGNIFICANT POTENTIAL TO IMPROVE INTERACTIONS BETWEEN OLDER ADULTS, LAY CAREGIVERS, AND CLINICIANS. THE FIFTH IS TO PROVIDE TRAINING TO DEVELOPERS, CLINICIANS, AND OTHER STAKEHOLDERS AND TO DISSEMINATE FINDINGS TO DIVERSE RESEARCH, DEVELOPMENT AND PRACTICE COMMUNITIES TO ACCELERATE FURTHER DEVELOPMENT OF PROMISING TECHNOLOGIES AND PROMOTE THE ADOPTION OF VALIDATED TECHNOLOGIES BEYOND THE MAITC. THROUGH THESE COORDINATED EFFORTS, WE HOPE TO IMPROVE THE LIVES OF OLDER ADULTS AND THEIR CAREGIVERS.

UNIVERSITY OF MASSACHUSETTS LOWELL EMERGENCY FINANCIAL AID GRANTS UNDER CARES ACT

COOPERATIVE AGREEMENT FOR RESEARCH AND DEVELOPMENT - SLIMMER3

CELLULAR IMMUNITY TO CATEGORY A-C VIRUSES IN HUMANS

ANALYSIS OF THE GENETIC POTENTIAL & GENE EXPRESSION OF MICROBIAL COMMUNITIES INVOLVED IN THE IN SITU BIOREMEDIATION OF URANIUM

CENTER FOR COLLABORATIVE ADAPTIVE SENSING OF THE ATMOSPHERE (CASA)

NATIONAL NETWORK OF LIBRARIES OF MEDICINE NEW ENGLAND (REGION 8) AND PUBLIC HEALTH COORDINATION OFFICE

MASSACHUSETTS MEDICAID INFRASTRUCTURE AND COMPREHENSIVE EMPLOYMENT OPPORTUNITIES

NSEC: CENTER FOR HIERARCHICAL MANUFACTURING

NONHUMAN PRIMATE REAGENT RESOURCE

HIGHER EDUCATION EMERGENCY RELIEF FUND-IHE/INSTITUTION

CENTER FOR THE PROMOTION OF HEALTH IN THE NEW ENGLAND WORKPLACE

MODELS AND GENE THERAPIES FOR AAT DEFICIENCY - PROJECT SUMMARY (OVERALL) ALPHA-1 ANTITRYPSIN DEFICIENCY (AATD) IS CAUSED BY MUTATIONS IN THE SERPINA1 GENE. THE E342K (PI*Z) MUTANT ALLELE IS VERY COMMON AMONG THOSE OF EUROPEAN ANCESTRY, AND E342K HOMOZYGOTES ENCODE A PROTEIN WITH IMPAIRED SECRETION, RESULTING IN DEFICIENT AAT SERUM LEVELS. SINCE AAT NORMALLY PROTECTS ELASTIN IN THE LUNG FROM DEGRADATION, LOSS OF EFFECTIVE AAT TRIGGERS LUNG INFLAMMATION, AIRWAYS OBSTRUCTION AND EMPHYSEMA, WHICH IS THE PRIMARY LIFE-LIMITING MANIFESTATION OF AATD. THE PROJECTS WITHIN THIS PROPOSAL SEEK TO PURSUE NUMEROUS PARALLEL STRATEGIES TO DEVELOP A GENE THERAPY FOR AATD. MOST OF THESE STRATEGIES REVOLVE AROUND THE USE OF RECOMBINANT ADENO-ASSOCIATED VIRUS (RAAV)-BASED VECTORS, A PLATFORM TECHNOLOGY THAT HAS BEEN VERY SUCCESSFUL FOR OTHER GENETIC DISEASES. IN PROJECT 1, OPTIMIZED RAAV VECTORS WILL BE STUDIED IN GENETICALLY DEFINED ANIMAL MODELS (INCLUDING MICE AND FERRETS) IN COMPARISON WITH TRANSGENIC RECONSTITUTION STUDIES USING A REGULATED CONDITIONAL TRANSGENIC SYSTEM TO COMPARE TWO RELEVANT POTENTIAL TARGET REPLACEMENT LEVELS (11ΜM AND 25ΜM) AND CLINICALLY RELEVANT ENDPOINTS WILL BE STUDIED. IN PROJECT 2, NOVEL CRISPR VARIANTS WILL BE USED FOR GENE EDITING, BASE EDITING AND PRIME EDITING STRATEGIES TO TREAT AATD. IN PROJECT 3, WE WILL SCREEN NATURALLY OCCURRING AAV CAPSID LIBRARIES OBTAINED FROM REMOTE POPULATIONS IN WESTERN CHINA TO IDENTIFY CAPSIDS WITH ENHANCED EFFICACY AND SAFETY FOR AATD GENE THERAPY. FINALLY, IN PROJECT 4, WE WILL USE NOVEL TREG AND CAR-TREG STRATEGIES TO SELECTIVELY MODULATE ANTI-VECTOR IMMUNE RESPONSES. THERE WILL ALSO BE TWO CORES. CORE A WILL PROVIDE EACH PROJECT WITH IMPORTANT VECTOR IMMUNOLOGY ASSAYS, WHICH CAN IDENTIFY LIMITATIONS DUE TO HOST IMMUNE RESPONSES TO AAV CAPSIDS, THE AAT TRANSGENE OR TO CAS9-DERIVED PROTEINS. CORE B WILL PROVIDE ANIMAL MODELS AND PHYSIOLOGIC MEASUREMENTS IN THE ANIMAL MODELS FOR TESTING OF OPTIMIZED RAAV VECTORS, GENE EDITING TOOLS AND IMMUNE MODULATION APPROACHES. PROGRAM INVESTIGATORS HAVE A TRACK RECORD OF INTERACTIONS AND COLLABORATIONS THAT WE ANTICIPATE WILL CONTINUE IN FUTURE YEARS.

BIOMARKERS FOR THERAPY OF FSHD (U54)

OPTIMIZATION OF HIV VACCINES FOR THE INDUCTION OF CROSS-REACTIVE ANTIBODIES

HIGHER EDUCATION EMERGENCY RELIEF FUND

CENTER FOR BRAIDING INDIGENOUS KNOWLEDGES AND SCIENCE (CBIKS) -THE NATURAL AND BUILT ENVIRONMENTS OF OUR MODERN WORLD INTERACT IN COMPLEX WAYS THAT AFFECT OUR GLOBAL COMMUNITY. UNDERSTANDING THESE INTERACTIONS AND THEIR EFFECTS ON SOCIETY REQUIRES COLLABORATION, COORDINATION, AND SHARING OF KNOWLEDGE AND DATA AMONG RESEARCHERS, COMMUNITIES, AND ORGANIZATIONS. THE CENTER FOR BRAIDING INDIGENOUS KNOWLEDGES AND SCIENCE (CBIKS) ADVANCES KNOWLEDGE ABOUT ENVIRONMENTAL VARIABILITY AND ITS EFFECTS ON FOOD AND CULTURAL SYSTEMS AT LOCAL AND GLOBAL SCALES THROUGH A FOCUS ON COMBINING INDIGENOUS KNOWLEDGE (IK) WITH WESTERN SCIENCE (WS) IN EFFECTIVE, ETHICAL, AND NOVEL WAYS. BASED ON A COMPARATIVE ANALYSIS OF OVER 30 PLACE-BASED PROJECTS TO BE CARRIED OUT BY CBIKS AND NEARLY 60 PARTNERING INSTITUTIONS AND INDIGENOUS COMMUNITIES, CBIKS DEVELOPS A SET OF GENERALIZABLE FINDINGS, TOOLS, TRAININGS, PROTOCOLS, AND BEST PRACTICES FOR INTEGRATING IK AND WS. THROUGH ITS RESEARCH ACTIVITIES, THE CBIKS TEAM ASPIRES TO FUNDAMENTALLY TRANSFORM HOW CHALLENGES RELATED TO ENVIRONMENTAL VARIABILITY, FOOD SYSTEMS, AND CULTURAL HERITAGE CONSERVATION ARE APPROACHED. CBIKS BROADENS THE PARTICIPATION OF GROUPS UNDERREPRESENTED IN SCIENCE, PRINCIPALLY THROUGH THE REALIZATION OF A COHORT OF INDIGENOUS SCIENTISTS WHO WILL LEAD FUTURE EFFORTS IN INTEGRATED WS AND IK RESEARCH IN THE AREAS OF ARCHAEOLOGY, GEOSCIENCES, NATURAL, AND ENVIRONMENTAL SCIENCES. THE CBIKS TEAM MENTORS AND PROVIDES RESEARCH OPPORTUNITIES FOR NUMEROUS POSTDOCTORAL RESEARCHERS, GRADUATE STUDENT RESEARCH ASSISTANTS, UNDERGRADUATE STUDENT RESEARCHERS, AND INDIGENOUS COMMUNITY MEMBER AND YOUTH RESEARCH ASSISTANTS, ACROSS MULTIPLE RESEARCH HUBS AND WORKING GROUPS. INSTITUTIONAL ENGAGEMENT INCLUDES TWO TRIBAL COLLEGES, FOUR AMERICAN INDIAN AND ALASKA NATIVE-SERVING INSTITUTIONS, TWO HISPANIC SERVING INSTITUTIONS, TWO ASIAN AMERICAN AND NATIVE AMERICAN PACIFIC ISLANDER SERVING INSTITUTIONS, A NATIVE HAWAIIAN SERVING INSTITUTION, A NATIVE AMERICAN SERVING NON-TRIBAL INSTITUTION, AND NUMEROUS OTHER PUBLIC AND PRIVATE RESEARCH INSTITUTIONS. DATA AND FINDINGS FROM CBIKS ARE WIDELY DISSEMINATED THROUGH A PUBLICLY ACCESSIBLE REPOSITORY AS WELL AS FORMAL AND INFORMAL LEARNING ACTIVITIES FOR K-12 STUDENTS AND TEACHERS, SCIENTISTS, AND COMMUNITIES. CBIKS IS ORGANIZED BASED ON INDIGENOUS MODELS OF CONSENSUS DECISION-MAKING AND INTERGENERATIONAL LEARNING AND RESPONSIBILITY AND HAS THREE MAIN AIMS: 1) TO DEVELOP A COMMON PUBLICLY ACCESSIBLE REPOSITORY FOR THE STORAGE, ORGANIZATION, AND SHARING OF METHODS, ETHICS, AND GUIDELINES FOR EFFECTIVE INTEGRATION OF IK AND WS SYSTEMS; 2) TO IMPLEMENT METHODOLOGIES THROUGH A SERIES OF PLACE-BASED STUDIES IN PARTNERSHIP WITH 57 INDIGENOUS COMMUNITIES AT 8 REGIONAL HUBS, EACH CONSTITUTING A DIFFERENT NATURAL ENVIRONMENT; AND 3) TO AGGREGATE AND DISTILL DATA FROM THE PLACE-BASED STUDIES THROUGH WORKING GROUPS WITH THE OBJECTIVES OF ADVANCING KNOWLEDGE ON ENVIRONMENTAL VARIABILITY, FOOD SYSTEMS, AND CULTURAL RESOURCES AND REFINING METHODOLOGIES AND ETHICAL GUIDELINES FOR INTEGRATED IK AND WS RESEARCH. EIGHT REGIONAL RESEARCH HUBS INCLUDE PARTNERS FROM MULTIPLE INSTITUTIONS ACROSS THE SOCIAL SCIENCES, GEOSCIENCES, AND ENVIRONMENTAL SCIENCES, AND EACH WORKS IN PARTNERSHIP WITH DIVERSE INDIGENOUS COMMUNITIES. SEVEN WORKING GROUPS SERVE ALL RESEARCH HUBS, FOCUSING ON A RANGE OF CROSS-CUTTING THEMES RELATED TO RESEARCH DEVELOPMENT AND DESIGN, DATA SHARING, AND SCIENCE EDUCATION, TRAINING, AND DISSEMINATION. THROUGH THIS CONVERGENT AND COLLABORATIVE MODEL, CBIKS CAN ADVANCE NOT ONLY WHAT WE KNOW ABOUT INTERACTIONS BETWEEN THE NATURAL WORLD AND HUMAN SOCIETIES, BUT ALSO HOW WE INVESTIGATE AND ADDRESS RELATED SOCIETAL CHALLENGES. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE PLANNED FOR THIS AWARD.

CENTER FOR 3D STRUCTURE AND PHYSICS OF THE GENOME

MATERIALS RESEARCH SCIENCE AND ENGINEERING CENTER ON POLYMERS

NSEC: CENTER FOR HIERARCHICAL MANUFACTURING

SSI/SSDI DEMONSTRATIONS

CENTER FOR REPRODUCIBLE NEUROIMAGING COMPUTATION (CRNC)

STRUCTURAL ANNOTATION OF THE HUMAN GENOME

AIDS EDUCATION TRAINING CENTERS

EVOLUTION & MAINTENANCE OF MEMORY CD8 T CELLS

RESEARCH AND DEVELOPMENT EFFORT CONDUCTED IN ACCORDANCE WITH THE RECIPIENT'S PROPOSAL ENTITLED 'SOLDIER LIGHTWEIGHT INTEGRATED MULTIFUNCTIONAL MATERI

INNATE AND ADAPTIVE IMMUNITY IN EXPERIMENTAL AND HUMAN GONOCCOCAL INFECTION

THE CENTER FOR ACCELERATING PRACTICES TO END SUICIDE THROUGH TECHNOLOGY TRANSLATION (CAPES) - CAPES OVERALL: PROJECT SUMMARY/ABSTRACT SIGNIFICANCE: RECENTLY, WE HAVE SEEN MASSIVE GROWTH IN AVAILABILITY OF EMPIRICALLY SUPPORTED TECHNOLOGIES ENABLING SUICIDE RISK IDENTIFICATION, MONITORING, AND PREVENTION IN HEALTHCARE SETTINGS. HOWEVER, OUR KNOWLEDGE OF EFFECTIVE, EFFICIENT STRATEGIES TO TRANSLATE THESE TECHNOLOGIES INTO CLINICAL PRACTICE IS WEAK. AS A RESULT, THESE TECHNOLOGIES ARE NOT BEING OPTIMALLY DEPLOYED TO PREVENT SUICIDES. THE CENTER FOR ACCELERATING PRACTICES TO END SUICIDE THROUGH TECHNOLOGY TRANSLATION ( CAPES ) WILL BRIDGE THIS RESEARCH-TO-PRACTICE GAP. INVESTIGATORS: CAPES TRANSDISCIPLINARY FACULTY, ADVISORS, AND CONSULTANTS HAVE EXTENSIVE EXPERTISE IN THE DISCIPLINES REQUIRED TO SUCCESSFULLY SUPPORT THE CAPES MISSION AND ITS INDIVIDUAL PROJECTS, PRODUCING SYNERGISTIC INSIGHTS AND DISCOVERY. COMBINED, THE TEAM HAS OVER 1,000 HIGH-IMPACT PUBLICATIONS IN FIELDS RELEVANT TO OR DIRECTLY STUDYING THE INTERSECTION OF SUICIDE PREVENTION, IMPLEMENTATION SCIENCE, DIGITAL HEALTH TECHNOLOGY DEVELOPMENT AND TRANSLATION TO PRACTICE, HEALTH DISPARITIES, STUDY DESIGN AND ANALYSIS, AND HEALTHCARE SYSTEMS- BASED CHANGE. THIS SCIENTIFIC DEPTH WILL BE ACCOMPANIED BY LONGITUDINAL ENGAGEMENT OF DIVERSE STAKEHOLDERS. INNOVATION: CAPES WILL BE THE FIRST NIMH CENTER FOCUSED ON ACCELERATING EVIDENCE-BASED SUICIDE CARE BY LEVERAGING TECHNOLOGY SOLUTIONS ACROSS MULTIPLE HEALTHCARE SETTINGS. FURTHER, IT WILL LEVERAGE INNOVATIONS IN IMPLEMENTATION SCIENCE, PERSON-CENTERED DESIGN, HYBRID CLINICAL TRIAL DESIGN, TECHNOLOGY-RELATED ECONOMICS EVALUATIONS, BUSINESS DEVELOPMENT, AND ETHICS TO MAXIMIZE SCIENTIFIC AND PUBLIC HEALTH IMPACT. APPROACH: THE CAPES ADMINISTRATIVE CORE WILL COLLABORATE WITH THE METHODS CORE TO MAXIMIZE THE CENTER’S IMPACT BY CREATING SYNERGY; PRIORITIZING EVIDENCE-BASED, SCALABLE TECHNOLOGIES FOR STUDY; CREATING RELEVANCE ACROSS MULTIPLE SETTINGS AND DIVERSE PATIENT POPULATIONS; LEVERAGING THE ZERO SUICIDE FRAMEWORK TO ALIGN WITH PRIORITIES OF THE NATIONAL ACTION ALLIANCE FOR SUICIDE PREVENTION AND NIMH; AND FOSTERING BUSINESS DEVELOPMENT AND TECHNOLOGY TRANSFER TO HELP ENSURE SUCCESSFUL PUBLIC DISSEMINATION, ADOPTION, AND SUSTAINABILITY. ENVIRONMENT: UMASS AND WORCESTER POLYTECHNIC INSTITUTE HAVE AN ESTABLISHED HISTORY OF SUCCESSFULLY CARRYING OUT COLLABORATIVE STUDIES AND ARE PERFECTLY SITUATED TO SUPPORT THIS CENTER. THEIR NETWORKED CAPABILITIES, COMBINED WITH OTHER ACADEMIC, HEALTH SYSTEM, BUSINESS, AND COMMUNITY PARTNERS, PROVIDE LAYERED, COMPLEMENTARY RESOURCE ACCESS FOR CLINICAL CARE IMPROVEMENT, TECHNOLOGY DEVELOPMENT, TECHNOLOGY TRANSFER FROM RESEARCH SETTINGS TO CLINICAL USE, AND WIDESPREAD DISSEMINATION OF CAPES RESOURCES. IMPACT: LED BY ACCOMPLISHED INVESTIGATORS WITH ACCESS TO POWERFUL RESOURCES, CAPES WILL BE IDEALLY SITUATED TO ANSWER THE CRITICAL RESEARCH QUESTIONS POSED IN THIS PROPOSAL AND REACH MANY DIVERSE SETTINGS AND PATIENT POPULATIONS. CAPES INNOVATIVE EMBRACE OF EVIDENCE-BASED SUICIDE CARE TECHNOLOGIES, COMBINED WITH A STRONG FOCUS ON ZERO SUICIDE ALIGNMENT, IMPLEMENTATION SCIENCE ADVANCES, TECHNOLOGY TRANSFER, AND MULTI-CHANNEL DISSEMINATION, POSITION IT FOR TRANSFORMATIONAL IMPACT ON SUICIDE PREVENTION IN HEALTHCARE SETTINGS.

SUPPORTING TREATMENT ACCESS AND RECOVERY FOR CO-OCCURRING OPIOID USE AND MENTAL HEALTH DISORDERS (STAR-COD) - PROJECT SUMMARY / ABSTRACT OPIOID USE HAS DRAMATICALLY INCREASED IN THE UNITED STATES SINCE 2000, AND DISPROPORTIONALLY AFFECTS INDIVIDUALS WITH CO-OCCURRING MENTAL HEALTH DISORDERS (COD). INDIVIDUALS WITH COD ARE VULNERABLE TO SUBSTANCE USE RELAPSES, MENTAL HEALTH SYMPTOM EXACERBATIONS, OPIOID OVERDOSES, SUICIDE, HOMELESSNESS, AND CRIMINAL JUSTICE INVOLVEMENT. ALTHOUGH MEDICATION FOR OPIOID USE DISORDER (MOUD) IS THE GOLD STANDARD OF CARE, ENGAGEMENT RATES ARE AS LOW AS 18% WHICH NEGATIVELY IMPACT OUTCOMES. IN ADDITION, THERE IS MIXED EVIDENCE REGARDING THE INCREMENTAL THERAPEUTIC BENEFIT OF ADDING SINGLE BEHAVIORAL INTERVENTIONS TO IMPROVE MOUD OUTCOMES, DESPITE BEING RECOMMENDED IN CLINICAL PRACTICE GUIDELINES. FURTHERMORE, WHILE MULTI-COMPONENT INTERVENTIONS EXIST, LITTLE IS KNOWN ABOUT THEIR INCREMENTAL THERAPEUTIC EFFECT ON OUTCOMES IN CONJUNCTION WITH MOUD AND STANDARD MEDICAL MANAGEMENT FOR THOSE WITH A COD. MAINTAINING INDEPENDENCE AND SOBRIETY THROUGH SYSTEMS INTEGRATION, OUTREACH AND NETWORKING (MISSION) IS ONE SUCH MULTI-COMPONENT, CROSS-DISCIPLINARY, TEAM-BASED TREATMENT APPROACH, COMBINING 3 EVIDENCE-BASED PRACTICES ALONG WITH MOUD: 1) DUAL RECOVERY THERAPY (DRT), WHICH IS INTEGRATED GROUP THERAPY FOR COD; 2) PEER SUPPORT (PS), OFFERING SUPPORT FOR PEOPLE IN RECOVERY BY PEOPLE IN RECOVERY; AND 3) CRITICAL TIME INTERVENTION (CTI), A TIME-LIMITED FORM OF ASSERTIVE COMMUNITY TREATMENT. ALTHOUGH THE EFFECTIVENESS OF MISSION IS WELL ESTABLISHED, GIVEN THE DIFFICULTY WITH IMPLEMENTATION UPTAKE IN LARGE SYSTEMS DUE TO ITS COMPLEXITY AND THE NEED TO IMPROVE OUTCOMES FOR THOSE WITH A COD WHO RECEIVE MOUD, A CRITICAL NEXT STEP IS TO UNDERSTAND THE INCREMENTAL THERAPEUTIC BENEFIT OF MISSION + MOUD, AND IDENTIFY HIGHEST VALUE MISSION COMPONENTS THAT DRIVE THE LARGEST CLINICAL IMPROVEMENT AND OFFER THE GREATEST RETURN ON INVESTMENT. IN RESPONSE TO RFA-MH-21-145, THE PROPOSED 4-YEAR STUDY WITH A HALF FRACTIONAL FACTORIAL DESIGN, “SUPPORTING TREATMENT ACCESS AND RECOVERY FOR CO-OCCURRING OPIOID USE AND MENTAL HEALTH DISORDERS (STAR-COD),” WILL RANDOMIZE 1,000 PATIENTS WITH COD ACROSS 9 MOUD PROGRAMS TO THE FOLLOWING 5 CONDITIONS: 1) MOUD ALONE; 2) FULL MISSION PROTOCOL (CTI & DRT & PS) + MOUD; 3) CTI & DRT + MOUD; 4) PS & DRT + MOUD; OR 5) CTI & PS + MOUD. THERE ARE FOUR SPECIFIC AIMS. AIM 1: TO EVALUATE THE EFFECTIVENESS OF MISSION OR ITS COMPONENTS WITH MOUD VERSUS MOUD ALONE, AS WELL AS THE INCREMENTAL BENEFITS OF MISSION OR BUNDLED PARTS + MOUD TO IMPROVE ENGAGEMENT, SUBSTANCE USE AND MENTAL HEALTH SYMPTOMS. AIM 2: TO EXAMINE MECHANISMS OF ACTION OF MISSION IN COD. AIM 3: TO CONDUCT A COMPREHENSIVE ECONOMIC EVALUATION OF MISSION OR ITS PARTS AND MOUD. EXPLORATORY AIM: 4. TO CONSTRUCT A PREDICTIVE MODEL TO MATCH OPTIMUM COMBINED USE OF MISSION PARTS WITH PATIENT NEEDS TO IMPROVE HEALTH OUTCOMES. THIS PROPOSAL IS ALIGNED WITH NIMH’S STRATEGIC PLAN GOAL 4 “TO INCREASE THE PUBLIC HEALTH IMPACT OF SERVICES STUDIES, INVESTIGATORS TEST WAYS TO ADAPT, IMPLEMENT, AND SCALE EFFECTIVE INTERVENTIONS FOR VARIED POPULATIONS ACROSS MULTIPLE SERVICE SETTINGS IN A COST-EFFECTIVE MANNER.” UPON COMPLETION, IT COULD OFFER MORE COST EFFECTIVE, ROBUST, PERSONALIZED TREATMENTS.

NEW ENGLAND CENTER OF EXCELLENCE IN VECTOR-BORNE DISEASES

AIDS EDUCATION AND TRAINING CENTERS PROGRAM

IMPROVING ORTHOPEDIC OUTCOMES THROUGH A NATIONAL TJR REGISTRY

CD4 T CELLS IN ANTI-VIRAL IMMUNITY AND IMMUNE PATHOLOGY

UNIVERSITY TRANSPORTATION CENTERS

EMERGENCY DEPARTMENT SAFETY ASSESSMENT AND FOLLOW-UP EVALUATION (EDSAFE) TRIAL

T CELL MEMORY TO PATHOGENS: GENERATION AND FUNCTION

1/2 PROSPECTIVE TREATMENT EFFICACY IN IPF USLNG GENOTYPE FOR NAC SELECTION (PRECISIONS) TRIAL AND MOLECULAR ENDOPHENOTYPING IN IDIOPATHIC PULMONARY FIBROSIS AND INTERSTITIAL LUNG DISEASES STUDY - ABSTRACT DESPITE BEING THE MOST FREQUENT AND DEADLY OF THE INTERSTITIAL LUNG DISEASES (ILD), IDIOPATHIC PULMONARY FIBROSIS (IPF) REMAINS CHALLENGING TO DIAGNOSE AND TREAT. THE DIAGNOSTIC PROCESS FOR IPF RELIES ON SUBJECTIVE INTERPRETATIONS OF CLINICAL DATA WHILE CURRENT ANTIFIBROTIC THERAPIES EMPLOY A “ONE SIZE FITS ALL” PARADIGM. MEMBERS OF OUR TEAM HAVE BEEN AT THE FOREFRONT OF DEVELOPING `OMICS APPROACHES TO DIAGNOSE AND DEFINE PROGNOSIS IN ILDS. IMPORTANTLY, WE IDENTIFIED THE FIRST PHARMACOGENOMIC INTERACTION SUGGESTING THAT IPF PATIENTS WITH TOLLIP RS3750920 T/T GENOTYPE STRONGLY BENEFITED FROM NAC. THERE IS A CRITICAL NEED FOR MOLECULAR CLASSIFICATIONS THAT DEFINE IPF, THUS ALLOWING PRECISION-BASED MANAGEMENT. OUR LONG-TERM GOALS ARE TO MOVE ILD DIAGNOSIS AND THERAPY INTO THE “ERA OF PRECISION MEDICINE.” IN A HIGHLY INNOVATIVE APPROACH WE HAVE PARTNERED WITH THE PULMONARY FIBROSIS FOUNDATION (PFF) CLINICAL CARE NETWORK (CCN) AND REGISTRY. THIS GROUP HAS RECRUITED ILD PATIENTS WHO HAVE PROVIDED EXTENSIVE BASELINE PHENOTYPIC AND LONGITUDINAL OUTCOME DATA, BIOLOGICAL SAMPLES AND HAVE CONSENTED TO BE RE-CONTACTED FOR FUTURE RESEARCH. OUR OVERALL OBJECTIVE IS TO EFFICIENTLY CONDUCT A NOVEL, PRECISION GENOTYPE-BASED TRIAL IN IPF WHILE LEVERAGING THE CCN AND ITS UNIQUE BIOSPECIMEN COLLECTION TO CHARACTERIZE A BROAD RANGE OF ILDS MOLECULARLY AND IDENTIFY GENETIC VARIANTS OF IPF RISK. TO ADDRESS OUR GOAL OF PRECISION-BASED ILD MANAGEMENT, WE WILL COMPLETE THREE COMPLEMENTARY SPECIFIC AIMS. IN AIM 1 WE WILL DETERMINE IF NAC IS AN EFFECTIVE TREATMENT IN IPF PATIENTS CHARACTERIZED BY A PRECISION GENOTYPE APPROACH. IN PARTNERSHIP WITH THE PFF, WE WILL IDENTIFY PFF REGISTRY SUBJECTS WITH THE TOLLIP T/T GENOTYPE TO BEGIN RANDOMIZING 200 IPF PATIENTS FOLLOWED BY ENROLLING NEW SUBJECTS AT THE SAME CLINICAL SITES TO RECEIVE NAC OR PLACEBO IN A DOUBLE-BLIND FASHION. THIS STUDY, THE “PROSPECTIVE TREATMENT EFFICACY IN IPF USING GENOTYPE FOR NAC SELECTION (PRECISIONS)” TRIAL, WILL DOCUMENT THE BENEFITS OF AN INNOVATIVE “PRECISION” GENOTYPE-SPECIFIC STUDY DESIGN OF A WELL-TOLERATED AND INEXPENSIVE THERAPY. IN AIM 2 WE WILL DISTINGUISH IPF FROM NON-IPF ILDS USING UNBIASED COMBINATIONS OF BLOOD TRANSCRIPTOMICS AND PROTEOMICS. WE PROPOSE TO CONDUCT RNA-SEQ AND PROTEOMICS TO CHARACTERIZE GENE EXPRESSION AND PROTEIN BIOMARKERS ON THE ENTIRE PFF REGISTRY COHORT. WE WILL DEFINE “SIGNATURES” FOR DISTINGUISHING IPF FROM NON-IPF ILDS. OUR UNBIASED APPROACHES TO `OMICS TRAITS WILL BE INTEGRATED TO REVEAL `OMICS RISK SCORES THAT DEFINE INDIVIDUAL DISEASES, PREDICT DISEASE COURSE, AND RESPONSE TO THERAPY. IN AIM 3 WE WILL IDENTIFY GENETIC VARIANTS PLAYING A ROLE IN IPF RISK. WE WILL CONDUCT WHOLE GENOME SEQUENCING OF THE ENTIRE PFF COHORT TO DETECT NOVEL GENETIC ASSOCIATIONS FOR IPF AND ILD RISK. WITH SUFFICIENT POWER, WE WILL ASSESS BOTH COMMON AND RARE/INFREQUENT VARIANTS IN COMPARISON TO ETHNICALLY MATCHED UN-AFFLICTED CASES, AND BETWEEN ILD COHORTS TO MEET OUR OBJECTIVE. THIS WILL ESTABLISH THE LARGEST COLLECTION OF ITS KIND AND ESTABLISH QUANTITATIVE TRAIT LOCI FOR ALL `OMICS' DATA. THE RESULTS OF OUR PROPOSED EXPERIMENTS WILL MOVE ILD MANAGEMENT, AND IPF THERAPY, IN PARTICULAR, INTO THE PRECISION MEDICINE ERA.