Case Western Reserve University

CASE COMPREHENSIVE CANCER CENTER SUPPORT GRANT

EPIDEMIOLOGY OF DIABETES INTERVENTIONS AND COMPLICATIONS (EDIC)

CLINICAL AND TRANSLATIONAL SCIENCE COLLABORATIVE OF CLEVELAND

CASE WESTERN RESERVE UNIVERSITY/CLEVELAND CLINIC CTSA (UL1)

CASE AIDS CLINICAL TRIALS UNIT

CENTER FOR AIDS RESEARCH(CFAR)

CLINICAL AND TRANSLATIONAL SCIENCE COLLABORATIVE OF CLEVELAND

NSF CENTER FOR LAYERED POLYMERIC SYSTEMS

CLINICAL AND TRANSLATIONAL SCIENCE COLLABORATIVE OF NORTHERN OHIO, CATALYZING LINKAGES TO EQUITY IN HEALTH (CLE HEALTH) - PROJECT SUMMARY/ABSTRACT FOR THE PAST 15 YEARS, THE CLINICAL AND TRANSLATIONAL SCIENCE COLLABORATIVE (CTSC) AT CASE WESTERN RESERVE UNIVERSITY (CWRU) HAS LINKED CLINICAL AND TRANSLATIONAL RESEARCH EFFORTS AT FIVE INDEPENDENT INSTITUTIONS— CWRU, CLEVELAND CLINIC, METROHEALTH SYSTEM, UNIVERSITY HOSPITALS OF CLEVELAND, AND LOUIS STOKES CLEVELAND VETERANS AFFAIRS MEDICAL CENTER. TWO NEW PARTNERS (UNIVERSITY OF TOLEDO SCHOOL OF MEDICINE AND NORTHEAST OHIO MEDICAL UNIVERSITY) ARE NOW BEING ADDED TO EXTEND THE CTSC’S REACH ACROSS NORTHERN OHIO. THE CWRU CTSC HAS A STRONG TRACK RECORD OF ENHANCING THE QUANTITY AND QUALITY OF CLINICAL AND TRANSLATIONAL SCIENCE (CTS) AMONG OUR PARTNERS BY FACILITATING NOVEL RESEARCH PARADIGMS, TECHNOLOGIES, AND TRAINING. OUR CTSC HAS DEVELOPED A NEW GENERATION OF RESEARCHERS, ENHANCED COLLABORATIONS AMONG INVESTIGATORS, STREAMLINED DISCOVERY BY BUILDING PARTNERSHIPS AMONG INDUSTRY AND COMMUNITY AND ORGANIZATIONAL PARTNERS, AND FACILITATED MANY SUCCESSFUL ENTREPRENEURIAL STARTUPS. BUILDING ON THIS SOLID FOUNDATION, THE CWRU CTSC PROPOSES AN EXPANDED FOCUS ON HEALTH EQUITY, REFLECTED IN THE PROJECT THEME CATALYZING LINKAGES TO EQUITY IN HEALTH (CLE HEALTH). SOCIAL, ECONOMIC, AND ENVIRONMENTAL DISADVANTAGES ARE LINKED TO POOR HEALTH OUTCOMES AND LEAD TO DISPARITIES IN LIFE EXPECTANCY, INFANT MORTALITY, AND RATES OF CHRONIC CONDITIONS. MINORITY GROUPS ARE OFTEN UNDERREPRESENTED IN CLINICAL TRIALS AS WELL, MEANING THERE CAN BE INSUFFICIENT DATA FOR UNDERSTANDING THE EFFECTIVENESS OR SAFETY OF NEW DRUGS, PROCEDURES, OR HEALTH INTERVENTIONS FOR DIFFERENT POPULATIONS. THE OVERALL GOALS OF THIS PROJECT ARE TO 1) UNDERSTAND THE FUNDAMENTAL BARRIERS TO OPTIMAL RECRUITMENT OF UNDERREPRESENTED GROUPS IN CLINICAL TRIALS AND TEST AND SCALE INTERVENTIONS AIMED AT BREAKING DOWN THESE BARRIERS TO DIVERSIFY STUDY ENGAGEMENT, 2) FACILITATE AND EXPEDITE INNOVATION IN MULTICENTER CLINICAL AND TRANSLATIONAL RESEARCH BY FULLY INTEGRATING COMMUNITY AND STAKEHOLDER PARTNERS AND ENSURING THAT THIS RESEARCH REPRESENTS THE EXPERIENCES OF ALL AND RESULTS IN HEALTH IMPROVEMENTS FOR ALL, 3) DISSEMINATE AND IMPLEMENT NOVEL AND RESPONSIVE RESEARCH PROGRAMS ACROSS CLINICAL AND COMMUNITY SETTINGS TO ADVANCE ACCESS TO HEALTH INTERVENTIONS THAT AIM TO PROMOTE HEALTH EQUITY, AND 4) CREATE AND DISSEMINATE INCLUSIVE AND HIGH IMPACT EDUCATIONAL AND TRAINING PROGRAMS FOR TRANSLATIONAL RESEARCH PROFESSIONALS OF ALL DISCIPLINES AND LEVELS, BOTH IN CLINICAL AND COMMUNITY SETTINGS. THE CTSC HAS DESIGNED A STRATEGIC MANAGEMENT CORE AND SIX CTS RESEARCH AND TRAINING ELEMENTS TO ACCOMPLISH THESE GOALS: WORKFORCE DEVELOPMENT, COMMUNITY & STAKEHOLDER ENGAGEMENT, RESOURCES & SERVICES, CTS PILOT, HEALTH INFORMATICS, AND CTS RESEARCH PROGRAM. WE ARE COMMITTED TO INNOVATIVE AND COLLABORATIVE PRACTICE AND DISSEMINATION OF RESULTS SO THAT EVERYONE IN NORTHERN OHIO—AND BEYOND—CAN BENEFIT FROM ADVANCES IN CTS IN OUR PROGRAMS AND DISCOVERIES.

CASE GI SPORE

MEDICAL SCIENTIST TRAINING PROGRAM

BREAKTHROUGH ELECTROLYTES FOR ENERGY STORAGE (BEES)

CONTINUING AN ENHANCED AND MULTIFACETED NATIONAL SURVEILLANCE PROGRAM FOR HUMAN PRION DISEASES

INNATE IMMUNITY END EXPERIMENTAL CROHN'S DISEASE

CWRU CENTER FOR EXCELLENCE ON THE IMPACT OF SUBSTANCE USE ON HIV - PROJECT SUMMARY - OVERVIEW THE NEWLY DEVELOPED CWRU (CASE WESTERN RESERVE UNIVERSITY) CENTER FOR EXCELLENCE ON THE IMPACT OF SUBSTANCE USE ON HIV WAS CONCEIVED IN AUGUST 2017 AND WAS INITIATED TO EFFECTIVELY PROMOTE EXCELLENCE IN BASIC, TRANSLATIONAL, AND CLINICAL RESEARCH CONCERNING THE INTERSECTION BETWEEN SUBSTANCE USE AND HIV. THE CENTER FOR EXCELLENCE INCLUDES 12 NIDA-FUNDED INVESTIGATORS WHO COLLECTIVELY HOLD 9 R01, 2 DP1, 3 R34, 2 R44, 1 U01, AND 2 K01 DRAWN FROM THE CWRU SCHOOL OF MEDICINE, UNIVERSITY HOSPITALS CLEVELAND MEDICAL CENTER, METROHEALTH MEDICAL CENTER, THE CLEVELAND CLINIC FOUNDATION, THE LOUIS STOKES CLEVELAND VETERANS ADMINISTRATION MEDICAL CENTER, THE CWRU MANDEL SCHOOL OF APPLIED SOCIAL SCIENCES, THE BEGUN CENTER FOR VIOLENCE PREVENTION RESEARCH AND EDUCATION, AND THE CUYAHOGA COUNTY, LORAIN COUNTY, AND CITY OF CLEVELAND DEPARTMENTS OF HEALTH. MAJOR RESEARCH STRENGTHS IN THE CENTER FOR EXCELLENCE INCLUDE IMPACT OF DRUG USE ON HIV IMMUNOPATHOGENESIS, HIV LATENCY AND CURE, NEUROAIDS, GASTROINTESTINAL DYSFUNCTION, SEXUAL RISK BEHAVIOR, AND HIV AND HCV CO-INFECTIONS. OUR STUDIES ARE ANCHORED BY ADVANCED COMPUTATIONAL, SYSTEMS BIOLOGY, BIOMIMETIC MODELS, AND INDUCED PLURIPOTENT STEM CELL (IPSC) TECHNOLOGIES THAT PROVIDE THE OPPORTUNITY TO PERFORM META-OMICS ANALYSES OF THE IMPACT OF OPIOID, METHAMPHETAMINE, CANNABIS, AND COCAINE MISUSE ON SEVERAL CLINICAL, VIROLOGICAL, IMMUNOLOGICAL, BEHAVIORAL, AND NEUROLOGICAL OUTCOMES OF HIV DISEASE. THE CENTER FOR EXCELLENCE HAS THE FOLLOWING SPECIFIC AIMS: - PROVIDE SCIENTIFIC LEADERSHIP TO POSITION THE CENTER AT THE FOREFRONT OF SUBSTANCE USE DISORDER RESEARCH AND FUNCTION AS A NATIONAL RESEARCH RESOURCE FOR THE STUDY OF DRUG USE IN PERSONS WITH HIV. - ESTABLISH AN ADMINISTRATIVE INFRASTRUCTURE THAT MAINTAINS FISCAL AND MANAGEMENT OVERSIGHT OF THE CORES. - APPLY ADVANCED COMPUTATIONAL BIOLOGY, PRIMARY CELLS, BIOMIMETIC MODELS, AND IPSC- DERIVED CELLS TO STUDY OF THE IMPACT OF SUBSTANCE USE ON HIV DISEASE. - SUPPORT TRANSLATIONAL, CLINICAL, AND BEHAVIORAL RESEARCH THROUGH ACCESS TO UNIQUE CLINICAL COHORTS OF PERSONS WITH SUBSTANCE USE DISORDER WITH HIV AND AT RISK FOR HIV. - ACCELERATE JUNIOR FACULTY DEVELOPMENT AND ENCOURAGE EXPERIENCED FACULTY TO ENTER THE SUBSTANCE USE RESEARCH ARENA TO SUPPORT THE NEXT GENERATION OF INVESTIGATORS. - PARTICIPATE IN COMMUNITY OUTREACH.

CONTINUING ENHANCED NATIONAL SURVEILLANCE FOR PRION DISEASES IN THE UNITED STATES

CLEVELAND OPEN SOURCE MODULAR IMPLANT INNOVATORS COMMUNITY (COSMIIC) - THE OVERALL GOAL OF THE CLEVELAND OPEN SOURCE MODULAR IMPLANT INNOVATORS COMMUNITY (COSMIIC) IS TO ESTABLISH AN OPEN SOURCE, MODULAR NETWORK OF ACTIVE IMPLANTABLE DEVICES FOR USE IN EARLY FEASIBILITY HUMAN RESEARCH AND TO PROVIDE ONGOING SUPPORT FOR THIS TECHNOLOGY THROUGH A VIBRANT, SUSTAINABLE COMMUNITY OF ACTIVE USERS. OUR TEAM IS POISED TO SUCCESSFULLY ACHIEVE ALL OF THE GOALS OF THE HORNET PROGRAM BECAUSE OUR PROPOSED CONCEPT IS BASED ON OUR ESTABLISHED PLATFORM ECOSYSTEM, THE NETWORKED NEUROPROSTHESIS (NNP). THIS PROVIDES A SOLID TECHNOLOGICAL PLATFORM WITH KNOWN REGULATORY STATUS FOR OUR COSMIIC HORNET PROJECT. CRITICALLY, ALL TECHNOLOGY DESCRIBED IN THIS PROPOSAL WAS INVENTED BY THE INVESTIGATIVE TEAM AND THEREFORE WE ARE ABLE TO FULLY EMBRACE THE OPEN SOURCE IDEOLOGY FOR THE END-TO-END TECHNOLOGY. THE PROPOSED COSMIIC HORNET SYSTEM, WHICH WILL BE ESTABLISHED ON THE PLATFORM NNP SYSTEM, IS A SYSTEM OF INTEROPERABLE AND INTEGRATED MODULES THAT CAN SIMULTANEOUSLY ELECTRICALLY ACTIVATE, BLOCK, AND SENSE THROUGHOUT THE BODY. THE SYSTEM CAN RECORD AND PROCESS ELECTRONEUROGRAM (ENG), ELECTROMYOGRAM (EMG), INTRACORTICAL SIGNALS, ELECTROCARDIOGRAM (EKG), KINEMATIC VARIABLES, PHOTOPLETHYSMOGRAM (PPG), AND TEMPERATURE. EACH MODULE CAN DIRECTLY COMMUNICATE WITH ALL OTHER MODULES THROUGH AN ESTABLISHED NETWORK COMMUNICATION PROTOCOL. THE SYSTEM CAN PROCESS SIGNALS TO IMPLEMENT COMPLEX CLOSED-LOOP CONTROL WITHOUT REQUIRING NON-IMPLANTED HARDWARE. IMPORTANTLY, THE EXISTING NNP PLATFORM COMPONENTS (POWER MODULE, STIMULATOR MODULE, BIOPOTENTIAL RECORDING MODULE, NETWORK CABLE, ELECTRODES) ALREADY HAVE IDE APPROVAL FROM THE FDA AND HAVE BEEN SUCCESSFULLY IMPLANTED AND IMPLEMENTED IN HUMAN RESEARCH PARTICIPANTS. THUS, THE COSMIIC HORNET SYSTEM HAS THE NECESSARY FEATURES TO PROVIDE THE MODULAR PLATFORM ECOSYSTEM FOR USE BY THE BIOELECTRONIC COMMUNITY FOR THE FORESEEABLE FUTURE. AIM #1. DISSEMINATION. WE WILL ESTABLISH THE COSMIIC COMMUNITY WITH FULL OPEN-SOURCE ACCESS TO AN ESTABLISHED MODULAR IMPLANTABLE DEVICE FOR USE IN THE PERIPHERAL AND CENTRAL NERVOUS SYSTEM. ACCESS WILL BE GIVEN FOR ALL CIRCUIT DESIGNS AND LAYOUTS; MECHANICAL DRAWINGS FOR ALL ENCLOSURES AND CONNECTORS AND CABLING; THE ANNOTATED CODE FOR ALL OPERATING SOFTWARE, FIRMWARE, AND BOOTLOADER; WRITTEN INSTRUCTIONS AND VIDEOS OF FABRICATION TECHNIQUES; AND ALL REGULATORY DOCUMENTS AND TEST DATA, INCLUDING OUR APPROVED IDE DOCUMENT. AIM #2. SUSTAINABILITY. WE WILL DEVELOP A SUSTAINABLE OPEN SOURCE MODEL THROUGH THE DEVELOPMENT OF TECHNOLOGY THAT ATTRACTS A BROAD INVESTIGATIVE TEAM TO ESTABLISH A CRITICAL MASS OF COSMIIC USERS. WE WILL PROVIDE ONGOING SUPPORT OF THE TECHNOLOGY AND PARTNER WITH COMMERCIAL PARTNERS TO CREATE A SUSTAINABLE BUSINESS PLAN SO THAT THE COSMIIC COMMUNITY REMAINS INDEPENDENTLY VIBRANT AND ACTIVE AFTER THREE YEARS.

THE ALZHEIMER DISEASE SEQUENCE ANALYSIS COLLABORATIVE

THE CLEVELAND DIGESTIVE DISEASES RESEARCH CORE CENTER (DDRCC)

GRANT AWARD TO CASE WESTERN RESERVE UNIVERSITY (CWRU) CONTRIBUTES TO NNSA’S STOCKPILE STEWARDSHIP MISSION BY ESTABLISHING A UNIQUE PUBLIC-PRIVATE PARTNERSHIP MERGING MATERIALS SCIENCE WITH NOVEL COMPUTER SCIENCE AND DATA SCIENCE TO ADVANCE THE UNDERSTANDING OF FUNDAMENTAL MECHANISMS OF MATERIALS DEGRADATION AND FAILURE IN OUR NUCLEAR STOCKPILE MATERIALS AND COMPONENTS, THROUGH COMBINED RESEARCH AND EDUCATIONAL MULTI-DISCIPLINARY VISION. PROJECT TITLE: CENTER TO MATERIALS DATA SCIENCE FOR STOCKPILE STEWARDSHIP (MDS3) COE

GENETIC DETERMINANTS OF BARRETT'S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA

PHARMACOLOGICAL TREATMENT OF RETINAL DISEASES

CWRU CENTER FOR MULTIMODAL EVALUATION OF ENGINEERED CARTILAGE

COHORT STUDY OF CHRONIC RENAL INSUFFICIENCY

HIGHER EDUCATION EMERGENCY RELIEF FUND-INSTITUTIONAL PORTION CARES ACT

CASE AIDS CLINICAL TRIALS UNIT

TARGETING OBESITY AND BLOOD PRESSURE IN URBAN YOUTH

P30 - CORE GRANT FOR VISION RESEARCH

DEVELOPMENT OF NEW DIAGNOSTIC METHODS/SURVEILLANCE PROGRAM

RESISTANCE TO MTB INFECTION IN HIV INFECTED INDIVIDUALS IN UGANDA AND S. AFRICA

CONTINUING THE DEVELOPMENT OF NEW DIAGNOSTIC METHODS/SURVEILLANCE PROGRAM

CASE COMPREHENSIVE CANCER CENTER NCTN LEAD ACADEMIC PARTICIPATING SITE

CLINICAL AND TRANSLATIONAL SCIENCE COLLABORATIVE OF CLEVELAND

DEFINING THE PATHOGENESIS OF IMMUNE DEFICIENCY IN CHRONIC HIV INFECTION

CLINICAL ONCOLOGY RESEARCH CAREER DEVELOPMENT PROGRAM (CORP)

HIGHER EDUCATION EMERGENCY RELIEF FUND CARES ACT

RESEARCH TO CONTROL AND ELIMINATE MALARIA IN SE ASIA AND SW PACIFIC

PILOT RANDOMIZED CONTROLLED TRIAL OF THE ISENS SYSTEM FOR SENSORIMOTOR RESTORATION AFTER LIMB LOSS

EMBODIED ROBOTICS FOR REMOTE OPERATIONS

INFLAMMASOME AND GASDERMIN SIGNALING NETWORKS FOR REGULATION OF PYROPTOSIS AND CYTOKINE RELEASE

PATHOGENETIC MECHANISMS OF PRION DISEASE

NEW CA CWRU

ORAL MUCOSAL IMMUNITY IN VULNERABLE HIV INFECTED POPULATIONS

CELLULAR S-NITROSOTHIOL SIGNALING IN RESPIRATORY BIOLOGY

ENGAGING COMMUNITIES AND INSTITUTIONS TO REDUCE HEALTH DISPARITIES IN CLEVELAND

CASE CENTER FOR SYNCHROTRON BIOSCIENCES

PROTECTIVE GENETIC VARIANTS FOR ALZHEIMER DISEASE IN THE AMISH

COCAINE EXPOSED CHILDREN AT SCHOOL AGE

RESTORATION OF GRASP AND REACH IN CERVICAL SPINAL CORD INJURY

NEURONEX: COMMUNICATION, COORDINATION, AND CONTROL IN NEUROMECHANICAL SYSTEMS (C3NS)

PROTECTIVE GENETIC VARIANTS FOR ALZHEIMER DISEASE IN THE AMISH - RENEWAL - ALZHEIMER DISEASE (AD) IS A DEVASTATING NEURODEGENERATIVE DISORDER THAT AFFECTS MILLIONS OF INDIVIDUALS IN THE U.S. IT HAS SO FAR RESISTED ATTEMPTS TO DEVELOP EFFECTIVE THERAPIES DESPITE NUMEROUS (FAILED) CLINICAL TRIALS BASED ON KNOWN TARGETS, MOST IDENTIFIED OVER 20 YEARS AGO. WHILE GENOMIC RESEARCH (E.G. THE ALZHEIMER’S DISEASE SEQUENCING PROJECT; ADSP) HAS IDENTIFIED NUMEROUS ADDITIONAL RISK LOCI, THESE RESULTS DERIVE PRIMARILY FROM CASE- CONTROL DATASETS. IN CONTRAST, COHORTS DESIGNED TO IDENTIFY VARIANTS THAT MAY PROTECT FROM AD, AND THOSE USING COMPLEMENTARY STUDY DESIGNS, ARE FEW. WE USED OUR EXTENSIVE EXPERIENCE WITH THE AMISH COMMUNITIES IN INDIANA AND OHIO TO ESTABLISH A COHORT OF OLDER INDIVIDUALS AT HIGH RISK OF DEVELOPING AD BUT WHO ARE COGNITIVELY UNIMPAIRED (CU). THE AMISH PROVIDE A UNIQUE OPPORTUNITY TO IDENTIFY PROTECTIVE VARIANTS FOR AD BECAUSE OF THEIR REDUCED BACKGROUND GENETIC VARIATION AND ENVIRONMENTAL RISK FACTORS. THEIR SMALL FOUNDING POPULATION AND ENDOGAMY PROVIDES ENRICHMENT FOR RARE VARIANTS. FOUNDER POPULATIONS ALSO ENABLE TESTING FOR NON-ADDITIVE ALLELIC EFFECTS AND CAN MAGNIFY SUB-SIGNIFICANT ASSOCIATION SIGNALS IDENTIFIED IN CASE-CONTROL STUDIES. THE STABILITY AND ENGAGEMENT OF OUR AMISH PARTICIPANTS ENABLES LONGITUDINAL ASSESSMENTS OF COGNITION AND BIOMARKERS. OUR PRIMARY GOALS ARE TO IDENTIFY AD PROTECTIVE LOCI AND CHARACTERIZE PRE-CLINICAL BIOMARKERS OF PROGRESSION TO COGNITIVE IMPAIRMENT. BUILDING ON OUR EXISTING LARGE COHORT, OUR REPLICATED PROTECTIVE LOCUS AND SEVERAL SUGGESTIVE PROTECTIVE LOCI, AND OUR EXISTING BIOBANK OF DNA AND PLASMA AND DATABANK OF GWAS AND WGS, WE PROPOSE TO: 1) PERFORM LONGITUDINAL ASSESSMENT OF COGNITION IN OUR FAMILY-BASED AMISH COHORT; 2) IDENTIFY PROTECTIVE FACTORS FOR AD AND PREDICTORS OF PROGRESSION TO COGNITIVE IMPAIRMENT BY ANALYZING GENOMIC AND LONGITUDINAL COGNITIVE, BIOMARKER, AND SDOH DATA; AND 3) EXAMINE THE FUNCTIONAL IMPLICATIONS OF CURRENT AND NOVEL GENES AND VARIANTS BY PRIORITIZING LOCI USING IN SILICO ANNOTATION FOR FUNCTIONAL CONSEQUENCES FOLLOWED BY IN VITRO FUNCTIONAL CHARACTERIZATION. OUR RESULTS WILL IDENTIFY POTENTIAL DRUGGABLE TARGETS AND ACCELERATE THE DEVELOPMENT OF BETTER TREATMENTS FOR AD.

MECHANISMS OF TRANSMISSIBILITY IN PRION DISEASES

MOLECULAR MECHANISMS AND PATHWAYS FOR GAS TRANSPORT ACROSS BIOLOGICAL MEMBRANES AND IMPLICATIONS FOR PHYSIOLOGY AND PERFORMANCE MURI 2016

NSF NEO-SMART ENGINE IN NORTHEAST OHIO -THIS NSF ENGINES AWARD TO NEO-SMART (NORTHEAST OHIO STRENGTHENING MANUFACTURING FOR AMERICAN RESILIENCE THROUGH TECHNOLOGY) IS OF NATIONAL SIGNIFICANCE FOR RESTORING U.S. LEADERSHIP IN ADVANCED MATERIALS AND MANUFACTURING. METALS, POLYMERS, AND CHEMICALS AND COATINGS FORM THE BACKBONE OF AMERICAN INDUSTRY. THEY ARE ESSENTIAL TO AEROSPACE, DEFENSE, ENERGY INFRASTRUCTURE, TRANSPORTATION, MANUFACTURING EQUIPMENT, AND CONSUMER PRODUCTS. THE NATION?S DEPENDENCE ON FOREIGN SOURCES FOR THESE MATERIALS HAS CREATED SUPPLY CHAIN VULNERABILITIES THAT THREATEN NATIONAL SECURITY AND ECONOMIC STABILITY. NORTHEAST OHIO POSSESSES HISTORICALLY DEEP STRENGTHS IN THESE SECTORS, WITH MANUFACTURING ACCOUNTING FOR 30 PERCENT OF REGIONAL EMPLOYMENT ACROSS MORE THAN 7,700 ESTABLISHMENTS. THE PROJECT AIMS TO TRANSFORM THIS CONCENTRATED INDUSTRIAL BASE INTO A COORDINATED NATIONAL HUB FOR MATERIALS INNOVATION BY INTEGRATING USE-INSPIRED RESEARCH AND DEVELOPMENT, TECHNOLOGY COMMERCIALIZATION, AND WORKFORCE TRAINING. THIS WORK IS POSITIONED TO ESTABLISH NORTHEAST OHIO AS THE LEADING CENTER FOR ADVANCED MATERIALS AND MANUFACTURING, CREATING HIGH-QUALITY JOBS, STRENGTHENING DOMESTIC SUPPLY CHAINS, AND REDUCING DEPENDENCE ON FOREIGN SUPPLIERS OF CRITICAL MATERIALS. THE REGION OF SERVICE ENCOMPASSES 18 COUNTIES IN NORTHEAST OHIO, SPANNING THE CLEVELAND-ELYRIA, AKRON, CANTON-MASSILLON, AND YOUNGSTOWN-WARREN-BOARDMAN METROPOLITAN AREAS, WITH A POPULATION OF 4.3 MILLION RESIDENTS AND A WORKFORCE OF OVER TWO MILLION. OHIO IS A KEY MANUFACTURING STATE SUPPORTING CRITICAL DOMESTIC SUPPLY CHAINS, WITH DEEP REGIONAL CONCENTRATION IN METALS, POLYMERS, AND CHEMICALS AND COATINGS PRODUCTION. THE REGION COMBINES ADVANCED MANUFACTURING FACILITIES, LEADING RESEARCH INSTITUTIONS, AND ESTABLISHED WORKFORCE TRAINING NETWORKS. STRATEGIC ACCESS TO GREAT LAKES SHIPPING ROUTES AND LOW-COST NATURAL GAS FEEDSTOCKS REINFORCES THE REGION?S COMPETITIVE POSITION FOR MATERIALS PRODUCTION. THESE ASSETS, COMBINED WITH FEDERAL AND STATE INVESTMENTS SUCH AS THE EDA POLYMER TECH HUB, POSITION NORTHEAST OHIO TO ANCHOR AND DRIVE A NATIONAL ADVANCED MATERIALS AND MANUFACTURING INNOVATION ECOSYSTEM. THE TECHNICAL SCOPE OF THE PROJECT COVERS USE-INSPIRED R&D WHOSE GOALS ARE TO CLOSE CRITICAL GAPS BETWEEN CURRENT MANUFACTURING CAPABILITIES AND NEXT-GENERATION MATERIALS TECHNOLOGIES ACROSS THREE INTERCONNECTED MATERIALS SYSTEMS ? METALS, POLYMERS, AND CHEMICALS AND COATINGS. THE SHARED SCIENTIFIC PRINCIPLES AND OVERLAPPING MANUFACTURING PROCESSES OF THESE MATERIALS CREATE STRONG OPPORTUNITIES FOR CROSS-SYSTEM INNOVATION. THE PROJECT AIMS TO ADVANCE RESEARCH AND DEVELOPMENT ACROSS THE FULL MATERIALS LIFE CYCLE, FROM SOURCING AND FEEDSTOCK DEVELOPMENT THROUGH PRODUCTION, PROCESSING, RECOVERY, AND PRODUCT DURABILITY, SUPPORTED BY EMERGING AI/ML AND COMPUTATIONAL METHODS THAT ACCELERATE MATERIALS DESIGN AND LIFE CYCLE ASSESSMENT. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE PLANNED FOR THIS AWARD.

CAPTURING SPATIAL PATTERNS OF NEW M. TUBERCULOSIS INFECTION IN KAMPALA, UGANDA

MULTI-FUNCTIONAL NEUROPROSTHETIC SYSTEMS FOR RESTORATION OF MOTOR FUNCTION

INVOLVING COMMUNITIES IN DELIVERING AND DISSEMINATING HEALTH DISPARITY INTERVENTIONS

REGULATION OF GENE EXPRESSION DURING STRESS

CASE WESTERN RESERVE UNIVERSITY/CLEVELAND CLINIC CTSA (KL2)

INSTITUTIONAL CAREER DEVELOPMENT CORE

PREVENTION RESEARCH CENTER FOR HEALTHY NEIGHBORHOODS

IDENTIFY AND VALIDATE NOVEL EPIGENETIC MOLECULAR MARKERS FOR COLORECTAL NEOPLASM

PATHWAYS OF INJURY AND REPAIR IN BARRETT'S CARCINOGENESIS - PROGRAM SUMMARY THE CENTRAL HYPOTHESIS OF THIS PROGRAM PROJECT IS THAT “ALTERED SQUAMOUS EPITHELIAL INTEGRITY (PRJ 1) AND INFLAMMATORY INJURY (PRJ 2) ACTIVATE SIGNALING PATHWAYS INCLUDING EPHB2 (PRJ 3) THAT AFFECT PRECURSOR CELLS AT THE SQUAMOCOLUMNAR JUNCTION (SCJ) TRANSITION, ESOPHAGEAL SUBMUCOSAL GLAND (ESMG), AND BASAL SQUAMOUS NICHES, RESULTING IN THE ALTERATION OF REGULATORY FACTORS THAT INCLUDE NOTCH, MYC, P63, AND SOX9, LEADING TO ACINAR DUCTAL METAPLASIA (ADM), MULTI-LAYERED EPITHELIUM (MLE), BARRETT'S ESOPHAGUS (BE), AND ULTIMATELY ESOPHAGEAL ADENOCARCINOMA (EAC).” THE SPECIFIC AIMS OF OUR PROGRAM ARE: 1) TO ELUCIDATE SIGNALING PATHWAYS BY WHICH MUTATED VSIG10L ALTERS EPITHELIAL INTEGRITY LEADING TO MLE AND BE LIKE METAPLASIA ON NOVEL MOUSE MODELS. 2) TO DEFINE THE SPATIAL AND TEMPORAL PATTERN OF CXCL8 (IL-8) IN ESMG FOLLOWING ESOPHAGEAL INJURY AND PHENOTYPE THE INFLAMMATORY INFILTRATE THAT LEADS TO THE DEVELOPMENT OF ACINAR DUCTAL METAPLASIA (ADM) IN ESMG ASSOCIATED WITH BE/EAC. 3)TO IDENTIFY MEDIATORS OF EPHB2 SIGNALING THAT LEAD TO C-MYC ACTIVATION AND METAPLASTIC CELLULAR DIFFERENTIATION AFTER INJURY IN THE DEVELOPMENT OF BE AND ITS PROGRESSION TO EAC. 4) TO DEFINE HOW ALTERED EPITHELIAL INTEGRITY, INFLAMMATORY CELLS, AND ALTERATION OF SIGNALING MOLECULES THAT CONTROL DIFFERENTIATION (EPHB2) LEAD TO METAPLASIA BY ALTERING TRANSCRIPTION FACTORS. 5) INTEGRATE PROJECTS BY PROVIDING INVESTIGATORS EFFECTIVE SUPPORT THROUGH CORE RESOURCES WITH STATE-OF-THE-ART BIOREPOSITORY, BIOINFORMATICS, AND ADMINISTRATIVE SERVICES. THESE OBJECTIVES BUILD AND SYNERGIZE ON THE CONSIDERABLE CLINICAL, BASIC SCIENCE, AND TRANSLATIONAL EXPERTISE AVAILABLE AT OUR INSTITUTIONS, 1) TO FOCUS LABORATORY RESEARCH ON UNDERSTANDING THE GENETIC SUSCEPTIBILITY AND MOLECULAR CHANGES THAT INFLUENCE THE DEVELOPMENT OF BE AND EAC; AND 2) TO THEN TRANSLATE LABORATORY DISCOVERIES INTO CLINICAL APPLICATIONS FOR EFFECTIVE DETECTION, MOLECULAR RISK STRATIFICATION, AND PREVENTION OF PROGRESSION FROM BE TO EAC.

TARGETING 15-PROSTAGLANDIN DEHYDROGENASE (15-PGDH) IN CANCER RISK, PREVENTION, AND TREATMENT

SIGNIFICANCE OF CYP46A1 AND OTHER P450S IN RETINAL FUNCTION

PSORIASIS CENTER OF RESEARCH TRANSLATION

PHOTOTRANSDUCTION IN HEALTH AND DISEASE

OPTICAL TOOLS TO ASSESS THE ROLE OF HEMODYNAMICS IN THE DEVELOPMENT OF CONGENITAL HEART DEFECTS

TRANSLATIONAL RESEARCH IN CYSTIC FIBROSIS

CIRCUIT ARCHITECTURE AND DYNAMICS REPRESENTATION IN ODOR PERCEPTION

MULTIDRUG RESISTANT ACINETOBACTER BAUMANNII,

A FAMILIAL STUDY OF SEVERE PHONOLOGY DISORDERS

MECHANISMS OF TUBULAR ATROPHY IN RENAL DISEASE

AN INTEGRATED COMPUTATIONAL AND EXPERIMENTAL APPROACH TOWARD THE DESIGN OF MATERIALS FOR FUEL CELLS SYSTEMS

CWRU CASE COMPREHENSIVE CANCER CENTER NCTN LEAD ACADEMIC PARTICIPATING SITE

TISSUE ENGINEERED CARTILAGE REPAIR

FUNCTION OF THE PET-1 ETS FACTOR IN THE MAMMALIAN 5-HT SYSTEM

LOCAL CIRCUITS IN THE OLFACTORY BULB

BASIC AND COMPARATIVE STUDIES OF CCR5 INHIBITION TO PREVENT HIV TRANSMISSION

EFFECTS OF IL-6 BLOCKADE IN TREATED HIV INFECTION

NERVE RESHAPING FOR IMPROVED ELECTRODE SELECTIVITY

EFFECT OF CORNEAL PRESERVATION TIME ON LONG-TERM GRAFT SUCCESS (CPTS)

UNDERSTANDING NEURAL CONTROL OF THE OCULAR SURFACE - PROJECT SUMMARY CURRENTLY OUR UNDERSTANDING OF HOW THE NERVOUS SYSTEM MAINTAINS OCULAR SURFACE HOMEOSTASIS IS EXTREMELY LIMITED. NEW TECHNOLOGIES, METHODS AND MODELS ARE NEEDED TO ADVANCE OUR SCIENTIFIC UNDERSTANDING AND ADDRESS KNOWLEDGE GAPS. THE OCULAR SURFACE AND TEAR FILM-SECRETING GLANDS (INCLUDING THE LACRIMAL AND MEIBOMIAN GLANDS, AS WELL AS THE GOBLET CELLS) ARE CAREFULLY CONTROLLED TO PROVIDE AN OPTICALLY SMOOTH, LOW-SCATTERING SURFACE WITH APPROPRIATE IMMUNE AND INJURY RESPONSES. SENSORY FEEDBACK TO MAINTAIN THE STRUCTURAL AND FUNCTIONAL INTEGRITY OF THE OCULAR SURFACE IS PROVIDED BY THE CORNEAL NERVES, WHICH SEND FEEDBACK FROM STIMULI (CHEMICAL, THERMAL, MECHANICAL) TO GANGLIA (E.G., TRIGEMINAL) AND BRAIN REGIONS (E.G., VENTRAL POSTEROMEDIAL THALAMUS) TO DRIVE PRODUCTION OF TEAR FILM COMPONENTS AS WELL AS THE BLINK REFLEX. THIS DELICATE BALANCE OF NEURAL CONTROL IS DISRUPTED BY DAMAGE, PERIPHERAL NEUROPATHIES, INFLAMMATION AND FURTHER COMPLICATED BY A WIDE ARRAY OF IMMUNE RESPONSES TO VARIOUS DISEASES. DYSFUNCTION OF THIS FEEDBACK LOOP CAN LEAD TO A DOWNWARD SPIRAL OF FURTHER DYSREGULATION. ABERRANT NEURAL CONTROL OF THE OCULAR SURFACE CAN LEAD TO ABNORMAL SENSATION AND PAIN, WHICH IN THE WORST CASES CAN BE DISABLING. TO FIND REMEDIES, IT IS FIRST ESSENTIAL TO UNDERSTAND THE UNDERLYING NEURAL CONTROL SYSTEM AND HOW IT ADAPTS TO ITS ENVIRONMENT. IN THIS PROPOSAL, WE AIM TO BRING NEW TOOLS AND MODELS TO STUDY MOLECULAR, CELLULAR, AND FUNCTIONAL INTERACTIONS ACROSS SYSTEMS RESPONSIBLE FOR NEURAL CONTROL OF THE OCULAR SURFACE AND EXAMINE HOW THEY CHANGE UNDER DIFFERENT INFLAMMATORY AND PAIN CONDITIONS. WE HAVE ASSEMBLED AN EXCELLENT TEAM WITH EXPERTISE ACROSS MULTIPLE FIELDS INCLUDING ADVANCED 3D MICROSCOPY, NEUROSCIENCE, ELECTROPHYSIOLOGY, PAIN, OCULAR IMMUNOLOGY, OCULAR LIPID METABOLISM, OCULAR SURFACE DISORDERS, SPATIAL STATISTICS, AND MACHINE/DEEP LEARNING. HERE, WE WILL UTILIZE CUTTING EDGE TECHNIQUES AND TECHNOLOGIES INCLUDING OPTICAL CLEARING, TRACT TRACING, ETHOLOGICALLY-VALID BEHAVIOR ANALYSIS, MACHINE/DEEP LEARNING, SPATIAL STATISTICS, GENETICALLY ENCODED CALCIUM IMAGING, LIGHT-SHEET MICROSCOPY, MULTIPLEXED 3D FLUORESCENCE IN SITU HYBRIDIZATION (FISH) IMAGING, AND MULTI-ARRAY ELECTRODES IMPLANTED IN THE BRAIN. THESE TOOLS WILL HELP US ASSESS MOLECULAR, CELLULAR, AND FUNCTIONAL INTERACTIONS ACROSS ORGANS AND BEGIN TO UNDERSTAND OCULAR SURFACE CONTROL AT THE ORGANISM LEVEL. WE WILL ALSO EMPLOY SEVERAL RELEVANT ANIMAL MODELS TO ASSESS OCULAR SURFACE CONTROL UNDER DIFFERENT INFLAMMATORY AND PAIN CONDITIONS. MODELS INCLUDE AWAT2 DEFICIENT MICE THAT MIMIC EVAPORATIVE DRY EYE DISEASE (DED), DIABETIC MICE, AN EPITHELIAL DEBRIDEMENT MODEL WITH PSEUDOMONAS AERUGINOSA THAT MIMICS BACTERIAL KERATITIS, AND HUMAN DONOR EYES. THE MOUSE MODELS ALL HAVE GCAMP6F EXPRESSED IN CORNEAL NERVES ALLOWING FUNCTIONAL IMAGING OF CALCIUM TRANSIENTS. WITH THESE MODELS WE WILL STUDY BOTH INNATE AND ADAPTIVE IMMUNITY AS WELL AS NOCICEPTIVE AND NEUROPATHIC PAIN RESPONSES. IN ADDITION, WE WILL APPLY NERVE GROWTH FACTOR (NGF) TO OUR MODELS TO STUDY HOW A POTENTIAL TREATMENT OPTION ALTERS THE OCULAR SURFACE CONTROL SYSTEM.

MULTI-LEVEL INTERVENTIONS TO REDUCE CARIES DISPARITIES IN PRIMARY CARE SETTINGS

INTERDISCIPLINARY BIOMEDICAL IMAGING TRAINING PROGRAM

DEVELOPMENT OF NETWORKED IMPLANTABLE NEUROPROSTHESES

AUTOMATIC CONTROL OF STANDING BALANCE WITH FNS

MODULATING GLIAL FATE AND FUNCTION IN DEVELOPMENT AND DISEASE

NIAMS: CORT (PSORIASIS CENTER OF RESEARCH TRANSLATION)

DEVELOPING A ONE-TUBE CIRCULARIZED LIGATION PRODUCT SEQUENCING (CLP-SEQ) METHOD FOR THE MAPPING OF 3D GENOME ARCHITECTURE IN SMALL CELL POPULATIONS OR SINGLE CELLS.

LRP4 SIGNALING IN NEUROMUSCULAR JUNCTION FORMATION

INTEGRATED ENGINEERING AND REHABILITATION TRAINING

MEDICAL SCIENTIST TRAINING PROGRAM AT CASE WESTERN RESERVE UNIVERSITY - OUR SCHOOL OF MEDICINE LAUNCHED THE FIRST MD-PHD TRAINING PROGRAM IN 1956, AND THE PROGRAM HAS A LONG HISTORY OF INNOVATION AND SUCCESS WITH MANY PROMINENT ALUMNI, INCLUDING TWO NOBEL LAUREATES. OUR MISSION IS TO DEVELOP MD-PHD TRAINING TO TRAIN A DIVERSE POOL OF PHYSICIAN-SCIENTIST LEADERS TO MEET FUTURE BIOMEDICAL RESEARCH WORKFORCE NEEDS FOR RESEARCH LEADERS TO ACCELERATE RESEARCH TO ADVANCE THE UNDERSTANDING, DETECTION, TREATMENT AND PREVENTION OF HUMAN DISEASE. OBJECTIVES INCLUDE DEVELOPMENT OF PHYSICIAN-SCIENTISTS WITH DEEP EXPERTISE IN ONE OR MORE BIOMEDICAL SCIENTIFIC DISCIPLINES COUPLED WITH A BROAD UNDERSTANDING ACROSS BIOMEDICAL DISCIPLINES; SKILLS TO INDEPENDENTLY DESIGN AND DEVELOP RESEARCH PROGRAMS; ABILITY TO USE CLINICAL INSIGHTS TO INFORM RESEARCH; AND COMMITMENT TO SCIENTIFIC INTEGRITY AND DEI GOALS. PROGRAM GOALS INCLUDE MD- PHD COMPLETION WITH AN EFFICIENT TIME TO DEGREE (TTD), PUBLICATION AND GRANTS ATTAINMENT PRODUCTIVITY, POST- GRADUATION PLACEMENT IN TRAINING PROGRAMS RELATED TO PHYSICIAN-SCIENTIST CAREER DEVELOPMENT, AND LONG-TERM ATTAINMENT OF PRODUCTIVE RESEARCH CAREERS. OUR AIMS INCLUDE DEVELOPMENT OF AN MD-PHD CURRICULUM THAT INTEGRATES RESEARCH AND CLINICAL TRAINING WITH DEEP RESEARCH EXPERIENCES FROM THE BEGINNING OF THE PROGRAM TO PROMOTE RETENTION OF TRAINEES IN THE RESEARCH MISSION AND FOSTER CURRICULAR EFFICIENCY. WE WILL DEVELOP REQUIRED AND ELECTIVE MSTP ACTIVITIES THAT PROMOTE THE PROGRAM OBJECTIVES, INCLUDING DIDACTIC, RESEARCH, MENTORING AND CAREER DEVELOPMENT ELEMENTS (RCR, RRR, GRANTSMANSHIP, RESEARCH COMMUNICATION AND OTHERS) AND PROGRAM ACTIVITIES (MSTP RETREAT, MSTP DINNER SEMINARS, MSTP VISITING PHYSICIAN-SCIENTIST CAREER SESSIONS). WE WILL WORK WITH OUR RESEARCH TRAINING COMMUNITY TO IMPROVE PHD PROGRAMS AND TRAINING OF RESEARCH MENTORS IN BEST PRACTICES. OUR APPROACH INCLUDES INTEGRATION OF RESEARCH AND CLINICAL TRAINING WITHIN EACH OF THE THREE BASIC PHASES: FIRST TWO YEARS (M1-M2), PHD PHASE (E.G. G1-4), AND LAST TWO YEARS (M3-M4). THE CURRICULUM HAS FLEXIBILITY TO MEET THE DIFFERING INTERESTS AND NEEDS OF INDIVIDUAL STUDENTS. A KEY STRATEGY IS EARLY AND DEEP ENGAGEMENT WITH RESEARCH TO PROMOTE RESEARCH CAREER DEVELOPMENT AND RETENTION - IN M1-M2, STUDENTS COMPLETE A RESEARCH ROTATION OR GRADUATE COURSE IN EVERY SEMESTER IN COMBINATION WITH THE MD CURRICULUM. ALMOST ALL STUDENTS MATCH INTO THEIR PHD LAB BY FALL OF M2, ALLOWING EARLY LAUNCH OF PHD RESEARCH IN M2. THIS IS A KEY DISTINCTION FOR THE CWRU MSTP AND PROVIDES UNIQUE CURRICULAR OPPORTUNITIES. WE WILL ESTABLISH A CULTURE OF SUPPORT FOR STUDENTS AND ENGAGEMENT OF STUDENT LEADERSHIP IN MSTP COUNCIL TO SHAPE THE PROGRAM TO SUPPORT STUDENT PROFESSIONAL DEVELOPMENT AND WELLNESS. WE WILL CONTINUE TO ADMIT 14-15 STUDENTS PER YEAR. THE INTEGRATED RESEARCH AND CLINICAL CURRICULUM, PROGRAM ACTIVITIES, DEI FOCUS AND ACTIVITIES, AND SUPPORT FOR STUDENTS WILL PRODUCE A HIGHLY SKILLED AND DIVERSE PHYSICIAN-SCIENTIST WORKFORCE, WHICH WILL CONTRIBUTE TO NATIONAL GOALS FOR BASIC, TRANSLATIONAL AND CLINICAL RESEARCH IN ACADEMIA, GOVERNMENT AND INDUSTRY.

REGULATORY MECHANISMS OF GLYCOPROTEIN SIALYLATION

REGENERATIVE AND DEGENERATIVE RESPONSES TO AXONAL INJURY

RESTORATION AND FUNCTION OF S-NITROSOTHIOL IN STORED BLOOD

PHOTOTRANSDUCTION ENZYMES

(CIRCADIAN) CIRCADIAN DISRUPTION AS MEDIATOR OF CARDIOMETABOLIC RISK IN AIR POLLUTION - ABSTRACT PARTICULATE MATTER AIR POLLUTION <2.5ΜM (PM2.5) IS THE LEADING ENVIRONMENTAL RISK FACTOR GLOBALLY, CONTRIBUTING MORE TO GLOBAL MORTALITY THAN AIDS, MALARIA, TUBERCULOSIS AND WARS/FAMINES COMBINED. THE HEALTH RISKS ASSOCIATED WITH PM2.5 ARE PREDOMINANTLY FROM CARDIOVASCULAR (CV) CAUSES, WITH DATA SUPPORTING A MAJOR PUBLIC HEALTH IMPACT DUE TO DISORDERS SUCH AS TYPE 2 DIABETES. BUILDING ON THE SUBSTANTIAL SUCCESSES OF OUR RESEARCH PROGRAM, THAT IN LARGE PART HAVE PROVIDED THE FOUNDATIONAL BASIS FOR OUR UNDERSTANDING OF MECHANISMS OF PM2.5-INDUCED CARDIOMETABOLIC DISORDERS, WE PROPOSE AN INNOVATIVE FRAMEWORK OF TRANSLATIONAL INVESTIGATIONS. OUR NEW DATA PROVIDE COMPELLING LINKS BETWEEN PM2.5 EXPOSURE AND CIRCADIAN RHYTHM (CR) DISRUPTION THROUGH EPIGENETIC REPROGRAMMING, RESULTING IN METABOLIC DYSFUNCTION AND INSULIN RESISTANCE. IN ACCORDANCE WITH THE NIEHS TRANSLATIONAL RESEARCH FRAMEWORK, WE PROPOSE AN AMBITIOUS PLAN ENCOMPASSING 3 GOALS OVER 8 YEARS THAT WILL ENCOMPASS HARMONIZED STUDIES INVOLVING CONCENTRATED AMBIENT PM2.5 EXPOSURES (ANIMAL) AND HUMAN INTERVENTION TRIALS ACROSS THE AMBIENT EXPOSURE SPECTRUM, PREDICATED AND SUPPORTED BY RESULTS FROM GENOME WIDE ASSOCIATION AND MENDELIAN RANDOMIZATION APPROACHES, THAT WILL IDENTIFY PATHWAYS OF AIR POLLUTION MEDIATED CV RISK. LEVERAGING ON-GOING TRANSLATIONAL CLINICAL TRIALS OF AIR POLLUTION REDUCTION USING PERSONALIZED STRATEGIES IN VULNERABLE POPULATIONS IN BEIJING, AND THROUGH ONE NEW STUDY INVOLVING MITIGATION OF AIR POLLUTION (ITS-MY-AIR), WE WILL EVALUATE THE IMPACT OF EXPOSURE REDUCTION ON CR DISRUPTION/SLEEP AND METABOLIC ENDPOINTS. COLLECTIVELY, RESULTS FROM THIS PROJECT WILL HELP SHED IMPORTANT NEW LIGHT ON AIR POLLUTION, ITS IMPACT ON CR AND CARDIOMETABOLIC DISORDERS AND PROVIDE INFLUENTIAL DATA ON PROTECTIVE EFFECTS OF PERSONAL INTERVENTION STRATEGIES, THAT TOGETHER COULD CHANGE PUBLIC HEALTH POLICY.

LUNG CANCER IN EAST AFRICA AND THE RELATIONSHIP TO HIV-1 INFECTION: EPIDEMIOLOGY, MOLECULAR CHARACTERIZATION AND IMAGING

CASE POSTBACCALAUREATE RESEARCH EDUCATION PROGRAM (PREP)

AUTOPHAGY AND OCULAR TOXOPLASMOSIS

TRANSLATIONAL CONTROL BY NUTRIENTS

(EPI)GENETIC RISK ARCHITECTURES IN OPIOID DEPENDENT BRAIN

VALIDATION OF BIOMARKERS FOR PREDICTING BARRETT'S ESOPHAGUS THAT WILL OR WILL NOT: I) PROGRESS TOWARDS CANCER, OR II) RECUR AFTER ABLATION - ABSTRACT THIS EDRN-CVC PROPOSAL IS AIMED AT THE VALIDATION OF MOLECULAR BIOMARKERS FOR DISTINGUISHING HIGH VERSUS LOW RISK ESOPHAGEAL NEOPLASIAS (BARRETT’S ESOPHAGUS) FOR THE PURPOSE OF GUIDING SELECTION AND MANAGEMENT OF PATIENTS FOR ENDOSCOPIC ERADICATION THERAPY (EET). TWO VALIDATION STUDIES ARE PROPOSED: THE FIRST, A PHASE 4 PROSPECTIVE STUDY TO IDENTIFY A PATIENT GROUP AT LOW PROGRESSION RISK WHO CAN BE SPARED EET; THE SECOND, A PHASE 3 RETROSPECTIVE STUDY TO DISTINGUISH INDIVIDUALS WHO FOLLOWING EET ARE AT LOW VERSUS HIGH RISK OF DISEASE RECURRENCE. BARRETT’S ESOPHAGUS (BE) IS THE PRECURSOR LESION OF ESOPHAGEAL ADENOCARCINOMA (EAC), A CANCER WITH 80% LETHALITY WHOSE INCIDENCE HAS INCREASED MORE THAN 7-FOLD IN THE PAST THREE DECADES. BE PROGRESSES TO EAC IN A STEP-WISE FASHION FROM NON-DYSPLASTIC BE, TO LOW GRADE DYSPLASIA (LGD), TO HIGH GRADE DYSPLASIA (HGD), AND FINALLY CANCER. EAC PREVENTION IS BASED ON USING EET TO ABLATE HGD BE BEFORE IT CAN PROGRESS TO EAC. HOWEVER, INCREASINGLY, EET IS ALSO BECOMING THE DEFAULT THERAPY FOR LGD, A HIGHLY IMPRECISE DIAGNOSIS ABOUT WHICH EXPERT PATHOLOGISTS FREQUENTLY DISAGREE, AND WHICH IS APPLIED TO AS MANY AS 40% OF BE PATIENTS AT SOME POINT DURING THEIR COURSE. AS EET HAS A 9% COMPLICATION RATE, THE RESULT IS AN EMERGING EPIDEMIC OF OVERTREATMENT OF BE WITH LGD. IN A PRIOR EDRN-BDL AWARD, OUR TEAM DEVELOPED THE “BAD” TECHNOLOGY FOR EARLY DETECTION OF BE PROGRESSION. IN BAD, WE USED A BRUSHING DEVICE TO SAMPLE A PATIENT’S FULL BE ESOPHAGEAL SEGMENT. WE THEN ANALYZED THE DNA FROM THIS SAMPLE USING NEXT-GENERATION SEQUENCING TECHNOLOGY (DEVELOPED FOR LIQUID BIOPSY ASSAYS) TO INSTEAD DETECT PRESENCE OF BE CLONES THAT HAD ACQUIRED GAINS OR LOSSES ON SPECIFIC DRIVER CHROMOSOMES ASSOCIATED WITH EAC. DETECTION OF DRIVER CHROMOSOME CHANGES (DUBBED VERY-BAD), TYPIFIED EAC AND HGD. IN CONTRAST, 28% OF LGD SHOWED COMPLETE ABSENCE OF ANY CHROMOSOMALLY ABERRANT CLONES (DUBBED NOT-BAD). WE WILL NOW VALIDATE NOT-BAD AS A BIOMARKER THAT IDENTIFIES LGD AT SUCH LOW PROGRESSION RISK AS TO NOT REQUIRE EET. WE WILL DO THIS BY PARTNERING WITH THE SURVENT TRIAL, THAT WILL BE THE FIRST U.S. PROSPECTIVE STUDY TO FOLLOW LGD PATIENTS MANAGED BY SURVEILLANCE, NOT ABLATION. A SECOND MAJOR CHALLENGE WITH EET IS THAT OVER 25% OF PATIENTS RECUR FOLLOWING ABLATION (WITH EITHER HIGH RISK BE, HGD, OR EAC). THESE PATIENTS FACE A SUBSTANTIAL BURDEN OF POST-EET SURVEILLANCE ENDOSCOPIES, INITIALLY AT EVERY 3-MONTH INTERVALS. IN OUR PRIOR EDRN-BDL, OUR TEAM IDENTIFIED A PANEL OF METHYLATED DNA BIOMARKERS FOR SENSITIVE MOLECULAR EARLY DETECTION OF BE (CURRENTLY AWARDED FDA BREAKTHROUGH DEVICE DESIGNATION). WE HAVE FURTHER IDENTIFIED THAT THESE MARKERS REMAIN RETAINED IN A SUBSET OF PATIENTS POST-EET. WE ACCORDINGLY NOW PROPOSE A RETROSPECTIVE PHASE 3 STUDY TO FURTHER VALIDATE THESE DNA MARKERS FOR MOLECULAR ASSESSMENT OF MINIMAL RESIDUAL DISEASE, WHOSE POST-EET ELIMINATION IDENTIFIES INDIVIDUALS ACHIEVING COMPLETE MOLECULAR ERADICATION OF BE, AND HENCE AT LOW RISK OF DISEASE RECURRENCE AND NOT IN NEED OF INTENSE POST-EET SURVEILLANCE. WE DO THIS BY PARTNERING WITH THE UNIQUE UNC-BEECAB BIOREPOSITORY OF POST-EET ESOPHAGEAL BIOPSIES FROM PATIENTS WHOSE DISEASE DID OR DID NOT RECUR FOLLOWING ABLATION.

ADVANCING GENETICS THROUGH THE AMDGENE CONSORTIUM

SKIN DISEASES RESEARCH CENTER

EARLY INTERVENTION TO REDUCE ALCOHOL MISUSE AND ABUSE IN THE OHIO ARMY NATIONAL GUARD

CAROTINOIDS IN VISION

TRANSLATIONAL CONTROL BY OSMOTICALLY ACTIVE SOLUTES

NON-INFERIORITY STUDY OF ADJUVANTED VS. HIGH DOSE FLU VACCINE IN RESIDENTS OF LONG TERM CARE

STRUCTURE AND FUNCTION OF PENTAMERIC LIGAND-GATED ION CHANNELS

CYTOKINES AND INFLAMMATORY BOWEL DISEASE

IDENTIFYING INBORN GENETIC SUSCEPTIBILITY TO DEVELOPMENT OF CANCER METASTASIS

CASE CENTER FOR TRANSDISCIPLINARY RESEARCH ON ENERGETIC*

THE ROLE OF PROTEASE ACTIVATED RECEPTORS ON PLATELETS.

CENTER FOR GENETIC RESEARCH, ETHICS, AND LAW

IMPROVED CARDIAC AND VASCULAR MAGNETIC RESONANCE IMAGING USING A COMBINATION OF P

TRAINING IN COMPUTATIONAL GENOMIC EPIDEMIOLOGY OF CANCER

MECHANISMS OF TH17 AND TREG CELL DYSREGULATION IN ORAL MUCOSAL INFLAMMATION DURING HIV DISEASE

NURSE FACULTY LOAN PROGRAM

TAS::57 3600::TAS "(MURI 11) NANOFABRICATION OF TUNABLE 3D NANOTUBE ARCHITECTURES"

TRAINING PROGRAM IN MUSCULOSKELETAL RESEARCH

MOLECULAR BASIS OF DROSOPHILA HOMEOTIC GENE REGULATION

STRUCTURAL DETERMINANTS OF AMYLOID STRAIN HETEROGENEITY IN DISTINCT PHENOTYPES OF ALZHEIMER'S DISEASE

CASE CCC YOUTH ENGAGED IN SCIENCE

ENHANCING WALKING AND INDEPENDENCE AFTER INCOMPLETE SCI WITH A FULLY IMPLANTED NEUROPROSTHESIS

GRADUATE TRAINING IN CELL AND MOLECULAR BIOLOGY

ELUCIDATING THE MOLECULAR MECHANISMS THAT SHAPE THE HAIR BUNDLE

COMPUTER MODELING OF MYOSIN BINDING PROTEIN C AND ITS EFFECTS ON CARDIAC CONTRACTION

NEUREGULIN-1 REGULATION OF NEUROTRANSMISSION

A MECHANISM-BASED APPROACH TO METALLO-BETA-LACTAMASE INHIBITION

THE ROLE OF THE PROXIMAL NEPHRON IN SALT-SENSITIVE HYPERTENSION

FUNCTIONAL CONSEQUENCES OF FHC MUTATIONS IN CARDIAC MYBPC

STRA6 AND OCULAR VITAMIN A HOMEOSTASIS

CHOLESTEROL METABOLIZING P450S: STRUCTURE AND FUNCTION

EARLY CLINICAL TRIALS OF NEW ANTI-CANCER AGENTS WITH PHASE I EMPHASIS

THE IMPACT OF INTRAVENOUS HEROIN USE ON IMMUNE ACTIVATION IN TREATED HIV

ENHANCING NEUROPROSTHESIS PERFORMANCE WITH NERVE CUFF ELECTRODES

IDENTIFICATION OF IMMUNE PROTECTIVE PATHWAYS DYSREGULATED BY OPIOID USE IN HIV INFECTION, USING A SYSTEMS BIOLOGY-BASED APPROACH, TOWARD THE GOAL OF

ACHIEVING OUTSTANDING CARDIOVASCULAR HEALTH OUTCOMES FOR ALL OHIOANS: A STATEWIDE CARDIOVASCULAR HEALTH COLLABORATIVE (CARDIO-OH) - PROJECT SUMMARY MODIFIABLE CARDIOVASCULAR DISEASE (CVD) RISK FACTORS SUCH AS HYPERTENSION, CHOLESTEROL AND SMOKING CONTRIBUTE STRONGLY TO CVD MORBIDITY, MORTALITY, AND HEALTH CARE COST. OHIO IS IN THE HIGHEST QUARTILE FOR CVD MORBIDITY AND MORTALITY AND HAS SIGNIFICANT DISPARITIES IN CVD RISK FACTORS BY GEOGRAPHIC REGION, RACE/ETHNICITY, AND INSURANCE TYPE DEMONSTRATING SUBSTANTIAL OPPORTUNITY FOR IMPROVEMENT. WE PROPOSE USING A UNIQUE FACILITATED CO-DESIGN APPROACH TO DEVELOP A HEART HEALTHY QI INTERVENTION BASED ON PATIENT-CENTERED OUTCOMES RESEARCH (PCOR) IN THE CONTEXT OF AN EXPANDED STATEWIDE OHIO CARDIOVASCULAR HEALTH COLLABORATIVE (CARDI-OH) TO ACCELERATE STATEWIDE CVD IMPROVEMENT AND REDUCTIONS IN DISPARITIES. THIS PROPOSAL BUILDS ON POCKETS OF REGIONAL QI STRENGTHS TO DEVELOP A LARGER, MORE EXTENSIVE AND SUSTAINABLE EXTERNAL QI SUPPORT INFRASTRUCTURE BY LINKING THE 3 REGIONAL HEALTH IMPROVEMENT COLLABORATIVES AND 7 MEDICAL SCHOOLS WITH GREATER REACH AND EXTENSION WITHIN PRIMARY CARE AND LINKED TO OUR STATEWIDE COLLABORATIVE, THE OHIO CARDIOVASCULAR HEALTH COLLABORATIVE. THIS 3-YEAR PROJECT HAS 3 AIMS. FOR AIM 1, WE PROPOSE TO EXPAND A NASCENT STATEWIDE CARDIOVASCULAR HEALTH COLLABORATIVE AND ESTABLISH A SUSTAINABLE EXTERNAL QI SUPPORT INFRASTRUCTURE. FOR AIM 2 WE WILL CO-DESIGN, IMPLEMENT AND EVALUATE THE EFFECTIVENESS, ADOPTION, IMPLEMENTATION, AND MAINTENANCE OF THE HEART HEALTHY QI INTERVENTION OVERALL AND BY SUBGROUP (E.G., GEOGRAPHY, INSURANCE, RACE/ETHNICITY) USING A GROUP RANDOMIZED STEPPED WEDGE DESIGN. AND FOR AIM 3, WE WILL DETERMINE PATIENT, PROVIDER, CLINIC, AND OTHER CONTEXTUAL FACTORS ASSOCIATED WITH GREATER IMPROVEMENTS IN CARDIOVASCULAR CARE AND OUTCOMES AT THE HEART HEALTHY QIP CLINICS WE WILL CONDUCT A ROBUST MIXED METHODS EVALUATION OF: 1) CARDI-OH’S EVOLUTION, NETWORK DEVELOPMENT, DISSEMINATION, AND SUSTAINABILITY; 2) THE CO-DESIGN, ADOPTION, IMPLEMENTATION, MAINTENANCE AND EFFECTIVENESS OF THE HEART HEALTHY QIP OVERALL AND BY SUBGROUP ; AND 3) THE FACTORS ASSOCIATED WITH BETTER CLINICAL PERFORMANCE ON CVD RISK FACTOR PROCESS IMPROVEMENT. PROJECT FINDINGS WILL BE USEFUL TO POLICYMAKERS, HEALTH INSURERS, PRACTICE MANAGERS, HEALTH CARE PROVIDERS, AND PATIENTS. THIS PROJECT COULD PROVIDE A TRANSFORMATIVE AND SUSTAINABLE STATEWIDE MODEL FOR CARDIOVASCULAR HEALTH IMPROVEMENT AND DISPARITY REDUCTION WHICH, THROUGH OUR MIXED METHODS EVALUATION, CAN BE SHARED BROADLY FOR REPLICATION.

IMPROVED DETECTION OF PROSTATE CANCER WITH NANOPARTICLE-BASED ULTRASOUND CONTRAST AGENTS TARGETED TO PSMA

ENZYMES AND ENZYME COMPLEXES IN RNA METABOLISM

BACTERIAL AND LIPOSOMAL ANTIGEN PROCESSING

AIR POLLUTION AND HYPERTENSION: VASCULAR MECHANISMS

HUMAN GENETIC ANALYSIS RESOURCE

NUCLEAR ACCUMULATION OF CYCLIN D1 AND ONCOGENESIS

UNDERSTANDING CEFTAZIDIME RESISTANCE IN SHV B-LACTAMASES

DIABETES ENDOTHELIAL KERATOPLASTY STUDY(DEKS): IMPACT OF DIABETES ON CORNEAL TRANSPLANT SUCCESS AND CELL LOSS - PROJECT SUMMARY THIS PROPOSAL ADDRESSES A SIGNIFICANT PUBLIC HEALTH QUESTION: DOES DIABETES, THE 3RD LEADING CAUSE OF DEATH IN THE UNITED STATES (US), IMPACT SUITABILITY OF DONOR CORNEAL TISSUE FOR TRANSPLANTATION? THIS QUESTION TAKES ON INCREASING URGENCY AS RECENT EYE BANK DATA SUGGESTS DONORS WITH DIABETES NOW COMPRISE ABOUT 30-35% OF THE CORNEA DONOR POOL, A 50-72% INCREASE IN JUST OVER A DECADE. THE IMPACT OF DIABETES ON KERATOPLASTY OUTCOMES REMAINS UNKNOWN, WITH CONFLICTING EVIDENCE FROM SECONDARY OR RETROSPECTIVE ANALYSES OF MULTIPLE CLINICAL STUDIES. PREVIOUS LARGE CLINICAL STUDIES DID NOT SHOW A DIABETIC DONOR EFFECT ON PENETRATING KERATOPLASTY (PKP) AND DESCEMET MEMBRANE ENDOTHELIAL KERATOPLASTY (DMEK) GRAFT SUCCESS, YET OUR RECENT CORNEA PRESERVATION TIME STUDY (CPTS) FOUND THE DIABETIC DONOR ADVERSELY AFFECTED GRAFT OUTCOMES FOLLOWING DESCEMET STRIPPING AUTOMATED ENDOTHELIAL KERATOPLASTY (DSAEK). ALTHOUGH CURRENT STANDARD OF CARE IS TO USE DIABETIC DONOR CORNEAS FOR ALL TYPES OF KERATOPLASTIES, SOME EYE BANKS AND SURGEONS ARE INCREASINGLY AVOIDING THEM FOR DMEK. AS BOTH THE DIABETIC DONOR POPULATION AND DMEK DEMAND INCREASES, A DEFINITIVE SUPERIORITY STUDY EVALUATING EFFECT OF DONOR DIABETES STATUS ON GRAFT OUTCOMES WILL ALLAY AND/OR DEFINE THESE CONCERNS. THE DIABETES ENDOTHELIAL KERATOPLASTY STUDY (DEKS) WILL ADDRESS THESE IMPORTANT QUESTIONS THROUGH A PROSPECTIVE MASKED CLINICAL TRIAL ENROLLING 1420 PARTICIPANT-EYES AT 30 CLINICAL SITES AND 15 EYE BANKS ACROSS THE US. THE DEKS WILL DETERMINE IF THE 3-YEAR GRAFT SUCCESS RATE FOLLOWING DMEK PERFORMED WITH CORNEAS FROM DONORS WITHOUT DIABETES IS SUPERIOR TO THE GRAFT SUCCESS RATE WITH CORNEAS FROM DONORS WITH DIABETES. IT WILL ALSO DETERMINE IF THE 3-YEAR CENTRAL ENDOTHELIAL CELL LOSS (ECL) AFTER DMEK WITH CORNEAS FROM DONORS WITHOUT DIABETES IS LESS THAN THE CENTRAL ECL WHEN CORNEAS FROM DONORS WITH DIABETES ARE USED. LASTLY, THE DEKS WILL EXPLORE THE RELATIONSHIP OF DONOR DIABETES SEVERITY, AS MEASURED BY EYE BANK-DETERMINED DIABETES RISK CATEGORIZATION SCORES, POST- MORTEM HBA1C, AND SKIN ADVANCED GLYCATION ENDPRODUCTS AND OXIDATION MARKERS, WITH DMEK GRAFT OUTCOMES 3 YEARS POSTOPERATIVELY IN CORNEAS FROM DIABETIC DONORS. THE DEKS COULD HAVE A MAJOR IMPACT ON THE TARGETED USE OF CORNEAS FROM AN INCREASING NUMBER OF DONORS WITH DIABETES WITH A RANGE OF DISEASE SEVERITY IN A DONOR POOL THAT MUST CONTINUE TO EXPAND TO MEET THE CLINICAL DEMANDS OF AN AGING POPULATION AND DMEK GROWTH.

ELUCIDATING HUMAN BETA CELL TRANSCRIPTIONAL REGULOME WITH LOW-INPUT GENOMIC TECHNOLOGIES

HETEROMULTIVALENT PEPTIDE-LIPID NANOCONSTRUCTS AS ARTIFICIAL PLATELET ANALOGS

AIRWAY REDOX BIOCHEMISTRY AS A DETERIMINANT OF ASTHMA PHENOTYPE DURING ADOLESCEN*

REGULATION OF HIV LATENCY BY MICROGLIAL-NEURONAL INTERACTIONS

PROMOTING HEALTH AND PREVENTING DISEASE IN DISADVANTAGED URBAN NEIGHBORHOODS

MANIPULATING EPIGENETIC CONTROL MECHANISMS TO CONTROL HIV TRANSCRIPTION

REPAIRING THE INTESTINAL EPITHELIUM FROM THE DUAL ACTION OF HIV AND DRUG USE

RESTORING MULTIDIMENSIONAL COORDINATED REACHING AND DEXTEROUS GRASPING TO PERSONS WITH CHRONIC TETRAPLEGIA THROUGH FUNCTIONAL ELECTRICAL STIMULATION

LINKING AN ACTIVITY-DEPENDENT BMP PATHWAY TO SYNAPSE STRUCTURE AND FUNCTION

MECHANISMS OF DEVELOPMENTAL PLASTICITY IN THE MAMMALIAN OLFACTORY SYSTEM

UNDERSTANDING GABAA RECEPTOR PROTEIN FOLDING AND MISFOLDING

CARDIOVASCULAR RISK FROM COMPREHENSIVE EVALUATION OF THE CT CALCIUM SCORE EXAM - AI PREDICTION OF AORTIC VALVE DISEASE AND ITS ROLE IN MACE USING FREE, OR LOW-COST, CT CALCIUM SCORE EX- AMS SUPPLEMENT TO NIH R01HL165218 PARENT, “CARDIOVASCULAR RISK FROM COMPREHENSIVE EVALUATION OF THE CT CALCI- UM SCORE EXAM” SUMMARY USING A COMPREHENSIVE MACHINE LEARNING ANALYSIS OF AORTIC VALVE CALCIFICATIONS, WE WILL PREDICT AORTIC VALVE STE- NOSIS AND FUTURE MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE). EARLIER IDENTIFICATION OF PATIENTS AT RISK OF AORTIC VALVE STENOSIS WILL IMPROVE PREEMPTIVE PATIENT MANAGEMENT (E.G., MONITORING, LIFESTYLE CHANGES, AND POSSIBLY EMERGING MEDICATIONS) FOR THIS DISEASE, WHICH CAN OFTEN GO UNNOTICED. IN ADDITION, DETECTION METHODS COULD ENABLE THE TREND OF PERFORMING TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR) EARLIER IN THE DISEASE PROCESS AND WILL ENABLE TRIALS OF MEDICAL TREATMENTS. ASIDE FROM THEIR ROLE IN AORTIC VALVE DISEASE, AORTIC VALVE CALCIFICA- TIONS HAVE BEEN SHOWN TO BE ASSOCIATED WITH MACE. IMPROVED CHARACTERIZATION OF MACE RISK WILL ALSO IMPROVE PERSONALIZED PATIENT MANAGEMENT. WITH IMPROVED MACE RISK PREDICTION AND IDENTIFICATION OF HIGH-RISK PHENO- TYPES, THERE WILL BE AN OPPORTUNITY TO GUIDE PRECISION PREVENTIVE THERAPIES, WHERE GUIDANCE IS NEEDED, GIVEN THE COST AND SIDE EFFECTS ASSOCIATED WITH SOME OF THESE THERAPIES. WE WILL USE LARGE ARCHIVES OF CT CALCIUM SCORE EXAMS, INCLUDING THOSE FROM THE UNIVERSITY HOSPITALS OF CLEVELAND, WHICH IS AN INSTITUTION WITH THE LARGEST NO-COST CT CALCIUM SCORING PROGRAM (>100,000 SCANNED PATIENTS, >13,000 SCANS PER YEAR), PROVIDING A UNIQUE OPPORTUNITY TO CREATE NEW PERSONALIZED APPROACHES FOR HEALTHCARE. NUMEROUS TECHNICAL INNOVATIONS ARE PLANNED, INCLUDING NOVEL METHODS FOR AORTIC VALVE CALCIUM IDENTIFICATION, CALCIUM FEATURES, AND MACHINE- LEARNING APPROACHES. RESEARCH IN THE SUPPLEMENT IS VERY SYNERGISTIC WITH RESEARCH IN THE PARENT GRANT, WHERE WE ARE PREDICTING MACE USING CORONARY CALCIUM-OMICS AND FAT-OMICS FEATURES. IN ADDITION TO CLINICAL RISK PRE- DICTION, OUR CT CALCIUM SCORE ANALYSES WILL DOVETAIL IN THE FUTURE WITH MANY RESEARCH INTERESTS, INCLUDING THE ROLE OF GENES, METABOLOMICS, CO-MORBIDITIES (E.G., CHRONIC KIDNEY DISEASE AND HYPERLIPIDEMIA), SOCIO-ECONOMIC STATUS, AND CARDIO-ONCOLOGY ON CARDIOVASCULAR RISK. AS THERE ARE INTERESTING SEX AND RACE IMPLICATIONS ASSOCIAT- ED WITH AORTIC VALVE STENOSIS, WE WILL CAREFULLY DETERMINE THE ROLE OF THESE VARIABLES IN OUR EARLY DIAGNOSIS RISK MODELS.

SKIN BIOMARKERS FOR DIAGNOSING AND CHARACTERIZING AD AND ADRD - ABSTRACT ALZHEIMER'S DISEASE (AD) AND AD-RELATED DEMENTIAS (ADRD) SUCH AS LEWY BODY DEMENTIA (LBD) ARE ALL ASSOCIATED WITH DEPOSITION OF MISFOLDED PROTEIN AGGREGATES IN THE BRAIN INCLUDING TAU IN AD AND NON-AD TAUOPATHIES, AND A-SYNUCLEIN (ASYN) IN LBD. CURRENTLY, A DEFINITE DIAGNOSIS OF THESE DISORDERS RELIES ON THE HISTOLOGICAL AND BIOCHEMICAL EXAMINATION OF THE BRAIN FOR THE MISFOLDED PROTEINS. DEVELOPMENT OF RELIABLE AND SENSITIVE ASSAYS FOR THESE MISFOLDED PROTEINS IN EASILY ACCESSIBLE PERIPHERAL SPECIMENS IS CRITICAL FOR EARLY OR DIFFERENTIAL DIAGNOSIS, DETERMINATION OF DISEASE SEVERITY, AND EVALUATION OF THERAPEUTIC EFFICACY IN CLINICAL TRIALS. INTERESTINGLY, BRAIN TAU AND ASYN AGGREGATES EXHIBIT PRION-LIKE AGGREGATION SEEDING ACTIVITY, WHICH CAN BE SPECIFICALLY DETECTED BY TWO HIGHLY SENSITIVE AMPLIFICATION ASSAYS INCLUDING REAL-TIME QUAKING-INDUCED CONVERSION (RT-QUIC) AND PROTEIN MISFOLDING CYCLIC AMPLIFICATION (PMCA). THEY HAVE BEEN PROVED TO BE HIGHLY SENSITIVE FOR DETECTION OF MISFOLDED PROTEINS IN THE BRAIN AND/OR CEREBROSPINAL FLUID IN PRION DISEASE (PRD), AD, OR PD (ATARASHI ET AL., 2011; PEDEN ET AL., 2012; FOUTZ ET AL., 2017; ORRU ET AL., 2015; SAIJO ET AL., 2017; KRAUS ET AL., 2018). USING RT-QUIC/PMCA, WE WERE ABLE TO DETECT PRION AND ASYN AGGREGATES IN THE SKIN OF INDIVIDUALS WITH PRD OR PD (ORRU ET AL., 2017; WANG ET AL., 2019; 2020). REMARKABLY, OUR PRELIMINARY RESULTS HAVE SHOWN THAT PRIONS-LIKE TAU- SEEDING ACTIVITY IS DETECTABLE BY RT-QUIC AND PMCA IN SKIN OF AD PATIENTS BUT NOT IN NORMAL CONTROLS. THUS, WE HYPOTHESIZE THAT SKIN TAU-SEEDING ACTIVITY DETECTED BY RT-QUIC AND PMCA IS A NOVEL BIOMARKER FOR DIAGNOSING, CHARACTERIZING, AND PREDICTING OUTCOMES OF AD AND NON-AD TAUOPATHIES AND FOR DIFFERENTIATING AD FROM LBD. TO TEST THIS HYPOTHESIS, THE FOLLOWING FOUR AIMS WILL BE PURSUED: (1) ESTABLISH THE TAU-SEEDING ACTIVITY IN AUTOPSIED SKIN SAMPLES AS A BIOMARKER FOR POSTMORTEM DIAGNOSIS AND CHARACTERIZATION OF AD USING RT-QUIC/PMCA ASSAYS; (2) ASSESS SKIN TAU-SEEDING ACTIVITY AS A BIOMARKER FOR PREMORTEM DIAGNOSIS, CHARACTERIZATION, AND PREDICTING CLINICAL OUTCOMES OF AD; (3) DETERMINE SKIN TAU-SEEDING ACTIVITY AS A BIOMARKER FOR DIFFERENTIATING AD FROM NON-AD TAUOPATHIES, AND FROM LBD, A COMMON ADRD; AND (4) DETERMINE WHETHER SKIN TAU-SEEDING ACTIVITY IS DETECTABLE AT AN ASYMPTOMATIC STAGE BY RT-QUIC/PMCA IN ANIMAL MODELS OF AD TAUOPATHIES. WE BELIEVE THAT THE SUCCESSFUL IMPLEMENTATION OF THIS PROJECT WILL DEVELOP RT-QUIC/PMCA ASSAYS OF SKIN TAU-SEEDING ACTIVITY AS A BIOMARKER FOR DIAGNOSTIC TESTING AND EVALUATING CLINICAL TRIALS ACROSS AD, NON-AD TAUOPATHIES, AND LBD.

IDENTIFICATION AND ELIMINATIONOF HIV RESERVOIRS IN ORAL LYMPHOID TISSUES BY ENGINEERED NK CELLS.

HIV/AIDS INTERNATIONAL TRAINING PROGRAM

NURSE FACULTY LOAN PROGRAM

PIRE: MATERIALS FOR RENEWABLE ENERGY NATURE'S WAY (RENEW)

SUPERCDMS 25 KG EXPERIMENT

THREE-DIMENSIONAL PATIENT-TAILORED RF PULSES FOR SPIN ECHO NEUROIMAGING AT 7 T

REGULATION OF VITAMIN A METABOLISM IN THE EYE

COSMIIC TSNIP TO TREAT CHRONIC KNEE PAIN - SUMMARY CHRONIC KNEE PAIN AFFECTS OVER 15 MILLION AMERICANS, COSTING BILLIONS ANNUALLY AND SEVERELY DIMINISHING MOBILITY AND QUALITY OF LIFE. CURRENT STANDARD TREATMENTS OFFER ONLY TEMPORARY RELIEF AND CARRY SIGNIFICANT RISKS. THUS, THERE'S A CRITICAL NEED FOR CONTINUOUS, LOCALIZED TREATMENTS THAT SELECTIVELY INHIBIT PAIN SIGNALS WITHOUT IMPAIRING MOTOR OR TACTILE FUNCTIONS. WE PROPOSE TO DEVELOP AND VALIDATE TRANSIENT SELECTIVE NEURAL INHIBITION VIA PHOTOBIOMODULATION (TSNIP) TO BLOCK C-FIBER–MEDIATED PAIN IN THE SAPHENOUS NERVE TO RELIEVE CHRONIC KNEE PAIN. BY INTEGRATING OPTIMIZED TSNIP PARAMETERS INTO THE FDA-QUALIFIED COSMIIC MODULAR PLATFORM, ALREADY PROVEN SAFE FOR ELECTRICAL STIMULATION AND SENSING IN HUMANS, THIS APPROACH PROMISES PRECISE, ADJUSTABLE, AND DURABLE PAIN RELIEF WITH MINIMAL SYSTEMIC EXPOSURE. THE LONG-TERM OBJECTIVE IS TO CREATE A HUMAN-GRADE DEVICE CAPABLE OF SUSTAINED ANALGESIA FOR CHRONIC KNEE PAIN AND A FLEXIBLE FOUNDATION FOR BROADER NEUROMODULATION APPLICATIONS. AIM 1 WILL OPTIMIZE THE OPTICAL SPECIFICATIONS OF THE COSMIIC TSNIP SYSTEM. WAVELENGTHS SPANNING THE RED TO NEAR-INFRARED SPECTRUM WILL BE EVALUATED FOR PEAK SMALL FIBER INHIBITION EFFICIENCY, AND ILLUMINATION GEOMETRIES WILL BE COMPARED TO DETERMINE THE OPTIMAL CIRCUMFERENCE AND LENGTH OF NERVE EXPOSURE. PHOTON PROPAGATION MEASUREMENTS IN EX VIVO RAT NERVE TISSUE WILL SUPPORT INTERNAL IRRADIANCE ESTIMATES, INFORMING THE IRRADIANCE REQUIREMENTS FOR AN IMPLANTABLE DESIGN TARGETING THE OVINE SAPHENOUS NERVE. AIM 2 WILL TRANSLATE THESE FINDINGS INTO HARDWARE: DESIGNING AND FABRICATING A HERMETICALLY SEALED LIGHT-DELIVERY CUFF WITH SIDE-EMITTING, OPTICAL WAVEGUIDES FOR CIRCUMFERENTIAL NERVE WRAPPING, AND A CONTROL MODULE COMPATIBLE WITH COSMIIC'S NETWORKED INTERFACE. THIS MODULE WILL DRIVE MINIATURE LASER DIODES WITH PROGRAMMABLE PARAMETERS. BENCH TESTING WILL THEN VERIFY OPTICAL OUTPUT ACCURACY, THERMAL SAFETY, AND ELECTRONIC STABILITY UNDER PHYSIOLOGIC LOADS. AIM 3 WILL ESTABLISH INITIAL FEASIBILITY IN AN OVINE MID-BODY TRANSECTION (MBT) OF THE MEDIAL MENISCUS MODEL. TWO CADAVERIC SHEEP WILL BE USED TO REFINE SURGICAL IMPLANTATION TECHNIQUES, FOLLOWED BY THREE LIVE ANIMALS FOR PROCEDURAL VALIDATION. A SUBSEQUENT PILOT STUDY WILL INVOLVE SIX MERINO EWES UNDERGOING UNILATERAL MBT; THREE WILL RECEIVE ACTIVE COSMIIC TSNIP IMPLANTS AND THREE WILL RECEIVE SHAM DEVICES. BEHAVIORAL ASSESSMENTS, INCLUDING PRESSURE-PLATFORM GAIT ANALYSIS AND ACCELEROMETER RECORDINGS, WILL QUANTIFY ANALGESIC EFFICACY, AND COMPREHENSIVE HISTOPATHOLOGY AFTER HUMANE EUTHANASIA WILL EVALUATE BIOCOMPATIBILITY AND DEVICE INTEGRITY. SUCCESSFUL COMPLETION WILL YIELD A FULLY INTEGRATED, IMPLANTABLE TSNIP SYSTEM OPTIMIZED FOR SELECTIVE C-FIBER BLOCKADE, READY FOR AN EXPANDED GLP LARGE-ANIMAL STUDY. THIS MULTIDISCIPLINARY EFFORT LEVERAGES PROVEN TECHNIQUES AND ADVANCED ENGINEERING TO DELIVER A TRANSFORMATIVE THERAPY FOR CHRONIC KNEE PAIN AND ACCELERATE TRANSLATION OF IMPLANTABLE NEUROMODULATION THERAPIES FOR VARIOUS CHRONIC PAIN AND NEUROLOGICAL DISORDERS.

MULTI-LEVEL INTERVENTIONS TO REDUCE ORAL HEALTH DISPARITIES AMONG ADULTS IN PRIMARY CARE SETTINGS - PROJECT SUMMARY/ABSTRACT NORTHEAST OHIO HAS ONE OF THE HIGHEST RATES OF ORAL DISEASES (CARIES, PERIODONTITIS) AND POOR DENTAL ATTENDANCE AMONG LOW-INCOME OLDER ADULTS. PROFESSIONAL ORGANIZATIONS AND THE IOM RECOMMEND INTEGRATION OF ORAL HEALTH (OH) ACTIVITIES INTO PRIMARY CARE FOR ADULTS IN ORDER TO REDUCE MEDICAL COSTS. BUT, PUBLISHED LITERATURE INDICATES A LACK OF OUTCOMES DATA TO ASSEMBLE AN EFFECTIVE MEDICAL-DENTAL INTEGRATION. IMPEDING INTEGRATION ARE ALSO FACTORS SUCH AS LACK OF AN ELECTRONIC HEALTH RECORD (EHR) BASED ORAL HEALTH (OH) ASSESSMENT AND REFERRAL, AND INADEQUATE OH EDUCATION AND TRAINING FOR MEDICAL PROVIDERS. OUR SURVEY DATA INDICATE THAT THE MAJORITY OF PROVIDERS WOULD LIKE OH FACTS TO BE COMMUNICATED AT PRIMARY CARE VISITS (PCV) BUT LACK EDUCATION AND RESOURCES. THERE ARE MISPERCEPTIONS ABOUT ORAL DISEASES AMONG OLDER ADULTS THAT PREVENT REGULAR DENTAL ATTENDANCE. THE PROPOSED MULTI-LEVEL INTERVENTIONS WILL ADDRESS FACTORS THAT IMPEDE OH INTEGRATION, AND SUBSEQUENTLY IMPROVE SELF-REGULATORY BEHAVIORS IN ADULTS. THE INTERVENTIONS ARE: PRACTICE (MEDICAL ASSISTANTS, NURSES): EHR SYSTEMS BASED CHANGES TO ASK, ADVISE, ASSESS, CONNECT (AAAC). PROVIDER (PHYSICIAN/NURSE PRACTITIONER): IMPROVE KNOWLEDGE AND SKILLS USING COMMON-SENSE MODEL OF SELF-REGULATION (CSM) THEORY BASED EDUCATION AND SKILLS TRAINING TO COMMUNICATE OH FACTS AND REINFORCE IMPORTANCE OF DENTAL VISITS. A CLUSTER-RANDOMIZED CLINICAL TRIAL IS PROPOSED TO TEST IMPLEMENTATION (PRACTICE) AND BEHAVIORAL (PROVIDER) INTERVENTION TO ADDRESS SELF-REGULATION AND INCREASE DENTAL ATTENDANCE AMONG LOW-INCOME ADULTS AGED ≥55 YEARS. THE PRIMARY AIMS ARE: 1) UG3, CONDUCT QUALITATIVE WORK WITH STAKEHOLDERS AND PRACTICES; SYSTEM-BASED CHANGES IN EHR; AND PILOT-TEST THE INTERVENTIONS IN 2 PRACTICES. UH3, RANDOMIZE 8 PRACTICES TO TWO ARMS TO INVESTIGATE THE EFFICACY OF A EHR BASED STRATEGY AT THE PRACTICE LEVEL TO ASK [OH RISK ASSESSMENT], ADVISE [GOING TO DENTIST], ASSESS [WILLINGNESS FOR REFERRAL], CONNECT [EREFERRAL AND/OR RESOURCES] TOGETHER WITH PROVIDER CSM THEORY-BASED EDUCATION AND SKILLS TO COMMUNICATE OH FACTS VERSUS PROVIDER ALONE (STANDARD OR USUAL ORAL HEALTH CARE) TO INCREASE DENTAL ATTENDANCE (PRIMARY OUTCOME); AND IMPROVE OH QUALITY OF LIFE, ORAL HYGIENE BEHAVIOR, AND BIOMETRIC MEASURES OF HEALTH (SECONDARY OUTCOMES). SECONDARY AIMS (UH3) ARE TO EXPLORE: THE DELIVERY AND DOCUMENTATION OF AAAC IMPLEMENTATION STRATEGY; AND TO INVESTIGATE CAUSAL PATHWAYS THAT AFFECT THE OUTCOMES. THE SAMPLE INCLUDES 209 PROVIDERS AND MEDICAL STAFF, AND 800 MEDICAID-ENROLLED ADULTS. DATA ANALYSIS (UG3) WILL UTILIZE A MIXED METHOD DESIGN FOR QUALITATIVE AND DESCRIPTIVE STATISTICS FOR QUANTITATIVE DATA. DATA COLLECTION (UH3) WILL FOLLOW THE RE-AIM FRAMEWORK: ADULTS (OUTCOME DATA FROM MEDICAID CLAIMS, QUESTIONNAIRES, EHR); PROVIDER, PRACTICE (QUESTIONNAIRES); PROVIDER, PRACTICE (PROCESS MEASURES: REACH, FIDELITY, ADOPTION, MAINTENANCE FROM AUDITS). A GENERALIZED ESTIMATING EQUATIONS APPROACH WILL BE USED TO ASSESS EFFECTS OF MULTI-LEVEL INTERVENTIONS ON DENTAL ATTENDANCE AND OTHER OUTCOMES, WHILE ACCOUNTING FOR CLUSTERING WITHIN PRACTICE. MEDIATION METHODS WILL DETERMINE IF INTERVENTION EFFECTS OCCUR THROUGH HYPOTHESIZED MEDIATORS. A SUSTAINABLE OH CARE MODEL IS PROPOSED FOR PRIMARY CARE CLINICIANS.

LINKAGE CONSORTIUM END-STAGE-RENAL DISEASE

EXECUTE A BALANCED SCIENCE PROGRAM BASED ON DISCIPLINE-SPECIFIC GUIDANCE FROM THE NATIONAL ACADEMIES OF SCIENCES ENGINEERING AND MEDICINE ADMINISTRATION PRIORITIES AND DIRECTION FROM CONGRESS. PARTICIPATE AS A KEY PARTNER AND ENABLER IN THE AGE

NOVEL REGULATION OF RENAL FUNCTION BY S-NITROSYLATION

USING MHEALTH TO IMPROVE ADHERENCE AND REDUCE BLOOD PRESSURE IN INDIVIDUALS WITH HYPERTENSION AND BIPOLAR DISORDER

FIELD-DEPLOYABLE DRIED PLATELET SURROGATE NANOTECHNOLOGY FOR HEMORRHAGE CONTROL IN RDCR

BIOMETRIC-GENETIC ANALYSIS OF CARDIOVASCULAR DISEASE

REVERSAL OF HIV LATENCY BY METH AND INFLAMMATION

REGULATION OF RETINOPATHIES

MAGNETIC RESONANCE IMAGING GUIDED ROBOTIC CATHETER SYSTEM FOR LEFT ATRIAL APPENDAGE OCCLUSION PROCEDURES - ABSTRACT ATRIAL FIBRILLATION IS THE MOST COMMON FORM OF CARDIAC ARRHYTHMIA, WITH PREVALENCE ESTIMATED TO BE 5.2 MILLION IN 2010 AND PREDICTED TO INCREASE TO 12.1 MILLION IN 2030. ATRIAL FIBRILLATION IS A MAJOR RISK FACTOR FOR BLOOD CLOTS AND STROKE, INDEPENDENTLY INCREASING STROKE RISK 4- TO 5-FOLD THROUGHOUT ALL AGES. THEREFORE, THE VAST MAJORITY OF PATIENTS WITH ATRIAL FIBRILLATION REQUIRE SOME FORM OF STROKE PREVENTION THERAPY. CURRENT FIRST LINE STROKE PREVENTION THERAPY FOR ATRIAL FIBRILLATION PATIENTS IS LIFE-LONG USE OF ORAL ANTI-COAGULATION MEDICATIONS, WHICH ARE ASSOCIATED WITH INCREASE IN BLEEDING RISK BY APPROXIMATELY 2- TO 2.5-FOLD, INCLUDING INTRACRANIAL HEMORRHAGE, THAT MAY LEAD TO HOSPITALIZATION, TRANSFUSION, SURGERY, AND DEATH. THE PURPOSE OF THE PRESENT STUDY IS TO IMPROVE STROKE PREVENTION TREATMENT FOR NON-VALVULAR ATRIAL FIBRILLATION BY TRANSFORMING THE LEFT ATRIAL APPENDAGE OCCLUSION (LAAO) PROCEDURE INTO A FIRST LINE THERAPY FOR A LARGER SEGMENT OF PATIENT POPULATIONS, ESPECIALLY FOR YOUNGER PATIENTS WITH 20+ YEAR OF LIFE EXPECTANCY WHO ARE LIKELY TO EXPERIENCE BLEEDING PROBLEMS IN THEIR LIFETIMES. LAAO IS A MINIMALLY INVASIVE PROCEDURE WHERE AN IMPLANT DELIVERED USING AN INTRAVASCULAR CATHETER IS USED TO PERMANENTLY SEAL OFF THE LEFT ATRIAL APPENDAGE MECHANICALLY TO REDUCE THE RISK OF BLOOD CLOTS. THE BARRIERS PREVENTING LAAO FROM BECOMING A FIRST LINE THERAPY ARE PRIMARILY SAFETY AND COST. THE INVESTIGATORS AIM TO OVERCOME THESE BARRIERS AND TRANSFORM LAAO INTO A FIRST LINE THERAPY BY DEVELOPING A REAL-TIME MAGNETIC RESONANCE IMAGING (MRI)-GUIDED ROBOTIC INTRAVASCULAR CATHETER SYSTEM FOR PERFORMING LAAO PROCEDURES BY SYNERGISTICALLY COMBINING NOVEL MEDICAL IMAGING, ROBOTIC CATHETER CONTROL, AND ADVANCED VISUALIZATION TECHNOLOGIES TO IMPROVE THE SAFETY, COST, AND WORKFLOW OF LAAO PROCEDURES. THE PROPOSED TECHNOLOGY EXPANDS ON NOVEL APPROACHES INITIATED BY THE INVESTIGATORS IN EARLIER WORK IN THE AREAS OF REAL-TIME MRI IMAGE ACQUISITION AND RECONSTRUCTION, ROBOTIC CATHETERS ACTUATED USING THE MAGNETIC FIELD OF THE MRI SCANNER, ADVANCED VISUALIZATION, AND VOLUMETRIC PLANNING OF LAAO. THE PROJECT IS ORGANIZED INTO THREE SPECIFIC AIMS, EACH FOCUSING ON ONE KEY ASPECT OF THE PROCEDURE WORKFLOW, NAMELY, PROCEDURE PLANNING, TRANSSEPTAL PUNCTURE, AND LAAO IMPLANT DELIVERY. THESE SPECIFIC AIMS BUILD ON CROSSCUTTING TECHNICAL RESEARCH ON MRI, ROBOTICS, AND HUMAN-MACHINE INTERFACE TECHNOLOGIES, WHERE THE INVESTIGATORS WILL DEVELOP NOVEL TECHNOLOGIES FOR RAPID AND FLEXIBLE 2D/3D CARDIAC MRI IMAGING, ROBOTICALLY CONTROLLED MRI-COMPATIBLE DEXTEROUS CARDIAC CATHETERS, AND HUMAN-MACHINE INTERFACES WITH ADVANCED VISUALIZATION. THE END RESULT OF THIS PROPOSAL WILL BE THE COMPLETE PROTOTYPE OF AN MRI-GUIDED ROBOTIC CATHETER SYSTEM FOR PERFORMING LAAO PROCEDURES COMBINING REAL-TIME INTRAOPERATIVE MRI, ROBOTIC CATHETER CONTROL, AND ADVANCED VISUALIZATION TECHNOLOGIES TO FACILITATE SAFER, MORE EFFICIENT, AND COST-EFFECTIVE LAAO PROCEDURES. THE DEVELOPED SYSTEM AND THE UNDERLYING TECHNOLOGIES WILL BE VALIDATED BY EXPERTS IN INTERVENTIONAL CARDIOLOGY IN VERTEBRATE ANIMAL AND NON-CLINICAL HUMAN STUDIES.

INFLAMMATION IN VASCULAR INJURY AND REPAIR

INNATE IMMUNE SIGNAL TRANSDUCTION SPECIFICITY IN INFLAMMATORY DISEASE

RESEARCH ONCOLOGY TRAINING GRANT

ASSESSING SKIN BIOMARKERS FOR PRECLINICAL DIAGNOSIS OF PD AND NON-PD PARKINSONISM

(PQ1) HIV-INFECTED T-CELL EXOSOMES IN LUNG CANCER PROGRESSION

DEFINING TARGETS OF PROTECTIVE IMMUNITY TO VIVAX MALARIA USING HUMAN MONOCLONAL ANTIBODIES

ROLE OF GENE ENHANCER ELEMENTS IN COLON CANCER

DRUGS OF ABUSE AND THE EPIGENETIC AND SIGNALING PATHWAYS CONTROLLING HIV LATENCY

MADAGASCAR P. VIVAX INVASION OF DUFFY-NEGATIVE RED CELLS

EFFECTIVENESS RCT OF CUSTOMIZED ADHERENCE ENHANCEMENT

EFFECTS OF GLP-L RECEPTOR AGONISTS ON CARDIOMETABOLIC ALTERATIONS IN HIV-ASSOCIATED LIPOHYPERTROPHY

CONTROL NUMBER: 0670-5371 HIGH ENERGY STORAGE CAPACITY LOW COST IRON FLOW BATTERY

EUNICE KENNEDY SHRIVER NICHD COOPERATIVE MULTICENTER NEONATAL RESEARCH NETWORK

NATURAL RESISTANCE TO MYCOBACTERIUM TUBERCULOSIS INFECTION

RANDOMIZED CONTROL TRIAL OF POSITIVE PEERS MHEALTH APP AS A CLINIC-BASED INTERVENTION TO OPTIMIZE HIV OUTCOMES AMONG YOUNG, MINORITY PERSONS LIVING WITH HIV - PROJECT SUMMARY/ABSTRACT THE POSITIVE PEERS MOBILE APP IS AN ORIGINAL PLATFORM DEVELOPED BY AND FOR THE HARDEST TO REACH HIV DISPARITY POPULATIONS, YOUNG PEOPLE WITH HIV WHO IDENTIFY AS RACIAL, ETHNIC AND/OR SEXUAL/ GENDER MINORITIES. THIS APP HOLDS POTENTIAL TO PROVIDE EXTENSIVE, CUSTOMIZABLE, SELF- MANAGEMENT TOOLS (I.E., WELLNESS TRACKER, COMMUNITY FORUM, CHAT, FREQUENT ORIGINAL BLOGS) TO YOUNG PEOPLE WITH HIV ANYWHERE IN THE US. THE POSITIVE PEERS APP PROVIDES HEALTH INFORMATION, HEALTH MANAGEMENT TOOLS AND VIRTUAL COMMUNITY SUPPORT. WHILE THE APP ITSELF OFFERS A SAFE PLACE FOR YOUNG PERSONS WITH HIV TO GET HEALTH INFORMATION AND SUPPORT, IT'S USE IS ENHANCED BY THE PRESENCE OF LOCAL PEER ADMINISTRATORS WHO PROVIDE NAVIGATION, SUPPORT AND COACHING TO USERS. THE PROPOSED STUDY SEEKS TO EVALUATE ITS EFFECTIVENESS IN IMPROVING VIRAL SUPPRESSION AMONG MINORITY DISPARITY POPULATIONS 18-30 YEARS OF AGE WHO ARE EITHER NEWLY DIAGNOSED, OUT OF CARE OR NOT VIRALLY SUPPRESSED USING A RANDOMIZED CONTROL TRIAL DESIGN SUPPLEMENTED BY AN OBSERVATIONAL COHORT OF PERSONS WHO DECLINE TO USE THE APP. CLINICS IN SIX HIGH PRIORITY ENDING THE HIV EPIDEMIC JURISDICTIONS WILL TRAIN STAFF AS APP ADMINISTRATORS AND UTILIZE THE APP AS A CLINIC- BASED TOOL. OUR PRIMARY OBJECTIVE IS TO IMPROVE HIV OUTCOMES BY OFFERING PEER INTERACTION, TARGETED RETENTION AND ADHERENCE MESSAGING, AND INTERACTIVE TRACKERS AND REMINDERS IN ONE SMARTPHONE APP. OUR SPECIFIC AIMS ARE: AIM 1: COMPARE THE EFFECTIVENESS OF HIV CARE SUPPORTED BY THE PPA TO USUAL CARE FOR RETENTION IN HIV CARE AND VIRAL SUPPRESSION OF NEWLY DIAGNOSED OR RE-ENGAGED HIGH PRIORITY YOUNGER ADULTS WITH HIV. AIM 2: TO IDENTIFY FACTORS THAT PREDICT USER ENGAGEMENT WITH PRIMARY PPA COMPONENTS AND ASSOCIATED EFFECTS ON RETENTION IN CARE, VIRAL SUPPRESSION, AND HIV RELATED PERCEIVED STIGMA. AIM 3: TO DETERMINE INTERVENTION ADOPTION, USABILITY, FIDELITY, AND COST ACROSS STUDY SITES. THESE AIMS WILL BE ADDRESSED IN A PARALLEL COHORT DESIGN RANDOMIZED CONTROLLED TRIAL OF 250 NEWLY DIAGNOSED OR OUT OF CARE YPWH FROM DESIGNATED HIGH PRIORITY SITES. PARTICIPANTS WILL BE ALLOCATED 1:1 TO RECEIVE THE PPA APP UPON STUDY ENTRY OR TO A DELAYED INTERVENTION ARM WHERE THEY WILL RECEIVE THE USUAL CARE WITH ATTENTION CONTROLS FOR 6 MONTHS. THIS WILL ALLOW FOR EFFECTIVENESS EVALUATION DURING THE EARLIEST PHASE OF ADJUSTMENT TO THE DIAGNOSIS WHILE ALSO ALLOWING FOR LONGITUDINAL OUTCOME EFFECTS.

CASE COMPREHENSIVE CANCER CENTER (CASE CCC) CANCER HEALTH DISPARITIES SPORE PLANNING GRANT

NICHD MATERNAL-FETAL MEDICINE UNITS (MFMU) NETWORK

MATRICELLULAR PROTEINS IN TRABECULAR MESHWORK INCREASE INTRAOCULAR PRESSURE

LEARNING SKILLS TOGETHER: A RANDOMIZED CONTROLLED TRIAL OF A COMPLEX CARE SKILLS INTERVENTION TO IMPROVE AD/ADRD CAREGIVER SELF-EFFICACY - PROJECT SUMMARY/ABSTRACT __________________________________________________________ TWO-THIRDS (67%) OF FAMILY CAREGIVERS TO PERSONS LIVING WITH ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (AD/ADRD) PROVIDE COMPLEX CARE TASKS, SUCH AS MEDICAL/NURSING TASKS (E.G., MANAGING MEDICATIONS, TRANSFERRING FROM BED TO CHAIR, MANAGING SWALLOWING DIFFICULTIES). YET, ONLY 53% OF AD/ADRD CAREGIVERS RECEIVE ANY TRAINING TO PREPARE THEM TO CONDUCT COMPLEX CARE. CONSEQUENTLY, AD/ADRD CAREGIVERS EXPERIENCE HIGH LEVELS OF WORRY ABOUT MAKING A MISTAKE. MOST RESPONSES TO CAREGIVERS’ NEED FOR COMPLEX CARE TRAINING ARE NOT SPECIFIC TO AD/ADRD CAREGIVERS, THOUGH COMPLEX CARE IS EXPONENTIALLY MORE CHALLENGING IN THE CONTEXT OF AD/ADRD. PROVISION OF COMPLEX CARE TO THIS POPULATION IS COMPLICATED BY THE PRESENCE OF BEHAVIORAL SYMPTOMS OF DEMENTIA (BPSD), DIFFICULTY WITH COMMUNICATION DUE TO COGNITIVE CHANGES, AND GREATER LIKELIHOOD OF MULTIMORBIDITY THAN FOUND AMONGST COGNITIVELY INTACT OLDER ADULT CARE RECIPIENTS. ANOTHER LIMITATION OF CURRENT RESPONSES TO CAREGIVERS’ NEED FOR COMPLEX CARE TRAINING IS CURRENT RESOURCES DO NOT FULLY INTEGRATE PRINCIPLES OF PSYCHOEDUCATION KNOWN TO BE EFFECTIVE AT IMPROVING CAREGIVER SELF-EFFICACY. HIGH LEVELS OF SELF-EFFICACY, A PERSON’S BELIEF IN THEIR ABILITY TO ACCOMPLISH A SPECIFIC TASK, ARE ASSOCIATED WITH MORE POSITIVE PERCEPTIONS OF CAREGIVING (E.G., MEANINGFULNESS), WHILE LOW SELF-EFFICACY CONTRIBUTES TO EMOTIONAL DISTRESS, INCLUDING DEPRESSION. TO BUILD CAREGIVERS’ SELF-EFFICACY IN THE PERFORMANCE ON COMPLEX CARE, LEARNING SKILLS TOGETHER (LST) WAS DEVELOPED IN 2017 AT THE UT HEALTH SAN ANTONIO CARING FOR THE CAREGIVER PROGRAM BY A MULTIDISCIPLINARY TEAM WITH EXPERTISE IN NURSING, OCCUPATIONAL THERAPY, SPEECH-LANGUAGE PATHOLOGY, NUTRITION, DENTAL HYGIENE, AND GERONTOLOGY. IN ITS MOST RECENT RENDITION, LST WAS DELIVERED ONLINE OVER 4 SYNCHRONOUS VIDEOCONFERENCING SESSIONS AND PROGRAM CONTENT INTEGRATED PRINCIPLES OF SELF-EFFICACY THEORY, SUCH AS PEER-LEARNING, MODELING, AND ASSIGNMENTS SO CAREGIVERS COULD PRACTICE SKILLS AND ACCESS FEEDBACK. IN A SINGLE-ARM PRE- AND POST-TEST PILOT STUDY OF LST, WE OBSERVED STATISTICALLY SIGNIFICANT INCREASES IN SELF-EFFICACY AT 4-WEEKS POST-INTERVENTION (P=0.003). NEAR SIGNIFICANT EFFECTS PERSISTED 8-WEEKS POST- INTERVENTION (P=0.057). TO RIGOROUSLY TEST THE EFFICACY OF PARTICIPATION IN LST ON CAREGIVER SELF-EFFICACY, WE PROPOSE TO TEST THE HYPOTHESIS THAT CAREGIVERS TO PERSONS LIVING WITH MID-STAGE AD/ADRD WHO PARTICIPATE IN LST WILL REPORT GREATER IMPROVEMENTS IN SELF-EFFICACY COMPARED TO A RANDOMIZED ACTIVE CONTROL GROUP (N=200). WE WILL ALSO TEST FOR SECONDARY OUTCOMES WE ANTICIPATE WILL BE AFFECTED BY IMPROVEMENTS IN SELF-EFFICACY, INCLUDING CAREGIVER DEPRESSION AND APPRAISAL OF BPSD. SUBGROUP ANALYSES WILL BE CONDUCTED WITH AFRICAN AMERICAN/BLACK, LATINX, AND WOMEN CAREGIVERS; RACE, ETHNICITY, AND GENDER WILL BE TESTED AS INTERVENTION EFFECT MODIFIERS GIVEN PRIOR RESEARCH DEMONSTRATING DIFFERENCES IN THE EFFECTS OF SELF-EFFICACY INTERVENTION ACCORDING TO THESE CHARACTERISTICS. IF FINDINGS DEMONSTRATE THE EFFICACY OF LEARNING SKILLS TOGETHER, THE NEXT STEP WILL BE TO EXAMINE EFFECTIVENESS WHEN DELIVERING THIS PROGRAM IN COMMUNITY SETTINGS (E.G., AREA AGENCIES ON AGING).

INTERSUBTYPE RECOMBINANTS FOR POLYVALENT ANTI-HIV VACCINE

OPTIMIZING TECHNOLOGY TO IMPROVE MEDICATION ADHERENCE AND BP CONTROL (OPTIMA-BP). - PROJECT SUMMARY HYPERTENSION DISPARITIES PERSIST AND ARE PARTICULARLY WORST IN AFRICAN AMERICANS (AA). SUBOPTIMAL HYPERTENSION SELF-MANAGEMENT, INCLUDING ADHERENCE TO MEDICATION-TAKING OF ANTIHYPERTENSIVES REMAINS A MAJOR PUBLIC HEALTH CONCERN. POOR ADHERENCE TO ANTIHYPERTENSIVE MEDICATIONS IS ESTIMATED TO OCCUR IN 43-78% OF PATIENTS, WITH APPROXIMATELY 50% DISCONTINUATION AFTER A YEAR, AND WORSE IN AA. EVEN MORE ALARMING, AA OLDER ADULTS MAY NOT BE PRESCRIBE EVIDENCE-BASED PRACTICE TREATMENT REGIMENS KNOWN TO MORE EFFICIENT IN THE AA POPULATION. THERE IS A CRITICAL NEED FOR BEHAVIORAL APPROACHES AND LONG-TERM SELF-MANAGEMENT STRATEGIES THAT ARE FEASIBLE, REPLICABLE, AND SCALABLE. MOBILE HEALTH (MHEALTH) TECHNOLOGIES (MOBILE PHONE APPLICATIONS [APP], TEXT, VIDEO MESSAGING) ARE PROMISING TOOLS TO FACILITATE BEHAVIORAL CHANGE AND SUSTAIN SELF-MANAGEMENT. WHILE REPORTS SUPPORT USING MHEALTH TECHNOLOGIES FOR THE MANAGEMENT OF CHRONIC DISEASES HAVE GROWN, THERE IS LIMITED DATA SPECIFIC TO AA OLDER ADULTS. OTHER GAPS IDENTIFIED IN THE LITERATURE REGARDING MHEALTH TECHNOLOGY INCLUDE THE LACK OF BEING THEORETICALLY DRIVEN, THE CLINICAL/EPIDEMIOLOGIC INVESTIGATIONS ARE PRIMARILY CONDUCTED OUTSIDE OF THE U.S. LIMITING GENERALIZABILITY, AND THE LACK OF EVIDENCE ON LONG-TERM SUSTAINABILITY AND IMPACT ON CLINICALLY RELEVANT HEALTH OUTCOMES. THIS R01 APPLICATION, OPTIMIZING TECHNOLOGY TO IMPROVE MEDICATION ADHERENCE AND BP CONTROL (OPTIMA-BP) IS TESTING A TECHNOLOGY-BASED INTERVENTIONS COMPARED TO A WAIT-LISTED CONTROL (WL) IN A PROSPECTIVE, RANDOMIZED CONTROLLED TRIAL (RCT) DESIGN. OPTIMA-BP INCLUDES EVIDENCED-BASED STRATEGIES, WEB-BASED EDUCATION, AND BEHAVIORAL SKILLS TRAINING TO USE A THEORETICALLY DRIVEN MHEALTH MEDICATION MANAGEMENT APP IN CONJUNCTION WITH A GUIDELINE DIRECTED TREATMENT REGIMEN AND NURSE COUNSELING. THE AIMS OF THIS STUDY ARE: [1] TO TEST THE EFFECTS OF OPTIMA-BP VS. WL ON SYSTOLIC BP AND SERUM HIGH- DENSITY LIPOPROTEIN CHOLESTEROL (HDL) IN AA OLDER ADULTS WITH HYPERTENSION IN A PROSPECTIVE, RCT FORMAT; AND [2] TO TEST IF THE ATTITUDINAL/KNOWLEDGE MECHANISMS OF SELF-MANAGEMENT (HYPERTENSION KNOWLEDGE, SELF-EFFICACY, PERCEIVED SOCIAL SUPPORT) AND PROXIMAL BEHAVIORAL TARGET MECHANISMS (TAKING MEDICATIONS TO REDUCE SYSTOLIC BP, DIET, EXERCISE) MEDIATE OPTIMA-BP VS. WL’S IMPACT ON THE PRIMARY AND SECONDARY OUTCOMES (SYSTOLIC BP, DIASTOLIC BP, HEALTH-RELATED QUALITY OF LIFE, SERUM LIPIDS, AND AT LEAST 62% OF THE SAMPLE WITH BP <130/80 MMHG) OVER A 12-MONTH TIME PERIOD. A SECONDARY AIM OF THIS STUDY WILL ASSESS OPTIMA-BP AND WL’S IMPACT ON THE PRIMARY AND SECONDARY OUTCOMES WHILE CONTROLLING FOR COVARIATES/CONTEXTUAL VARIABLES SUCH AS AGE AND GENDER. A SUPPLEMENTAL AND COMPLEMENTARY FEATURE OF THIS PROPOSAL IS THE QUALITATIVE EVALUATION TO CONFIRM SELF- MANAGEMENT BARRIERS AND PERCEIVED STRENGTHS OR LIMITATIONS OF THE INTERVENTION, WHICH WILL INFORM FUTURE REFINEMENTS SHOULD THESE RCT FINDINGS BE POSITIVE.