Drexel University

THIS IS FUNDING FROM THE DEPARTMENT OF EDUCATION IN CONJUNCTION WITH THE CARES ACT EMERGENCY FINANCIAL AID GRANTS TO STUDENTS

THIS IS FUNDING FROM THE DEPARTMENT OF EDUCATION IN CONJUNCTION WITH THE CARES ACT EMERGENCY FINANCIAL AID GRANTS TO STUDENTS

PROMISE NEIGHBORHOODS IMPLEMENTATION GRANTS

STRUCTURE-BASED ANTAGONISM OF HIV-1 ENVELOPE FUNCTION IN CELL ENTRY

ECOG CCOP RESEARCH BASE

EARLY AUTISM RISK LONGITUDINAL INVESTIGATION (EARLI) NETWORK

COLLABORATION FOR HIERARCHICAL AND AGILE RESONANT MATERIALS (CHARM)

CATALYZING SYSTEMIC CHANGE AT DREXEL UNIVERSITY TO SUPPORT DIVERSE FACULTY IN HEALTH DISPARITIES RESEARCH - PROJECT SUMMARY IN RESPONSE TO THE NIH U54 FACULTY INSTITUTIONAL RECRUITMENT FOR SUSTAINABLE TRANSFORMATION (FIRST) PROGRAM (RFA-RM-20-022), DREXEL UNIVERSITY PROPOSES TO ESTABLISH A ROBUST, TRANSFORMATIVE AND SUSTAINABLE PROGRAM TO SUPPORT DIVERSE EARLY CAREER SCIENTISTS ENGAGED IN HEALTH DISPARITIES RESEARCH SPANNING POPULATION SCIENCE TO INTERVENTION RESEARCH. THIS PROPOSAL, A COLLABORATION ACROSS DREXEL UNIVERSITY LED BY DREXEL’S DORNSIFE SCHOOL OF PUBLIC HEALTH AND COLLEGE OF NURSING AND HEALTH PROFESSIONS, LEVERAGES OUR NATIONALLY AND INTERNATIONALLY RECOGNIZED NIH AND OTHER EXTRAMURALLY SUPPORTED RESEARCH, OUR COMMUNITY-BASED CLINICAL PRACTICES SERVING DIVERSE, UNDERSERVED COMMUNITIES, AND OUR SHARED CORE VALUES OF SOCIAL JUSTICE AND HEALTH EQUITY GUIDING OUR PEDAGOGY, RESEARCH AND HIRING PRACTICES. OUR PROPOSAL ALSO STRONGLY REFLECTS DREXEL UNIVERSITY’S UNWAVERING COMMITMENT AND NEWLY INSTITUTED STRATEGIC GOALS TO PROMOTE INCLUSIVE EXCELLENCE AND ENSURE DIVERSITY, EQUITY, RETENTION, AND PROMOTION ACROSS FOR DIVERSE FACULTY ACROSS THEIR CAREER PATHWAYS. OUR PROPOSED PROGRAM WILL CREATE A COLLABORATIVE STRUCTURE INVOLVING MULTI-LEVEL INPUTS FROM UNIVERSITY LEADERS, ACADEMIC UNITS AND FACULTY TO CATALYZE SUSTAINABLE INSTITUTIONAL CHANGE THAT SUPPORTS SCIENTIFIC AND INCLUSIVE EXCELLENCE IN THE CONDUCT OF HEALTH DISPARITIES RESEARCH. WITH SUPPORT FROM THE FIRST PROGRAM, WE WILL HIRE AND MENTOR A DIVERSE (GENDER, RACE, ETHNICITY) GROUP OF 10 EARLY-STAGE FACULTY IN THREE CLUSTERS WHO ARE COMPETITIVE FOR TENURE-TRACK RESEARCH POSITIONS WITH JOINT OR SECONDARY APPOINTMENTS ACROSS RELEVANT DEPARTMENTS, PROGRAMS, OR COLLEGES, USING EVIDENCE-BASED, MULTI-LEVEL MENTORSHIP STRATEGIES AT THE INDIVIDUAL, DEPARTMENT, COLLEGE AND UNIVERSITY LEVELS, WE WILL FORM A SCIENTIFICALLY RIGOROUS AND SUPPORTIVE LEARNING COMMUNITY IN WHICH FIRST FACULTY WILL ENGAGE IN INDIVIDUAL AND GROUP ACTIVITIES LEADING TO SUBMISSIONS OF COMPETITIVE NIH R01 RESEARCH PROPOSALS. FIRST FACULTY WILL BE HIRED WHO ARE COMMITTED TO DIVERSITY AND WHOSE RESEARCH ADDRESSES ONE OF 3 PILLARS OF HEALTH DISPARITIES RESEARCH: DETECTING (DEFINING/MEASURING HEALTH DISPARITIES), UNDERSTANDING (IDENTIFYING DETERMINANTS OF DISPARITIES), AND/OR REDUCING (INTERVENE, EVALUATE, TRANSLATE, SCALE, POLICY) HEALTH INEQUITIES IN CROSS-CUTTING THEMATIC AREAS (AGING, CHRONIC DISEASE, AND/OR ENVIRONMENTAL DETERMINANTS). DEVELOPING AND SUPPORTING A CADRE OF DIVERSE RESEARCHERS HAS BEEN IDENTIFIED AS AN EVIDENCE-BASED STRATEGY FOR ADVANCING NEW METHODOLOGIES, MEASURES, AND NOVEL MULTI-LEVEL/MULTI-MODAL INTERVENTIONS THAT ADDRESS INEQUITIES AND IMPROVE INDIVIDUAL AND POPULATION HEALTH OUTCOMES. WE WILL DEPLOY A MULTI-LEVEL AND MULTI-METHODS EVALUATIVE APPROACH GUIDED BY CRITICAL AND INTERSECTIONALITY THEORIES TO EVALUATE NUANCED EXPERIENCES OF BIAS AND STRUCTURAL DISCRIMINATORY PRACTICES AS WELL AS PROGRAM SUCCESSES AT THE INDIVIDUAL, DEPARTMENT, MENTOR, COLLEGE AND UNIVERSITY LEVELS OF ACHIEVING INCLUSIVE EXCELLENCE. OUR FIRST PROGRAM IS CO-LED BY NATIONALLY/INTERNATIONALLY RECOGNIZED LEADERS IN POPULATION HEALTH, INTERVENTION SCIENCE, MENTORSHIP OF RACIALLY/ETHNICALLY DIVERSE FACULTY AND EVALUATION OF PROGRAMS SEEKING INCLUSIVITY.

CONNECTING THE DOTS: AN RCT INTEGRATING STANDARDIZED ASD SCREENING, HIGH-QUALITY TREATMENT, AND LONG-TERM OUTCOMES

AN ASD ENRICHED RISK (ASD-ER) ECHO COHORT

NEW CA - COLLABORATIVE FOR HIERARCHICAL, AGILE AND RESPONSIVE MATERIALS (CHARM)

SPINAL CORD INJURY, PLASTICITY AND TRANSPLANT MEDIATED REPAIR

MEDICAL MARIJUANA, EMERGING ADULTS & COMMUNITY: CONNECTING HEALTH AND POLICY

PUBLIC HEALTH AND AUTISM SCIENCE ADVANCING EQUITABLE STRATEGIES ACROSS THE LIFE COURSE (PHASES) - AUTISM IS A COMMON NEURODEVELOPMENTAL CONDITION THAT AFFECTS FUNCTIONING AND WELL-BEING IN A MYRIAD OF DOMAINS ACROSS THE LIFE COURSE. THE PROPOSED AUTISM CENTER OF EXCELLENCE, “PUBLIC HEALTH AND AUTISM SCIENCE ADVANCING EQUITABLE STRATEGIES ACROSS THE LIFE COURSE” (PHASES) APPLICATION PROPOSES TO EMPLOY AN OVERARCHING PUBLIC HEALTH RESEARCH FRAMEWORK TO EXAMINE HEALTH DETERMINANTS, HEALTH INEQUITY – ESPECIALLY IN UNDER-REPRESENTED DIVERSE POPULATIONS – AND HEALTH SERVICES DELIVERY AND THEIR IMPACT ON HEALTH OUTCOMES. PROJECTS IN OUR CENTER HIGHLIGHT DIFFERENT STAGES OF THE LIFE COURSE – EARLY CHILDHOOD, ADOLESCENCE TO YOUNG ADULTHOOD, AND OLDER ADULTS. PROJECT 1 ADDRESSES PREDICTORS OF AGE OF DIAGNOSIS AMONG YOUNG CHILDREN WITH AUTISM, WITH EMPHASIS ON INEQUITIES IN ACCESS TO UNIVERSAL, HIGH-FIDELITY SCREENING DURING PRIMARY CARE VISITS. PROJECTS 2 AND 3 EXAMINE MEDICAID CLAIMS AND OTHER NATIONAL DATA TO ADDRESS KEY ISSUES ARISING FROM THE DISPROPORTIONATE BURDEN OF CO-OCCURRING HEALTH CONDITIONS IN AUTISTIC ADOLESCENTS AND YOUNG ADULTS (PROJECT 2) AND MIDDLE AGE-TO-OLDER ADULTS (PROJECT 3). PROJECT 4 DEVELOPS A NEW TOOL TO SUPPORT TRANSITION FROM PEDIATRIC TO ADULT HEALTHCARE IN YOUNG ADULTS ON THE SPECTRUM, WITH EMPHASIS ON MINIMALLY VERBAL ADULTS. EACH OF THE FOUR STUDIES TARGETS UNIQUE UNDERSTUDIED GROUPS CHARACTERIZED BY POTENTIALLY MODIFIABLE ADVERSE OUTCOMES: YOUNG CHILDREN WITH DELAYED AUTISM DETECTION, AUTISTIC ADOLESCENTS AND YOUNG ADULTS WITH CO-OCCURRING CONDITIONS, OLDER AUTISTIC ADULTS WITH CO-OCCURRING HEALTH AND COGNITIVE DETERIORATION, AND YOUNG AUTISTIC, MINIMALLY VERBAL ADULTS AT RISK FOR POOR HEALTH CARE TRANSITION. THE THREE CENTER AIMS ADDRESS THE FOLLOWING RESEARCH GOALS AT THREE DIFFERENT KEY LIFE STAGES: AIM 1 INVESTIGATES MODIFIABLE HEALTH DETERMINANTS FOR AUTISTIC INDIVIDUALS; AIM 2 EVALUATES INEQUITIES IN HEALTH AND HEALTH SERVICES, ESPECIALLY IN UNDER-REPRESENTED MINORITIES AND ECONOMICALLY DISADVANTAGED PERSONS ON THE AUTISM SPECTRUM; AND AIM 3 EXAMINES THE RELATIONS BETWEEN HEALTH SERVICES DELIVERY AND HEALTH OUTCOMES. THE CENTER WILL BE SUPPORTED BY THREE CORES FACILITATING SYNERGY ACROSS PROJECTS: THE ADMINISTRATIVE CORE STREAMLINES COMMUNICATION AND COLLABORATION ACROSS PROJECTS; THE DISSEMINATION AND OUTREACH CORE FACILITATES ENGAGEMENT WITH DIVERSE STAKEHOLDERS AND EXPANDS OUR EXISTING ACTIVITIES TO EMPHASIZE BIDIRECTIONAL COMMUNICATION BETWEEN OUR TEAM AND THE COMMUNITY; AND THE DATA CORE ENSURES QUALITY, INTEGRITY, AND SECURITY OF DATA FROM LARGE AND DIVERSE SOURCES (E.G. MEDICAID, MEDICARE, ELECTRONIC HEALTH RECORDS). OVERALL, THE CENTER WILL ADDRESS PREVENTABLE ADVERSE OUTCOMES AND PROMOTE WELLBEING IN INDIVIDUALS ON THE AUTISM SPECTRUM, WITH A FOCUS ON SEVERAL PRIORITIES IDENTIFIED BY THE INTERAGENCY AUTISM COORDINATING COMMITTEE, INCLUDING RESEARCH ACROSS THE LIFESPAN, REDUCING INEQUITIES, AND IMPROVING HEALTH OUTCOMES FOR AUTISTIC PERSONS.

EARLY DETECTION OF PERVASIVE DEVELOPMENTAL DISORDERS

CENTER FOR SUSTAINABLE CORROSION PROTECTION

EASTERN COOPERATIVE ONCOLOGY GROUP CHAIR'S OFFICE

STRUCTURE-BASED ANTAGONISM OF HIV-1 ENVELOPE FUNCTION IN CELL ENTRY

OP EARLY INTERVENTION SVCS W/RESPECT TO HIV DISEASE

MITOCHONDRIAL FUNCTIONS IN MALARIA PARASITES

ADVANCING HEALTH EQUITY THROUGH INNOVATIVE COMMUNITY CAPACITY BUILDING, DATA SCIENCE & DELIVERING COMMUNITY-CENTERED STRUCTURAL INTERVENTIONS & OUTCOMES: DREXEL'S COMPASS COORDINATING CENTER (C3) - PROJECT SUMMARY THE PROPOSED ADVANCING HEALTH EQUITY THROUGH INNOVATIVE COMMUNITY CAPACITY BUILDING, DATA SCIENCE & DELIVERING COMMUNITY-CENTERED STRUCTURAL INTERVENTIONS & OUTCOMES: DREXEL'S COMPASS COORDINATION CENTER (C3) WILL PROVIDE OVERSIGHT FOR THE PLANNING, IMPLEMENTATION, AND EVALUATION OF THE COMMUNITY PARTNERSHIPS TO ADVANCE SCIENCE FOR SOCIETY (COMPASS) PROGRAM, A FIRST-OF-ITS-KIND NATIONAL EFFORT TO ADVANCE COMMUNITY-LED HEALTH EQUITY STRUCTURAL INTERVENTION RESEARCH. ACTING AS ITS BACKBONE, THE C3 WILL ADMINISTER AND COORDINATE MULTIPLE COMPONENTS OF THE COMPASS PROGRAM THROUGH ITS THREE INTERDEPENDENT CORES (ADMINISTRATIVE, DATA, AND CAPACITY-BUILDING) INCLUDING CREATION AND FACILITATION OF A NATIONAL HEALTH EQUITY RESEARCH ASSEMBLY (HERA), ESTABLISHING COMMUNITIES OF PRACTICE (COPS) AND RELATED AFFINITY GROUPS TO FOSTER CROSS-INTERVENTION AND MULTI-SECTOR COLLABORATION AND CO-LEARNING, PLANNING AND DELIVERY OF A VIRTUAL KICK-OFF AND IN-PERSON ANNUAL MEETINGS, DEVELOPING CONTENT FOR THE PROGRAMMATIC WEBSITE, OVERSIGHT OF DATA COLLECTION, HARMONIZATION, REPORTING, AND SHARING PROCESSES, AND DELIVERY OF EXPERT-LEAD TRAININGS, ONE-ON-ONE AND GROUP CONSULTATIONS, AND TECHNICAL ASSISTANCE FOR COMPASS GRANTEES. OUR DIVERSE TEAM OF INVESTIGATORS AND STAFF HAS A SUSTAINED HISTORY OF WORKING WITH COMMUNITY-BASED ORGANIZATIONS (CBOS) TO CONDUCT HEALTH EQUITY RESEARCH AND DEVELOP AND EVALUATE STRUCTURAL INTERVENTIONS IN PARTNERSHIP WITH COMMUNITIES EXPERIENCING HEALTH AND SOCIAL INEQUITIES, WHO HAVE BEEN TRADITIONALLY UNDERSERVED, NEGLECTED, AND/OR MISTREATED BY THE ACADEMIC AND RESEARCH ENTERPRISE. OUR COLLECTIVE WORK SPANS URBAN AND RURAL SETTINGS, LOCAL, NATIONAL AND GLOBAL CONTEXTS, AND A VARIETY OF RACIAL, ETHNIC, INDIGENOUS, IMMIGRANT, BORDER, FAITH, DISABILITY, AND SEXUAL AND GENDER MINORITY COMMUNITIES. THE C3 WILL PLAY A CRITICAL ROLE IN ENSURING NIH’S INVESTMENT MAXIMIZES ITS IMPACT, PROVIDING COMMUNITY GRANTEES THE TOOLS, RESOURCES, AND NETWORK THEY NEED TO CONDUCT HIGH-QUALITY, IMPACTFUL STRUCTURAL INTERVENTIONS IN THEIR COMMUNITIES, ENSURING THE SUCCESSES AND LESSONS LEARNED FROM THOSE INTERVENTIONS ARE PROMOTED WIDELY AND SCALED UP (AS APPROPRIATE), AND REBUILDING COMMUNITY TRUST AFTER DECADES OF NEGLECT AND HARM. MOREOVER, OUR OVERARCHING GOAL IS TO HELP CBOS IN THE COMPASS PROGRAM (AND BEYOND) TO ADVANCE HEALTH EQUITY IN THEIR COMMUNITIES AND ACHIEVE THE SUSTAINABILITY NEEDED TO ENSURE LONG-TERM BENEFITS.

GENE EDITING STRATEGIES TO TARGET HIV FOR ELIMINATION IN PERIPHERY AND BRAIN

REGULATION OF CYCLIC GMP SYNTHESIS IN PHOTORECEPTORS

INTEGRATIVE OMICS OF HEPB VACCINE RESPONSE IN CO-INFECTION WITH PARASITES

OP EARLY INTERVENTION SVCS W/RESPECT TO HIV DISEASE

AN ASD ENRICHED RISK (ASD-ER) ECHO COHORT

MRI-R2: DEVELOPMENT OF COMMON PLATFORM FOR UNIFYING HUMANOIDS RESEARCH

HIV RISK AND ACCESS TO HEALTH CARE AMONG MEXICAN MIGRANTS

CRISOL MENTE: A MULTILEVEL COMMUNITY INTERVENTION TO REDUCE MENTAL HEALTH DISPARITIES AMONG LATINOS - LATINOS IN THE U.S. EXPERIENCE SIGNIFICANT DISPARITIES IN ACCESS TO MENTAL HEALTH SERVICES DUE TO LACK OF HEALTH INSURANCE, COST OF SERVICES, LIMITED AWARENESS OF MENTAL HEALTH RESOURCES, MENTAL HEALTH STIGMA, AND FEAR OF DEPORTATION. LIMITED ENGLISH PROFICIENCY COUPLED WITH AN ACUTE LACK OF BILINGUAL AND CULTURALLY COMPETENT PROVIDERS FURTHER IMPEDE LATINOS’ ADEQUATE ACCESS TO QUALITY MENTAL HEALTH SERVICES. THE COVID-19 PANDEMIC HAS ONLY AMPLIFIED THE NEED FOR MENTAL HEALTH CARE AND EXACERBATED MENTAL HEALTH DISPARITIES FOR LATINO COMMUNITIES, MAKING IT URGENT TO IDENTIFY LOW-COST, EFFECTIVE STRATEGIES TO REDUCE THESE GAPS. THIS 5-YEAR PROJECT SEEKS TO DEVELOP AND TEST A MULTI-LEVEL, COMMUNITY INTERVENTION TO IMPROVE MENTAL HEALTH OUTCOMES AND PROMOTE ACCESS TO CULTURALLY APPROPRIATE MENTAL HEALTH TREATMENT FOR LATINO COMMUNITIES IN PHILADELPHIA. CRISOL MENTE WILL INCLUDE COMPONENTS AT VARIOUS LEVELS OF THE SOCIO-ECOLOGICAL MODEL: A CLINIC-BASED, STEPPED-CARE PROGRAM RELYING ON LATINO LAY HEALTH WORKERS (LHW) FOR THE DELIVERY OF MENTAL HEALTH SERVICES (AIM 1), OUTREACH AND EDUCATION ACTIVITIES TO REDUCE MENTAL HEALTH STIGMA IN THE COMMUNITY (AIM 2), AND EFFORTS TO STRENGTHEN LATINO-SERVING ORGANIZATIONS’ CAPACITY TO ADDRESS MENTAL HEALTH AND OTHER SYNDEMIC CONDITIONS CONTRIBUTING TO UNTREATED MENTAL HEALTH AMONG LATINOS (AIM 3). TO IMPROVE MENTAL HEALTH SYMPTOMS AND ENGAGEMENT IN CARE, WE WILL RECRUIT, TRAIN AND SUPERVISE A COHORT OF LATINO LHW WHO WILL BE EMBEDDED INTO TWO LATINO-SERVING CLINICS, EXTENDING THE REACH AND EFFECTIVENESS OF THE CLINICS’ MENTAL HEALTH SERVICES. WE WILL COMPARE THE IMPACT OF THREE DIFFERENT LEVELS OF LHW INVOLVEMENT: A) COMMUNITY OUTREACH/NAVIGATION (I.E. SCREENING AND REFERRAL OF COMMUNITY MEMBERS); B) AUXILIARY CARE (I.E. SCREENING, REFERRAL, AND HELP OVERCOMING BARRIERS TO BETTER MENTAL HEALTH); AND C) TASK SHIFTING (I.E. SCREENING, REFERRAL, ASSISTANCE, AND SUPERVISED DELIVERY OF BASIC MENTAL HEALTH TREATMENT). THE LHWS WILL ALSO CONDUCT OUTREACH/EDUCATION ACTIVITIES IN THE COMMUNITY (E.G. RADIO TALKS, INFO SESSIONS, TABLES IN COMMUNITY VENUES) TO REDUCE MENTAL HEALTH STIGMA. OUR EXPERIENCED AND LARGELY LATINO COMMUNITY-ACADEMIC RESEARCH TEAM WILL ALSO ENGAGE IN CAPACITY BUILDING ACTIVITIES (I.E. MONTHLY TOWN HALLS, ANNUAL RETREATS, WEEKLY NEWSLETTERS, PROVISION OF TRAININGS AND TECHNICAL SUPPORT) WITH THE LATINO HEALTH COLLECTIVE, A COALITION OF LATINO-SERVING ORGANIZATIONS. USING MIXED-METHODS AND THE RE-AIM FRAMEWORK, CRISOL MENTE’S IMPACT WILL BE EVALUATED WITH CLINICAL DATA, BASELINE AND 6-MONTH PATIENT SURVEY DATA (N=200 FROM EACH LEVEL OF LHW INVOLVEMENT), AND QUALITATIVE INTERVIEWS WITH COMMUNITY MEMBERS (N=30) REFERRED TO MENTAL HEALTH SERVICES BY THE LHW (AIM 1); PRE/POST MENTAL HEALTH STIGMA DATA FROM TWO RESPONDENT DRIVEN SAMPLING (RDS) SURVEYS OF LATINOS (N=400 EACH) CONDUCTED IN 2022 (PRELIMINARY STUDY) AND IN 2027 (AIM 2); COMMUNITY CAPACITY INDICATORS FROM THREE SURVEYS OF LATINO-SERVING ORGANIZATIONS CONDUCTED IN 2019, 2021 (PRELIMINARY STUDIES) AND 2027, AND KEY INFORMANT INTERVIEWS (KII) WITH LATINO-SERVING PROVIDERS (N=30) IN 2019 (PRELIMINARY STUDY) AND 2027 (AIM 3).

MOLECULAR PATHWAYS AFFECTED BY DRUGS THAT DISRUPT NA+ HOMEOSTASIS IN MALARIA PARASITES

PREDICTING WEIGHT REGAIN FOLLOWING WEIGHT LOSS USING PHYSIOLOGICAL MEASURES OF APPETITE AND ENERGY EXPENDITURE - PROJECT SUMMARY THE SUCCESS OF BEHAVIORAL WEIGHT LOSS PROGRAMS IS UNDERMINED BY WEIGHT REGAIN. CONTROVERSY EXISTS ABOUT HOW MUCH PHYSIOLOGICAL ADAPTATIONS TO THE WEIGHT REDUCED STATE CONTRIBUTE TO WEIGHT REGAIN. FURTHER, LITTLE IS KNOWN ABOUT THE RELATIVE CONTRIBUTIONS TO RELAPSE OF INCREASED METABOLIC EFFICIENCY AND INCREASED APPETITIVE DRIVE. EVEN IF METABOLIC EFFICIENCY INCREASES WITH WEIGHT LOSS, THIS DOES NOT NECESSARILY MEAN THAT SUCCESSFUL DIETERS ARE HYPO-METABOLIC IN THEIR WEIGHT-REDUCED STATE. TO ADDRESS THESE SCIENTIFIC QUESTIONS, WE WILL RECRUIT 100 INDIVIDUALS INTO A WEIGHT LOSS PROGRAM BASED ON A MODIFIED VERSION OF THE DIABETES PREVENTION PROGRAM. QUALIFIED PARTICIPANTS WILL BE ASSESSED AT BASELINE AND REASSESSED IF THEY ATTAIN A MINIMUM 7% WEIGHT LOSS (CALLED MONTH 0) AND UNDERGO FOLLOW-UP ASSESSMENTS 2 AND 18-MONTHS LATER. REASSESSMENT AT MONTH 2 WILL ALLOW US TO STUDY THE TRANSITION TO MAINTENANCE AS A DYNAMIC PROCESS (I.E., CHANGE FROM MONTH 0 TO 2), NOT JUST AS A DISCRETE CHANGE OF STATE (FROM BASELINE TO MONTH 0). A CONTROL GROUP OF 33 WEIGHT-STABLE OVERWEIGHT INDIVIDUALS, MATCHED TO SUCCESSFUL WEIGHT LOSERS ON BMI AND OTHER VARIABLES, WILL BE RECRUITED AT TIME 0 AND COMPARED TO WEIGHT LOSERS ON ALL OUTCOME MEASURES. CHANGES IN PHYSIOLOGICAL MEASURES OF METABOLISM AND APPETITE DURING WEIGHT LOSS WILL BE USED TO PREDICT INDIVIDUAL DIFFERENCES IN WEIGHT REGAIN. BY COMPARING WEIGHT-LOSING TO WEIGHT-STABLE INDIVIDUALS, WE WILL DEVELOP A UNIQUE REFERENCE POINT FOR INTERPRETING THE RESULTS OF THE WITHIN-GROUP PREDICTIVE ANALYSES. PHYSIOLOGICAL OUTCOME MEASURES WILL INCLUDE: 1) ENERGY METABOLISM (E.G., RESTING AND NON-RESTING ENERGY EXPENDITURE, 2) NEURAL INDICATORS OF APPETITIVE DRIVE (E.G., STRIATAL ACTIVATION TO FOOD CUES AND FOOD TASTES) AND 3) NEUROENDOCRINE RESPONSES TO FASTING AND FED STATES (E.G., LEPTIN, GLP-1). A COMPREHENSIVE BIOBANK OF BLOOD, FECAL, MUSCLE AND ADIPOSE TISSUE WILL ALSO BE COLLECTED FOR FUTURE DISCOVERY STUDIES. OUR MEASURES AND EXPERTISE WILL PROVIDE NEW INSIGHT INTO THE PHYSIOLOGICAL DETERMINANTS OF WEIGHT REGAIN FOLLOWING WEIGHT LOSS THAT COULD HELP IMPROVE OBESITY TREATMENTS IN THE FUTURE.

LONG-ACTING, SELF-ADMINISTERED HIV THERAPY WITH TH CCR5 ANTIBODY PRO 140

HIV-1 TAT GENETIC VARIATION IMPACTS NEUROAIDS

CONTRIBUTION OF LONGITUDINAL NEIGHBORHOOD DETERMINANTS TO COGNITIVE HEALTH AND DEMENTIA DISPARITIES WITHIN A MULTI-ETHNIC COHORT - PROJECT SUMMARY/ABSTRACT BEYOND THE ROLE THAT INDIVIDUAL FACTORS (E.G. AGE, RACE, GENDER, AND SOCIOECONOMIC STATUS) PLAY IN THE PROGRESSION OF ALZHEIMER'S DISEASE AND RELATED DEMENTIAS (ADRD), NEIGHBORHOOD FACTORS (E.G. SOCIAL AND BUILT ENVIRONMENTS) MAY AFFECT COGNITIVE HEALTH. CRITICALLY, ALTHOUGH AFRICAN AMERICAN AND HISPANIC INDIVIDUALS FACE THE HIGHEST AND MOST DISPROPORTIONATE RISK FOR ADRD, RESEARCH HAS TRADITIONALLY EXCLUDED DIVERSE POPULATIONS. GIVEN HISTORIC AND CURRENT PATTERNING OF HEALTHY NEIGHBORHOOD FACTORS BY RACIAL AND SOCIOECONOMIC CHARACTERISTICS, THESE FEATURES MAY PARTIALLY EXPLAIN OBSERVED DISPARITIES IN ADRD RISK. TO DATE THERE HAS BEEN NO RESEARCH ON THE ROLE OF NEIGHBORHOOD ENVIRONMENTS IN DISPARITIES IN ADRD RISK. IN THIS STUDY, WE PROPOSE TO LEVERAGE AND EXTEND EXTENSIVE LONGITUDINAL DATA FROM THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA) TO ADDRESS MAJOR GAPS IN RESEARCH ON NEIGHBORHOODS AND DISPARITIES IN ADRD. WE PROPOSE TO UNDERTAKE LARGE-SCALE COLLECTION, PROCESSING, AND DISTRIBUTION OF NEW NEIGHBORHOOD DATA WITHIN MESA. OUR MAIN OBJECTIVE IS TO IDENTIFY UNIQUE PATTERNS OF NEIGHBORHOOD CHANGE RELATED TO THE CAUSES OF PREVALENCE AND DISPARITIES IN COGNITIVE DECLINE AND DEMENTIA. WE WILL ATTAIN OUR MAIN OBJECTIVE BY (AIM 1) CHARACTERIZING DYNAMIC, LONGITUDINAL NEIGHBORHOOD SOCIAL AND BUILT ENVIRONMENT VARIABLES (SURVEY-BASED AND GIS-DERIVED) RELEVANT TO COGNITION FOR RESIDENTIAL ADDRESSES OF A MESA; (AIM 2) EXAMINING ASSOCIATIONS OF NEIGHBORHOOD ENVIRONMENTAL CHARACTERISTICS WITH COGNITION AND CLINICALLY RELEVANT ADRD OUTCOMES; (AIM 3) INVESTIGATE DETERMINANTS OF DISPARITIES IN ADRD OUTCOMES BY SOCIOECONOMIC POSITION AND RACE/ETHNICITY AND ASSESS THE CONTRIBUTION OF NEIGHBORHOOD ENVIRONMENTS. THIS PROJECT IS POISED TO PROVIDE ROBUST NEW EVIDENCE ABOUT PATHWAYS AND LINKS BETWEEN NEIGHBORHOOD ENVIRONMENTS AND COGNITIVE OUTCOMES, WITH IMPORTANT IMPLICATIONS FOR BUILT ENVIRONMENT SCIENCE, ADRD PROGRESSION RESEARCH, AND POLICIES TO SUPPORT HEALTHY AGING. AIM 1 WILL CREATE THE MOST COMPREHENSIVE LONGITUDINAL NEIGHBORHOOD DATASET ON A DIVERSE SAMPLE WITH DETAILED COGNITIVE AND ADRD OUTCOMES FOR WIDESPREAD DISSEMINATION TO A NETWORK OF RESEARCHERS. ANALYSES IN AIM 2 WILL CONTRIBUTE TO DEVELOPING SUBSTANTIVE THEORY ON THE ROLE OF NEIGHBORHOODS IN ADRD PROGRESSION AND PROVIDE GUIDANCE FOR URBAN PLANNERS TO DESIGN NEIGHBORHOODS THAT SUPPORT HEALTHY AGING. AIM 3 EXAMINES COMPONENT CONTRIBUTIONS TO RACIAL DISPARITIES IN COGNITION AND ADRD. THROUGH THIS, WE EXPECT TO IDENTIFY ACTIONABLE, COMMUNITY AND CLINICAL INTERVENTIONS TO ADDRESS AND REMEDIATE RACIAL AND SOCIOECONOMIC INEQUALITIES DERIVED FROM THE UNEQUAL DISTRIBUTION OF ENVIRONMENTAL SUPPORTS FOR HEALTHY AGING. WE EXPECT THIS EVIDENCE TO SUPPORT AND AMPLIFY EFFORTS TO REDUCE DISPARITIES.

BIOBASED THERMOSETTING POLYMERS FOR COMPOSITE, ADHESIVE, AND COATING APPLICATIONS

UNDERSTANDING AND CONTROLLING MACROPHAGE BEHAVIOR IN ANGIOGENESIS

MICROTUBULE DYNAMICS AND AXON GROWTH

PROTECTIVE POLYMER SYSTEMS

EFFICACY OF A TRAUMA INTERVENTION FOR AFFECT REGULATION, ADHERENCE, AND SUBSTANCE USE TO OPTIMIZE PREP FOR WOMEN WHO INJECT DRUGS - PROJECT SUMMARY/ ABSTRACT WOMEN WHO INJECT DRUGS (WWID), ESPECIALLY THOSE ENGAGING IN SEX WORK, BEAR A DISPROPORTIONATE BURDEN OF NEW HIV INFECTIONS. WHILE WWID WOULD BENEFIT FROM WOMAN-CONTROLLED HIV PREVENTION STRATEGIES, SUCH AS PRE- EXPOSURE PROPHYLAXIS (PREP), THEY HAVE BEEN UNDERREPRESENTED IN ALL PHASES OF PREP RESEARCH AND UPTAKE REMAINS LOW. THE GOAL OF THIS RANDOMIZED CONTROLLED TRIAL (RCT) IS TO TEST THE EFFICACY OF A TRAUMA-INFORMED EXPRESSIVE WRITING (EW) INTERVENTION FOR BOOSTING THE EFFECTIVENESS OF CONTINGENCY MANAGEMENT (CM) TO REDUCE HIV ACQUISITION RISK IN WWID WHO INITIATE PRE-EXPOSURE PROPHYLAXIS (PREP). THE RATIONALE IS THAT EW+CM WILL ADDRESS THE INTERSECTION OF TRAUMA, SUBSTANCE USE, AND SUBOPTIMAL PREP ADHERENCE TO ACHIEVE MORE DURABLE REDUCTIONS IN HIV ACQUISITION RISK (I.E., THE CO-OCCURRENCE OF HIV RISK BEHAVIORS AND PREP NON-ADHERENCE). THIS RCT WILL LEVERAGE OUR LONGSTANDING PARTNERSHIP WITH PREVENTION POINT PHILADELPHIA. WWID WHO ARE AT RISK FOR HIV (E.G., REPORT SYRINGE SHARING OR CONDOMLESS SEX AND NO PREP USE WITHIN 30 DAYS) AND INTERESTED IN PREP WILL BE LINKED TO PREP CARE AT PREVENTION POINT. A COHORT OF 360 WWID WHO INITIATE PREP WILL BE ENROLLED AND IMMEDIATELY BEGIN A 3-MONTH CM PERIOD THAT INCLUDES DAILY DIRECTLY OBSERVED PREP DOSES, STIMULANT/OPIOID ABSTINENCE (MEASURED THRICE WEEKLY THROUGH URINE SCREENING), AND 4 WRITING SESSIONS. AFTER A RUN-IN PERIOD, WOMEN WILL BE RANDOMIZED TO ONE OF TWO STUDY ARMS: EW+CM (N=180) OR NEUTRAL WRITING+CM (N=180). FOLLOW- UP ASSESSMENTS WILL BE CONDUCTED AT 3, 6, AND 12 MONTHS POST-RANDOMIZATION AND WILL INCLUDE COLLECTION OF SCALP HAIR TO QUANTIFY MONTHLY LEVELS OF TENOFOVIR, AN OBJECTIVE METRIC OF PREP ADHERENCE. THE SPECIFIC AIMS OF THIS RCT ARE TO: (1) DETERMINE THE EFFICACY OF EW+CM FOR IMPROVING THE PROPORTION OF PARTICIPANTS ACHIEVING REDUCTIONS IN HIV ACQUISITION RISK (OPERATIONALIZED AS THE PROPORTION OF WWID REPORTING SYRINGE SHARING OR CONDOMLESS SEX DURING OBJECTIVELY MEASURED PERIODS OF PREP NON-ADHERENCE) AT 12 MONTHS. (2) EXAMINE KEY SECONDARY OUTCOMES SUCH AS GREATER PREP PERSISTENCE, REDUCTIONS IN SUBSTANCE USE, PTSD SYMPTOMS, DEPRESSION, ENTRY INTO DRUG TREATMENT, AND COST-EFFECTIVENESS OVER 12 MONTHS. (3) EVALUATE MEDIATING PATHWAYS THROUGH WHICH THE INTERVENTION OPERATES (E.G., MEDIATED BY REDUCTIONS IN SUBSTANCE USE OR EMOTIONAL EXPRESSION AND PROCESSING IN EW ESSAYS) AND MODERATORS OF THESE RELATIONSHIPS (E.G., MORE PRONOUNCED AMONG THOSE WITH HIGHER PTSD SEVERITY AT BASELINE). THIS RCT COULD HAVE EXCEPTIONAL IMPACT BY YIELDING ONE OF THE FIRST EVIDENCE-BASED INTERVENTIONS TO ADDRESS HIV ACQUISITION RISK IN THE ERA OF PREP AMONG WWID. IT IS HIGHLY INNOVATIVE TO INTEGRATE THIS GENDER-SPECIFIC RCT INTO KNOWN AND NEEDED COMMUNITY-BASED SSP SERVICES AND TO INCLUDE A ROBUST COST-EFFECTIVENESS ANALYSIS TO GUIDE IMPLEMENTATION AND SCALE UP SHOULD EW+CM BE EFFICACIOUS. THE LONG-TERM OUTCOME OF THIS RESEARCH PROGRAM WILL BE A REDUCTION IN HIV THROUGH A REPLICABLE MODEL THAT THAT OPTIMIZES PREP ENGAGEMENT AMONG WWID.

DEVELOPMENT OF PROM, VALIDATION OF CLINICAL OUTCOME MEASURES, NATURAL HISTORY, AND INTERVENTION FOR MILD TRAUMATIC BRAIN INJURY-RELATED VISION DISORDERS

CYBERCORPS MENTORING AND SCHOLARSHIP PROGRAM (CMSP)

MRI: TRACK 2 DEVELOPMENT OF A PLATFORM FOR ACCESSIBLE DATA-INTENSIVE SCIENCE AND ENGINEERING -LOW-COST, HIGH-PERFORMANCE SENSORS ARE PRODUCING AN EXPLOSION OF DATA IN EVERY FIELD, FROM THE MYSTERIES OF THE COSMOS TO THE TINIEST PARTICLES. DESPITE THIS ABUNDANCE OF DATA, THE ABSENCE OF ROBUST INFRASTRUCTURE AND TOOLS IMPEDES THE ABILITY TO EFFECTIVELY ANALYZE AND UTILIZE IT. THE DEVELOPMENT OF A PLATFORM FOR ACCESSIBLE DATA-INTENSIVE SCIENCE AND ENGINEERING (DISE) WILL BE A SYSTEM FOR DATA MANAGEMENT, SHARING, AND ANALYSIS THAT ALLOWS AUTOMATIC DATA COLLECTION AND CURATION, INSTANT ACCESS FOR COMPUTATIONAL ANALYSIS, AND RESEARCH RESULT SHARING FOR REPRODUCIBILITY. THE SYSTEM WILL PAVE THE WAY FOR NEW RESEARCH IN DATA-DRIVEN SCIENCE ? AND SCIENTIFIC OUTCOMES. A KEY ISSUE THAT DISE ADDRESSES IS THE COMPLEXITY AND COST OF DATA MOVEMENT FROM STORAGE TO ANALYSIS SITES, ESPECIALLY IN CLOUD-BASED SCENARIOS. DISE AIMS FOR A MORE COHESIVE SYSTEM INTEGRATING DATA STORAGE AND ANALYSIS. BY MAKING RESEARCH FINDINGS MORE ACCESSIBLE TO THE PUBLIC, DISE WILL PROVIDE INCREASED RETURN ON RESEARCH INVESTMENTS TO THE RESEARCH COMMUNITY AND SOCIETY AT LARGE. CRITICALLY, DISE WILL SERVE TO TRAIN THE NEXT GENERATION OF SCIENTISTS IN DATA-INTENSIVE RESEARCH, ENSURING ACCESSIBILITY FOR DIVERSE LEARNERS, AND CONTRIBUTING TO AN EQUITABLE SCIENTIFIC COMMUNITY. DISE AIMS TO ADVANCE DATA-INTENSIVE SCIENCE AND ENGINEERING AND MAKE RESEARCH MORE ACCESSIBLE AND REPRODUCIBLE, FOSTERING EQUITABLE OUTCOMES ACROSS ALL SOCIETAL SECTORS. DISE WILL INTRODUCE AN INNOVATIVE PLATFORM THAT FACILITATES AUTOMATIC DATA CURATION FROM SCIENTIFIC INSTRUMENTS, DETAILED METADATA QUERYING, INTELLIGENT TIERING FOR INSTANT DATA ACCESSIBILITY FOR COMPUTATIONAL WORKLOADS, INTERACTIVE ACCESS TO GRAPHICS PROCESSING UNIT (GPU)-ACCELERATED RESOURCES, HOSTING AND SHARING OF CONTAINERIZED RESEARCH PRODUCTS AND DEPLOYMENT OF SELF-HEALING MICRO-SERVICES FOR REAL-TIME DATA ANALYSIS. THE PLATFORM WILL BE EQUIPPED WITH A 2-PETABYTE SCIENTIFIC DATA MANAGEMENT SYSTEM, A 500-TERABYTE ALL-FLASH HIGH-PERFORMANCE PARALLEL FILE SYSTEM, AND GPU-ACCELERATED COMPUTATION. THESE FEATURES PROMISE NOT ONLY TO STREAMLINE DATA MANAGEMENT BUT ALSO TO FACILITATE INPUT/OUTPUT OPERATIONS PER SECOND (IOPS) INTENSIVE WORKFLOWS, INCLUDING DATA MINING, DATA-DRIVEN RESEARCH, FOUNDATIONS IN AI, DATA-INTENSIVE COMPUTATION FOR GOOD, AND RELIABLE AND TRUSTWORTHY AI. DISE IS DEDICATED TO AIDING THE EXPLORATION OF NEW AREAS OF STUDY BY UTILIZING COMMUNITY DATA REPOSITORIES WHILE SIMULTANEOUSLY FOSTERING THE GROWTH OF THE UPCOMING GENERATION OF SCIENTISTS SKILLED IN DATA-INTENSIVE RESEARCH. DISE WILL ALSO IMPROVE ACCESS TO RESEARCH DATA AND COMPUTATION, THUS INCREASING THE RETURN ON PRIOR RESEARCH INVESTMENTS. THE AUTOMATED CURATION FEATURE OF DISE IS SET TO REVOLUTIONIZE HOW RESEARCH DATA IS ORGANIZED AND SHARED, MAKING IT ACCESSIBLE AND INTEROPERABLE BEYOND THE ORIGINATING RESEARCHERS. ADDITIONALLY, DISE IS COMMITTED TO PROVIDING HIGH-PERFORMANCE GPU RESOURCES TO FOSTER DATA-INTENSIVE SCIENCE. THE PLATFORM WILL CONNECT WITH RESEARCHERS ACROSS VARIOUS DISCIPLINES AND INTENDS TO FURTHER EXPAND ITS REACH BY AUTOMATING DATA CURATION FROM SHARED USER FACILITIES. IN ADDITION, THE USE OF GPU-ACCELERATED COMPUTING RESOURCES VIA AN EASILY ACCESSIBLE JUPYTERHUB WILL AID IN EDUCATING AND TRAINING THE NEXT GENERATION OF RESEARCHERS. FINALLY, DISE IS COMMITTED TO PROMOTING DIVERSITY IN THE FIELD BY PROVIDING EQUITABLE ACCESS TO RESOURCES AND PARTNERING WITH INSTITUTIONS SUCH AS MORGAN STATE UNIVERSITY TO TRAIN A NEW GENERATION OF DIVERSE DATA-INTENSIVE SCIENTISTS AND ENGINEERS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

SBIRT FOR ADOLESCENTS AND THEIR FAMILIES IN MENTAL HEALTH SETTINGS - OVER FIVE YEARS, DREXEL UNIVERSITY AIMS TO SCREEN NEARLY 28,000 ADOLESCENTS AND PROVIDE AT LEAST BRIEF INTERVENTION TO NEARLY 5,000 YOUTH AND THEIR PARENTS. WE WILL USE A FAMILY CENTERED CARE MODEL AND HOST MOST OF OUR SCREENING AND DATA COLLECTION (GPRA) ON A WEB-BASED, INFORMATICS PLATFORM CALLED BH-WORKS. OUR TARGET POPULATION IS ADOLESCENTS AGED 12-18 YEARS BEING SERVED IN OUTPATIENT BEHAVIORAL AND HEALTH SPECIALTY CARE SERVICES. ADOLESCENTS WILL BE INITIALLY SCREENED WITH THE CRAFT FOR RISK OF SUBSTANCE USE. BASED ON OUR COMMUNITY SURVEY DATA, WE ESTIMATE ABOUT 30% OF YOUTH WILL BE IN NEED OF SERVICES. UNFORTUNATELY, PHILADELPHIA HAS VERY FEW TREATMENT PROGRAMS AND EVEN FEWER EARLY INTERVENTION PROGRAMS FOR YOUTH AT RISK. TO ADDRESS THIS SIGNIFICANT NEED, WE PROPOSE IMPLEMENTING A FAMILY-BASED, ADOLESCENT, CO-OCCURRING SBIRT PROJECT IN SETTINGS BEYOND WHERE SBIRT HAS TRADITIONALLY BEEN USED. WE HAVE PARTNERED WITH THREE COMMUNITY-BASED AGENCIES THAT, COMBINED, HAVE OVER 25 UNIQUE PROGRAMS RANGING FROM TRADITIONAL OUTPATIENT TO CRISIS, TO HOME-BASED SERVICES FOR CHILDREN IN THE WELFARE SYSTEM. WE HAVE 15 YEARS OF EXPERIENCE IMPLEMENTING SCREENING, ASSESSMENT, TREATMENT, AND REFERRAL PROGRAMS ACROSS THE STATE OF PENNSYLVANIA AND FEEL CONFIDENT WE CAN ADAPTED SBIRT TO THESE VARIOUS SETTINGS. EACH AGENCY WILL BE TRAINED IN THE SBIRT MODEL. WE WILL INTEGRATE OUR WEB-BASED CLINICAL MANAGEMENT SYSTEM WITH THE EMR AT EACH AGENCY. FOR BRIEF INTERVENTION, WE WILL TRAIN STAFF IN MOTIVATIONAL INTERVIEWING. WE WILL ALSO PROVIDE AN ONLINE SUPPORT/PSYCHO EDUCATION GROUP FOR PARENTS OF THESE YOUTH. FOR ADOLESCENTS IN NEED OF BRIEF INTERVENTION, THE CMHC AGENCIES WILL LEARN TO DELIVER ATTACHMENT BASED FAMILY THERAPY, AN EMPIRICALLY-SUPPORTED THERAPY THAT ADDRESSES TRAUMA, FAMILY DISTRESS AND OTHER CO-OCCURRING CHALLENGES. WE WILL ALSO OFFER THIS TREATMENT AS AN ONLINE OPTION. WE ANTICIPATE SCREENING 600 YOUTH IN YEAR ONE, 2,460 IN YEAR TWO, 6,860 IN YEAR THREE, 8,960 IN YEAR FOUR, AND 8,960 IN YEAR FIVE FOR A TOTAL OF NEARLY 28,000 YOUTH OVER THE COURSE OF FIVE YEARS.

ANTIPSYCHOTIC MECHANISMS OF MGLUR AGONISTS IN THE MK-801 MODEL OF SCHIZOPHRENIA

DESCRIPTION:THIS AGREEMENT PROVIDES FUNDING UNDER THE INFLATION REDUCTION ACT (IRA) TO DREXEL UNIVERSITY FOR HYDROFLUOROCARBON (HFC) INNOVATIVE DESTRUCTION. THE RECIPIENT WILL DEVELOP A PORTABLE AND ENERGY EFFICIENT HFCS DESTRUCTION DEVICE BY INTEGRATING LIQUID INJECTION INCINERATOR AND NONTHERMAL GLIDING ARC PLASMA, WHICH WILL PROVIDE REFRIGERANT RECLAMATION COMPANIES WITH AN ONSITE TREATMENT OPTION TO HELP REDUCE HFC EMISSIONS. HFCS ARE MAN-MADE CHEMICALS COMMONLY USED IN REFRIGERATION AND AIR CONDITIONING THAT HAVE NEGATIVE ENVIRONMENTAL IMPACTS WHEN RELEASED INTO THE ATMOSPHERE. THE TEAM OF RESEARCHERS WILL COLLABORATE WITH INDUSTRY STAKEHOLDERS IN THE DEVELOPMENT OF THIS TECHNOLOGY AND DEVELOP MEANINGFUL ENGAGEMENT ACTIVITIES WITH DISADVANTAGED COMMUNITIES FOR ENVIRONMENTAL JUSTICE INITIATIVES RELATED TO THE IMPACTS OF HFCS ON CLIMATE AND HEALTH.ACTIVITIES:THE ACTIVITIES INCLUDE: PROCURING SERVICES FOR CONSULTATION ON PILOT-SCALE TESTING OF TECHNOLOGY IN THE FIELD AS WELL AS A TECHNOLOGY DEVELOPMENT LIAISON; CREATION OF AN PROJECT ADVISORY BOARD TO HELP GUIDE THE DEVELOPMENT OF THE PROJECT; LAB-SCALE DEVELOPMENT AND TESTING OF THE TECHNOLOGY; PILOT-SCALE TECHNOLOGY DEVELOPMENT AND FIELD TESTING; ADVANCING TECHNOLOGY DEVELOPMENT AND TECHNOLOGY TRANSFER; AND ENGAGING WITH UNDERSERVED COMMUNITIES TO ADDRESS CONCERNS ABOUT ENVIRONMENTAL JUSTICE, INCLUDING THE DEVELOPMENT OF EDUCATIONAL MATERIALS.SUBRECIPIENT:NO SUBAWARDS ARE INCLUDED IN THIS ASSISTANCE AGREEMENT.OUTCOMES:THE ANTICIPATED DELIVERABLES INCLUDE: THE DEVELOPMENT OF A PROJECT ADVISORY COMMITTEE; A COMPETITIVE PROCESS TO SELECT CONTRACTORS FOR TECHNOLOGY DEVELOPMENT AND FIELD TESTING; QUARTERLY AND END OF YEAR REPORTS; THE DESIGN, CONSTRUCTION, AND TESTING OF A DEMONSTRATION TECHNOLOGY TO DESTROY HFCS IN WASTE OILS; ANALYSIS OF FINAL CHEMICAL PRODUCTS, INCLUDING BYPRODUCTS; INCREASED KNOWLEDGE OF HFC DESTRUCTION THROUGH INNOVATIVE TECHNIQUES; ENGAGEMENT WITH UNDERSERVED COMMUNITIES ON HFC DESTRUCTION AND ANY POTENTIAL ENVIRONMENTAL JUSTICE CONCERNS. THE EXPECTED OUTCOMES INCLUDE: SAFE AND COMPLIANT TESTING OF HFC DESTRUCTION THROUGH THE DEVELOPMENT OF A PROJECT ADVISORY BOARD; INCREASED KNOWLEDGE ON THIS TYPE OF DESTRUCTION TECHNOLOGY, INCLUDING WITH INDUSTRY STAKEHOLDERS; TECHNOLOGY TRANSFER TO OTHER INTERESTED ENTITIES; THE DEVELOPMENT OF A PORTABLE TREATMENT TECHNOLOGY FOR WASTE REFRIGERANT TO REDUCE EMISSIONS AND IMPROVE CLIMATE BENEFITS THROUGH EFFICIENTLY DESTROYING HFCS; REDUCED TOXIC BY-PRODUCTS BY CONTROLLING AND MINIMIZING THE FORMATION OF HARMFUL BY-PRODUCTS; VALIDATED HFC DESTRUCTION TECHNOLOGY BY CONFIRMING THE SYSTEM'S ABILITY TO DESTROY HFCS IS ENVIRONMENTALLY EFFECTIVE; VALIDATED ENVIRONMENTAL BENEFITS OF THE HFC DESTRUCTION TECHNOLOGY; INCREASED COMMUNITY INVOLVEMENT IN ENVIRONMENTAL DECISION-MAKING; REDUCED ENVIRONMENTAL IMPACT BY HEIGHTENED PUBLIC AWARENESS. THE INTENDED BENEFICIARIES INCLUDE THE PUBLIC, WHO WILL BENEFIT FROM IMPROVED AIR QUALITY AND REDUCED CLIMATE IMPACTS ASSOCIATED WITH HFCS, AND THE DESTRUCTION AND RECLAMATION INDUSTRIES, THAT BENEFIT FROM IMPROVED TECHNOLOGIES THAT ARE MORE EFFICIENT AND INNOVATIVE. IN ADDITION, DIRECT BENEFICIARIES OF THIS PROJECT INCLUDE FUNDING RECIPIENTS IN THE GREATER PHILADELPHIA AREA (PA, NJ) AND ADDITIONAL SITES THAT DEPEND ON THE CONTRACTORS SELECTED THROUGH THE COMPETITIVE PROCESS.

EFFICACY OF THE WECAREADVISOR: AN ONLINE TOOL TO HELP CAREGIVERS MANAGE BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS IN PERSONS WITH DEMENTIA

LOUIS STOKES STEM PATHWAYS AND RESEARCH ALLIANCE: GREATER PHILADELPHIA REGION LSAMP (PHILADELPHIA AMP)

EFFECTS OF OPIATES ON NEURONS AND THEIR IMPACT ON HIV NEUROPATHOLOGY

OPIOID MODULATION OF THE COERULEO-CORTICAL PATHWAY

DARPA ROBOTICS CHALLENGE

IMPROVING HEALTH THROUGH HUD HOUSING ASSISTANCE FOR CHRONIC DISEASE CARE - HOUSING IS CLOSELY LINKED TO HEALTH OUTCOMES, AND STABLE HOUSING IS ESSENTIAL FOR OVERALL HEALTH AND WELLBEING. HOUSING PROVIDES CONTINUITY IN HOME ENVIRONMENTS, ACCESS TO SOCIAL SUPPORT, REDUCED FAMILY STRESS, AND IMPROVED LONG-TERM OUTCOMES. FOR ADULTS WITH CHRONIC HEALTH CONDITIONS, HOUSING STABILITY IS EVEN MORE CRUCIAL DUE TO HEIGHTENED NEED FOR CONSISTENT ACCESS TO SERVICES AND SUPPORT. FEW STUDIES HAVE EXAMINED HOW HOUSING INFLUENCES ACCESS TO APPROPRIATE CARE FOR PEOPLE WITH CHRONIC HEALTH CONDITIONS. FEDERAL HOUSING ASSISTANCE FROM THE US DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (HUD) PLAYS A VITAL ROLE IN PROVIDING AFFORDABLE HOUSING OPTIONS FOR FAMILIES WITH LIMITED FINANCIAL MEANS, INCLUDING A SUBSET OF THE 150 MILLION AMERICANS WHO LIVE WITH AT LEAST ONE CHRONIC HEALTH CONDITION. HUD ASSISTANCE INCLUDES PROGRAMS LIKE HOUSING CHOICE VOUCHERS, MULTI-FAMILY HOUSING, AND PUBLIC HOUSING. YET THERE IS LIMITED UNDERSTANDING OF HOW NEWLY RECEIVING HUD ASSISTANCE AS AN INTERVENTION TO ADDRESS HOUSING INSTABILITY IMPACTS ACCESS TO AND UTILIZATION OF APPROPRIATE TREATMENT REGIMENS FOR ADULTS WITH CHRONIC HEALTH CONDITIONS. FACTORS SUCH AS HOUSING AND ECONOMIC STABILITY, INSURANCE ENROLLMENT FACTORS, COMMUNITY CHARACTERISTICS, AND INDIVIDUAL ATTRIBUTES MAY FURTHER INFLUENCE APPROPRIATE CARE FOR CHRONIC HEALTH CONDITIONS AND OUTCOMES FOR THESE ADULTS. MEDICAID, AS THE LARGEST PUBLIC INSURER IN THE US, AND HUD, AS THE PRIMARY HOUSING ASSISTANCE PROVIDER, BOTH PLAY CRITICAL ROLES IN SERVING IMPOVERISHED ADULTS WITH CHRONIC HEALTH CONDITIONS. HOWEVER, LITTLE NATIONAL DATA EXISTS ON THE CONNECTION BETWEEN THE TWO PROGRAMS, MAKING IT DIFFICULT TO IDENTIFY WAYS TO IMPROVE EFFICIENCY AND EFFECTIVENESS. THE PROPOSED RESEARCH AIMS TO ADDRESS THIS GAP BY LINKING MEDICAID AND HUD DATASETS TO EACH OTHER AND TO ADDITIONAL SOURCES OF DATA ON COMMUNITY FACTORS, TO EXAMINE THE RELATIONSHIP BETWEEN NEWLY GAINED HOUSING ASSISTANCE AND APPROPRIATE HEALTH SERVICE USE AND OUTCOMES FOR A LARGE NATIONAL COHORT OF ADULTS WITH CHRONIC HEALTH CONDITIONS. THIS STUDY WILL BE THE FIRST TO EXAMINE APPROPRIATE HEALTH CARE AND HOUSING OUTCOMES OF ADULTS WITH KEY CHRONIC CONDITIONS (INCLUDING ASTHMA, CORONARY HEART DISEASE, DEPRESSION, AND DIABETES) WHO NEWLY RECEIVE HUD ASSISTANCE AND HOW INDIVIDUAL AND COMMUNITY FACTORS INFLUENCE THESE OUTCOMES. IN ADDITION TO QUANTITATIVE ANALYSES, QUALITATIVE INTERVIEWS WITH POLICYMAKERS AND ADVOCATES WORKING IN MEDICAID, HOUSING, AND HEALTH WILL HELP ILLUMINATE CONNECTIONS BETWEEN HOUSING AND APPROPRIATE HEALTH CARE. BY PRODUCING A ROBUST EVIDENCE BASE THAT HIGHLIGHTS BOTH THE IMPACT OF HOUSING ASSISTANCE AND MECHANISMS THROUGH WHICH IT CAN BE OPTIMIZED, THIS STUDY WILL INFORM POLICY AND PUBLIC HEALTH STRATEGIES TO IMPROVE HOUSING STABILITY AND HEALTH CARE ACCESS FOR PEOPLE WITH CHRONIC HEALTH CONDITIONS AND LAY THE GROUNDWORK FOR COORDINATED, SYSTEMS-LEVEL INTERVENTIONS THAT ARE IMMEDIATELY ACTIONABLE, TO FOSTER IMPROVED HEALTH OUTCOMES FOR ADULTS WITH CHRONIC CONDITIONS.

ROLE OF CHEMOKINES IN NEURONAL FUNCTION AND SURVIVAL

PORTABLE DIFFUSE OPTICAL SENSORS FOR POINT-OF-CARE MONITORING IN PROLONGED FIELD CARE

CRUCIAL SPINAL CIRCUIT CHANGES THAT MEDIATE LOCOMOTION BENEFITS OF COMBINED BIOLOGICAL/BIONIC/REHABILITATION THERAPIES AFTER SPINAL CORD INJURY.

ADVANCING FAST-ACTING ANTIMALARIALS THAT DISRUPT NA+ HOMEOSTASIS IN PARASITES

MECHANICS AND PERFORMANCE OF TRACEABLE UHMWPE IMPLANTS

GREATER PHILADELPHIA REGION LOUIS STOKES ALLIANCE FOR MINORITY PARTICIPATION (PHILADELPHIA AMP) INITIATIVE (SENIOR -LEVEL ALLIANCE)

HIGH SPECIFICITY HIV-1 MARKERS PREDICTIVE OF NEURO-AIDS

IMINO SUGARS FOR FLAVIVIRUS INFECTIONS OF BIOTERROR

CHARACTERIZING HEALTH IMPACTS OF BUILT ENVIRONMENT FEATURES USING COMPLEX DATA

THE ROLE OF SONIC HEDGEHOG SIGNALING ON ASTROCYTE FUNCTION IN THE ADULT CNS

MULTIPRONGED APPROACH TO PROMOTE FUNCTIONAL AXONAL REGENERATION AFTER SCI

HYPOCRETIN/OREXIN REGULATION OF DOPAMINE SIGNALING AND COCAINE REINFORCEMENT

MOLECULAR ANALYSIS OF PATHOGENS IN OTITIS MEDIA BY PCR

UNITYPHILLY RESPONSE APP FOR OVERDOSE REVERSAL: ASSESSING CITYWIDE EFFECTIVENESS AND SUSTAINABILITY - PROJECT SUMMARY/ABSTRACT REDUCING OVERDOSE MORTALITY IMMEDIATELY AND LONG-TERM IS A TOP PUBLIC HEALTH PRIORITY AS THE OVERDOSE EPIDEMIC IN THE U.S. CONTINUES TO WORSEN. THE COVID-19 PANDEMIC, WHICH BEGAN HITTING THE U.S. IN EARLY 2020, HAS EXACERBATED THE OVERDOSE CRISIS - PARTICULARLY AMONG AFRICAN AMERICANS AND LATINXS. OPIOID OVERDOSE DEATHS, WHICH ACCOUNTED FOR THE MOST OVERDOSE DEATHS IN 2020, CONTINUE TO DRIVE THE EPIDEMIC. OVERDOSE DEATHS LINKED TO SYNTHETIC OPIOIDS, SUCH AS ILLICITLY MANUFACTURED FENTANYL, HAVE INCREASED SIGNIFICANTLY AND COMPRISED MOST OF THE OPIOID-RELATED DEATHS IN 2020. DESPITE INCREASING AVAILABILITY AND ACCEPTABILITY OF NALOXONE AMONG LAYPERSONS, OPIOID OVERDOSE DEATHS REMAIN CATASTROPHICALLY HIGH IN COMMUNITIES ACROSS THE U.S. THE UNITYPHILLY SMARTPHONE APP WAS DEVELOPED IN 2018-19 ALONGSIDE SEVERAL COMMUNITY-BASED ORGANIZATIONS AS A PUBLIC HEALTH INTERVENTION IN RESPONSE TO THE OPIOID OVERDOSE CRISIS IN PHILADELPHIA, WHICH HAS THE MOST ACUTE OVERDOSE EPIDEMIC AMONG LARGE CITIES IN THE U.S. UNITYPHILLY AUTOMATICALLY CONNECTS BYSTANDERS AND VICTIMS OF OPIOID OVERDOSE WITH NEARBY COMMUNITY MEMBERS WHO CAN RESPOND IMMEDIATELY WITH NALOXONE. THE OBJECTIVE OF THIS PROPOSAL, FOLLOWING A SUCCESSFUL FEASIBILITY STUDY (R34) AND CLEAR EVIDENCE OF OVERDOSE REVERSAL SUPPORTED BY UNITYPHILLY, IS TO CREATE AN EASY-TO-USE, EFFECTIVE, SUSTAINABLE, AND SCALABLE SMARTPHONE APP TO BE DEPLOYED ACROSS THE CITY OF PHILADELPHIA. THIS OBJECTIVE WILL BE ACHIEVED BY STUDYING SUBGROUPS OF PEOPLE EQUIPPED WITH NALOXONE AND UNITYPHILLY (N=450) AND DISSEMINATING UNITYPHILLY TO 3,000 CITIZEN VOLUNTEERS FOR EVERYDAY USE TO RESPOND TO OPIOID OVERDOSE EMERGENCIES. THE LONG-TERM GOAL OF THIS RESEARCH IS TO CREATE A SCALABLE APP THAT CAN BE DISSEMINATED TO COMMUNITIES ACROSS THE U.S. EXPERIENCING HIGH LEVELS OF OPIOID OVERDOSE DEATH. THE RATIONALE FOR THIS STUDY IS THAT EXPANDING THE AVAILABILITY OF THE UNITYPHILLY APP TO LAYPERSONS CITYWIDE WILL INCREASE THE SPEED AND DELIVERY OF NALOXONE TO OPIOID OVERDOSE EVENTS ACROSS PHILADELPHIA WHILE LAYING THE GROUNDWORK FOR SCALABILITY AND BROADER NATIONAL UPTAKE. OUR GOALS WILL BE ACHIEVED WITH THREE SPECIFIC AIMS: 1) REDEVELOP UNITYPHILLY TO ENSURE EASE OF USE; 2) ASSESS DIFFERENCES IN THE EFFECTIVENESS OF UNITYPHILLY ACROSS VARIED URBAN ENVIRONMENTS AND PARTICIPANT PROFILES; AND 3) BUILD AND STUDY A SUSTAINABLE ENVIRONMENT FOR UNITYPHILLY TO EXPAND CITY-WIDE. THIS 5-YEAR STUDY WILL HAVE SIGNIFICANT IMPACT BY PROVIDING ACTIONABLE EVIDENCE REGARDING THE EFFECTIVENESS OF AN APP-BASED NALOXONE INTERVENTION TO SCALE UP FOR NATIONWIDE USE. THE STUDY WILL BE CONDUCTED IN PARTNERSHIP WITH LONG-STANDING COMMUNITY-BASED ORGANIZATIONS TO ENSURE USABILITY AND ACCEPTABILITY. THIS INTERVENTION IS HIGHLY SIGNIFICANT SINCE IT DIRECTLY ADDRESSES ONE OF THE MOST SIGNIFICANT PUBLIC HEALTH PROBLEMS IN THE U.S. – THE OPIOID OVERDOSE EPIDEMIC – WHICH IS WORSENING DUE TO THE EFFECTS OF COVID-19. THIS INTERVENTION IS HIGHLY INNOVATIVE AS IT IMPROVES UPON A PREVIOUS DEVELOPED SUCCESSFUL MOBILE PHONE APP AND EXPANDS ITS USE TO A BROADER POPULATION OF USERS IN A LARGE CITY MOST IMPACTED BY THE OPIOID CRISIS.

BENZODIAZEPINE MEDIATED MECHANISMS OF TRANSCRIPTIONAL SEMI-QUIESCENCE IN DISCRETE MYELOID POPULATIONS - ONE OF THE PRINCIPAL OBSTACLES TO CURING HIV IS THE EXISTENCE OF VIRAL RESERVOIRS IN DISTINCT COMPARTMENTS AND CELL TYPES THAT ARE UNAFFECTED BY ANTIRETROVIRAL THERAPY (ART). IN THE CENTRAL NERVOUS SYSTEM (CNS), THESE RESERVOIRS ARE COMPRISED OF MYELOID CELLS, SUCH AS PERIVASCULAR MACROPHAGES AND MICROGLIA. CRITICALLY, THESE RESERVOIRS ARE GENERALLY ESTABLISHED PRIOR TO THE INITIATION OF ART AND THE PRESENCE OF ART IN THE CNS DOES NOT AFFECT THE ESTABLISHED RESERVOIR IN LONG-LIVED MYELOID POPULATIONS. THUS, EVEN IN INDIVIDUALS ON SUPPRESSIVE ART, PERSISTENTLY INFECTED CNS MACROPHAGES AND MICROGLIA CAN DRIVE ONGOING NEUROINFLAMMATION AND PROVIDE A SOURCE OF HIV FOR VIRAL RECRUDESCENCE DURING MEDICATION HIATUS OR FAILURE. OUR ABILITY TO ELIMINATE THESE RESERVOIRS IS SEVERELY LIMITED BY THE LACK OF UNDERSTANDING OF THE TRANSCRIPTIONAL AND EPIGENETIC REGULATION OF HIV IN MYELOID CELLS. TO EFFECTIVELY TARGET AND ELIMINATE CNS RESERVOIRS IN PEOPLE LIVING WITH HIV (PLWH), IT IS CRITICAL TO DEFINE THE TRANSCRIPTIONAL MECHANISMS MEDIATING PERSISTENT INFECTION IN DISTINCT CNS MYELOID POPULATIONS. THE IMPACT OF HIV INFECTION IN THE CNS IS HEIGHTENED IN PLWH WHO HAVE SUBSTANCE USE DISORDERS, INCLUDING THOSE WHO TAKE AND/OR MISUSE THERAPEUTIC DRUGS SUCH AS BENZODIAZEPINES (BDZ). BENZODIAZEPINES ARE USED BY MORE THAN 30 MILLION AMERICANS, HAVE HIGH ABUSE LIABILITY AND MISUSE OF THESE DRUGS ACCOUNTS FOR 15 – 20% OF THEIR USE. BENZODIAZEPINES ARE PRESCRIBED TO A GROWING NUMBER OF PLWH AND ARE ASSOCIATED WITH AN INCREASED RISK OF NEUROCOGNITIVE SYMPTOMS IN THIS POPULATION. LITTLE IS KNOWN ABOUT THE MECHANISMS BY WHICH BDZ IMPACT HIV NEUROPATHOGENESIS. OUR PUBLISHED AND PRELIMINARY DATA INDICATE THAT BDZ CAN ALTER THE TRANSCRIPTIONAL REGULATION OF HIV INFECTION. TO BETTER UNDERSTAND AND TREAT THE DEVELOPMENT OF NEUROHIV IN PLWH WHO USE AND/OR MISUSE BDZ, IT IS VITAL TO DETERMINE WHO BENZODIAZEPINES AFFECT THE TRANSCRIPTIONAL PROGRAMS IN MYELOID CELLS. WE HYPOTHESIZE THAT BOTH MACROPHAGES AND MICROGLIA ENTER A SEMI-QUIESCENT TRANSCRIPTIONAL STATE DURING ART EXPOSURE AND THAT BENZODIAZEPINES DISRUPT THIS STATE AND INCREASE TRANSCRIPTIONAL ACTIVITY AND VIRAL REPLICATION. OUR DATA SHOW THAT THE BDZ XANAX, AS WELL AS SOME LATENCY REACTIVATION AGENTS, MEDIATE A DOSE-DEPENDENT INCREASE IN P24 PRODUCTION IN INFECTED, ART-TREATED CELLS. OUR PRELIMINARY STUDIES SUGGEST THESE EFFECTS MAY RESULT FROM BDZ INTERACTIONS WITH THE EPIGENETIC REGULATOR RUNX1. WE POSIT THAT THESE CHANGES IN HIV REPLICATION IN MYELOID CELLS REFLECT THE EPIGENETIC STATE OF THE PROVIRUS. THUS, THE GROWING POPULATION OF PLWH WHO USE BDZ IS AT GREATER RISK OF MORE SEVERE NEUROPATHOGENESIS. IT ALSO SUGGESTS THAT BDZ MAY PROVIDE THE BASIS FOR NOVEL THERAPEUTICS TO MANIPULATE HIV TRANSCRIPTION IN MYELOID CELLS. THEREFORE, WE WILL EVALUATE THE TRANSCRIPTIONAL AND EPIGENETIC MECHANISMS SUSTAINING THE SEMI-QUIESCENT STATE OF HIV TRANSCRIPTION IN ART- TREATED HUMAN MACROPHAGES (AIM 1), DEFINE THE DIFFERENCES IN TRANSCRIPTIONAL AND EPIGENETIC PROCESSES IN DIFFERENT TYPES OF MYELOID CELLS USING HUMAN SYNGENEIC IPSC-DERIVED MACROPHAGES AND MICROGLIA (AIM 2), AND EXAMINE THE EFFECT OF BENZODIAZEPINES ON TRANSCRIPTION HIV-INFECTED, ART-TREATED MYELOID CELLS (AIM 3).

ENHANCED ULTRASOUND TREATMENT OF CHRONIC WOUNDS WITH MONITORING OF HEALING AND QUALITY OF LIFE OUTCOMES

REGULATION OF NEUROPATHIC PAIN BY EXERCISE: EFFECTS ON NOCICEPTOR PLASTICITY AND INFLAMMATION

MULTISCALE, TRANSPORT-DEPENDENT NO SIGNALING: CELLS TO VASCULAR NETWORKS

LIMB COORDINATION DURING LOCOMOTION BEFORE AND AFTER SPINAL CORD INJURY

REDUCING AGITATION IN DEMENTIA PATIENTS AT HOME: THE CUSTOMIZED ACTIVITY TRIAL

IMMUNE MODULATING THERAPIES TO TREAT COMPLEX REGIONAL PAIN SYNDROME - ABSTRACT COMPLEX REGIONAL PAIN SYNDROME (CRPS) IS A CHRONIC PAIN DISORDER OF UNKNOWN ETIOLOGY THAT CAN AFFECT ONE OR MORE EXTREMITIES. DIFFICULTY IN TREATING CRPS STEMS FROM INCOMPLETE UNDERSTANDING OF THE UNDERLYING MECHANISMS. DESPITE DIFFERENT CLINICAL PRESENTATIONS, CLEAR EVIDENCE FOR ALTERED PROCESSING OF SENSORY STIMULI LEADING TO ALLODYNIA, HYPERALGESIA, AND HYPERAESTHESIA HAS BEEN DEMONSTRATED IN CRPS. ABERRANT IMMUNE FUNCTION IS REPORTED TO CONTRIBUTE TO CRPS PATHOLOGY. AUTOINFLAMMATORY AND AUTOIMMUNE MECHANISMS IN THE SKIN OF THE AFFECTED LIMB, AND SYSTEMICALLY IN CIRCULATION, REPORTEDLY CONTRIBUTE TO INCREASED PAIN HYPERSENSITIVITY. SYSTEMICALLY, CRPS PATIENTS HAVE INCREASED PROINFLAMMATORY MONOCYTES, AND ALTERED CIRCULATING MEMORY T CELLS (TCIRCM). AN EXPANSION OF LONG-LIVED CENTRAL MEMORY CD8+ AND CD4+ T CELLS WITH INCREASED PROINFLAMMATORY SIGNALING IS REPORTED IN CRPS PATIENTS. HOWEVER, CURRENT STUDIES ON TCIRCM DO NOT ACCOUNT FOR LOCAL TISSUE-RESIDENT MEMORY T CELLS (TRM) WHICH HAVE BEEN IMPLICATED IN SEVERAL AUTOIMMUNE DISORDERS. CLUSTER OF DIFFERENTIATION 69 (CD69) IS A TYPE II C-LECTIN MEMBRANE RECEPTOR THAT IS RAPIDLY INDUCED UPON T CELL ACTIVATION, ENABLING THEIR ACCUMULATION IN NONLYMPHOID TISSUES LIKE SKIN. CD69 ANTAGONIZES THE CELL-SURFACE EXPRESSION OF G-PROTEIN– COUPLED SPHINGOSINE-1-PHOSPHATE RECEPTOR-1 AND 5 (S1PR1/5). BY INHIBITING THE EXPRESSION OF S1PR1/5, CD69 IMPAIRS EGRESS AND PROMOTES T CELL RESIDENCY. WE HAVE IDENTIFIED DYSREGULATION OF CIRCULATING MIRNA SIGNATURES COMMON TO BOTH CRPS PATIENTS AND MOUSE TIBIA FRACTURE MODEL (TFM) OF CRPS THAT CAN REGULATE TCIRCM. INTERESTINGLY SEVERAL MIRNAS, INCLUDING A MIRNA DIRECTLY ASSOCIATED WITH POSITIVE OUTCOMES FOR CRPS PATIENTS, CAN TARGET GENES CRITICAL TO TRM DEVELOPMENT. THIS LED US TO EVALUATE TCIRCM AND TRM DYSFUNCTION IN TFM MICE, WHERE PRELIMINARY DATA DEMONSTRATE FORMATION OF PATHOLOGICAL TRM IN TFM MICE. WE HYPOTHESIZE THAT DYSREGULATION OF T CELLS IN CRPS CONVERGES ON TARGETS CRUCIAL FOR BOTH TCIRCM HOMEOSTASIS AND TRM FORMATION. WE WILL TEST WHETHER PATHOLOGICAL TCIRCM AND TRM CONTRIBUTE TO CRPS PATHOLOGY, AND IF THERAPIES THAT COOPERATIVELY TARGET BOTH POPULATIONS CAN SERVE AS A NOVEL THERAPEUTIC STRATEGY. BY FOLLOWING TCIRCM AND TRM, WE WILL ELUCIDATE MECHANISMS OF T CELL DYSFUNCTION AND INVESTIGATE NOVEL IMMUNE MODULATING THERAPIES FOR TREATING CRPS.

CARDIOMETABOLIC RISK DEVELOPMENT AND MANAGEMENT IN CHANGING NEIGHBORHOODS: THE JACKSON HEART STUDY

EFFECTIVENESS OF POPULATION LEVEL INTERVENTIONS IN SCHOOLS AND ACADEMIC PERFORMANCE - PROJECT SUMMARY AFRICAN AMERICAN AND LATINO POPULATIONS HAVE WORSE ADULT HEALTH THAN THEIR WHITE PEERS (HEREAFTER “HEALTH DISPARITIES”). THESE HEALTH GAPS OFTEN BEGIN IN CHILDHOOD, AND HAVE PERSISTED, IN PART, BECAUSE OF CONTINUING INEQUALITIES IN THE SOCIAL DETERMINANTS OF HEALTH. FAR LESS RESEARCH HAS IDENTIFIED POPULATION-LEVEL INTERVENTIONS THAT LEVEL THE PLAYING FIELD ON THE SOCIAL DETERMINANTS OF HEALTH ACROSS POPULATION SUBGROUPS. THE SCANT EVIDENCE ON EFFECTIVE POPULATION-LEVEL INTERVENTIONS IS A SIGNIFICANT BARRIER TO REDUCING HEALTH GAPS. RIGOROUS PRIOR STUDIES HAVE REVEALED THE PLAUSIBILITY FOR LARGE-SCALE NUTRITION POLICIES TO REDUCE RACIAL/ETHNIC GAPS IN CHILDREN’S ACADEMIC PERFORMANCE—A STRONG PREDICTOR OF ADULT EDUCATIONAL ATTAINMENT, WHICH IS ONE OF THE MOST FUNDAMENTAL DETERMINANTS OF HEALTH. THESE STUDIES HAVE ILLUMINATED THE INTERMEDIARY MECHANISMS IN THE PATHWAY BETWEEN SCHOOL NUTRITION POLICIES, (JUNK) FOOD AVAILABILITY IN COMMUNITIES NEAR SCHOOLS AND CHILDREN’S ACADEMIC PERFORMANCE. NO LONGITUDINAL STUDIES HAVE THOROUGHLY INVESTIGATED THE POPULATION-LEVEL INFLUENCES ON ACADEMIC PERFORMANCE OF NUTRITION POLICIES TOGETHER WITH MODIFIABLE CHARACTERISTICS OF NEARBY-SCHOOL NEIGHBORHOODS. THIS LONGITUDINAL STUDY CAPITALIZES ON A SERIES OF NATURAL EXPERIMENTS GENERATED BY CALIFORNIA’S POLICIES TO IMPROVE NUTRITION STANDARDS FOR FOODS AND DRINKS SOLD TO CHILDREN IN SCHOOLS, AND THE CHANGES IN NUTRITION STANDARDS FOR SCHOOL MEALS PUT IN PLACE BY THE HEALTHY, HUNGER FREE KIDS ACT OF 2010. THE STUDY WILL DETERMINE (A) THE EFFECTIVENESS OF POPULATION-LEVEL SCHOOL NUTRITION POLICY INTERVENTIONS IN IMPROVING CHILDREN’S ACADEMIC PERFORMANCE AND REDUCING RELATED GAPS AMONG AFRICAN AMERICAN AND LATINO VS. WHITE PEERS; (B) THE EXTENT TO WHICH MODIFIABLE, FOOD-RELATED FACTORS IN COMMUNITIES NEAR SCHOOLS INFLUENCE LONGITUDINAL CHANGES IN ACADEMIC PERFORMANCE DISPARITIES; AND (C) IF SCHOOL NUTRITION POLICY EFFECTIVENESS VARIES BY THOSE COMMUNITY FACTORS. TO GENERATE VALID INFERENCES ABOUT THE POPULATION-LEVEL EFFECTIVENESS OF THESE POLICIES ON ACADEMIC PERFORMANCE, THIS STUDY USES THE STRONGEST POSSIBLE APPROACH TO EVALUATE NON-RANDOMIZED EXPOSURES: A DIFFERENCE-IN-DIFFERENCES ANALYSIS THAT INCLUDES WITHIN-CHILD CHANGE IN EXPOSURES. DIFFERENCE IN DIFFERENCE ANALYSES WILL ALSO EXAMINE THE EFFECTS OF CHILD-LEVEL CHANGES IN MODIFIABLE CHARACTERISTICS OF COMMUNITIES NEAR THEIR SCHOOLS AND CHANGES IN ACADEMIC PERFORMANCE (AND DISPARITIES). THIS STUDY IS UNPARALLELED BECAUSE WE USE POWERFUL LONGITUDINAL DATA ON ACADEMIC PERFORMANCE AMONG A DIVERSE POPULATION OF 11.8 MILLION CHILDREN. POLICY AND COMMUNITY INTERVENTIONS IN AND AROUND SCHOOLS HOLD POTENTIAL TO REDUCE DISPARITIES GIVEN THEIR COMMUNITY-ORIENTED FOCUS, EXISTING INFRASTRUCTURES AND NETWORKS THAT FACILITATE THEIR LARGE-SCALE IMPLEMENTATION AND BROAD REACH. GIVEN ITS ROBUST DESIGN, THE STUDY WILL HAVE A SIGNIFICANT IMPACT ON EVIDENCE-BASED NUTRITION POLICY AND POPULATION-LEVEL INTERVENTIONS TO MITIGATE RACIAL/ETHNIC HEALTH GAPS; IDENTIFY OPPORTUNITIES TO ENHANCE EDUCATIONAL ATTAINMENT; AND BROADEN THE SCOPE OF INTERVENTIONS TO IMPROVE FUNDAMENTAL DETERMINANTS OF HEALTH.

MECHANISMS OF SPG4 HEREDITARY SPASTIC PARAPLEGIA

A10 - HUMAN FACTORS CONSIDERATION OF UAS PROCEDURES & CONTROL STATIONS

DREXEL CLIMATE CHANGE AND URBAN HEALTH RESEARCH CENTER (DREXEL CCUH) - SUMMARY– OVERALL THE CENTRAL THEME OF THE DREXEL CLIMATE CHANGE AND URBAN HEALTH RESEARCH CENTER (CCUH) IS THE CREATION AND DISSEMINATION/TRANSLATION OF EVIDENCE THAT WILL SUPPORT URBAN POLICIES TO ADDRESS THE HEALTH AND EQUITY IMPACTS OF CLIMATE CHANGE IN CITIES. URBAN AREAS ARE KEY CONTRIBUTORS TO CLIMATE CHANGE AND ARE HOME TO LARGE INEQUITIES, BUT ALSO PRESENT MANY OPPORTUNITIES FOR ACTION. URBANIZATION IS OCCURRING MORE RAPIDLY IN LOWER-AND MIDDLE-INCOME COUNTRIES, AND CLIMATE CHANGE IS SPURRING MIGRATION ACROSS COUNTRIES. RESEARCH ON THE HEALTH IMPACTS OF CLIMATE CHANGE MUST SPAN URBAN COMMUNITIES ACROSS COUNTRIES, YET LITTLE WORK HAS FOCUSED ON INTRA- URBAN INEQUITIES OR CONDUCTED COMPARATIVE ANALYSES OF THESE INEQUITIES ACROSS HETEROGENEOUS CITIES. BASED ON OUR ESTABLISHED, PRODUCTIVE COLLABORATION ACROSS 13 INSTITUTIONS IN THE US AND LATIN AMERICA, WE AIM TO BUILD INSTITUTIONAL CAPACITY AT DREXEL AND AT THREE PARTNER SITES INCLUDED IN THIS FORMATIVE CENTER (UNIVERSITY OF CALIFORNIA BERKELEY, UNIVERSITY OF SÃO PAULO IN BRAZIL, AND INCAP IN GUATEMALA) TO SUPPORT ACTION-ORIENTED RESEARCH ON THE IMPACTS OF CLIMATE CHANGE ON POPULATION HEALTH AND HEALTH INEQUITIES IN DIVERSE CITIES ACROSS THE AMERICAS. SPECIFICALLY, WE WILL LEVERAGE EXISTING STRENGTHS AT DREXEL IN URBAN HEALTH AND HEALTH EQUITY, OUR RESEARCH NETWORK ON URBAN HEALTH IN LATIN AMERICA (THE SALUD URBANA EN AMERICA LATINA OR SALURBAL STUDY) AND OUR WORK WITH US PARTNERS INCLUDING US BIG CITIES HEALTH COALITION. THIS ROBUST, EXISTING INFRASTRUCTURE WILL ENABLE US TO EXPAND OUR URBAN HEALTH AND HEALTH EQUITY WORK TO ENCOMPASS THE GENERATION OF SOLUTIONS- ORIENTED EVIDENCE ON THE IMPACTS OF CLIMATE CHANGE ON HEALTH IN CITIES AND TRANSLATE THAT EVIDENCE INTO ACTIONS IN PARTNERSHIP WITH COMMUNITIES AND POLICYMAKERS. OUR AIMS ARE: (1) TO CREATE AN ORGANIZATIONAL STRUCTURE THAT PROMOTES COLLABORATIVE AND INCLUSIVE TRANSDISCIPLINARY AND POLICY-RELEVANT RESEARCH ON CLIMATE CHANGE AND HEALTH ACROSS CITIES OF THE AMERICAS (ADMINISTRATIVE CORE); (2) TO SUPPORT CAPACITY-STRENGTHENING FOR RESEARCH ON CLIMATE CHANGE HEALTH IMPACTS IN URBAN SETTINGS THROUGH STRUCTURED TRAINING ACTIVITIES, FUNDING PILOT GRANTS AND RESEARCH METHODS TRANSLATION AND SUPPORT (RESEARCH CAPACITY BUILDING CORE); (2) TO DEMONSTRATE THE INFORMATIVENESS AND POLICY-RELEVANCE OF MULTI-COUNTRY RESEARCH ON CLIMATE CHANGE AND HEALTH EQUITY THROUGH A RESEARCH PROJECT ON INTRA-URBAN INEQUITIES ENGAGING RESEARCHERS FROM THE US AND LATIN AMERICA (RESEARCH PROJECT); AND (4) TO INCREASE CAPACITY FOR POLICY TRANSLATION AND POLICY IMPACT THROUGH THE ENGAGEMENT OF POLICY MAKERS AND IMPACTED URBAN COMMUNITIES IN ORDER TO INFORM FUTURE RESEARCH QUESTIONS, AS WELL AS DISSEMINATION AND TRANSLATION EFFORTS TO MAXIMIZE IMPACT (COMMUNITY ENGAGEMENT CORE.) THROUGH THESE AIMS WE WILL SUPPORT THE CREATION OF THE INFRASTRUCTURE, RESEARCH AND ENGAGEMENT CAPACITY, AND PARTNERSHIPS NEEDED TO EXPAND POLICY RELEVANT RESEARCH ON THE IMPACTS OF CLIMATE CHANGE ON HEALTH AND HEALTH EQUITY IN URBAN AREAS. OUR ULTIMATE GOAL IS TO BECOME A CENTER OF EXCELLENCE ON CLIMATE CHANGE AND URBAN HEALTH WITH A STRONG EQUITY FOCUS, GLOBAL REACH AND MEANINGFUL ENGAGEMENT OF POLICY MAKERS AND COMMUNITIES TO MAXIMIZE POLICY IMPACT.

SPINAL CORD NEURAL CIRCUITS FOR LEFT-RIGHT AND FLEXOR-EXTENSOR COORDINATION

COMPONENT B: COORDINATING CENTER FOR COMMUNITY CHARACTERISTICS ASSOCIATED WITH GEOGRAPHIC DISPARITIES IN DIABETES

REGULATION OF MICROTUBULE-BASED MEMBRANE TRAFFIC BY SEPTIN GTPASES

TRANSITION TO TEACHING PROGRAM -- NATIONAL

PANTEX FORMER WORKER MEDICAL SURVEILLANCE PROGRAM

DEVICE DEVELOPMENT FOR REMOTE NONDESTRUCTIVE TESTING AND MEASUREMENT OF POWER SYSTEMS

FMRG: CYBER: A CYBER NANOMANUFACTURING PLATFORM FOR LARGE-SCALE PRODUCTION OF HIGH-QUALITY MXENES AND OTHER TWO-DIMENSIONAL NANOMATERIALS

IGERT FELLOWSHIPS IN NANOSCALE SCIENCE AND ENGINEERING: THE TWO-UNIVERSITY/ONE CAMPUS APPROACH

GRADUATE RESEARCH FELLOWSHIP

SHARING DIGITAL SELF-MONITORING DATA WITH OTHERS TO ENHANCE LONG-TERM WEIGHT LOSS: A RANDOMIZED TRIAL USING A FACTORIAL DESIGN - ABSTRACT ADULTS ATTEMPTING WEIGHT LOSS THROUGH LIFESTYLE MODIFICATION (LM) TYPICALLY FIND MAINTENANCE OF BEHAVIOR CHANGE DIFFICULT. OUTCOMES MIGHT BE IMPROVED IF PARTICIPANTS ARE PROVIDED WITH SUSTAINED SOURCES OF ACCOUNTABILITY AND SUPPORT AND ONGOING OPPORTUNITIES TO REFLECT WITH OTHERS ON GOAL PROGRESS. THIS STUDY PROPOSES THAT SHARING DIGITAL DATA (I.E., BODY WEIGHT FROM WIRELESS SCALE, PHYSICAL ACTIVITY FROM WEARABLE SENSOR, AND DIETARY INTAKE FROM SMARTPHONE APP) WITH OTHER PARTIES HAS THE POTENTIAL TO IMPROVE LONG-TERM WEIGHT LOSS. THE BENEFIT OF DEVICE DATA SHARING HAS NOT YET BEEN RIGOROUSLY TESTED, AND TRADITIONAL LM PROGRAMS DO NOT YET INCORPORATE DIGITAL DATA SHARING IN A SYSTEMATIC WAY. THE PROPOSED STUDY WILL ENROLL ADULTS (N = 320) WITH OVERWEIGHT/ OBESITY IN A 24-MONTH LM PROGRAM AND INSTRUCT THEM TO USE DIGITAL TOOLS FOR SELF-MONITORING OF WEIGHT, PHYSICAL ACTIVITY, AND EATING ON A DAILY BASIS. GROUPS WILL MEET FACE-TO-FACE WEEKLY IN MONTHS 1-3 TO INITIATE WEIGHT LOSS. IN MONTHS 4-24, INTERVENTION CONTACT WILL BE REMOTE AND WILL INCLUDE THE FOLLOWING: QUARTERLY GROUP MEETINGS HELD VIA VIDEOCONFERENCE; BRIEF PHONE CALLS WITH THE COACH HELD TWICE PER QUARTER; AND MONTHLY TEXT MESSAGES WITH THE COACH, WITH A SMALL GROUP OF FELLOW GROUP PARTICIPANTS, AND WITH A FRIEND OR FAMILY MEMBER OUTSIDE OF THE PROGRAM. A 2 X 2 X 2 FACTORIAL DESIGN WILL TEST THE INDEPENDENT EFFECTS OF THREE TYPES OF DATA SHARING PARTNERSHIPS: COACH SHARE, GROUP SHARE, AND FRIEND/FAMILY SHARE. HALF OF THE PARTICIPANTS WILL RECEIVE COACH SHARE AND HALF WILL NOT; HALF WILL RECEIVE GROUP SHARE AND HALF WILL NOT; AND HALF WILL RECEIVE FRIEND/FAMILY SHARE AND HALF WILL NOT. IN COACH SHARE, THE BEHAVIORAL COACH WILL VIEW DIGITAL SELF-MONITORING DATA THROUGHOUT THE PROGRAM AND WILL DIRECTLY ADDRESS DATA OBSERVATIONS DURING INTERVENTION CONTACTS. IN GROUP SHARE, PARTICIPANTS IN A GIVEN LM GROUP WILL VIEW EACH OTHER’S SELF-MONITORING DATA IN THEIR SMALL-GROUP TEXT MESSAGES. IN FRIEND/FAMILY SHARE, A FRIEND OR FAMILY MEMBER OUTSIDE OF THE GROUP WILL VIEW THE PARTICIPANT’S DATA VIA AUTOMATED TEXT MESSAGE. EACH PARTY WITH WHOM DATA ARE SHARED WILL BE TRAINED TO RESPOND BY ELICITING REFLECTION FROM THE INDEX PARTICIPANT ON HIS/HER GOAL PROGRESS, WHICH IS A KEY COMPONENT OF SELF-REGULATION, AND SUPPORTING THE PARTICIPANT’S MOTIVATION TO MEET PROGRAM GOALS. AMOUNT OF INTERVENTION CONTACT BETWEEN THE PARTICIPANT AND EACH PARTY (COACH, GROUP, FRIEND/FAMILY) WILL BE COMPARABLE ACROSS TREATMENT CONDITIONS, ISOLATING THE EFFECTS OF DATA SHARING COMPONENTS. OUTCOMES WILL BE MEASURED AT MONTHS 0, 6, 12, AND 24. THE STUDY WILL DETERMINE IF COACH SHARE, GROUP SHARE, AND FRIEND/FAMILY SHARE EACH IMPROVE LONG-TERM WEIGHT LOSS, PA, AND CALORIE INTAKE (I.E., OUTCOMES WILL BE COMPARED FOR PARTICIPANTS WHO ARE RANDOMIZED TO ENGAGE IN THAT DATA SHARING PARTNERSHIP, VERSUS THOSE WHO ARE NOT). THE STUDY ALSO WILL EXAMINE IF EFFECTS ARE ADDITIVE WHEN PARTICIPANTS ARE ASSIGNED TO ENGAGE IN MORE THAN ONE TYPE OF DATA SHARING PARTNERSHIP. MEDIATORS AND MODERATORS OF INTERVENTION EFFECTS WILL BE EXAMINED. AS DIGITAL TECHNOLOGY MAKES DATA SHARING INCREASINGLY FEASIBLE, IT IS CRITICAL TO DETERMINE HOW TO OPTIMIZE THESE PARTNERSHIPS TO IMPROVE LONG-TERM OUTCOMES IN LM.

NEUTRINO AND DARK MATTER RESEARCH AT DREXEL

MINDFULNESS AND ACCEPTANCE-BASED INTERVENTIONS FOR OBESITY: USING A FACTORIAL DESIGN TO IDENTIFY THE MOST EFFECTIVE COMPONENTS

ROLE OF O-GLCNACOME ON BREAST CANCER INITIATING CELLS

SOLUBLE TNFA IN THE DEVELOPMENT OF AUTONOMIC DYSREFLEXIA AFTER SPINAL CORD INJURY

AN ONLINE REFLECTION AND COMMUNITY-BASED INSTRUCTIONAL DEVELOPMENT SYSTEM FOR MATHEMATICS EDUCATION

CATALYZING STEM EDUCATION VIA THE NAE ENGINEERING GRAND CHALLENGES

THE MECHANISM OF ALLOSTERIC MODULATION OF GLUTAMATE TRANSPORTERS

A TEST OF NUTRITIONAL INTERVENTIONS TO ENHANCE WEIGHT LOSS MAINTENANCE

RYAN WHITE TITLE IV WOMEN, INFANTS, CHILDREN, YOUTH AND AFFECTED FAMILY MEMBERS AIDS HEALTHCARE

MULTISCALE MODEL OF NEURAL CONTROL OF BREATHING

BOOSTING ANTI-HIV IMMUNITY THROUGH MANIPULATION OF TFH FUNCTION.

SENSORY PATHWAYS FOR CONDITIONED STIMULUS DETECTION DURING AVOIDANCE BEHAVIOR

NEURAL ALGORITHMS UNDERLYING DIVERSITY IN VISUAL FEATURE INTEGRATION

FUNCTIONAL ASSAYS OF PLASMODIUM VIVAX DBP, EBP, AND RBP2B IN ERYTHROCYTE INVASION IN DUFFY-NEGATIVE AFRICANS - PROJECT SUMMARY TITLE: PLASMODIUM VIVAX ERYTHROCYTE INVASION MECHANISMS AND HUMORAL IMMUNE RESPONSE IN DUFFY NEGATIVE AFRICANS INDIVIDUALS OF AFRICAN ANCESTRY WERE THOUGHT TO BE PROTECTED FROM PLASMODIUM VIVAX BECAUSE THEY LACK DUFFY ANTIGEN EXPRESSION ON THE SURFACE OF THEIR ERYTHROCYTES RENDERING P. VIVAX UNABLE TO INVADE THEIR RED BLOOD CELLS. HOWEVER, AN INCREASING NUMBER OF P. VIVAX CASES REPORTED ACROSS AFRICA AND IN DUFFY-NEGATIVE INDIVIDUALS CHALLENGES THIS CONVENTIONAL DOGMA, RAISING THE POSSIBILITY THAT SOME P. VIVAX LINEAGES HAVE EVOLVED TO USE LIGANDS OTHER THAN DUFFY BINDING PROTEIN FOR ERYTHROCYTE INVASION. THE INTRINSIC INVASION MECHANISM AND IMMUNE RESPONSE OF DUFFY-NEGATIVE INDIVIDUALS TO P. VIVAX ARE LARGELY UNKNOWN. IN THIS APPLICATION, WE WILL INVESTIGATE THE EXPRESSION AND FUNCTION OF ERYTHROCYTE BINDING GENES IN DUFFY-NEGATIVE P. VIVAX AND THE ANTIBODY RESPONSE OF DUFFY-NEGATIVE INDIVIDUALS TO P. VIVAX ANTIGENS. THERE ARE THREE SPECIFIC AIMS: 1) TO IDENTIFY GENES WITH DIFFERENTIAL EXPRESSION BETWEEN DUFFY-POSITIVE AND DUFFY-NEGATIVE P. VIVAX BY RNA-SEQ; 2) TO DETERMINE IN VITRO BINDING AND INVASION ACTIVITIES OF P. VIVAX CANDIDATE LIGAND PROTEINS TO DUFFY-NEGATIVE RED BLOOD CELLS; AND 3) TO EXAMINE IN VIVO ANTIBODY LEVELS TO TARGETED P. VIVAX ANTIGENS ASSOCIATED WITH ERYTHROCYTE INVASION IN DUFFY- NEGATIVE PATIENTS. THE PROPOSED RESEARCH WILL BE CONDUCTED IN ETHIOPIA, WHERE MALARIA IS A MAJOR PUBLIC HEALTH PROBLEM AND ABOUT 30% OF THE 1.2 MILLION CONFIRMED MALARIA CASES WERE P. VIVAX. AS OUR STUDY SITES HAVE A LARGE NUMBER OF P. VIVAX CASES AND A SIGNIFICANT PROPORTION OF DUFFY-NEGATIVE INDIVIDUALS, WE HAVE A UNIQUE OPPORTUNITY TO STUDY THE INVASION MECHANISMS OF P. VIVAX IN AFRICA. WE HAVE A COLLABORATIVE TEAM AND LOGISTICS IN PLACE FOR SAMPLE COLLECTION AND PROCESSING. OUR ESTABLISHED LAB CULTURE FACILITY CLOSES TO THE HEALTH CENTERS AND SUCCESSFUL P. VIVAX TRANSCRIPTOME DATA OBTAINED FROM CULTURED SCHIZONTS HAVE DEMONSTRATED THE FEASIBILITY OF THIS RESEARCH. COMPARISON OF P. VIVAX TRANSCRIPTOMES BETWEEN DUFFY-NEGATIVE AND DUFFY-POSITIVE INDIVIDUALS FROM BOTH IN VITRO AND IN VIVO SAMPLES WILL PROVIDE THE FIRST DESCRIPTION OF GENETIC AND FUNCTIONAL ATTRIBUTES OF P. VIVAX THAT PERMIT INFECTION OF DUFFY-NEGATIVE ERYTHROCYTES. THIS RESEARCH WILL SIGNIFICANTLY ENHANCE THE UNDERSTANDING OF INVASION MECHANISM OF P. VIVAX IN DUFFY- NEGATIVE INDIVIDUALS AND LAY A FOUNDATION FOR MOLECULAR AND BIOCHEMICAL CHARACTERIZATIONS OF P. VIVAX LIGAND-RECEPTOR INTERACTIONS. KNOWLEDGE OF P. VIVAX INVASION MECHANISMS AND HOST IMMUNE RESPONSES WILL HAVE IMPORTANT IMPLICATIONS FOR P. VIVAX VACCINE DEVELOPMENT AND VIVAX MALARIA RISK ASSESSMENT BOTH WITHIN AND OUTSIDE AFRICA.

RESPONSE TECHNOLOGIES FOR COMPLEX EMERGENCIES

COMMUNITIES DESIGNED TO SUPPORT CARDIOVASCULAR HEALTH FOR OLDER ADULTS

MULTIVALENT CHIMERIC SUBUNIT MALARIA VACCINES

THE HEALTH CONSEQUENCES OF URBAN SCALING

MODULATION OF NOREPINEPHRINE BY CANNABINOIDS

ACCEPTANCE-BASED BEHAVIORAL TREATMENT FOR OBESITY: MAINTENANCE AND MECHANISMS.

ROLE OF CHEMOKINE RECEPTORS IN NEURONAL SURVIVAL

FOOD INSECURITY, NEIGHBORHOOD ENVIRONMENT, AND WEIGHT TRAJECTORIES IN YOUNG CHILDREN: IMPLICATIONS FOR FOOD ASSISTANCE POLICY - PROJECT SUMMARY NEARLY 14% OF US HOUSEHOLDS WITH CHILDREN WERE FOOD INSECURE BEFORE THE START OF THE COVID-19 CRISIS, AND THIS NUMBER INCREASED DRAMATICALLY DURING THE PANDEMIC. FOOD INSECURITY (FI)— INADEQUATE ACCESS TO ENOUGH FOOD FOR EVERY PERSON IN A HOUSEHOLD TO LIVE AN ACTIVE, HEALTHY LIFE—THREATENS CRITICAL EARLY CHILDHOOD GROWTH AND CAN PUT CHILDREN AT RISK FOR POOR SHORT- AND LONG-TERM HEALTH. FI IS ALSO A MAJOR SOURCE OF INEQUITY AMONG CHILDREN: COMPARED TO WHITE HOUSEHOLDS WITH CHILDREN, BLACK HOUSEHOLDS ARE 3 TIMES AS LIKELY AND LATINX HOUSEHOLDS OVER TWICE AS LIKELY TO EXPERIENCE FI. THE DEGREE TO WHICH HOUSEHOLD FI IMPACTS CHILDREN’S DIET AND WEIGHT MAY VARY DEPENDING ON CAREGIVERS’ SHIELDING BEHAVIORS (E.G., SKIPPING MEALS TO PRIORITIZE FEEDING THEIR CHILDREN), CHARACTERISTICS OF THE NEIGHBORHOODS WHERE FAMILIES LIVE (E.G., HEALTHY FOOD ACCESS), AND PARTICIPATION IN FOOD ASSISTANCE PROGRAMS. THE SPECIAL SUPPLEMENTAL NUTRITION PROGRAM FOR WOMEN, INFANTS, AND CHILDREN (WIC) IS AN IMPORTANT EVIDENCE-BASED PROGRAM THAT SUPPORTS EQUITABLE CHILD HEALTH BY PROVIDING FAMILIES WITH CHILDREN AGED 0–4 ACCESS TO NUTRITIONALLY AND DEVELOPMENTALLY APPROPRIATE FOODS AND COUNSELING. HOWEVER, ONLY HALF OF THOSE WHO ARE ELIGIBLE FOR WIC PARTICIPATE; AMONG THOSE WHO DO PARTICIPATE, NONREDEMPTION OR PARTIAL REDEMPTION OF THE MONTHLY BENEFIT IS COMMON. MAXIMIZING THE EFFECTIVENESS OF THIS CORNERSTONE FOOD ASSISTANCE PROGRAM REQUIRES UNDERSTANDING THE MULTILEVEL FACTORS THAT INFLUENCE FAMILIES’ PARTICIPATION AND USE OF THE BENEFIT. THE GOAL OF THE PROPOSED EXPLORATORY SEQUENTIAL MIXED-METHODS STUDY IS TO INFORM IMPLEMENTATION OF WIC AND OTHER FOOD ASSISTANCE POLICIES BY ANALYZING HOW HOUSEHOLD FI IS ASSOCIATED WITH WEIGHT TRAJECTORIES AMONG YOUNG CHILDREN, AND HOW THIS ASSOCIATION IS MODIFIED BY NEIGHBORHOOD ENVIRONMENT AND PUBLIC FOOD ASSISTANCE PROGRAMS. WE WILL ACCOMPLISH THIS GOAL THROUGH THE FOLLOWING SPECIFIC AIMS: AIM 1: CONDUCT IN-DEPTH QUALITATIVE FOCUS GROUPS WITH CAREGIVERS WITH LOW INCOMES TO INVESTIGATE FAMILIES’ FOOD PURCHASING, FEEDING PRACTICES, AND FOOD INSECURITY DURING THE COVID-19 CRISIS AND ECONOMIC RECOVERY, INCLUDING RECENT CHANGES IN WIC AND NEIGHBORHOOD CHARACTERISTICS. AIM 2: ASSESS WHETHER FI AT AGE 2 TO 36 MONTHS PREDICTS WEIGHT GAIN TRAJECTORIES TO AGE 3 AND 6 YEARS BEFORE AND AFTER ONSET OF THE COVID-19 CRISIS. AIM 3: ASSESS INTERACTIONS BETWEEN FI AND (FOCUS GROUP-IDENTIFIED) NEIGHBORHOOD ENVIRONMENTS IN EARLY LIFE AS PREDICTORS OF CHILD WEIGHT GAIN TRAJECTORIES TO AGE 3 AND 6 YEARS BEFORE AND AFTER ONSET OF THE COVID-19 CRISIS. WE WILL INTEGRATE QUALITATIVE AND QUANTITATIVE FINDINGS IN AN INTEGRATIVE REPORT TO INFORM WIC PROGRAM RECOMMENDATIONS TO BEST SUPPORT FAMILIES’ HEALTHY FEEDING CHOICES AND CHILDREN’S HEALTHY GROWTH IN THE CONTEXT OF MULTILEVEL CONTRIBUTING FACTORS. THE EVIDENCE WE PRODUCE CAN BE USED TO IMPROVE WIC IMPLEMENTATION TO SUPPORT FAMILIES WITH YOUNG CHILDREN IN METROPOLITAN AREAS LONG-TERM AND IN TIMES OF CRISIS.

WE PROPOSE TO DEVELOP A 3D MODEL OF A CORONAL ACTIVE REGION'S MAGNETIC FIELD. THE MODEL WILL HAVE FIVE PRINCIPAL SOFTWARE COMPONENTS, 1. A MAGNETOGRA

EXPANDING THE DREXEL CENTER OF EXCELLENCE FOR URBAN INTEGRATED OUD HEALTHCARE: PREVENTION, IDENTIFICATION, ENGAGEMENT AND TREATMENT FOR OUD IN PHILADELPHIA - EXPANDING OUD TREATMENT IN PHILADELPHIA: IN 2019, THE STATE OF PENNSYLVANIA (PA) HAD THE 3RD HIGHEST DRUG OVERDOSE DEATH RATE IN THE COUNTRY. IN PHILADELPHIA, THE OPIOID EPIDEMIC HAS WORSENED AMID COVID-19. DESPITE SIGNIFICANT EFFORTS TO IDENTIFY AND ENGAGE INDIVIDUALS WITH OPIOID USE DISORDER (OUD), THERE WERE 1.150 OVERDOSE DEATHS, MANY IN NON-PUBLIC PLACES, WITH INCREASES PREDICTED DURING THE PANDEMIC. DREXEL UNIVERSITY (DU), A LARGE COMMUNITY FOCUSED UNIVERSITY PROVIDING HEALTHCARE SERVICES AND HEALTHCARE EDUCATION TO HIGH-RISK POPULATIONS, WILL EXPAND OUR OUD PREVENTION, IDENTIFICATION AND ENGAGEMENT INTO INTEGRATED TREATMENT SERVICES INCLUDING MAT FOR 470 NEWLY IDENTIFIED INDIVIDUALS OVER FIVE YEARS. OUR PRIMARY GOAL IS TO REDUCE OUD BY PROVIDING ENHANCED AND INNOVATIVE TREATMENT ENGAGEMENT AND SUSTAINED RECOVERY WITH A FAMILY CENTERED FOCUS. DU, WITH 1060 MEDICAL STUDENTS, 24,205 UNDERGRADUATE AND GRADUATE STUDENTS INCLUDING PUBLIC HEALTH AND NURSING STUDENTS, A STRONG FAMILY THERAPY PROGRAM AND OVER 520 CLINICAL FACULTY, PROPOSES TO EXPAND OUR URBAN CENTER OF EXCELLENCE IN OUD HEALTHCARE TO: 1) EXPAND ENGAGEMENT IN MAT ADDICTION TREATMENT SERVICES AND TREATMENT FOR CO-OCCURRING PSYCHIATRIC DISORDERS FROM HIV CLINICS, OBSTETRICAL SERVICES, PRIMARY AND PEDIATRIC CARE PRACTICES, AND INPATIENT HOSPITALS, FOR CITIZENS RETURNING FROM INCARCERATION AND INPATIENT OUD TREATMENT, IN FREE CLINICS AND SHELTERS SERVING THE HOMELESS AND FOR INDIVIDUALS IN EMERGENCY DEPARTMENTS; 2) EXPAND ASSESSMENT AND ENGAGEMENT FOR MOTHERS WHO DELIVER SUBSTANCE EXPOSED INFANTS IN COLLABORATION WITH THE PHILADELPHIA DEPT. OF HUMAN SERVICES (DHS); 3)ADDRESS THE INTERGENERATION NATURE OF SUD/OUDS BY CREATING EXPERTISE AT ST CHRISTOPHER'S HOSPITAL FOR CHILDREN'S (SCHC) CLINICAL PRACTICES TO IDENTIFY/ENGAGE CHILDREN, TEENS AND FAMILIES AT RISK FOR OUD FOR PREVENTION, NARCAN TRAINING AND TREATMENT SERVICES; 4) EXPAND SCREENING OF DU STUDENTS AT RISK FOR OUD VIA STUDENT HEALTH SERVICES; 5) EXPAND OUR COHORT OF TRAINED PEER SPECIALIST TO IDENTIFY AND ENGAGE AT RISK INDIVIDUALS IN RECOVERY ACROSS THE CITY; AND 6) EXPAND EDUCATIONAL PROGRAMS TO ALL DU HEALTHCARE PROVIDERS, TRAINEES AND AFFILIATES IN SAFE PRESCRIBING, ASSESSMENT OF AT-RISK INDIVIDUALS, NARCAN TRAINING, INITIATION OF MAT AND REFERRAL FOR ADDICTION TREATMENT TO INCREASE THE OUD HEALTHCARE WORKFORCE. DU WILL EXPAND ITS EXISTING PROGRAMS. 1) THE CARING TOGETHER PROGRAM (CTP) PROVIDES ADDICTION/MAT AND PSYCHIATRIC TREATMENT FOR WOMEN INCLUDING THOSE PREGNANT/PARENTING WOMEN AND REENTERING THE COMMUNITY. DHS HAS DESIGNATED CTP AS A PRIMARY SITE TO EVALUATE/TREAT CASES OF PERI-NATAL SUBSTANCE EXPOSURE; 2) SCHC PROVIDES PRIMARY AND TERTIARY CARES FOR OVER 20,000 PATIENTS IN HIGH RISK AREAS; 3) PARTNERSHIP PRACTICE FOR 1,600 HIV+ INDIVIDUALS; 4) FAMILY MEDICINE/STUDENT HEALTH SERVICES; 5) MERAKEY, WHICH PROVIDES MAT/ADDICTION SERVICES ACROSS THE CITY, AND: 6) OFFICE OF MEDICAL EDUCATION AND BEHAVIORAL HEALTH EDUCATION, SCHOOLS OF NURSING AND HEALTH PROFESSIONS AND PUBLIC HEALTH. QUANTITATIVE AND QUALITATIVE DATA WILL BE COLLECTED DURING INTAKE, AT 6 MONTHS POST-INTAKE AND AT DISCHARGE TO EVALUATE ATTAINMENT OF THE PROJECT GOALS

NOVEL LONGEVITY ENHANCING PATHWAYS REGULATED BY MTOR - ABSTRACT/SUMMARY INHIBITORS OF THE MTOR PATHWAY ARE AMONG THE MOST PROMISING INTERVENTIONS TO TARGET AGE-RELATED DYSFUNCTION, HOWEVER, THERE IS A CRITICAL NEED TO FURTHER DEFINE THE PRO LONGEVITY EFFECTS TO FACILITATE CLINICAL DEVELOPMENT OF MTOR INHIBITORS. THE CURRENT PROPOSAL WILL SIGNIFICANTLY ADVANCE THIS EFFORT PROVIDING NEW TARGETS FOR INTERVENTION AND NOVEL MARKERS TO MONITOR INDIVIDUAL RESPONSES TO MTOR INHIBITION. THE OVERARCHING GOAL OF THIS RESEARCH PROGRAM IS TO DEVELOP A MECHANISTIC UNDERSTANDING OF NOVEL DOWNSTREAM TARGETS OF RAPAMYCIN, IN ORDER TO FACILITATE SAFER AND MORE EFFECTIVE STRATEGIES TO PROMOTE HEALTHY AGING. CELLULAR SENESCENCE OCCURS IN BOTH SOMATIC AND STEM CELL POPULATIONS AND CONTRIBUTES TO AGE-RELATED DYSFUNCTION, AND OUR LABORATORY HAS SHOWN THAT MTOR INHIBITION USING RAPAMYCIN, CAN PREVENT ENTRY INTO THE SENESCENT STATE. THE MTOR PATHWAY ALSO REGULATES SENESCENCE A N D PLURIPOTENCY IN A VARIETY OF STEM CELL POPULATIONS. THE CENTRAL HYPOTHESIS OF THE APPLICATION IS THAT MTOR INHIBITION BY RAPAMYCIN PREVENTS SENESCENCE AND ENHANCES PLURIPOTENCY BY INCREASING THE LNCRNA H19. THE RATIONALE FOR THIS HYPOTHESIS IS OUR OBSERVATION THAT RAPAMYCIN INCREASES LEVELS OF THE NON- CODING RNA (LNCRNA) H19. WE FIND THAT LEVELS OF H19 DECREASE DURING SENESCENCE AND IN PLURIPOTENT CELLS. H19 PLAYS A CENTRAL ROLE DURING DEVELOPMENT AND DIFFERENTIATION, AND MAINTENANCE OF ADULT STEM CELL POPULATIONS. RAPAMYCIN INCREASES H19 LEVELS, PREVENTS SENESCENCE AND MAINTAINS PLURIPOTENCY. THE RESULTS SUGGEST THAT INCREASING H19 LEVELS IN RESPONSE TO MTOR INHIBITION MAY PLAY A DUAL ROLE, INHIBITING SENESCENCE WHILE SIMULTANEOUSLY INCREASING PLURIPOTENCY IN ADULT STEM CELL POPULATIONS. THE PROPOSED WORK WILL PROVIDE TRANSFORMATIVE DATA REGARDING A NOVEL MECHANISM FOR LIFESPAN EXTENSION AND IMPROVEMENT OF LATE-LIFE FUNCTION IN MULTIPLE TISSUES.

EXAMINING DIETARY MODIFIERS OF ASSOCIATIONS BETWEEN AIR POLLUTION AND AUTISM-RELATED OUTCOMES IN TWO COHORTS - PROJECT SUMMARY PRENATAL AIR POLLUTION EXPOSURE HAS BEEN REPEATEDLY IDENTIFIED AS RISK FACTOR FOR AUTISM SPECTRUM DISORDER (ASD), WITH SUPPORT FOR ASSOCIATIONS WITH PARTICULATE MATTER LESS THAN 2.5 MICRONS IN DIAMETER (PM2.5), OZONE, AND NITROGEN DIOXIDE (NO2). RESEARCH FROM OTHER FIELDS SUGGESTS DIET MAY BE A KEY MODULATOR OF AIR POLLUTION RISKS IN PATHWAYS RELEVANT TO AUTISM, YET ONLY ONE STUDY, EXAMINING THE JOINT EFFECTS OF FOLATE AND AIR POLLUTION, HAS BEEN PUBLISHED ON ASD RISK. HOWEVER, A RANGE OF DIETARY FACTORS BEYOND FOLATE, INCLUDING POLYUNSATURATED FATTY ACIDS (PUFAS) AND VITAMIN D, MAY SERVE TO OFFSET EFFECTS OF EXPOSURES. IN ADDITION, GIVEN THAT NUTRIENTS DO NOT ACT IN ISOLATION, STUDYING SINGLE NUTRIENT-POLLUTANT INTERACTIONS MAY PROVIDE ONLY PART OF THE PICTURE. FURTHER, TIME- WINDOWS FOR SUCH MODIFICATION HAVE NOT BEEN IDENTIFIED. IN THE PROPOSED STUDY, WE WILL ADDRESS THESE GAPS AND EXAMINE HOW PRENATAL DIET MAY MODIFY AIR POLLUTANT ASSOCIATIONS WITH ASD-RELATED OUTCOMES IN TWO PROSPECTIVE COHORTS. THE NURSES’ HEALTH STUDY 3 (NHS3) IS AN ONGOING, LARGE PROSPECTIVE COHORT OF NURSES FROM ACROSS THE US THAT INCLUDES A PREGNANCY SUB-COHORT (N>7,000). THE EARLY AUTISM RISK LONGITUDINAL INVESTIGATION (EARLI) IS A HIGH-RISK COHORT THAT FOLLOWED MOTHERS WHO ALREADY HAD A CHILD WITH ASD THROUGH A SUBSEQUENT PREGNANCY UNTIL THAT CHILD WAS AGE 3 (N~200). ASD-RELATED OUTCOMES WILL BE CAPTURED IN BOTH STUDIES ACCORDING TO SOCIAL RESPONSIVENESS SCALE (SRS) SCORES, AS WELL AS ASD DIAGNOSIS, ALLOWING US TO CONSIDER BOTH DIMENSIONAL TRAITS ACROSS THE POPULATION AND DIAGNOSTIC-LEVEL RISKS. BOTH STUDIES WILL HAVE AIR POLLUTION EXPOSURE ASSIGNMENTS FOR PM2.5, NO2, AND OZONE FROM THE SAME METHOD AND PRENATAL NUTRIENT DATA FROM VALIDATED FOOD FREQUENCY QUESTIONNAIRES. USING THESE DATA, OUR AIMS ARE TO: 1) EXAMINE MODIFICATION OF AIR POLLUTANT-ASD ASSOCIATIONS BY FOLATE, VITAMIN D, AND PUFAS; 2) EVALUATE INTERACTIONS BETWEEN AIR POLLUTANTS AND NUTRIENTS ON ASD-RELATED OUTCOMES WITHIN A MULTI-EXPOSURE FRAMEWORK; AND 3) EXAMINE TIME WINDOWS IN THE AIR POLLUTION-ASD RELATIONSHIP WHEN DIETARY NUTRIENTS MIGHT BE MOST IMPACTFUL. AIM 1 ANALYSES WILL USE LINEAR AND LOGISTIC REGRESSION TO EXAMINE ASSOCIATIONS WITH SRS SCORES AND ASD DIAGNOSIS, RESPECTIVELY, WITHIN STRATA OF NUTRIENTS DEFINED BY DEFICIENCY STATUS AND PRIOR INTERACTION IN EACH COHORT. IN AIM 2, WE WILL USE BAYESIAN KERNEL MACHINE REGRESSION (BKMR) TO CONSIDER NUTRIENT-POLLUTANT INTERACTIONS WITHIN THE CONTEXT OF BROADER DIET, ACCOUNTING FOR A WIDER SET OF NUTRIENTS AND CONSIDERING POTENTIAL COMBINED EFFECTS ON ASD OUTCOMES. IN AIM 3, WE WILL USE DISTRIBUTED LAG MODELS TO CONSIDER POTENTIAL CRITICAL WINDOWS OF AIR POLLUTANT ASSOCIATIONS WITH ASD-RELATED OUTCOMES IN WHICH NUTRIENT MODIFIERS MAY HAVE STRONGEST EFFECTS. IN THIS PROPOSAL WE ADDRESS A CRITICAL, YET UNDERSTUDIED, AREA OF RESEARCH. DUE TO THE WIDESPREAD OCCURRENCE OF AIR POLLUTION EXPOSURE, AND BECAUSE DIET IS A READILY ACCESSIBLE, INDIVIDUAL- LEVEL MODIFIABLE FACTOR, FINDINGS FROM THIS PROJECT PRESENT THE POTENTIAL FOR A LARGE PUBLIC HEALTH IMPACT.

RYAN WHITE TITLE IV WOMEN, INFANTS, CHILDREN, YOUTH AND AFFECTED FAMILY MEMBERS AIDS HEALTHCARE

COMPOSITIONAL CONTROL OF FUNDAMENTAL ELECTRONIC AND MAGNETIC PROPERTIES OF ORDERED LAYERED MULTIELEMENTAL MXENES

AN INNOVATIVE, PHYSICAL ACTIVITY-FOCUSED APPROACH TO WEIGHT LOSS MAINTENANCE

SCI-INDUCED DEFICITS IN ANTIVIRAL IMMUNITY: THE ROLE OF STNF.

PIRE: HUMANOIDS - UNIVERSALLY ACCESSIBLE INFRASTRUCTURES TO ADVANCE CAPABILITIES

PHILADELPHIA URBAN HEALTH COLLABORATIVE FOR SUBSTANCE USE DISORDER: MOBILE SERVICES FOR PREVENTION, ENGAGEMENT IN CARE AND TREATMENT

SENSITIVITY OF TODDLER SCREENING: INTEGRATING CONCURRENT AND PROSPECTIVE STRATEGIES TO DETECT ASD - SCREENING FOR AUTISM SPECTRUM DISORDER (ASD) DURING WELL-CHILD PEDIATRIC CHECK-UPS REDUCES THE AGE OF DIAGNOSIS, ALLOWING MORE TIME FOR CRITICAL EARLY INTERVENTION. FURTHERMORE, UNIVERSAL SCREENING MITIGATES DISPARITIES IN THE AGE OF DIAGNOSIS FOR MINORITIES, AND HAS BEEN DEMONSTRATED TO BE FEASIBLE IN COMMUNITY- BASED PRIMARY CARE SETTINGS. HOWEVER, LIMITED FOLLOW-UP OF TODDLERS WHO SCREENED NEGATIVE IS A NOTABLE GAP IN THE LITERATURE THAT CONTRIBUTED TO THE UNITED STATES PREVENTIVE SERVICES TASK FORCE’S (USPSTF) DETERMINATION OF INSUFFICIENT EVIDENCE TO RECOMMEND UNIVERSAL ASD SCREENING AT PRESENT. FOLLOW-UP OF CHILDREN WHO ARE NOT IDENTIFIED AT RISK IS COST- AND LABOR-INTENSIVE, BUT IS CRITICAL TO DETERMINE THE SENSITIVITY OF TODDLER ASD SCREENING. THIS STUDY WILL BE AMONG THE FIRST TO USE RIGOROUS PROSPECTIVE DETECTION STRATEGIES IN A LARGE, LOW-RISK SAMPLE THAT PREVIOUSLY HAD CONCURRENT DETECTION. THE GOAL OF THE PROPOSED STUDY IS TO FIND MISSED CASES BY RESCREENING CHILDREN WHO WERE NOT IDENTIFIED WITH ASD DURING THE COURSE OF THREE PRIOR SCREENING STUDIES THAT ADMINISTERED THE MODIFIED CHECKLIST FOR AUTISM IN TODDLERS, REVISED, WITH FOLLOW-UP DURING TODDLER WELL CHILD VISITS. THIS INCLUDES THOSE WHO SCREENED NEGATIVE AS TODDLERS, AS WELL AS CHILDREN WHO SCREENED POSITIVE BUT EITHER WERE LOST TO FOLLOW-UP OR WERE EVALUATED AND NOT DIAGNOSED WITH ASD. THE SPECIFIC AIMS ARE TO MEASURE PROSPECTIVE SENSITIVITY USING RIGOROUS CASE CONFIRMATION FOR POTENTIAL MISSED CASES. WE WILL IDENTIFY PATTERNS IN TODDLER SCREENING OUTCOMES FOR THESE MISSED CASES; WE PREDICT THAT CHILDREN WHOSE FIRST SCREEN WAS YOUNGER AND THOSE WHO DID NOT COMPLETE MULTIPLE SCREENS ARE MORE LIKELY TO BE MISSED CASES COMPARED TO THOSE SCREENED AT OLDER TODDLER VISITS AND RESCREENED BY AGE THREE. FINALLY, WE WILL EXAMINE WHETHER MISSED CASES ARE MORE LIKELY TO HAVE MILDER ASD SYMPTOMS, GREATER LIKELIHOOD OF PSYCHIATRIC COMORBIDITIES, AND BE FEMALE COMPARED TO CHILDREN WHO DEMONSTRATED RISK AS TODDLERS BUT WERE NOT DIAGNOSED WITH ASD UNTIL THEY WERE OLDER. ALTHOUGH THESE CHARACTERISTICS HAVE BEEN HYPOTHESIZED, RIGOROUS EVIDENCE IS LACKING TO DEMONSTRATE DIFFERENCES BETWEEN CHILDREN WITH ASD MISSED BY TODDLER SCREENING. THE MAJORITY OF THE MULTI-SITE SAMPLE (TOTAL N = 8,751) SCREENED NEGATIVE AT ONE OR MORE PEDIATRIC VISITS BETWEEN 1 AND 3 YEARS OLD (N = 8,091). IN ADDITION, WE WILL RESCREEN CHILDREN WHO SCREENED POSITIVE BUT DID NOT ATTEND THE EVALUATION (N = 426), WHICH OFTEN SIGNALS LACK OF PARENT CONCERN, AND CHILDREN EVALUATED AND CLASSIFIED AS NONASD (N = 234), WHO MAY HAVE DEVELOPED CLINICALLY SIGNIFICANT ASD SYMPTOMS AS THEY AGED. PARENTS WILL BE INVITED TO ENROLL AND RESCREEN THEIR CHILD, NOW 7-14 YEARS OLD, USING A SECURE WEB-BASED PORTAL. ALL AT RISK CHILDREN, AND A RANDOM SAMPLE OF LOW-RISK CASES, WILL BE INVITED FOR A COMPREHENSIVE, RESEARCH-RELIABLE EVALUATION; FINAL ASD OUTCOMES WILL BE USED TO CALCULATE PROSPECTIVE SENSITIVITY, WHICH WILL BE COMPARED TO LITERATURE REPORTING SENSITIVITY BASED ON RECORD REVIEW STRATEGIES. RESULTS OF THIS PROPOSED STUDY WILL DIRECTLY ADDRESS A GAP IDENTIFIED BY THE USPSTF, AND WILL ADDRESS THE INTERAGENCY AUTISM COORDINATING COMMITTEE’S QUESTION 1 ABOUT EARLY DETECTION OF ASD.

INTEGRATING PRECLINICAL MODELS TO DEVELOP CONVERGING MECHANISTIC DATA IN CO-OCCURRING HIV AND SUBSTANCE USE

WEIGHT SUPPRESSION, DIETING AND BULIMIA NERVOSA: A BIOBEHAVIORAL STUDY

PLASMODIUM INVASION MACHINERY

ENVIRONMENTAL AND ACCEPTANCE-BASED INNOVATIONS FOR WEIGHT LOSS MAINTENANCE

WEIGHT HISTORY, BRAIN ACTIVATION TO FOOD CUES AND EATING DISORDER PSYCHOPATHOLOGY

COMBINING MOLECULAR SIMULATIONS AND BIOPHYSICAL METHODS TO CHARACTERIZE CONFORMATIONAL DYNAMICS OF THE HIV-1 ENVELOPE GLYCOPROTEIN - PROJECT SUMMARY THE HIV-1 ENVELOPE GLYCOPROTEIN SPIKE (ENV) MEDIATES VIRAL ENTRY INTO TARGET CELLS. BECAUSE ENV IS THE ONLY VIRAL PROTEIN ON THE VIRION SURFACE, IT IS CENTRAL TO THE DEVELOPMENT OF POTENTIAL VACCINES AND SMALL-MOLECULE ENTRY INHIBITORS. ENV IS A UNIQUELY FLEXIBLE MOLECULAR MACHINE, AND DEEP UNDERSTANDING OF ITS IMMUNOGENICITY AND SUSCEPTIBILITY TO INHIBITION REQUIRES AN APPRECIATION OF ITS ATOMICALLY RESOLVED CONFORMATIONAL DYNAMICS. STRUCTURAL STUDIES USING TRUNCATED, SOLUBILIZED, AND STABILIZED ENV CONSTRUCTS HAVE YIELDED DETAILED ATOMIC MODELS OF ITS MAIN OPEN AND CLOSED CONFORMATIONAL STATES. EMERGING STRUCTURAL STUDIES OF FULL-LENGTH ENV SUPPORT IDENTIFICATION OF ASYMMETRIC CLOSED CONFORMATIONS AS THE “DEFAULT INTERMEDIATE STATE” (DIS), REVEALING DETAILS OF A POTENTIALLY PIVOTAL ROLE OF QUATERNARY ASYMMETRY IN ENV CONFORMATIONAL DYNAMICS. AT THE SAME TIME, BOTH SINGLE-MOLECULE FRET (SMFRET) AND CROSSLINKING MASS SPECTROMETRY (XL-MS) OF ENV SUGGEST THE EXISTENCE OF AT LEAST ONE, SOMETIMES DOMINANT CONFORMATIONAL STATE THAT HAS NOT BEEN STRUCTURALLY CHARACTERIZED. THIS “STATE-1” CONFORMATION NONETHELESS SEEMS RELEVANT FOR BOTH IMMUNE RECOGNITION AND SUSCEPTIBILITY TO SMALL-MOLECULE INHIBITORS. WE WILL LEVERAGE ADVANCED MOLECULAR DYNAMICS (MD) METHODS INCLUDING TARGETED MD, TEMPERATURE-ACCELERATED MD, AND STRING METHOD TO PROVIDE ATOMIC LEVEL MODELS FOR THE OPENING OF HIV-1 ENV FROM CLOSED (STATE 2) TO OPEN (STATE 3) CONFORMATIONAL STATES AND TO IDENTIFY CRITICAL STRUCTURAL CHANGES SEPARATING STATE-2 FROM THE POORLY UNDERSTOOD STATE-1 ENV. THE MD SIMULATION METHODS WE USE WILL INCORPORATE BIASES FROM MULTI-PERSPECTIVE SMFRET AND XL-MS, AND THEY WILL IN TURN PROVIDE DIRECTION FOR EXPANDING THE SET OF ENV CONSTRUCTS USED IN THOSE EXPERIMENTS, ESTABLISHING AN ITERATIVE APPROACH THAT PROGRESSIVELY BETTER DEFINES TRANSITION MECHANISMS AND STATE 1. AN ATOMIC-LEVEL UNDERSTANDING OF HIV-1 ENV CONFORMATIONAL DYNAMICS, IDENTIFICATION OF A YET TO BE STRUCTURALLY CHARACTERIZED PRE-TRIGGERED CONFORMATIONAL STATES, AS WELL AS THE MECHANISM OF ENV ACTIVATION FOR FUSION WILL INFORM IMMUNOGEN DESIGN AND ANTIVIRAL THERAPIES.

APPROACHES TO COMPUTING DIFFUSION RATES IN PROTEINS FROM TRANSITION PATH THEORY

ENGAGING MEN IN WEIGHT LOSS WITH A GAME-BASED MHEALTH AND NEUROTRAINING PROGRAM - ABSTRACT MEN IN THE UNITED STATES HAVE AN EXCEPTIONALLY HIGH PREVALENCE OF OVERWEIGHT AND OBESITY, I.E., 71.3%, AND 42% OF MEN ARE CURRENTLY ATTEMPTING WEIGHT LOSS. HOWEVER, MEN ARE DRAMATICALLY UNDERREPRESENTED IN WEIGHT LOSS PROGRAMS. MEN FIND CONVENTIONAL WEIGHT LOSS PROGRAM (I.E., GROUP-BASED, EDUCATION AND COUNSELING- ORIENTATED, DIETARY/CALORIE-FOCUSED) UNAPPEALING BECAUSE THEY INVOLVE RECEIVING COUNSELING, FOCUS ON REPLACING “MASCULINE” FOODS (E.G., MEAT) WITH “FEMININE” ONES (E.G., SALAD), AND PROVIDE MINIMAL PERSONALIZATION OR AUTONOMY. AS SUCH, ATTEMPTS HAVE BEEN MADE TO INCREASE RECRUITMENT AND APPEAL THROUGH TARGETED RECRUITMENT AND ADAPTATIONS TO STANDARD WEIGHT LOSS PROGRAMS. HOWEVER, THESE EFFORTS HAVE BEEN DISAPPOINTING. MOBILE APPLICATIONS (MHEALTH APPS) HAVE ATTRACTIVE FEATURES, BUT HAVE LOW MALE ENROLLMENT AND POOR EFFICACY AS CONVENTIONALLY DELIVERED. A GAMIFIED MHEALTH PROGRAM OFFERS THE POSSIBILITY OF ENGAGING MEN AND ENHANCING EFFICACY GIVEN THAT (1) VIDEO GAMING IS HIGHLY APPEALING TO MEN; (2) GAMIFICATION FEATURES (E.G., DIGITAL REWARDS FOR ATTAINING “STREAKS” AND MILESTONES, COMPETITION) ARE KNOWN ENHANCE ENJOYMENT AND MOTIVATION AND FACILITATE DESIRED BEHAVIORS; AND (3) “NEUROTRAINING” VIDEO GAMES FEATURING REPETITIVE ACTION MECHANICS, ADAPTIVE DIFFICULTY, AND FEEDBACK CAN TRAIN INHIBITORY CONTROL, A BASIC BRAIN CAPACITY TO INHIBIT INTRINSICALLY-GENERATED APPROACH RESPONSES THAT IS STRONGLY LINKED TO BODY MASS AND THE CONSUMPTION OF HIGH- CALORIE FOODS. INHIBITORY CONTROL TRAINING (ICT) GAMES HAVE BEEN SUCCESSFUL AT REDUCING CONSUMPTION OF TARGETED FOODS/BEVERAGES AND IMPROVING SHORT-TERM WEIGHT LOSS. FOR INSTANCE, IN OUR PRELIMINARY WORK WE DEMONSTRATED THAT A WEIGHT LOSS WORKSHOP PLUS A SHORT, DAILY ICT PRODUCED GREATER WEIGHT LOSS FOR INDIVIDUALS WITH HIGHER- THAN-AVERAGE IMPLICIT PREFERENCES FOR HIGH-SUGAR FOODS, COMPARED TO A ROBUST ATTENTION CONTROL (I.E., THE WORKSHOP PLUS A SHAM TRAINING), AND WE FOUND THAT ADDING GAMIFICATION ELEMENTS (E.G., STORY, MUSIC, LEVELS) TO A RUDIMENTARY GAME PRODUCED ADDITIONAL 8-WEEK WEIGHT LOSS FOR MEN (4.1% VS 2.5%). THIS PROJECT EXTENDS PREVIOUS WORK BY EVALUATING THE INDEPENDENT EFFECTS OF GAMIFICATION AND ICT ON LONG-TERM ENGAGEMENT AND OUTCOMES. AS SUCH, 243 MEN WITH BMI = 25 WILL BE RECRUITED, WITH 15 PARTICIPATING IN USABILITY TESTING AND 228 ASSIGNED TO A 12-MONTH MHEALTH WEIGHT LOSS PROGRAM THAT PRESCRIBES DIGITAL SELF-MONITORING AND DIETARY AND PHYSICAL ACTIVITY TARGETS. UTILIZING AN EFFICIENT 2 X 2 FACTORIAL DESIGN, PARTICIPANTS WILL BE RANDOMIZED TO RECEIVE EITHER A STANDARD OR FULLY-GAMIFIED PROGRAM, COMPRISED OF A BEHAVIOR CHANGE PROGRAM FEATURING TEAM-BASED COMPETITION, AND DIGITAL REINFORCERS FOR ATTAINMENT OF STREAKS AND MILESTONES, AND ALSO RANDOMIZED TO RECEIVE EITHER SHAM OR ACTIVE INHIBITORY CONTROL NEUROTRAINING. AIMS INCLUDE EVALUATING THE EFFICACY OF GAMIFICATION AND ICTON WEIGHT LOSS, DIET AND PHYSICAL ACTIVITY AT 12 MONTHS, AS WELL AS EVALUATING HYPOTHESIZED MEDIATORS (ENGAGEMENT AND INHIBITORY CONTROL) AND MODERATORS (BASELINE FREQUENCY OF VIDEO GAME PLAY AND IMPLICIT PREFERENCES FOR ICT-TARGETED FOODS).

EXPLORING THE MODULATION OF SYNAPTIC/EXTRASYNAPTIC NMDAR BALANCE AS A NOVEL THERAPEUTIC STRATEGY IN ALZHEIMER'S DISEASE AND OTHER NEURODEGENERATIONS

USING ARTIFICIAL INTELLIGENCE TO OPTIMIZE DELIVERY OF WEIGHT LOSS TREATMENT - ABSTRACT SEVENTY PERCENT OF AMERICAN ADULTS ARE OVERWEIGHT OR OBESE, PRESENTING AN UNPRECEDENTED CHALLENGE TO THE NATION’S HEALTH SYSTEMS. EFFECTIVE BEHAVIORAL PROGRAMS EXIST, BUT THESE PROGRAMS ARE INTENSIVE, LONG-TERM AND REQUIRE HIGHLY-TRAINED CLINICIANS, MAKING THEM PROHIBITIVELY EXPENSIVE AND THUS LIMITING DISSEMINABILITY. APPROACHES TO DECREASING COSTS INCLUDE REPLACING HIGHLY-TRAINED CLINICIANS WITH PARAPROFESSIONALS, REDUCING CONTACT FREQUENCY, AND/OR AUTOMATING INTERVENTION. HOWEVER, ALTHOUGH THESE ALTERNATIVE INTERVENTIONS RESULT IN CONSIDERABLY LOWER AVERAGE WEIGHT LOSSES, VARIABILITY OF WEIGHT LOSS IS HIGH. SPECIFICALLY, AND CONSISTENT WITH A SUPPORTIVE ACCOUNTABILITY MODEL, A SUBSTANTIAL MINORITY OF PARTICIPANTS IN HIGH-INTENSITY INTERVENTIONS RECEIVE NO BENEFIT, WHILE A SUBSET OF THOSE RECEIVING LOW-INTENSITY INTERVENTIONS ACHIEVE CLINICALLY SIGNIFICANT WEIGHT LOSS. AN IDEAL WEIGHT LOSS TREATMENT SYSTEM WOULD ENHANCE OUTCOMES AND REDUCE COSTS BY MATCHING EACH PARTICIPANT TO THE INTERVENTION HE/SHE NEEDS, THUS ADAPTING TO PARTICIPANTS’ NEEDS AND CONSERVING RESOURCES WHERE THEY ARE NOT NEEDED. STEPPED CARE REPRESENTS ONE SUCH SYSTEM, BUT HAS HAD MIXED SUCCESS AND SUFFERS FROM A NUMBER OF SHORTCOMINGS. THE INNOVATIVE ARTIFICIAL INTELLIGENCE (AI) STRATEGY OF REINFORCEMENT LEARNING (RL) PROVIDES RAPIDLY AND REPEATEDLY-VARYING FEATURES OF INTERVENTION, CONTINUOUSLY "LEARNING" WHICH FEATURES PROVIDE OPTIMAL RESPONSES FOR WHICH PARTICIPANTS. OUR TEAM RECENTLY COMPLETED A PILOT OF AN AI WEIGHT LOSS SYSTEM IN WHICH OVERWEIGHT ADULTS RECEIVED A BRIEF IN-PERSON WEIGHT LOSS INTERVENTION AND THEN WERE RANDOMLY ASSIGNED TO RECEIVE 3 MONTHS OF NON-OPTIMIZED INTERVENTIONS (I.E., 12-MINUTE PHONE CALLS) OR AN OPTIMIZED COMBINATION OF PHONE CALLS, TEXT EXCHANGES, AND AUTOMATED MESSAGES, SELECTED BASED ON EACH PARTICIPANTS’ RESPONSE TO EACH INTERVENTION AS DETERMINED BY WEIGHT AND BEHAVIORAL DATA. AS HYPOTHESIZED, WE ACHIEVED EQUIVALENT WEIGHT LOSSES AT A FRACTION OF THE TIME COST. THE PROPOSED STUDY WOULD RECRUIT 320 OVERWEIGHT ADULTS, PROVIDE 1 MONTH OF GROUP-BASED BEHAVIORAL WEIGHT LOSS TREATMENT AND THEN RANDOMIZE PARTICIPANTS TO EITHER CONTINUE TO RECEIVE GROUP-BASED BEHAVIORAL WEIGHT LOSS IN A REMOTE FORMAT FOR 11 MONTHS (BWL-S) OR TO REINFORCEMENT LEARNING-BASED TREATMENT (BWL-AI). IN LINE WITH OUR SUPPORTIVE ACCOUNTABILITY MODEL, BWL-AI WOULD VARY MODALITY, INTENSITY AND COUNSELOR SKILL BASED ON CONTINUOUSLY-MONITORED PARTICIPANT DIGITAL DATA. THE PROPOSED STUDY--THE FIRST OF ITS KIND--WOULD EXPAND ON OUR PILOT IN SEVERAL WAYS INCLUDING SAMPLE SIZE, DURATION, AND FEATURES OF INTERVENTION SELECTED BY THE AI SYSTEM. AIMS OF THIS PROJECT ARE TO TEST THE HYPOTHESES THAT WEIGHT LOSS OUTCOMES IN BWL-AI WILL BE EQUIVALENT TO OR BETTER THAN BWL-S, AND THAT THE COST PER PARTICIPANT AND PER KG OF LOST WEIGHT WILL BE LESS IN BWL-AI THAN IN BWL-S. OTHER INCLUDE CHARACTERIZING THE AI SYSTEM (IN TERMS OF INTERVENTIONS SELECTED), ASSESSING FEASIBILITY AND ACCEPTABILITY OF THE REFINED AI SYSTEM, EVALUATING PSYCHOLOGICAL AND DEMOGRAPHIC PREDICTORS OF AI INTERVENTION SELECTION AND INVESTIGATING DIFFERENCES BETWEEN RESPONDERS AND NON-RESPONDERS IN HOW THE AI SYSTEM ALLOCATES RESOURCES.

HTLV-1 & CELLULAR FACTORS IN NEUROINFLAMMATORY DISEASE

GREATER PHILADELPHIA REGION LOUIS STOKES ALLIANCE FOR MINORITY PARTICIPATION - PHILADELPHIA AMP INITIATIVE (SENIOR LEVEL ALLIANCE)

TRANSITION TO TEACHING PROGRAM - TRANSITION TO TEACHING PROGRAM -- NATIONAL

MECHANISMS UNDERLYING TIP60 HAT ACTION IN NEUROPROTECTION OF COGNITIVE FUNCTION

PACIFIC ATMOSPHERIC SULFUR EXPERIMENT

MUSIC4PAIN NETWORK: A RESEARCH NETWORK TO ADVANCE THE STUDY OF MECHANISMS UNDERLYING THE EFFECTS OF MUSIC AND MUSIC-BASED INTERVENTIONS ON PAIN. - PROJECT SUMMARY/ABSTRACT PAIN IS ONE OF THE MOST COMMON AND COSTLY HEALTH PROBLEMS WORLDWIDE. DUE IN PART TO THE INADEQUACIES OF PURELY BIOMEDICAL APPROACHES, MANY PEOPLE ARE INCREASINGLY SEEKING COMPLEMENTARY APPROACHES TO PAIN MAN- AGEMENT, INCLUDING MUSIC-BASED INTERVENTIONS (MBIS). ALTHOUGH THE PAIN-RELIEVING EFFECTS OF MBIS ARE WELL-ES- TABLISHED, LACK OF UNDERSTANDING OF MBIS' MECHANISMS OF ACTION PREVENTS US FROM EXPLOITING THEIR FULL THERAPEU- TIC POTENTIAL. IN ORDER FOR MECHANISTIC RESEARCH ON MUSIC AND PAIN TO PROGRESS IN AN EFFICIENT AND RIGOROUS MAN- NER, THE BUILDING OF A MULTIDISCIPLINARY RESEARCH WORKFORCE CAPABLE OF LEADING INNOVATIVE MECHANISTIC STUDIES IS NEEDED. TO THIS END, WE PROPOSE TO CREATE THE MUSIC4PAIN NETWORK, A MULTIDISCIPLINARY RESEARCH NETWORK THAT WILL BRING TOGETHER NEUROSCIENTISTS, MUSIC THERAPISTS, MUSICIANS, NEUROPSYCHOLOGISTS, REHABILITATION SCIENTISTS, PSYCHOPHYSIOLOGISTS, AND MORE. THE MUSIC4PAIN NETWORK AIMS TO ACCELERATE KNOWLEDGE IN THREE KEY AREAS: (1) DEVELOPMENT OF A TAXONOMY OF KEY TERMS AND DEFINITIONS RELATED TO MBIS AND MUSIC, (2) INCREASED UNDERSTAND- ING OF THE MECHANISMS UNDERLYING THE BENEFITS OF MUSIC FOR PAIN, AND (3) IDENTIFICATION OF BIOMARKERS AND PER- SON VARIABLES THAT PREDICT TREATMENT RESPONSE TO MBIS. NETWORK ACTIVITIES WILL BE GUIDED BY A FORMAL RESEARCH AGENDA THAT WILL BE DEVELOPED BY THE NETWORK'S CORE INVESTIGATOR TEAM IN COLLABORATION WITH SCIENTISTS WITH COMPLEMENTARY EXPERTISE. THE MUSIC4PAIN NETWORK WILL FORGE NEW MULTIDISCIPLINARY RESEARCH COLLABORATIONS BY (1) ACTIVELY PROMOTING THE NETWORK ACROSS DISCIPLINES TO RECRUIT EXPERTS WITH RELEVANT AND COMPLIMENTARY KNOWLEDGE, (2) BUILDING AN INTERACTIVE NETWORK WEBSITE TO ENABLE IDENTIFICATION OF POTENTIAL COLLABORATORS, SHAR- ING OF RESOURCES, AND FEATURING OF NETWORK ACTIVITIES AND PRODUCTS, (3) PROMOTING THE NETWORK USING SOCIAL ME- DIA PLATFORMS, AND (4) ORGANIZING ANNUAL MEETINGS, WEBINARS, AND MUSIC AND PAIN SPECIAL INTEREST GROUPS. IN ADDITION, THE MUSIC4PAIN NETWORK WILL STIMULATE INNOVATIVE, MULTIDISCIPLINARY MECHANISTIC RESEARCH THROUGH PILOT FUNDING. THE PILOT FUNDING WILL SUPPORT THE COLLECTION OF INNOVATIVE DATA TO STRENGTHEN INDEPENDENT RESEARCH FUNDING APPLICATIONS. THE NETWORK WILL ALSO FUND VISITING SCHOLAR POSITIONS TO HELP PHD STUDENTS AND POSTDOC- TORAL FELLOWS GAIN SKILLS AND EXPERTISE RELATED TO NETWORK GOALS. IN ADDITION, THE NETWORK WILL BUILD THE MUSIC AND PAIN RESEARCH WORKFORCE BY MENTORING NEW AND EARLY CAREER INVESTIGATORS TO DEVELOP RESEARCH SKILLS AND SUP- PORT THEIR EFFORTS IN OBTAINING EXTRAMURAL FUNDING. THE WORK THAT WILL BE MADE POSSIBLE THROUGH THE MUSIC4PAIN NETWORK WILL ENABLE THE DEVELOPMENT OF NEW, OR OPTIMIZATION OF EXISTING, MBIS SO THAT ACUTE AND CHRONIC PAIN CAN BE BETTER MANAGED WITH A LOW-COST, NON-PHARMACOLOGICAL APPROACH THAT HAS WIDE APPEAL TO A LARGE NUMBER OF PEOPLE. IMPROVED EFFICACY OF MBIS AND BETTER UNDERSTANDING OF THEIR MECHANISMS OF ACTION WILL SPEED UP THEIR ADOPTION IN CLINICAL CARE. THIS COULD HAVE IMPORTANT CONSEQUENCES FOR THE MILLIONS OF AMERICANS CURRENTLY LIVING WITH PAIN.

REWARD RE-TRAINING: A NEW TREATMENT TO ADDRESS REWARD IMBALANCE DURING THE COVID-19 PANDEMIC

BIOMECHANICS OF CARTILAGE: ROLES OF DECORIN IN ECM ASSEMBLY AND DEGRADATION

LONG-ACTING HIV THERAPY FOR INJECTION DRUG USERS

IMPROVING WEIGHT LOSS OUTCOMES FOR BINGE EATING DISORDER

AUTISM TRANSITIONS RESEARCH PROJECT - PROBLEM: RESEARCH FOCUSED ON AUTISTIC YOUTH TRANSITIONING INTO ADULTHOOD HAS NOT KEPT PACE WITH THE RAPID GROWTH IN SIZE, NEEDS, OR DIVERSITY OF THIS GROUP. RESEARCH EFFORTS TO DATE HAVE BEEN LIMITED IN SCOPE, CONDUCTED IN SILOES (E.G., FOCUSED ONLY ON HEALTH CARE), AND HAVE NOT DEPLOYED A COMPREHENSIVE DEFINITION OF HEALTHY LIFE TRANSITIONS THAT EMPHASIZES HEALTH EQUITY. GOAL(S) AND OBJECTIVES: THE GOAL OF THE PROPOSED PROJECT IS TO PRODUCE HIGH-IMPACT RESEARCH ACROSS A DIVERSE RESEARCH TEAM THAT CORRESPONDS TO KEY AREAS OF NEED TO GROW THE EVIDENCE BASE TO SUPPORT HEALTHY AND EQUITABLE LIFE OUTCOMES AMONG TRANSITION-AGE AUTISTIC YOUTH AND YOUNG ADULTS. OUR OBJECTIVES INCLUDE: (1) THE PRODUCTION OF PEER-REVIEWED PUBLICATIONS AND NATIONAL AUTISM INDICATORS REPORTS, (2) THE DEVELOPMENT OF A NEW INTERVENTION TO SUPPORT LATINX AUTISTIC TRANSITION-AGE YOUTH, AND (3) CAPACITY BUILDING FOR EQUITY IMPACT WITHIN (A) TITLE V PROGRAMS AND (B) MINORITY-SERVING INSTITUTIONS AND COMMUNITY COLLEGES. PROPOSED ACTIVITIES AND TARGET POPULATION(S): OUR PROPOSED PROJECT ACTIVITIES INCLUDE: (1) THE USE OF INNOVATIVE APPROACHES TO DATA ANALYSIS THAT UTILIZE POPULATION-LEVEL METRICS TO UNDERSTAND TRANSITION OUTCOMES AND PINPOINT OPPORTUNITIES FOR IMPROVEMENT; (2) THE DEVELOPMENT OF A NEW INTERVENTION TO SUPPORT LATINX AUTISTIC YOUTH TO LEARN ESSENTIAL SKILLS FOR SUCCESSFUL TRANSITION TO ADULTHOOD AND HEALTHY LIFE OUTCOMES; (3) CAPACITY BUILDING FOR EQUITY IMPACT THAT CATALYZES ENGAGEMENT OF KEY INSTITUTIONS, PROGRAM INFRASTRUCTURE, AND POLICIES THAT ARE PRIME OPPORTUNITIES TO BOLSTER IMPROVED HEALTHY LIFE OUTCOMES AMONG AUTISTIC TRANSITION-AGE YOUTH AND YOUNG ADULTS. COORDINATION: COMMUNICATION ACROSS PROJECT SITES AND ACTIVITIES WILL BE SCAFFOLDED ACROSS FOUR PATHWAYS. ENGAGEMENT WITH AUTISTIC INDIVIDUALS AND FAMILIES TO LEAD INPUT INTO PROJECT GOALS, OBJECTIVES, AND ACTIVITIES WILL OCCUR MONTHLY. QUARTERLY MEETINGS OF ALL PROJECT SITES WILL FACILITATE REPORTING OF PROGRESS AND CATALYZE COORDINATION OF EFFORTS ACROSS SITES TO ENSURE EFFICIENCY AND PRODUCTIVITY. NEW DISSEMINATION CHANNELS WILL MAXIMIZE THE REACH OF PROJECT PRODUCTS AND EXTEND THE REACH OF ATRP IMPACT BY STRATEGICALLY ALIGNING OUTPUT AND AUDIENCES. CLOSE COORDINATION AND COLLABORATION WITH HRSA TO EVOLVE ACTIVITIES IN RESPONSE TO FUNDER GOALS WILL BE PROACTIVELY SOUGHT, DOCUMENTED, AND DEPLOYED TO SHAPE ATRP ACTIVITY AT ALL PHASES. PRODUCTS: TO MAXIMIZE IMPACT, WE WILL CONSTRUCT PRODUCTS FOR RELEASE ACROSS MULTIPLE AUDIENCES. WE PROPOSE TO PRODUCE AT LEAST 25 PEER-REVIEWED PUBLICATIONS, WHICH BUILDS UPON OUR CURRENT ATRP SUCCESS. WE ALSO PROPOSE TO PRODUCE AT LEAST 7 NATIONAL AUTISM INDICATORS REPORTS ALIGNED WITH KEY TOPICS THAT HAVE BEEN UNDEREXPLORED AND UNDERDEVELOPED, BUT THAT ARE NECESSARY FOR SUPPORTING HEALTHY LIFE OUTCOMES AND EQUITY FOR AUTISTIC YOUTH AND YOUNG ADULTS. ADDITIONAL PRODUCTS WILL BE CATERED TO DISSEMINATION CHANNELS, INCLUDING SOCIAL MEDIA, CONFERENCES, PARTNERSHIPS WITH EMERGING SCHOLARS (INCLUDING A PILOT FUNDING PROGRAM), AND WEB-BASED CONTENT. EVALUATION: A MULTI-PRONGED STRATEGY WILL BE USED TO ASSESS PROGRESS TOWARD BENCHMARKS AT EACH STAGE OF PROJECT DEVELOPMENT AND EXECUTION. STRATEGIC CONSULTATION WITH FIELD-LEADING EXPERTS WILL BE PAIRED WITH THE HISTORICAL SUCCESS OF THE RESEARCH TEAM IN PRODUCING DELIVERABLES ACROSS PEER-REVIEWED PUBLICATIONS AND NATIONAL AUTISM INDICATORS REPORTS TO GENERATE NEW, INNOVATIVE PROJECT ACTIVITY AND OUTPUT. WE WILL PRIORITIZE RESEARCH QUESTIONS IN CONJUNCTION WITH ADVISORY FEEDBACK AND EMERGING FINDINGS TO ENSURE THAT ACTIVITIES ARE RESPONSIVE TO THE NEEDS REPORTED BY AND OBSERVED ACROSS COMMUNITIES. KEY TERMS: - ACCESS TO HEALTH CARE - HEALTH DISPARITIES - LIFE COURSE - YOUTH WITH SPECIAL HEALTH CARE NEEDS TRANSITION TO ADULTHOOD - INSURANCE COVERAGE - ADOLESCENCE (12-18 YEARS) - YOUNG ADULTHOOD (19-25 YEARS) - PERSONS WITH DISABILITIES OR SPECIAL HEALTH CARE NEEDS - H

COMPLEX SYSTEMS APPROACHES TO IDENTIFY POLICY LEVERS TO REDUCE RACIAL/ETHNIC DISPARITIES IN DIET AND OBESITY IN CITIES - PROJECT SUMMARY RACIAL/ETHNIC DISPARITIES IN DIET AND OBESITY ARE REMARKABLY CONSISTENT ACROSS U.S. CITIES. FIRST, WE WILL USE GROUP MODEL BUILDING TO SYSTEMATICALLY ENGAGE ACADEMIC, POLICY, AND COMMUNITY STAKEHOLDERS TO BUILD CAPACITY FOR SYSTEMS THINKING, DEVELOP AND REFINE A “MAP” OF THE MULTILEVEL FACTORS THAT DRIVE DIET DISPARITIES, AND IDENTIFY POLICY LEVERS TO REDUCE DIET DISPARITIES IN CITIES. THE NEED FOR THIS WORK IS MOTIVATED BY THE LACK OF AN EXISTING CONCEPTUAL FRAMEWORK THAT EXPLICATES MECHANISMS VIA WHICH OBESOGENIC ENVIRONMENTS AND SYSTEMATIC STRUCTURAL DISADVANTAGE DISPROPORTIONATELY AFFECT MINORITIES AND LEAD TO DISPARITIES. PREVIOUS RESEARCH AND EXISTING CONCEPTUAL FRAMEWORKS HAVE IDENTIFIED MYRIAD INFLUENCES ON DIET AMONG THE GENERAL POPULATION, BUT A MORE SPECIFIC CONCEPTUAL FRAMEWORK CAN ADVANCE UNDERSTANDING OF SOCIAL, ENVIRONMENTAL, AND POLICY FACTORS THAT WORK IN COMBINATION TO CONSTRAIN HEALTHY FOOD CHOICES OF BLACKS, LATINOS, AND OTHER RACIAL/ETHNIC MINORITIES. SECOND, WE WILL IMPLEMENT AN AGENT-BASED SIMULATION MODEL (ABM) TO EXAMINE HOW RESIDENTIAL SEGREGATION, THE INEQUITABLE DISTRIBUTION OF FOOD OUTLETS, THE LOWER PRICE OF UNHEALTHY FOODS, AND INCOME INEQUALITY WORK IN COMBINATION TO CONSTRAIN FOOD CHOICES OF RACIAL/ETHNIC MINORITIES AND LEAD TO DIET AND OBESITY DISPARITIES. THE ABM BRIDGES LINES OF RESEARCH CONDUCTED BY OUR GROUP AND OTHERS THAT HAVE USED ABM TO EXAMINE HOW FOOD ACCESS AND FOOD PRICES SEPARATELY AFFECT DIETS. BY INTEGRATING THESE SEPARATE MODELING PARADIGMS, WE CAN EXAMINE HOW DIET DISPARITIES EMERGE DUE TO INTERSECTING DISADVANTAGE IN FOOD ACCESS AND AFFORDABILITY. IN THE ABM, INDIVIDUAL-AGENTS IN A VIRTUAL CITY MAKE A SERIES OF DAILY DECISIONS ABOUT WHERE TO SHOP FOR FOOD, WHAT TYPES OF FOOD TO PURCHASE, AND WHAT TO EAT. EACH DECISION IS BASED ON SIMPLE RULES THAT REFLECT INFLUENCES ON FOOD PURCHASING AND DIET, INCLUDING HOUSEHOLD FOOD BUDGETS; TRAVEL COSTS TO FOOD STORES; BETWEEN-STORE VARIATION IN PRICE, INVENTORY, AND QUALITY; AND THE PRICES OF 12 NUTRITIONALLY IMPORTANT FOOD CATEGORIES (E.G., PROTEIN, WHOLE GRAINS) AND 6 BEVERAGE CATEGORIES. WE USE GOLD STANDARD DATA REGARDING HOUSEHOLD INCOME AND FOOD SPENDING, FOOD PRICES AND PURCHASING, AND DIET. WE PROPOSE TWO USES FOR THE ABM: FIRST, WE WILL ASSESS THE IMPACT OF JOB AND INCOME LOSS RELATED TO THE COVID-19 PANDEMIC AND FEDERAL POLICIES THAT RESTRICT ELIGIBILITY AND ENROLLMENT OF IMMIGRANTS IN FOOD ASSISTANCE PROGRAMS – BOTH OF WHICH HAVE A DISPROPORTIONATE EFFECT ON MINORITIES AND THUS ARE LIKELY TO EXACERBATE DISPARITIES. SECOND, WE WILL ENGAGE POLICY STAKEHOLDERS TO INFORM DISSEMINATION AND EVALUATE HOW SCALING UP EXISTING PILOT PROGRAMS (E.G., HEALTHY FOOD DELIVERY, MULTIPLYING THE VALUE OF SNAP DOLLARS SPENT AT FARMERS’ MARKETS, INCREASING HEALTHY FOOD ACCESS IN MINORITY NEIGHBORHOODS) AND IMPLEMENTING CURRENT POLICY PROPOSALS (E.G., USDA PROPOSAL TO REPLACE SNAP WITH “HARVEST BOXES”) WILL EXACERBATE OR REDUCE DIET DISPARITIES. THE ABM IS GROUNDED IN THE PHILADELPHIA CONTEXT, BUT THE RESEARCH QUESTIONS AND FINDINGS ARE HIGHLY RELEVANT TO DIET DISPARITIES IN ESSENTIALLY ALL U.S. CITIES.

VERTICAL CHARGE ORDERING TRANSISTORS ENABLED BY STRUCTURALLY COUPLED HETEROINTERFACES

PRE-CLINICAL TESTING OF A NOVEL IMMUNOTHERAPY FOR HTLV-INDUCED NEUROLOGIC DISEASE

MULTIPRONGED APPROACH TO DIMINISH SYMPATHETIC HYPERREFLEXIA AND ENSUING CARDIOVASCULAR AND IMMUNE DYSFUNCTION AFTER SPINAL CORD INJURY - PROJECT SUMMARY SPINAL CORD INJURY (SCI) IS A DEVASTATING EVENT SUSTAINED BY AS MANY AS 1.3 MILLION AMERICANS. WHILE NOT OFTEN APPRECIATED, CARDIOVASCULAR DISEASE AND SUSCEPTIBILITY TO INFECTION ARE LEADING CAUSES OF MORTALITY AND MORBIDITY IN INDIVIDUALS LIVING WITH SCI. ONE MAJOR REASON THOUGHT TO UNDERLIE THESE ISSUES IS SCI-INDUCED DYSREGULATION OF THE SYMPATHETIC NERVOUS SYSTEM. IN THIS PROPOSAL, WE WILL USE A CLINICALLY-RELEVANT CONTUSION RODENT SCI MODEL TO TEST THE HYPOTHESIS THAT INTRACELLULAR SIGMA PEPTIDE (ISP) WILL PROMOTE SUFFICIENT SPROUTING OF SEROTONERGIC AXONS ONTO NEURONS IN THE SPINAL SYMPATHETIC CIRCUIT BELOW THE SCI TO NORMALIZE SYMPATHETIC ACTIVITY AFTER INJURY. FURTHERMORE, WE HYPOTHESIZE THAT ADMINISTERING A COMBINING ISP AND INHIBITION OF SOLUBLE TUMOR NECROSIS FACTOR ALPHA (STNFA) WITH XPRO1595 – WHICH TARGET DIFFERENT ROOT CAUSES OF SYMPATHETIC HYPERREFLEXIA AFTER SCI (I.E., INTERRUPTED SUPRASPINAL INPUT THE SPINAL SYMPATHETIC CIRCUIT AND STNFA-INDUCED MALADAPTIVE PLASTICITY OF THE SPINAL SYMPATHETIC CIRCUIT, RESPECTIVELY) – WILL HAVE SYNERGISTIC EFFECTS ON IMPROVING CARDIOVASCULAR AND IMMUNE FUNCTION AFTER SCI.

DE-EE0009153 - DREXEL UNIVERSITY - ''HARDWARE-IN-THE-LOOP LABORATORY PERFORMANCE VERIFICATION OF FLEXIBLE BUILDING EQUIPMENT IN A TYPICAL COMMERCIAL BUILDING''.

ALTERNATIVE APPROACHES TO SUPPORTING ASD SERVICES FOR YOUNG ADULTS

BRAIN HIV-1 ISOLATES/ENVELOPES: CD4 DEPENDENCE, FUSOGENICITY AND NEUROTOXICITY

UNDERSTANDING THE OVERLAP OF CHROMATIN ALTERATION IN HIV-1 AND DRUG ABUSE

THE HOUSING ENVIRONMENT AND AMBIENT TEMPERATURE (HEAT) STUDY - ABSTRACT WITHOUT INTERVENTION, BY THE END OF THIS CENTURY, EXTREME HEAT WILL CAUSE TENS OF THOUSANDS OF EXCESS DEATHS, PARTICULARLY FROM RESPIRATORY AND CARDIOVASCULAR CAUSES. BEYOND THE IMPACTS OF SHORT-DURATION HEAT EVENTS, SUCH AS HEAT WAVES, IT IS CRITICAL TO UNDERSTAND THE EFFECTS OF CHRONIC HEAT EXPOSURE, ASSESSED WHERE MOST HEAT-RELATED DEATHS OCCUR: INDOORS. IMPROVING UNDERSTANDING OF INDIVIDUAL AND NEIGHBORHOOD CHARACTERISTICS THAT HEIGHTEN OR REDUCE HEAT VULNERABILITY IS ALSO CRUCIAL, FOR INFORMING THE DESIGN OF EFFECTIVE HEAT ADAPTATION STRATEGIES. YET, CURRENT KNOWLEDGE OF HEAT-RELATED MORTALITY AND VULNERABILITY REMAINS LIMITED IN AT LEAST THREE WAYS. FIRST, MOST RESEARCH ON HEAT-RELATED DEATH HAS QUANTIFIED ASSOCIATIONS BETWEEN SHORT-TERM TEMPERATURE SPIKES AND ACUTE MORTALITY OUTCOMES, LEAVING UNCERTAINTY ABOUT THE TOTAL MORTALITY BURDEN OF CHRONIC HEAT EXPOSURE. SECOND, MOST RESEARCH HAS CALCULATED ASSOCIATIONS WITH OUTDOOR RATHER THAN INDOOR TEMPERATURES, THUS POTENTIALLY UNDER-ESTIMATING THE MORTALITY IMPACTS OF HEAT AND LEAVING CRITICAL GAPS IN KNOWLEDGE ABOUT SAFE MAXIMUM INDOOR TEMPERATURE THRESHOLDS. THIRD, LITTLE IS KNOWN ABOUT THE EXTENT TO WHICH HOUSING INTERVENTIONS THAT PROMOTE THERMAL COMFORT AND CONSERVE ENERGY, SUCH AS IMPROVING INSULATION OR ALTERING ROOFING MATERIAL, MAY PREVENT EXCESS DEATHS FROM CHRONIC INDOOR HEAT EXPOSURE. THERE IS AN URGENT NEED TO FILL THESE GAPS SINCE MOST PEOPLE, AND ESPECIALLY HEAT VULNERABLE SUBPOPULATIONS INCLUDING INDIVIDUALS OVER AGE 65, SPEND THE MAJORITY OF THEIR TIME INDOORS. WE PROPOSE THE FIRST EVER POPULATION-BASED, NATIONALLY REPRESENTATIVE, QUASI-EXPERIMENTAL, LONGITUDINAL COHORT STUDY OF THE EFFECTS OF CHRONIC INDOOR HEAT EXPOSURE ON MORTALITY IN THE UNITED STATES. WE WILL USE DATA ON AGE 65 AND OLDER ADULT PARTICIPANTS OF THE MORTALITY DISPARITIES IN AMERICA COMMUNITIES (MDAC) STUDY LINKED WITH MEDICARE AND NATIONAL DEATH INDEX DATA. THIS REMARKABLY RICH DATA SET, WHICH CONTAINS FOLLOW UP ON INDIVIDUALS FOR UP TO EIGHT YEARS, WILL BE COMBINED WITH INDOOR TEMPERATURE AND HUMIDITY VARIABLES CALCULATED USING RIGOROUS, EXTENSIVELY VALIDATED, PHYSICS-BASED SIMULATION MODELS; INDIVIDUAL-LEVEL HOUSING CHARACTERISTICS; AND HIGH-RESOLUTION LAND COVER DATA. TO IMPROVE UNDERSTANDING OF ASSOCIATIONS BETWEEN THE HOUSING ENVIRONMENT, CHRONIC INDOOR HEAT EXPOSURES AND MORTALITY, AND PERSON- AND NEIGHBORHOOD-LEVEL DETERMINANTS OF HEAT VULNERABILITY, WE PURSUE THREE AIMS. IN AIM 1, WE QUANTIFY ASSOCIATIONS BETWEEN CHRONIC INDOOR HEAT EXPOSURES AND ALL-CAUSE AND CAUSE-SPECIFIC MORTALITY, AND IDENTIFY CLIMATE-ZONE SPECIFIC, SAFE UPPER THRESHOLDS FOR HOT-SEASON INDOOR TEMPERATURES. IN AIM 2, WE ELUCIDATE PERSON- AND NEIGHBORHOOD-LEVEL FACTORS THAT ENHANCE OR REDUCE VULNERABILITY TO CHRONIC INDOOR HEAT EXPOSURE. IN AIM 3, WE QUANTIFY THE TOTAL EXCESS DEATHS THAT MAY BE PREVENTED THROUGH HOUSING INTERVENTIONS THAT IMPROVE THERMAL COMFORT, UNDER CURRENT AND FUTURE GREENHOUSE GAS EMISSION SCENARIOS. THIS IMPACTFUL PROJECT WILL PROVIDE INFORMATION THAT IS CRITICALLY NEEDED TO GUIDE INTERVENTIONS THAT BALANCE HEAT ADAPTATION FOR HEALTH PROTECTION IN THE MOST VULNERABLE SUBGROUPS WITH CLIMATE CHANGE MITIGATION GOALS.

COLLABORATIVE RESEARCH: SUPPORTING THE EMERGENCE OF A PROFESSIONAL TEACHING COMMUNITY THROUGH COLLECTIVE KNOWLEDGE-BUILDING IN ASSESSMENT AND FEEDBAC

MECHANISMS OF LOCOMOTOR RHYTHM GENERATION IN RODENT SPINAL CORD - ABSTRACT LOCOMOTION IS A FUNDAMENTAL BEHAVIOR THAT ALLOWS HUMANS AND ANIMALS TO MOVE THROUGH THEIR ENVIRONMENTS AND IS CRITICALLY INVOLVED IN ALL ASPECTS OF LIFE. THIS BEHAVIOR IS IMPEDED IN A NUMBER OF DISEASES, DISORDERS, AND INJURIES, INCLUDING SPINAL CORD INJURY, STROKE, AND VARIOUS ATAXIAS. ALL OF THE ESSENTIAL CIRCUITY TO GENERATE LOCOMOTOR RHYTHM AND PATTERN IS LOCATED IN THE THORACOLUMBAR SPINAL CORD, MOST OFTEN BELOW THE LEVEL OF NEURAL DAMAGE. THESE CIRCUITS CAN BE ACCESSED DIRECTLY VIA VARIOUS CENTRAL AND PERIPHERAL STIMULATION METHODS, INCLUDING BUT NOT LIMITED TO EPIDURAL STIMULATION. RHYTHM GENERATING CIRCUITS ARE THE ENTRY POINT FOR INITIATION AND CONTROL OF LOCOMOTION, AFFECT ALL DOWNSTREAM NEURONS RELATED TO LOCOMOTION, AND, THEREFORE, ARE THE FIRST STEP IN ESTABLISHING SPINAL CONTROL OF LOCOMOTION. SUCCESSFUL ACTIVATION OF THE RHYTHM GENERATOR CLINICALLY HAS BEEN HAMPERED BECAUSE THE MECHANISMS BY WHICH SPINAL NEURONAL CIRCUITS GENERATE COORDINATED RHYTHMIC OUTPUT REMAIN POORLY UNDERSTOOD AND REPRESENTS A MAJOR GAP IN OUR UNDERSTANDING OF NEURAL CONTROL OF MOVEMENT. THE GENERATION OF RHYTHMIC MOTOR BEHAVIORS IS BASED ON A TRIAD INVOLVING: (1) SPECIFIC “RHYTHMOGENIC” PROPERTIES ALLOWING INDIVIDUAL NEURONS TO GENERATE RHYTHMIC OSCILLATIONS, (2) MUTUAL EXCITATORY INTERACTIONS TO SYNCHRONIZE NEURONAL ACTIVITY INTO RHYTHMIC POPULATIONAL BURSTING, AND (3) NETWORK INHIBITION TO COORDINATE ACTIVITY BETWEEN DIFFERENT NEURONAL POPULATIONS, WHICH CAN BOTH SHAPE LOCOMOTOR PATTERN AND CONTROL FREQUENCY. TRIAD COMPONENTS ARE HIGHLY INTERCONNECTED AND THE INVOLVEMENT OF EACH COMPONENT IS CONDITION-DEPENDENT. THE PROPOSED STUDY WILL USE HIGHLY INTEGRATED ELECTROPHYSIOLOGICAL, PHARMACOLOGICAL, GENETIC, AND COMPUTATIONAL APPROACHES TO SYSTEMATICALLY EXPLORE THE SPECIFIC CONTRIBUTIONS OF THESE MECHANISMS AND THE INTERACTIONS BETWEEN THEM, IN THE GENERATION AND PATTERNING OF THE LOCOMOTOR RHYTHM. UTILIZING SPINAL NEURONS IDENTIFIED IN TRANSGENIC MICE BY THE TRANSCRIPTION FACTOR SHOX2 AS A REPRESENTATIVE RHYTHM GENERATING POPULATION, WE WILL TEST THE OVERARCHING HYPOTHESIS THAT RHYTHM GENERATING MECHANISMS IN THE SPINAL CORD INVOLVE INTERPLAY BETWEEN THE TRIAD OF CELLULAR, POPULATION, AND NETWORK PROPERTIES, WHOSE CONTRIBUTION TO RHYTHMOGENESIS IS INTERDEPENDENT, LEADING TO FLEXIBILITY AND ADAPTABILITY SEEN AS ALTERATIONS IN THE RELATIVE BALANCE OF THE TRIAD IN DIFFERENT CONDITIONS. WE WILL FIRST DETERMINE THE VOLTAGE-GATED CURRENTS UNDERLYING SPONTANEOUS CELLULAR OSCILLATIONS IN ADULT SHOX2 NEURONS. WE WILL THEN ASSESS EXCITATORY INTERACTIONS BETWEEN RHYTHM GENERATING NEURONS. LASTLY, WE WILL ESTABLISH THE ROLE OF IPSILATERAL AND CONTRALATERAL NETWORK INTERACTIONS IN REGULATING LOCOMOTOR FREQUENCY, AND DETERMINE THE OPERATION OF THESE PATHWAYS DURING AFFERENT-EVOKED LOCOMOTION. TOGETHER, OUR MULTIDISCIPLINARY STUDY WILL REVEAL MECHANISMS OF RHYTHM GENERATION, ESTABLISH THE FIRST MAMMALIAN LOCOMOTOR NEURAL NETWORK MODEL BASED ON “REAL” RHYTHM GENERATING CELLULAR AND NETWORK PROPERTIES, AND DETERMINE THE WAYS BY WHICH AFFERENT STIMULATION MAY INFLUENCE THE LOCOMOTOR RHYTHM AND PATTERN GENERATED IN THE SPINAL CORD. THE RESULTS OF THESE STUDIES WILL IDENTIFY SPECIFIC NEURAL TARGETS FOR THE FUTURE DEVICES AND STRATEGIES AIMED AT RESTORATION OF LOCOMOTION FOLLOWING INJURY OR MOTOR DISORDERS.

A RAPHE-HIPPOCAMPUS PATHWAY FOR REGULATION OF MEMORY SPECIFICITY DURING CONSOLIDATION

THE CIRCUIT LOGIC OF MODULATION OF LOCOMOTION BY ODORS

DUAL-ACTION VIROLYTIC ENTRY INHIBITORS AGAINST HIV-1

FORMER PANTEX WORKER MEDICAL SURVEILLANCE PROGRAM

TELE-EXERCISE TO PROMOTE EMPOWERED MOVEMENT IN INDIVIDUALS WITH SPINAL CORD INJURY: TEEMS

NEUTRINOLESS DOUBLE BETA DECAY WITH EXO‐200 AND NEXO

SMALL EXTRACELLULAR VESICLES MEDIATED SIGNALING AND PAIN - ABSTRACT CHRONIC PAIN IS THE MOST PREVALENT, DISABLING, AND EXPENSIVE PUBLIC HEALTH CONDITION IN THE UNITED STATES. THE GOAL OF THIS PROJECT IS TO ELUCIDATE HOW TO HARNESS BODY’S OWN ANALGESIC MECHANISMS TO PROVIDE PAIN RELIEF. WE PROPOSE TO INVESTIGATE 30-150 NM SMALL EXTRACELLULAR VESICLES (SEVS) THAT TRANSPORT MRNAS, MIRNAS, PROTEINS, AND LIPID MEDIATORS TO RECIPIENT CELLS VIA CIRCULATION. UPTAKE OF SEVS INDUCE GENE EXPRESSION CHANGES IN RECIPIENT CELLS AND THUS, SEVS PLAY AN IMPORTANT ROLE IN INTERCELLULAR COMMUNICATION. WE OBSERVED THAT SEVS FROM RAW 264.7 MACROPHAGE CELLS SHOW THERAPEUTIC AND PROPHYLACTIC EFFICACY IN A COMPLETE FREUD ADJUVANT (CFA) MOUSE MODEL OF INFLAMMATORY PAIN. OUR PRELIMINARY STUDIES SHOW THAT MOUSE SERUM DERIVED SEVS ALSO CONFERRED PROPHYLAXIS WHEN INJECTED INTRATHECALLY IN NAÏVE RECIPIENT MICE THAT, TWO WEEKS LATER, RECEIVED A HIND PAW INJECTION OF CFA. THUS, MICE THAT RECEIVED SEVS CAN REMEMBER THIS STIMULATION FOR AT LEAST 2 WEEKS AND SHOW AN ATTENUATED RESPONSE TO CFA. HOW THIS LONG-TERM MEMORY DEVELOP IS UNKNOWN. THOUGH CHRONIC PAIN IS PREVALENT, AN IMMUNIZATION STRATEGY HAS NOT YET BEEN TESTED AND OUR STUDIES WILL PROVIDE THE RATIONALE AND MECHANISTIC BASIS FOR SUCH A STRATEGY. HERE WE PROPOSE TO TEST THE HYPOTHESIS THAT MONOCYTE/MACROPHAGE-DERIVED SEV SUBSETS IN SERUM ARE NECESSARY AND SUFFICIENT TO ATTENUATE INFLAMMATORY PAIN HYPERSENSITIVITY AND CONFER PROPHYLAXIS. WE WILL ALSO INVESTIGATE IF MONOCYTE/MACROPHAGE SEVS RECRUIT, OR PROMOTE ANTI- INFLAMMATORY PHENOTYPE SWITCHING OF IMMUNE CELLS IN DORSAL ROOT GANGLION AND SPINAL CORD BY QUANTITATIVE IMMUNOPHENOTYPING IN SITU, BEFORE AND AFTER CFA TREATMENT. RECENT STUDIES SHOW THAT MICROGLIA, THE RESIDENT MACROPHAGES OF THE CENTRAL NERVOUS SYSTEM CAN ENHANCE OR SUPPRESS RESPONSES TO A DELAYED SECONDARY INSULT THROUGH EPIGENETIC MODIFICATIONS. WE HYPOTHESIZE THAT MONOCYTE/MACROPHAGE-DERIVED SEVS IMPART EPIGENETIC IMMUNE MEMORY IN SPINAL MICROGLIA OF RECIPIENT MICE, GRANTING THE CAPACITY TO ATTENUATE PAIN FROM A FUTURE INSULT AND CONTRIBUTE TO THE PROPHYLACTIC EFFECT OF SEVS. THE STUDIES PROPOSED WILL ELUCIDATE THE ROLE OF SEVS IN IMMUNE REGULATION AND MEMORY.

REGULATING DOPAMINE TRANSPORT THROUGH ALLOSTERIC MODULATION - FUNCTIONAL AND BEHAVIORAL STUDIES - THE PLASMA-MEMBRANE MONOAMINE TRANSPORTERS (MATS), INCLUDING THE SEROTONIN (SERT), NOREPINEPHRINE (NET) AND DOPAMINE (DAT) TRANSPORTERS, SERVE A PIVOTAL ROLE IN LIMITING MONOAMINE-MEDIATED NEUROTRANSMISSION THROUGH THE REUPTAKE OF THEIR RESPECTIVE NEUROTRANSMITTERS. MATS ARE TARGETS FOR THE TREATMENT OF NUMEROUS NEUROLOGICAL DISORDERS SUCH AS DEPRESSION, ANXIETY, AND ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD), AND THEY SERVE AS TARGET PROTEINS FOR MAJOR DRUGS OF ABUSE SUCH AS AMPHETAMINE AND COCAINE. THE CONTINUING NEED FOR THERAPEUTIC DRUGS TO TREAT BRAIN DISORDERS INVOLVING ABERRANT MONOAMINE SIGNALING PROVIDES A COMPELLING REASON TO FURTHER OUR UNDERSTANDING OF TRANSPORTER FUNCTION AND TO IDENTIFY NOVEL WAYS OF TARGETING THEM. THIS PROJECT BUILDS ON OUR RECENT DISCOVERY OF AN ALLOSTERIC SITE (A2) WITHIN THE MATS THAT CAN SERVE AS A TARGET SITE FOR MODULATING THEIR ACTIVITY. PREVIOUS EXPERIMENTS IN OUR GROUP TARGETED THE ALLOSTERIC A2 SITE IN SERT AND IDENTIFIED MOLECULES THAT INTERACT WITH THIS SITE AND DISPLAY REMARKABLE TRANSPORTER-MODULATING ACTIVITIES. THESE COMPOUNDS HAVE REVEALED THAT ENGAGING THIS SITE MODULATE MAT ACTIVITY IN ENTIRELY NOVEL WAYS, INCLUDING AFFECTING THE INTERACTION WITH TRANSPORTER LIGANDS SUCH AS THE SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS) AND PSYCHOSTIMULANTS. IN CORRESPONDING EXPERIMENTS ON DAT, WE HAVE IDENTIFIED COMPOUNDS, KM822 AND SYDNOCARB AMONG OTHERS, THAT SIMILARLY MODIFIES DAT FUNCTION. WE FIND THAT THESE COMPOUNDS INTERFERE WITH THE INTERACTION OF DAT WITH EXOGENOUS LIGANDS AND ATTENUATES PSYCHOSTIMULANT-ELICITED BEHAVIORS IN RODENTS. COMPUTATIONAL SIMULATIONS FURTHER SUPPORT THE PREMISE THAT COMPOUNDS INTERACTING WITH THE ALLOSTERIC A2 SITE CAN ALLOW TRANSPORT WHILE INTERFERING WITH THE INTERACTION OF THE TRANSPORTER WITH EXOGENOUS LIGANDS LIKE COCAINE. THE OVERARCHING HYPOTHESIS OF THIS PROJECT IS THAT THE SPECIFIC ENGAGEMENT OF THE ALLOSTERIC SITE IN DAT WILL PROVIDE VALUABLE INFORMATION REGARDING MECHANISMS OF THE DOPAMINE TRANSPORT PROCESS AND COULD PROVIDE NOVEL THERAPEUTIC AVENUES FOR DEVELOPING DAT-BASED MEDICATIONS. WE PROPOSE TO PURSUE THIS IDEA BY FURTHER CHARACTERIZING THE COMPOUNDS TO STUDY ALLOSTERIC MODULATION OF DAT. WE WILL IN AIM 1 ELUCIDATE MECHANISMS OF ALLOSTERIC TRANSPORTER MODULATION THROUGH COMPUTATIONAL MODELLING AND MOLECULAR SIMULATIONS COUPLED WITH FUNCTIONAL AND BIOCHEMICAL STUDIES. IN AIM 2 WE WILL EVALUATE THE IN VIVO UTILITY OF THE COMPOUNDS BY EXAMINING THEIR EFFECTS ON PSYCHOSTIMULANT-ELICITED BEHAVIORS IN RODENTS. FINALLY, IN AIM 3, WE WILL EMPLOY STRUCTURE-BASED DESIGN TO IDENTIFY A2-SPECIFIC COMPOUNDS WITH IMPROVED PROPERTIES. CONSEQUENTLY, THE SUCCESSFUL COMPLETION OF THIS PROJECT WILL RESULT IN THE DEVELOPMENT OF NOVEL LIGANDS OF DAT THAT CAN BE EMPLOYED AS EXPERIMENTAL TOOLS TO PROVIDE CRITICAL MECHANISTIC INFORMATION REGARDING ALLOSTERIC TRANSPORTER MODULATION. FURTHERMORE, THE DESIGN AND DEVELOPMENT OF NOVEL ALLOSTERIC MODULATORS OF DAT WILL ENABLE A SYSTEMATIC EVALUATION OF THE BENEFICIAL POTENTIAL OF THESE COMPOUNDS TO ULTIMATELY PROVIDE NEW THERAPEUTIC OPPORTUNITIES.

DYNAMIC NETWORK NEUROSCIENCE AND CONTROL THEORY: TOWARD INTERVENTIONS FOR COGNITIVE CONTROL DYSFUNCTION

DESIGNING SUPRAMOLECULAR DELIVERY STRATEGIES TO UNDERSTAND AND EXPLOIT SYNERGIES IN IMMUNOREGENERATIVE MEDICINE - ABSTRACT IT REMAINS UNCLEAR WHY SOME TISSUE INJURIES REGENERATE AND HEAL WHILE OTHERS FIBROSE AND SCAR. IT IS EVIDENT, HOWEVER, THAT THE INFLAMMATORY RESPONSE UNDERLIES THESE DIVERGENT OUTCOMES. THIS IMMUNE SYSTEM’S RESPONSE TO INJURY DEPENDS ON A MULTITUDE OF CELL TYPES AND ORGAN SYSTEMS THAT REMAIN IN COMMUNICATION TO EVOLVE COLLECTIVELY, GUIDING TISSUE-LEVEL OUTCOMES. MY LAB’S EXPERTISE IS IN THE DESIGN OF LOCAL DRUG DELIVERY SYSTEMS FOR IMMUNE MODULATION. WE WILL LEVERAGE THESE DELIVERY PLATFORMS TO EXPLORE IMMUNE SYSTEMS INTERACTIONS AFTER LOCAL THERAPEUTIC DELIVERY, WITH APPLICATIONS TOWARD TISSUE HEALING AND ARRESTING INFLAMMATORY DISEASE PROGRESSION. THEME 1: HOW DOES CELL-TARGETED DELIVERY OF THERAPEUTICS ALTER MONOCYTE & MACROPHAGE CROSSTALK? MACROPHAGES ARE A PRIMARY COMPONENT OF THE INNATE IMMUNE SYSTEM, ACTING AS FIRST-RESPONDERS TO INJURY AND INITIATING THE ACTIVATION OF OTHER CELL TYPES – INCLUDING THEIR REPLACEMENT BY MONOCYTE PRECURSORS RECRUITED FROM THE BONE MARROW. PROMOTING A PRO-REGENERATIVE MACROPHAGE PHENOTYPE IS A PROMISING THERAPEUTIC AVENUE UNDER WIDESPREAD INVESTIGATION. HOWEVER, LITTLE IS KNOWN ABOUT HOW MACROPHAGE POLARIZATION ALTERS MONOCYTE RECRUITMENT AND DIFFERENTIATION. THIS PROJECT AREA BUILDS ON MY EXPERIENCE IN THERAPEUTIC MACROPHAGE POLARIZATION TO DEVELOP CELL-TARGETED THERAPEUTICS THAT PROMOTE A PRO-HEALING MACROPHAGE PHENOTYPE AT THE INJURY SITE, EXPLORING THE HYPOTHESIS THAT ALTERED MONOCYTE RECRUITMENT AND DIFFERENTIATION, NOT THE LONG-LASTING GENERATION OF PRO-HEALING MACROPHAGES, IS THE CRITICAL AXIS SUPPORTING AN IMMUNOREGENERATIVE RESPONSE. THEME 2: HOW DOES THE PROMOTION OF EARLY POST-INJURY INFLAMMATION ALTER ADAPTIVE IMMUNE RESPONSE? THE MAGNITUDE AND TEMPORAL SEQUENCE OF CELL SIGNALS, INCLUDING CHEMOKINES AND CYTOKINES, IS A CRITICAL REGULATOR OF CELL MIGRATION, DIFFERENTIATION, AND POLARIZATION; THESE PROCESSES GUIDE EVOLUTION OF THE INJURY IMMUNE MICROENVIRONMENT AND RESULTING TISSUE-LEVEL OUTCOMES. IT HAS BEEN RECENTLY OBSERVED THAT EXOGENOUS DELIVERY OF INFLAMMATORY SIGNALING PROMOTES TISSUE HEALING AFTER ISCHEMIC INJURY. HERE, WE WILL EXPLORE THE HYPOTHESIS THAT BENEFICIAL EFFECTS RESULT FROM THE RECRUITMENT AND DIFFERENTIATION OF REGULATORY T CELLS BY MACROPHAGE-DERIVED SIGNALS, WHICH CAN BE RE- CAPITULATED BY SEQUENTIAL BIOMOLECULE RELEASE FROM INJECTABLE HYDROGELS. IF SUCCESSFUL, THIS PROJECT WILL ELUCIDATE NEW DESIGN PRINCIPLES FOR GUIDING THE INJURY IMMUNE MICROENVIRONMENT TOWARD A FUNCTIONAL ORIENTATION THAT SUPPORTS TISSUE HEALING. THEME 3: CAN REMOTE DRUG DELIVERY SYSTEMS MODULATE DAMAGING SYSTEMIC INFLAMMATION? A SEQUELA OF DYSREGULATED SYSTEMIC INFLAMMATION OFTEN RESULTS FROM SIGNIFICANT TISSUE INSULTS (HEART ATTACK, KIDNEY INJURY) OR CHRONIC INFLAMMATORY DISEASE (INFLAMMATORY BOWEL, RHEUMATOID ARTHRITIS). SUCH INSULTS ARE ASSOCIATED WITH DELETERIOUS MULTI-ORGAN EFFECTS, INCLUDING RENAL AND PULMONARY FIBROSIS, ATHEROSCLEROSIS, AND HEART FAILURE. THIS AREA OF RESEARCH EXPLORES THE CAPACITY TO DEVELOP REFILLABLE DRUG RESERVOIRS FOR DELIVERING IMMUNOMODULATORY DRUGS TO DISTANT IMMUNE ORGANS, THEREBY MODULATING INFLAMMATION AT THE PRIMARY CELL SOURCES.

THIS PROJECT WILL DEVELOP A DATABASE OF PREMISE PLUMBING CONDITIONS (WATER AGE, DISINFECTANT TYPE AND CONCENTRATION, FLOW RATES, ETC.) AND CONCENTRAT

LIVER CANCER AND THE ROLE OF PROTEIN HYPER-FUCOSYLATION

DOPAMINERGIC MECHANISMS UNDERLYING BEHAVIORAL DEFICITS FOLLOWING MILD TBI

COMPUTATIONAL AND FUNCTIONAL STUDIES OF ALLOSTERIC MONOAMINE TRANSPORTER MODULATION

INTERLEUKIN-1BETA AND AR-NEGATIVE TUMOR CELLS IN METASTATIC CASTRATE-RESISTANT PROSTATE CANCER - TREATMENT OF PROSTATE CANCER PATIENTS RELIES HEAVILY ON THERAPEUTIC STRATEGIES DEPRIVING TUMOR CELLS OF THE TRANSCRIPTIONAL ACTIVITY OF THE ANDROGEN RECEPTOR (AR). DESPITE THEIR INITIAL EFFICACY, ANDROGEN-DEPRIVATION THERAPIES (ADT) ARE EVENTUALLY CIRCUMVENTED BY THE EMERGENCE OF CASTRATE-RESISTANT PROSTATE CANCER (CRPC), WHICH IS CHARACTERIZED BY SKELETAL METASTASES IN MORE THAN 90% OF PATIENTS. WE HAVE RECENTLY DEMONSTRATED THAT APPROXIMATELY 30% OF BONE-METASTATIC PROSTATE CANCER CELLS LACK AR (ARNEG) AND EXPRESS INTERLEUKIN-1SS (IL-1SS). OUR HYPOTHESIS IS THAT ARNEG CANCER CELLS, BY SECRETING IL-1SS, ESTABLISH A SUPPORTIVE BONE HABITAT, ALLOWS ARPOS CELLS TO WITHSTAND ANDROGEN-DEPRIVATION AND AR INHIBITION. THUS, A MAJOR GOAL OF THIS PROPOSAL IS TO DEFINE THE MODALITIES BY WHICH ARNEG/IL-1SS CANCER CELLS SUSTAIN SKELETAL COLONIZATION IN PROSTATE CANCER UNDER ANDROGEN-DEPRIVED CONDITIONS. THIS PROPOSAL IS STRUCTURED IN THREE AIMS: AIM 1. IL-1SS INVOLVEMENT IN ADT RESISTANCE; AIM 2. ROLE OF BONE STROMA IN IL-1SS INDUCED REGULATION OF ARPOS CELLS; AIM 3. REGULATION OF IL-1SS EXPRESSION BY AR. THE PROPOSED STUDIES WILL EMPLOY ANIMAL MODELS OF METASTASIS, HUMAN CELL LINES, PDX-DERIVED CELLS AND HUMAN TISSUE AMPLES TO ASCERTAIN THE FUNCTIONAL ROLE OF IL-1SS IN SKELETAL COLONIZATION OF PROSTATE CANCER CELLS, DISCRIMINATING BETWEEN DIRECT AUTOCRINE-PARACRINE EFFECTS ON CANCER CELLS AND TARGETING CELLS OF THE TUMOR- ASSOCIATED BONE STROMA. FURTHERMORE, WE WILL IDENTIFY THE BONE STROMA CELLS TARGETED BY IL-1SS AND EVALUATE THREE STROMAL FACTORS SECRETED IN RESPONSE TO IL-1SS FOR THE ABILITY TO INDUCE AR SIGNALING AND EXPRESSION OF AR- REGULATED GENES. FINALLY, USING A COMBINATION OF MOLECULAR BIOLOGY APPROACHES WE WILL DEFINE THE MECHANISM FOR THE TRANSCRIPTIONAL REGULATION OF IL-1SS BY THE AR AND THE TRANSLATIONAL CONTROL EXERTED ON THIS CYTOKINE BY MIRNAS. OUR STUDIES WILL DEFINE THE UNIQUE ROLE OF ARNEG PROSTATE CANCER CELLS IN METASTASES AND PROVIDE CONCEPTUAL AND PRE-CLINICAL GROUND FOR COMPLEMENTARY STRATEGIES TO IMPROVE THERAPEUTIC OUTCOMES.

LOCUS COERULEUS FUNCTION AND METHYLPHENIDATE ACTION

ANTIBIOTIC RECOGNITION AND SIGNALING IN VANCOMYCIN-RESISTANT ENTEROCOCCI (VRE)

MECHANISMS OF DOPAMINE MEDIATED INCREASE IN HIV INFECTION OF MACROPHAGES

HEALING HURT PEOPLE (HHP): INTEGRATING PEER SERVICES WITH TF-CBT FOR VIOLENTLY INJURED YOUTH. - HEALING HURT PEOPLE (HHP): INTEGRATING PEER SERVICES (PS) WITH TRAUMA-FOCUSED COGNITIVE BEHAVIORAL THERAPY (TF-CBT) FOR VIOLENTLY INJURED (VI) RACIAL AND ETHNIC MINORITY YOUTH. HHP IS A HOSPITAL AND COMMUNITY-BASED VIOLENCE INTERVENTION PROGRAM PROVIDING PEER SUPPORT, TRAUMA THERAPY, AND CASE MANAGEMENT TO PHILADELPHIA CHILDREN (AGES 8 TO 18) WHO HAVE BEEN VIOLENTLY INJURED (SHOOTINGS, STABBINGS, ASSAULTS) OR WITNESSED SUCH VIOLENCE. FOUNDED IN 2007, HHP IS PART OF DREXEL UNIVERSITY'S CENTER FOR NONVIOLENCE AND SOCIAL JUSTICE (CNSJ) IN THE COLLEGE OF MEDICINE AND DORNSIFE SCHOOL OF PUBLIC HEALTH. IN 2020, 199 CHILDREN WERE SHOT IN PHILADELPHIA, AN INCREASE OF 83% FROM 2019. PHYSICAL ASSAULTS ARE ALSO HIGHLY PREVALENT. THE SCHOOL DISTRICT OF PHILADELPHIA REPORTED 774 ASSAULTS IN THE 2018-2019 ACADEMIC YEAR. MANY VIOLENTLY INJURED YOUTHS (VIY) ARE RELEASED FROM THE HOSPITAL HAVING RECEIVED PHYSICAL CARE, BUT NO SERVICES RELATED TO THEIR EMOTIONAL SUFFERING. OVER 60% OF VIY IN PHILADELPHIA EXPERIENCE PTSD SYMPTOMS. UNTREATED PTSD WILL POTENTIALLY DERAIL A CHILD'S HEALTHY DEVELOPMENT AND SIGNIFICANTLY INCREASE THE RISK FOR SUBSTANCE ABUSE, SUICIDALITY, POOR MENTAL HEALTH, AND IMPAIRING OVERALL FUNCTIONING AT HOME, SCHOOL, AND IN THE COMMUNITY. GOAL 1: INCREASE THE NUMBER OF VIOLENTLY INJURED CHILDREN WHO ACCESS TRAUMA-SPECIFIC SERVICES VIA FLEXIBLE/ASSERTIVE OUTREACH STRATEGIES. OBJECTIVE 1.1: STAFF WILL INTRODUCE SERVICES THROUGH BEDSIDE VISITS, PHONE OUTREACH, AND HOME-VISITS TO 200 UNDUPLICATED CHILDREN/FAMILIES IN YR1; 220 IN YR2; 220 IN TR3; 220 IN YR4, AND 220 IN YR5. OBJECTIVE 1.2: 60% OF THOSE OUTREACHED EACH YEAR WILL RECEIVE TRAUMA PSYCHOEDUCATION. OBJECTIVE 1.3: A BRIEF ACUTE NEEDS ASSESSMENT WILL BE COMPLETED WITH 60% OF PARTICIPANTS OUTREACHED. GOAL 2: DECREASE TRAUMATIC STRESS SYMPTOMS/INCREASE DAILY FUNCTIONING IN VIY BY DELIVERING PS WITH TF-CBT. OBJECTIVE 2.1: 70% OF CHILDREN WHO RECEIVE PS WITH TF-CBT WILL REPORT REDUCED TRAUMA SYMPTOMS AT DISCHARGE. OBJECTIVE 2.2: 70% OF CHILDREN WHO RECEIVE PS AND TF-CBT WILL REPORT IMPROVED DAILY FUNCTIONING AT DISCHARGE. GOAL 3: INCREASE COPING SKILLS/WELLBEING AMONG VIY THROUGH PARTICIPATION IN A CULTURALLY RELEVANT GROUP THERAPY. OBJECTIVE 3.1: 10 CHILDREN WILL ATTEND CYPHER GROUP SESSION IN YR1; 20 IN YR2; 30 IN YR3; 40 IN YR4; 50 IN YR5. OBJECTIVE 3.2: 80% OF THOSE ATTENDING CYPHER WILL IMPROVE WELLBEING AS MEASURED AT DISCHARGE. GOAL 4: INCREASE CHILD SERVING ORGANIZATIONS KNOWLEDGE OF TRAUMA/IMPACT ON VIY TO INCREASE REFERRALS TO HHP AND ACCESS TO TRAUMA SERVICES. OBJECTIVE 4.1: STAFF WILL PROVIDE IN-SERVICE OR "TRAUMA 101" PRESENTATIONS TO 60 DIRECT CARE PROFESSIONALS ACROSS CHILD SERVING SYSTEMS IN YR1; 80 IN YR2; 100 IN YR3; 120 IN YR4 AND 140 IN YR5. 65% OF ATTENDEES WILL EXHIBIT INCREASED KNOWLEDGE OF TRAUMA AND ABILITY TO USE TRAUMA-INFORMED PRACTICES THROUGH POST SESSION EVALUATION SURVEYS. OBJECTIVE 4.2: REFERRALS TO HHP FROM PARTNER CHILD SERVING ORGANIZATIONS WILL INCREASE 15% EACH YEAR. NUMBER OF UNDUPLICATED INDIVIDUALS TO BE SERVED: YR 1, 120; YR 2, 132; YR 3, 132; YR 4, 132; YR 5, 132; TOTAL, 648.

MOLECULAR PATHWAYS TARGETED BY POTENT ANTIMALARIAL PYRAZOLE COMPOUNDS

NEURAL BASIS OF ACTIVE AVOIDANCE BEHAVIOR

EXOSOME-MEDIATED SIGNALING IN NEUROPATHIC PAIN

THE AWARD APPROVES FUNDING FOR THE FY2022 NATIONAL SERVICE AND CIVIC ENGAGEMENT RESEARCH FUNDING OPPORTUNITY DESCRIBED IN THE APPROVED PROGRAM NARRATIVE AND BUDGET.THE 2022 REQUIRED MATCH IS 0%. THIS AWARD ALSO FORWARD FUNDS $105,818 FOR THE 2023-24 PROGRAM YEAR.

SOCIAL DETERMINANTS OF FATTY LIVER DISEASE AND ITS RACIAL/ETHNIC DISPARITIES: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS - PROJECT SUMMARY LIVER DISEASE MORTALITY IS A KEY CONTRIBUTOR TO RECENT DECLINES IN LIFE EXPECTANCY IN THE US. DECADES OF RESEARCH HAVE DEMONSTRATED THE DISPROPORTIONATE BURDEN OF LIVER DISEASE AMONG RACIAL/ETHNIC MINORITIES AND THOSE WITH LOW-SOCIOECONOMIC POSITION. WITH THE ONGOING EPIDEMIC OF OBESITY, AND THE INCREASE IN ALCOHOL CONSUMPTION, FATTY LIVER DISEASES (FLD), INCLUDING NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) AND ALCOHOL-RELATED LIVER DISEASE (ALD), HAVE BECOME THE MOST PREVALENT CHRONIC LIVER CONDITIONS AFFECTING MILLIONS OF PEOPLE WORLDWIDE, CONSTITUTING A MAJOR AND GROWING PUBLIC HEALTH PROBLEM. FLD EPIDEMIOLOGY HAS LARGELY FOCUSED ON THE ROLE OF INDIVIDUAL-LEVEL BEHAVIORAL FACTORS, SUCH AS OBESITY AND ALCOHOL CONSUMPTION, IN FLD DEVELOPMENT. HOWEVER, INDIVIDUAL-FOCUSED THERAPEUTIC AND PREVENTIVE EFFORTS HAVE HAD LIMITED SUCCESS. FOR MANY CHRONIC DISEASES, ABUNDANT LITERATURE HAS DOCUMENTED HOW SOCIAL AND PHYSICAL ENVIRONMENTS PATTERN POPULATION HEALTH. IN CONTRAST, THE EMPIRICAL EVIDENCE OF THE ROLE OF SOCIAL DETERMINANTS OF HEALTH WITH FLD AND ITS DISPARITIES IS EXTREMELY LIMITED. FURTHERMORE, THE CURRENT PARADIGM TO EXPLAIN FLD DISPARITIES IS HEAVILY FOCUSED ON GENETIC SUSCEPTIBILITY (E.G. PNPLA3 GENE VARIANTS). TO ADDRESS THESE RESEARCH GAPS, THIS PROJECT WILL TEST THE NOVEL HYPOTHESIS THAT INDIVIDUAL AND COMMUNITY- LEVEL SOCIAL DETERMINANTS INFLUENCE FLD RISK AND THEIR SOCIAL AND RACIAL/ETHNIC DISPARITIES. TO TEST THIS HYPOTHESIS, WE PROPOSE TO OBTAIN AND ANALYZE LONGITUDINAL MEASURES OF LIVER FAT AND INFLAMMATION AMONG PARTICIPANTS OF THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA), THE LARGEST ONGOING MULTI-RACIAL POPULATION-BASED COHORT STUDY INVOLVING 6,814 MEN AND WOMEN (22% HISPANIC, 38% WHITES, 28% BLACKS, 12% CHINESE) FROM 6 GEOGRAPHICALLY DISTINCT AREAS OF THE US. MESA HAS THE MOST COMPREHENSIVE LONGITUDINAL DATA ON SOCIOECONOMIC (BOTH INDIVIDUAL AND COMMUNITY LEVEL), PSYCHOSOCIAL, NEIGHBORHOOD PHYSICAL AND SOCIAL ENVIRONMENT, ENVIRONMENTAL, BEHAVIORAL, AND BIOMEDICAL (INCLUDING GENETICS) FACTORS AND HEALTH OUTCOMES WITH UP TO 21 YEARS OF FOLLOW UP. OUR SPECIFIC AIMS ARE: 1) CHARACTERIZE RACIAL/ETHNIC DISPARITIES IN FLD INCIDENCE, AS MEASURED BY 10-YEAR CHANGES IN CT- MEASURED LIVER FAT AND LIVER ENZYMES, WHILE ACCOUNTING FOR GENETIC VARIANTS. 2) EXAMINE THE PROSPECTIVE ASSOCIATION OF INDIVIDUAL-LEVEL SOCIOECONOMIC POSITION (SEP) AND PSYCHOSOCIAL STRESSORS WITH FLD INCIDENCE AND THE CONTRIBUTION OF SEP AND PSYCHOSOCIAL FACTORS TO SOCIOECONOMIC AND RACIAL/ETHNIC DISPARITIES IN FLD INCIDENCE. 3) EXAMINE THE PROSPECTIVE ASSOCIATION OF COMMUNITY-LEVEL SOCIAL AND PHYSICAL FEATURES WITH FLD INCIDENCE AND ITS RACIAL/ETHNIC DISPARITIES IN FLD INCIDENCE. 4) EXAMINE THE ROLE OF COMMUNITY-LEVEL SOCIAL AND PHYSICAL FEATURES IN MAGNIFYING INDIVIDUAL-LEVEL GENETIC VULNERABILITY BY TESTING GENE-BY-ENVIRONMENT INTERACTIONS IN THE INCIDENCE OF FLD BETWEEN GENETIC VARIANTS AND CONTEXTUAL FACTORS. THIS PROJECT WILL CONSTITUTE THE LARGEST, MOST RIGOROUS AND COMPREHENSIVE INVESTIGATION OF THE ROLE OF SOCIAL DETERMINANTS OF HEALTH IN THE DEVELOPMENT AND PROGRESSION OF FLD AND ITS DISPARITIES.

DEFINE THE ROLE OF DENDRITIC CELLS IN HTLV-1 ASSOCIATED NEUROINFLAMMATORY DISEASE

ELUCIDATING THE ETIOLOGY OF SPAST-BASED HEREDITARY SPASTIC PARAPLEGIA - PROJECT SUMMARY HEREDITARY SPASTIC PARAPLEGIA (HSP) IS A HERITABLE NEURODEGENERATIVE DISORDER IN WHICH PATIENTS SUFFER FROM PROGRESSIVE WEAKNESS, SPASTICITY OF LOWER LIMBS AND GAIT DEFICIENCIES. THE DISEASE MAINLY MANIFESTS AS ADULT- ONSET DIE-BACK DEGENERATION OF THE CORTICOSPINAL TRACTS (CSTS). SPAST, ALSO CALLED SPG4, ENCODES SPASTIN, WHICH IS AN ENZYME THAT SEVERS MICROTUBULES. BY FAR, SPAST IS THE MOST COMMON GENE MUTATED IN HSP. TO DATE, HAPLOINSUFFICIENCY RESULTING FROM REDUCED FUNCTIONAL SPASTIN LEVELS HAS BEEN THE PREVALENT MECHANISTIC EXPLANATION FOR HSP-SPG4. HOWEVER, HAPLOINSUFFICIENCY FAILS TO EXPLAIN WHY THERE ARE NO DEVELOPMENTAL ABNORMALITIES IN HSP PATIENTS AND WHY AXONAL DEGENERATION IS MOSTLY CONFINED TO THE CSTS. IN ADDITION, SPG4 KNOCKOUT (KO) MICE DISPLAY ONLY VERY MILD MOTOR DEFICITS, WITH NO REPORTS OF CST DIE-BACK. A NEW MOUSE MODEL IN THE LABORATORY OF THE PI HAS BEEN DESIGNED SPECIFICALLY TO TEST GAIN-OF-FUNCTION TOXICITY OF MUTANT SPASTIN PROTEINS AS THE CAUSE OF CST DIE-BACK AND HSP-LIKE MOTOR DEFICITS. THE CENTRAL HYPOTHESIS OF THIS PROPOSAL IS THAT THE TOXIC PROPERTIES OF MUTANT SPASTIN PROTEINS ARE THE CAUSE OF HSP-SPG4, WHEREAS REDUCED FUNCTIONAL SPASTIN LEVELS DO NOT CAUSE HSP BUT RENDER AXONS MORE VULNERABLE TO THE DISEASE-SPECIFIC HIT. MECHANISTIC HYPOTHESES WILL BE INVESTIGATED VIA TRANSGENIC MOUSE MODELS (INCLUDING A NEW MOUSE ESTABLISHED IN THE PI’S LABORATORY, THE SPAST KNOCKOUT MOUSE, AND THE MOUSE THAT IS GENERATED BY CROSSING THE TWO), AS WELL AS FOREBRAIN GLUTAMATERGIC NEURONAL CULTURES DERIVED FROM ISOGENIC HUMAN INDUCED PLURIPOTENT STEM CELL (HIPSC) LINES. CATWALK GAIT ANALYSES AND CST ANATOMICAL ASSESSMENTS ON THE MICE WILL BE CONDUCTED TO COMPARE AND CONTRAST THE PHENOTYPES RESULTING FROM TOXICITY OF MUTANT SPASTINS WITH THOSE RESULTING FROM REDUCED FUNCTIONAL SPASTIN LEVELS. THE HYPOTHESIS WILL BE TESTED THAT CROSSING THE TWO MOUSE LINES WILL RESULT IN A MORE EXTREME HSP- LIKE PHENOTYPE THAN DISPLAYED BY EITHER OF THE PARENT LINES. DOSE DEPENDENT CYTOTOXICITY OF ACCUMULATED MUTATED SPASTIN PROTEINS, A KEY PREDICTION OF A GAIN-OF-FUNCTION MECHANISM FOR THE DISEASE, WILL BE EVALUATED. DECREASED MICROTUBULE ACETYLATION OBSERVED IN THE AFFLICTED AXONS IS POSITED TO RESULT FROM HIGHER HISTONE DEACETYLASE 6 (HDAC6) ACTIVITY ELICITED BY MUTANT SPASTINS AND IS POSITED TO BE THE MAIN CAUSE OF THE DIE-BACK DEGENERATION OF CSTS. POTENTIAL MECHANISTIC EXPLANATIONS FOR THE GREATER HDAC6 ACTIVITY WILL BE EXPLORED. REDUCED MICROTUBULE MOBILITY RESULTING FROM REDUCED MICROTUBULE SEVERING (DUE TO LESS FUNCTIONAL SPASTIN) IS POSITED TO BE THE MAIN CAUSE OF THE GREATER VULNERABILITY OF THE AXON TO THE MUTANT SPASTINS. CONTEMPORARY MOLECULAR BIOLOGICAL, LIVE-CELL IMAGING, ANATOMICAL AND BEHAVIORAL APPROACHES WILL BE USED TO TEST THESE HYPOTHESES. SUCCESSFUL RESOLUTION OF THESE ISSUES WILL LEAD TO BETTER PROSPECTS FOR TREATING PATIENTS WITH HSP-SPG4, AND ALSO PROVIDE INSIGHTS INTO MICROTUBULE-BASED MECHANISMS THAT MAY BE COMMON ACROSS HSPS CAUSED BY MUTATIONS OF OTHER GENES.

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

SPINAL DOPAMINERGIC MECHANISMS REGULATING THE MICTURITION REFLEX AFTER SPINAL CORD INJURY

MECHANISMS OF ACTION CONTRIBUTING TO DECREASE SPASTICITY AND IMPROVE MOTOR RECOVERY WITH REPEATED TRANSCUTANEOUS STIMULATION AFTER SPINAL CORD INJURY - SPASTICITY IS A DEBILITATING CONDITION WHICH EMERGES IN UP TO ~75% OF INDIVIDUALS WITH SPINAL CORD INJURY (SCI), WITH MOST EXPERIENCING SPASTIC EPISODES ONE YEAR AFTER INJURY. CURRENT PHARMACOLOGICAL APPROACHES TO DECREASE SPASTICITY (I.E. BACLOFEN, TIZANIDINE, BOTULINUM TOXIN) LEAD TO SIGNIFICANT UNDESIRABLE SIDE EFFECTS SUCH AS SEDATION AND DIZZINESS. MORE IMPORTANTLY, THEY ALSO INDUCE A PROFOUND DEPRESSION OF SPINAL REFLEX EXCITABILITY WHICH SIGNIFICANTLY REDUCES MUSCLE ACTIVITY AND IMPEDES CONVENTIONAL REHABILITATIVE EFFORTS. THERE IS THEREFORE A CRITICAL NEED TO IDENTIFY ALTERNATE AVENUES. THE LAST DECADE HAS SEEN A CRITICAL BREAKTHROUGH IN THE SCI FIELD WITH THE USE OF STIMULATION-BASED THERAPIES, IN PARTICULAR EPIDURAL STIMULATION, TO FURTHER MODULATE THE EXCITABILITY OF SPINAL NETWORKS AND ENHANCE FUNCTIONAL RECOVERY AFTER SCI. ALTHOUGH PROMISING, THESE TREATMENTS ARE INVASIVE, COSTLY, AND REQUIRE HIGHLY SKILLED AND SPECIALIZED TEAMS. IN CONTRAST, NON-INVASIVE TRANSCUTANEOUS SPINAL CORD STIMULATION (TSCS) HAS THE POTENTIAL TO BE RAPIDLY ADAPTED IN CLINICAL REHABILITATION SETTINGS. THIS PROJECT IS DESIGNED TO ADVANCE OUR UNDERSTANDING OF THE NEUROPLASTICITY TRIGGERED BY 6 WEEKS OF REPEATED LUMBAR TSCS INITIATED ACUTELY, TO PREVENT THE DEVELOPMENT OF SPASTICITY, OR CHRONICALLY, TO DECREASE SPASTICITY ONCE SPINAL HYPEREXCITABILITY HAS FULLY DEVELOPED. AIM 1 WILL DETERMINE IF TSCS CONTRIBUTES TO DECREASE SPASTICITY/HYPERREFLEXIA THROUGH RESTORING SPINAL INHIBITION IN LUMBAR SPINAL NETWORKS. BEHAVIORAL CORRELATES OF SPASTICITY WILL BE MONITORED OVER TIME. IN A TERMINAL EXPERIMENT, THE EFFECT OF TSCS ON SPINAL INHIBITORY PATHWAYS (HOMOSYNAPTIC DEPRESSION, RECIPROCAL INHIBITION, AND PRESYNAPTIC INHIBITION) WILL BE CORRELATED TO THE REORGANIZATION OF INHIBITORY/EXCITATORY INPUTS TO MOTONEURONS AND PRIMARY AFFERENTS. AIM 2 WILL DETERMINE IF TSCS RESTORES MOTOR-EVOKED POTENTIALS (MEPS) ORIGINATING FROM ABOVE AND BELOW THE INJURY AFTER SCI. DURING A TERMINAL EXPERIMENT, MEPS INITIATED BY A STIMULATION TO THE SPINAL CORD BELOW OR ABOVE THE INJURY WILL BE RECORDED AS WELL AS SYNAPTIC TRANSMISSION IN THE CORTICO-RETICULOSPINAL PATHWAY. THE MODULATORY EFFECT OF PROPRIOCEPTIVE FEEDBACK ON THE MEPS OF VARIOUS ORIGIN WILL ALSO BE EVALUATED. THE CONTRIBUTION OF PRIMARY AFFERENTS (VGLUT1+/PARAVALBUMIN) AND DESCENDING TRACTS (VGI) TO INCREASED MOTOR OUTPUT AND NORMALIZATION OF THE SCI-INDUCED FACILITATION OF PROPRIOCEPTIVE AFFERENTS WILL BE EVALUATED. BECAUSE SPASTIC SYMPTOMS, SUCH AS SPASMS AND UNCONTROLLABLE REFLEXES, RENDER REHABILITATION AND ACTIVITY-BASED THERAPIES SUCH AS LOCOMOTOR TRAINING CHALLENGING AND LESS EFFECTIVE, AIM 3 WILL DETERMINE IF DECREASING SPASTICITY WITH TSCS PRIOR TO THE INITIATION OF A STEP-TRAINING PROGRAM IMPROVES LOCOMOTOR RECOVERY. SPASTICITY AND LOCOMOTOR RECOVERY WILL BE EVALUATED OVER TIME AND WILL BE CORRELATED TO THE RETURN OF SPINAL INHIBITION AND CORTICO-RETICULOSPINAL TRANSMISSION. THE PROPOSED RESEARCH PROJECT IS CONSISTENT WITH THE GOALS OF THE NIH/NINDS BY ADDRESSING A CURRENT GAP IN KNOWLEDGE AND DELINEATING THE MECHANISMS OF TSCS. UNDERSTANDING THE MECHANISMS UNDERLYING THE BENEFICIAL EFFECT OF NON-INVASIVE INTERVENTIONS IS CRITICAL TO OPTIMIZE EVIDENCE-BASED CLINICAL PRACTICE AND FAST-TRACK ITS USE IN THE SCI COMMUNITY.

SLEEP DISTURBANCES DURING COCAINE ABSTINENCE, DOPAMINE ADAPTATIONS, AND MOTIVATION FOR COCAINE - PROJECT SUMMARY/ABSTRACT COCAINE USE DISORDER IS A CHRONIC DISEASE AND CURRENTLY NO APPROVED PHARMACOTHERAPIES EXIST FOR ITS TREATMENT. AMONG THE GREATEST CHALLENGES IN THE TREATMENT OF COCAINE USE DISORDER IS PREVENTION OF RELAPSE TO DRUG USE. IN RATS, PERIODS OF ABSTINENCE FOLLOWING COCAINE USE INTENSIFIES SEEKING AND MOTIVATION FOR DRUG, WHICH HAS BEEN ASSOCIATED WITH INCREASED PROPENSITY FOR RELAPSE. ALTHOUGH EXTENSIVE EVIDENCE INDICATES THAT MESOLIMBIC DOPAMINE INFLUENCES COCAINE REINFORCEMENT, THE INVOLVEMENT OF DOPAMINE IN THE REGULATION OF SLEEP HAS RECEIVED COMPARATIVELY LESS ATTENTION. WE RECENTLY DEMONSTRATED THAT THE DOPAMINE TRANSPORTER GOVERNS DIURNAL FLUCTUATIONS IN EXTRACELLULAR DOPAMINE TONE IN THE NUCLEUS ACCUMBENS AND THAT DOPAMINE UPTAKE FLUCTUATES ACROSS THE SLEEP/WAKE CYCLE, WHICH IMPACTS THE EFFECTS OF COCAINE AT INHIBITING THE DOPAMINE TRANSPORTER. MOREOVER, OUR PRELIMINARY AND RECENTLY PUBLISHED DATA SUGGEST THAT SLEEP DISTURBANCES THAT OCCUR DURING ABSTINENCE PROMOTE COCAINE SEEKING AND THAT ALTERATIONS IN DOPAMINE TRANSPORTER FUNCTION IN THE NUCLEUS ACCUMBENS MAY CONTRIBUTE TO THESE EFFECTS. TOGETHER, THESE FINDINGS RAISE THE POSSIBILITY THAT DOPAMINE NEUROTRANSMISSION IN THE NUCLEUS ACCUMBENS MAY FUNCTION AS A NODE THAT INTEGRATES BOTH MOTIVATIONAL AND SLEEP/WAKE PROCESSES. IN THE PROPOSED STUDIES, WE HYPOTHESIZE THAT COCAINE-RELATED SLEEP DISRUPTIONS DURING ABSTINENCE CONTRIBUTE TO DOPAMINE TRANSPORTER ADAPTATIONS THAT PROMOTE INCUBATION OF COCAINE SEEKING AND INCREASE DOPAMINE TRANSPORTER SENSITIVITY TO COCAINE. FURTHER, WE PROPOSE THAT RESTORATION OF RAPID-EYE MOVEMENT SLEEP AND/OR NORMALIZATION OF DOPAMINE TRANSPORTER FUNCTION DURING ABSTINENCE WILL ATTENUATE INCUBATION OF COCAINE SEEKING AND REDUCE DOPAMINE TRANSPORTER SENSITIVITY TO COCAINE. COMPLETION OF THE PROPOSED EXPERIMENTS WILL OFFER NEW INSIGHTS INTO THE LINK BETWEEN SLEEP DISRUPTIONS AND DEVELOPMENT OF COCAINE SEEKING, AND THE EXTENT TO WHICH THIS INVOLVES ALTERATIONS IN DOPAMINE NEUROTRANSMISSION IN THE NUCLEUS ACCUMBENS. CONSEQUENTLY, EXPECTED RESULTS SHOULD SIGNIFICANTLY INFORM THE FIELD AND HELP TO IDENTIFY FUTURE TREATMENT STRATEGIES FOR COCAINE USE DISORDER.

OPTIMIZING DIGITAL HEALTH TECHNOLOGIES TO IMPROVE THERAPEUTIC SKILL USE AND ACQUISITION - PROJECT SUMMARY BINGE EATING (I.E., EATING A LARGE AMOUNT OF FOOD WITHIN A DISCRETE TIME PERIOD ACCOMPANIED BY A SENSE OF LOSS OF CONTROL OVER EATING) IS A KEY SYMPTOM OF SEVERAL EATING DISORDERS INCLUDING BULIMIA NERVOSA (BN) AND BINGE EATING DISORDER (BED). WHILE COGNITIVE BEHAVIORAL THERAPY (CBT) CAN BE AN EFFECTIVE TREATMENT APPROACH FOR BINGE EATING, 40-50% OF PATIENTS WITH BED AND NEARLY 70% OF PATIENTS WITH BN FAIL TO ACHIEVE REMISSION. A GROWING BODY OF RESEARCH SUGGESTS THAT A KEY REASON MANY PATIENTS MAY FAIL TO BENEFIT FROM CBT IS SUBOPTIMAL RATES OF SKILL ACQUISITION (I.E., THE ABILITY TO SUCCESSFULLY PERFORM A SKILL LEARNED IN TREATMENT) AND UTILIZATION (I.E., THE FREQUENCY WITH WHICH A PATIENT PRACTICES OR EMPLOYS THERAPEUTIC SKILLS). POOR SKILL USE AND ACQUISITION MAY BE PARTICULARLY HIGH AMONG CERTAIN SUBSETS OF PATIENTS SUCH AS THOSE WHO EXPERIENCE DEFICITS IN SELF-REGULATION. THIS RESEARCH SUGGESTS THAT TREATMENT AUGMENTATIONS THAT COULD IMPROVE SKILL USE AND ACQUISITION (PARTICULARLY FOR THOSE WHO NEED ADDITIONAL SUPPORT TO SUCCEED IN CBT) COULD HAVE HIGH POTENTIAL TO ENHANCE OUTCOMES. THE NIMH HAS RECENTLY IDENTIFIED THAT DIGITAL HEALTH TECHNOLOGIES (DHTS) HAVE HIGH POTENTIAL TO “PROMOTE BETWEEN-SESSION SKILL PRACTICE/ACQUISITION” AND HAVE SELECTED THIS AS A HIGH PRIORITY RESEARCH INITIATIVE (NOT- MH-18-031). DHTS MAY BE ABLE TO IMPROVE SKILL USE AND ACQUISITION VIA SEVERAL PATHWAYS, ONE OF WHICH IS THE USE OF MICRO-INTERVENTIONS (I.E., SHORT DIGITAL INTERVENTIONS DELIVERED TO PEOPLE AS THEY GO ABOUT THEIR DAILY LIVES). MICRO-INTERVENTIONS CAN RANGE IN COMPLEXITY FROM SOMETHING AS SIMPLE AS AN AUTOMATED REMINDER TO PRACTICE A THERAPEUTIC SKILL TO ADVANCED JUST-IN-TIME ADAPTIVE INTERVENTION (JITAI) SYSTEMS THAT USE MACHINE LEARNING OR OTHER ADVANCED ALGORITHMS TO DELIVER PERSONALLY TAILORED INTERVENTIONS IN SPECIFIC MOMENTS OF NEED. RECENT PILOT WORK FROM OUR TEAM SUPPORTS THE UTILITY OF JITAIS AS A WAY TO IMPROVE SKILL UTILIZATION AND ACQUISITION WHEN USED AS A TREATMENT AUGMENTATION BUT DID NOT COMPARE JITAIS TO MORE SIMPLE AUTOMATED REMINDER MICRO- INTERVENTIONS. ADDITIONALLY, OUR PILOT WORK ALSO FOUND THAT FREQUENT MONITORING OF SKILL USE WAS IN AND OF ITSELF A SURPRISINGLY EFFECTIVE METHOD FOR ENCOURAGING SKILL PRACTICE. THESE RESULTS SUGGEST THAT THE ADDED COMPLEXITY OF JITAIS MAY NOT BE NECESSARY FOR ALL INDIVIDUALS TO EXPERIENCE BENEFIT FROM A DHT AUGMENTATION. THE ABILITY TO DEVELOP MAXIMALLY EFFECTIVE DHTS REQUIRES THE USE OF A LARGER CLINICAL TRIAL THAT CAN HELP TO IDENTIFY WHICH DIGITAL COMPONENTS (AND AT WHICH COMPLEXITY) ARE MOST EFFECTIVE AT IMPROVING SKILL USE AND ACQUISITION AS WELL CLINICAL OUTCOMES. WE PROPOSE TO USE A 2 X 3 FULL FACTORIAL DESIGN IN WHICH 264 INDIVIDUALS WITH BN OR BED ARE ASSIGNED TO ONE OF SIX TREATMENT CONDITIONS, I.E., REPRESENTING EACH PERMUTATION OF SELF-MONITORING COMPLEXITY (SKILLS-MONITORING ON VS. SKILLS-MONITORING OFF) AND MICRO-INTERVENTION COMPLEXITY (NO MICRO- INTERVENTIONS VS. AUTOMATED REMINDER MESSAGES VS. JITAIS) AS AN AUGMENTATION TO CBT. RESULTS OF THE COMPONENT ANALYSIS SET UP FUTURE WORK TO EVALUATE AN OPTIMIZED DHT CONTAINING ONLY EFFECTIVE COMPONENTS (WHICH CAN BE EXPECTED TO HAVE SUPERIOR TARGET ENGAGEMENT, EFFICACY, EFFICIENCY AND DISSEMINABILITY).

OP EARLY INTERVENTION SVCS W/RESPECT TO HIV DISEASE

SCHOLARSHIPS FOR DISADVANTAGED STUDENTS

MECHANISMS GOVERNING STEM CELL COORDINATION BY THE NICHE

ROLE OF CX3CR1 IN BREAST CANCER METASTASIS

ROLES OF TYPE III COLLAGEN IN THE MATRIX ASSEMBLY AND MECHANOBIOLOGY OF CARTILAGE - ABSTRACT OSTEOARTHRITIS (OA) IS CHARACTERIZED BY THE IRREVERSIBLE BREAKDOWN OF CARTILAGE EXTRACELLULAR MATRIX (ECM). CURRENT REGENERATIVE STRATEGIES CANNOT FULLY RESTORE THE BIOMECHANICAL FUNCTIONS OF CARTILAGE, AS THEY DO NOT FULLY RECAPITULATE THE COLLAGEN FIBRILLAR ARCHITECTURE OF NATIVE ECM. THIS PROJECT WILL STUDY THE ACTIVITIES OF THE REGULATORY FIBRIL-FORMING TYPE III COLLAGEN (COLLAGEN III) IN DIRECTING CARTILAGE MATRIX ASSEMBLY AND CHONDROCYTE MECHANOTRANSDUCTION AT DIFFERENT STAGES OF POST-NATAL GROWTH, MAINTENANCE AND DISEASE. OUR CENTRAL HYPOTHESIS IS THAT COLLAGEN III REGULATES CARTILAGE ECM BIOMECHANICS AND CHONDROCYTE MECHANOTRANSDUCTION THROUGH ITS EFFECTS ON COLLAGEN FIBRIL ASSEMBLY AND INTEGRIN SWITCHING, AND THAT LOSS OF COLLAGEN III INCREASES CARTILAGE SUSCEPTIBILITY TO OA. SPECIFICALLY, WE WILL ELUCIDATE THE ACTIVITIES OF COLLAGEN III IN THE FORMATION AND MAINTENANCE OF CARTILAGE (AIM 1), IN INJURY-INDUCED CARTILAGE DEGRADATION IN OA (AIM 2), AS WELL AS IN THE NEO-MATRIX ASSEMBLY AND CHONDROCYTE MECHANOTRANSDUCTION (AIM 3). IN AIM 1, WE WILL DETERMINE IF LOSS OF COLLAGEN III IMPAIRS ECM FIBRIL ASSEMBLY, PERICELLULAR MATRIX (PCM) INTEGRITY, CHONDROCYTE MECHANOSENSING AND GENE EXPRESSION DURING THE POST-NATAL GROWTH AND AGING. IN AIM 2, WE WILL FIRST DETERMINE IF LOSS OF COLLAGEN III ACCELERATES CARTILAGE DEGENERATION AND OA PROGRESSION IN POST-TRAUMATIC OA INDUCED BY THE FOLLOWING DESTABILIZATION OF THE MEDIAL MENISCUS SURGERY (DMM MODEL). WE WILL THEN DETERMINE IF COLLAGEN III DELAYS THE DEGRADATION OF COLLAGEN II AND AGGRECAN IN RESPONSE TO INFLAMMATORY FACTORS KNOWN TO DRIVE OA PROGRESSION. IN AIM 3, WE WILL FIRST DETERMINE IF COLLAGEN III REGULATES THE ASSEMBLY OF NEO-MATRIX SYNTHESIZED BY CHONDROCYTES CULTURED IN 3D HYDROGEL UNDER THE STIMULATION OF DYNAMIC LOADING. NEXT, WE WILL DELINEATE THE EFFECTS OF COLLAGEN III ON REGULATING THE INTEGRIN SWITCHING OF CHONDROCYTES AND DOWNSTREAM MECHANOSENSITIVE PATHWAYS, WITH A FOCUS ON INTEGRIN Α11. TO ELUCIDATE THE ROLE OF COLLAGEN III IN CARTILAGE, A NUMBER OF INNOVATIVE APPROACHES WILL BE USED. WE GENERATED A NOVEL INDUCIBLE COLLAGEN III DEFICIENT (I.E., COL3A1F/+, COL3A1F/F) MOUSE MODEL TO STUDY THE DOSE-DEPENDENT EFFECTS OF COLLAGEN III BY TEMPORAL TARGETING OF COLLAGEN III IN CARTILAGE. WE WILL APPLY A MULTIDISCIPLINARY ANALYSIS PARADIGM THAT INTEGRATES ATOMIC FORCE MICROSCOPY (AFM)-NANOMECHANICAL TESTS, IMMUNOFLUORESCENCE IMAGING AND LASER CAPTURE MICRODISSECTION. THESE TECHNIQUES WILL ENABLE US TO STUDY THE IMPACT OF COLLAGEN III ON CARTILAGE COMPOSITION, STRUCTURE, MECHANICS AND CELL MECHANOTRANSDUCTION, AND TO DETERMINE MECHANISMS BY WHICH IT REGULATES MATRIX REMODELING AND MECHANOSENSATION. SUCCESSFUL COMPLETION OF THIS STUDY WILL ESTABLISH COLLAGEN III AS AN ESSENTIAL CONSTITUENT RESPONSIBLE FOR ECM STRUCTURAL INTEGRITY AND CELL MECHANOTRANSDUCTION OF CARTILAGE. OUTCOMES WILL PROVIDE A NEW BASIS FOR IMPROVING CARTILAGE TISSUE ENGINEERING USING COLLAGEN III-BASED BIOMATERIALS AND ELUCIDATE NEW COLLAGEN III-DEPENDENT MECHANISMS TO SERVE AS TARGETS FOR OA INTERVENTION.

NON-MEDICAL PRESCRIPTION DRUG USE AMONG HIGH-RISK YOUTH

NEB: META-CAPACITANCE AND SPATIALLY PERIODIC ELECTRONIC EXCITATION DEVICES (MC-SPEEDS)

VIRTUAL REALITY DRIVING AND BRAIN INJURY IN THE CLINIC

ANALYZING NEURAL STEM CELL CLONAL DEVELOPMENT

NEUROTRANSPLANTATION AND TRAINING TO PROMOTE RECOVERY OF CHRONIC SCI CATS

VARIANT SURFACE ANTIGENS AND IMMUNITY TO MALARIA

PROTON PUMPING AND ENERGY METABOLISM OF THE RING STAGE MALARIA PARASITES - MALARIA REMAINS A MAJOR GLOBAL HEALTH BURDEN, AFFECTING 40% OF THE WORLD’S POPULATION. IN 2021, THERE WERE 247 MILLION REPORTED CASES, RESULTING IN OVER 619,000 DEATHS. THE DISEASE IS CAUSED BY REPETITIVE GROWTH OF THE PROTOZOAN PARASITES KNOWN AS PLASMODIUM SPP. INSIDE RED BLOOD CELLS (RBCS), LEADING TO RBC LYSIS. AMONG THE FIVE MALARIA SPECIES INFECTING HUMANS, PLASMODIUM FALCIPARUM IS THE MOST LETHAL, RESPONSIBLE FOR MORE THAN 80% OF THE DISEASE’S MORBIDITY AND MORTALITY. THIS PARASITE UNDERGOES ASEXUAL REPRODUCTION WITHIN RBCS OVER ITS 48-HOUR LIFECYCLE, WHICH CONSISTS OF THREE MAJOR STAGES: THE RING STAGE (~ 20 HOURS), THE TROPHOZOITE STAGE (~ 16 HOURS) AND THE SCHIZONT STAGE (~12 HOURS). DURING THE RING STAGE, INFECTED RBCS (IRBCS) HAVE A SMOOTH SURFACE LIKE UNINFECTED RBCS, ENABLING THEM TO EVADE CLEARANCE BY THE SPLEEN AND CIRCULATE IN THE PERIPHERAL BLOODSTREAM. THIS STAGE IS METABOLICALLY QUIESCENT AND CHALLENGING TO TARGET WITH AVAILABLE ANTIMALARIALS, AS MOST OF THESE DRUGS ARE NOT HIGHLY EFFECTIVE AGAINST THE SLOW-GROWING PARASITE. FURTHERMORE, THE RING STAGE CAN ENTER A DORMANT STATE AFTER DRUG TREATMENT, CONTRIBUTING TO DRUG RESISTANCE. THEREFORE, THERE IS AN URGENT NEED FOR A BETTER UNDERSTANDING OF THE FUNDAMENTAL BIOLOGY OF RING STAGE MALARIA PARASITES. OUR LABORATORY HAS MADE A SIGNIFICANT DISCOVERY BY REVEALING THAT THE METABOLICALLY INACTIVE RING STAGE PARASITE EMPLOYS AN ANCIENT PYROPHOSPHATE-DRIVEN PROTON PUMP TO SURVIVE FOR 20 HOURS INSIDE THE RBC FOLLOWING THE TIME OF INVASION. THIS ATP-INDEPENDENT PROTON PUMP IS KNOWN AS PFVP1 (PLASMODIUM FALCIPARUM VACUOLAR PYROPHOSPHATASE 1), AND IT DERIVES ENERGY FROM THE HYDROLYSIS OF PYROPHOSPHATE (PPI), A METABOLIC BY-PRODUCT GENERATED DURING SYNTHESIS OF DNA, RNA, AND PROTEIN. BASED ON THESE OBSERVATIONS, WE HYPOTHESIZE THAT THE RING-STAGE P. FALCIPARUM RELIES ON AN ATP-INDEPENDENT MECHANISM FOR PROTON EXPORTING AND ESTABLISHING PLASMA MEMBRANE POTENTIAL, IDENTIFYING A DISTINCTIVE VULNERABILITY IN THIS CHALLENGING STAGE OF THE ASEXUAL LIFECYCLE. TO TEST THIS HYPOTHESIS, WE OUTLINE TWO SPECIFIC AIMS. AIM I. INVESTIGATE THE IMPACT OF PFVP1’S LOOP SEQUENCES ON ITS PROTON PUMPING FUNCTIONALITY. AIM II. EXAMINE POLYPHOSPHATE METABOLISM AND PPI METABOLISM TO UNDERSTAND THE ENERGY SOURCE FOR PFVP1. THE OUTCOMES OF THIS RESEARCH PROPOSAL WILL PROVIDE INSIGHTS INTO HOW THE METABOLICALLY QUIESCENT RING STAGE PARASITE SURVIVES WITHIN THE RBC FOR NEARLY A DAY FOLLOWING INVASION. GIVEN THE ESSENTIAL NATURE OF PFVP1 AND ITS ABSENCE IN HUMANS, PFVP1 EMERGES AS AN IDEAL TARGET FOR COMBATING THE RING STAGE PARASITES. INHIBITING THIS LESS ACTIVE STAGE IS OF UTMOST IMPORTANCE TO ADVANCE MALARIA CONTROL AND ERADICATION EFFORTS.

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

IMPROVING CARDIOMETABOLIC HEALTH IN INDIVIDUALS WITH SCI USING HOME-BASED INTERACTIVE VIRTUAL GAMING

PHYSICAL MECHANISMS OF 3D CELL MOTILITY

DYSREGULATION OF GLUTAMATE TRANSPORTER-DEPENDENT NEUROVASCULAR COUPLING IN ALZHEIMER'S DISEASE - DYSREGULATION OF GLUTAMATE TRANSPORTER-DEPENDENT NEUROVASCULAR COUPLING IN ALZHEIMER’S DISEASE DECREASES IN CEREBRAL BLOOD FLOW, GLUCOSE METABOLISM, AND IMPAIRMENT OF NEUROVASCULAR COUPLING ARE ASSOCIATED WITH A NUMBER OF NEURODEGENERATIVE DISEASE AND COGNITIVE DECLINE, INCLUDING ALZHEIMER’S DISEASE AND MAY PRECEDE OR EXACERBATE DISEASE. THESE DEFICITS ARE ALSO ACCOMPANIED BY LOSS OF GLUTAMATE TRANSPORTERS, NA+/CA2+ EXCHANGER (NCX) ISOFORMS, AND DEFICITS IN MITOCHONDRIAL DYNAMICS AND OVER THE LAST FEW YEARS, WE HAVE DEMONSTRATED THAT ASTROCYTIC GLU TRANSPORTERS COUPLE TO INCREASES IN INTRACELLULAR CA2+ THROUGH REVERSED OPERATION OF NA+/CA2+ EXCHANGE (NCX). WE DEMONSTRATED THAT MITOCHONDRIA CO-COMPARTMENTALIZE WITH GLU TRANSPORTERS IN ASTROCYTE PROCESSES AND THAT MITOCHONDRIAL POSITIONING RELATIVE TO GLU TRANSPORTERS AND SYNAPSES IS DEPENDENT UPON CA2+ AND THAT MITOCHONDRIA SHAPE CA2+ SIGNAL. MOREOVER, WE FOUND THAT GLUTAMATE TRANSPORT IS SUFFICIENT TO EVOKE INCREASES IN ARTERIOLE DIAMETER (TRANSPORTER-DEPENDENT NVC) DOWNSTREAM OF REVERSED NCX. THESE AND OTHER OBSERVATIONS HAVE PROMPTED THE CENTRAL HYPOTHESIS THAT GLU TRANSPORT AND REVERSED NA+/CA2+ EXCHANGE FORM A FUNCTIONAL SIGNALING PATHWAY IN ASTROCYTES THAT IS MODULATED BY MITOCHONDRIA AND THAT EXCESSIVE ACTIVATION OF THIS PATHWAY CONTRIBUTES TO PATHOLOGY OBSERVED DURING THE DEVELOPMENT OF AD. IN BIOENERGETICS. AIM 1DETERMINE IF TRANSPORTER-MEDIATED NVC IS IMPAIRED IN AD. IN AIM 2, WE WILL DETERMINE IF ALTERED ASTROCYTIC MITOCHONDRIA DISTRIBUTION FUNCTION EFFECTS OF AD. USING IN VIVO IMAGING OR CORTICAL BLOOD FLOW, LOCAL APPLICATION OF GLUTAMATE TRANSPORTERS, AND SELECTIVE MANIPULATION (GENETIC AND PHARMACOLOGIC) OF DOWNSTREAM SIGNALING AND MITOCHONDRIAL DYNAMICS, WE WILL DISSECT THE RELATIONSHIP BETWEEN GLUTAMATE TRANSPORT, NCX, AND MITOCHONDRIA IN THE CONTROL OF CORTICAL BLOOD FLOW AND DETERMINE IF LOSS OF THIS SIGNALING AXIS IMPACTS BLOOD FLOW REGULATION/NEUROVASCULAR COUPLING IN AD.

A TLR3-STAT3-MIR-155 AXIS AND ASTROCYTE-MYELOID CROSSTALK IN VIRAL ENCEPHALITIS