New York University

NIDA CLINICAL TRIALS NETWORK: GREATER NEW YORK NODE

THE ISCHEMIA TRIAL - CCC

CLINICAL AND TRANSLATIONAL SCIENCE AWARD

NEW YORK UNIVERSITY RECIPIENT’S FUNDING CERTIFICATION AND AGREEMENT -- SECOND CERTIFICATION

CANCER CENTER SUPPORT GRANT

1 OF 5 ARIC NEUROCOGNITIVE STUDY (ARIC-NCS)

NYU PEDIATRIC OBESITY, METABOLISM AND KIDNEY COHORT CENTER

NEW YORK UNIVERSITY RECIPIENT’S FUNDING CERTIFICATION AND AGREEMENT

ED-LEAD: EMERGENCY DEPARTMENTS LEADING THE TRANSFORMATION OF ALZHEIMER'S AND DEMENTIA CARE - PROJECT SUMMARY IN PERSONS LIVING WITH DEMENTIA (PLWD), AN EMERGENCY DEPARTMENT (ED) VISIT IS A CRITICAL EVENT AND AN OPPORTUNITY TO ADDRESS THE UNMET NEEDS THAT PRECEDED THE VISIT. OUR MULTIPLE PI (MPI) TEAM HAVE TOGETHER CONDUCTED CLUSTER-RANDOMIZED, MULTI-SITE TRIALS IN >50 EDS AS WELL AS MULTIPLE HOSPICE AND HOME HEALTH AGENCIES, AND ARE UNIQUELY POISED TO ADDRESS PREVIOUS SHORTCOMINGS IN THE DEVELOPMENT OF SCALABLE MODELS OF CARE FOR PLWD. THROUGH THIS WORK, AND THAT OF OUR CO-INVESTIGATORS, WE HAVE DEVELOPED AND TESTED THREE INTERVENTIONS RELEVANT TO PLWD AND THEIR CARE PARTNERS WHO VISIT THE ED: 1) EMERGENCY CARE REDESIGN (UH3AT009844) OF NEW AND INTENTIONAL WORKFLOWS FOR EMERGENCY PROVIDERS REINFORCED BY DIGITAL ALERTS AND STRUCTURED COLLABORATION BETWEEN SITES, ALREADY SHOWN TO INCREASE IDENTIFICATION OF ADVANCE CARE PLANS AND ENLISTED MULTIDISCIPLINARY SUPPORT; 2) A NURSE-LED TELEPHONIC CARE PROGRAM (PCORI) THAT INCREASED ADVANCE CARE PLANNING AND CONNECTED PATIENTS TO HOSPICE; AND 3) A COMMUNITY PARAMEDIC-LED STRUCTURED COACHING INTERVENTION (R01AG050504) THAT REDUCED THE ODDS OF AN ED REVISIT WITHIN 30 DAYS BY 75%. BUILDING ON THIS EVIDENCE, THE OVERARCHING GOAL OF EDS LEADING THE TRANSFORMATION OF ALZHEIMER’S AND DEMENTIA CARE (ED- LEAD) IS TO TURN AN ED VISIT FROM A CRISIS INTO AN OPPORTUNITY TO IMPROVE THE WELL-BEING OF PLWD AND THEIR CARE PARTNERS. ED-LEAD WILL BE EMBEDDED IN A DIVERSE GROUP OF 14 HEALTH SYSTEMS, INCLUDING 80 EDS WITH SUBSTANTIAL RACIAL AND ETHNIC DIVERSITY, WITH THE ED AS THE UNIT OF RANDOMIZATION. AN ADMINISTRATIVE CORE WILL OVERSEE COMPLETION OF ALL ADMINISTRATIVE MILESTONES INCLUDING INTEGRATING EXPERTISE AND GUIDANCE FROM TWO NIA- FUNDED NETWORKS AND AN EXTERNAL ADVISORY BOARD. AN IMPLEMENTATION CORE WILL: 1) HARMONIZE CORE FUNCTIONS AND PROCESSES; 2) OPTIMIZE CLINICAL DECISION SUPPORT; AND 3) AND ENABLE INTERVENTION FIDELITY ACROSS THE THREE INTERVENTIONS. FINALLY, A STATISTICAL ANALYSIS CORE WILL PROVIDE BIOSTATISTICAL AND DATA MANAGEMENT SUPPORT. OUR SPECIFIC AIMS ARE TO: 1) OPTIMIZE A CONCURRENTLY RUN EMERGENCY CARE REDESIGN, NURSE-LED TELEPHONIC CARE, AND COMMUNITY PARAMEDIC-LED TRANSITIONS INTERVENTION IN PLWD FOR FEASIBILITY, FIDELITY AND USABILITY IN TWO EDS; 2) STUDY THE EFFECTIVENESS OF THESE THREE INTERVENTIONS, ALONE AND IN COMBINATION, FOR PLWD WITH SERIOUS ILLNESS IN A CLUSTER-RANDOMIZED MULTIFACTORIAL TRIAL EMBEDDED WITHIN 80 EDS ON: ED REVISITS, HOSPITALIZATIONS, AND HEALTHY DAYS AT HOME FOLLOWING THE INDEX ED VISIT; AND 3) DETERMINE SITE, PROVIDER, PATIENT, AND CARE PARTNER-LEVEL CHARACTERISTICS WITHIN A DIVERSE POPULATION ASSOCIATED WITH VARIATION IN IMPLEMENTATION OF EACH INTERVENTION. ED- LEAD WILL ADDRESS SHORTCOMINGS NOTED IN THE NATIONAL ACADEMIES OF SCIENCES, ENGINEERING, AND MEDICINE REPORT ON PLWD BY PROVIDING HIGH-QUALITY, REAL-WORLD EVIDENCE THAT MAY IMPROVE THE LIVES AND REDUCE SUFFERING OF PLWD AND THEIR CARE PARTNERS. IT WILL ADDRESS KEY STRATEGIC GOALS OF NIA AND THE NATIONAL ALZHEIMER’S PLAN TO “IMPLEMENT AND EVALUATE NEW CARE MODELS TO SUPPORT EFFECTIVE CARE TRANSITIONS”, AND PROVIDE HEALTH SYSTEMS WITH THE NECESSARY EVIDENCE TO SCALE INTERVENTIONS FOR THIS VULNERABLE POPULATION.

AN INTERDISCIPLINARY APPROACH TO HIV AND OTHER INFECTIOUS DISEASES OF DRUG USERS

RESEARCH FACILITIES RESTORATION PROGRAM NEW SCIENCE BUILDING

OXYTOCIN MODULATION OF NEURAL CIRCUIT FUNCTION AND BEHAVIOR

EPPIC-NET DCC

NYU PEDIATRIC OBESITY, METABOLISM AND KIDNEY COHORT CENTER

MACROPHAGE DYSFUNCTION IN OBESITY, DIABETES AND ATHEROSCLEROSIS

ESTABLISHMENT OF THE NEW YORK UNIVERSITY VACCINE AND TREATMENT EVALUATION UNIT (NYU VTEU)

ALZHEIMER'S DISEASE CORE CENTER

CENTER FOR THE STUDY OF COMPLEX MALARIA IN INDIA

EARLY LIFE STRESS AND THE ENVIRONMENTAL ORIGINS OF DISEASE: A POPULATION-BASED PROSPECTIVE LONGITUDINAL STUDY OF CHILDREN IN RURAL POVERTY

CENTER FOR SYNTHETIC REGULATORY GENOMICS

LONG-TERM SUPPRESSIVE VALACYCLOVIR TREATMENT FOR HERPES ZOSTER OPHTHALMICUS

LONG-ACTING BUPRENORPHINE VS. NALTREXONE OPIOID TREATMENTS IN CJS-INVOLVED ADULTS

GENOME-WIDE ASSOCIATION ANALYSIS IN ESSENTIAL HYPERTENSION (FEHGAS STUDY)

RESEARCH FACILITIES RESTORATION PROGRAM ALEXANDRIA CENTER FOR LIFE SCIENCES-WEST

NANOMEDICINE CENTER FOR MECHANICAL BIOLOGY (RMI)

ALZHEIMER'S DISEASE RESEARCH CENTER

CRACKING THE OLFACTORY CODE

CENTER FOR ADVANCED IMAGING INNOVATION AND RESEARCH (CAI2R)

INSTITUTIONAL CLINICAL AND TRANSLATIONAL SCIENCE AWARD

INSTITUTIONAL CLINICAL AND TRANSLATIONAL SCIENCE AWARD

DEVELOPMENT AND FUNCTION OF 5HT3AR-EXPRESSING CORTICAL GABAERGIC INTERNEURONS

EPITOPE-TARGETED VACCINES FOR HIV-1 PREVENTION

MEDICAL SCIENTIST RESEARCH SERVICE AWARD

USING PRACTICE FACILITATION IN PRIMARY CARE SETTINGS TO REDUCE RISK FACTORS FOR CARDIOVASCULAR DISEASE

THE IMPACT OF CHANGES IN CHROMATIN ARCHITECTURE ON CANCER PHENOTYPES AND TUMOR PROGRESSION

NYU MATERIALS RESEARCH SCIENCE AND ENGINEERING CENTER

RESEARCH IN ENVIRONMENTAL HEALTH SCIENCES

NYU CENTER FOR THE STUDY OF ASIAN AMERICAN HEALTH - RESEARCH CENTER OF EXCELLENCE

MOLECULAR TUMORIGENESIS OF BLADDER CANCER

OMICS-BASED PREDICTIVE MODELING OF AGE-DEPENDENT OUTCOME TO INFLUENZA INFECTION

BEHAVIORAL SCIENCES TRAINING IN DRUG ABUSE RESEARCH

NOVEL THERAPEUTIC APPROACHES TO TREATMENT OF BOTULINUM NEUROTOXIN POISONING

CENTER FOR STROKE DISAPARITIES SOLUTION

NYU MELANOMA SPORE

MACROPHAGES, CELL-CELL COMMUNICATION, ISCHEMIC INJURY IN DIABETES AND THE RAGE/DIAPH1 SIGNALING AXIS

ALTERED MECHANOTRANSDUCTION AS A THERAPEUTIC TARGET FOR THORACIC AORTIC ANEURYSM

NYU CENTER FOR THE STUDY OF ASIAN AMERICAN HEALTH (CSAAH)

NOVEL APPROACHES TO UNDERSTAND THE PATHOGENESIS AND TREAT ALZHEIMER'S DISEASE

THIS PROPOSAL IS TO PROVIDE OVERALL SUPPORT AND TRAINING FOR ALL ASPECTS OF THE ARMY'S TRANSITION TO THE IN-CIDENT DETERMINATION COMMITTEE (IDC) MODEL, INCLUDING ESTABLISHING READINESS WITHIN FAMILY ADVOCACY PER-SONNEL AND OTHER STAKEHOLDERS, LAUNCHING THE IDC MODEL ENTERPRISE-WIDE, IMPLEMENTING AND EVALUATING ALL COMPONENTS OF THE MODEL ACROSS THE ARMY, AND SUSTAINING THE ENTIRE MODEL AT A HIGH LEVEL OF QUALITY. THIS SUPPORT WILL INCLUDE DEVELOPING AND DELIVERING TAILORED TRAININGS TO SUPPORT THE DEVELOPMENT OF EXPERTS (MAS-TER REVIEWERS) WITHIN THE ARMY USING THE IDC MODEL. THE ARMY COMMISSIONED A PILOT STUDY (2015-2019), WHICH FOUND THAT THE PRIOR MODEL AND THE IDC COST ALMOST IDENTICAL AMOUNTS TO RUN, AND THAT THE IDC MODEL WAS SUPERIOR IN WAYS MOST LIKELY TO IMPACT SERVICE MEMBERS: (1) INDEPENDENT OBSERVERS JUDGED ITS MEETINGS TO BE MORE FAITHFUL TO ARMY AND DOD INSTRUCTIONS; (2) UNIT REPRESENTATIVES WERE MORE LIKELY TO ATTEND AND BE-LIEVED THE IDC SYSTEM TO BE FAIRER (TO BOTH ALLEGED OFFENDERS AND VICTIMS) AND BETTER FUNCTIONING. IN COORDINATION WITH INSTALLATION MANAGEMENT COMMAND (IMCOM) FAP AND OTHER KEY STAKEHOLDERS, WE WILL (A) CREATE A WORK PLAN WITH MILESTONES, AND (B) TRAIN MASTER REVIEWERS, IMCOM REGIONAL ASSETS, AND GAR-RISON PERSONNEL IN THE COMPONENTS OF THE IDC MODEL. WE WILL ALSO (A) TRAIN, MONITOR, AND MENTOR GOVERN-MENT PERSONNEL AT EACH SITE TO ENSURE THE SUCCESSFUL IMPLEMENTATION OF ALL COMPONENTS OF THE IDC IN ACCORD-ANCE WITH THE POLICIES, REGULATIONS, AND PROCEDURES, AND (B) EVALUATE THE QUALITY OF THE IMPLEMENTATION AND SUSTAINMENT OF THE IDC MODEL ELEMENTS.

INTEGRATED MODEL FOR PROMOTING PARENTING AND EARLY SCHOOL READINESS IN PEDIATRICS

GROWTH, DIFFERENTIATION AND DISEASE OF UROTHELIUM

CORE GRANT FOR VISION RESEARCH

MOLECULAR REGULATION OF ATHEROSCLEROSIS REGRESSION

RAGE AND MECHANISMS OF VASCULAR DYSFUNCTION

THE INTERNATIONAL STUDY OF COMPARATIVE HEALTH EFFECTIVENESS WITH MEDICAL AND INVASIVE APPROACHES (ISCHEMIA) TRIAL EXTENDED FOLLOW-UP (EXTEND) - PROJECT SUMMARY/ ABSTRACT THE INTERNATIONAL STUDY OF COMPARATIVE HEALTH EFFECTIVENESS WITH MEDICAL AND INVASIVE APPROACHES (ISCHEMIA) EXTENDED FOLLOW-UP (EXTEND) IS THE LONG-TERM FOLLOW-UP OF RANDOMIZED, SURVIVING PARTICIPANTS IN ISCHEMIA. THIS NHLBI-SUPPORTED TRIAL RANDOMIZED 5,179 PARTICIPANTS WITH STABLE ISCHEMIC HEART DISEASE TO TWO DIFFERENT MANAGEMENT STRATEGIES: 1) AN INITIAL INVASIVE STRATEGY (INV) OF CARDIAC CATHETERIZATION AND REVASCULARIZATION WHEN FEASIBLE PLUS GUIDELINES-BASED MEDICAL THERAPY (GBMT), OR 2) AN INITIAL CONSERVATIVE STRATEGY OF GBMT. THE TRIAL DID NOT DEMONSTRATE A REDUCTION IN THE PRIMARY ENDPOINT WITH AN INITIAL INVASIVE STRATEGY. THERE WAS AN EXCESS OF PERI-PROCEDURAL MYOCARDIAL INFARCTION (MI) AND A REDUCTION IN SPONTANEOUS MI IN THE INV GROUP. PRIOR EVIDENCE DEMONSTRATES THAT SPONTANEOUS MI CARRIES A HIGHER RISK OF SUBSEQUENT DEATH THAN PERI-PROCEDURAL MI. THERE WAS A LATE SEPARATION IN THE CARDIOVASCULAR (CV) MORTALITY CURVES, OVER A MEDIAN OF 3.2 YEARS FOLLOW-UP IN ISCHEMIA. THE OVERALL REDUCTION IN MI RATES WITH AN INV STRATEGY DID NOT EMERGE UNTIL AFTER 2 YEARS. THEREFORE, BASED ON THE OBSERVED REDUCTION IN SPONTANEOUS MI, IT IS IMPERATIVE TO ASCERTAIN LONG-TERM VITAL STATUS TO PROVIDE PATIENTS AND CLINICIANS WITH ROBUST EVIDENCE ON WHETHER INV STRATEGY REDUCES CV AND ALL-CAUSE DEATH OVER THE LONG-TERM. WITH PROJECTED 728 CV DEATHS (1000 TOTAL) WE HAVE ADEQUATE POWER TO DETECT A BETWEEN GROUP DIFFERENCE. IT IS EQUALLY IMPORTANT TO IMPROVE PRECISION AROUND THE POINT ESTIMATE TO RULE OUT A BENEFIT IF NONE EXISTS. REGARDLESS OF THE STUDY FINDINGS, ROBUST LONG-TERM MORTALITY DATA HAVE ENORMOUS IMPLICATIONS FOR CLINICAL GUIDELINES AND PRACTICE, AS AFFIRMED BY INDEPENDENT EXPERTS WHO WRITE AND OVERSEE THE DEVELOPMENT OF NATIONAL GUIDELINES, AND WHO PROVIDED LETTERS OF SUPPORT. WE WILL ALSO QUANTIFY THE IMPACT OF NONFATAL CV EVENTS ON SUBSEQUENT MORTALITY IN ISCHEMIA-EXTEND, CONSTRUCT A RISK SCORE FOR MORTALITY USING BASELINE DEEP PHENOTYPIC DATA, AND PROVIDE ESTIMATES OF THE IMPACT OF INV IN THE HIGHEST RISK SUBGROUP – THOSE WITH SEVERE CORONARY ARTERY DISEASE FOR WHOM CURRENT PRACTICE GUIDELINES RECOMMEND CORONARY ARTERY BYPASS (CABG) TO IMPROVE SURVIVAL. WE HAVE OBTAINED ALL REQUIRED APPROVALS AND 99% OF CONSENTS. WE ARE READY TO CONDUCT EXTENDED FOLLOW-UP OF DEATH, INCLUDING CAUSE OF DEATH, ON >99% OF SURVIVING PARTICIPANTS RESULTING IN 10-YEAR MEDIAN FOLLOW-UP. WE WILL ASCERTAIN VITAL STATUS BY PARTICIPANT/PROXY CONTACT EVERY 6 MONTHS VIA TELEPHONE OR EMAIL, OR BY SEARCHING HIGH-QUALITY NATIONAL/REGIONAL HEALTH/DEATH DATABASES. PARTICIPANT LAST CONTACT DATE, DATE OF DEATH, CAUSE OF DEATH, AND SOURCE OF INFORMATION WILL BE COLLECTED AND ENTERED INTO A WEB-BASED ELECTRONIC DATA CAPTURE SYSTEM. OUR EXCELLENT PARTICIPANT RETENTION, ADHERENCE TO PROTOCOL, DATA COMPLETENESS AND QUALITY DURING THE INITIAL TRIAL PHASE, AND OUR SUBSEQUENT PROGRESS, WITH REQUIRED APPROVALS AND CONSENTS SECURED, ASSURE CONFIDENCE THAT THE STUDY WILL MEET ITS GOALS.

CENTER FOR SYSTEMS BIOLOGY OF RETROTRANSPOSITION

PURPOSE: THIS PROJECT DEVELOPS SALSA (SPECTRALLY AGILE LARGE-SCALE ARRAYS), A WIDEBAND, SPECTRALLY AGILE AND SCALABLE RADIO FREQUENCY INTEGRATED CIRCUIT (RFIC) AND TRANSCEIVER FOR USE IN FUTURE COMMERCIAL, DEFENSE, AND RESEARCH APPLICATIONS. THE RFIC WILL BE INTEGRATED WITH ANTENNAS AND A DIGITAL INTERFACE TO DEVELOP AS AN OPEN RADIO UNIT (O-RU) IN THE OPEN RADIO ACCESS NETWORK (O-RAN WITH A FOCUS ON THE CRITICAL 6?15 GIGAHERTZ (GHZ) BAND. ACTIVITIES TO BE PERFORMED: THE PROJECT HAS FOUR KEY TASKS: TASK 1. DESIGN AND FABRICATION OF A MONOLITHIC, SPECTRALLY AGILE RFIC IN GLOBALFOUNDRIES FD-SOI 22 NM PLATFORM THAT CAN COVER THE ENTIRE 6-15 GHZ BAND WITH HIGH LINEARITY, FREQUENCY HOPPING AND PROGRAMMABLE FILTERING; TASK 2. DEVELOPMENT OF MODULAR AND FLEXIBLE MASSIVE MULTIPLE INPUT, MULTIPLE OUTPUT (MIMO) SOFTWARE-DEFINED RADIO (SDR) PLATFORMS USING THE RFIC MODULES AS BUILDING BLOCKS; TASK 3. DEVELOPMENT OF A SPECTRALLY AGILE, UPPER MID-BAND OPEN-RU AND INTEGRATION OF THE O-RUS INTO THE O-RAN COSMOS TESTBED. TASK 4. DEMONSTRATION OF THE SYSTEM IN SPECTRUM SHARING AND ADVERSARIAL SETTINGS WITH A PATH FOR TECHNOLOGY TRANSITION USING THE TESTBED. EXPECTED OUTCOMES: AS A CAPSTONE DEMONSTRATION, WHEN THE OUTDOOR COSMOS (NORTH AMERICAN OPEN TESTING AND INTEGRATION CENTER [OITC] IN NYC METRO AREA/EAST) PLATFORM IS AVAILABLE, THE RECIPIENT WILL DEMONSTRATE THE MULTI-FREQUENCY HOPPING LINK OUTSIDE. THE RECIPIENT EXPECTS TO SEE A RICH BLOCKING ENVIRONMENT AS IT OBSERVED IN ITS RAY TRACING STUDY. THIS WILL BE THE FIRST COMPREHENSIVE, FREQUENCY HOPPING SYSTEM IN FREQUENCY RANGE (FR) 3 DEMONSTRATED OUTSIDE. INTENDED BENEFICIARIES: MOBILE NETWORK OPERATORS (MNOS), U.S. DEFENSE OPERATIONS AND INDUSTRY RESEARCH SUBRECIPIENT ACTIVITIES: PRINCETON WILL BE RESPONSIBLE FOR THE DESIGN AND TESTING OF THE TRANSMISSION (TX) PATH DEVELOPMENT OF THE RFIC. RUTGERS WILL BE RESPONSIBLE FOR THE INSTALLATION OF THE O-RU?S IN THE COSMOS/O-TIC CENTER. NOKIA WILL BE RESPONSIBLE FOR SPECTRUM SHARING USE CASE, REQUIREMENTS, AND CAPACITY ANALYSIS, SPECTRUM SENSING AND SPECTRUM SHARING ALGORITHMS, RU TESTING AND RU PRODUCT DESIGN FOR ENVISIONED COMMERCIAL RU. PI RADIO WILL BE RESPONSIBLE FOR THE DESIGN, MANUFACTURING, AND TESTING OF THE RADIO FREQUENCY MODULE AND THE INTEGRATION OF THE MODULES INTO THE MIMO PLATFORMS, DRIVER DEVELOPMENT AND TECHNICAL DOCUMENTATION.

PRACTITIONERS ENGAGED IN APPLIED RESEARCH AND LEARNING

RISK FACTORS FOR AIDS AMONG INTRAVENOUS DRUG USERS

BIOGENESIS AND CATABOLISM OF ATHEROGENIC LIPOPROTEINS - SUMMARY/ABSTRACT – OVERALL: MORE PEOPLE DIE OF CARDIOVASCULAR DISEASE (CVD) THAN ANY OTHER DISEASE WORLDWIDE. OUR PROPOSAL FOCUSES ON THE BIOGENESIS AND CATABOLISM OF ATHEROGENIC APOB- CONTAINING LIPOPROTEINS (APOB-LPS), WHICH ARE MAJOR RISK FACTORS FOR CVD. APOB-LPS COMPRISE BOTH CHOLESTEROL AND TRIGLYCERIDES (TGS). WHEREAS REDUCING CHOLESTEROL IS WELL ESTABLISHED TO REDUCE ATHEROSCLEROSIS, IT REMAINS TO BE CONVINCINGLY DETERMINED WHETHER DECREASING LEVELS OF TGS OR THE APOB-LPS THAT CARRY TGS WILL DECREASE CVD. BLOCKING SECRETION OF APOB-LPS BY THE LIVER REDUCES LEVELS OF CHOLESTEROL-RICH APOB-LPS, SUCH AS LDL AND ITS TG-RICH PRECURSOR VLDL. UNFORTUNATELY, SUCH APPROACHES HAVE LED TO HEPATOSTEATOSIS. HOWEVER, HUMAN GENETIC MUTATION AND ANIMAL STUDIES DEMONSTRATE THAT REDUCED LIVER SECRETION OF TGS DOES NOT INVARIABLY CAUSE STEATOSIS. BY CHARACTERIZING NOVEL FACTORS AND PATHWAYS REGULATING LIVER APOB-LP PRODUCTION, INTRAVASCULAR LIPOLYSIS, AND ADIPOSE TG RETENTION AND MOBILIZATION, WE WILL IDENTIFY UNIQUE TARGETS TO REDUCE CIRCULATING APOB- LPS, THEIR INFILTRATION INTO THE ARTERY WALL, AND ATHEROSCLEROSIS. WE WILL DEFINE BASIC MECHANISMS IN CELLS AND IN NEW RODENT MODELS AND THEN CORRELATE OUR DISCOVERIES WITH HUMAN DATA, EMPHASIZING A TRANSLATIONAL AND TRANSFOMATIVE APPROACH. OUR OVERALL GOALS ARE TO: 1) IDENTIFY NEW PROCESSES AND FACTORS REGULATING CIRCULATING TG AND FA LEVELS, 2) INVESTIGATE THE LIPIDATION AND INTRACELLULAR TRANSPORT OF APOB IN HEPATOCYTES, AND 3) STUDY HOW DIFFERENT APOB-LPS INTERACT WITH CELLS AND ULTIMATELY CATALYZE ATHEROGENESIS. THIS APPLICATION COMPRISES THREE PROJECTS (P1–P3) THAT HAVE INTEGRATED WORK FROM THREE ESTABLISHED INVESTIGATORS OF APOB-LP METABOLISM AND ATHEROSCLEROSIS. P1 WILL INVESTIGATE THE ROLE OF ADIPOSE MTP AND FIT2 IN REGULATING ADIPOSE LIPOLYSIS, CIRCULATING LIPIDS, HEPATIC APOB-LP PRODUCTION, AND ATHEROSCLEROSIS. P2 WILL STUDY TWO POORLY CHARACTERIZED PROTEINS IN THE LIVER, KLHL12 AND FIT2, WHICH CONTROL HEPATIC APOB-LP LIPID-LOADING AND SECRETION, AND THE COMPOSITION OF ATHEROGENIC APOB-LPS. P3 WILL STUDY HOW TG-RICH APOB-LPS INTERACT WITH THE VASCULAR WALL, AND SPECIFICALLY DETERMINE THE ROLE OF THE N-TERMINAL REGION OF APOB ON LIPID UPTAKE AND TRANSCYTOSIS OF APOB-LPS BY VASCULAR ECS AND THEIR LINKS TO ATHEROSCLEROSIS. THE PPG HAS AN ADMINISTRATIVE CORE AND THREE SCIENTIFIC CORES (C1–C3). THE ADMINISTRATIVE CORE WILL OVERSEE THE OVERALL PPG FUNCTION AND FINANCES. TO ASSIST P1–P3, C1 WILL PROVIDE BIOSTATISTICS AND BIOINFORMATICS SUPPORT, C2 WILL PERFORM LIPIDOMICS AND PROTEOMICS ON APOB-LPS AND TISSUES AND PROVIDE HUMAN SAMPLES, AND C3 WILL PERFORM STATE-OF-THE-ART ATHEROSCLEROSIS ASSAYS. OUR STUDIES WILL GENERATE NOVEL MOUSE MODELS INVALUABLE TO UNDERSTAND THE FACTORS THAT REGULATE LIPID METABOLISM AND ATHEROSCLEROSIS, IDENTIFY NEW THERAPEUTIC TARGETS, AND BETTER DEFINE HOW HIGH CIRCULATING LEVELS OF ATHEROGENIC APOB-LPS AND OTHER FACTORS CONTRIBUTE TO ATHEROGENESIS. DISSECTING PATHWAYS THAT REGULATE THE PRODUCTION AND ATHEROGENICITY OF APOB- LPS PROMISES TO REVEAL NOVEL APPROACHES TO REDUCE CVD. THIS REQUIRES THE INTEGRATION OF RESEACH IN OUR THREE PROJECTS, AS EXPERIMENTS IN EACH REQUIRE ASSISTANCE FROM THE OTHERS AND CORE RESOURCES.

THE ISCHEMIA-CKD TRIAL-CCC-LEAD APPLICATION

CLEARANCE AND IN VIVO DETECTION OF TAU PATHOLOGY

SELF-ASSEMBLY AND SELF-REPLICATION OF NOVEL MATERIALS FROM PARTICLES WITH SPECIFIC RECOGNITION

WOUND EMR TO DECREASE LIMB AMPUTATIONS IN PERSONS WITH DIABETES

NEW YORK UNIVERSITY CLINICAL AND TRANSLATIONAL SCIENCE HUB - THE NEW YORK UNIVERSITY (NYU) CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE (CTSI) IS A VIBRANT PUBLIC–PRIVATE COLLABORATION BETWEEN NYU LANGONE HEALTH (NYULH), THE NYU GROSSMAN SCHOOL OF MEDICINE AND NYU GROSSMAN LONG ISLAND SCHOOL OF MEDICINE; THE FAMILY HEALTH CENTERS AT NYULH, OUR COMMUNITY AND PATIENT ADVISORY BOARDS, AND ALL OTHER NYU SCHOOLS AND COLLEGES. MOREOVER, OUR PARTNERSHIPS WITH NYC HEALTH AND HOSPITALS, THE NATION’S LARGEST MUNICIPAL HEALTHCARE SYSTEM; THE NATHAN KLINE INSTITUTE, A PSYCHIATRIC RESEARCH INSTITUTE; KINGSBOROUGH COMMUNITY COLLEGE, AND >150 ADDITIONAL COMMUNITY PARTNERS ALLOW US TO REACH ALL POPULATIONS ACROSS NEW YORK CITY. OUR FOCUS OVER THE NEXT 7 YEARS IS TO EMPHASIZE COLLABORATION AS A FUNDAMENTAL APPROACH TO ADVANCING CLINICAL TRANSLATIONAL SCIENCE (CTS) WHILE OVERCOMING BARRIERS, BRIDGING COMMUNITIES, FOSTERING A WELL-ROUNDED SCIENCE WORKFORCE, AND CONTINUOUSLY EVALUATING AND IMPROVING THE QUALITY AND IMPACT OF OUR RESEARCH. WE WILL PARTNER WITH COMMUNITIES TO BRING RESEARCH TO WHERE PEOPLE LIVE AND PROMOTE PRACTICE AND POLICY THROUGH FIVE OVERARCHING AIMS. AIM 1: ENHANCE COMMUNITY-ENGAGED RESEARCH. WE WILL LEVERAGE OUR UNIQUE STRENGTHS COLLABORATING WITH PATIENT, COMMUNITY, AND MULTISECTOR PARTNERS TO ESTABLISH INNOVATIVE RESEARCH PROGRAMS AND PRACTICE-BASED LEARNING HEALTH SYSTEMS. AIM 2: DEMOCRATIZE HEALTH INFORMATICS (HI) RESOURCES. WE WILL FOSTER A COLLABORATIVE ENVIRONMENT TO DEVELOP, IMPLEMENT, AND DISSEMINATE INNOVATIVE HI RESOURCES THAT ENHANCE THE QUALITY, SAFETY, EFFICIENCY, AND REPRODUCIBILITY OF CLINICAL TRANSLATIONAL RESEARCH (CTR) AND CTS. AIM 3: DEVELOP A WELL-ROUNDED WORKFORCE TO ADVANCE CTS. WE WILL CREATE COLLABORATIVE LEARNING INITIATIVES THAT INVOLVE RESEARCH FACULTY, STAFF, CLINICIANS, STUDENTS, AND COMMUNITY MEMBERS. AIM 4: CATALYZE REGIONAL AND NATIONAL COLLABORATIONS TO ACCELERATE CTS RESEARCH. WE WILL PROMOTE AND FACILITATE PARTNERSHIPS AT REGIONAL AND NATIONAL LEVELS TO ACCELERATE CTS RESEARCH THROUGH INTERDISCIPLINARY TEAM SCIENCE AND KNOWLEDGE SHARING. AIM 5: ADVANCE CLINICAL TRIALS THROUGH COLLABORATIVE PARTNERSHIPS. WE WILL DEVELOP AND IMPLEMENT OPERATIONAL INNOVATIONS TO ACCELERATE START-UP AND COMPLETION OF CLINICAL TRIALS, WHILE ELEVATING THEIR QUALITY, SAFETY, EFFECTIVENESS, AND IMPACT. THESE GOALS CAPITALIZE ON OUR MAJOR STRENGTHS, EMPHASIZING COLLABORATIONS WITH COMMUNITY AND MULTISECTOR PARTNERS, INTERDISCIPLINARY ENGAGEMENT ACROSS NYU AND ITS 11 COLLEGES AND SCHOOLS, AND ACTIVE PARTICIPATION IN THE CTSA CONSORTIUM. FOR THE NEXT 7 YEARS, WE ENVISION A FUTURE IN WHICH SCIENTIFIC BREAKTHROUGHS MORE SWIFTLY TRANSITION FROM BENCH TO THE BEDSIDE AND INTO OUR COMMUNITIES SO EVERY INDIVIDUAL RECEIVES ACCESS TO INNOVATIVE HEALTHCARE SOLUTIONS.

NEURAL MECHANISMS OF VESTIBULAR FUNCTION

MSB CENTRAL ANIMAL FACILITY RENOVATION

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

AGING & VULNERABILITY TO ISCHEMIA: PATHWAYS & RESCUE

NYU-CUNY PREVENTION RESEARCH CENTER

TRAINING PROGRAM IN MOLECULAR ONCOLOGY AND IMMUNOLOGY

BUILDING ACCESS TO FOOD THROUGH SYSTEMS AND SOLIDARITY - SUMMARY / ABSTRACT LEVERAGING OUR DEEP EXPERIENCE WITH CONDUCTING COMMUNITY-ENGAGED RESEARCH, THE GOAL OF THE BUILDING ACCESS TO FOOD THROUGH SYSTEMS AND SOLIDARITY (BASIS) STUDY IS TO IMPROVE DIET BY PROVIDING CULTURALLY APPROPRIATE FOOD ACCESS AND ATTENDING TO DRIVERS THAT LIMIT THE ABILITY TO ACHIEVE NUTRITION SECURITY IN SUNSET PARK – A COMMUNITY OF MEXICAN AND CHINESE AMERICAN FAMILIES IN BROOKLYN, NY THAT HAS BEEN HARD-HIT DURING THE COVID-19 PANDEMIC, HAS LAGGED IN ECONOMIC RECOVERY, AND WHERE RESIDENTS ARE DISCONNECTED FROM GOVERNMENT SUPPORTS. SIGNIFICANCE. LATINX AND ASIAN AMERICAN COMMUNITIES FACE UNIQUE, YET SIMILAR STRUCTURAL AND SOCIAL INEQUITIES CONTRIBUTING TO POOR DIET QUALITY, WHICH HAVE CONTRIBUTED TO THE INCREASED BURDEN OF DIABETES AND NON-ALCOHOLIC FATTY LIVER DISEASE IN THESE GROUPS. THE PAST TWO YEARS HAS EXACERBATED THESE BARRIERS DUE TO OVERT ANTI-IMMIGRANT AND ANTI-ASIAN SENTIMENT DURING THE PANDEMIC, INVOKING FEAR, CULTURAL SHAME, AND LOSS OF A SENSE OF SECURITY FOR THESE GROUPS – FACTORS WHICH HAVE FUELED CHALLENGES TOWARDS ACCESSING FOOD AND ECONOMIC STABILITY. APPROACH. WORKING COLLABORATIVELY WITH FOUR FARMING/GARDENING ORGANIZATIONS, ONE ELEMENTARY SCHOOL AND THREE COMMUNITY-BASED ORGANIZATIONS, OUR AIMS ARE: AIM 1: TO IMPLEMENT A WHOLE-OF-COMMUNITY INTERVENTION IN SUNSET PARK FOR IMPROVING DIET AND THE SOCIAL/BUILT ENVIRONMENTS FOR LOW-INCOME MEXICAN AND CHINESE AMERICAN IMMIGRANTS. THE BASIS PROGRAM WILL INCLUDE INLANGUAGE NAVIGATION FOR FOOD BUSINESS OWNERS/RESIDENTS TO GOVERNMENT ASSISTANCE / WORKFORCE DEVELOPMENT PROGRAMS; A SUBSIDIZED FRESH PRODUCE BOX PROGRAM; GARDENING AND NUTRITION EDUCATION; AND A SOCIAL MARKETING CAMPAIGN TO PROMOTE HEALTHY EATING BEHAVIOR CHANGES AND CULTURAL AWARENESS. MATERIALS WILL BE CULTURALLY APPROPRIATE AND SPECIFIC TO EACH COMMUNITY, YET ALSO HIGHLIGHT SIMILARITIES ACROSS BOTH GROUPS. AIM 2: TO EVALUATE THE BASIS PROGRAM IMPACT AT THE COMMUNITY, INTERPERSONAL AND INDIVIDUAL LEVELS . THE EVALUATION PLAN WILL EMPLOY ADMINISTRATIVE DATA SOURCES AND MIXED METHODS TO ASSESS OUTCOMES AT MULTIPLE LEVELS. OUTCOMES WILL BE ASSESSED IN SUNSET PARK AND IN 4 COMPARISON COMMUNITIES THAT ARE PREDOMINANTLY MEXICAN AND CHINESE AMERICAN (CORONA, EAST HARLEM; CHINATOWN, ELMHURST, RESPECTIVELY). WE HYPOTHESIZE THAT STABILITY IN THE FOOD RETAIL SECTOR AND IMPROVEMENTS IN NEIGHBORHOOD SOCIAL COHESION, DIET, ETHNIC PRIDE AND SENSE OF BELONGING WILL BE OBSERVED IN SUNSET PARK VS. COMPARISON COMMUNITIES. AIM 3: TO CO-DEVELOP A MULTI-FACETED SUSTAINABILITY STRATEGY WITH MULTI-SECTOR STAKEHOLDERS. SUSTAINABILITY IS A CENTRAL PRIORITY OF THE BASIS PROGRAM AND IS DRIVEN BY COMMITMENT TO COMMUNITY PRIORITIES; INVESTMENT IN INFRASTRUCTURE AND WORKFORCE DEVELOPMENT; AND ENGAGEMENT IN THE LOCAL FOOD POLICY DIALOGUE. IMPACT.BASIS PRESENTS A POWERFUL MODEL TO IMPROVE DIET IN IMMIGRANT COMMUNITIES BY ADDRESSING DETERMINANTS OF FOOD ACCESS IN A COMMUNITY-CENTERED, CULTURALLY COMPETENT WAY, AND BY FORTIFYING COMMUNITY EMPOWERMENT.

DECONSTRUCTION OF A NEURAL CIRCUIT FOR AGGRESSION

MECHANISMS OF FGF RECEPTOR REGULATION AND SIGNALING

UNIVERSITY TRANSPORTATION CENTERS

TRANSCONTINENTAL EM INITIATIVE FOR MEMBRANE PROTEIN STRUCTURE

NATIONAL CENTER FOR ENGAGEMENT IN DIABETES EQUITY RESEARCH: NATIONAL CEDER - PROJECT SUMMARY: OVERALL OF THE ~37 MILLION AMERICANS WITH DIABETES, 90–95% HAVE TYPE 2 DIABETES (T2D).1 T2D AND DIABETES COMPLICATIONS DISPROPORTIONATELY IMPACT UNITED STATES (U.S.) RACIAL AND ETHNIC MINORITY COMMUNITIES. ADDITIONALLY, POPULATIONS WITH LOW SOCIOECONOMIC STATUS (SES), THOSE LIVING IN RURAL AREAS, AND LOW-RESOURCED COMMUNITIES BEAR A DISPROPORTIONATE BURDEN OF DIABETES ILLNESS. ADVANCING EQUITY IN T2D DISPARITIES NECESSITATES ADDRESSING THE SOCIAL DETERMINANTS OF HEALTH; ENHANCING ENGAGEMENT IN THE RESEARCH PROCESS; AND TRANS- DISCIPLINARY COLLABORATION THAT INCORPORATES MULTI-LEVEL INTERVENTIONS AND METHODS OF ANALYSIS, PRAGMATIC DESIGNS THAT ENHANCE IMPLEMENTATION AND DISSEMINATION OF EFFECTIVE STRATEGIES, AND MIXED-METHODS APPROACHES. THE OVERALL GOAL OF THE NATIONAL CENTER FOR ENGAGEMENT IN DIABETES EQUITY RESEARCH: NATIONAL CEDER IS TO STRENGTHEN THE ENGAGEMENT OF COMMUNITIES AND INDIVIDUALS FROM DIVERSE BACKGROUNDS AND SECTORS IN T2D RESEARCH ACROSS THE U.S. THROUGH A PUBLIC–PRIVATE PARTNERSHIP OF THE NYU GROSSMAN SCHOOL OF MEDICINE (SOM), UCLA SOM, ALBERT EINSTEIN COLLEGE OF MEDICINE, AMERICAN DIABETES ASSOCIATION, HEALTH PEOPLE, AND VISION Y COMPROMISO. OUR NATIONAL REACH IS AMPLIFIED THROUGH AN EXPANSIVE PARTNERSHIP OF 18 ACADEMIC INSTITUTIONS, INCLUDING SCHOOLS OF PUBLIC HEALTH, SCHOOLS OF MEDICINE, AND MINORITY-SERVING INSTITUTIONS; AND 10 REGIONAL AND NATIONAL COMMUNITY BASED ORGANIZATIONS REACHING DIVERSE AFRICAN AMERICAN, LATINX, ASIAN AMERICAN, NATIVE HAWAIIAN, PACIFIC ISLANDER, AND AMERICAN INDIAN/ALASKA NATIVE COMMUNITIES. NATIONAL CEDER, WHICH COMPRISES THREE SYNERGISTIC CORES, INCLUDING AN ADMINISTRATIVE CORE, STAKEHOLDER ENGAGEMENT STUDIO CORE, AND RESEARCH CONSULTATION SERVICES CORE, AIMS TO: 1. STRENGTHEN ESTABLISHED COMMUNITY-ENGAGED, MULTI-SECTORAL REGIONAL PARTNERSHIPS TO CREATE A CENTRALIZED, NATIONAL NETWORK INFRASTRUCTURE DESIGNED TO FOSTER EQUITABLE ENGAGEMENT IN T2D RESEARCH; 2. ACCELERATE EQUITABLE ENGAGEMENT OF DIVERSE COMMUNITIES AND SECTORS THROUGH A PARTNERSHIP HUB MODEL AND INTEGRATED SDOH AND HEALTH EQUITY FRAMEWORKS THAT WILL INFORM T2D RESEARCH PRIORITIES AND METHODS; 3. USE COMMUNITY ENGAGEMENT, IMPLEMENTATION SCIENCE, CULTURAL ADAPTATION, AND INTERSECTIONALITY FRAMEWORKS TO IMPROVE UPTAKE OF RESEARCH PRINCIPLES, METHODS AND ENGAGEMENT STRATEGIES IN T2D RESEARCH THROUGH A ROBUST STUDIO AND CONSULTANCY MODEL ROOTED IN BI-DIRECTIONAL CAPACITY BUILDING AND CO-LEADERSHIP BETWEEN COMMUNITY, HEALTHCARE, MUNICIPAL, AND RESEARCH PARTNERS; AND 4. COLLABORATE WITH RESEARCHERS FROM DIVERSE DISCIPLINES AND MULTI-SECTOR STAKEHOLDER GROUPS TO SYNTHESIZE AND DISSEMINATE BEST PRACTICES AND LESSONS LEARNED IN ADVANCING EQUITABLE, SUSTAINABLE, AND REPLICABLE COMMUNITY ENGAGEMENT ACROSS THE T2D RESEARCH SPECTRUM. NATIONAL CEDER EFFORTS WILL FOSTER COMMUNITY-LED AND -INFORMED T2D EQUITY RESEARCH BY INTEGRATING COMMUNITY ENGAGEMENT ACROSS THE RESEARCH SPECTRUM.

ADVANCED CENTER FOR STATE RESEARCH TO SCALE UP EBPS FOR CHILDREN

EVALUATION OF SMOKE-FREE HOUSING POLICY IMPACTS ON TOBACCO SMOKE EXPOSURE AND HEALTH OUTCOMES

THE PURPOSE OF THIS RESTORATIVE PRACTICES PILOT PROGRAM EVALUATION AWARD IS TO CONDUCT RESEARCH AND EVALUATION ON RESTORATIVE PRACTICES IN COLLABORATION WITH PILOT SITES AND TRAINING AND TECHNICAL ASSISTANCE (TTA) PROVIDERS. THIS PROJECT WILL BUILD EVIDENCE AND DATA FOR VICTIM-CENTERED, TRAUMA-INFORMED, AND CULTURALLY RESPONSIVE RESTORATIVE PRACTICES ADDRESSING DOMESTIC VIOLENCE, DATING VIOLENCE, SEXUAL ASSAULT, AND STALKING. NEW YORK UNIVERSITY WILL CONDUCT A MIXED-METHODS EVALUATION OF THE RESTORATIVE PRACTICES PILOT PROGRAM. THIS AWARD WILL SUPPORT RESEARCH PROJECTS THAT WILL GENERATE KNOWLEDGE THAT PRACTITIONERS, POLICYMAKERS, AND THE PUBLIC CAN USE TO MAKE DECISIONS ABOUT DEVELOPING, IMPLEMENTING, AND USING RESTORATIVE PRACTICES TO REDRESS THE HARM CAUSED BY DOMESTIC VIOLENCE, SEXUAL ASSAULT, DATING VIOLENCE, AND STALKING. NEW YORK UNIVERSITY WILL WORK IN CLOSE COLLABORATION WITH OVW STAFF, TTA PROVIDERS, EVALUATION LIAISONS, AND PILOT SITE PRACTITIONERS TO DEVELOP REASONABLE AND USEFUL EVALUATION MEASURES ACROSS AND WITHIN PILOT SITES. ADDITIONALLY, THE RESEARCH THAT OVW WILL FUND THROUGH THIS AWARD WILL MIRROR THE AIMS OF RESTORATIVE PRACTICES, USE MIXED-METHODS APPROACHES, AND BE ADAPTABLE AND COMMUNITY-SPECIFIC WITH STRONG RESEARCHER-PRACTITIONER-COMMUNITY PARTNERSHIPS.

INTEGRATED CLINICAL PREDICTION RULES:BRINGING EVIDENCE TO DIVERSE PRIMARY CARE SE

EPITOPE-SPECIFIC TARGETING OF TAU AGGREGATES.

PRIMARY PALLIATIVE CARE FOR EMERGENCY MEDICINE

BEHAVIORAL PHENOSCREENING: REMOTE ASSESSMENT OF CHILD MENTAL HEALTH (REACH) - SUMMARY EXTERNALIZING PROBLEMS, CHARACTERIZED BY DISRUPTIVE CONDUCT, AGGRESSION, HYPERACTIVITY, ATTENTIONAL PROBLEMS, AND THE INABILITY TO ADEQUATELY ADAPT TO NEW SITUATIONS, ARE LEADING CONTRIBUTORS TO HEALTH BURDEN AMONGST CHILDREN AND ADOLESCENTS GLOBALLY. A RECENT MENTAL HEALTH SURVEILLANCE AMONG CHILDREN IN THE UNITED STATES INDICATES ONE IN 11 CHILDREN HAVE AN ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD) DIAGNOSIS. DESPITE THE EXTRAORDINARILY IMPROVED OUTCOMES ASSOCIATED WITH EARLY DIAGNOSIS AND TARGETED INTERVENTION, EXTERNALIZING DISORDERS SUCH AS ADHD AND OPPOSITIONAL DEFIANCE DISORDER (ODD) ARE USUALLY ONLY DIAGNOSED AFTER SYMPTOMS HAVE CLEARLY EMERGED AND ARE CAUSING SIGNIFICANT IMPAIRMENTS IN DAILY FUNCTIONING. THIS CRITICAL NEED FOR EARLY- LIFE PREDICTION OF EXTERNALIZING DISORDERS CAN NOW BE ADDRESSED, THANKS TO EXPLOSIVE ADVANCES IN ARTIFICIAL INTELLIGENCE (AI) AND WIDESPREAD ACCESSIBILITY OF REMOTE TECHNOLOGY. THERE IS UNTAPPED OPPORTUNITY TO BRING SIMPLE, SCALABLE AND ACCESSIBLE SOLUTIONS TO FAMILIES TO IMPROVE DETECTION AND INTERVENTION OF EARLY EMERGING EXTERNALIZING DISORDERS. OUR PROPOSAL IS RESPONSIVE TO THE INDIVIDUALLY MEASURED PHENOTYPES TO ADVANCE COMPUTATIONAL TRANSLATION IN MENTAL HEALTH INITIATIVE, WITH THE KEY OBJECTIVE OF USING COMPUTER VISION AND MACHINE LEARNING BASED APPROACHES TO FACILITATE EARLY IDENTIFICATION OF EXTERNALIZING DISORDERS. TO ACHIEVE THIS, WE PROPOSE SYNERGISTIC AIMS: AIM 1: IDENTIFY MATERNAL-INFANT HEALTH AND SOCIAL DETERMINANTS OF HEALTH PREDICTORS OF EXTERNALIZING DISORDERS (ADHD, ODD, AND CONDUCT DISORDER (CD)) BY EMPLOYING A SUITE OF MACHINE LEARNING MODELS TO LEVERAGE AN EXPANSIVE NATION-WIDE, REPRESENTATIVE COHORT OF >9M CHILDREN WITH BIRTHING PARENT LINKAGE (EPIC COSMOS). AIM 2: ISOLATE A PARSIMONIOUS SET OF INFANT AND TODDLER BEHAVIORS, DERIVED VIA COMPUTER VISION MICROCODING, BY LEVERAGING THE EXPANSIVE HEALTHY BRAIN AND CHILD DEVELOPMENT (HBCD) STUDY TO INTEGRATE VIDEO, BEHAVIORAL, COGNITIVE, AND SURVEY DATA FROM 3,100 INFANTS 9–15 MONTHS OF AGE TO PREDICT ANTECEDENTS OF PSYCHOPATHOLOGY AT 2 YEARS OF AGE; FURTHER, EVALUATE IF SPECIFIC PATTERNS OF INFANT AFFECT, AROUSAL, AND ATTENTION, AS MEASURED BY MICROCODING, WILL SIGNIFICANTLY IMPROVE THE PREDICTION OF EXTERNALIZING PROBLEMS AT AGE 2 COMPARED TO MODELS USING CAREGIVER REPORTS AND EHR DATA. AIM 3: DEVELOP AND VALIDATE A SCALABLE, REMOTE INFANT PHENOSCREENING TO CHARACTERIZE INDIVIDUAL PREDICTION MODELS OF EXTERNALIZING BEHAVIORS. WE WILL COMBINE AND EXTEND FINDINGS FROM SA1 AND SA2 TO DEVELOP A FULLY REMOTE, LOW- COST, BRIEF PARENT-ADMINISTERED SMARTPHONE/WEB-BASED SCREENING ASSESSMENT OF INFANT BEHAVIOR IN A NEW, NATIONALLY REPRESENTATIVE COHORT OF 1,500 TODDLERS AT 9–15 MONTHS OF AGE. THE INNOVATION OF THIS PROJECT IS THREE- FOLD: (I) IDENTIFICATION OF MATERNAL AND INFANT HEALTH PREDICTORS OF EXTERNALIZING DISORDERS USING LARGE-SCALE, MULTI- LEVEL DATA, (II) ADDRESSING STRUCTURAL INEQUITIES IN HEALTHCARE ACCESS AND TIME TO DIAGNOSIS THROUGH EVALUATION OF A HIGHLY SCALABLE PORTAL FOR MULTI-TRAIT ASSESSMENT AT INFANT AGE 12 MONTHS, AND (III) USE OF AI TO AUTOMATICALLY QUANTIFY INFANT BEHAVIORS PREDICTIVE OF FUTURE EXTERNALIZING OUTCOMES. THE TRANSLATIONAL SIGNIFICANCE OF THIS WORK WILL BE ADVANCING LOW COST, ACCESSIBLE, SCALABLE AND ACCURATE POPULATION SCREENING IN INFANCY; DEVELOPMENT OF MORE PRECISE INTERVENTIONAL TARGETS; AND ALLEVIATING SOCIOECONOMIC DISPARITIES IN DIAGNOSIS AND INTERVENTION.

MAPPING THE OPTIC LOBES FOR COLOR VISION

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) -THE NATIONAL SCIENCE FOUNDATION (NSF) GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) IS A HIGHLY COMPETITIVE, FEDERAL FELLOWSHIP PROGRAM. GRFP HELPS ENSURE THE VITALITY AND DIVERSITY OF THE SCIENTIFIC AND ENGINEERING WORKFORCE OF THE UNITED STATES. THE PROGRAM RECOGNIZES AND SUPPORTS OUTSTANDING GRADUATE STUDENTS WHO ARE PURSUING RESEARCH-BASED MASTER'S AND DOCTORAL DEGREES IN SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS (STEM) AND IN STEM EDUCATION. THE GRFP PROVIDES THREE YEARS OF FINANCIAL SUPPORT FOR THE GRADUATE EDUCATION OF INDIVIDUALS WHO HAVE DEMONSTRATED THEIR POTENTIAL FOR SIGNIFICANT RESEARCH ACHIEVEMENTS IN STEM AND STEM EDUCATION. THIS AWARD SUPPORTS THE NSF GRADUATE FELLOWS PURSUING GRADUATE EDUCATION AT THIS GRFP INSTITUTION. 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.

ANALYTICAL AND COMPUTATIONAL MATHEMATICAL PHYSICS

GENOMICS OF BLOOD PRESSURE-INDUCED TARGET ORGAN DAMAGE

8/24 THE HEALTHY BRAIN AND CHILD DEVELOPMENT NATIONAL CONSORTIUM - PROJECT SUMMARY/ABSTRACT NEURODEVELOPMENTAL PROCESSES ARE SHAPED BY DYNAMIC INTERACTIONS BETWEEN GENES AND ENVIRONMENTS. MALADAPTIVE EXPERIENCES EARLY IN LIFE CAN ALTER DEVELOPMENTAL TRAJECTORIES, LEADING TO HARMFUL AND ENDURING DEVELOPMENTAL SEQUELAE. PRE- AND POSTNATAL HAZARDS INCLUDE MATERNAL SUBSTANCE EXPOSURE, TOXICANT EXPOSURES IN PREGNANCY AND EARLY LIFE, MATERNAL HEALTH CONDITIONS, PARENTAL PSYCHOPATHOLOGY, MALTREATMENT, STRUCTURAL RACISM, AND EXCESSIVE STRESS. TO ELUCIDATE HOW VARIOUS ENVIRONMENTAL HAZARDS IMPACT CHILD DEVELOPMENT, IT IS IMPERATIVE THAT A NORMATIVE TEMPLATE OF DEVELOPMENTAL TRAJECTORIES OVER THE FIRST 10 YEARS OF LIFE BE ESTABLISHED BASED ON A SUFFICIENTLY LARGE AND DEMOGRAPHICALLY DIVERSE SAMPLE OF THE US POPULATION. TO ACCOMPLISH THIS, THE HEALTHY BRAIN AND CHILD DEVELOPMENT NATIONAL CONSORTIUM (HBCD-NC) HAS BEEN FORMED TO DEPLOY A HARMONIZED, OPTIMIZED, AND INNOVATIVE SET OF NEUROIMAGING (MRI, EEG) MEASURES COMPLEMENTED BY AN EXTENSIVE BATTERY OF BEHAVIORAL, PHYSIOLOGICAL, AND PSYCHOLOGICAL TOOLS, AND BIOSPECIMENS TO UNDERSTAND NEURODEVELOPMENTAL TRAJECTORIES IN A SAMPLE OF 7,500 MOTHERS AND INFANTS ENROLLED AT 24 SITES ACROSS THE UNITED STATES (US). THE HBCD-NC WILL CARRY OUT A COMMON RESEARCH PROTOCOL UNDER DIRECTION OF THE HBCD- NC ADMINISTRATIVE CORE (HCAC) AND WILL ASSEMBLE AND DISTRIBUTE A COMPREHENSIVE AND WELL-CURATED RESEARCH DATASET TO THE SCIENTIFIC COMMUNITY AT LARGE UNDER THE DIRECTION OF THE HBCD-NC DATA COORDINATING CENTER (HDCC). THE OVERARCHING GOAL OF THE HBCD-NC IS TO CREATE A COMPREHENSIVE, HARMONIZED, AND HIGH- DIMENSIONAL DATASET THAT WILL CHARACTERIZE TYPICAL NEURODEVELOPMENTAL TRAJECTORIES IN US CHILDREN AND THAT WILL ASSESS HOW BIOLOGICAL AND ENVIRONMENTAL EXPOSURES AFFECT THOSE TRAJECTORIES. A SPECIAL EMPHASIS WILL BE PLACED ON UNDERSTANDING THE IMPACT OF PRE- AND POSTNATAL EXPOSURE TO OPIOIDS, MARIJUANA, ALCOHOL, TOBACCO AND/OR OTHER SUBSTANCES. TO ADDRESS THESE BROAD OBJECTIVES, THE SAMPLE OF WOMEN ENROLLED WILL INCLUDE: 1) A RACIALLY, ETHNICALLY, AND SOCIOECONOMICALLY DIVERSE COHORT THAT IS REPRESENTATIVE OF THE US POPULATION; 2) PREGNANT WOMAN WITH USE OF TARGETED SUBSTANCES (OPIOIDS, MARIJUANA, ALCOHOL, TOBACCO); AND 3) DEMOGRAPHICALLY AND BEHAVIORALLY SIMILAR WOMEN WITHOUT SUBSTANCE USE IN PREGNANCY TO ENABLE VALID CAUSAL INFERENCES. IN ADDITION, THE HBCD-NC WILL IDENTIFY KEY DEVELOPMENTAL WINDOWS DURING WHICH BOTH HARMFUL AND PROTECTIVE ENVIRONMENTS HAVE THE MOST INFLUENCE ON LATER NEURODEVELOPMENTAL OUTCOMES. THE LARGE, MULTI- MODAL, LONGITUDINAL, AND GENERALIZABLE DATASET THAT WILL BE PRODUCED FOR THE FIRST TIME BY THIS STUDY WILL PROVIDE NOVEL INSIGHTS INTO CHILD DEVELOPMENT USING STATE-OF-THE-ART METHODS. THE HBCD-NC STUDY WILL INFORM PUBLIC POLICY TO IMPROVE THE HEALTH AND DEVELOPMENT OF CHILDREN ACROSS THE NATION.

PEER-DRIVEN INTERVENTION TO SEEK, TEST & TREAT HETEROSEXUALS AT HIGH RISK FOR HIV

DISAPPEARING GASTROINTESTINAL MICROBIOTA IN EPIDEMIC OBESITY.

ADVANCING PRECISION PSYCHIATRY FOR MILITARY SERVICE-RELATED PTSD BY ENHANCING KNOWLEDGE OF CLINICAL SUBTYPES AND THEIR ENDOPHENOTYPES

RYAN WHITE PART C OUTPATIENT EIS PROGRAM

METABOLIC ALDEHYDES AS IMMUNE EFFECTORS AGAINST TUBERCULOSIS

SAFETY AND EFFICACY OF BELATACEPT IN HEART TRANSPLANTATION - PROJECT SUMMARY: ALTHOUGH CALCINEURIN INHIBITORS (CNIS), INCLUDING TACROLIMUS HAVE LED TO EXCELLENT 1-YEAR OUTCOMES IN HEART TRANSPLANTATION, LONG-TERM SURVIVAL REMAINS LIMITED BY CARDIAC ALLOGRAFT VASCULOPATHY, DRIVEN BY DONOR-SPECIFIC-ANTIBODIES (DSA), AND BY CNI-ASSOCIATED MORBIDITY, DOMINATED BY CHRONIC KIDNEY DISEASE. BELATACEPT, A SELECTIVE COSTIMULATION BLOCKER, IS FDA APPROVED FOR USE IN KIDNEY TRANSPLANTATION AS A CNI- ALTERNATIVE. BY INHIBITING CD28/CD80/CD86 INTERACTIONS BELATACEPT PREVENTS ACTIVATION OF BOTH NAÏVE T CELL AND T FOLLICULAR HELPER CELLS ASSOCIATED WITH THE DEVELOPMENT OF DSA, BUT LESS EFFECTIVELY INHIBITS MEMORY T CELLS. IN KIDNEY TRANSPLANT RECIPIENTS, THIS HAS TRANSLATED TO SUSTAINED IMPROVEMENT IN KIDNEY FUNCTION, SUPPRESSION OF DSA, AND IMPROVED GRAFT/PATIENT SURVIVAL, ALBEIT AT THE COST OF MORE EARLY REJECTION WHICH HAS SINCE BEEN MARKEDLY REDUCED BY USING A DELAYED CNI SUBSTITUTION STRATEGY. BUILDING ON THESE FINDINGS, WE PROPOSE A RANDOMIZED CONTROLLED TRIAL OF BELATACEPT IN FIRST-TIME HEART TRANSPLANT RECIPIENTS, IN CONJUNCTION WITH GRADUAL TACROLIMUS WITHDRAWAL OVER 9-MONTHS TO ACHIEVE A CNI-FREE IMMUNOSUPPRESSIVE REGIMEN (WITH MYCOPHENOLATE MOFETIL AND PREDNISONE). WE HYPOTHESIZE THAT THE GRADUAL APPROACH TO CNI WITHDRAWAL WILL PROMOTE QUIESCENCE IN GRAFT-REACTIVE T CELLS, THEREBY PREVENTING REJECTION, INHIBITING THE DEVELOPMENT OF DSA, AND ELIMINATING CNI- RELATED MORBIDITY, TOGETHER INCREASING SURVIVAL AFTER HEART TRANSPLANTATION. THE SPECIFIC AIMS ARE: AIM 1. CLINICAL TRIAL TO DETERMINE SAFETY OF BELATACEPT IN HEART TRANSPLANTATION. WE WILL PERFORM A MULTICENTER CLINICAL TRIAL IN EBV SEROPOSITIVE HEART TRANSPLANT RECIPIENTS RANDOMIZED 2:1 TO RECEIVE BELATACEPT WITH GRADUAL TACROLIMUS WITHDRAWAL (9-MONTHS) POST-HEART TRANSPLANT OR STANDARD-OF-CARE TACROLIMUS (CONTROL). THE OBJECTIVES ARE TO A) ESTABLISH SAFETY OF THE PROTOCOL BASED ON STOPPING CRITERIA DEFINED BY THE COMPOSITE OF HISTORICAL CONTROL EVENT RATES AND B) TEST EFFICACY FOR KIDNEY SPARING AND DSA. AIM 2. IMPACT OF CNI WITHDRAWAL UNDER COSTIMULATION BLOCKADE ON GRAFT-REACTIVE IMMUNE RESPONSES. WE WILL SERIALLY ANALYZE DONOR REACTIVE, AND AUTOANTIGEN REACTIVE T CELL AND B CELL SUBSETS USING STATE-OF-THE-ART PHENOTYPIC AND FUNCTIONAL ASSAYS AND WILL QUANTIFY DSA AND AUTOANTIBODIES. RESULTS WILL BE COMPARED BETWEEN STUDY ARMS AND THE KINETICS OF RESPONSES WILL BE EVALUATED IN INDIVIDUAL SUBJECTS OVER TIME. AIM 3. OTHER MECHANISTIC/BIOMARKER STUDIES RELEVANT TO PRIMARY AND SECONDARY ENDPOINTS IN THE TRIAL. WE WILL USE MOLECULAR APPROACHES TO DEFINE DIFFERENCES IN THE INTRAGRAFT RESPONSE, EXPLORE MARKERS OF KIDNEY INJURY AND FIBROSIS, AND TEST DONOR DERIVED CELL-FREE DNA AS A POTENTIAL BIOMARKER OF IMPEDING REJECTION DURING CNI WITHDRAWAL. IF SUCCESSFUL, BELATACEPT HAS THE POTENTIAL TO TRANSFORM THE HEART TRANSPLANT FIELD, REMOVING CNI-MORBIDITIES AND PREVENTING DSA AS MAJOR BARRIERS TO IMPROVING LONG-TERM SURVIVAL. THE COMPREHENSIVE MECHANISTIC STUDIES WILL PROVIDE NOVEL INFORMATION, REGARDLESS OF OUTCOMES OF THE TRIAL.

NYU MRSEC: SEMANTOPHORETIC ASSEMBLIES

TRANSFORMING CLINICAL PRACTICES INITIATIVE - PTN

EVONET: A PHYLOGENOMIC AND SYSTEMS BIOLOGY APPROACH TO IDENTIFY GENES UNDERLYING PLANT SURVIVAL IN MARGINAL, LOW‐N SOILS

MECHANISMS UNDERLYING THE CONTROL OF RECOMBINATION AND GENE REGULATION

SYNAPTIC BASIS OF PERCEPTUAL LEARNING IN PRIMARY AUDITORY CORTEX

THE REGULATION OF MELANOCYTE STEM CELLS BY WNT SIGNALING

ALZHEIMER?S DISEASE RELATED BIOMARKERS FOLLOWING SARS-COV-2 INFECTION - ABSTRACT COGNITIVE IMPAIRMENT IS A MAJOR SYMPTOM AMONG PATIENTS WITH POST-ACUTE SEQUELAE OF COVID-19. OLDER INDIVIDUALS AND THOSE WITH DEMENTIA RISK FACTORS ARE PARTICULARLY AT RISK. IN OUR OWN PROSPECTIVE STUDY OF 4,491 HOSPITALIZED COVID-19 PATIENTS, THE MEDIAN AGE WAS 65 YEARS, 606 (14%) DEVELOPED NEW NEUROLOGICAL DISORDERS (MOST COMMONLY ENCEPHALOPATHY) DURING HOSPITALIZATION, INDICATING A POPULATION AT HIGH RISK FOR DEVELOPMENT OF ALZHEIMER’S DISEASE OR RELATED-DEMENTIA (AD/ADRD). OF THIS GROUP, 48% OF PATIENTS WHO WERE COGNITIVELY NORMAL PRE-COVID HAD ABNORMAL TELEPHONE MOCA SCORES (<18) 6-MONTHS POST HOSPITAL DISCHARGE. WE IDENTIFIED SIGNIFICANT ELEVATIONS IN PLASMA BIOMARKERS OF NEURODEGENERATION/AD INCLUDING TOTAL TAU, P-TAU-181, UCH-L1, NEUROFILAMENT LIGHT CHAIN (NFL) AND GFAP IN HOSPITALIZED COVID-19 PATIENTS WHO DEVELOPED ENCEPHALOPATHY COMPARED TO THOSE WHO DID NOT. THESE BIOMARKERS SIGNIFICANTLY CORRELATED WITH IL-6, CRP, FERRITIN AND D-DIMER MEASURES OF INFLAMMATION. WE HYPOTHESIZE THAT OLDER SUBJECTS WITH COVID-19, IN PARTICULAR THOSE WITH NEW POST-COVID SUBJECTIVE OR OBJECTIVE COGNITIVE ABNORMALITIES, WILL HAVE INCREASED PLASMA AND RADIOGRAPHIC AD/ADRD BIOMARKERS, AND A GREATER LIKELIHOOD OF ABNORMAL COGNITIVE TESTING AND PROGRESSION TO ALZHEIMER’S DISEASE OR RELATED DEMENTIAS OVER TIME. WE WILL ENROLL 3 GROUPS OF PATIENTS AGED =60 YEARS INCLUDING: 1) SARS-COV-2 POSITIVE SUBJECTS WHO HAVE A NEW SUBJECTIVE OR OBJECTIVE COGNITIVE SYMPTOMS =6 MONTH FROM INDEX SARS-COV-2 INFECTION (COVID+COG+) 2) SARS-COV-2 POSITIVE SUBJECTS WITHOUT SUBJECTIVE OR OBJECTIVE COGNITIVE SYMPTOMS =6 MONTH FROM INFECTION (COVID+COG-); AND 3) SARS-COV-2 NEGATIVE, NEUROLOGICALLY/COGNITIVELY NORMAL SUBJECTS, ENROLLED IN THE NYU ADRC CLINICAL CORE (CONTROLS). WE WILL EXCLUDE INDIVIDUALS WITH A HISTORY OF MCI OR AD/ADRD PRIOR TO SARS-COV-2 INFECTION. OUR PRIMARY OUTCOME WILL BE THE DIFFERENCES IN TRAJECTORIES OF GLOBAL COGNITION/FUNCTION (CLINICAL DEMENTIA RATING SCALE SUM OF BOXES [CDR-SB]) OVER THE 5-YEAR STUDY ACROSS THE 3 GROUPS. SECONDARY OUTCOMES WILL INCLUDE: DIFFERENCES IN PLASMA AND RADIOGRAPHIC AD/ADRD BIOMARKERS OVER TIME COMPARED ACROSS THE 3 GROUPS. AIM 1: CHARACTERIZE AND COMPARE COGNITIVE AND NEUROPSYCHOLOGICAL ABNORMALITIES AT ENROLLMENT AND OVER TIME (EVERY 12 MONTHS), AMONG: COVID+COG+, COVID+COG- AND CONTROLS USING THE CDR-SB, AND UNIFORM DATA SET VERSION 3. AIM 2: CHARACTERIZE AND COMPARE PLASMA AD/ADRD-RELATED BIOMARKERS OF NEURODEGENERATION, INFLAMMATION AND BBB DYSFUNCTION AT ENROLLMENT AND OVER TIME (EVERY 12 MONTHS), AMONG COVID+COG+, COVID+COG- AND CONTROLS. AIM 3: CHARACTERIZE AND COMPARE AD/ADRD NEUROIMAGING BIOMARKERS IN COVID+COG+, COVID+COG- AND CONTROLS AT ENROLLMENT AND OVER TIME (EVERY 18 MONTHS) USING 3T MRI. COLLECTIVELY, THESE STUDIES WILL ELUCIDATE PREDISPOSING RISK FACTORS AND BIOMARKERS FOR COVID-RELATED COGNITIVE ABNORMALITIES, PROVIDE MECHANISTIC INSIGHTS INTO UNDERLYING PATHOGENESIS, AND PROVIDE DATA ON LONG-TERM OUTCOMES, INCLUDING THE DEVELOPMENT OF AD/ADRD- RELATED DISORDERS.

NEW YORK UNIVERSITY, CITY UNIVERSITY OF NEW YORK HEALTH PROMOTION & PREVENTION RE

PERSON-CENTERED QUALITY MEASUREMENT AND MANAGEMENT IN A SYSTEM FOR ADDICTIONS TREATMENT IN NEW YORK STATE - PROJECT SUMMARY IN 2021, THE NUMBER OF DRUG OVERDOSES IN NEW YORK CONTINUED TO RISE, WITH 4,946 DEATHS INVOLVING OPIOIDS. SYNTHETIC OPIOIDS ARE DRIVING THE RISE AS THESE ARE MIXED WITH OTHER SUBSTANCES TAKEN BY PEOPLE WHO USE DRUGS (PWUD). ALARMINGLY, THE RATES OF OVERDOSE DEATHS ARE RISING FASTER FOR BLACK AND LATINX INDIVIDUALS, EXACERBATING HEALTH INEQUITIES. THE NEW YORK STATE AGENCY THAT REGULATES ADDICTIONS TREATMENT—THE OFFICE OF ADDICTION SERVICES AND SUPPORTS (OASAS)—OVERSEES A SYSTEM THAT ANNUALLY SERVES 350,000 INDIVIDUALS WITH SUBSTANCE USE DISORDERS (SUD). WITHIN THE SYSTEM, OUTPATIENT CLINICS PROVIDE THE MAJORITY OF TREATMENT SERVICES FOR INDIVIDUALS WITH OPIOID USE DISORDERS (OUD). IN RESPONSE TO THE CONTINUING OPIOID CRISIS, OASAS IS CALLING FOR NEW APPROACHES THAT EMBRACE PERSON-CENTERED CARE, EVIDENCE-BASED PRACTICES, EQUITABLE TREATMENT, AND HARM REDUCTION PRINCIPLES. OASAS ENVISIONS A REVISED TREATMENT SYSTEM THAT BETTER RETAINS CLIENTS IN TREATMENT, MITIGATES ADVERSE HEALTHCARE EVENTS, AND REDUCES DEATHS. TO DRIVE CHANGE, OASAS WILL INVEST IN A QUALITY MEASUREMENT AND MANAGEMENT (QM2) STRATEGY THAT PROVIDES PERFORMANCE FEEDBACK TO ACTIVATE LEADERSHIP AND STAFF OF CLINICS TO IMPROVE PRACTICE AS WELL AS PUBLICIZES QUALITY MEASURES TO ENSURE PUBLIC ACCOUNTABILITY. USING THE DONABEDIAN FRAMEWORK AS A GUIDE, THE OASAS QM2 STRATEGY WILL INCLUDE A SUITE OF STRUCTURAL (E.G., CLIENT/COUNSELOR RATIOS), PROCESS (E.G., USE OF MEDICATIONS FOR OUD), AND OUTCOME (E.G., HOSPITALIZATION FOR DETOXIFICATION) QUALITY MEASURES. IN SUPPORT OF THE STRATEGY, OASAS WILL ALSO PROVIDE FUNDING TO ENSURE ALL CLINICS HAVE ELECTRONIC HEALTH RECORDS (EHR) THAT HAVE CAPACITY TO CAPTURE AND REPORT ON QUALITY MEASURES. THE OASAS STRATEGY WILL ADDRESS COMMON BARRIERS TO QM2 EFFORTS, INCLUDING: INADEQUATE TECHNOLOGICAL CAPACITY AT CLINICS, DEARTH OF VALIDATED QUALITY MEASURES FOR SUD TREATMENT, LIMITED DATA LITERACY IN THE WORKFORCE, INSUFFICIENT EXPERTISE IN CHANGE MANAGEMENT AMONG STAFF, AND CLINIC LEADERSHIP RESISTANCE DUE TO CONCERNS ABOUT FAIRNESS IN ACCOUNTING FOR THE CLINICAL COMPLEXITY OF THEIR CLIENTS. IN ADDITION, OASAS RECOGNIZES THAT GATHERING DATA DIRECTLY FROM PATIENTS IS ESSENTIAL TO ASSESSING WHETHER THEIR GOALS AND NEEDS ARE ADDRESSED IN A PERSON-CENTERED SYSTEM OF CARE. OASAS WILL WORK WITH ACADEMIC PARTNERS TO DEVELOP MEASURES AND PROVIDE SUPPORT TO CLINICS TO ADDRESS THESE BARRIERS. THIS QM2 RESEARCH CENTER (QM2-RC) PROPOSAL COMES FROM AN ACADEMIC-GOVERNMENT PARTNERSHIP THAT HAS A LONGSTANDING HISTORY OF COLLABORATING ON STUDIES TO IMPROVE TREATMENT FOR SUD. THE BROAD AIM IS TO BUILD THEN TEST A SCIENCE-BASED QM2 STRATEGY FOR PERSON-CENTERED TREATMENT. THE PROJECT WILL LEVERAGE OASAS'S INVESTMENT IN ITS NEW QM2 STRATEGY AND POLICY LEADERSHIP. THE ACADEMIC PARTNERS WILL OFFER EXPERTISE IN STATISTICAL METHODS FOR MEASUREMENT VALIDATION, RISK ADJUSTMENT, AND CAUSAL INFERENCE THAT WILL ADDRESS SOME OBSTACLES TO QM2 AS WELL AS BUILD THE EVIDENCE BASE FOR THE BENEFITS OF THE STRATEGY. THE TEAM WILL ALSO ASSESS HOW CLINICS AND OTHER STAKEHOLDERS—E.G., PATIENTS, PAYERS—INCORPORATE THE QM2 STRATEGY INTO PRACTICE IMPROVEMENT, CONTRACT NEGOTIATIONS, AND CHOOSING CLINICS.

EXTRACELLULAR REGULATION OF LIPOPROTEIN LIPASE ACTIVITY

ACCELERATOR STRATEGIES FOR STATES TO IMPROVE SYSTEM TRANSFORMATIONS AFFECTING CHILDREN, YOUTH AND FAMILIES

CLINICAL AND TRANSLATIONAL SCIENCE AWARD

RESTORING ANIMAL RESEARCH RESOURCES LOST DUE TO SUPER STORM SANDY

NON-CODING RNA REGULATION OF CHOLESTEROL HOMEOSTASIS AND ATHEROSCLEROSIS

GENETIC CONTROL OF CIRCUIT ASSEMBLY IN THE VERTEBRATE SPINAL CORD

SLOW WAVE SLEEP (SWS) AND THE EFFECT OF AFRICAN ANCESTRY ON AMYLOID BURDEN, A LONGITUDINAL STUDY

TRANSLATIONAL CENTER OF MOLECULAR PROFILING IN PRECLINICAL AND ESTABLISHED LUPUS (COMPEL)

ONCOGENIC RAS-INDUCED MACROPINOCYTOSIS: A NEW PARADIGM FOR METABOLIC ADAPTATION

CHARACTERIZATION OF PUPYLATION IN MYCOBACTERIUM TUBERCULOSIS

NYULH METASTASIS RESEARCH NETWORK CENTER (NYULH METNET CENTER) - OVERALL SUMMARY CONVENTIONAL VIEWS OF CANCER AS A PREDOMINANTLY GENETIC DISEASE THAT PROCEEDS IN A STEP-WISE, LINEAR MANNER, HAVE CEDED TO AN UNDERSTANDING THAT TUMOR PROGRESSION INVOLVES A MULTIFACETED SET OF TUMOR CELL-INTRINSIC AND MICRO-ENVIRONMENTAL ADAPTATIONS THAT CO-EVOLVE DYNAMICALLY AND NON-LINEARLY. HOWEVER, MUCH REMAINS TO BE DISCOVERED ABOUT HOW DIFFERENT CELL POPULATIONS IN THE LOCAL ENVIRONMENT DRIVE METASTATIC BEHAVIOR AT DIFFERENT STAGES OF TUMOR PROGRESSION. PRIMARY MELANOMAS THAT ARE ONLY MILLIMETERS THICK CAN DISSEMINATE TO LYMPH NODES AND DISTANT ORGANS. THIS CLINICAL FEATURE SUGGESTS THAT EGRESS OF TUMOR CELLS FROM A PRIMARY SITE OCCURS EARLY IN MELANOMA DEVELOPMENT MAKING MELANOMA AN EXCEPTIONAL MODEL TO STUDY THESE DYNAMIC ADAPTATIONS DURING THE EARLIEST STAGES OF TUMOR PROGRESSION. OUR CENTRAL HYPOTHESIS IS THAT MELANOMA METASTASIS IS DRIVEN BY A COMBINATION OF TUMOR CELL–INTRINSIC FEATURES AND INTERACTIONS WITH MICRO-ENVIRONMENTAL COMPARTMENTS THAT GOVERN EARLY DISSEMINATION AND IMMUNE EVASION IN THE REGIONAL DRAINING LYMPH NODES. TO TEST THIS HYPOTHESIS, WE PROPOSE THREE INTER-RELATED PROJECTS, SUPPORTED BY THREE CORES THAT WILL COLLECTIVELY BUILD AN IN- DEPTH TRANSCRIPTIONAL AND CELLULAR MAP OF CRITICAL COMPARTMENTS IN THE TUMOR MICROENVIRONMENT DURING EARLY MELANOMA DISSEMINATION, IN BOTH MOUSE MODELS AND PATIENT BIOSPECIMENS. SUCCESSFUL COMPLETION OF THESE PROJECTS WILL IDENTIFY GENES AND TRANSCRIPTIONAL PROGRAMS WITHIN THOSE COMPARTMENTS THAT DRIVE AND MAINTAIN TUMORIGENIC ADAPTATIONS AND ULTIMATELY METASTATIC DISSEMINATION. OUR AIMS ARE TO: 1. MAP THE CELLULAR AND MOLECULAR EVOLUTION OF PRIMARY MELANOMAS AND THEIR LOCAL AND REGIONAL MICROENVIRONMENTS TO IDENTIFY CRITICAL ‘SWITCHES’ THAT DRIVE NON-LINEAR TUMOR PROGRESSION; 2. MECHANISTICALLY DISSECT THE EMERGENCE AND FUNCTIONAL RELEVANCE OF TRANSCRIPTIONALLY DEFINED CELL STATE HETEROGENEITY OF MALIGNANT AND NON-MALIGNANT CELL POPULATIONS; 3. IDENTIFY NOVEL THERAPEUTIC VULNERABILITIES TO INTERCEPT EARLY DISSEMINATION, MOBILIZE SYSTEMIC IMMUNE SURVEILLANCE, AND IMPROVE PATIENT OUTCOMES; AND 4. LEVERAGE THE INFORMATION GAINED TO DEFINE NEW BIOMARKERS OF MELANOMA METASTASIS. WE EXPECT THAT KNOWLEDGE GENERATED THROUGH OUR APPROACH MAY DEFINE NEW BIOMARKERS OF MELANOMA METASTASIS AND THERAPEUTIC STRATEGIES TO MANAGE EARLY DISEASE. OUR APPROACH CAN SERVE AS A ROADMAP TO STUDY EARLY TUMOR PROGRESSION AT AN UNPRECEDENTED LEVEL OF CELLULAR, SPATIAL AND TEMPORAL RESOLUTION. IT WILL PROVIDE A COMPREHENSIVE PICTURE OF INTERACTIONS BOTH WITHIN THE TUMOR MICROENVIRONMENT AND TUMOR DRAINING LYMPH NODES THAT INFLUENCE TUMOR CELL BEHAVIOR AND CONDITION THE HOST TO BE RECEPTIVE TO METASTATIC SPREAD. WE WILL LEVERAGE THE COMPLEMENTARY AND SYNERGISTIC EXPERTISE OF OUR RESEARCH TEAM WITH AN ESTABLISHED RECORD OF PRODUCTIVE COLLABORATION, OUR NOVEL GENETICALLY ENGINEERED MOUSE MODEL THAT RECAPITULATES EARLY PROGRESSION OF HUMAN MELANOMA, AND OUR ACCESS TO HIGH QUALITY, CLINICALLY ANNOTATED PATIENT SAMPLES FROM OVER 4,700 PATIENTS ENROLLED IN A PROSPECTIVE CLINICOPATHOLOGICAL DATABASE. THE SCOPE AND SCALABILITY OF THE KNOWLEDGE GAINED WILL SERVE OTHER SITES OF THE METASTASIS RESEARCH NETWORK.

TRANSLATIONAL CONTROL IN MEMORY AND BRAIN DISORDERS - PROJECT SUMMARY/ABSTRACT OVER THE LAST 15 YEARS, SEVERAL LABORATORIES, INCLUDING MY LABORATORY, HAVE IDENTIFIED MULTIPLE SIGNALING PATHWAYS THAT REGULATE TRANSLATION VIA THE TRANSLATION INITIATION FACTORS EIF4E AND EIF2A DURING PROTEIN SYNTHESIS-DEPENDENT FORMS OF LONG-LASTING SYNAPTIC PLASTICITY AND VARIOUS MEMORY PROCESSES IN RODENTS, INCLUDING THE CONSOLIDATION, RECONSOLIDATION, AND EXTINCTION OF AUDITORY AND CONTEXTUAL THREAT MEMORY. THESE FINDINGS HAVE GENERATED MUCH EXCITEMENT BECAUSE THEY DEMONSTRATE THE COMPLEX BIOCHEMICAL REGULATION OF TRANSLATION DURING SYNAPTIC PLASTICITY AND MEMORY. DESPITE THIS PROGRESS, A NUMBER OF CRITICAL AND UNRESOLVED QUESTIONS REGARDING THE REQUIREMENT FOR DE NOVO PROTEIN SYNTHESIS IN MEMORY CONSOLIDATION REMAIN UNANSWERED. WE PLAN TO FOCUS ON AUDITORY AND CONTEXTUAL THREAT MEMORY TO DETERMINE THE CELL TYPES IN THE AMYGDALA AND HIPPOCAMPUS, RESPECTIVELY, THAT REQUIRE EIF4E- AND EIF2A-DEPENDENT TRANSLATION FOR MEMORY CONSOLIDATION, RECONSOLIDATION, EXTINCTION, AND DISCRIMINATION. WE ALSO PLAN TO EXAMINE THE CELL TYPE-SPECIFIC REQUIREMENT FOR DE NOVO TRANSLATION IN MEMORY USING MORE COMPLEX TYPES OF BEHAVIORAL PARADIGMS, INCLUDING DYSREGULATED TRANSLATION HAS BEEN SHOWN BY A NUMBER OF LABORATORIES, INCLUDING MY LABORATORY, TO CONTRIBUTE TO SYNAPTIC DYSFUNCTION AND ABERRANT BEHAVIORS IN NEURODEGENERATIVE DISEASES SUCH AS ALZHEIMER’S DISEASE (AD) AND NEURODEVELOPMENTAL DISORDERS SUCH AS FRAGILE X SYNDROME (FXS) AND AUTISM SPECTRUM DISORDER (ASD). HOWEVER, USING MOLECULAR APPROACHES TO DISSECT CIRCUIT DYSFUNCTION IN THESE DISEASES/DISORDERS HAS BEEN LACKING. THEREFORE, WE PLAN TO EXAMINE THE ROLE OF CELL TYPE-SPECIFIC TRANSLATIONAL DYSREGULATION IN MOUSE MODELS OF AD, FXS, AND ASD. MOREOVER, WE WILL IDENTIFY THE INAPPROPRIATELY TRANSLATED MRNAS AND THEIR NEWLY SYNTHESIZED PROTEIN PRODUCTS USING TRANSLATOMIC AND DE NOVO PROTEOMIC APPROACHES THAT WE DEVELOPED TO IDENTIFY MRNAS/PROTEINS THAT ARE TRANSLATED/SYNTHESIZED IMPROPERLY IN MOUSE MODELS OF AD AND FXS. THESE QUESTIONS WILL BE ADDRESSED BY UTILIZING THE POWERFUL MULTIDISCIPLINARY COMBINATION OF NEW GROUNDBREAKING GENETICALLY-ENGINEERED MICE AND VIRUSES, ELECTROPHYSIOLOGICAL RECORDINGS, IMMUNO-CYTOCHEMISTRY, INNOVATIVE METHODS TO MEASURE DE NOVO PROTEIN SYNTHESIS IN VIVO, CELL-TYPE SPECIFIC TRANSLATIONAL PROFILING, AND DE NOVO PROTEOMICS. THE RESULTS OF THESE STUDIES WILL PROVIDE FUNDAMENTAL INSIGHTS INTO THE MOLECULAR EVENTS IN BOTH EXCITATORY AND INHIBITORY NEURONS THAT SUPPORT CONSOLIDATION, RECONSOLIDATION, AND EXTINCTION OF MEMORY. MOREOVER, THESE STUDIES HAVE THE POTENTIAL TO PROVIDE THERAPEUTIC TARGETS FOR MULTIPLE BRAIN DISORDERS THAT ARE ASSOCIATED WITH DYSREGULATED TRANSLATION.

DEVELOPMENT OF VISUAL FUNCTION

CONTROL OF SPHINGOSINE-1-PHOSPHATE DISTRIBUTION.

IDENTIFYING METABOLIC DEPENDENCIES OF PANCREATIC CANCERS

STRESS, SELF-REGULATION AND PSYCHOPATHOLOGY IN MIDDLE CHILDHOOD

GRADUATE RESEARCH FELLOWSHIP (GRFP)

ADDRESSING THE RESEARCH CAPACITY GAP IN GLOBAL CHILD AND ADOLESCENT HEALTH DISPARITIES UTILIZING IMPLEMENTATION AND DATA SCIENCES AMONG VULNERABLE POPULATIONS IN RESOURCE-LIMITED SETTINGS (ACHIEVE) - PROJECT ABSTRACT SIGNIFICANT ADVANCES IN GLOBAL HEALTH HAVE BEEN ACHIEVED IN RECENT DECADES. YET, SERIOUS DISPARITIES IN HEALTH OUTCOMES PERSIST, ESPECIALLY AMONG CHILDREN, ADOLESCENTS AND THEIR ADULT CAREGIVERS. SUB-SAHARAN AFRICA (SSA) IS ONE OF THE REGIONS DISPROPORTIONATELY BURDENED BY MULTIPLE HEALTH THREATS, INCLUDING ENDEMIC CDS; EMERGING AND RE-EMERGING INFECTIOUS DISEASES; INCREASING INCIDENCE OF NCDS, AND A SET OF EXACERBATING FACTORS THAT HAVE CONTRIBUTED TO POOR PUBLIC HEALTH AND INCREASED OVERALL DISEASE BURDEN AFFECTING CHILDREN, ADOLESCENTS AND THEIR ADULT CAREGIVERS. SIMILAR TRENDS ARE DOCUMENTED IN SEVERAL OTHER LMICS, INCLUDING COUNTRIES IN ASIA AND EASTERN EUROPE. IN LIGHT OF WIDESPREAD HEALTH INEQUITIES AND GAPS IN THE TRANSLATION AND UPTAKE OF SCIENTIFIC EVIDENCE IN REAL-WORLD SETTINGS IN LMICS, DISSEMINATION AND IMPLEMENTATION (D&I) SCIENCE CAN ADVANCE TIMELY AND CONTEXT- SPECIFIC PUBLIC HEALTH SOLUTIONS. MOREOVER, SIGNIFICANT METHODOLOGICAL ADVANCES IN DATA SCIENCE CAN CREATE NEW OPPORTUNITIES TO MORE ACCURATELY IDENTIFY AT-RISK POPULATIONS, BETTER UNDERSTAND PATTERNS AND MECHANISMS OF HEALTH BURDENS, AND ALLOW FOR MORE IN-DEPTH ANALYSIS OF IMPLEMENTATION GAPS AND DISPARITIES IN HEALTHCARE SYSTEMS AND ACROSS POPULATIONS IN LMICS. THE PROPOSED RESEARCH TRAINING PROGRAM, ENTITLED “ADDRESSING THE RESEARCH CAPACITY GAP IN GLOBAL CHILD, ADOLESCENT & FAMILY HEALTH DISPARITIES UTILIZING IMPLEMENTATION AND DATA SCIENCES AMONG VULNERABLE POPULATIONS IN RESOURCE-LIMITED SETTINGS (ACHIEVE)”, FOCUSES ON INCREASING D&I AND DATA SCIENCE CAPACITY TO ADDRESS GLOBAL HEALTH DISPARITIES AFFECTING CHILDREN, ADOLESCENTS AND THEIR ADULT CAREGIVERS. THE PROGRAM ADDRESSES THE FOLLOWING SPECIFIC AIMS: AIM 1: TO PROVIDE A RESEARCH TRAINING PROGRAM TO FIVE COHORTS (~50 TRAINEES) OF HEALTH CARE PROFESSIONALS AND POST-DOCTORAL TRAINEES FROM THE U.S., AND POST-PROFESSIONAL DEGREE GRADUATES FROM SSA THAT EQUIPS TRAINEES WITH D&I AND DATA SCIENCE RESEARCH SKILLS AND KNOWLEDGE THROUGH EXPERIENTIAL LEARNING, MENTORING, “HANDS-ON” IMMERSION IN GLOBAL HEALTH IMPLEMENTATION AND DATA SCIENCE RESEARCH AND METHODOLOGIES, INDIVIDUALIZED CONSULTATION, GOAL SETTING AND MONITORING AND WEB- BASED SUPPORT ACROSS TIME; AIM 2: BRING TOGETHER AN INTERPROFESSIONAL NETWORK OF COMMITTED MENTORS FROM THE GLOBAL NORTH AND THE GLOBAL SOUTH TO PROMOTE EQUITABLE BI-DIRECTIONAL LEARNING AND COLLABORATION AND ENSURE QUALITY TRAINING FOR PROMISING NEW INVESTIGATORS COMMITTED TO APPLYING D&I AND DATA SCIENCE RESEARCH METHODS TO ADDRESS HEALTH DISPARITIES IMPACTING CHILDREN, ADOLESCENTS, AND THEIR FAMILIES IN LOW-RESOURCE SETTINGS; AIM 3: TO EXAMINE THE SHORT-TERM AND LONGITUDINAL OUTCOMES OF THE ACHIEVE TRAINING PROGRAM; AND AIM 4. DELINEATE KEY FACTORS THAT UNDERLIE SUCCESSFUL MENTORSHIP AND TRAINING OF NEW INVESTIGATORS– WITH POTENTIAL IMPLICATIONS FOR NEW INVESTIGATORS WHO ARE FOCUSED ON D&I AND DATA SCIENCE RESEARCH THAT SEEK TO ADDRESS HEALTH DISPARITIES IMPACTING CHILDREN, ADOLESCENTS, AND THEIR ADULT CAREGIVERS. THE FOUR U.S. UNIVERSITIES HAVE EACH COMMITTED MATCHING FUNDS TOTALING $600,000 TO SUPPORT THE ACHIEVE PROGRAM.

PATTERNING THE RETINA FOR COLOR VISION

QUALITY CONTROL MECHANISMS AGAINST MISFOLDED RHODOPSINS IN DROSOPHILA.

LEVERAGING BIOMARKERS FOR PERSONALIZED TREATMENT OF ALCOHOL USE DISORDER COMORBID WITH PTSD

EVALUATION OF PSILOCYBIN AS AN ADJUNCTIVE TREATMENT FOR OPIOID USE DISORDER IN METHADONE-MAINTAINED PATIENTS WHO CONTINUE TO USE ILLICIT OPIOIDS - PROJECT SUMMARY BACKGROUND: THERE IS AN URGENT NEED FOR NEW MEDICATIONS FOR OUD THAT CAN IMPROVE TREATMENT OUTCOMES WHEN USED ALONE OR IN COMBINATION WITH EXISTING TREATMENTS. EARLY STAGE TRIALS OF PSILOCYBIN FOR THE TREATMENT OF SUBSTANCE USE DISORDERS HAVE CONSISTENTLY SHOWN ROBUST EFFECTS ON TARGET DRUG USE AND UNDERLYING NEUROPSYCHOPATHOLOGY. DESPITE THESE PROMISING FINDINGS, THERE ARE NO PUBLISHED DATA ON THE CLINICAL EFFECTS OF PSILOCYBIN IN OUD, EITHER ALONE OR IN COMBINATION WITH EMPIRICALLY SUPPORTED TREATMENT. OBJECTIVE: WE PROPOSE TO USE THE UG3/UH3 MECHANISM TO JUMP-START RESEARCH ON PSILOCYBIN TO TREAT OUD. THE STUDY WILL USE AN INNOVATIVE “SEAMLESS” ADAPTIVE DESIGN AND AN EQUALLY INNOVATIVE TREATMENT MODEL TO TEST THE EFFICACY OF PSILOCYBIN IN OUD PATIENTS WHO CONTINUE TO USE NON-PRESCRIBED OPIOIDS DESPITE ADHERENCE TO METHADONE TREATMENT. METHOD: WE WILL RECRUIT 240 PARTICIPANTS (90 IN THE UG3 PHASE, 150 IN THE UH3 PHASE) FROM FOUR OPIOID TREATMENT PROGRAMS (OTPS) SERVING PREDOMINANTLY MINORITIZED AND MARGINALIZED COMMUNITIES IN NEW YORK AND NEW MEXICO. PSILOCYBIN TREATMENT—IMPLEMENTED AS AN ADJUNCT TO ONGOING OTP TREATMENT—WILL BE PROVIDED BY A CLINICIAN FROM AN ACADEMIC RESEARCH CENTER WHO HAS TRAINING IN PSYCHEDELIC TREATMENT, WORKING WITH AN OTP STAFF MEMBER WHO HAS A CLINICAL RELATIONSHIP WITH THE PATIENT. PARTICIPANTS WILL CONTINUE METHADONE TREATMENT AND WILL RECEIVE A SINGLE DOSE OF INVESTIGATIONAL PRODUCT (IP) DURING AN ALL-DAY IP ADMINISTRATION SESSION. WEEKLY URINE DRUG SCREENS AND CONTINUOUS SELF-REPORT OF OPIOID AND OTHER DRUG USE WILL BE COLLECTED FOR 24 WEEKS AFTER IP ADMINISTRATION, ALONG WITH MEASURES PROBING OUD-RELATED NEUROPSYCHOPATHOLOGY AND FUNCTIONAL OUTCOMES. IN THE UG3 PHASE, PARTICIPANTS WILL BE RANDOMLY ASSIGNED TO ONE OF THREE GROUPS: HIGH DOSE PSILOCYBIN, MEDIUM DOSE PSILOCYBIN, AND LOW-DOSE PSILOCYBIN CONTROL. IN ORDER FOR THE STUDY TO CONTINUE TO THE UH3 PHASE, THE UG3 PHASE MUST DEMONSTRATE SUCCESSFUL COMPLETION OPERATIONAL MILESTONES, AND AN INTERIM ANALYSIS MUST DEMONSTRATE THAT PRE-SPECIFIED “GO” CRITERIA FOR SAFETY AND EFFICACY HAVE BEEN MET. USING A PRIORI DECISION RULES, THE INTERIM ANALYSIS WILL ALSO DETERMINE WHICH OF THE ACTIVE TREATMENT GROUPS (HIGH-DOSE, MEDIUM-DOSE, OR BOTH) WILL BE RETAINED OF THE UH3 PHASE OF THE TRIAL. SIGNIFICANCE: THIS RIGOROUS, WELL-POWERED EFFICACY TRIAL WILL RAPIDLY AND EFFICIENTLY ADVANCE UNDERSTANDING OF THE POTENTIAL VALUE OF PSILOCYBIN IN THE TREATMENT OF OUD. IF THE TRIAL FINDS A ROBUST EFFICACY SIGNAL, THE DATA WILL PROVIDE STRONG EVIDENCE AND A PRACTICAL TREATMENT MODEL FOR A FULL-SCALE DRUG DEVELOPMENT PROGRAM TO ACHIEVE AN FDA INDICATION FOR PSILOCYBIN AS A TREATMENT FOR OUD.

DENDRITIC PHYSIOLOGY AND CALCIUM SIGNALING IN PYRAMIDAL NEURONS OF THE PREFRONTAL

NYU LUNG CANCER BIOMARKER CENTER

MULTI-ETHNIC TRANSLATIONAL RESEARCH OPTIMIZATION (METRO) LUPUS CONSORTIUM

PLAY & LEARNING ACROSS A YEAR (PLAY)

EFFECTIVENESS AND IMPROVEMENT OF RURAL, SCHOOL-BASED, CARIES PREVENTION PROGRAMS

1/2 PULMONARY EMBOLISM: THROMBUS REMOVAL WITH CATHETER-DIRECTED THERAPY (PE-TRACT TRIAL) - PROJECT SUMMARY THE OPTIMAL MANAGEMENT OF PATIENTS WITH SUBMASSIVE PULMONARY EMBOLISM (PE), WHO HAVE RIGHT HEART DYSFUNCTION BUT A NORMAL BLOOD PRESSURE, IS UNCERTAIN. IN ADDITION TO BEING AT RISK FOR POOR SHORT-TERM OUTCOMES, THESE PATIENTS SUFFER FROM REDUCED FUNCTIONAL CAPACITY AND A LOWER QUALITY OF LIFE OVER THE LONG-TERM. WHILE SYSTEMIC THROMBOLYSIS REDUCES CLINICAL DETERIORATION FROM PE, THIS BENEFIT IS OFFSET BY SUBSTANTIAL INCREASES IN MAJOR AND INTRACRANIAL BLEEDING. CATHETER-DIRECTED THERAPY (CDT), WHICH DISSOLVES PULMONARY ARTERY THROMBUS WITH A MUCH LOWER DOSE OF THROMBOLYTIC DRUG, APPEARS TO BE AS EFFECTIVE AS SYSTEMIC THROMBOLYTIC THERAPY WITHOUT SUBSTANTIALLY INCREASING BLEEDING. CONSEQUENTLY, CDT IS OFTEN USED IN THE U.S. TO TREAT SUBMASSIVE PE. HOWEVER, CDT HAS RISK AND IS COSTLY, AND IT IS NOT KNOWN IF IT IMPROVES CARDIOPULMONARY HEATH, PARTICULARLY OVER THE LONG-TERM. WE THEREFORE PLAN TO DO AN OPEN-LABEL, ASSESSOR-BLINDED, RANDOMIZED TRIAL, THE PULMONARY EMBOLISM: THROMBUS REMOVAL WITH CATHETER-DIRECTED THERAPY (PE-TRACT) STUDY, TO COMPARE CDT WITH NO-CDT IN 500 PATIENTS WITH SUBMASSIVE PE. WE WILL USE AN "ADAPTIVE SAMPLE SIZE" WHICH COULD RESULT IN ENROLLMENT BEING STOPPED FOR SUPERIOR EFFICACY OR FOR FUTILITY AT AN INTERIM ANALYSIS. THERE WILL BE TWO PRIMARY EFFICACY OUTCOMES; PEAK OXYGEN CONSUMPTION AT 3 MONTHS (SHORT-TERM) AND NYHA CLASS AT 12 MONTHS (LONG-TERM). THESE WILL BE ANALYZED SEQUENTIALLY USING A "GATEKEEPING" APPROACH; FOR NYHA CLASS TO BE COMPARED, PEAK OXYGEN CONSUMPTION MUST FIRST BE SHOWN TO BE INCREASED BY CDT (P<0.05). THE PRIMARY SAFETY OUTCOME WILL BE MAJOR BLEEDING WITHIN 30 DAYS OF RANDOMIZATION. SECONDARY OUTCOMES INCLUDE GENERIC QUALITY OF LIFE (QOL) (SF- 36), 6-MINUTE WALK DISTANCE, CLINICAL DETERIORATION FROM PE, AND COST-EFFECTIVENESS. EXPLORATORY ANALYSES WILL ASSESS: DISEASE-SPECIFIC QOL, OTHER CARDIOPULMONARY EXERCISE TEST PARAMETERS, RECURRENT VENOUS THROMBOEMBOLISM AND COMPLICATIONS OF THE CDT PROCEDURE. PREDICTORS OF THERAPEUTIC RESPONSE WILL ALSO BE SOUGHT. THE PE-TRACT STUDY WILL CHANGE CLINICAL PRACTICE: IF CDT IS EFFECTIVE AND SAFE, IT WILL BECOME PART OF STANDARD THERAPY FOR PATIENTS WITH SUBMASSIVE PE; IF NOT, A RISKY AND COSTLY THERAPY WILL BE AVOIDED. HENCE, EITHER STUDY OUTCOME WILL IMPROVE PUBLIC HEALTH AND ADVANCE THE NHLBI’S MISSION.

EXCLUSION AND COORDINATION OF DROSOPHILA RHODOPSIN GENE

EMOTIONS MATTER:CLASSROOM-BASED INTEGRATED INTERVENTION

LUPUS OMICS CUTANEOUS KIDNEY INVESTIGATIVE TEAM (LOCKIT) - AS THE PACE OF DISCOVERY IN THE BIOLOGY, GENETICS, AND ENVIRONMENTAL REGULATION OF SLE ACCELERATES, THE SPEED AND EFFICIENCY OF TRANSLATIONAL APPLICATION ASSUMES EVEN GREATER IMPORTANCE. THERE IS NOW UNPRECEDENTED OPPORTUNITY TO HARNESS TECHNOLOGICAL ADVANCES TO DE-AND RECONSTRUCT THE ENORMITY OF PHENOTYPIC AND IMMUNOLOGIC HETEROGENEITY IN THIS PROTOTYPIC AUTOIMMUNE DISEASE. BUILDING ON OUR CLINICAL INFRASTRUCTURE AND TECHNICAL PROTOCOLS THAT YIELDED HIGH-QUALITY TISSUE, URINE AND PERIPHERAL CELLS FOR TRANSCRIPTOMIC AND PROTEOMIC ANALYSES IN AMP1, AN EXPANDED TEAM OF MULTI-DISCIPLINARY INVESTIGATORS TOGETHER FORM THE LUPUS OMICS CUTANEOUS KIDNEY INVESTIGATION TEAM (LOCKIT) IN RESPONSE TO THE FOA: ACCELERATING MEDICINE PARTNERSHIP AUTOIMMUNE AND IMMUNE-MEDIATED DISEASES (AMP AIM) PROGRAM. COLLECTIVE TEAM DISCUSSIONS ALIGNED THE MOST SIGNIFICANT SCIENTIFIC OPPORTUNITIES WITH CLINICAL NEEDS TO FOCUS ON THE KIDNEY AND SKIN, EACH WITH ITS OWN CHALLENGING HETEROGENEITY. UNDERSTANDING THE MOLECULAR UNDERPINS OF BOTH VERY EARLY KIDNEY DISEASE (WITH COMPARISONS TO DATA ON ESTABLISHED/RELAPSED DISEASE GENERATED IN AMP1) AND TREATMENT INADEQUACIES OVERALL WERE CONSIDERED HIGH PRIORITY GOALS IN THE FIELD, AS WERE DIFFERENTIATING ACUTE FROM CHRONIC CUTANEOUS DISEASE AND MONITORING DIFFERENCES IN TREATMENT RESPONSES IN THESE SKIN DISEASE SUBSETS. AVAILABILITY OF TISSUES TO OTHER TEAMS WILL BE COMPLEMENTARY AS BIOLOGY IS COMPARED ACROSS DISEASES. REPLICATING SUCCESSES OF AMP1, LOCKIT WILL BE LED BY THE CO-CHAIRS OF AMP1 SLE CLINICAL WORKING GROUP, JILL BUYON, NYU SCHOOL OF MEDICINE AND MICHELLE PETRI, JOHNS HOPKINS UNIVERSITY. THEY ARE JOINED BY NEPHROLOGIST BRAD ROVIN, OHIO STATE UNIVERSITY, AND DERMATOLOGIST VICTORIA WERTH, UNIVERSITY OF PENNSYLVANIA, EACH RECOGNIZED FOR TRANSLATIONAL CONTRIBUTIONS TO SLE. TO ACCOMPLISH OUR DIRECTIVES AND ASSURE SUFFICIENT REPRESENTATION OF UNDERREPRESENTED MINORITIES AMONG PATIENTS, INCLUDED ARE THREE HIGH-RECRUITING AMP1 SITES LED BY ANNA BRODER, ALBERT EINSTEIN COLLEGE OF MEDICINE; MARIA DALL’ERA, UNIVERSITY OF CALIFORNIA SAN FRANCISCO; AND JENNIFER ANOLIK, UNIVERSITY OF ROCHESTER (CO-CHAIR OF AMP1 AND PI OF RA SITE, ADDING B CELL EXPERTISE). TWO NEW SITES, LED BY KAREN COSTENBADER, BRIGHAM AND WOMEN’S HOSPITAL, AND BEN CHONG, UNIVERSITY OF TEXAS, SOUTHWESTERN, BRING EXPERTISE IN PATIENT OUTCOMES AND CUTANEOUS LUPUS, RESPECTIVELY. ALL COLLABORATE AND PUBLISH TOGETHER WITH COHORTS COLLECTIVELY TOTALING 5,541 PATIENTS CONSENTING TO REGISTRIES, AND ARCHIVED SPECIMENS INCLUDING 98,980 LONGITUDINAL BLOOD DERIVATIVES, AND 3,311 KIDNEY AND 715 SKIN BIOPSIES. TO UNIFORMLY ANCHOR DISCOVERIES, AS IN AMP1, JEFF HODGIN, UNIVERSITY OF MICHIGAN WILL LEAD A DIGITAL IMAGING REPOSITORY. LOCKIT IS POISED TO APPLY STATE-OF-THE-ART TECHNOLOGIES AND NEXT GENERATION ANALYTICS PROVIDED BY SCIENTIFIC PARTNERSHIP WITH AMP AIM CORES TO INTERROGATE TISSUES AND BIOLOGIC FLUIDS FROM INFORMATIVE POPULATIONS. ALTHOUGH FOCUSING ON THE KIDNEY AND SKIN, OUR COHORTS INCLUDE ALL SLE MANIFESTATIONS, PROVIDING AGILITY TO ADDRESS OTHER ORGANS AS AMP AIM EVOLVES. LOCKIT COMMITS TO HARMONIZE AND OPTIMIZE ALL ASPECTS OF THE DATA PIPELINE, FROM COLLECTION TO ANALYSIS, INTERPRETATION AND DISSEMINATION.

TUMOR MICROENVIRONMENT CROSSTALK DRIVES EARLY LESIONS IN PANCREATIC CANCER - OVERALL - ABSTRACT PANCREATIC DUCTAL ADENOCARCINOMA (PDAC) IS THE 3RD MOST COMMON CAUSE OF CANCER-RELATED MORTALITY IN THE UNITED STATES, WITH THE OVERHWHELMING MAJORITY OF PATIENTS PRESENTING ADVANCED STAGE DISEASE. INVASIVE NEOPLASIA IN THE PANCREAS REPRESENTS THE CULMINATION OF A MULTISTEP PROGRESSION THAT BEGINS WITH NON-INVASIVE PRECURSOR LESIONS, WHICH REMAIN AN UNTAPPED “WINDOW OF OPPORTUNITY” FOR EARLY DETECTION AND CANCER INTERCEPTION. TWO MAJOR HISTOLOGICAL SUBTYPES OF PRECURSOR LESIONS ARE RECOGNIZED - THE MORE COMMON NON-CYSTIC PATHWAY, REPRESENTED BY PANCREATIC INTAREPITHELIAL NEOPLASIA OR PANIN LESIONS, ESTIMATED TO PRECEDE ~90% OF PDAC, AND THE CYSTIC PATHWAY, MOST COMMONLY REPRESENTED BY INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS OR IPMNS, ACCOUNTING FOR THE REMAINING 10%. WHILE MEMBERS OF THIS TEAM HAVE PLAYED A SEMINAL ROLE IN CHARACTERIZING THE HISTOLOGY AND GENETICS OF PANINS AND IPMNS, MUCH REMAINS TO BE ELUCIDATED IN TERMS OF THE MOLECULAR DEPENDENCIES THAT SUSTAIN EARLY PANCREATIC NEOPLASIA, AND HOW SIGNALING CUES FROM THESE EARLY LESIONS REPROGRAM THE “PRECURSOR MICROENVIRONMENT” (PME), INCLUDING “PRECURSOR-ASSOCIATED FIBROBLASTS” (PAFS). THE GOAL OF OUR TRI-STATE PANCREATIC ADENOCARCINOMA TBEL (TRI-PACT) CENTER - INCORPORATING UT MD ANDERSON CANCER CENTER (UTMDACC), UNIVERSITY OF MICHIGAN (UMICH) AND JOHNS HOPKINS UNIVERSITY (JHU) - IS TO CREATE A COLLABORATIVE AND INTEGRATED U54 CENTER TO CONDUCT BASIC AND TRANSLATIONAL STUDIES IN EARLY PANCREATIC NEOPLASIA. THE TRI-PACT CENTER WILL BE LED BY DR. ANIRBAN MAITRA (UTMDACC) AND CO-PI DR. MARINA PASCA DI MAGLIANO (UMICH). THE TITLE OF OUR TRI-PACT CENTER PROPOSAL IS “TUMOR MICROENVIRONMENT CROSSTALK DRIVES EARLY LESIONS IN PANCREATIC CANCER”, AND WE ARE PROPOSING THREE PROJECTS (TWO BASIC, ONE TRANSLATIONAL), EACH OF WHICH WILL BE SUPPORTED BY A MULTISCALE COMPUTATIONAL ONCOLOGY RESEARCH CORE (M-CORE) AND AN ADMINISTRATIVE CORE (AC). PROJECT 1 (BASIC) WILL STUDY THE FUNCTIONAL REQUIREMENT OF A PIVOTAL CYTOKINE, INTERLEUKIN IL-33, WHICH IS INDUCED IN THE PAF AND EPITHELIAL COMPARTMENTS OF PANINS AND IPMNS IN RESPONSE TO KRAS AND GNAS MUTATIONS, RESPECTIVELY, IN DISEASE PROGRESSION AND REPROGRAMMING OF THE PME. PROJECT 2 (BASIC) WILL STUDY A UNIQUE METABOLIC “SYNTHETIC ESSENTIALITY” CENTERED ON MITOCHONDRIAL QUALITY CONTROL CREATED IN CYSTIC PRECURSORS THAT HARBOR LOSS OF RNF43, A E3 UBIQUITIN LIGASE LOST IN ~50% OF IPMNS. NOTABLY, THE TRI-PACT INVESTIGATORS HAVE DEVELOPED GENETICALLY ENGINEERED MODELS (GEMS) OF PANCREATIC PRENEOPLASIA THAT RECAPITULATE THE COGNATE HUMAN LESIONS, AND WILL BE EXTENSIVELY LEVERAGED IN THE TWO BASIC PROJECTS, WITH CROSS-SPECIES VALIDATION IN PATIENT-DERIVED PRECLINICAL MODELS. PROJECT 3 (TRANSLATIONAL) WILL DEPLOY A UNIQUE 3D RECONSTRUCTION TOOL (CODA) PAIRED WITH MULTI-REGION SEQUENCING OF HUMAN PRECURSOR LESIONS TO MAP THE EVOLUTIONARY TRAJECTORY OF INDIVIDUAL PRECURSORS AT AN UNPRECEDENTED RESOLUTION, AND CORRELATE SUBCLONAL ARCHITECTURE WITH HIGH DIMENSIONAL ANALYSIS OF THE IMMUNE AND PAF COMPOSITION WITHIN THE PME. CUMULATIVELY, THESE PROJECTS WILL ENHANCE OUR UNDERSTANDING OF THE DRIVERS OF EARLY PANCREATIC NEOPLASIA, AND A SEEDBED FOR EARLY DETECTION APPROACHES.

NEW YORK UNIVERSITY HIV/AIDS CLINICAL TRIAL UNIT

GENETIC ANALYSIS OF HIRSCHSPRUNG DISEASE

AGING AND REJUVENATION: AN ANT MODEL TO STUDY THE REGULATION OF LONGEVITY

IMAGING NEONATAL HYPOXIC ISCHEMIC INJURY

INFECTIOUS DISEASES AND BASIC MICROBIOLOGICAL MECHANISMS

FOREGUT MICROBIOME IN DEVELOPMENT OF ESOPHAGEAL ADENOCARCINOMA

ASSEMBLY OF THE NODE OF RANVIER

MACROPHAGE AND VASCULAR SMOOTH MUSCLE CELL DIALOGUE: ROLE IN AORTIC ANEURYSM

PROTEIN DOMAIN MIMICS AS MODULATORS OF BIOMOLECULAR INTERACTIONS

APPLIED ANALYSIS AND COMPUTATIONAL MATHEMATICS

USING MOST TO OPTIMIZE AN HIV CARE CONTINUUM INTERVENTION FOR VULNERABLE POPULATIONS

MECHANISMS OF DNA MOTOR PROTEINS IN GENOME MAINTENANCE

SUBSTANCE ABUSE RESEARCH EDUCATION AND TRAINING (SARET)

A COMPARATIVE EVALUATION OF OVERDOSE PREVENTION PROGRAMS IN NEW YORK CITY AND RHODE ISLAND - ABSTRACT MORE THAN ONE MILLION PEOPLE HAVE DIED FROM ACCIDENTAL DRUG OVERDOSE IN THE UNITED STATES (US) IN THE PAST TWENTY YEARS. IN RESPONSE TO THIS UNABATING CRISIS, NEW YORK CITY IMPLEMENTED THE FIRST TWO PUBLICLY RECOGNIZED OVERDOSE PREVENTION CENTERS (OPCS) IN THE NATION IN NOVEMBER 2021. RHODE ISLAND BECAME THE FIRST STATE TO AUTHORIZE OPCS THROUGH STATE LEGISLATION AND THEY ARE EXPECTED TO OPEN IN LATE 2022. OPCS ARE COMMUNITY- BASED FACILITIES THAT PERMIT CLIENTS TO CONSUME PRE-OBTAINED CONTROLLED SUBSTANCES UNDER THE SUPERVISION OF PERSONNEL WHO ARE TRAINED TO INTERVENE IN THE EVENT OF AN OVERDOSE. STAFF AT OPCS ALSO PROVIDE SAFER DRUG CONSUMPTION EDUCATION, ACCESS TO STERILE DRUG USE SUPPLIES, OFFER HEALTH AND ANCILLARY SERVICES, AND PROVIDE REFERRALS TO OTHER TREATMENT, HEALTH, AND RECOVERY SERVICES. WHILE RESEARCH FROM OTHER COUNTRIES AND FROM AN UNSANCTIONED SITE IN THE US SUGGEST THAT OPCS PRODUCE INDIVIDUAL HEALTH AND COMMUNITY BENEFITS, NO EVALUATIONS EXIST OF SANCTIONED OPCS IN THE US. THE PROPOSED STUDY HAS EXTRAORDINARILY HIGH POLICY SIGNIFICANCE, AS IT WILL EVALUATE THE PUBLIC HEALTH, PUBLIC SAFETY, AND COMMUNITY BENEFITS—AND POTENTIAL UNINTENDED EFFECTS—OF THE FIRST SANCTIONED OPCS IN THE US. WE PROPOSE TO CONDUCT A RIGOROUS, MULTI-SITE, MULTI-COMPONENT EVALUATION OF OPCS IN NEW YORK CITY AND RHODE ISLAND IN 2023-2027. AT THE INDIVIDUAL LEVEL, WE AIM TO EVALUATE WHETHER A PROSPECTIVE COHORT OF 500 PERSONS ATTENDING OPCS EXPERIENCE LOWER RATES OF OVERDOSE, OTHER HEALTH PROBLEMS, AND EMERGENCY DEPARTMENT USE, AND A HIGHER RATE OF SUBSTANCE USE DISORDER TREATMENT INITIATION, COMPARED TO A COHORT OF 500 PERSONS WHO DO NOT ATTEND OPCS (AIM 1). AT THE COMMUNITY LEVEL, WE WILL EXAMINE WHETHER NEIGHBORHOODS SURROUNDING THE OPCS EXPERIENCE A GREATER CHANGE IN OVERDOSE, MEASURES OF DRUG-RELATED PUBLIC DISORDER, AND ACUTE ECONOMIC CONDITIONS FOLLOWING THE OPENING OF OPCS, COMPARED TO NEIGHBORHOODS UNEXPOSED TO OPCS (AIM 2). THIRD, WE AIM TO DELVE INTO THE ROLE THAT THE OPERATIONAL CONTEXT, INCLUDING NEIGHBORHOOD LOCATION, PROGRAM MODELS, AND OPERATING PROCEDURES, PLAYS IN SHAPING THE EFFECTIVENESS OF OPCS USING QUALITATIVE AND ETHNOGRAPHIC APPROACHES (AIM 3). FINALLY, WE WILL ESTIMATE ADDITIONAL COSTS AND COST SAVINGS TO THE HEALTHCARE AND CRIMINAL JUSTICE SYSTEMS ASSOCIATED WITH OPC USE, TO SUPPORT FUTURE COST-EFFECTIVENESS ANALYSES OF OPCS (AIM 4). TO ACCOMPLISH THESE AIMS, WE HAVE ASSEMBLED AN INTERNATIONALLY RENOWNED INVESTIGATIVE TEAM AND ESTABLISHED STRONG, COMMUNITY-ENGAGED RESEARCH PARTNERSHIPS WITH HARM REDUCTION ORGANIZATIONS IN NEW YORK CITY AND RHODE ISLAND. AS MORE JURISDICTIONS THROUGHOUT THE US CONSIDER OPENING OPCS, FINDINGS FROM THE PROPOSED RESEARCH WILL HAVE CRITICAL IMPLICATIONS FOR US DRUG POLICY. THE STUDY’S RESULTS WILL HAVE POWERFUL, LASTING IMPLICATIONS FOR COMMUNITIES THAT WISH TO OFFER OPCS, GENERATE CRITICAL DATA TO OPTIMIZE THEIR EFFECTIVENESS, AND PROVIDE MODELS FOR SUSTAINABILITY AND EXPANSION OF THESE INTERVENTIONS.

METABOLOMICS AND GENOMICS IN AFRICAN AMERICANS WITH CKD

DIFFERENTIAL FUNCTION AND TUMOR VULNERABILITIES REVEALED BY RAS MEMBRANE TRAFFICKING

MEDICATION USE AND ADVERSE EVENTS IN CKD

MEASURE DEVELOPMENT TO ACCELERATE THE TRANSLATION OF EVIDENCE BASED CLINICAL GUIDELINES INTO PRACTICE

APPLYING GENOMICS AND OMICS IN PIG TO HUMAN DECEDENT XENOTRANSPLANTATION - PROJECT SUMMARY – OVERALL XENOTRANSPLANTATION HAS THE POTENTIAL TO PROVIDE NEARLY UNLIMITED ORGANS FOR TRANSPLANTATION. EXTENSION OF XENOGRAFT SURVIVAL IN NONHUMAN PRIMATES (NHP) AND XENOTRANSPLANTS TO LIVING AND BRAIN-DEAD HUMANS HAVE ADVANCED THE FIELD TOWARD CLINICAL TRIALS. DESPITE THESE ADVANCES, XENOGRAFT SURVIVAL IN THE FEW CLINICAL CASES PERFORMED TO DATE HAVE BEEN LIMITED BY INFECTIOUS COMPLICATIONS (OF BOTH HOST AND DONOR ORIGIN) AND BY THE DEVELOPMENT OF CELLULAR AND ANTIBODY-MEDIATED REJECTION. THE DEVELOPMENT OF SENSITIVE ASSAYS TO DETECT HOST AND DONOR MICROBES, COUPLED WITH PLATFORMS TO GUIDE CLINICAL RESPONSES, AND ASSAYS TO DETECT EARLY MARKERS OF XENOGRAFT REJECTION WOULD IMPROVE OUTCOMES OF CLINICAL XENOTRANSPLANTS. AT NYU LANGONE, WE DEVELOPED AN INNOVATIVE DECEDENT MODEL TO STUDY THE RESULTS OF XENOGRAFTS TRANSPLANTED TO HUMANS AND GAIN EXPERIENCE IN A FAIL-SAFE ENVIRONMENT THAT ALSO ENABLES FREQUENT SAMPLING OF RECIPIENT BLOOD AND TISSUES. WE HAVE NOW PERFORMED THREE KIDNEY AND TWO HEART XENOTRANSPLANTS IN THE DECEDENT MODEL, ALONG WITH ONE CLINICAL KIDNEY XENOTRANSPLANT. WE HAVE PERFORMED INNOVATIVE MULTI-OMIC ANALYSES OF THE RECIPIENTS OF THESE TRANSPLANTS. OUR PRELIMINARY DATA SHOW THAT WE CAN DETECT BOTH HOST AND DONOR-DERIVED MICROBES IN DECEDENTS WITH AN UNBIASED APPROACH, AND THAT WE CAN DETECT DONOR-DERIVED CELL-FREE DNA IN RECIPIENTS AT THE TIME OF BIOPSY- PROVEN REJECTION EPISODES. WE NOW PLAN TO BIOBANK SPECIMENS FROM 21 ADDITIONAL DECEDENTS AND PERFORM MULTI-OMIC ANALYSES OF THESE RECIPIENTS. OUR PROGRAM CONSISTS OF TWO PROJECTS: PROJECT 1 DEVELOP SENSITIVE ASSAYS TO DETECT HOST- AND DONOR-DERIVED MICROBES POST-TRANSPLANT AND DEVELOP PLATFORMS THAT GUIDE EFFECTIVE CLINICAL MANAGEMENT OF INFECTIONS IN XENOGRAFT RECIPIENTS; PROJECT 2 WILL DEVELOP ASSAYS TO DETECT DONOR-DERIVED CELL-FREE DNA IN RECIPIENT BLOOD. WE WILL EXPAND THESE STUDIES BY DEVELOPING A METHYLATION ATLAS OF PIG CELLS THAT WILL ENABLE US TO IDENTIFY THE CELL OF ORIGIN OF ANY DONOR-DERIVED CELL-FREE DNA WE DETECT. THE PROJECTS WILL BE SUPPORTED BY TWO CORES: THE MOLECULAR SCIENCE CORE CONTAINS BIOBANKED SPECIMENS FROM THE 5 DECEDENTS WE HAVE PERFORMED TO DATE. WE WILL BIOBANK SPECIMENS FROM THE ADDITIONAL 21 DECEDENTS AND THEN PERFORM MULTI-OMIC ANALYSES OF THESE SAMPLES. THE CORE WILL ALSO SUPPORT DATA ANALYSIS OF THESE RESULTS. THE ADMINISTRATIVE CORE WILL PROVIDE ADMINISTRATIVE OVERSIGHT, COORDINATE INTERNAL SCIENTIFIC MEETINGS, ORGANIZE TRAVEL TO CONSORTIA MEETINGS, AND ENSURE EACH PROJECT IS MEETING THEIR DEFINED MILESTONES. COLLECTIVELY, THESE PROJECTS WILL PROVIDE A NEW LEVEL OF UNDERSTANDING OF THE MANAGEMENT OF XENOGRAFT RECIPIENTS AND THE HUMAN IMMUNE RESPONSE TO XENOGRAFTS. UPON SUCCESSFUL COMPLETION OF THE PROPOSED RESEARCH, WE EXPECT TO DEVELOP PLATFORMS THAT IMPROVE THE CLINICAL MANAGEMENT OF PATIENTS WHO ENROLL IN THE FIRST CLINICAL TRIALS OF XENOTRANSPLANTATION, WITH THE LONG-TERM GOAL OF DEVELOPING XENOTRANSPLANTATION INTO A STANDARD CLINICAL TREATMENT OPTION FOR ORGAN FAILURE.

QUANTITATIVE MRI AND 1H-MRS IN TRAUMATIC BRAIN INJURY

GENE EXPRESSION IN LONG-TERM MEMORY

CRAC CHANNEL DEFICIENCY IN IMMUNITY TO INFECTION

ESTROGEN METABOLITES, RELATED GENES AND BREAST CANCER

MUTOGRAPHS DIFFERENTIATING THE RACIAL AND TEMPORAL INCIDENCE OF MULTIPLE MYELOMA - PROJECT SUMMARY/ABSTRACT AFRICAN AMERICANS (AA) HAVE A HIGHER INCIDENCE OF MULTIPLE MYELOMA (MM) COMPARED TO EUROPEAN AMERICANS (EA) DUE TO GENETIC PREDISPOSITION, ENVIRONMENTAL EXPOSURE OR BOTH. MM IS PRECEDED BY TWO PRECURSOR PHASES, MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE (MGUS) AND SMOLDERING MYELOMA (SMM) THAT ARE ALSO INCREASED IN AA. WE HAVE SHOWN USING EUROPEAN MM SAMPLES THAT THERE IS A LONG LAG PERIOD BETWEEN THE GENETIC INITIATION OF THE DISEASE AND THE TIME AT WHICH PRECURSOR CLINICAL STAGES ARE DETECTABLE. IT IS CRITICAL TO UNDERSTAND THE GENETIC BASIS OF THESE EARLY EVOLUTIONARY STEPS IF WE ARE TO TRULY UNDERSTAND THE EXCESS RISK OF MM IN AA. DURING THE EVOLUTIONARY PROGRESSION OF MM AFTER GENETIC INITIATION, GENETIC HITS ARE ACCUMULATED PROVIDING A UNIQUE ARCHEOLOGICAL FINGERPRINT OF THE MUTATIONAL SIGNATURES OR “MUTOGRAPHS” OVER TIME. USING WHOLE GENOME SEQUENCING (WGS) ANALYZED WITH ADVANCED COMPUTER ALGORITHMS BASED ON A-PRIORI KNOWLEDGE OF THE TIMING OF ACQUIRED GENETIC VARIANTS WE HAVE BEEN ABLE TO EXTRACT MUTOGRAPHS ACTIVE AT DIFFERENT TIME POINTS. THIS ANALYSIS HAS SHOWN IN EA THAT MM IS SHAPED BY MUTATIONAL PROCESSES VARIABLY ACTIVE DURING THE EARLY, INTERMEDIATE AND LATE EVOLUTIONARY PHASES OF DISEASE. A KEY FINDING OF OUR PILOT DATA IS THE IDENTIFICATION OF A MUTOGRAPH OCCURRING AS A CONSEQUENCE OF THE IMMUNE RESPONSE IN THE GERMINAL CENTER REACTION AND THIS DIFFERS BY RACE. WE WILL ADDRESS THE HYPOTHESIS THAT A MAJOR CONTRIBUTOR TO THE OBSERVED EXCESS OF MM IN AA COMPARED TO EA IS DUE TO AN EXCESS IMMUNE RESPONSE THAT CAN BE RECOGNIZED BY A GC MUTOGRAPH THAT IS ACTIVE IN THE EARLY EVOLUTIONARY PHASES OF DISEASE. TO ACCURATELY EXTRACT EARLY MUTOGRAPHS SEQUENTIAL SAMPLES FROM THE SAME INDIVIDUAL CASES ARE NEEDED. SMM, WHICH TRANSFORMS TO MM AT A RATE OF 10% PER ANNUM, PROVIDES A SYSTEM WHERE SAMPLES CAN BE OBTAINED AT DIFFERENT TIME POINTS IN THE ABSENCE OF TREATMENT. TO ADDRESS OUR HYPOTHESIS WE WILL GENERATE MUTOGRAPHS FROM NEW WGS DATA FROM AA SMM AND COMPARE THEM TO EXISTING DATASETS OF EA WITH SMM AS WELL AS FROM A LARGE PRE-EXISTING SET OF MM FROM WHICH WE WILL INFER ANCESTRY DIRECTLY. WE WILL ALSO ESTABLISH A LONGITUDINAL COHORT STUDY OF SMM CASES AND STUDY MUTOGRAPHS OVER TIME AND COMPARE THE PROFILES BETWEEN AA AND EA. IN ADDITION TO GENETIC MUTOGRAPHS WE WILL CHARACTERIZE AND COMPARE IMMUNOLOGICAL MUTOGRAPHS OF T-CELL RESPONSE IN THE BONE MARROW IMMUNE MICROENVIRONMENT IDENTIFIED USING A FLOW-CYTOMETRIC APPROACH. TO PROVIDE A LINK TO THE EXTERNAL ENVIRONMENT WE WILL CHARACTERIZE BACTERIAL SPECIES SIGNATURES DERIVED FROM 16S RRNA SEQUENCING OF THE GUT FLORA, AND LINK FINDINGS TO THE GENETIC AND T-CELL MUTOGRAPHS. THIS STUDY WILL IDENTIFY GENOMIC, IMMUNE AND ENVIRONMENTAL SIGNATURES RESPONSIBLE FOR THE HIGHER RISK OF MM OBSERVED AMONG AAS AND WILL PROVIDE NEW INSIGHTS INTO THE IMMUNE RESPONSE IN MM PATHOGENESIS, OPENING THE WAY FOR THE GENERATION OF EFFECTIVE INTERVENTION STRATEGIES. 1

NEW YORK UNIVERSITY, INC. THE CONTRIBUTION OF NON-TARGETED EFFECTS IN HZE CANCER RISK CLEAR MECHANISTIC UNDERSTANDING OF THE BIOLOGICAL PROCESSES ELI

NEURONAL ADAPTATION AND PLASTICITY AFTER CHRONIC DISUSE

PLASMA PROPERTIES

SYNAPTIC AND CIRCUIT MECHANISMS OF LEARNED VOCAL PRODUCTION

TO INCREASE IDENTIFICATION AND SERVICES FOR DNTS IN TWO DISTRICTS IN INDIA

CONTROL OF TRANSLATION IN HERPESVIRUS INFECTED CELLS

PROTEIN MASS SPECTROMETRY CORE FACILITY FOR NEUROSCIENCE

THE PURPOSE OF THIS AGREEMENT IS TO FUND FUNDAMENTAL RESEARCH SUPPORTING THE DEFENSE ADVANCED RESEARCH PROJECTS AGENCY DARPA SECURING INFORMATION FOR ENCRYPTED VERIFICATION AND EVALUATION SIEVE PROGRAM.

MECHANISMS OF PLATELET ACTIVITY IN VASCULAR DISEASE

RECURRENT NEUAL CIRCUIT BASIS OF TIME INTEGRATION AND DECISION MAKING

ACCUMULATION OF MICRO- AND NANOPLASTIC PARTICLES IN MAMMALIAN TISSUES: A TRANSLATIONAL STUDY - ABSTRACT THE UTILIZATION AND SUBSEQUENT DISPOSAL OF PLASTICS AND PLASTIC BASED PRODUCTS CONTINUES TO RISE EXPONENTIALLY. CURRENT PERVASIVENESS OF MICRO- AND NANOPLASTIC PARTICLES (MNPS) IN THE ENVIRONMENT RESULTS IN SIGNIFICANT EXPOSURE TO HUMAN POPULATIONS VIA INHALATION AND INGESTION. MNP CONTAMINANTS HAVE BEEN DISCOVERED IN THE AIR WE BREATHE, THE FOOD WE EAT, AND IN 81% OF TAP WATER SAMPLES TESTED AROUND THE GLOBE. SAMPLES TAKEN FROM HUMAN SUBJECTS, INCLUDING OUR PRELIMINARY DATA, IDENTIFY MNP DEPOSITION IN TISSUES (E.G., LUNG, HEART, BLOOD, THROMBI, AND PLACENTA) AND EXCRETA (E.G., SEMEN, BREAST MILK, BRONCHOALVEOLAR LAVAGE FLUID, AND FECES). THESE FINDINGS INDICATE THAT NOT ONLY ARE HUMANS EXPOSED TO MNP, BUT THESE PERVASIVE PART ICLES BYPASS PROTECTIVE ANATOMICAL BARRIERS, ACCUMULATING WITHIN SYSTEMIC TISSUES. ANIMAL MODELS REPRODUCE THESE FINDINGS IN A LABORATORY ENVIRONMENT, RESULTING IN MNP ACCUMULATION IN SYSTEMIC TISSUES AND ASSOCIATIONS WITH PATHOLOGIC CHANGES. MNPS HAVE ALSO BEEN IDENTIFIED IN THE PLACENTA AND FETAL ORGANS OF RODENT MODELS AFTER PULMONARY OR GASTRIC EXPOSURE. OUR PRELIMINARY DATA SUGGEST MATERNAL TRANSFER OF MNP TO THE OFFSPRING, WITH MNP DEPOSITION REMAINING IN OFFSPRING TISSUES FOR AT LEAST 2 WEEKS AFTER BIRTH, 16 DAYS AFTER THE LAST MATERNAL EXPOSURE. DESPITE THE EXTENT OF WORLD-WIDE MNP EXPOSURE, THE QUANTIFIED CONCENTRATION OF MNP WITHIN SYSTEMIC TISSUES IS UNKNOWN. ANALYSES HAVE BEEN CONDUCTED USING MICROSCOPIC FIXED TISSUE ANALYSES OR CHEMICAL EXTRACTION- BASED TECHNIQUES. UNFORTUNATELY, THESE METHODOLOGIES CANNOT CURRENTLY BE ADEQUATELY COMPARED. CURRENTLY, THERE IS NO “GOLD STANDARD” METHODOLOGY THAT MEETS ALL REQUIREMENTS FOR IDENTIFYING MNPS IN BIOLOGICAL TISSUES. FURTHERMORE, THE ROLE OF SEX, AGE, AND ETHNICITY IN THE ACCUMULATION OF MNPS IN HUMAN TISSUES HAS NOT YET BEEN EXPLORED. THIS PROJECT WILL INVESTIGATE INTER-TISSUE MNP ACCUMULATION IN RODENT MODELS OF MNP EXPOSURE VIA INTRATRACHEAL INSTALLATION OR GAVAGE, USING OVERLAPPING STATE-OF-THE-ART DETECTION METHODOLOGIES TO QUANTIFY AND CONFIRM MNP DEPOSITION. WE WILL THEN COMPARE THESE CONCENTRATIONS TO THOSE OBTAINED FROM HUMAN AUTOPSY SAMPLES. INNOVATIVE STATISTICAL METHODS FOR INTEGRATING CALIBRATION SAMPLES WITH RESULTS FROM DIFFERENT ANALYTICAL METHODS WILL BE EMPLOYED TO CORRECT FOR MEASURE ERRORS. THESE TRANSLATIONAL STUDIES WILL PROVIDE FURTHER RATIONALE TO RELATE HUMAN AND LABORATORY MNP TRANSLOCATION AND DEPOSITION STUDIES. TO FULLY ASSESS MNP TOXICITIES, WE MUST FIRST UNDERSTAND THE MEASURED MASS DEPOSITION BASED ON KNOWN EXPOSURE DOSES. SUCCESSFUL COMPLETION OF THESE STUDIES WILL PROVIDE THE FOUNDATIONAL PHYSIOLOGICAL DOSES TO ADVISE FUT URE IN VITRO AND EX VIVO MNP TOXICOLOGICAL STUDIES.

REGULATION OF MUSCLE FATE SPECIFICATION AND CELL MIGRATION IN CARDIOGENIC LINEAGE

RESCUE OF CORTICAL INHIBITORY SYNAPSES FOLLOWING DEVELOPMENTAL HEARING LOSS

CLINICAL AND TRANSLATIONAL SCIENCE AWARD

TRAINING PROGRAM IN CARDIOVASCULAR SCIENCES

OPTIMIZING THE USE OF KETAMINE TO REDUCE CHRONIC POSTSURGICAL PAIN - CHRONIC PAIN CONTRIBUTES SIGNIFICANTLY TO THE CURRENT OPIOID EPIDEMIC. UP TO 20% OF POSTOPERATIVE PATIENTS DEVELOP CHRONIC POSTSURGICAL PAIN (CPSP). CPSP IS HIGHLY ASSOCIATED WITH CHRONIC OPIOID USE AND DEPENDENCE, AND YET ROUTINE MULTIMODAL ANALGESIA AS A COMBINATION OF ACETAMINOPHEN, NSAIDS, AND ANTI-NEUROPATHIC AGENTS IS ONLY MODERATELY EFFECTIVE IN PREVENTING CPSP. THE INCIDENCE FOR CPSP IS PARTICULARLY HIGH IN PATIENTS UNDERGOING MASTECTOMY OR BREAST CONSERVING SURGERY WITH LYMPH NODE DISSECTIONS (25-60%). THIS SPECIFIC POSTSURGICAL PAIN CONDITION IS KNOWN AS POST-MASTECTOMY PAIN SYNDROME (PMPS), AND A RECENT STUDY SHOWED THAT 1 IN 10 PATIENTS CONTINUE TO USE OPIOIDS 3 MONTHS AFTER SURGERY. WE AIM TO STUDY THE EFFECTIVENESS OF PERIOPERATIVE KETAMINE FOR THE PREVENTION OF PMPS, WITHIN THE NIH HEAL PAIN MANAGEMENT EFFECTIVENESS RESEARCH NETWORK (PAIN ERN). OUR RATIONALE IS THAT KETAMINE CAN REDUCE KEY RISKS FOR CPSP INCLUDING ACUTE PAIN SEVERITY, ANXIETY AND DEPRESSION, AND PAIN CATASTROPHIZING, AND IN DOING SO CAN PREVENT THE DEVELOPMENT OF PMPS. MECHANISTICALLY, KETAMINE IS KNOWN TO ENHANCE ENDOGENOUS CORTICAL CONTROL OF PAIN AND MOOD. THERE IS STRONG CLINICAL EVIDENCE FOR PERIOPERATIVE KETAMINE INFUSION IN REDUCING POSTSURGICAL PAIN, AND FOR A SINGLE KETAMINE BOLUS (0.3-0.5MG/KG) TO TREAT DEPRESSION AND ANXIETY ASSOCIATED WITH POSTSURGICAL PAIN. HOWEVER, STUDIES ARE URGENTLY NEEDED TO TEST THE EFFICACY OF KETAMINE IN THE PERIOPERATIVE PERIOD FOR PREVENTING CPSP, PARTICULARLY PMPS, IN A LARGE COHORT OF PATIENTS AND TO ASSESS CLINICAL VARIABLES PREDICTIVE FOR CHRONIC PAIN SEVERITY AND FOR TREATMENT EFFECTS. WE AIM TO CONDUCT A MULTI-SITE, THREE-ARM RCT TO STUDY THE EFFECTIVENESS OF KETAMINE IN REDUCING THE INCIDENCE AND SEVERITY OF PMPS. 750 PATIENTS AFTER MASTECTOMY OR BREAST CONSERVING SURGERY WITH LYMPH NODE DISSECTION WILL BE RANDOMIZED TO RECEIVE EITHER A STANDARD CONTINUOUS KETAMINE INFUSION STARTING AFTER INDUCTION (BOLUS OF 0.35MG/KG FOLLOWED BY INFUSION AT THE RATE OF 0.25MG/KG/HR) AND CONTINUED FOR 3 HOURS AFTER SURGERY, A REGIMEN OF SINGLE-BOLUS KETAMINE (0.6MG/KG) ADMINISTERED RIGHT AFTER SURGERY, OR PLACEBO (SALINE) CONTROL. TO MAINTAIN THE PRAGMATIC NATURE OF AN EFFECTIVENESS TRIAL, ALL PATIENTS WILL RECEIVE ROUTINE POSTOPERATIVE MULTIMODAL ANALGESIA. COMPATIBLE WITH RECENT NIH RECOMMENDATIONS, WE WILL ASSESS PAIN, FUNCTION AND MOOD OVER 12 MONTHS AFTER SURGERY. WE WILL USE BRIEF PAIN INVENTORY (BPI) SEVERITY SCORE AT 3 MONTHS AFTER SURGERY AS PRIMARY ENDPOINTS. SECONDARY ENDPOINTS INCLUDE PAIN INCIDENCE, BPI, SHORT- FORM MCGILL'S PAIN QUESTIONNAIRE, OPIOID USE, NIH PROMIS SCALES, HOSPITAL ANXIETY AND DEPRESSION SCALE, PAIN CATASTROPHIZING SCALE, AND BREAST CANCER PAIN QUESTIONNAIRE. WE WILL ALSO BUILD PRECISION MEDICINE MODELS TO ANALYZE CLINICAL VARIABLES ASSOCIATED WITH CPSP AND WITH SUCCESS OF KETAMINE TREATMENT. AGREEMENTS HAVE BEEN REACHED WITH 11 SITES, INCLUDING 7 CLINICAL AND TRANSLATIONAL SCIENCE AWARDS (CTSA) HUBS, NYU, COLUMBIA, EINSTEIN, BWH, WASHINGTON UNIVERSITY AT ST. LOUIS, DUKE, AND UNIV. WASHINGTON, TO CARRY OUT THIS STUDY SUCCESSFULLY.

SOAR: SMARTPHONES FOR OPIOID ADDICTION RECOVERY - PROJECT SUMMARY OVER 2 MILLION AMERICANS SUFFER FROM OPIOID USE DISORDER (OUD) AND ANOTHER 9 MILLION MISUSE OPIOIDS. TREATMENTS FOR OPIOID ADDICTION EXIST, BUT EFFECTIVENESS IS COMPROMISED WHEN SUBJECTS USE ILLICIT OPIATES DURING TREATMENT. REUSE RATES DURING TREATMENT CAN BE HIGH, AND REDUCING ILLICIT OPIATE USE DURING TREATMENT HAS THUS RECENTLY BECOME A MAJOR NIDA POLICY GOAL. ELEVATED REUSE RATES NOT ONLY COMPROMISE TREATMENT EFFECTIVENESS, BUT THIS BEHAVIOR PREDICTS, AND LIKELY DRIVES, TREATMENT DROPOUT. WITH THE SUPPORT OF A NIDA BASIC SCIENCE R01, WE DEVELOPED A SET OF EASY-TO-USE INSTRUMENTS THAT PREDICT OPIOID REUSE EVENTS WITH ABOUT TWICE THE ACCURACY OF ANY EXISTING TOOL. THE 5-MINUTE BATTERY WE DEVELOPED INDICATES THE NUMERICAL PROBABILITY THAT A PATIENT WILL REUSE ILLICIT OPIATES WITHIN THE NEXT 7-10 DAYS. IN A PILOT COHORT, WE SUCCESSFULLY MIGRATED THIS BATTERY TO A COMMERCIAL SMARTPHONE PLATFORM, AND DEMONSTRATED 100% RETENTION AND >85% COMPLIANCE (MEDIAN COMPLIANCE > 95%) OVER A USE PERIOD OF UP TO 4 MONTHS. IN A SURVEY OF OUR LARGELY HOMELESS MOUD PATIENTS WE FOUND THAT 85% ALREADY HAD SMARTPHONES AND DATA CONTRACTS APPROPRIATE FOR USING THIS PLATFORM AS A PART OF THEIR TREATMENT. IN A SURVEY OF OUD TREATMENT PHYSICIANS, WE FOUND THAT OUR SYSTEM AND THE REUSE PREDICTION IT PROVIDES, WAS BOTH HIGHLY DESIRABLE AND USABLE AS IMPLEMENTED. FINALLY, WE FOUND IN A REANALYSIS OF DATA FROM CTN-0051 THAT DYNAMIC DOSING OF THIS VERY KIND REDUCES RELAPSE RATES. OUR PRIMARY GOAL IN THIS MID-SCALE CLINICAL TRIAL IS TO TEST THE HYPOTHESIS THAT CLINICIANS WHO USE THE OUTPUT OF OUR MOBILE SYSTEM TO ADJUST BUPRENORPHINE AND METHADONE DOSING ACHIEVE LOWER OPIATE REUSE RATES THAN PHYSICIANS WHO PROVIDE CARE-AS-USUAL. OUR SECONDARY GOAL IS TO EXAMINE THE USABILITY AND DESIRABILITY OF THIS SOLUTION FOR CLINICIANS WITH AN EYE TO USABILITY AND LARGE-SCALE DEPLOYMENT. OUR THIRD AND FINAL GOAL IS TO MEASURE THE COST-EFFECTIVENESS OF THIS SOLUTION FROM MULTIPLE PERSPECTIVES. IF WE ARE SUCCESSFUL IT WILL BE POSSIBLE TO EMPLOY AN ALGORITHMIC AND MEASUREMENT-BASED APPROACH TO OUD TREATMENT WITH METHADONE AND BUPRENORPHINE WHICH REDUCES REUSE RATES AND RELAPSE RATES AMONGST OUD PATIENTS.

D18AP00007

EXTENDED-RELEASE VS. ORAL NALTREXONE ALCOHOL TREATMENT IN PRIMARY CARE

CROSSTALK AMONG ORAL & GASTROINTESTINAL SOLUBLE INNATE FACTORS, HIV, & MICROBES

ROLE OF UHRF1 IN LIVER DEVELOPMENT, REGENERATION AND CARCIOGENESIS

GENE EXPRESSION IN LONG-TERM MEMORY

MEDICAL SCIENTIST RESEARCH SERVICE AWARD

BIOFEEDBACK-ENHANCED TREATMENT FOR SPEECH SOUND DISORDER: RANDOMIZED CONTROLLED TRIAL AND DELINEATION OF SENSORIMOTOR SUBTYPES

NEURAL CIRCUITRY AND PLASTICITY FOR MATERNAL BEHAVIOR

BRIDGING THE EVIDENCE-TO-PRACTICE GAP: EVALUATING PRACTICE FACILITATION AS A STRATEGY TO ACCELERATE TRANSLATION OF A SYSTEMS-LEVEL ADHERENCE INTERVENTION INTO SAFETY NET PRACTICES

TRANSLATIONAL REGULATION OF T REGULATORY CELLS

VISUAL PATTERN REPRESENTATION IN EXTRASTRIATE CORTEX

THE ROLE OF AUTOPHAGY GENE ATG16L1 IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION - RESUBMISSION - 1

MESOSCOPIC BIOMARKERS OF NEURODEGENERATION WITH DIFFUSION MRI

PLASMA PROPERTIES (TASK III) ADVANCED TOROIDAL THEORY (TASK VII)

CORTICAL MECHANISMS IN SPEECH PERCEPTION: MEG STUDIES

MECHANISMS OF FATTY ACID UPTAKE BY CARDIAC MUSCLE

PURKINJE CELLS AND ARRHYTHMIA MECHANISMS

USING A HEALTH DISPARITY RESEARCH FRAMEWORK TO EXAMINE MECHANISMS LINKING OBSTRUCTIVE SLEEP APNEA WITH HIGHER ALZHEIMER?S DISEASE RISK IN OLDER BLACKS/AFRICAN-AMERICANS - PROJECT ABSTRACT/SUMMARY BLACKS/AFRICAN-AMERICANS (BLACKS) HAVE TWO TIMES THE RISK OF DEVELOPING ALZHEIMER’S DISEASE (AD) COMPARED TO NON-HISPANIC WHITES (WHITES), IN PART ATTRIBUTABLE TO THE HIGHER PREVALENCE OF VASCULAR RISK FACTORS. EXAMINING OTHER RISK FACTORS AND DELINEATING PATHOLOGICAL MECHANISMS ASSOCIATED WITH THIS HIGHER AD-RISK IN OLDER BLACKS IS A CRITICAL INITIAL STEP NEEDED TO OPTIMIZE PATIENT CARE PARADIGMS. OBSTRUCTIVE SLEEP APNEA (OSA) IS ONE SUCH RISK FACTOR. NOTABLY, BLACKS HAVE A HIGHER BURDEN OF OSA WITH EXCESSIVE DAYTIME SLEEPINESS (EDS), WHICH IS ASSOCIATED WITH LONGITUDINAL AMYLOID-PET UPTAKE. OSA IS ASSOCIATED WITH DECREASED NON RAPID EYE MOVEMENT (NREM) SLOW WAVE SLEEP/ACTIVITY (SWS/SWA) AND INCREASED INFLAMMATION, BOTH OF WHICH AFFECT AMYLOID AND TAU PATHOLOGY. NREM SWS/SWA AND INFLAMMATION ARE ALSO ASSOCIATED WITH CHANGES IN COGNITION IN LATE-LIFE, AND ARE MORE BURDENSOME IN BLACKS. THE CURRENT PROPOSAL WILL UTILIZE A HEALTH DISPARITIES RESEARCH FRAMEWORK RELATED TO AGING TO: (I) INVESTIGATE WITHIN AND BETWEEN RACE EFFECTS OF OSA ON AD PATHOLOGY. (II) IDENTIFY DECREASED NREM SWS/SWA AND INCREASED INFLAMMATION AS POTENTIAL INTERMEDIATE MECHANISMS LINKING OSA AND AD. (III) EXAMINE WHETHER SOCIO-STRUCTURAL DETERMINANTS OF HEALTH (SDOH) CAN HELP EXPLAIN RACIAL HETEROGENEITY IN OSA- AD OUTCOMES. OUR NEURODEGENERATION, CENTRAL HYPOTHESIS IS THAT BLACK OSA SUBJECTS WILL EXHIBIT HIGHER TAU AND GREATER AS WELL AS REDUCED NREM SWS/SWA AND INCREASED INFLAMMATION COMPARED TO WHITE OSA SUBJECTS, IN THE CONTEXT OF AMYLOID BURDEN. FURTHERMORE, WE HYPOTHESIZE SDOH (I.E., ENVIRONMENTAL, SOCIO- STRUCTURAL, AND BEHAVIORAL FACTORS) AND VASCULAR RISK WILL MEDIATE RACIAL HETEROGENEITY IN OSA-AD OUTCOMES. WE WILL TEST OUR CENTRAL HYPOTHESIS IN A SAMPLE OF 300 COMMUNITY-DWELLING COGNITIVELY NORMAL (CN) SUBJECTS; AGES 55-85 MATCHED ON RACE (2:1), AGE AND SEX, AND BALANCED BY EDUCATION, INCOME AND BMI. SUBJECTS WILL INCLUDE 150 CONTROLS (100 BLACKS & 50 WHITES), AND 150 NEWLY DIAGNOSED OSA SUBJECTS WITH EDS (100 BLACKS & 50 WHITES). THIS PROPOSAL WILL RECRUIT FROM THE COMMUNITY, 125 NEW BLACK SUBJECTS [80 OSA AND 45 CONTROLS] AND LEVERAGE EXISTING DATA AND RESOURCES IN 175 (75 BLACKS [20 OSA AND 55 CONTROLS] & 100 WHITES [50 OSA AND 50 CONTROLS]) COMMUNITY-DWELLING CN SUBJECTS WITH SIMILAR ELIGIBILITY CRITERIA, FROM NYU ALZHEIMER’S DISEASE RESEARCH CENTER AND TWO-AFFILIATED ONGOING NIH SUPPORTED R01 STUDIES (R01AG056031 AND R01AG056531). SUBJECTS WILL UNDERGO 2 NIGHTS OF AT-HOME SLEEP MONITORING FOR OSA, FOLLOWED BY 5 DAYS OF ACTIGRAPHY AND SLEEP LOGS. CLINICAL VISITS WILL INCLUDE FULL CLINICAL EVALUATION, NEUROPSYCHOLOGICAL TESTS AND CLINICAL LABS ON VISIT 1; 1 NIGHT OF NOCTURNAL POLYSOMNOGRAPHY (NPSG) RECORDING ON VISIT 2; NEUROIMAGING MEASURES OF VASCULAR BURDEN, AMYLOID (18F- FLORBETABEN) AND TAU (18F-PI2620) PET-MRI ON VISITS 3 AND 4 RESPECTIVELY, AT BASELINE AND AT 2.5 YEARS FOLLOW-UP. IMPORTANTLY, WE WILL PRIORITIZE ACQUISITION OF SDOH DATA TO ELUCIDATE DISEASE MECHANISMS TO AID FUTURE DISCOVERY OF NOVEL AD PREVENTION TARGETS E.G. TARGETING STRESS MANAGEMENT, INFLAMMATION AND SLEEP QUALITY IN OSA.

CPS: FRONTIER: SONYC: A CYBER-PHYSICAL SYSTEM FOR MONITORING, ANALYSIS AND MITIGATION OF URBAN NOISE POLLUTION

PERCEPTION AND ACTION: IDEAL OBSERVERS AND ACTORS

EFFECTIVENESS OF SMOKING-CESSATION INTERVENTIONS FOR URBAN HOSPITAL PATIENTS

NOVEL SOFTWARE TOOLS FOR RATIONAL DESIGN AND ASSESSMENT OF MR COILS

MOLECULAR GENETICS OF SENSORY MODULATION OF MOTOR PROGRAMS