Rs Foundation Inc

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

THE DELAWARE COMPREHENSIVE SICKLE CELL RESEARCH CENTER

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

CATEGORY C: STATEWIDE EARLY CARE AND EDUCATION (ECE) NON-PROFIT ORGANIZATIONS

TAKING STEPS TO HEALTHY SUCCESS: AN EARLY CARE AND EDUCATION LEARNING COLLABORATI

RESEARCH EXPANDING ACCESS TO CHILD HEALTH (REACH) - PROJECT SUMMARY IN ORDER TO IMPROVE THE HEALTH AND WELLBEING OF OUR NATION’S CHILDREN, IT IS ESSENTIAL TO TRANSFORM PEDIATRIC HEALTH CARE TO ADDRESS THE COMPLEX SOCIAL ECOLOGICAL FACTORS THAT PERSISTENTLY HAMPER ACCESS TO CHILD HEALTH AND CONTRIBUTE TO PERVASIVE HEALTH INEQUITIES IN THE UNITED STATES. TRANSFORMING THE DELIVERY OF PEDIATRIC HEALTH CARE REQUIRES ROBUST PROGRAMS OF HEALTHCARE DELIVERY RESEARCH, USING INNOVATIVE STAKEHOLDER-ENGAGED APPROACHES TO ENSURE THE DEVELOPMENT OF ACCEPTABLE, FEASIBLE, EFFECTIVE INTERVENTIONS READY FOR EQUITABLE IMPLEMENTATION. THE OVERALL GOAL OF THIS CENTER OF BIOMEDICAL RESEARCH EXCELLENCE (COBRE) IS TO STRENGTHEN PEDIATRIC HEALTHCARE DELIVERY RESEARCH INFRASTRUCTURE IN DELAWARE, SPECIFICALLY AT THE ALFRED I. DUPONT HOSPITAL FOR CHILDREN. CONSISTENT WITH THIS GOAL, WE WILL ESTABLISH A THEMATIC, MULTIDISCIPLINARY HEALTH RESEARCH SYSTEM – THE REACH (RESEARCH EXPANDING ACCESS TO CHILD HEALTH) CENTER – ROOTED IN THE PRINCIPLES AND METHODS OF PEDIATRIC HEALTHCARE DELIVERY SCIENCE, BRIDGING OUR BIOMEDICAL RESEARCH AND HEALTH CARE SYSTEMS, AND FOCUSED ON ENSURING EQUITABLE ACCESS TO HIGH QUALITY PEDIATRIC HEALTH CARE FOR ALL. WITH STRONG SCIENTIFIC LEADERSHIP AND INSTITUTIONAL COMMITMENT, THE REACH CENTER WILL CREATE RESOURCES AND PROVIDE MENTORING TO EFFECTIVELY ACCOMPLISH THREE AIMS: 1) EXPAND INNOVATIVE PROGRAMS OF STAKEHOLDER-ENGAGED INTERVENTION-FOCUSED RESEARCH USING ADVANCES IN TECHNOLOGY TO COUNTER NEGATIVE SOCIAL ECOLOGICAL FOCUSES AND IMPROVE CHILD HEALTH; 2) ENHANCE EXISTING EXPERTISE AND EXPAND RESEARCH INFRASTRUCTURE THROUGH CORE RESOURCES SUPPORTIVE OF HEALTH EQUITY RESEARCH FOR CHILDREN; AND, 3) ESTABLISH A CRITICAL MASS OF INDEPENDENT MULTIDISCIPLINARY INVESTIGATORS TO SUSTAIN A COBRE EXPANDING ACCESS TO CHILD HEALTH. TWO OUTSTANDING JUNIOR INVESTIGATORS WHO ARE IDEALLY POISED FOR ACHIEVING INDEPENDENT NIH FUNDING PROPOSE INITIAL RESEARCH PROJECTS. EACH FOCUSES ON REFINING AND EVALUATING TECHNOLOGY-ENABLED INTERVENTIONS TO IMPROVE EQUITY IN CHILD HEALTH - THE FIRST FOR CHILDREN WITH OBESITY IN RURAL DELAWARE AND THE SECOND FOR FAMILIES WITH A PRENATAL DIAGNOSIS OF CONGENITAL HEART DISEASE. THREE ADMINISTRATIVE CORE PROGRAMS: PROJECT FUNDING, MENTORSHIP, AND RESEARCH MANAGEMENT WILL SUPPORT THE CONDUCT OF THESE AND FUTURE REACH CENTER-FUNDED PROJECTS ACROSS THE FIVE YEARS OF THE COBRE1 TO INCREASE AND SUSTAIN PEDIATRIC HEALTH CARE RESEARCH IN DELAWARE. TWO RESEARCH CORES WILL ENSURE THE RIGOROUS DESIGN AND CONDUCT OF THESE REACH CENTER-FUNDED PROJECTS. THE PROMISE (PEDIATRIC RESEARCH OPTIMIZING METHODS IN STAKEHOLDER ENGAGEMENT) CORE ASSURES THE INFRASTRUCTURE NECESSARY TO ENGAGE IMPORTANT COMMUNITY AND STAKEHOLDER PARTNERS IN RESEARCH. THE IMPACT (INTERVENTION METHODS: PROVISION AND CONNECTION THROUGH TECHNOLOGY) CORE ASSURES THE NECESSARY TECHNOLOGICAL AND SCIENTIFIC RESOURCES TO DEVELOP, TEST AND EVALUATE OUTCOMES OF TECHNOLOGY-ENABLED INTERVENTIONS. IN PARTNERSHIP WITH OTHER IDEA STATE PROGRAMS, REACH CENTER RESOURCES WILL EXTEND EXISTING ASSETS AND EXPAND THE DELAWARE RESEARCH COMMUNITY WITH IMPORTANT AND UNIQUE EMPHASES IN CHILD AND FAMILY HEALTH AND PEDIATRIC HEALTH EQUITY.

NATIONAL FIREFIGHTER AND FIRST RESPONDER SURVIVOR SUPPORT PROGRAMS

TAKING STEPS TO HEALTHY SUCCESS: AN EARLY CARE AND EDUCATION LEARNING COLLABORATI

NEMOURS NCI COMMUNITY ONCOLOGY RESEARCH PROGRAM (NCORP)

TYPE 1 DIABETES AND THE BRAIN IN CHILDREN: METABOLIC INTERVENTIONS

CENTER FOR PEDIATRIC RESEARCH

NATIONAL FIREFIGHTER AND FIRST RESPONDER SURVIVOR SUPPORT PROGRAMS: PEER SUPPORT, COUNSELING, AND PSOB

NATIONAL FIRE SERVICE SURVIVORS SUPPORT PROGRAMS - PEER SUPPORT AND PSOB

THE NATIONAL FALLEN FIREFIGHTERS FOUNDATION (NFFF) PROPOSES TO IMPLEMENT THE NATIONAL FIREFIGHTER AND FIRST RESPONDER SURVIVOR SUPPORT PROGRAMS. THE PURPOSE IS TO COLLABORATE WITH THE DEPARTMENT OF JUSTICES BUREAU OF JUSTICE ASSISTANCE TO PROVIDE ESSENTIAL SUPPORT TO THE FAMILIES AND AGENCIES OF EMERGENCY RESPONDERS WHO HAVE DIED IN THE LINE OF DUTY. THE NFFF EXPECTS TO RAISE AWARENESS OF THE PUBLIC SAFETY OFFICERS' BENEFITS (PSOB) PROGRAMS, WHICH OFFER DEATH, DISABILITY, AND EDUCATIONAL ASSISTANCE, THEREBY ENHANCING THE BUREAUS ABILITY TO DELIVER THESE BENEFITS TO THE FAMILIES OF FIREFIGHTERS AND FIRST RESPONDERS WHO HAVE BEEN KILLED OR CATASTROPHICALLY INJURED WHILE SERVING THEIR COMMUNITIES. THE NFFF OFFERS A RANGE OF ACTIVITIES THROUGH ITS FAMILY PROGRAMS AND THE NFFFS LOCAL ASSISTANCE STATE TEAMS (LAST), AVAILABLE IN EVERY STATE. LAST TEAMS PROVIDE IMMEDIATE SUPPORT, INCLUDING COORDINATING INTERIM STAFFING, GUIDING FUNERAL AND MEMORIAL ARRANGEMENTS, AND OFFERING BEHAVIORAL HEALTH SERVICES TO COWORKERS AND VOLUNTEERS. LAST MEMBERS ARE TRAINED TO HELP FAMILIES NAVIGATE THE PSOB BENEFITS APPLICATION PROCESS AND CAN ALSO ADVISE ON STATE, LOCAL, AND OTHER BENEFITS. TO SUPPORT THOSE AFFECTED BY LINE-OF-DUTY DEATHS, INCLUDING DEATHS BY SUICIDE AND COVID-19, THE NFFF HAS DEVELOPED PEER SUPPORT AND COUNSELING SERVICES FOR FAMILIES OF CAREER, VOLUNTEER, AND WILDLAND FIREFIGHTERS AND FIRST RESPONDERS FROM FEDERAL, STATE, LOCAL, AND TRIBAL DEPARTMENTS. THESE PROGRAMS ARE BASED ON RECOGNIZED SUPPORT AND COUNSELING PRACTICES AND CONTINUOUSLY EVOLVE TO BETTER SERVE THE FAMILIES AND COWORKERS OF FALLEN AND CATASTROPHICALLY INJURED FIREFIGHTERS AND FIRST RESPONDERS. THE NFFF ALSO EXPANDS ITS PEER SUPPORT NETWORKS FOR DEPARTMENT CHIEFS, INCIDENT COMMANDERS, COMPANY OFFICERS, CREW BOSSES, DIRECT SUPERVISORS, AND OTHER COWORKERS OF THE DECEASED. RECOGNIZING THE EMOTIONAL, SOCIAL, AND FINANCIAL IMPACTS ON THE FAMILIES OF FALLEN FIRST RESPONDERS, THE NFFF ASSISTS IN SECURING PSOB BENEFITS TO ADDRESS THEIR FINANCIAL NEEDS. THE ORGANIZATION ALSO PROVIDES ONGOING SUPPORT THROUGH COUNSELING, PEER SUPPORT, BEREAVEMENT CAMPS, AND RETREATS FOR CHILDREN AND ADULTS. THESE ACTIVITIES AIM TO FOSTER COMMUNITY AND HELP FAMILIES CONNECT WITH OTHERS WHO HAVE EXPERIENCED SIMILAR LOSSES, THEREBY BUILDING A SUPPORTIVE NETWORK. THE NFFFS SERVICE AREA INCLUDES ALL STATES AND TERRITORIES, AND ITS INTENDED BENEFICIARIES ARE THE FAMILIES OF FIREFIGHTERS AND FIRST RESPONDERS WHO HAVE DIED OR BEEN CATASTROPHICALLY INJURED IN THE LINE OF DUTY. BY PROVIDING COMPREHENSIVE SUPPORT AND RESOURCES, THE NFFF SEEKS TO HONOR THE SACRIFICES OF FALLEN FIREFIGHTERS AND ENSURE THAT THEIR FAMILIES RECEIVE THE NECESSARY ASSISTANCE TO NAVIGATE THEIR GRIEF AND REBUILD THEIR LIVES.

CENTER FOR PEDIATRIC RESEARCH

CENTER FOR PEDIATRIC RESEARCH (CPR)

NATIONAL HEMOPHILIA FOUNDATION PROPOSAL TO PREVENT COMPLICATIONS OF BLEEDING DISO

DELAWARE NEMOURS/DUPONT HOSPITAL FOR CHILDREN SITE FOR THE IDEA STATES PEDIATRIC CLINICAL TRIALS NETWORK

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

SICKLE CELL IMPROVEMENT: ENHANCING CARE IN THE EMERGENCY DEPARTMENT (SCIENCE) - PROJECT SUMMARY SICKLE CELL DISEASE (SCD) IS AN INHERITED BLOOD DISORDER AFFECTING APPROXIMATELY 36,000 CHILDREN IN THE UNITED STATES, APPROXIMATELY 90% OF WHOM ARE BLACK. THE DISEASE IS CHARACTERIZED BY RECURRENT, SEVERE PAIN CRISES WHICH RESULT IN HIGH RATES OF EMERGENCY DEPARTMENT VISITS AND HOSPITALIZATIONS, AND DECREASED QUALITY OF LIFE. THE NATIONAL HEART, LUNG AND BLOOD INSTITUTE, AS WELL AS THE AMERICAN SOCIETY OF HEMATOLOGY, HAVE ENDORSED PAIN MANAGEMENT GUIDELINES REGARDING THE TIMELINESS OF CARE FOR CHILDREN PRESENTING WITH THESE ACUTE PAIN CRISES. THESE EVIDENCE BASED GUIDELINES ARE INFREQUENTLY FOLLOWED, RESULTING IN INCREASED PAIN AND HOSPITALIZATIONS. IN ADDITIONAL TO OTHER BARRIERS TO FOLLOWING THE GUIDELINE, STRUCTURAL RACISM HAS BEEN PROPOSED AS A SIGNIFICANT CONTRIBUTOR AND THE NEW ENGLAND JOURNAL OF MEDICINE RECENTLY CALLED FOR THE INSTITUTION OF SCD- SPECIFIC PAIN MANAGEMENT PROTOCOLS TO COMBAT STRUCTURAL RACISM AND REDUCE TIME TO OPIOID ADMINISTRATION. OUR LONG-TERM GOAL IS TO IMPROVE THE CARE AND HEALTH OUTCOMES OF CHILDREN WITH ACUTE PAINFUL VASO-OCCLUSIVE CRISIS TREATED IN THE EMERGENCY DEPARTMENT. OUR OVERALL AIM IS TO TEST A CARE PATHWAY USING MULTIFACETED IMPLEMENTATION STRATEGIES TO INCREASE GUIDELINE ADHERENT CARE FOR CHILDREN IN THE EMERGENCY DEPARTMENT WITH ACUTE PAINFUL VASO-OCCLUSIVE CRISIS. OUR PRIMARY AIMS ARE: 1) TO COMPARE THE PRIMARY IMPLEMENTATION OUTCOMES OF REACH, ADOPTION, AND IMPLEMENTATION FOR THE CARE PATHWAY FOR TREATMENT OF CHILDREN WITH ACUTE PAINFUL VASO- OCCLUSIVE CRISIS IN THE EMERGENCY DEPARTMENT, BETWEEN CONTROL AND INTERVENTION GROUPS AND 2) TO COMPARE THE PRIMARY CLINICAL OUTCOMES OF GUIDELINE ADHERENT CARE FOR OPIOID DOSE TIMING, HOSPITALIZATION RATES, AND PAIN SCORES FOR THE CARE PATHWAY FOR THE TREATMENT OF CHILDREN WITH ACUTE PAINFUL VASO-OCCLUSIVE CRISES IN THE EMERGENCY DEPARTMENT BETWEEN CONTROL AND INTERVENTION GROUPS. WE WILL TEST THESE AIMS USING A RANDOMIZED, MULTICENTER STEPPED WEDGE DESIGN TO CONDUCT A TYPE III HYBRID EFFECTIVENESS-IMPLEMENTATION TRIAL OF THE CARE PATHWAY. OUR PROPOSAL WILL INSTITUTE THE CARE PATHWAY ACROSS SEVEN EMERGENCY DEPARTMENTS WITH THE GOAL OF IMPROVING GUIDELINE ADHERENT CARE FOR CHILDREN WITH SCD PRESENTING WITH AN ACUTE PAIN CRISIS, THEREBY IMPROVING PAIN, DECREASING HOSPITALIZATIONS AND IMPROVING QUALITY OF LIFE FOR THIS VULNERABLE POPULATION.

NATIONAL FIRE SERVICE SURVIVORS SUPPORT PROGRAM

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

IMPROVING MEDICATION ADHERENCE WITH TELEHEALTHCARE MEDICATION THERAPY MANAGEMENT TO CHANGE HEALTH OUTCOMES IN ADOLESCENTS AND YOUNG ADULTS WITH ASTHMA (MATCH) ADMINISTRATIVE SUPPLEMENT

HEALTH CARE INNOVATION CHALLENGE

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

MAINTENANCE OF HEALTH CARE PROVIDERS' CLINICAL PROFICIENCY: TRANSDISCIPLINARY ANALYSIS, MODELING AND INTERVENTION

A RANDOMIZED CONTROLLED TRIAL OF ESCCIP: AN EHEALTH PSYCHOSOCIAL INTERVENTION FOR ENGLISH AND SPANISH SPEAKING PARENTS OF CHILDREN WITH CANCER - THE PSYCHOSOCIAL NEEDS AND RISKS OF CHILDREN WITH CANCER AND THEIR FAMILIES ARE WELL-DOCUMENTED IN THE LITERATURE, INCLUDING THE INCREASED RISK OF PARENTAL DISTRESS, POSTTRAUMATIC STRESS, AND ANXIETY. THERE IS A CRITICAL NEED TO PROVIDE EVIDENCE-BASED PSYCHOSOCIAL CARE TO PARENTS AND CAREGIVERS OF CHILDREN WITH CANCER (PCCC), ALTHOUGH MANY CHALLENGES EXIST REGARDING IN-PERSON INTERVENTION DELIVERY. EHEALTH INTERVENTIONS REPRESENT AN EXCITING POTENTIAL OPPORTUNITY TO ADDRESS MANY OF THE BARRIERS TO IN-PERSON INTERVENTION DELIVERY IN THIS POPULATION, BUT ARE NOT YET WIDELY UTILIZED IN PEDIATRIC PSYCHOSOCIAL CANCER CARE. THE COVID-19 PANDEMIC HAS FURTHER ILLUMINATED THE NEED FOR FLEXIBLE, ACCEPTABLE, AND ACCESSIBLE EHEALTH PSYCHOSOCIAL INTERVENTIONS. THE ELECTRONIC SURVIVING CANCER COMPETENTLY INTERVENTION PROGRAM (ESCCIP) IS AN INNOVATIVE EHEALTH INTERVENTION FOR PCCC, DELIVERED THROUGH A COMBINATION OF SELF-GUIDED INTERACTIVE ONLINE CONTENT AND TELEHEALTH FOLLOW-UP WITH A THERAPIST. ESCCIP AIMS TO DECREASE SYMPTOMS OF ACUTE DISTRESS, ANXIETY, AND POSTTRAUMATIC STRESS WHILE IMPROVING COPING ABILITIES BY DELIVERING EVIDENCE-BASED THERAPEUTIC CONTENT THROUGH A FLEXIBLE, EASILY ACCESSIBLE EHEALTH TOOL. THE INTERVENTION IS DELIVERED TO ONE OR TWO PCCC PER FAMILY, BUT CONTENT IS DESIGNED TO APPLY TO THE WHOLE FAMILY SYSTEM. ESCCIP IS GROUNDED IN PRINCIPLES OF COGNITIVE-BEHAVIORAL AND FAMILY SYSTEMS THERAPY AND IS ADAPTED FROM TWO EFFICACIOUS IN-PERSON INTERVENTIONS FOR CAREGIVERS OF CHILDREN WITH CANCER, THE SURVIVING CANCER COMPETENTLY INTERVENTION PROGRAM (SCCIP) AND THE SURVIVING CANCER COMPETENTLY INTERVENTION PROGRAM – NEWLY DIAGNOSED (SCCIP-ND). ESSCIP HAS BEEN RIGOROUSLY DEVELOPED THROUGH A STAKEHOLDER-ENGAGED DEVELOPMENT PROCESS INVOLVING CLOSE COLLABORATION WITH PCCC, CONTENT EXPERTS IN PEDIATRIC ONCOLOGY AND EHEALTH, AND WEB DESIGN AND DEVELOPMENT EXPERTS. A SPANISH LANGUAGE ADAPTATION OF ESCCIP, EL PROGRAMA ELECTRONICO DE INTERVENCION PARA SUPERAR CANCER COMPETENTEMENTE (ESCCIP-SP), HAS RECENTLY BEEN DEVELOPED FOLLOWING A RIGOROUS PROCESS AND IS NOW READY FOR TESTING AS WELL. THE SELF-GUIDED ONLINE MODULES OF ESCCIP/ESCCIP-SP FEATURE A MIX OF DIDACTIC VIDEO CONTENT, NOVEL MULTIFAMILY VIDEO DISCUSSION GROUPS FEATURING PARENTS OF CHILDREN WITH CANCER, AND HANDS-ON INTERACTIVE ACTIVITIES. PILOT TESTING IS CURRENTLY UNDERWAY WITH PROMISING INITIAL RESULTS. THE OBJECTIVE OF THE PROPOSED STUDY IS TO TEST ESCCIP/ESCCIP-SP IN A RIGOROUS, MULTISITE RCT COMPARED TO AN EDUCATION CONTROL CONDITION. THE PRIMARY STUDY ENDPOINT IS A REDUCTION IN ACUTE DISTRESS FROM BASELINE TO POST-INTERVENTION, WITH SECONDARY ENDPOINTS FOCUSED ON REDUCTIONS IN SYMPTOMS OF POSTTRAUMATIC STRESS AND ANXIETY ,AND IMPROVEMENTS IN COPING SELF- EFFICACY AND COGNITIVE COPING. DATA WILL BE COLLECTED AT THREE TIMEPOINTS (BASELINE, POST-INTERVENTION, AND THREE- MONTH FOLLOW-UP). AN ADDITIONAL, EXPLORATORY AIM WILL BE FOCUSED ON IMPLEMENTATION STRATEGIES AND POTENTIAL COSTS AND COST-SAVINGS OF ESCCIP/ESCCIP-SP, LAYING THE GROUNDWORK FOR FUTURE TRIALS FOCUSED ON DISSEMINATION AND IMPLEMENTATION, STEPPED-CARE MODELS, AND INTERVENTION REFINEMENT.

REMEDY TO DIABETES DISTRESS (R2D2): A SCALABLE SCREEN TO TREAT PROGRAM FOR SCHOOL-AGE FAMILIES

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

BEHAVIORAL HEALTH WORKFORCE EDUCATION AND TRAINING (BHWET) PROGRAM

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

HEALTHY MARRIAGE DEMONSTRATION GRANTS: PRIORITY AREA 2

NON-INVASIVE FUNCTIONAL ASSESSMENT AND PATHOGENESIS OF MORQUIO A - 7. PROJECT SUMMARY/ABSTRACT MUCOPOLYSACCHARIDOSIS IVA (MPS IVA, MORQUIO A DISEASE) IS A RARE AUTOSOMAL RECESSIVE DISORDER CAUSED BY A DEFICIENCY OF THE LYSOSOMAL ENZYME, N-ACETYLGALACTOSAMINE 6-SULFATE SULFATASE (GALNS). GALNS CATALYZES THE DEGRADATION OF THE GLYCOSAMINOGLYCANS: KERATAN SULFATE (KS) AND CHONDROITIN-6-SULFATE (C6S). MPS IVA PATIENTS DEVELOP A CHARACTERISTIC SKELETAL DYSPLASIA DUE TO THE PROGRESSIVE STORAGE OF KS AND C6S. PATIENTS APPEAR HEALTHY AT BIRTH, ALTHOUGH SOME PATIENTS PRESENT WITH ABNORMAL SKELETAL DYSPLASIA EVEN AT BIRTH. PATIENTS USUALLY COME TO MEDICAL ATTENTION WITHIN TWO YEARS OF LIFE BECAUSE OF SHORT TRUNK DWARFISM, ODONTOID HYPOPLASIA, PECTUS CARINATUM, KYPHOSIS, GENU VALGUM, OR HYPERMOBILE JOINTS. PATIENTS WITH SEVERE PHENOTYPE OFTEN DO NOT SURVIVE BEYOND A FEW DECADES OF LIFE BECAUSE OF CERVICAL INSTABILITY/STENOSIS, TRACHEAL OBSTRUCTION, AND CARDIOPULMONARY COMPROMISE. PATIENTS REQUIRE MULTIPLE ORTHOPEDIC SURGERIES (CERVICAL DECOMPRESSION/FUSION, OSTEOTOMY, HIP RECONSTRUCTION AND REPLACEMENT, ETC.) THROUGHOUT THEIR LIFETIME. ENZYME REPLACEMENT THERAPY AND HEMATOPOIETIC STEM CELL THERAPY ARE AVAILABLE CLINICALLY. GENE THERAPY AND ENZYME DEGRADATION SUBSTRATE THERAPY ARE UNDER DEVELOPMENT. IN 1998, WE BEGAN COLLECTING MEDICAL INFORMATION FROM PATIENTS IN THE REGISTRY DATABASE. THE DATABASE CONTAINS AROUND 400 PATIENTS AND HAS ESTABLISHED A GROWTH CHART THAT INDICATES MARKED POOR GROWTH WITH THE IMBALANCE AND CONSEQUENT POOR HEALTH IN MPS IVA. HOWEVER, SINCE THESE DATA ARE BASED ON RESPONSES TO A SELF-COMPLETION QUESTIONNAIRE, THERE ARE INHERENT LIMITATIONS TO THE DATA AND THEIR INTERPRETATION. CURRENT CLINICAL ASSESSMENTS OF THERAPIES FOR MPS IVA PATIENTS ARE A 6-MIN WALK TEST, A 3-MIN STAIR CLIMB TEST, AND FORCED PULMONARY FUNCTION TEST. THESE ENDURANCE TESTS ARE DIFFICULT FOR SMALL CHILDREN, PATIENTS IN WHEELCHAIRS, AND PATIENTS UNDERGOING SURGICAL PROCEDURES. METHODS USED TO ASSESS SKELETAL DYSPLASIA DISORDERS CAN BE EXPENSIVE, TIME-CONSUMING, AND EXHAUSTING FOR THE PATIENTS. BETTER METHODS FOR ASSESSMENT, INCLUDING IN-HOME EVALUATIONS, ARE NEEDED TO EVALUATE CLINICAL EFFICACY AND TO PROVIDE OPTIMAL CLINICAL TREATMENTS FOR MPS IVA PATIENTS. THE PROPOSED PROJECT WILL ASSESS MULTIPLE DOMAINS NON-INVASIVELY, WHICH INCLUDES PULMONARY FUNCTION, BONE MINERALIZATION, GAIT PATTERN, LAXITY OF JOINTS, TRACHEAL FUNCTION, AND HEARING FUNCTION. PROPOSED NON-INVASIVE ASSESSMENTS WILL PROVIDE AN EFFECTIVE AND INNOVATIVE WAY OF CHARACTERIZING THE DISEASE AND EVALUATING THE BENEFITS OF THERAPIES EVEN IN SMALL BUT DIVERSE PATIENT POPULATIONS DESPITE AGE AND PHYSICAL HANDICAPS. OVER 100 MPS IVA PATIENTS HAVE BEEN ENROLLED IN OUR CLINIC, MAKING OUR INSTITUTION THE MOST POPULAR SITE IN THE WORLD AND IDEALLY SUITED TO COMPLETE THIS PROJECT. THE ASSESSMENT PROGRAM WITH NON-INVASIVE METHODS WILL HAVE A SIGNIFICANT IMPACT ON SCIENCE AND HEALTH BY DETAILING THE PROGRESSION AND PATHOGENESIS OF MAJOR SKELETAL PROBLEMS IN MPS IVA. THE OUTCOME OF THIS PROJECT WILL ALSO DEFINE CLINICAL ENDPOINTS TO MEASURE THE EFFICACY OF FUTURE CLINICAL PRODUCTS AND INTERVENTIONS AND MAY APPLY TO OTHER SKELETAL DYSPLASIAS. 1

HEALTH INFORMATION, EDUCATION, AND PROMOTION FOR THE PREVENTION OF COMPLICATIONS IN HEMOPHILIA AND BLEEDING DISORDERS IN WOMEN.

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

USE OF CONTINUOUS GLUCOSE SENSORS IN ADOLESCENTS WITH INADEQUATE DIABETIC CONTROL

ADVANCED NURSING EDUCATION- NURSE PRACTITIONER RESIDENCY FELLOWSHIP PROGRAM

EVALUATION OF HEALTH PROMOTION AND PREVENTION PROGRAMS FOR BLOOD DISORDERS

HOME VIDEO-BASED TELEMEDICINE TO REDUCE HYPOGLYCEMIA FEAR IN PARENTS OF YOUNG CHILDREN

A CLUSTER RANDOMIZED CLINICAL TRIAL OF UMBILICAL CORD MILKING TO IMPROVE SHORT AND LONG-TERM OUTCOMES IN NEONATES WHO ARE NON-VIGOROUS AT BIRTH - PROJECT SUMMARY AT BIRTH, IT IS CRITICAL THAT AN INFANT BEGINS BREATHING QUICKLY. THE INFANT HAS TO SWITCH FROM RELYING ON THE PLACENTA FOR OXYGEN TO USING ITS LUNGS FOR THE FIRST TIME. WORLDWIDE EACH YEAR, 10 MILLION BABIES DO NOT BREATHE IMMEDIATELY AT BIRTH, AND APPROXIMATELY ONE MILLION BABIES DIE ANNUALLY IN LOW AND MIDDLE-INCOME COUNTRIES DUE TO A BRAIN INJURY CAUSED BY INADEQUATE BLOOD FLOW AND OXYGEN DELIVERY TO THE NEONATAL BRAIN, A CONDITION KNOWN AS HYPOXIC ISCHEMIC ENCEPHALOPATHY (HIE). THE USUAL PRACTICE FOR INFANTS WHO NEED RESUSCITATION IS TO IMMEDIATELY CLAMP THE UMBILICAL CORD. ANIMAL STUDIES SHOW THAT CLAMPING THE CORD BEFORE THE BABY BREATHES CAN CAUSE THE HEART BEAT TO SLOW AND CAN DECREASE THE AMOUNT OF BLOOD BEING PUMPED OUT OF THE HEART EACH MINUTE. WE PROPOSE A STUDY TO SEE IF UMBILICAL CORD MILKING (UCM) FOR THOSE INFANTS WHO NEED RESUSCITATION IS BETTER THAN IMMEDIATELY CLAMPING AND CUTTING THE UMBILICAL CORD AT BIRTH. WE WONDER IF IT WILL REDUCE DEATH AND/OR HIE. IN ADDITION, IT MAY REDUCE DEVELOPMENTAL PROBLEMS IN SURVIVORS BY TWO YEARS OF AGE. THIS STUDY IS IMPORTANT BECAUSE WHEN THERE IS NEED FOR RESUSCITATION, NEITHER UCM OR DELAYED CORD CLAMPING, ARE RECOMMENDED BY NATIONAL AND INTERNATIONAL ORGANIZATIONS DUE TO LACK OF EVIDENCE. YET, SEVERAL LARGE STUDIES FROMAROUND THE WORLD HAVE IDENTIFIED THAT INFANTS NEEDING RESUSCITATION ARE MORE LIKELY TO DIE OR DEVELOP CONDITIONS SUCH AS CEREBRAL PALSY, AUTISM AND OTHER DEVELOPMENTAL PROBLEMS. THE LARGE AMOUNT OF FETAL BLOOD LEFT IN THE PLACENTA AFTER IMMEDIATE CORD CLAMPING MEANS THAT THE BABY GETS LESS BLOOD FOR THE BRAIN, LUNGS, AND HEART, WHICH CAN CONTRIBUTE, TO BRAIN INJURY AND EVEN DEATH. CORD MILKING AT BIRTH MAY HELP TO PROTECT THESE INFANTS BY INCREASING THE TRANSFER OF BLOOD VOLUME. OUR PRIOR WORK HAS SHOWN THAT, COMPARED TO IMMEDIATE CORD CLAMPING, UCM RESULTS IN BETTER HEART RATE, BLOOD PRESSURE, LESS EARLY ANEMIA, AND MORE OXYGEN IN THE BRAIN. NO HARM FROM UCM HAS BEEN NOTED IN TERM INFANTS IN ANY STUDIES. WE WILL USE A DESIGN IN WHICH EACH HOSPITAL WILL BE RANDOMLY ASSIGNED TO USE EITHER IMMEDIATE CORD CLAMPING OR UCM FOR ANY INFANT NEEDING RESUSCITATION OVER A PERIOD OF 6 MONTHS. THEN SITES WILL CHANGE TO THE OTHER METHOD FOR AN ADDITIONAL 6 MONTHS. THIS TRIAL WILL INVOLVE 3442 TERM NEWBORNS WHO ARE DEPRESSED AT BIRTH AT SEVEN (7) HOSPITALS IN INDIA. THIS TRIAL WILL PROVIDE EVIDENCE TO PROMOTE A CHANGE IN GUIDELINES SUPPORTING THE USE OF UCM – A SIMPLE, NO-COST INTERVENTION AS STANDARD OF CARE IN TERM AND NEAR-TERM NEWBORNS NEEDING RESUSCITATION.

COMMUNITY PROJECT FUNDING/CONGRESSIONALLY DIRECTED SPENDING - NON-CONSTRUCTION

STUDY OF CHRONIC FATIGUE SYNDROME USING COMPREHENSIVE MOLECULAR PROFILING WITH NE

EXTRACELLULAR MATRIX STRUCTURE AND FUNCTION IN DIABETIC WOUND HEALING

WELLNESS ACHIEVED THROUGH CHANGING HABITS (WATCH): AN ACCEPTANCE-BASED HEALTHY LIFESTYLE INTERVENTION FOR DIVERSE ADOLESCENTS - ABSTRACT OVERWEIGHT/OBESITY (OW/OB) AFFECTS 14 MILLION ADOLESCENTS IN THE UNITED STATES, DISPROPORTIONATELY AFFECTING GIRLS AND RACIAL/ETHNIC MINORITIES, INCREASING THEIR RISK OF CARDIOVASCULAR DISEASE AND TYPE 2 DIABETES. BEHAVIORAL WEIGHT LOSS INTERVENTIONS ARE THE FOUNDATION OF OBESITY TREATMENT MODALITIES, YET MANY HAVE LED TO LIMITED WEIGHT LOSS AND WEIGHT REGAIN IS COMMON. LIMITED SUCCESS IN ADOLESCENT WEIGHT LOSS INTERVENTIONS MAY BE ATTRIBUTED PRIMARILY TO ADOLESCENTS’ LACK OF SELF-REGULATION SKILLS, WHICH ARE ESSENTIAL FOR ADHERING TO DIET AND PHYSICAL ACTIVITY GOALS. THERE IS A CRITICAL NEED FOR DEVELOPMENT OF INTERVENTIONS THAT TEACH SELF-REGULATION SKILLS TO ADOLESCENTS IN ORDER TO ADAPT TO PERVASIVE BIOLOGICAL AND ENVIRONMENTAL CUES THAT ARE OFTEN EXPERIENCED DURING WEIGHT LOSS. AN INNOVATIVE BEHAVIORAL TREATMENT, ACCEPTANCE-BASED THERAPY (ABT), FOCUSES ON SELF- REGULATION SKILLS AND INCREASING MINDFULNESS AND TOLERANCE OF NEGATIVE OR UNCOMFORTABLE EMOTIONS. ABT HAS DEMONSTRATED STRONG EVIDENCE AS AN EFFECTIVE WEIGHT LOSS STRATEGY IN ADULTS. OUR GROUP UTILIZED AN ADOLESCENT- ENGAGED APPROACH TO DEVELOP, IMPLEMENT, AND TEST THE FEASIBILITY AND ACCEPTABILITY OF AN ABT WEIGHT LOSS INTERVENTION FOR ADOLESCENT GIRLS WITH OW/OB. THE FEASIBILITY STUDY WAS A 6-MONTH ABT BEHAVIORAL WEIGHT LOSS INTERVENTION COMPRISED OF 15 IN-PERSON GROUP SESSIONS (90-MINUTES EACH) OVER A 6-MONTH PERIOD LED BY AN INSTRUCTOR TRAINED IN ABT. THE FEASIBILITY STUDY DEMONSTRATED STRONG ACCEPTABILITY AMONG ADOLESCENT GIRLS WITH OW/OB. THE OBJECTIVE OF THIS STUDY, CALLED THE WELLNESS ACHIEVED THROUGH CHANGING HABITS (WATCH) TRIAL, IS TO TEST THE EFFICACY OF AN ABT INTERVENTION VERSUS AN ENHANCED CARE (EC) INTERVENTION ON MARKERS OF CARDIOMETABOLIC HEALTH, HEALTH RELATED BEHAVIORS, AND PSYCHOLOGICAL FACTORS. DURING THE R61 PHASE (YEAR ONE), WE WILL FINALIZE ALL WATCH POLICIES AND PROCEDURES INCLUDING CLINICAL TRIALS REGISTRATION, MANUAL OF OPERATIONS, IRB APPROVALS, CONVENING THE DSMB BOARD, AND BEGIN RECRUITMENT. WE WILL ALSO SUBMIT A NIH PROGRESS REPORT ON PARTICIPANT RECRUITMENT, DEMOGRAPHICS, AND INTERVENTION FIDELITY. DURING THE R33 PHASE (YEARS 2-5), WE PROPOSE A RANDOMIZED CONTROLLED TRIAL OF 148 ADOLESCENT GIRLS (≥40% RACIAL/ETHNIC MINORITIES) WITH OW/OB TO TEST THE HYPOTHESIS THAT THOSE RANDOMIZED TO ABT (VS. EC) WILL HAVE SIGNIFICANTLY DECREASED BMI Z-SCORE (PRIMARY OUTCOME) AND BODY FAT, AND IMPROVED BLOOD PRESSURE AND BLOOD LIPIDS AT POST-TREATMENT, 6-MONTH FOLLOW-UP, AND 12-MONTH FOLLOW-UP. WE ALSO HYPOTHESIZE THAT RELATIVE TO EC INTERVENTION, ABT WILL SIGNIFICANTLY IMPROVE HEALTH-RELATED BEHAVIORS AND PSYCHOLOGICAL FACTORS. AS AN EXPLORATORY AIM, WE WILL EXAMINE THE EXTENT TO WHICH ABT’S EFFECTS ON WEIGHT AND BODY COMPOSITION ARE MEDIATED BY IMPROVEMENTS IN BEHAVIORAL AND PSYCHOLOGICAL FACTORS, AND IDENTIFY KEY MODERATORS OF ABT INTERVENTION EFFECTS INCLUDING BASELINE DEMOGRAPHIC AND PSYCHOLOGICAL FACTORS. THIS STUDY WILL YIELD A NOVEL, OBESITY INTERVENTION TAILORED TO THE NEEDS OF ADOLESCENTS WITH OW/OB BY DEVELOPING SELF-REGULATION SKILLS AND PROVIDING TOOLS TO PROMOTE CARDIOMETABOLIC HEALTH.

DEVELOPING A COORDINATED SYSTEM TO IDENTIFY AND SUPPORT STUDENTS EXPERIENCING HOMELESSNESS

GENETIC BASIS OF CRYPTORCHIDISM

USE OF MOBILE DEVICES AND THE INTERNET TO STREAMLINE AN ASTHMA CLINICAL TRIAL (MI

GROUP WELL CHILD CARE INTERVENTION FOR INFANTS OF MOTHERS IN TREATMENT FOR OPIOID USE DISORDER

NATIONAL FIRE SERVICE SURVIVORS SUPPORT PROGRAMS

EVICTION PROTECTION GRANT PROGRAM

COMPREHENSIVE SUPPORT SERVICES FOR FAMILIES AFFECTED BY SUBSTANCE ABUSE AND/OR HIV/AIDS

TRANSDISCIPLINARY VERSUS USUAL CARE FOR TYPE 1 DIABETES IN ADOLESCENCE

DELAWARE SMALL COMMUNITIES

TARGETING MECHANOSIGNALING IN PEDIATRIC BRAIN CANCER - PROJECT SUMMARY DESPITE MULTIMODAL TREATMENT, CANCER-RELATED MORTALITY IN PEDIATRIC BRAIN CANCERS REMAINS HIGH AND SURVIVORS OFTEN SUFFER FROM SERIOUS, LIFE-LONG, THERAPY-RELATED SIDE EFFECTS AND SECONDARY MALIGNANCIES. THERE IS A CLEAR NEED FOR MORE EFFECTIVE THERAPIES, INCLUDING FOR THE MOST COMMON MALIGNANT PEDIATRIC BRAIN CANCER MEDULLO- BLASTOMA, A TUMOR THAT ORIGINATES IN THE CEREBELLUM. MECHANOSENSITIVE SIGNALING PATHWAYS HAVE EMERGED AS POWERFUL TARGETS IN CANCER DRUG DISCOVERY, INCLUDING FOR THE TREATMENT OF MEDULLOBLASTOMA. YET, WHEN TARGETING SIGNALING PATHWAYS THAT SERVE AS SENSORS FOR A TUMOR CELL'S MICROENVIRONMENT, TRADITIONAL MONOLAYER CULTURES THAT ARE MOST COMMONLY USED IN CELL-BASED HIGH-THROUGHPUT DRUG DISCOVERY, DO NOT ACCURATELY RECAPITULATE CRITICAL ENVIRONMENTAL CUES SUCH AS TISSUE STIFFNESS OR EXTRACELLULAR MATRIX COMPOSITION. DRUG DISCOVERY AIMED AT KEY MEDIATORS OF MECHANOSENSITIVE SIGNALING REQUIRE CELL-BASED SCREENING ASSAYS IN A CELL CULTURE ENVIRONMENT THAT MORE CLOSELY RESEMBLES IN VIVO TISSUE. THREE-DIMENSIONAL (3D) CELL CULTURES HAVE MOVED TO THE FOREFRONT IN THE EFFORT TO CREATE MORE IN VIVO-LIKE EXPERIMENTAL ENVIRONMENTS THAT CAN MIMIC INTRICATE CELL-CELL AND CELL-EXTRACELLULAR MATRIX INTERACTIONS FOUND IN TISSUE. OUR PREVIOUS COLLABORATIVE WORK DEMONSTRATED THE SUITABILITY OF THE SELF- ASSEMBLING AND HYDROGELATING MAX8 SS-HAIRPIN PEPTIDE AS A 3D CELL CULTURE SCAFFOLD FOR AUTOMATED HIGH- THROUGHPUT DRUG DISCOVERY. WE DEMONSTRATED THAT MAX8 COMBINES BIOCOMPATIBILITY AND TUNABILITY IN FUNCTION AND STIFFNESS WITH UNIQUE MECHANICAL PROPERTIES (E.G., SHEAR-THINNING, INJECTABLE SOLID WITH IMMEDIATE REHEALING) THAT ALLOW AUTOMATIC HANDLING WITH STANDARD HIGH-THROUGHPUT SCREENING (HTS) LIQUID HANDLING EQUIPMENT COMMONLY FOUND IN A DRUG DISCOVERY LABORATORY. THE PRIMARY OBJECTIVE OF THIS PROPOSAL IS TO USE THE VERSATILE AND TUNABLE MAX8 PEPTIDE TO DEVELOP A 3D CELL CULTURE SCAFFOLD THAT MIMICS KEY FEATURES OF BRAIN EXTRACELLULAR MATRIX WHILE ALSO RETAINING MATERIAL PROPERTIES CRITICAL FOR USE WITH AUTOMATED LIQUID HANDLING EQUIPMENT, ALL FOR A HIGH- THROUGHPUT DRUG DISCOVERY APPROACH TARGETING MECHANOSIGNALING. AIM 1 WILL ESTABLISH A TARGETED ASSAY FOR A WELL- CHARACTERIZED MECHANOSENSITIVE SIGNALING PATHWAY THAT IS COMPATIBLE WITH MAX8 PEPTIDE HYDROGEL SCAFFOLD- BASED 3D CELL CULTURES IN A HIGH THROUGHPUT-COMPATIBLE SETUP. AIM 2 WILL EXAMINE HOW TUNING HYDROGEL STIFFNESS AND PEPTIDE FUNCTIONALIZATION WITH BRAIN EXTRACELLULAR MATRIX COMPONENTS AFFECTS ASSAY PERFORMANCE AND PHENOTYPE OF CEREBELLAR NEURONS AND PEDIATRIC BRAIN CANCER CELLS. AIM 3 WILL VALIDATE THE NEWLY DEVELOPED ASSAY PLATFORM BY PERFORMING A PILOT DRUG SCREEN AND IN VIVO EFFICACY TESTING OF CANDIDATE COMPOUNDS. THE OUTCOME OF THESE STUDIES WILL BE A 3D CELL CULTURE PLATFORM THAT WILL PROVIDE FUNDAMENTAL UNDERSTANDING OF HOW EXTRACELLULAR MATRIX COMPOSITION AND TISSUE STIFFNESS REGULATE MECHANOSIGNALING IN BOTH NORMAL NEURONS AND PEDIATRIC BRAIN CANCER CELLS. ADDITIONALLY, THESE STUDIES WILL LAY THE FOUNDATION FOR A FUTURE HIGH-THROUGHPUT DRUG DISCOVERY APPROACH TARGETING MECHANOSIGNALING IN SCAFFOLD-BASED 3D CULTURES OPTIMIZED FOR PEDIATRIC BRAIN TUMORS.

A CROWDSOURCED SOCIAL MEDIA PORTAL FOR PARENTS OF VERY YOUNG CHILDREN WITH TYPE 1 DIABETES

IMPROVING ACCESS TO MENTAL AND BEHAVIORAL HEALTH SERVICES FOR DELAWARE'S CHILDREN AND YOUTH - THE PROJECT WILL SUPPORT A TWO YEAR TRAINING FELLOWSHIP PROGRAM FOR TEN PRE LICENSED, MASTER'S TRAINED THERAPISTS. THE PROJECT GOAL IS TO INCREASE ACCESS TO PEDIATRIC MENTAL AND BEHAVIORAL HEALTH SERVICES FOR DELAWARE CHILDREN AND YOUTH WITH A FOCUS ON INCREASING WORKFORCE DIVERSITY AND BETTER MEETING THE NEEDS OF UNDERSERVED COMMUNITIES. OUR PROJECT WILL RECRUIT MINORITIZED TRAINEES, WITH A GOAL OF INCLUDING TWENTY PERCENT SPANISH SPEAKING THERAPISTS. ALL SELECTED THERAPISTS WILL RECEIVE TRAINING IN EVIDENCE-BASED SCREENING, PREVENTION AND TREATMENT, DEVELOPMENTAL DISABILITIES, INTEGRATED PRIMARY CARE AND SCHOOL-BASED HEALTHCARE AND ACUTE RISK ASSESSMENT AND CRISIS MANAGEMENT. THEY WILL PROVIDE CLINICAL CARE SUPERVISED BY LICENSED MENTAL HEALTH PROVIDERS THAT WILL SUPPLY THE HOURS REQUIRED TO OBTAIN INDEPENDENT LICENSURE. SAMHSA CDS FUNDS WILL SUPPORT YEAR 1. NEMOURS CHILDREN'S WILL SUPPORT YEAR 2. PROJECT NAME: IMPROVING ACCESS TO MENTAL AND BEHAVIORAL HEALTH SERVICES FOR DELAWARE'S CHILDREN AND YOUTH POPULATION TO BE SERVED. THE PROJECT WILL TRAIN AND EMPLOY TEN MASTER'S LEVEL THERAPISTS TO ADDRESS THE NEED FOR MENTAL AND BEHAVIORAL HEALTH SERVICES AMONG DELAWARE'S CHILDREN AND YOUTH. FOCUS WILL BE ON TRAINEES FROM MINORITIZED BACKGROUNDS, WITH A GOAL OF INCLUDING 20% SPANISH SPEAKING. THE PATIENTS SERVED WILL BE PRIMARILY FROM NEW CASTLE COUNTY, DELAWARE WHERE 15.6% OF HOUSEHOLDS SPEAK A LANGUAGE OTHER THAN ENGLISH AT HOME AND 45% OF THE RESIDENTS ARE NON-WHITE. BOTH INDICATE A NEED FOR BILINGUAL CLINICIANS AND CLINICIANS OF COLOR, REPRESENTATIVE OF AND RESPONSIVE TO THE DIVERSE NEEDS OF DELAWAREANS. STRATEGIES AND INTERVENTIONS: TIS PROJECT WILL INCREASE AND DIVERSIFY DELAWARE'S PEDIATRIC BEHAVIORAL HEALTH WORKFORCE; PROVIDE HIGHLY SPECIALIZED, EVIDENCE BASED TRAINING AND SUPERVISION FOR MASTER'S LEVEL THERAPISTS; MEET THE NEED FOR PEDIATRIC MENTAL AND BEHAVIORAL HEALTH SERVICES IN DELAWARE; SUPPORT INCREASED DIVERSITY IN DELAWARE'S PEDIATRIC BEHAVIORAL HEALTH WORKFORCE, INCLUDING INCREASING ACCESS TO BILINGUAL PROVIDERS AND CULTURALLY HUMBLE AND RELEVANT CARE. PROJECT GOALS AND OBJECTIVES: GOAL 1: INCREASE THE NUMBER OF LICENSED BEHAVIORAL HEALTH PROVIDERS ACROSS THE CONTINUUM OF BEHAVIORAL HEALTH TRAINED TO WORK WITH CHILDREN AND YOUTH. GOAL 2: INCREASE ACCESS TO PROVIDERS COMPETENT TO OFFER EVIDENCE-BASED, TRAUMA INFORMED, CULTURALLY RELEVANT CARE FOR CHILDREN AND YOUTH. GOAL 3: INCREASE COLLABORATIVE COMMUNICATION AMONG TRAINEES AND COMMUNITY BEHAVIORAL HEALTH PROVIDERS ABOUT BEHAVIORAL HEALTH RESOURCES FOR CHILDREN, YOUTH AND FAMILIES. GOAL 4: INCREASE NUMBER OF PROVIDERS WITH COMPETENCY FOR SUICIDE ASSESSMENT AND MANAGEMENT. GOAL 5: INCREASE KNOWLEDGE OF SYMPTOMS, SCREENING PROCESSES, AND EFFECTIVE SUPPORTS FOR AUTISTIC YOUTH. GOAL 6: IMPROVE SUCCESSFUL COMPLETION OF LICENSURE EXAM-75% OF TRAINEES WILL PASS ON FIRST TRY. GOAL 7: IMPROVE CULTURAL HUMILITY OF BEHAVIORAL HEALTH PROVIDERS. GOAL 8: INCREASE THOSE TRAINED IN SCHOOL BASED BEHAVIORAL HEALTH. NUMBER OF PEOPLE TO BE SERVED: WE WILL PROVIDE DIDACTIC EXPERIENTIAL TRAINING AND CLINICAL SUPERVISION FOR 10 PRE LICENSED, MASTER'S LEVEL THERAPISTS; WE WILL OFFER 6 COMMUNITY TRAININGS TO 3 COMMUNITY AGENCIES WHO EMPLOY OR WITH SPANISH SPEAKING OR MINORITIZED CHILDREN AND YOUTH, ALLOWING US TO PROVIDE TRAINING TO AN ADDITIONAL 10 COMMUNITY THERAPISTS.

ASSISTANCE TO FIREFIGHTERS GRANT

ASSISTANCE TO FIREFIGHTERS GRANT

FIRE PREVENTION AND SAFETY

IRONBOND ? FORGING STRONGER FATHERS, FAMILIES, AND FUTURES - IRONBOND – FORGING STRONGER FATHERS, FAMILIES, AND FUTURES

ASSISTANCE TO FIREFIGHTERS GRANT

FIRE PREVENTION AND SAFETY

ASSISTANCE TO FIREFIGHTERS GRANT

FIRE PREVENTION AND SAFETY

FIRE PREVENTION AND SAFETY

FIRE PREVENTION AND SAFETY

ASSISTANCE TO FIREFIGHTERS GRANT

ASSISTANCE TO FIREFIGHTERS GRANT

THE ROLE OF E3-UBIQUITIN LIGASE COMPLEX IN GENITOURINARY TRACT DEVELOPMENT AND FUNCTION.

ASSISTANCE TO FIREFIGHTERS GRANT

ASSISTANCE TO FIREFIGHTERS GRANT

ASSISTANCE TO FIREFIGHTERS GRANT

ASSISTANCE TO FIREFIGHTERS GRANT

ASSISTANCE TO FIREFIGHTERS GRANT

ASSISTANCE TO FIREFIGHTERS GRANT

CELL INSTRUCTIVE MATERIALS FOR ENGINEERING VASCULAR GRAFTS

COGNITIVE, STRUCTURAL AND FUNCTIONAL IMPACT OF NEW ONSET TYPE 1 DIABETES ON THE BRAIN OF YOUNG CHILDREN: UNDERSTANDING RISKS AND PROTECTIVE FACTORS - AN INCREASING BODY OF DATA SHOW THE BRAIN IS A TARGET OF DIABETES COMPLICATIONS. WE AND OTHERS HAVE INVESTIGATED THE IMPACT OF TYPE 1 DIABETES (T1D) IN THE DEVELOPING BRAIN IN CHILDREN AS YOUNG AS 4-YEARS OLD. USING STRUCTURAL AND FUNCTIONAL BRAIN MRI, NEUROCOGNITIVE ASSESSMENTS, AND CONTINUOUS GLUCOSE MONITORING (CGM) WE OBSERVED QUANTIFIABLE DIFFERENCES IN GRAY AND WHITE MATTER VOLUME (AND MICROSTRUCTURE) IN CHILDREN WITH T1D COMPARED TO AGE-MATCHED NONDIABETIC CONTROLS, AND MEANINGFUL DIFFERENCES IN WORKING MEMORY, EXECUTIVE FUNCTION SCORES, AND PERFORMANCE IQ. THESE DIFFERENCES WIDENED WHEN CHILDREN WERE FOLLOWED AT 4-TIME POINTS OVER NEARLY 8- YEARS, FINDINGS STRONGLY CORRELATED TO HYPERGLYCEMIA. THIS FUNDING OPPORTUNITY SEEKS TO FURTHER INVESTIGATE NEUROCOGNITIVE AND PSYCHOSOCIAL FUNCTION NOW IN CHILDREN WITH NEW ONSET DIABETES, INCLUDING THOSE OF DIVERSE RACIAL AND SOCIOECONOMIC (SES) BACKGROUNDS. THIS IS TIMELY GIVEN OUR PRELIMINARY DATA RAISE IMPORTANT QUESTIONS AS TO THE IMPACT OF BETTER NORMALIZATION OF BLOOD GLUCOSE USING ADVANCED INSULIN DELIVERY (AID)/CLOSED-LOOP SYSTEMS. WE PROPOSE AN OBSERVATIONAL, LONGITUDINAL STUDY IN A LARGE COHORT OF 4-10-YEAR OLD PREPUBERTAL CHILDREN WITH NEW ONSET T1D (N=525) PRESENTING WITH OR WITHOUT DIABETIC KETOACIDOSIS (DKA), STUDIED WITHIN 4-6 WEEKS OF DIAGNOSIS, COMPARED TO AGE-MATCHED NONDIABETIC CONTROLS (PREFERABLY SIBLINGS AND CLASSMATES) (N=175). PRIMARY AIMS: (1) TO DETERMINE THEIR NEUROCOGNITIVE FUNCTION (PRINCIPAL); (2) TO CORRELATE NEUROCOGNITIVE FUNCTION SCORES WITH METRICS OF DYSGLYCEMIA, AND SEVERITY OF DIABETES AND DKA AT PRESENTATION; (3) TO ASSESS PATIENT/FAMILY REPORTED PERCEPTIONS OF QUALITY OF LIFE, INCLUDING DIABETES DISTRESS AND PSYCHOSOCIAL ASPECTS, IN CHILDREN, AND MOOD IN PARENTS; (4) TO CORRELATE ABOVE AIMS WITH USE OF AID CLOSED-LOOP TECHNOLOGIES; (5) TO ASSESS STRUCTURAL GRAY AND WHITE MATTER VOLUME AND WHITE MATTER MICROSTRUCTURE AND FUNCTIONAL (F)MRI DURING COGNITIVE TASKS (BASELINE & 24-MONTHS). PERTINENT SOCIAL DETERMINANTS OF HEALTH (SDOH) WILL BE COLLECTED, AND ALL OUTCOMES ADJUSTED BY SEX AND SES AND LEVEL OF GLYCEMIA. TO ACCOMPLISH THIS, WE WILL PERFORM STANDARDIZED NEUROCOGNITIVE TESTING USING NIH TOOLBOX, PSYCHOSOCIAL ASSESSMENTS, STRUCTURAL AND FUNCTIONAL MRI USING MULTIMODAL IMAGING, CGM DOWNLOADS AND HBA1C, SDOH DATA COLLECTED USING NIH TOOLBOX PHENX. CHILDREN WILL BE RECRUITED ACROSS 10 CENTERS SELECTED ALONG A BIOSTATISTICAL RESEARCH CORE, IN A NEW NETWORK. CHILDREN WITH T1D WILL BE FOLLOWED QUARTERLY, CGM AND PUMP (IF APPLICABLE) DATA DOWNLOADED, PRINCIPAL ASSESSMENTS DONE AT BASELINE, 12 AND 24-MONTHS. THIS PRINCIPAL INVESTIGATOR, AND THE EXPERIENCED TEAM ASSEMBLED, WOULD BRING CONSIDERABLE EXPERTISE AND STRENGTH TO THE NEW NETWORK, WITH AN OUTSTANDING RECORD OF ACCOMPLISHMENTS STUDYING T1D AND THE BRAIN IN CHILDREN AND WELL-ESTABLISHED CLINICAL AND RESEARCH INFRASTRUCTURE. THIS INNOVATIVE PROPOSAL IS A PROTOTYPE OF THE OBSERVATIONAL STUDY WE CAN PERFORM. RESULTS WILL OFFER CRITICAL INSIGHT ON DEVELOPMENTAL AND COGNITIVE TRAJECTORIES IN YOUNG CHILDREN WITH NEW ONSET T1D, RACIALLY AND SOCIOECONOMICALLY DIVERSE, AND WHETHER BETTER GLYCEMIC CONTROL, INCLUDING EARLY USE OF AID TECHNOLOGY CAN PREVENT OR IMPROVE COGNITIVE OUTCOMES.

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ASSISTANCE TO FIREFIGHTERS GRANT

DLK1 AS A NOVEL TARGET FOR DOWN SYNDROME MYELOID LEUKEMIA - PROJECT SUMMARY DOWN SYNDROME (DS), WITH TRIPLICATION OF CHROMOSOME 21, IS RECOGNIZED AS ONE OF THE MOST IMPORTANT LEUKEMIA-PREDISPOSING SYNDROMES. 1-2% OF DS CHILDREN DEVELOP MYELOID LEUKEMIA (DS-ML) BEFORE AGE 5, WHICH IS PRECEDED BY A PRE-LEUKEMIC PHASE TERMED TRANSIENT ABNORMAL MYELOPOIESIS (TAM). 30% OF TAM CASES PROGRESSING TO DS-ML. ASIDE FROM LOW DOSE CHEMOTHERAPY, THERE ARE NO TREATMENT OPTIONS FOR TAM AND NO PREVENTATIVE MEASURES TO STALL DS-ML ONSET. NEARLY 10-15% OF CHILDREN WITH DS-ML ARE EITHER REFRACTORY TO TREATMENT OR SUFFER EARLY RELAPSE. THESE CHILDREN WITH REFRACTORY DISEASE FACE A DISMAL OUTCOME WITH 3-YEAR EVENT-FREE SURVIVAL LESS THAN 21%. MOREOVER, TREATMENT-RELATED TOXICITY AND MORBIDITY IS A MAJOR CAUSE OF DEATH IN DS-ML PATIENTS. THEREFORE, NOVEL THERAPEUTIC OPTIONS ARE NEEDED FOR THIS RARE DISEASE. BOTH TAM AND DS- ML ARE CHARACTERIZED BY THE PATHOGNOMONIC MUTATION IN THE GENE ENCODING ESSENTIAL HEMATOPOIETIC TRANSCRIPTION FACTOR GATA1, RESULTING IN N-TERMINALLY TRUNCATED MUTANT GATA1 PROTEIN (GATA1S). TRISOMY 21 AND GATA1S ARE SUFFICIENT TO INDUCE TAM, WHILE ADDITIONAL CO-OPERATING MUTATIONS IN GENES SUCH AS STAG2 ARE REQUIRED FOR DS-ML LEUKEMOGENESIS. THE INDIVIDUAL AND SYNERGISTIC CONTRIBUTION OF THESE GENETIC EVENTS TOWARDS DS-ML REFRACTORINESS AND REMODELING THE BONE MARROW MICROENVIRONMENT REMAIN POORLY DEFINED. USING CRISPR/CAS9 MEDIATED GENE TARGETING FOR STEPWISE INTRODUCTION OF GATA1 OR GATA1 AND STAG2 MUTATIONS IN IPSCS WITH TRISOMY 21, WE MODELLED TAM AND DS-ML RESPECTIVELY. WE GENERATED PATIENT-DERIVED XENOGRAFT (PDX) MODELS REPRESENTING REFRACTORY DS-ML. OUR TRANSCRIPTOME ANALYSIS TO IDENTIFY NOVEL DS-ML SPECIFIC CELL SURFACE PROTEINS REVEALED DELTA-LIKE NON-CANONICAL NOTCH LIGAND 1 (DLK1) AS ONE OF THE TOP TARGETS. DLK1 TRANSCRIPT WAS UNDETECTABLE IN NORMAL BONE MARROW SPECIMENS, WHILE IT WAS MORE ABUNDANT IN DS-ML COMPARED TO TAM. ENHANCED EXPRESSION OF DLK1 WAS ALSO DETECTED IN OUR IPSC-GENERATED DS-ML MODELS, BUT NOT IN TAM MODELS. OUR PRELIMINARY DATA SHOWS THAT DLK1 KNOCKOUT IN DS-ML CELL LINE SUPPRESSED PROLIFERATION AND DELAYED ENGRAFTMENT. FURTHERMORE, TARGETING DLK1 VIA AN IMMUNO-CONJUGATE SIGNIFICANTLY REDUCED LEUKEMIC BURDEN AND PROLONGED SURVIVAL IN REFRACTORY DS-ML PDX LINES. THESE RESULTS INDICATE THAT DLK1 MAY PROMOTE DS-ML LEUKEMOGENESIS AND CAN BE USED AS A THERAPEUTIC TARGET. CONSISTENT WITH THE EFFECT OF DLK1 ON THE INHIBITION OF INTERFERON SIGNALING VIA SUPPRESSION OF NOTCH1 ACTIVITY, WE IDENTIFIED THAT DOWNREGULATION OF DLK1 RESULTED IN INCREASED INTERFERON SIGNALING. INTERESTINGLY, WE DEMONSTRATED THAT GATA1S SUPPRESSED INTERFERON SIGNALING VIA DOWNREGULATION OF THE RIG-I PATHWAY IN IPSC-DERIVED TAM AND DS-ML MODELS. EXOGENOUS TREATMENT OF DS-ML CELLS WITH INTERFERON-A RESURRECTED INTERFERON SIGNALING, CONFIRMING THAT THE PATHWAY IS INTACT. THUS, SUPPRESSION OF INTERFERON SIGNALING VIA GATA1S AND/OR DLK1 IS A DS-ML DEPENDENCY THAT CAN BE EXPLOITED THERAPEUTICALLY. UPON STUDY COMPLETION, WE WILL IDENTIFY NOVEL TREATMENT OPTIONS FOR TAM/DS-ML, AND A NEWLY CHARACTERIZED TARGET THAT MAY ALSO BE EXPLOITED IN NON-DS LEUKEMIA.

THE DELAWARE COMPREHENSIVE SICKLE CELL RESEARCH CENTER - PROJECT SUMMARY (OVERALL) THE DELAWARE COMPREHENSIVE SICKLE CELL RESEARCH CENTER (DE SCD COBRE) IS A BIOMEDICAL RESEARCH CENTER OF EXCELLENCE THAT HAS ESTABLISHED ITSELF AS A COMPREHENSIVE CENTER FOR THE CARE OF PEOPLE WITH SICKLE CELL DISEASE. DURING COBRE PHASE 1 AND PHASE 2 FUNDING, THE DE SCD COBRE SUCCESSFULLY DEVELOPED MULTIPLE EARLY CAREER INVESTIGATORS TO COMPLETE TRANSLATIONAL, CLINICAL AND IMPLEMENTATION SCIENCE RESEARCH. THE SUCCESSFUL RECRUITMENT OF SICKLE CELL RESEARCHERS PROVIDED ADDITIONAL EXPERIENCE TO THE CENTER TO FACILITATE THE UTILIZATION OF THE MATRIX MENTORING MODEL FOR DEVELOPMENT OF INVESTIGATORS ACROSS MULTIPLE DISCIPLINES WITH AN INTEREST IN IMPROVING THE CARE OF PEOPLE WITH SICKLE CELL DISEASE. TOTAL FUNDING BOUGHT TO THE STATE OF DELAWARE FROM COBRE PHASE 1 AND PHASE 2 RESEARCH DEVELOPMENT NOW EXCEEDS $69 MILLION, INCLUDING A LARGE PHILANTHROPIC GIFT TO FURTHER STRENGTHEN RESEARCH IN CANCER AND BLOOD DISORDERS AT NEMOURS CHILDREN’S HOSPITAL IN DELAWARE. DURING PHASE 3 FUNDING, WE WILL CONTINUE TO INTEGRATE WITH OTHER INSTITUTIONAL DEVELOPMENT AWARDS (IDEA) STATE PROGRAMS, INCLUDING THE DELAWARE IDEA NETWORK OF BIOMEDICAL RESEARCH EXCELLENCE (INBRE) AND THE DELAWARE ACCEL CLINICAL AND TRANSLATIONAL RESEARCH (CTR) PROGRAM. THE CENTER WILL ALSO CONTINUE TO INTEGRATE WITH THE GROWING RESEARCH INFRASTRUCTURE AT NEMOURS CHILDREN’S HOSPITAL TO HELP FACILITATE SUSTAINABILITY AFTER THE COMPLETION OF COBRE PHASE 3 FUNDING. THE SUCCESSFUL RECRUITMENT AND DEVELOPMENT OF SICKLE CELL RESEARCHERS, CONTINUED ROBUST IMPLEMENTATION OF THE PILOT PROJECT PROGRAM, AND EFFICIENT UTILIZATION OF THE CLINICAL RESEARCH AND DATA INFORMATICS CORE WILL LEAD TO THE FINANCIAL SUSTAINABILITY OF A COMPREHENSIVE SICKLE CELL CENTER THAT BOTH INNOVATES IN SICKLE CELL CARE AND DELIVERS THE HIGHEST QUALITY CARE TO PEOPLE WITH SICKLE CELL DISEASE. CENTRAL TO ALL ASPECTS OF THE DELAWARE SICKLE CELL RESEARCH PROGRAM IS THE OVERARCHING HYPOTHESIS THAT EFFECTIVE MANAGEMENT OF A COMMON, CONGENITAL, MULTI-SYSTEM DISEASE REQUIRES COMPREHENSIVE INVESTIGATIONS SPANNING THE BIOLOGICAL AND MEDICAL FACTORS THAT IMPACT BOTH THE SEVERITY OF THE DISEASE AND THE EFFICACY OF INTERVENTIONS.

MOLECULAR GENETICS OF PELIZAEUS-MERZBACHER DISEASE

RESTORING COGNITIVE FUNCTION THROUGH PRECISION NEUROSTIMULATION: A DISEASE-AGNOSTIC APPROACH BASED ON CONVERGENT HIPPOCAMPAL DYNAMICS. - PROJECT SUMMARY THE HIPPOCAMPUS, A KEY PART OF OUR BRAIN INVOLVED IN MEMORY AND EMOTIONAL REGULATION, OFTEN MALFUNCTIONS IN MANY BRAIN DISORDERS, FROM DEVELOPMENTAL ISSUES LIKE AUTISM TO NEURODEGENERATIVE DISEASES SUCH AS ALZHEIMER’S DISEASE. THIS DYSFUNCTION CAN SEVERELY AFFECT MEMORY, SOCIAL INTERACTIONS, AND OVERALL QUALITY OF LIFE. TRADITIONAL TREATMENTS USUALLY TARGET SPECIFIC DISEASE-RELATED CHANGES AT THE MOLECULAR OR PROTEIN LEVEL BUT HAVE HAD LIMITED SUCCESS. OUR RESEARCH AIMS TO REVOLUTIONIZE THIS APPROACH BY FOCUSING ON THE FUNDAMENTAL BRAIN ACTIVITY PATTERNS OF THE HIPPOCAMPUS. WE PROPOSE THAT BY CORRECTING THESE DISRUPTED ACTIVITY PATTERNS, WE CAN IMPROVE COGNITIVE FUNCTION REGARDLESS OF THE DISORDER’S CAUSE. WE WILL USE SIX MODELS OF THREE COMMON NEUROLOGICAL DISORDERS TO DEFINE SIMILAR ABNORMALITIES IN BRAIN ACTIVITY ACROSS DISEASE GROUPS AND EXAMINE WHETHER BRAIN STIMULATION CAN IMPROVE BOTH DYNAMICS AND PERFORMANCE IN COGNITIVE TESTS. WE WILL EXTEND THIS APPROACH WITH IN-SILICO EXPERIMENTS THAT WILL MODEL AN EXTENSIVE RANGE OF PATHOPHYSIOLOGICAL PROCESSES AND EVALUATE MANY MORE STIMULATION PARAMETERS THAN IS CURRENTLY FEASIBLE IN BIOLOGICAL MODELS. OUR ITERATIVE APPROACH THAT COMBINES IN-VIVO AND IN-SILICO APPROACHES IS POISED TO ACCELERATE CLINICAL TRANSLATION OF OUR STUDIES. THIS NEW STRATEGY COULD LEAD TO GROUNDBREAKING TREATMENTS FOR A WIDE RANGE OF COGNITIVE ISSUES, POTENTIALLY BENEFITING MILLIONS OF PEOPLE. BY USING ADVANCED TECHNIQUES TO UNDERSTAND AND ADDRESS THESE BRAIN ACTIVITY DISRUPTIONS, OUR WORK PROMISES TO PAVE THE WAY FOR INNOVATIVE THERAPIES AND BETTER QUALITY OF LIFE FOR THOSE WITH COGNITIVE IMPAIRMENTS.

INTEGRATING BEHAVIORAL HEALTH INTO PRIMARY CARE THROUGH TELEHEALTH EVIDENCE-BASED TELEHEALTH NETWORK

PARTNERSHIPS TO IMPROVE COMMUNITY HEALTH

LEVERAGING GENETICALLY-ENCODED HETEROGENEITY TO UNDERSTAND TANDS AND SEIZURES IN NOVEL MODELS OF TSC - PROJECT SUMMARY THE LONG-TERM GOAL OF THIS PROJECT IS TO UNDERSTAND THE MECHANISMS THAT UNDERLIE THE NEUROLOGICAL CONSEQUENCES OF TUBEROUS SCLEROSIS COMPLEX (TSC). TSC IS A PROFOUNDLY COMPLEX GENETIC DISORDER CAUSED BY MUTATIONS IN EITHER THE TSC1 OR TSC2 GENE AND CHARACTERIZED BY BENIGN TUMOR GROWTH IN MULTIPLE SYSTEMS IN THE BODY. TSC IS ASSOCIATED WITH EPILEPSY IN UP TO 90% OF PATIENTS THAT IS OFTEN REFRACTORY TO SURGICAL OR TARGETED PHARMACOLOGICAL INTERVENTION. IN ADDITION TO SEIZURES, TSC-ASSOCIATED NEUROLOGICAL DISORDERS (TANDS) ARE PRESENT IN UP TO 85% AND INTELLECTUAL DISABILITY IS PRESENT IN UP TO 70% OF PATIENTS. INTERESTINGLY, SINGLE TSC1 OR TSC2 MUTATIONS CAN HAVE DIFFERENTIAL EFFECTS BETWEEN AFFECTED INDIVIDUALS, AND EVEN IDENTICAL INHERITED VARIANTS CAN RESULT IN DIFFERENT DISEASE PROFILES. THIS INDICATES SIGNIFICANT HETEROGENEITY IN PATIENT OUTCOMES, THE MECHANISMS FOR WHICH IS CURRENTLY UNKNOWN; UNDERSTANDING THE MECHANISM FOR THIS DIFFERENCE IN PROGNOSIS WILL ALLOW US TO IDENTIFY NOVEL THERAPEUTIC APPROACHES CAPABLE OF MODIFYING OUTCOME IN TSC. WE RECENTLY DEVELOPED AND VALIDATED A MODEL SYSTEM OF THIS HETEROGENEITY TO IMPROVE OUR ABILITY TO PROBE THE BASIC BIOLOGY OF TSC AND EXPLORE THE NEURAL NETWORK DIFFERENCES UNDERLYING SEIZURES AND TANDS. OUR NOVEL MICE HAVE A GERMLINE TSC1 HETEROZYGOUS KNOCKOUT WHICH, WHEN INTRODUCED TO CONTROLLED GENETIC BACKGROUND DIVERSITY, FAITHFULLY RECAPITULATE PATIENT HETEROGENEITY IN TSC OUTCOMES WITH THE CLINICALLY RELEVANT GENE DOSAGE AND EXPRESSION PATTERN. WE HAVE REMARKABLE PRELIMINARY DATA SHOWING THAT THE SAME TSC1 HAPLOINSUFFICIENCY RESULTS IN A SPECTRUM OF BACKGROUND-DEPENDENT DIFFERENCES IN TSC OUTCOMES. THIS SPECTRUM ALLOWS US TO EXPLORE HOW NETWORKS UNDERLYING COGNITION AND SEIZURE ARE DIFFERENTIALLY AFFECTED BY THE SAME PRECIPITATING GENETIC INSULT. WE HYPOTHESIZE THAT GENETIC BACKGROUND-ASSOCIATED DIFFERENCES IN SEIZURE AND TANDS OUTCOMES RESULTING FROM TSC1 HAPLOINSUFFICIENCY WILL MANIFEST AS CHANGES IN NEURONAL DYNAMICS, PARTIALLY MEDIATED BY ABERRANT ASTROCYTE MODULATION OF THESE NEURONAL DYNAMICS. WE WILL TEST THIS HYPOTHESIS WITH THE FOLLOWING AIMS: 1) PHENOTYPE THE REPERTOIRE OF BEHAVIORAL IMPAIRMENTS IN TSC1 HAPLOINSUFFICIENT MICE, 2) CHARACTERIZE THE RELATIONSHIP BETWEEN CHANGES IN NEURONAL DYNAMICS, SEIZURE AND TANDS, 3) DESCRIBE CHANGES IN EXCITATORY/INHIBITORY DYNAMICS AND EXPLORE THE ROLE OF NON-NEURONAL POPULATIONS IN CHANGES IN E/I BALANCE THAT UNDERLIE EPILEPSY.

HYPOGLYCEMIA IN CHILDREN AND ADOLESCENTS WITH T1DM: MECHANISMS AND PREVENTION

VA OUTDOORS FY 2016 CWG- RAPPAHONNOCK AND JAMES RIVER PROJECT

COASTAL SC WETLANDS PARTNERSHIP, SC

ASSISTANCE TO FIREFIGHTERS GRANT

ASSISTANCE TO FIREFIGHTERS GRANT

ASSISTANCE TO FIREFIGHTERS GRANT

ASSISTANCE TO FIREFIGHTERS GRANT

COIN2DOSE: BEHAVIORAL ECONOMICS TO PROMOTE INSULIN BOLUS ACTIVITY AND IMPROVE HBA1C IN TEENS - PROJECT SUMMARY THIS R01 RESPONDS TO PAS-20-160 (SMALL R01S FOR CLINICAL TRIALS TARGETING DISEASES WITHIN THE MISSION OF NIDDK). OUR OBJECTIVE IS TO TEST THE FEASIBILITY, ACCEPTABILITY, AND INITIAL EFFICACY OF USING BEHAVIORAL ECONOMICS INCENTIVES (BEI) IN A NOVEL, SEMI-AUTOMATED INTERVENTION TO TARGET DAILY INSULIN BOLUS SCORES IN ADOLESCENTS WITH SUBOPTIMAL INSULIN USE. THERE IS A CRITICAL NEED FOR EFFICACIOUS AND EASY-TO-IMPLEMENT INTERVENTIONS TARGETING SELF- MANAGEMENT BEHAVIORS IN ADOLESCENTS WITH TYPE 1 DIABETES (T1D). THIS IS BECAUSE NATIONAL REGISTRY DATA SUGGEST THAT ONLY BETWEEN 15-28% OF ADOLESCENTS ACHIEVE THEIR GLYCATED HEMOGLOBIN (HBA1C) TARGET, THEREBY PLACING THE MAJORITY OF THEM AT INCREASED RISK FOR SERIOUS ACUTE AND LONG-TERM COMPLICATIONS. BEI INTERVENTIONS ARE EFFICACIOUS FOR PROMOTING HEALTH BEHAVIORS INCLUDING FREQUENCY OF SELF-MONITORING BLOOD GLUCOSE (SMBG) IN YOUTH. MOREOVER, THERE IS EVIDENCE THAT BEI CAN BE RELATIVELY EASY TO IMPLEMENT, ESPECIALLY WHEN USING NON-CONTINGENT BEI. BUT WITH THE UPTAKE OF INTEGRATED INSULIN PUMP AND CONTINUOUS GLUCOSE MONITOR (CGM) SYSTEMS AND THE NEW FDA APPROVAL ENABLING YOUTH TO DOSE FOR INSULIN BASED SOLELY ON CGM, WE BELIEVE THE LONG-TERM VALUE OF TARGETING SMBG ALONE IN BEI INTERVENTIONS IS LIMITED AND THAT DAILY INSULIN USE IS THE NEXT LOGICAL SELF-MANAGEMENT TARGET. BUILDING OFF OF OUR PRIOR WORK, THE INSULIN BOLUS SCORE OFFERS A SPECIFIC, MEASURABLE, AND VALID TREATMENT TARGET FOR DAILY INSULIN USE THAT IS ALSO MORE CLOSELY RELATED TO HBA1C THAN SMBG OR TOTAL INSULIN BOLUSES PER DAY. THUS OUR AIMS ARE: 1) EXAMINE THE FEASIBILITY AND ACCEPTABILITY OF OUR SEMI-AUTOMATED BEI INTERVENTION (CALLED COIN2DOSE) TARGETING DAILY BOLUS SCORES IN ADOLESCENTS AND 2) EXAMINE THE PRELIMINARY EFFICACY OF COIN2DOSE VERSUS A STANDARD CARE CONTROL (SC) GROUP ON YOUTH DAILY BOLUS SCORES, HBA1C, AND GLUCOSE TIME IN RANGE (TIR). WE ALSO INCLUDE AN EXPLORATORY AIM TO EXAMINE THE INCREMENTAL IMPACT OF USING CONTINGENT VERSUS NON- CONTINGENT BEI WITHIN OUR COIN2DOSE INTERVENTION ON YOUTH’S BOLUS SCORES, HBA1C, AND TIR. COIN2DOSE WILL DELIVER AUTOMATED TEXT MESSAGES TO CUE ADOLESCENTS TO BOLUS FOR INSULIN, PLUS BEI FOR DAILY BOLUS ACTIVITY. TO ENHANCE THE SCIENTIFIC RIGOR OF THIS R01, WE WILL USE THE ORBIT MODEL FOR BEHAVIORAL INTERVENTION DEVELOPMENT. CONSISTENT WITH THIS MODEL, WE WILL RECRUIT 180 ADOLESCENTS AND A PARENT TO PARTICIPATE IN 1- A TELEHEALTH FOCUS GROUP (ORBIT PHASE 1A: DEFINE; N= 20), 2- A FORMATIVE PRE-TEST (ORBIT PHASE 1B: REFINE; N=10), OR 3- A PILOT RANDOMIZED CLINICAL TRIAL (ORBIT PHASE 2: RCT PILOT; N=150). OUR RCT PILOT WILL RANDOMIZE TEENS WITH SUBOPTIMAL INSULIN USE (BOLUS SCORE <2.5; ~70% OF TEENS BASED ON PILOT DATA) TO SC OR 1 OF 2 VERSIONS OF COIN2DOSE THAT ONLY DIFFER BASED ON OUR USE OF PERSONALIZED (CONTINGENT) V. NON-PERSONALIZED (NON-CONTINGENT) BEI. ADOLESCENTS WILL PARTICIPATE IN 12-WEEKS OF ACTIVE TREATMENT, PLUS A 12-WEEK FOLLOW-UP PERIOD. THIS SMALL R01 IS SIGNIFICANT FOR ITS POTENTIAL TO YIELD: 1- PRELIMINARY DATA EXAMINING OUR NEW BEI INTERVENTION TARGETING DAILY BOLUS SCORES, WHICH MAY ALSO IMPROVE YOUTH HBA1C, 2- NOVEL DATA EXPLORING THE INCREMENTAL IMPACT OF CONTINGENT V. NON-CONTINGENT BEI, WHICH HAS IMPLICATIONS FOR COIN2DOSE AS WELL AS THE BROADER UPTAKE OF BEI INTERVENTIONS.

HEALTH AND PUBLIC SAFETY WORKFORCE RESILIENCY TRAINING PROGRAM

ASSAY DEVELOPMENT FOR NSD1 METHYLTRANSFERASE INHIBITOR DISCOVERY

STUDY OF HEALTHY ADAPTATION AND RESILIENCE TO PAIN IN EMERGING ADULTHOOD (SHARPE) - PROJECT SUMMARY/ABSTRACT CHRONIC MUSCULOSKELETAL (MSK) PAIN IS THE LEADING SOURCE OF PERSISTENT PAIN AMONG LATE ADOLESCENTS AND YOUNG ADULTS (AYAS) AND CONTRIBUTES TO SIGNIFICANT FUNCTIONAL DISABILITY, PSYCHOSOCIAL IMPAIRMENT, AND REDUCED QUALITY OF LIFE. MOREOVER, THE TRANSITIONAL STAGE OF EMERGING ADULTHOOD PRESENTS UNIQUE CHALLENGES WHICH CAN FURTHER COMPLICATE PAIN-RELATED COPING AND ADJUSTMENT IN LATE AYAS. THE INFLUENCE OF RISK FACTORS ON MALADAPTIVE PAIN- RELATED OUTCOMES IN YOUTH IS WELL-DOCUMENTED. HOWEVER, MUCH LESS IS KNOWN ABOUT PROTECTIVE FACTORS THAT MAY MITIGATE THESE NEGATIVE CONSEQUENCES AND PROMOTE HEALTHY ADAPTATION TO PAIN DURING THE TRANSITION TO ADULTHOOD. IT IS IMPERATIVE TO IDENTIFY THESE PROTECTIVE VARIABLES TO FOSTER POSITIVE OUTCOMES THROUGHOUT THE LIFE COURSE. RESILIENCE, CHARACTERIZED AS A DYNAMIC, MALLEABLE PROCESS LEADING TO POSITIVE ADAPTATION IN THE FACE OF ADVERSITY, PLAYS AN IMPORTANT ROLE IN CONFERRING ADAPTIVE RESPONSES TO PAIN. HOWEVER, RESILIENCE EXAMINED ACROSS MULTIPLE DOMAINS OF FUNCTIONING (I.E., PSYCHOLOGICAL, SOCIAL, BIOLOGICAL, AND HEALTH/LIFESTYLE) IS YET TO BE EXPLORED IN LATE AYAS WITH AND WITHOUT CHRONIC MSK PAIN. THUS, THE OVERARCHING GOAL OF THIS CAREER DEVELOPMENT AWARD (K23) IS TO FILL THIS KNOWLEDGE GAP BY: 1) CHARACTERIZING MULTI-DOMAIN PAIN RESILIENCY (MDPR) PROFILES DURING THE TRANSITION TO ADULTHOOD, AND 2) INVESTIGATING THE UTILITY OF THESE PROFILES IN PREDICTING PAIN, FUNCTIONING, AND PAIN MODULATORY CAPACITY OVER TIME. INFORMATION GAINED FROM THIS PROJECT WILL BE INVALUABLE FOR DEVELOPING PATIENT-CENTERED PREVENTION/INTERVENTION EFFORTS. THIS K23 PROPOSES SCIENTIFIC AND TRAINING OBJECTIVES THAT WILL BE INSTRUMENTAL FOR LAUNCHING AN INDEPENDENT PROGRAM OF RESEARCH THAT ADVANCES THE SCIENCE AND TREATMENT OF PAIN AND DISABILITY IN LATE AYAS. THE MULTIDISCIPLINARY MENTORING TEAM INCLUDES EXPERTS IN BIOPSYCHOSOCIAL PAIN MECHANISMS, RESILIENCE/POSITIVE PSYCHOLOGY, PEDIATRIC/ADOLESCENT PAIN, AND BIOSTATISTICS WHO WILL PROVIDE GUIDANCE AND TRAINING NECESSARY FOR ACHIEVEMENT OF PROFESSIONAL GOALS THAT WILL FACILITATE THE PI'S TRANSITION TO INDEPENDENCE. PRIMARY TRAINING OBJECTIVES FOR THE CURRENT PROPOSAL ARE TO: 1) EXPAND KNOWLEDGE OF BIOPSYCHOSOCIAL DETERMINANTS OF CHRONIC PAIN, SPECIFICALLY FACTORS RELATED TO PROMOTING PAIN RESILIENCE ACROSS MULTIPLE DOMAINS OF FUNCTIONING, 2) DEVELOP A COMPREHENSIVE KNOWLEDGE BASE FOR VARIABLES INFLUENCING PAIN DURING THE TRANSITION TO ADULTHOOD AND ENHANCE TRAINING IN THE ASSESSMENT AND TREATMENT OF PAIN IN LATE ADOLESCENTS AND YOUNG ADULTS, 3) AUGMENT STATISTICAL ACUMEN BY INCREASING FAMILIARITY WITH ADVANCED STATISTICAL ANALYTICS NECESSARY FOR CLINICAL RESEARCH, ESPECIALLY FOR PATIENT CLASSIFICATION TO INFORM PATIENT-CENTERED CARE, 4) ENHANCE KNOWLEDGE AND SKILLS NECESSARY FOR CLINICAL TRIAL DESIGN AND IMPLEMENTATION, AS WELL AS PREVENTION SCIENCE METHODOLOGY, AND 5) ADVANCE LEADERSHIP, MENTORING, SCHOLARLY PRODUCTIVITY, AND OTHER PROFESSIONAL SKILLS INTEGRAL FOR FOSTERING COMPETENCY AS AN ACADEMIC AND INDEPENDENT CLINICAL AND TRANSLATIONAL INVESTIGATOR. THE PROPOSED CAREER DEVELOPMENT PLAN EXTENDS FROM THE PI'S PRIOR WORK ON VULNERABILITY MECHANISMS IN PAIN, AND WILL FORGE A PATH TOWARDS INVESTIGATING STRATEGIES THAT PROMOTE RESILIENCE AND IMPROVE PAIN AND DISABILITY DURING THE TRANSITION TO ADULTHOOD.

ORAL FEEDING DIFFICULTY IN LARGE FOR GESTATIONAL AGE INFANTS: DEFINING INTERRELATIONSHIPS BETWEEN BODY COMPOSITION, ORAL FEEDING ABILITY, AND APPETITE-REGULATING HORMONES - PROJECT SUMMARY/ABSTRACT PREVALENCE OF ORAL FEEDING DIFFICULTY IN INFANTS ADMITTED TO A NEONATAL INTENSIVE CARE UNIT (NICU) IS INCREASING. THIS NOT ONLY LEADS TO PROLONGED NICU STAY, BUT AN ESCALATION OF HEALTHCARE COSTS AS WELL. A MAJOR CONTRIBUTOR IS THE INCREASE IN LARGE FOR GESTATIONAL AGE (LGA) INFANT BIRTH RATE BECAUSE OF RISING MATERNAL OBESITY AND DIABETES DURING PREGNANCY. LGA INFANTS ARE CONSIDERED POOR ORAL FEEDERS. SIGNIFICANT KNOWLEDGE GAPS EXIST IN UNDERSTANDING THE COMPLEX MECHANISMS IMPLICATED IN LGA INFANTS WITH ORAL FEEDING DIFFICULTY. LGA INFANTS ARE EXPOSED TO EXCESS ENERGY IN UTERO AND BODY COMPOSITION STUDIES HAVE SHOWN THAT THEY HAVE HIGHER FAT MASS (FM) AND LOWER FAT-FREE MASS (FFM) PROPORTION. ORAL FEEDING ABILITY CAN BE INFLUENCED BY HUNGER AND SATIETY, WHICH MAY HAVE A FEEDBACK MECHANISM WITH THE STATE OF THE BODY'S ENERGY STORES (FM AS PROXY) AND RESTING METABOLIC RATE (RMR, FFM AS PROXY), AND THESE EFFECTS MAY BE MEDIATED THROUGH THE APPETITE-REGULATING HORMONE (ARH) LEVELS. OUR PRELIMINARY DATA SUGGEST THAT INFANTS WITH A HIGHER FM AND LOWER FFM PROPORTION (DISPROPORTIONATE BODY COMPOSITION) TOOK LONGER TO REACH INDEPENDENT ORAL FEEDS, REQUIRED LONGER HOSPITALIZATION, AND REQUIRED HIGHER G-TUBE PLACEMENT. FFM IS BETTER ASSOCIATED WITH ORAL (ENERGY) INTAKE THAN FM, SUGGESTING THAT FFM IS MAJOR DETERMINANT OF ENERGY INTAKE AND APPETITE IN INFANTS. THE STANDARD NICU FEEDING STRATEGY IS FOCUSED ON PROMOTING WEIGHT GAIN IRRESPECTIVE OF BIRTH WEIGHT OR BODY COMPOSITION, WHICH IS INAPPROPRIATE IN LGA INFANTS AS LGA INFANTS WHO DEMONSTRATED ‘CATCH-DOWN’ GROWTH IN EARLY INFANCY HAD BETTER LONG-TERM OUTCOMES. THESE INFANTS HAD A GREATER PROPORTION OF FM LOSS COMPARED TO FFM DURING THE CATCH-DOWN PERIOD. LGA INFANTS WITH ORAL FEEDING DIFFICULTY IN THE NICU ARE DEPENDENT ON TUBE-FEEDING AND THE FEEDING INTAKE IS REGULATED BY THE CARE TEAM RATHER THAN BEING INFANT-DRIVEN. THE LOWER FFM% IN THESE INFANTS MAY REDUCE THEIR ABILITY TO MEET THE STANDARD ORAL INTAKE VOLUMES INDEXED TO TOTAL MASS (150 ML/KG/DAY). THE CONTINUED PROVISION OF EXCESS CALORIES ABOVE THE METABOLIC NEEDS FROM TUBE-FEEDING MAY INCREASE THEIR BODY ADIPOSITY, PREVENT NATURAL CATCH-DOWN GROWTH, AND EXACERBATE THEIR ORAL FEEDING DIFFICULTY. THE PROPOSED RESEARCH WILL EVALUATE THE INTERRELATIONSHIP BETWEEN BODY COMPOSITION, ORAL FEEDING ABILITY, AND ARH LEVELS IN LGA INFANTS. FURTHER, WE WILL EVALUATE THE EFFECTS OF A SHORT-TERM FFM-INDEXED FEEDING (TARGET FEEDING VOLUME INDEXED TO FFM) VERSUS THE STANDARD APPROACH TO FEEDING (TARGET FEEDING VOLUME INDEXED TO TOTAL MASS) ON ORAL FEEDING OUTCOMES, CATCH-DOWN WEIGHT, AND BODY COMPOSITION IN LGA INFANTS WITH ORAL FEEDING DIFFICULTY. KNOWLEDGE GAINED FROM THIS PROPOSAL WILL PROVIDE A RATIONALE FOR FUTURE STUDIES DESIGNED TO EVALUATE PRECISION NUTRITIONAL THERAPIES FOR LGA INFANTS. THIS MAY ULTIMATELY SHORTEN THE LENGTH OF HOSPITAL STAY AND ENHANCE THE QUALITY OF LIFE FOR THESE INFANTS.

MECHANISMS FOR IMPROVING COGNITIVE OUTCOME IN PEDIATRIC EPILEPSY WITH ACTH

ROLE OF ALVEOLAR EPITHELIAL CELL-DERIVED CELLULAR COMMUNICATION NETWORK FACTOR 2 (CCN2) IN ALVEOLOGENESIS AND BRONCHOPULMONARY DYSPLASIA

INVESTIGATION OF MECP2 FUNCTION IN RETT SYNDROME

COASTAL SC WETLANDS PARTNERSHIP II

ASSISTANCE TO FIREFIGHTERS GRANT

OBESITY AND ASTHMA: GENETICS AND NUTRIGENETIC RESPONSE TO OMEGA-3 FATTY ACIDS

STAFFING FOR ADEQUATE FIRE AND EMERGENCY RESPONSE (SAFER)

PARTNERING WITH ADOLESCENTS AND YOUNG ADULTS WITH SICKLE CELL DISEASE IN TREATMENT DECISIONS - SICKLE CELL DISEASE (SCD) IS A LIFE-THREATENING CONDITION MARKED BY DEBILITATING COMPLICATIONS, POOR QUALITY OF LIFE, AND EARLY MORTALITY. HISTORICALLY, SCD HAS RECEIVED FAR LESS FUNDING AND PUBLIC POLICY EFFORTS THAN OTHER CHRONIC DISEASES, RESULTING IN DECADES OF STAGNATION IN MEDICAL ADVANCES. HOWEVER, TREATMENT OPTIONS FOR SCD ARE NOW EXPANDING WITH RECENT FEDERAL AND INDUSTRY INVESTMENTS. FOR THE FIRST TIME, PATIENTS LIVING WITH SCD ARE MAKING DECISIONS ABOUT MULTIPLE DISEASE-MODIFYING THERAPIES, EACH WITH UNIQUE CLINICAL INDICATIONS AND TRADEOFFS IMPACTING QUALITY OF LIFE. UNFORTUNATELY, MOST DO NOT REAP THE BENEFITS OF THESE ADVANCES. HYDROXYUREA IS THE MAINSTAY TREATMENT, YET ONLY ABOUT 25% RECEIVE IT; UPTAKE OF OTHER THERAPIES IS ESTIMATED AT LESS THAN 5% OF THE POPULATION. USE OF THERAPIES IS ESPECIALLY SUBOPTIMAL AMONG ADOLESCENTS AND YOUNG ADULTS (AYAS) DUE TO PATIENT (LACK OF INVOLVEMENT IN DECISIONS, INADEQUATE KNOWLEDGE), PROVIDER (NOT OFFERING HU DUE TO CONCERNS ABOUT AYAS’ ADHERENCE), AND HEALTHCARE ACCESS CHALLENGES (LIMITED TRANSPORTATION, INADEQUATE INSURANCE). IN TURN, SUBOPTIMAL USE OF THERAPIES CONTRIBUTES TO HIGH MORBIDITY AND MORTALITY AMONG AYAS WITH SCD. HEALTH PROMOTION INTERVENTIONS THAT CAN EFFECTIVELY OVERCOME THESE BARRIERS ARE URGENTLY NEEDED TO OPTIMIZE UPTAKE AND ADHERENCE TO SCD THERAPIES AMONG AYAS AND THEREBY REDUCE PREVENTABLE DISEASE COMPLICATIONS. SHARED DECISION-MAKING (SDM) ENHANCES PATIENT KNOWLEDGE, ENGAGEMENT AND SATISFACTION WITH CARE, ADHERENCE TO TREATMENTS, AND HEALTH OUTCOMES. HOWEVER, SDM IS DIFFICULT TO ACHIEVE IN ROUTINE CARE, AND THERE ARE NO INTERVENTIONS THAT SUPPORT SDM FOR AYAS WITH SCD. TO ADDRESS THIS UNMET NEED, WE DEVELOPED THE SCD SHARED DECISION-MAKING TOOLKIT FOR AYAS (SDMT-AYA). SDMT-AYA TARGETS MULTI-LEVEL BARRIERS TO USE OF DISEASE-MODIFYING THERAPIES BY PROVIDING TOOLS FOR: 1) MULTIDISCIPLINARY CLINICIANS (SKILLS-BASED TRAINING, COMMUNICATION SUPPORT TOOLS USED AT POINT-OF-CARE); 2) AYAS AND CAREGIVERS (DECISION AIDS THAT LEVERAGE ADVANCED LEARNING TECHNOLOGIES); AND 3) IMPLEMENTATION (PROCESS MAPPING, AUDIT AND FEEDBACK). PRELIMINARY FINDINGS SUGGEST HIGH USABILITY, ACCEPTABILITY, AND FEASIBILITY OF THE TOOLKIT. THIS STEPPED-WEDGE CLUSTER RANDOMIZED TRIAL WILL EVALUATE EFFECTIVENESS OF SDMT-AYA ON PATIENT EXPERIENCES OF SDM, PATIENT KNOWLEDGE OF SCD AND TREATMENT OPTIONS, AND CLINICAL OUTCOMES (USE OF THERAPIES, ACUTE CARE UTILIZATION), TEST MECHANISMS OF ACTION, AND EXAMINE BARRIERS AND FACILITATORS TO IMPLEMENTING AND SUSTAINING SDMT-AYA. FOUR SITES WILL BE RANDOMIZED TO CROSS OVER FROM USUAL CARE (USE OF A POCKET GUIDE FOR DISEASE-MODIFYING THERAPY DISCUSSIONS) TO THE INTERVENTION CONDITION (USE OF SDMT-AYA TO DISCUSS DISEASE-MODIFYING THERAPIES) AT DISTINCT TIME POINTS. WE WILL INTERVIEW KEY INFORMANTS AT EACH SITE TO EXPLORE BARRIERS AND FACILITATORS AFFECTING IMPLEMENTATION AND SUSTAINMENT OF THE TOOLKIT. THIS RESEARCH HAS THE POTENTIAL TO REINVENT HOW HEALTHCARE SYSTEMS EDUCATE, ENGAGE, AND PARTNER WITH AYAS IN MAKING CARE DECISIONS. IF SUCCESSFUL, THIS PROJECT CAN SERVE AS A MODEL FOR FACILITATING SDM TO IMPROVE CARE AND OUTCOMES FOR AYAS WITH OTHER CHRONIC CONDITIONS.

INTEGRATING PARENTING INTERVENTIONS INTO PEDIATRIC OBESITY CARE

VA MCWCG FU 2014 ,PIMT AORU RAPPAHANNOCK RIVER COASTAL WETLAND CONSERVATION

PROJECT TITLE: SPHINGOLIPIDS AND EICOSANOIDS FROM PLASMA AND TEAR FLUID AS DISEASE-RELEVANT BIOMARKERS IN GULF WAR ILLNESS.

TYPE 1 TOGETHER: A MULTISITE RCT OF A PEER MENTOR PROGRAM FOR TEENS WITH TYPE 1 DIABETES - PROJECT SUMMARY FEWER THAN 1 IN 5 ADOLESCENTS WITH TYPE 1 DIABETES (T1D) ACHIEVE THE GLYCEMIC LEVELS RECOMMENDED BY THE AMERICAN DIABETES ASSOCIATION, INCREASING THEIR RISK FOR ACUTE AND LONG-TERM HEALTH COMPLICATIONS. CONTINUOUS GLUCOSE MONITORING SYSTEMS (CGM) CAN IMPROVE THE PHYSICAL AND MENTAL HEALTH OF YOUTH WITH T1D, BUT ONLY IF WORN CONSISTENTLY (≥ 80% OF THE TIME). HOWEVER, ADOLESCENTS ARE LESS LIKELY THAN CHILDREN AND YOUNG ADULTS TO WEAR CGM CONSISTENTLY. BARRIERS TO USING CGM ALIGN WITH THE THREE DOMAINS OF SOCIAL COGNITIVE THEORY, A WIDELY USED THEORY TO UNDERSTAND INFLUENCES ON INDIVIDUALS’ HEALTH BEHAVIORS: PERSONAL (E.G., PERCEIVED BENEFITS AND BURDENS OF CGM, SELF-EFFICACY TO MANAGE DIABETES), BEHAVIORAL (E.G., FAMILY INVOLVEMENT, ADHERENCE), AND ENVIRONMENTAL (E.G., COST, INSURANCE). UNFORTUNATELY, RIGOROUSLY TESTED INTERVENTIONS TO BOLSTER CONSISTENT USE OF CGM ARE LACKING. TYPE 1 TOGETHER IS AN INTERVENTION THAT WAS CO-DEVELOPED IN PARTNERSHIP WITH YOUTH WITH T1D AND THEIR FAMILIES. TYPE 1 TOGETHER COMBINES PEER MENTORING AND SUPPORT FROM A COMMUNITY HEALTH WORKER TO TARGET PERSONAL, BEHAVIORAL, AND ENVIRONMENTAL BARRIERS TO CONSISTENTLY USING CGM. DATA FROM A PILOT RANDOMIZED CONTROLLED TRIAL (RCT) SUGGESTS THAT TYPE 1 TOGETHER IS ACCEPTABLE, FEASIBLE, AND MAY IMPROVE GLYCEMIC LEVELS, CGM WEAR TIME, AND MENTAL HEALTH OUTCOMES AMONG ADOLESCENTS WITH T1D. THE CURRENT PROPOSAL EXTENDS THIS LINE OF RESEARCH AND PROPOSES TO RIGOROUSLY EVALUATE THE EFFICACY OF TYPE 1 TOGETHER IN A MULTISITE RCT. ADOLESCENT-CAREGIVER DYADS (N=180) WILL BE RECRUITED FROM THREE SITES (NEMOURS – DELAWARE, NEMOURS – ORLANDO, UNIVERSITY OF TENNESSEE – MEMPHIS) AND RANDOMIZED 1:1 TO TYPE 1 TOGETHER OR A 6MONTH WAITLIST CONTROL. DURING THE INTERVENTION PHASE, FAMILIES WILL MEET AT LEAST MONTHLY WITH A PEER MENTOR FAMILY AND A COMMUNITY HEALTH WORKER. WE WILL THEN EVALUATE THE EFFICACY OF TYPE 1 TOGETHER IN IMPROVING HEALTH AND PSYCHOSOCIAL OUTCOMES (AIM 1) AND THE EFFECT OF TYPE 1 TOGETHER ON SOCIAL COGNITIVE THEORY CONSTRUCTS (AIM 2). WHILE THE MULTI-SITE RCT IS UNDERWAY, WE WILL ALSO USE A MIXED-METHODS APPROACH INFORMED BY THE PRACTICAL, ROBUST IMPLEMENTATION AND SUSTAINABILITY MODEL TO IDENTIFY STRATEGIES TO IMPLEMENT TYPE 1 TOGETHER AS PART OF ROUTINE CLINICAL CARE. UPON COMPLETION OF THIS PROJECT, WE WILL HAVE DATA REGARDING THE EFFICACY OF TYPE 1 TOGETHER (AIM 1), ELUCIDATE POTENTIAL MECHANISMS UNDERLYING THE INTERVENTION (AIM 2), AND HAVE STRATEGIES TO OVERCOME POTENTIAL BARRIERS TO IMPLEMENTING TYPE 1 TOGETHER MORE BROADLY (AIM 3).

RAPPAHANNOCK RIVER CONSERVATION PARTNERSHIP PHASE I

SYNOVIAL BIOMARKERS IN OLGOARTICULAR JUVENILE IDIOPATHIC ARTHRITIS

ASSISTANCE TO FIREFIGHTERS GRANT

STAFFING FOR ADEQUATE FIRE AND EMERGENCY RESPONSE (SAFER)

CAROL M. WHITE PHYSICAL EDUCATION PROGRAM

DETERMINING THE ANTI-INFLAMMATORY MECHANISM AND THERAPEUTIC POTENTIAL OF WNT2B IN COLITIS - DETERMINING THE ANTI-INFLAMMATORY MECHANISM AND THERAPEUTIC POTENTIAL OF WNT2B IN COLITIS ABSTRACT WNT SIGNALING HAS BEEN SHOWN TO MODULATE INFLAMMATION, AND HAS BEEN LINKED TO IMPORTANT DISEASE PROCESSES IN THE INTESTINE INCLUDING INFLAMMATORY BOWEL DISEASE, BUT THE EFFECTS OF WNT SIGNALING DEPENDS ON THE CONTEXT OF THE INTERACTION AND THE SPECIFIC WNT LIGANDS INVOLVED. STUDYING INDIVIDUAL WNTS HAS BEEN A MAJOR BARRIER TO THE FIELD, BUT WE HAVE IDENTIFIED HUMANS WITH WNT2B LOSS OF FUNCTION (LOF) AND HAVE SUBSEQUENTLY SHOWN THAT WNT2B LOF RESULTS IN INCREASED COLON INFLAMMATION, PARTICULARLY THROUGH IL-6 SIGNALING, AND INCREASED IMMUNE CELL RECRUITMENT IN HUMANS AND MICE. THE OVERARCHING GOAL OF THIS PROPOSAL IS TO DETERMINE HOW WNT2B FUNCTIONS TO PREVENT COLITIS. WE WILL TEST THE NOVEL HYPOTHESIS THAT WNT2B FROM INTESTINAL MESENCHYMAL FIBROBLASTS SIGNALS NON-CANONICALLY AND NEGATIVELY REGULATES NFΚB TO PREVENT IL-6 ASSOCIATED INFLAMMATION IN THE COLON, SO THAT INCREASING WNT2B IS BENEFICIAL IN HUMAN COLITIS. FURTHERMORE, WE WILL EXAMINE HOW WNT2B INTERACTS WITH NFΚB SIGNALING TO IMPACT INFLAMMATION AND WHETHER THERE IS A NEGATIVE FEEDBACK RELATIONSHIP. THE IMPACTS OF WNT2B ON INNATE IMMUNE CELL RECRUITMENT WILL ALSO BE ASSESSED. FINALLY, WE WILL EVALUATE WHETHER WNT2B HOLDS POTENTIAL AS A THERAPEUTIC TARGET FOR HUMAN COLITIS BY TESTING WHETHER INCREASED EXPRESSION OF WNT2B CAN EITHER DECREASE ACTIVE COLITIS OR PREVENT THE DEVELOPMENT OF COLITIS.

THE USE OF COMPREHENSIVE MOLECULAR PROFILING WITH NETWORK AND CONTROL THEORY TO BETTER UNDERSTAND GWI AND MODEL THERAPEUTIC STRATEGIES

UPTAKE OF EVIDENCE-BASED BEHAVIORAL INTERVENTION FOR PEDIATRIC TYPE 1 DIABETES

FEASIBILITY AND ACCEPTABILITY OF BIOFEEDBACK-BASED VIRTUAL REALITY FOR POSTOPERATIVE PAIN MANAGEMENT IN CHILDREN AND ADOLESCENTS - PROJECT SUMMARY MIND-BODY THERAPIES, LIKE BIOFEEDBACK (BF), ARE EFFECTIVE TREATMENTS TO DECREASE PAIN IN CHILDREN AND ADULTS. WHILE DECADES OF LITERATURE SUPPORT THE USE OF BF TO DECREASE PAIN, BF IS NOT CURRENTLY AVAILABLE FOR USE IN THE POSTOPERATIVE PERIOD AS IT IS A RESOURCE-RICH INTERVENTION. WITH THE HELP OF NOVEL TECHNOLOGIC INNOVATIONS, LIKE VIRTUAL REALITY (VR), BF CAN BE DELIVERED IN AN ENGAGING, LESS RESOURCE-INTENSIVE MANNER, RESULTING IN A MORE ACCESSIBLE THERAPY THAT CAN BE APPLIED IN BROADER CLINICAL SETTINGS. VR HAS ALSO DEMONSTRATED EFFICACY TO DECREASE PAIN, BUT TRANSIENT REDUCTIONS IN PAIN DUE TO THE REDIRECTION OF ATTENTION ARE INSUFFICIENT TO TREAT PROLONGED ACUTE PAIN EXPERIENCES. FOREVR VR (FUNCTIONAL OUTCOME RESPONSE TO ENGAGING VR) IS A FIRST-OF- ITS-KIND, VR-BASED BF INTERVENTION AND DELIVERY SYSTEM. COMBINING VR AND BF (VR-BF) SYNERGIZES THE IMMERSION AND ENTERTAINMENT OF VR WITH THE PHYSIOLOGICAL MODIFICATIONS OF BF TO ENHANCE AND SUSTAIN EACH MODALITY’S THERAPEUTIC EFFECTS. VR-BF IS AN ENGAGING AND MOTIVATING THERAPY THAT CHILDREN CAN PERFORM INDEPENDENTLY AND THAT HAS SHOWN EFFICACY IN TREATING SEVERAL DISORDERS. DESPITE EARLY EVIDENCE OF EFFICACY, VR-BF IS A NEW THERAPY AND HAS NOT YET BEEN EMPLOYED IN PERIOPERATIVE CARE, THUS NO OPTIMAL DURATION AND FREQUENCY OR DEFINED TREATMENT PROTOCOLS FOR PREOPERATIVE TRAINING AND POSTOPERATIVE APPLICATION OF VR-BF EXIST. THIS STUDY MARKS THE FIRST TO ASSESS THE IMPLEMENTATION AND USE OF VR-BF IN THE PERIOPERATIVE SETTING AND SEEKS TO ESTABLISH MEASURABLE MILESTONES THAT HAVE NOT BEEN ADDRESSED IN PRIOR STUDIES. THE GOAL OF THIS TWO- PHASE STUDY IS TO UNDERSTAND HOW TO IMPLEMENT A NOVEL VR-BF THERAPY FOR POSTOPERATIVE PAIN MANAGEMENT IN CHILDREN. BEFORE CONDUCTING AN EFFICACY TRIAL OF VR-BF VERSUS ACTIVE CONTROL, IT IS IMPERATIVE TO ASSESS FACTORS THAT WILL IMPACT THE VR-BF INTERVENTION AND, CONSEQUENTLY, THE EFFICACY OF VR-BF TO REDUCE PAIN AND OPIOID USE. OUR CENTRAL HYPOTHESIS IS THAT THE USE OF VR-BF IN PEDIATRIC PATIENTS UNDERGOING SURGERY RESULTING IN MODERATE TO SEVERE PAIN WILL BE FEASIBLE AND ACCEPTABLE, AND THAT FINDINGS FROM THIS PILOT TRIAL WILL INFORM DESIGN OF A LARGE- SCALE EFFICACY TRIAL OF VR-BF IN THIS PATIENT POPULATION. SPECIFIC AIMS: (1) REFINE A TREATMENT PROTOCOL FOR PREOPERATIVE EDUCATION AND TRAINING AND POSTOPERATIVE APPLICATION OF VR-BF USING FOREVR VR IN CHILDREN AND ADOLESCENTS UNDERGOING SURGERY; AND (2) CONDUCT A PILOT RANDOMIZED CONTROLLED TRIAL TO ASSESS THE FEASIBILITY AND ACCEPTABILITY OF PERIOPERATIVE USE OF VR-BF USING FOREVR VR IN CHILDREN AND ADOLESCENTS UNDERGOING SURGERY. THE MULTIDISCIPLINARY RESEARCH TEAM, A UNIQUE COLLABORATION OF AN ANESTHESIOLOGIST, PAIN EXPERTS, CLINICAL PSYCHOLOGISTS, A BIOSTATISTICIAN, AND A CLINICAL TRIAL DESIGN EXPERT; ARE IDEALLY SUITED TO ACCOMPLISH THESE RESEARCH GOALS. DATA FROM THIS R34 WILL INFORM DESIGN OF A LARGE-SCALE, RANDOMIZED, CLINICAL EFFICACY TRIAL USING VR-BF TO ASSESS PAIN AND OPIOID REDUCTION IN CHILDREN AND ADOLESCENTS WITH ACUTE POSTOPERATIVE PAIN. IT WILL PROVIDE INSIGHT ON PREOPERATIVE EDUCATION AND TRAINING AND POSTOPERATIVE APPLICATION OF VR-BF, IN EFFORTS TO IMPROVE POSTOPERATIVE ANALGESIA, REDUCE OPIOID AND ANALGESIC USE, AND ASSIST IN PAIN AND STRESS MANAGEMENT.

MEASUREMENT OF BIOMARKERS IN SAMPLES COLLECTED IN A COENZYME Q10 TREATMENT TRIAL IN GULF WAR ILLNESS AND CONTROL SUBJECTS

GRADUATE PSYCHOLOGY EDUCATION PROGRAMS

NEMOURS COMMUNITY CLINICAL ONCOLOGY PROGRAM

REGULATION OF AXONAL PROTEINS SYNTHESIS

GULF WAR ILLNESS: EXPLORING THE EYE-BRAIN CONNECTION

PARTNERSHIPS TO IMPROVE COMMUNITY HEALTH

PURPLE DOOR PROJECT: LEGAL ASSISTANCE FOR SURVIVORS IN FULTON COUNTY, GA

CENTER FOR PEDIATRIC TRAUMATIC STRESS - THE CENTER FOR PEDIATRIC TRAUMATIC STRESS (CPTS) WILL REDUCE HEALTH-RELATED TRAUMATIC STRESS AMONG CHILDREN WITH ACUTE AND CHRONIC MEDICAL CONDITIONS AND THEIR FAMILIES BY ADVANCING TRAUMA-INFORMED CARE IN PEDIATRIC HEALTHCARE NATIONWIDE. THROUGH 3 HOSPITAL-BASED SITES ACROSS 7 STATES, CPTS WILL DEVELOP, EVALUATE, DISSEMINATE, IMPLEMENT, AND SUSTAIN EVIDENCE-BASED TOOLS AND INTERVENTIONS FOR HEALTHCARE SYSTEMS, HEALTHCARE AND MENTAL HEALTH PROVIDERS, PATIENTS, AND FAMILIES. DURING 2026-2031, CPTS WILL STRENGTHEN PROVIDER AND SYSTEM AWARENESS AND RESPONSIVENESS, DEEPEN MENTAL HEALTH WORKFORCE EXPERTISE IN CARING FOR MEDICALLY AFFECTED CHILDREN, AND EXPAND FAMILY ACCESS TO PSYCHOSOCIAL RESOURCES. CPTS WILL UPDATE HEALTHCARETOOLBOX ANNUALLY AND, OVER THE GRANT CYCLE, PROMOTE ITS RESOURCES THROUGH TRAINING, SOCIAL MEDIA, AND PARTNERSHIPS TO REACH 30,000 HEALTHCARE PROVIDERS AND 2,500 MENTAL HEALTH PROVIDERS. OTHER GRANT-CYCLE OBJECTIVES INCLUDE SUPPORTING TRAUMA-INFORMED CARE IMPLEMENTATION THROUGH THE TICKET PLATFORM IN AT LEAST 15 ORGANIZATIONS; ADAPTING AND DISSEMINATING THE TECHS PROVIDER STRESS AND BURNOUT PROGRAM TO AT LEAST 5,000 INDIVIDUALS; SUPPORTING 100 HEALTHCARE SYSTEMS IN IMPLEMENTING THE PAT AND ASC-KIDS SCREENING TOOLS WITH 7,500 FAMILIES; AND DISSEMINATING SCCIP, A CAREGIVER COPING PROGRAM FOR FAMILIES AFFECTED BY PEDIATRIC CANCER, TO AT LEAST 150 MENTAL HEALTH PROVIDERS.

ROLE OF PSMA IN ABERRANT CELL CYCLE PROGRESSION IN PROSTATE CANCER

DEVELOPMENT AND EVALUATION OF RADIOTRACERS FOR PET IMAGING ANGIOTENSIN-CONVERTING ENZYME 2 (ACE2) - PROJECT SUMMARY THE CORONAVIRUS DISEASE2019 (COVID-19) PANDEMIC IS AN ONGOING GLOBAL PANDEMIC CAUSED BY THE SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2). NEW COVID-19 CASES AND COVID-19 RELATED DEATHS CONTINUE TO RISE RAPIDLY AND NO EFFECTIVE DRUGS OR VACCINES ARE CURRENTLY AVAILABLE. THE FUNCTIONAL ENTRY RECEPTOR UTILIZED BY SARS-COV-2 IS ANGIOTENSIN-CONVERTING ENZYME 2 (ACE2). SARS-COV-2 BINDS TO ACE2 IN THE LOWER RESPIRATORY TRACTS OF INFECTED PATIENTS TO GAIN ENTRY INTO LUNG CELLS, LEADING TO VIRAL PNEUMONIA AND POTENTIALLY FATAL RESPIRATORY FAILURE. MANY STUDIES HAVE SHOWN THAT PATIENTS WITH COMORBID CONDITIONS INCLUDING RESPIRATORY DISEASE, CARDIOVASCULAR DISEASE, KIDNEY DISEASE, DIABETES, AND HYPERTENSION HAVE MUCH HIGHER MORTALITY RATES. ACE INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS (ARB) ARE FREQUENTLY USED TO TREAT THESE PRE-EXISTING CONDITIONS AND THE QUESTION REMAINS WHETHER SUCH TREATMENT MAY AFFECT THE OUTCOME IN COVID-19 PATIENTS DUE TO THE INHIBITORS' EFFECTS ON ACE2 EXPRESSION. MANY EXPERTS ARE CONCERNED THAT THOSE INHIBITORS FOR THE TREATMENT OF PATIENTS WITH SUCH UNDERLYING CONDITIONS MAY EXACERBATE COVID-19 SYMPTOMS AND LEAD TO HIGHER MORTALITY RATES. CURRENTLY THE PRECISE RELATIONSHIP BETWEEN ACE2 LEVELS AND SEVERITY OF THE INFECTION IS NOT WELL UNDERSTOOD, DUE TO A LACK OF UNDERSTANDING OF WHOLE-BODY ACE2 EXPRESSION LEVELS AND DISTRIBUTION. HERE WE PROPOSE TO DESIGN AND SYNTHESIZE A SERIES OF NEW FLUORINE-18 LABELED POSITRON EMISSION TOMOGRAPHY (PET) TRACERS TARGETING ACE2. THE RADIOTRACERS WILL BE EVALUATED IN VITRO FOR CELLULAR BINDING AFFINITY, SELECTIVITY, AND METABOLIC STABILITY. THE MOST PROMISING RADIOTRACER WILL BE MOVED TO IN VIVO STUDIES INCLUDING WHOLE BODY BIODISTRIBUTION WITH DYNAMIC PET IMAGING, AND CORRELATION WITH BIOMOLECULAR ANALYSIS IN MICE THAT EXPRESS HUMAN ACE2. THE PET IMAGING MODALITY WILL PROVIDE A POWERFUL TOOL FOR NONINVASIVE AND QUANTITATIVE EVALUATION OF ACE2 LEVELS IN LIVING SUBJECTS. FURTHERMORE, THE RADIOTRACER MAY HELP TO UNVEIL THE PRECISE RELATIONSHIP BETWEEN ACE2 LEVELS AND SEVERITY OF COVID-19.

TESTING THE MODEL: A PHASE I/II RANDOMIZED DOUBLE BLIND PLACEBO CONTROL TRIAL OF TARGETED THERAPEUTICS: LIPOSOMAL GLUTATHIONE AND CURCUMIN

ROLE OF BETA SUBUNIT OF SODIUM PUMP IN CELL ADHESION

CHARACTERIZATION OF PLEXIFORM NEUROFIBROMA TREATMENT SUSCEPTIBILITY AND RESPONSE THROUGH MULTIDIMENSIONAL CIRCULATING BIOMARKERS

THE ROLE OF KCTD-13 IN GENITOURINARY DEVELOPMENT. - PROJECT SUMMARY HYPOSPADIAS AND UNDESCENDED TESTES (UDT, AKA: CRYPTORCHIDISM) ARE TWO OF THE MOST COMMON CONGENITAL GENITOURINARY (GU) DEFECTS, AFFECTING 1 IN 200 AND 1 IN 30 LIVE MALE BIRTHS, RESPECTIVELY. PROXIMAL HYPOSPADIAS, THE MOST SEVERE FORM, IS ASSOCIATED WITH SIGNIFICANT SURGICAL MORBIDITY AND PSYCHOSOCIAL CONSEQUENCES. UDT INCREASES THE RISK OF INFERTILITY AND TESTICULAR CANCER, AND UP TO 40% OF AFFECTED INDIVIDUALS PRESENT WITH BOTH CONDITIONS, SUGGESTING A SHARED MOLECULAR ETIOLOGY. DESPITE THEIR HIGH PREVALENCE, THEIR MOLECULAR BASIS IS POORLY UNDERSTOOD. RECENT GENOMIC STUDIES, INCLUDING OUR OWN, HAVE IDENTIFIED COPY NUMBER VARIANTS (CNVS) IN KCTD13 IN ~21% OF BOYS WITH PROXIMAL HYPOSPADIAS AND/OR UDT, IMPLICATING KCTD13 AS A CENTRAL REGULATOR OF MALE REPRODUCTIVE DEVELOPMENT. KCTD13 ENCODES A SUBSTRATE-SPECIFIC ADAPTER OF THE BCR (BTB-CUL3-RBX1) E3 UBIQUITIN-PROTEIN LIGASE COMPLEX. WE DEVELOPED A KCTD13-KNOCKOUT (KO) MOUSE THAT RECAPITULATES FEATURES OF HUMAN UNDERVIRILIZATION, INCLUDING MICROPENIS, UDT, AND SUBFERTILITY. KCTD13 REGULATES BOTH THE ANDROGEN RECEPTOR (AR) AND THE SERTOLI CELL MASCULINIZATION FACTOR, SOX9. KCTD13 LOSS INCREASES AR UBIQUITINATION AND DEGRADATION, RESULTING IN LOWER LEVELS OF AR IN THE TESTIS AND PENIS. REPLENISHMENT OF AR AND SOX9 IN THE PENISES OF TISSUE-SPECIFIC KNOCK-IN MICE REVERTS THE MICROPENIS AND SUBFERTILITY PHENOTYPE, SUGGESTING THAT KCTD13 IS, AT LEAST IN PART, ACTING VIA ITS REGULATION OF AR AND SOX9. TRANSCRIPTOMIC ANALYSIS OF KCTD13-KO MICE SHOWED DISRUPTIONS IN OTHER CRITICAL DEVELOPMENTAL PATHWAYS ASSOCIATED WITH UDT AND HYPOSPADIAS IN THE TESTIS AND PENIS, SUCH AS THE WNT/Β-CATENIN AND FGFR2 SIGNALING PATHWAY. THIS PROJECT WILL TEST THE HYPOTHESIS THAT KCTD13 COORDINATES AR, SOX9, WNT/Β-CATENIN, AND FGFR2 SIGNALING IN A TISSUE-SPECIFIC MANNER TO REGULATE PENILE AND TESTICULAR DEVELOPMENT. IN AIM 1, WE WILL INITIALLY USE SPATIAL TRANSCRIPTOMICS TO IDENTIFY THE PRECISE CELLULAR LOCATION OF DISRUPTED KCTD13 SIGNALING IN THE GENITAL TUBERCLE, AND THE DISRUPTED PATHWAYS WILL BE VALIDATED IN DIFFERENT CELLULAR ASSAYS. IN ADDITION, WE WILL DETERMINE THE INCIDENCE AND ROLE OF KCTD13 AND ASSOCIATED PROTEINS IN PROXIMAL HYPOSPADIAS IN PATIENTS. IN AIM 2, WE WILL EVALUATE HOW KCTD13 REGULATES AR, SOX9, AND WNT/Β- CATENIN PATHWAYS IN THE TESTIS AND USE SURGICAL ORCHIDOPEXY TO DISTINGUISH THE EFFECTS OF GENE LOSS FROM TESTICULAR MALPOSITION. BY INTEGRATING GENETIC, MOLECULAR, AND SPATIAL TRANSCRIPTOMIC APPROACHES, WE WILL DEFINE THE MECHANISTIC ROLE OF KCTD13 IN MALE REPRODUCTIVE DEVELOPMENT AND INFORM FUTURE DIAGNOSTIC AND THERAPEUTIC STRATEGIES FOR HYPOSPADIAS AND UDT.

NOVEL IMMUNOTHERAPY OPTIONS FOR PEDIATRIC ACUTE MYELOID LEUKEMIA

HEALTH INFORMATION, EDUCATION, AND PROMOTION FOR THE PREVENTION OF COMPLICATIONS IN HEMOPHILIA AND BLEEDING DISORDERS IN WOMEN.

ADAPTING SINGLE SESSIONS INTERVENTIONS FOR TYPE 1 DIABETES (ASSISTED): INTEGRATED PEDIATRIC CARE TO REDUCE DEPRESSION AND HBA1C - PROJECT SUMMARY/ABSTRACT TYPE 1 DIABETES (T1D) IS A COMMON PEDIATRIC CHRONIC MEDICAL CONDITION THAT INVOLVES A COMPLEX DAILY REGIMEN. MOST CHILDREN AND ADOLESCENTS WITH T1D DO NOT MEET GLYCEMIC CONTROL RECOMMENDATIONS, SUGGESTING THAT MANY LIKELY STRUGGLE TO MANAGE T1D EFFECTIVELY. BEHAVIORAL INTERVENTIONS EXIST TO HELP YOUTH WITH T1D ENGAGE WITH THEIR TREATMENT REGIMEN AND ACHIEVE LOWER GLYCEMIC LEVELS. HOWEVER, IN DIABETES CLINICS, IT IS CHALLENGING TO IMPLEMENT THESE INTERVENTIONS BECAUSE THEY ARE COSTLY TO DELIVER, OFTEN INVOLVE MULTIPLE SESSIONS SPANNING WEEKS OR MONTHS, AND REQUIRE ACCESS TO MENTAL HEALTH PROVIDERS. THE RECENTLY EMPHASIZED PRACTICE OF DEPRESSION SCREENING IN PEDIATRIC DIABETES CLINICS HAS INCREASED THE NUMBER OF MENTAL HEALTH REFERRALS, AS 20-30% OF YOUTH WITH T1D ENDORSE ELEVATED DEPRESSIVE SYMPTOMS. YET, MOST PEDIATRIC DIABETES CLINICS ARE UNDERSTAFFED WITH MENTAL HEALTH PROVIDERS, AND ONLY <25% OF YOUTH REFERRED FOR OUTPATIENT TREATMENT FOLLOW THROUGH WITH AN APPOINTMENT. TARGETED SINGLE-SESSION INTERVENTIONS (SSIS) MAY ALLEVIATE BARRIERS TO ACCESSING TRADITIONAL OUTPATIENT THERAPY AND REDUCE DEPRESSIVE SYMPTOMS IN YOUTH WITH T1D, BUT AN SSI THAT INCORPORATES EVIDENCE-BASED STRATEGIES TO TREAT DEPRESSIVE SYMPTOMS AND LOWER HBA1C FOR YOUTH WITH T1D DOES NOT YET EXIST. THE PROPOSED K23 CAREER DEVELOPMENT AWARD AIMS TO ADDRESS THESE GAPS IN RESEARCH AND CLINICAL CARE BY ADAPTING AND PILOT TESTING A T1D-SPECIFIC DEPRESSION SSI INTEGRATED INTO PEDIATRIC T1D MEDICAL CARE. THE FIRST GOAL IS TO CREATE A T1D-SPECIFIC DEPRESSION SSI TREATMENT MANUAL BY ELICITING FEEDBACK FROM A SMALL GROUP OF ADOLESCENTS. THE SECOND GOAL IS TO EXAMINE THE FEASIBILITY, ACCEPTABILITY, AND INITIAL EFFICACY OF AN INTEGRATED T1D-SPECIFIC DEPRESSION SSI APPROACH IN A RANDOMIZED PILOT TRIAL TO REDUCE DEPRESSIVE SYMPTOMS AND LOWER GLYCEMIC LEVELS IN YOUTH WITH T1D. THE THIRD GOAL IS TO UNDERSTAND THE BARRIERS AND FACILITATORS OF IMPLEMENTING THE SSI APPROACH IN DIABETES CLINICS FOR FURTHER REFINEMENT IN FOLLOW-UP TESTING. PILOTING AN INTEGRATED SSI APPROACH COULD LEAD TO IMPROVEMENTS IN THE ACUTE AND LONG-TERM PSYCHOLOGICAL AND PHYSICAL HEALTH OF YOUTH WITH T1D AND INCREASE THE ACCESSIBILITY, SCALABILITY, AND COST-EFFECTIVENESS OF PSYCHOLOGICAL TREATMENT WITHIN PEDIATRIC T1D CARE. MOREOVER, THIS RESEARCH PLAN SUPPORTS THE CANDIDATES’ CAREER DEVELOPMENT GOALS OF GAINING ADVANCED TRAINING IN CLINICAL TRIAL RESEARCH DESIGN AND METHODS, BECOMING AN EXPERT IN FEASIBLE AND FLEXIBLE INTERVENTION DESIGNS (E.G., SSIS), ENHANCING KNOWLEDGE OF INTEGRATED HEALTHCARE IN PEDIATRIC DIABETES, AND DEVELOPING INTERVENTIONS THAT MINIMIZE BARRIERS TO CARE. THROUGH A COMBINATION OF FORMAL DIDACTICS AND DIRECT MENTORED TRAINING EXPERIENCES WITH HER MENTORING TEAM, DR. MONZON WILL GAIN THE NECESSARY KNOWLEDGE AND SKILLS TO IMPLEMENT THE PROPOSED RESEARCH PROJECT AND TRANSITION TOWARD AN INDEPENDENT RESEARCH CAREER. FURTHER, THE FINDINGS FROM THE PROPOSED PROJECT WILL INFORM AN R01 APPLICATION TO CONDUCT A LARGER, MULTISITE RANDOMIZED TRIAL THAT HAS SUFFICIENT POWER TO EXAMINE THE EFFICACY OF THE T1D-SPECIFIC DEPRESSION SSI.

PHARMACOGENETICS OF BETA2-AGONISTS IN ASTHMA

CONGRESSIONALLY-MANDATED HEALTH INFORMATION TECHNOLOGY GRANTS

LUNG SELECTIVE CRISPR DELIVERY FOR TREATMENT OF GENETIC SURFACTANT DISEASE - NEONATAL RESPIRATORY DISTRESS SYNDROME (RDS) IS THE MOST COMMON RESPIRATORY CAUSE OF DEATH AND MORBIDITY IN INFANTS <1 YEAR OF AGE IN THE UNITED STATES. MONOGENIC MUTATIONS IN GENES REGULATING SURFACTANT HOMEOSTASIS, NAMELY SURFACTANT PROTEIN B (SFTPB), SURFACTANT PROTEIN C (SFTPC), AND ATP BINDING CASSETTE SUBFAMILY A MEMBER 3 (ABCA3), ARE CAUSATIVE DRIVERS OF RDS IN 25% OF INFANTS WITH SEVERE REFRACTORY RESPIRATORY FAILURE. STANDARD THERAPEUTIC REGIMENS FOR GENETIC LUNG DISEASE ARE LIMITED TO SYMPTOMATIC TREATMENTS AND LUNG TRANSPLANT, A PROCEDURE WITH POOR PROGNOSIS FOR LONG-TERM SURVIVAL AND HIGH COMPLICATION RATES. THESE UNSATISFACTORY OUTCOMES HIGHLIGHT THE PRESSING NEED FOR MORE PRECISE THERAPIES THAT DIRECTLY ADDRESS THE GENETIC ABERRATIONS UNDERLYING RDS. HEREIN, WE COMBINE HIGHLY COMPLEMENTARY EXPERTISE IN NEONATAL LUNG DISEASE TREATMENT (DR. ALAPATI) AND NON-VIRAL GENE DELIVERY (DR. SULLIVAN) NECESSARY TO DEVELOP A NON-SURGICAL APPROACH TO GENETICALLY CORRECT LUNG PROGENITOR CELLS DURING EARLY POSTNATAL LUNG DEVELOPMENT, A WIDELY ACCESSIBLE STRATEGY DESIGNED TO PREVENT DISEASE MANIFESTATION. WE WILL ESTABLISH THIS INNOVATIVE AND TRANSLATIONALLY-RELEVANT APPROACH VIA TWO AIMS: AIM 1. DESIGN NON-VIRAL NANOCARRIERS (‘POLYPLEXES’) THAT ARE BIOCOMPATIBLE, STABLE IN LUNG FLUIDS, AND CAPABLE OF CELL-SELECTIVE AND EFFICIENT GENE EDITING IN NEONATAL AT2 CELLS. AIM 2. ENGINEER A PARTIAL-LIQUID VENTILATION APPROACH FOR CRISPR-CAS9 DELIVERY TO MAXIMIZE AT2 CELL ACCESS AND GENE EDITING PERSISTENCE IN MODELS OF NEONATAL LUNG, AND DEMONSTRATE THIS APPROACH FOR DURABLE, WIDESPREAD, AND SAFE NON-VIRAL GENE EDITING IN LUNG EPITHELIUM. OUR HYPOTHESIS IS BUILT ON OUR PUBLISHED STUDIES DEMONSTRATING THAT (I) HISTONE POLYPLEX GENE TRANSFER HINGES UPON POLYPLEX UPTAKE VIA THE CAVEOLIN-1 TRANSPORTER, A MECHANISM THAT ENABLES HIGHLY EFFICIENT TRANSFECTION IN CAVEOLIN-1- EXPRESSING CELLS AND PERMITS PRECISE CELL ‘TARGETING’ BASED UPON DIFFERENCES IN CAVEOLIN-1 AVAILABILITY; AND (II) AIRWAY DELIVERY OF CRISPR-CAS9 CARGO INTO FLUID FILLED FETAL LUNGS RESULTS IN EFFICIENT PULMONARY EPITHELIAL CELL GENE EDITING. THIS WORK WILL THUS UNCOVER IMPORTANT NEW INFORMATION ON NEONATAL PULMONARY EPITHELIAL GENE TRANSFER MECHANISMS WHILE SIMULTANEOUSLY ESTABLISHING NEW, MORE CELL-SELECTIVE GENE THERAPY STRATEGIES RELEVANT TO A VARIETY OF PULMONARY GENETIC DISORDERS. THE STUDY OUTCOME WILL DEMONSTRATE A NEW DELIVERY PLATFORM FOR EFFECTIVE, CELL- SPECIFIC, AND SAFE GENE EDITING IN POSTNATAL LUNG EPITHELIUM, A STRATEGY THAT WOULD ENABLE WIDE USAGE EVEN IN BASIC-LEVEL NICUS, WHILE SIMULTANEOUSLY ALIGNING WITH THE TIMING OF DISEASE DIAGNOSIS, AND LAY GROUNDWORK FOR FUTURE TRANSLATION TO FUNDAMENTALLY NEW, MORE EFFECTIVE, AND ONE-SHOT TREATMENT MODES FOR GENETIC SURFACTANT PROTEIN DISEASES.

NON-INVASIVE MEASUREMENT OF PULMONARY DYSFUNCTION IN CHILDREN WITH CEREBRAL PALSY - PROJECT SUMMARY THIS R21 APPLICATION PROPOSES THE UTILIZATION OF A NOVEL NON-INVASIVE REAL-TIME BREATHING SENSOR – PNEURIP- TO MEASURE PULMONARY FUNCTION (PF) IN CHILDREN WITH HIGH-LEVEL CEREBRAL PALSY. CURRENTLY THE STANDARD MEASURES OF PF SUCH AS SPIROMETRY AND PEAK FLOW METERS ARE TOO STRENUOUS FOR CHILDREN AND THOSE WITH SEVERE CP, AS A RESULT THEY HAVE LOW COMPLIANCE RATES. THE PNEURIP DOES NOT REQUIRE ACTIVE USER PARTICIPATION AND CAN PASSIVELY MEASURE PF. IT CONSISTS OF TWO INDUCTIVE BANDS WORN AROUND THE CHEST AND ABDOMEN THAT MEASURE AND DIFFERENTIATE DIAPHRAGMATIC AND CHEST BREATHING THROUGH RESPIRATORY INDUCTANCE PLETHYSMOGRAPHY (RIP). READINGS ARE RECORDED AND ANALYZED ON A SMALL CHEST-WORN UNIT AND WIRELESSLY TRANSMITTED TO AN IPAD. THE PNEURIP YIELDS INDICES OF WORK OF BREATHING (WOB) WHICH INCLUDES THE PHASE ANGLE BETWEEN THE CHEST AND ABDOMEN; PERCENTAGE BREATHING THROUGH THE RIBCAGE; RESPIRATORY RATE; AND LABORED BREATHING INDEX. THIS SENSOR TAKES LITTLE TIME TO SET UP AND READINGS ARE PROVIDED INSTANTANEOUSLY. THE WOB INDICES PROVIDE A SCREENING TOOL FOR PULMONARY DIAGNOSIS AND TREATMENT, DECREASE THE RISK FOR PNEUMONIA AND RESPIRATORY ILLNESS, AND HAS THE POTENTIAL TO ACT AS A MARKER FOR SCOLIOSIS IN CHILDREN WITH HIGH- LEVEL CP. OUR RESEARCH TEAM (CLINICIANS, BASIC SCIENTISTS, BIOENGINEERS & THERAPISTS) HAS SHOWN THE EFFECTIVENESS OF THE PROPOSED PF METHODOLOGY IN BOTH INTENSIVE CARE, EMERGENCY DEPARTMENTS, OPERATING ROOMS, AND NEUROMUSCULAR CLINICS. THE IMPACT ON THE FIELD WILL BE TO HAVE A SIMPLE AND FAST WAY TO MEASURE PULMONARY FUNCTION IN CHILDREN AND ADULTS WITH SEVERE CP AND CORRELATE THIS TO MEASURES OF FUNCTION AND SCOLIOSIS SEVERITY AS THE EFFECTS OF SCOLIOSIS, WHICH IS COMMON IN CP, ON PULMONARY FUNCTION IS UNCLEAR. MEASURES OF MOTOR FUNCTION ARE CLASSIFIED BY THE GROSS MOTOR FUNCTIONAL CLASSIFICATION SYSTEM (GMFCS), RANKING FROM I TO V, WITH WORSENING DISABILITY FROM NEAR NORMAL GAIT IN TYPE I TO COMPLETE WHEELCHAIR USE IN TYPE V. THIS PROJECT WILL ADDRESS GMFCS LEVELS IV AND V WHICH INCLUDES PEOPLE USING WHEELCHAIRS. THE TWO SPECIFIC AIMS ARE A) MEASURE WOB INDICES NON- INVASIVELY USING THE PNEURIP SENSOR IN CHILDREN WITH CP WHO USE A WHEELCHAIR (GMFCS LEVEL IV, V) AND VALIDATE THE USE OF WOB INDICES AS A SCREENING TEST FOR PULMONARY DYSFUNCTION., 2) DETERMINE THE CORRELATION BETWEEN WOB INDICES AND THE DEGREE OF SCOLIOSIS USING THE PNEURIP SENSOR IN 250 CHILDREN WITH CP WHO USE A WHEELCHAIR (GMFCS LEVEL IV, V). THE PROPOSED RESEARCH IS INNOVATIVE BECAUSE THIS RIP TECHNOLOGY TO DATE HAS NOT BEEN INCORPORATED IN THE DIAGNOSIS AND TREATMENT OF CHILDREN WITH CP. THE ADVANTAGES INCLUDE PROVISION OF THE DIAGNOSTIC DATA IN REAL-TIME, LESS STRESS TO THE PATIENTS, AND A REDUCTION IN LAB TESTING AND IMAGING. COLLECTIVELY, WE EXPECT THE OUTCOMES OF THESE CLINICAL STUDIES WILL GREATLY ADD TO PULMONARY TREATMENT IN CP.

RURAL HEALTH CARE SERVICES OUTREACH GRANT PROGRAM

NEW JERSEY MENTORING INITIATIVE

SPOOCI: SELF-REFERENCED PERSONAL OMNI-PURPOSE ORTHOTIC CONTROL INTERFACE

IDENTIFY RECEPTORS FOR B7 FAMILY IMMUNE CHECKPOINT ORPHAN LIGANDS USING A NOVEL CELLBASED APPROACH

UNKNOWN TITLE

BEHAVIORAL FAMILY SYSTEMS THERAPY FOR TEENS WITH TYPE 2 DIABETES: A PILOT

REDIRECT T CELL SPECIFICITY TO IGE-EXPRESSING B CELLS FOR SEVERE ALLERGIC ASTHMA

PROFILING AND CHARACTERIZING AXONAL PRECURSOR MICRO RNAS IN REGENERATING NERVE

IMPROVING COMMUNICATION WITH LOW LITERACY CARETAKERS

FUNCTION OF PILRNA/MIWI PATHWAYS IN NEURONAL AXON GROWTH AND REGENERATION

GROWSMART: PILOT TRIAL OF AN AI-BASED OBESITY PREVENTION TOOL IN PEDIATRIC PRIMARY CARE - PROJECT SUMMARY CHILDHOOD OBESITY IS A SIGNIFICANT LONG-TERM PUBLIC HEALTH PROBLEM AFFECTING NEARLY 1 IN 5 CHILDREN IN THE UNITED STATES AND CONTRIBUTING TO SIGNIFICANT PHYSICAL AND MENTAL HEALTH PROBLEMS, INCLUDING DIABETES AND KIDNEY DISEASE. DECADES OF RIGOROUS RESEARCH HAVE SHOWN THAT OBESITY DEVELOPS IN EARLY CHILDHOOD AND THAT ONCE A CHILD HAS DEVELOPED OBESITY, TREATMENT IS CHALLENGING. HOWEVER, FRONT-LINE PEDIATRIC PRIMARY CARE PROVIDERS (PCPS) FACE CHALLENGES IN IDENTIFYING CHILDREN AT RISK FOR DEVELOPING OBESITY AND COUNSELING FAMILIES ON PREVENTIVE HEALTHY LIFESTYLE BEHAVIORS. THIS PROJECT AIMS TO FILL THIS IMPORTANT GAP BY TESTING GROWSMART, A TOOL DEVELOPED OVER SEVEN YEARS BY OUR INTERDISCIPLINARY TEAM TO HELP PCPS UNDERSTAND A CHILD’S PREDICTED GROWTH AND RISK FOR OBESITY USING ADVANCED MACHINE LEARNING APPLIED TO ELECTRONIC HEALTH RECORD (EHR) DATA. THE CURRENT TOOL HAS BEEN EXTENSIVELY VALIDATED USING LARGE-SCALE DATA ACROSS DIFFERENT PERIODS AND GEOGRAPHIC REGIONS AND TESTED WITH PCPS TO IMPROVE ITS USABILITY AND ACCEPTABILITY. FOR THIS PROJECT WE PLAN TO INTEGRATE GROWSMART INTO THE EHR WORKFLOW AND CONDUCT FORMATIVE USABILITY TESTING WITH PCPS TO ENSURE THAT THE RESULTING TOOL IS ACCEPTABLE AND USEFUL TO PCPS (AIM 1). WE WILL THEN CONDUCT A PILOT CLUSTER RCT AT TWENTY PRIMARY CARE CLINICS IN THE NEMOURS NETWORK TO TEST THE IMPACT OF GROWSMART ON PCP DISCUSSION OF HEALTHY LIFESTYLE BEHAVIORS WITH FAMILIES USING CUSTOMIZED NATURAL LANGUAGE PROCESSING METHODS (AIM 2). WE WILL ALSO ASSESS THE PRELIMINARY IMPACT OF GROWSMART ON CHILD GROWTH USING ADVANCED STATISTICAL METHODS TO UNDERSTAND GROWTH TRAJECTORIES (AIM 3). THROUGHOUT THE PILOT STUDY, WE WILL EMPLOY COMMUNITY- ENGAGED STRATEGIES TO ENSURE THE DESIGN AND IMPLEMENTATION OF THE STUDY ARE FEASIBLE AND THAT FINDINGS FROM THE STUDY CAN BE USED TO IMPROVE CLINICAL PRACTICE. HAVING A RELIABLE PREDICTIVE TOOL THAT IS INTEGRATED INTO THE CLINICAL WORKFLOW OF PCPS CAN FACILITATE TIMELY DISCUSSIONS BETWEEN PCPS AND FAMILIES TO PROMOTE HEALTHY LIFESTYLES AND HEALTHY GROWTH IN EARLY CHILDHOOD. BECAUSE OF THE INTEROPERABLE DESIGN OF GROWSMART, THIS PILOT TRIAL WILL BE EASILY SCALED FOR LARGER MULTI-SITE STUDIES TO SUPPORT CHILDHOOD OBESITY EFFORTS IN MULTIPLE HEALTHCARE SYSTEMS.

BRAIN STIMULATION FOR PREVENTION OF EPILEPTOGENESIS

HEALTH CARE AND OTHER FACILITIES

OTHER HEALTH PROFESSIONS PROGRAMS (EARMARKS): IOWA BRACES FOR THE ?CARE GAP?: BUILDING A STABLE DIRECT CARE WORKFORCE

MEASUREMENT OF BIOMARKERS IN SAMPLES COLLECTED IN A COENZYME Q10 TREATMENT TRIAL IN GULF WAR ILLNESS AND CONTROL SUBJECTS

STAFFING FOR ADEQUATE FIRE AND EMERGENCY RESPONSE (SAFER)

WESTERN ARTS ALLIANCE (WAA) WILL HELP U.S. ARTISTS AND ARTISTIC COMPANIES EXPORT LIVE PERFORMANCES TO COLOMBIA, AUSTRALIA, AND GERMANY. WAA WILL UNDERWRITE THE COST OF U.S. ARTS ORGANIZATIONS AND ARTISTS' PARTICIPATION IN PROMOTIONAL EVENTS ABROAD.

AWARD PURPOSE THE PURPOSE OF THE AWARD IS TO PROVIDE AN UPDATE TO THE REPORT ENTITLED ECONOMIC CONTRIBUTION OF THE US TUGBOAT TOWBOAT AND BARGE INDUSTRY HEREAFTER REFERRED TO AS THE STUDY WHICH WAS RELEASED IN JUNE 2021. THE REPORT QUANTIFIED THE INDUSTRYS ECONOMIC IMPACT AND VALUE AT THE NATIONAL AND STATE LEVELS. THE SCOPE OF THE STUDY INCLUDED ALL US FLAG TUGBOATS TOWBOATS AND BARGES THAT OPERATE IN WHOLE OR IN PART ON THE DOMESTIC WATERWAYS AND PORTS OF THE US INCLUDING THOSE ON RIVERS INTRACOASTAL WATERWAYS ATLANTIC PACIFIC AND GULF COASTS THE GREAT LAKES THE SAINT LAWRENCE SEAWAY AND BETWEEN THE US MAINLAND AND NONCONTIGUOUS STATES AND TERRITORIES. SINCE RELEASE OF THE STUDY IN 2021 THE INDUSTRY HAS UNDERGONE SIGNIFICANT CHANGES AND HAS BEEN IMPACTED GREATLY BY CHANGES IN GLOBAL AND DOMESTIC TRADE AS WELL AS THE CONTINUED ADVANCEMENT IN INFRASTRUCTURE DEVELOPMENT ON OUR NATIONS INLAND WATERWAYS. ACTIVITIES TO BE PERFORMED EVALUATION AND INVESTIGATION OF ECONOMIC IMPACTS AND POSSIBLE EFFECTS OF INFRASTRUCTURE INVESTMENT. CALCULATE THE TOTAL AMOUNT OF INDUSTRY BUSINESS REVENUE GENERATED AND TAXES PAID. CALCULATE THE INDUSTRY CONTRIBUTIONS TO NATIONAL GDP. CALCULATE THE JOB EFFECTS AND MULTIPLIERS NATIONALLY BY DIRECT INDIRECT AND INDUCED JOBS. QUANTIFY THE ECONOMIC VALUE OF THE TUGBOAT TOWBOAT AND BARGE INDUSTRY AS AN ENABLER TO IMPORTS AND EXPORTS AND HOW THIS INDUSTRY PROMOTES THE EXPORTS OF US GOODS TO GLOBAL MARKETS. ARTICULATE THE ECONOMIC VALUE THE INDUSTRY CONTRIBUTES TO MOVING GOODS FROM SOURCE TO CONSUMPTION IN THE US DOMESTIC MARKET. DESCRIBE THE TYPES OF CARGOES CARRIED AND INDUSTRIES SUPPORTED NATIONALLY. BASIC UNDERLYING DETAILED INDUSTRY FREIGHT FLOW DATA. COMPARISON OF INDUSTRY WAGES TO SIMILAR SECTORS. INDUSTRY WAGES NATIONALLY. QUANTIFY THE PRIVATE INVESTMENT IN THE INDUSTRY THAT HAS OCCURRED IN THE LAST FIVE YEARS AND WHAT IS PLANNED FOR THE NEXT FIVE YEARS. CALCULATE IN AGGREGATE TERMS THE RETURN ON INVESTMENT TO THE INDUSTRY E G TIMES DOLLARS INVESTED RESULTS IN Y DOLLARS IN OUTPUT. ANALYZE AND DISCUSS NEW TRENDS SUCH AS AGING FLEETS DIGITALIZATION AND AUTOMATION INNOVATIONS INCLUDING ARTIFICIAL INTELLIGENCE AND MACHINE LEARNING FOR ONBOARD OPERATIONS VESSEL MANAGEMENT SCHEDULING AND DEPLOYMENTS LNG TERMINALS AND OTHER. CALCULATE THE TOTAL AMOUNT OF INDUSTRY BUSINESS REVENUE GENERATED AND TAXES PAID BY STATE. CALCULATE THE JOBS EFFECT AND MULTIPLIERS BY STATE DATA FOR DIRECT INDIRECT AND INDUCED JOBS. INDUSTRY WAGES BY STATE. DESCRIBE THE TYPES OF CARGOES CARRIED AND INDUSTRIES SUPPORTED BY STATE. DESCRIBE HOW THE TUGBOAT TOWBOAT AND BARGE INDUSTRY ASSISTS WITH TRANSPORTING THE VOLUME OF CARGO COMING IN AND GOING OUT OF EACH STATES PORTS.DESCRIBE WHAT INDUSTRIAL AND AGRICULTURAL SECTORS RELY ON WATER TRANSPORTATION AND THE VOLUME OF CERTAIN KEY COMMODITIES THAT MOVE ON THE WATER IN EACH STATE. LIST THE WATERWAYS AND TOP FIVE CARGOES CARRIED IN THE WATERWAYS OF EACH STATE. DESCRIBE HOW THE TUGBOAT TOWBOAT AND BARGE INDUSTRY ASSISTS WITH TRANSPORTING THE VOLUME OF CARGO COMING IN AND GOING OUT OF THE NATIONS PORTS. DESCRIBE THE TYPES OF CARGOES CARRIED AND INDUSTRIES SUPPORTED BY WATERWAY. QUANTIFY THE IMPACTS BY WATERWAY. INDUSTRY IMPACT FROM A SHIPPING COST POINT OF VIEW. DESCRIBE THE TYPES OF CARGOES CARRIED AND INDUSTRIES SUPPORTED BY WATERWAY. DESCRIBE WHAT RETAIL AGRICULTURAL INDUSTRIAL AND AGRICULTURAL SECTORS RELY ON WATER TRANSPORTATION AND THE VOLUME OF KEY COMMODITIES THAT MOVE ON THE WATER. WHERE POSSIBLE CHARACTERIZE INDUSTRYS CONTRIBUTIONS TO MOVING GOVERNMENT OWNED AND OR GOVERNMENT-IMPELLED CARGO. DELIVERABLES EXPECTED OUTCOMES A WELL WRITTEN COMPREHENSIVE REPORT PLUS AN EXECUTIVE SUMMARY THAT UPDATES AND BUILDS UPON THE PRINCIPLES AND FINDINGS OF THE ORIGINAL REPORT PRODUCED IN MAY 2017. SET OF STANDALONE VERSIONS OF RELEVANT GRAPHS MAPS AND CHARTS THAT VISUALLY DEPICT THE INFORMATION PRESENTED IN THE REPORT. TABLES OF BOTH NATIONAL AND STATE LEVEL RAW DATA THAT CAN BE INDEPENDENTLY USED AND MANIPULATED IN ISOLATION OF ANY OTHER PORTION OF THE REPORT. TWO BRIEFINGS AND PRESENT THE STUDY FINDINGS TO SELECT AUDIENCES IN THE WASHINGTON DC AREA AT THE DIRECTION OF MARAD. THESE DELIVERABLES TO BE PRESENTED IN ELECTRONIC AND HARD COPY FORMATS. INTENDED BENEFICIARY MARAD AND AWO AND THE GENERAL PUBLIC. SUBRECIPIENT ACTIVITIES NOT APPLICABLE.

SERVICE FOCUSED SPECIAL CONGRESSIONAL INITIATIVE

FUELING SENIORS: MEAL SUSTAINABILITY THROUGH CO-GENERATION PROJECT

EARMARK

GRADUATE PSYCHOLOGY EDUCATION PROGRAMS

OTHER HEALTH PROFESSIONS PROGRAMS (EARMARKS)

STAFFING FOR ADEQUATE FIRE AND EMERGENCY RESPONSE (SAFER)

BEHAVIORAL HEALTH WORKFORCE EDUCATION AND TRAINING (BHWET) PROGRAM

REDUCING THE EFFECTS ON TRAIN CREWS OF TRAUMATIC EXPOSURE TO GRADE CROSSING AND TRESPASSER INCIDENTS

AFA LONG ISLAND EDUCATION, RESOURCE & TRAINING CENTER

AWARD PURPOSE TO ADD COOPERATIVE AGREEMENT INTO USA SPENDING SINCE IT WAS NEVER PUT IN THE DATABASE. THIS ACTION WAS ONLY FOR 8 MONTHS. ACTIVITIES TO BE PERFORMED TO UPDATE ON A STUDY RELASED IN 2016 BY THE AWO ENTITLED ECONOMIC CONTRIBUTION OF THE UNITED STATES TUGBOAT. DELIVERABLES EXPECTED AN UPDATE ON A 2016 STUDY BY AWO. INTENDED BENEFICIARY AMERICAN WATERWAYS OPERATORS AWO MARAD AND THE GENERAL PUBLIC. SUBRECIPIENT ACTIVITIES NOT APPLICABLE.

GRADUATE PSYCHOLOGY EDUCATION PROGRAMS

ADAPTING A PEER MENTORSHIP PROGRAM TO IMPROVE CGM USE AMONG LATINO YOUTH WITH TYPE 1 DIABETES FROM FAMILIES WITH LIMITED ENGLISH PROFICIENCY - PROJECT SUMMARY LIMITED ENGLISH PROFICIENCY CONTRIBUTES TO ADVERSE HEALTH OUTCOMES. LATINO YOUTH WITH TYPE 1 DIABETES (T1D) TEND TO HAVE HIGHER GLYCEMIC LEVELS THAN NON-LATINO WHITE (WHITE) YOUTH AND ARE LESS LIKELY TO USE CONTINUOUS GLUCOSE MONITORING SYSTEMS (CGM), AN ADVANCED DIABETES TECHNOLOGY THAT CAN LOWER GLYCEMIC LEVELS AND IMPROVE HEALTH. BARRIERS TO CGM USE EXIST AT FAMILY (E.G., SKEPTICISM ABOUT CGM), PROVIDER (E.G., NOT TAILORING EDUCATION TO FAMILIES), AND HEALTHCARE SYSTEM LEVELS (E.G., COMPLEX INSURANCE APPROVAL PROCESS, COST OF DEVICES). DUE TO LIMITATIONS OF OUR HEALTHCARE SYSTEM (E.G., FEW BILINGUAL PROVIDERS), LATINO FAMILIES WITH LIMITED ENGLISH PROFICIENCY MAY HAVE EVEN MORE DIFFICULTY OVERCOMING THESE BARRIERS. IN OUR ONGOING RESEARCH, WE PARTNERED WITH ENGLISH-PROFICIENT BLACK AND LATINO YOUTH WITH T1D AND THEIR CAREGIVERS TO CO-DEVELOP TYPE 1 TOGETHER, AN INTERVENTION TO PROMOTE USE OF CGM. IN TYPE 1 TOGETHER, FAMILIES MEET MONTHLY WITH PEER MENTOR FAMILIES AND A COMMUNITY HEALTH WORKER. FAMILIES OF YOUTH WITH T1D AND LIMITED ENGLISH PROFICIENCY REPORT UNIQUE CHALLENGES TO MANAGING T1D, INDICATING A NEED FOR INTERVENTIONS TAILORED TO FAMILY BELIEFS AND VALUES AND DELIVERED IN THEIR PREFERRED LANGUAGE. THE OBJECTIVE OF THIS PROPOSAL IS TO ADAPT AND PILOT-TEST TYPE 1 TOGETHER FOR LATINO YOUTH FROM FAMILIES WITH LIMITED ENGLISH PROFICIENCY. DURING THE FIRST YEAR OF THIS PROPOSAL, WE WILL CONDUCT FOCUS GROUPS TO GATHER LATINO ADOLESCENT AND CAREGIVER PERSPECTIVES ON THE INTERVENTION AND THEN WORK WITH FAMILY RESEARCH PARTNERS TO ADAPT THE INTERVENTION ACCORDINGLY. THEN, WE WILL CONDUCT A PILOT RANDOMIZED CONTROLLED TRIAL. FAMILIES (N=20) WILL BE RECRUITED DURING OR AFTER ENDOCRINOLOGIST CLINIC VISITS AND RANDOMIZED (1:1) TO THE ADAPTED TYPE 1 TOGETHER OR A 3-MONTH WAITLIST CONTROL. PRIMARY OUTCOMES WILL BE INTERVENTION ACCEPTABILITY AND FEASIBILITY, USE OF CGM, AND GLYCEMIC LEVELS (I.E., HBA1C, TIME IN RANGE). FINDINGS FROM THE CURRENT STUDY WILL INFORM FUTURE RESEARCH AIMED AT TESTING THE EFFICACY OF THE INTERVENTION IN A LARGER, MULTISITE RANDOMIZED CONTROLLED TRIAL.

FEEDING CHALLENGES AND PARENTAL DISTRESS AMONG FAMILIES OF YOUNG CHILDREN WITH FOOD ALLERGY - FEEDING DIFFICULTIES ARE PREVALENT AMONG YOUTH WITH FOOD ALLERGIES (FA) AND POSE A RISK FOR SOCIAL, PHYSICAL, AND PSYCHOLOGICAL CHALLENGES. YET, SPECIFIC FEEDING PROBLEMS DURING MEALS AND HOW PARENTS RESPOND TO PROBLEMS HAVE NOT BEEN DIRECTLY OBSERVED, WHICH PRECLUDES BEHAVIORAL INTERVENTION DEVELOPMENT. PARENTS ARE ACTIVE PARTICIPANTS IN THE DEVELOPMENT OF CHILD FEEDING HABITS DURING EARLY CHILDHOOD. HOWEVER, PARENTS OF YOUTH WITH FA EXPERIENCE HIGH RATES OF DISTRESS, WHICH MAY CONTRIBUTE TO THE FEEDING DIFFICULTIES AND MEALTIME BEHAVIOR PROBLEMS THAT THEY REPORT. DESPITE PARENT-REPORTED MEALTIME BEHAVIOR PROBLEMS AND A LARGE BODY OF EVIDENCE DOCUMENTING THE PSYCHOSOCIAL IMPACT OF FA ON PARENTS AND FAMILIES, FEW INTERVENTIONS EXIST TO ADDRESS THIS NEED. TO ADDRESS THIS GAP, THE PROPOSED K23 AIMS TO: 1) UNDERSTAND PARENT PERSPECTIVES AND CHARACTERIZE CORE FEATURES OF FEEDING PROBLEMS IN FA, 2) DIRECTLY OBSERVE MEALTIME BEHAVIOR PROBLEMS AND UNDERSTAND THEIR ASSOCIATION WITH PARENT AND FAMILY PSYCHOSOCIAL FACTORS, AND 3) CROWDSOURCE PARENT FEEDBACK ON CONTENT TO INFORM A FUTURE, NOVEL, BEHAVIORAL INTERVENTION FOR PARENTS OF YOUTH WITH FA. THE DATA FROM THE PROPOSED STUDY WILL DIRECTLY INFORM THE DEVELOPMENT OF AN INNOVATIVE BEHAVIORAL INTERVENTION FOR PARENTS OF YOUNG CHILDREN WITH FA AND WILL PROVIDE PRELIMINARY DATA FOR AN R01 PROPOSAL TO EXAMINE EFFICACY OF THE FUTURE INTERVENTION. THIS K23 PROPOSAL AIMS TO PROVIDE DR. CAMPBELL WITH ADDITIONAL RESEARCH TRAINING IN 1) CONTENT KNOWLEDGE RELATED TO PEDIATRIC FOOD ALLERGY, 2) STAKEHOLDER ENGAGEMENT METHODS, 3) OBSERVATIONAL MEALTIME DATA COLLECTION AND ANALYSIS, AND 4) DEVELOPMENT OF NOVEL BEHAVIORAL INTERVENTIONS. A TEAM OF ACCOMPLISHED MENTORS WITH EXPERTISE IN MEALTIME BEHAVIOR ASSESSMENT, PEDIATRIC FOOD ALLERGY, AND BEHAVIORAL INTERVENTION DEVELOPMENT IN ADDITION TO AN INSTITUTION WITH A TRACK RECORD OF SUPPORTING EARLY CAREER INVESTIGATORS WILL ENSURE DR. CAMPBELL’S SUCCESS. COMPLETION OF THESE TRAINING GOALS WILL FACILITATE DR. CAMPBELL’S LONG-TERM GOAL OF BECOMING AN INDEPENDENT INVESTIGATOR AND LEADER IN DEVELOPING PARENT-FOCUSED PSYCHOSOCIAL INTERVENTIONS IN PEDIATRIC FOOD ALLERGY.

EXPANDING FOOD SAFETY OUTREACH AND EDUCATION FOR LOCAL FOOD SYSTEMS IN CALIFORNIA

STAFFING FOR ADEQUATE FIRE AND EMERGENCY RESPONSE (SAFER)

HOUSING COUNSELING

INHIBITION OF THE MLL-AF4-AF9 INTERACTION IN PEDIATRIC LEUKEMIA

NEURAL CORRELATES OF THE Y CHROMOSOME IN AUTISM: XYY SYNDROME AS A GENETIC MODEL

AN ANTICOAGULATION-FREE ARTIFICIAL PLACENTA OXYGENATOR - PROJECT SUMMARY DR. DAVID BLAUVELT IS COMMITTED TO HIS DEVELOPMENT AS A CLINICIAN-SCIENTIST DEDICATED TO HELPING CRITICALLY ILL CHILDREN THROUGH BIOENGINEERING, WITH A SPECIFIC FOCUS ON INNOVATION IN EXTRACORPOREAL LIFE SUPPORT (ECLS). IN THIS PROPOSAL, HE AIMS TO DEVELOP AN ANTICOAGULATION-FREE ARTIFICIAL PLACENTA OXYGENATOR TO SUPPORT PRETERM INFANTS. EXTREME PREMATURITY HAS A HIGH BURDEN OF MORBIDITY AND MORTALITY; INFANTS BORN AT 23 WEEKS HAVE ONLY A 2% CHANCE OF SURVIVAL WITHOUT A MAJOR MORBIDITY. AN ARTIFICIAL PLACENTA IS AN ADAPTATION OF ECLS THAT MAY REDUCE MORTALITY AND CHRONIC LUNG DISEASE IN EXTREMELY PRETERM INFANTS. HOWEVER, CURRENT OXYGENATOR TECHNOLOGY IS UNSAFE FOR USE IN PRETERM INFANTS DUE TO HEMOCOMPATIBILITY LIMITATIONS. DR. BLAUVELT’S IMMEDIATE GOAL IS TO DETERMINE IF A MICROFLUIDIC SILICON MEMBRANE (SM) CAN IMPROVE OXYGENATOR HEMOCOMPATIBILITY. HIS LONG-TERM GOAL IS TO DEVELOP THE SKILLS NEEDED TO DESIGN, BUILD, AND TEST NEW ECLS TECHNOLOGIES AND TRANSLATE THEM TO THE BEDSIDE. SMS ARE RIGID, FLAT-PLATE SEMIPERMEABLE MEMBRANES THAT CAN REDUCE OXYGENATOR SURFACE AREA, OPTIMIZE BLOOD FLOW DYNAMICS, AND IMPROVE THE BLOOD-CONTACTING SURFACE CHEMICAL PROPERTIES. DR. BLAUVELT WILL USE THESE ADVANTAGES TO BUILD AND TEST SM OXYGENATORS WITH AN ULTIMATE GOAL OF DEVELOPING AN ANTICOAGULATION-FREE ARTIFICIAL PLACENTA. IN AIM 1, HE WILL EVALUATE THE GAS-EXCHANGE PERFORMANCE, PRESSURE DROP, AND PRIMING VOLUME OF AN SM OXYGENATOR OPTIMIZED WITH COMPUTATIONAL METHODS. IN AIM 2, HE WILL INVESTIGATE THE EFFECTS OF HEMOCOMPATIBLE SURFACE COATINGS ON CLOT FORMATION AND PROTEIN ADSORPTION. FINALLY, IN AIM 3, HE WILL DIRECTLY COMPARE THE HEMOCOMPATIBILITY OF AN SM OXYGENATOR TO A COMMERCIAL OXYGENATOR USING A NON-ANTICOAGULATED SWINE MODEL. THIS CAREER DEVELOPMENT AWARD WILL ALLOW DR. BLAUVELT TO ACHIEVE HIS SHORT AND LONG-TERM GOALS THROUGH A COMBINATION OF MENTORSHIP, RESEARCH EXPERIENCES, COURSEWORK, AND PROFESSIONAL DEVELOPMENT. HIS TEAM CONSISTS OF MENTORS AND ADVISORS WHO ARE EXPERTS IN BIOENGINEERING, ANIMAL MODELS, BIOMATERIALS, TRANSLATIONAL RESEARCH, ARTIFICIAL WOMB TECHNOLOGY, AND MEDICAL ETHICS. COMPLETION OF THE PROPOSED AIMS WILL PROVIDE FOUNDATIONAL DATA TO JUSTIFY CONTINUED TESTING OF AN SM OXYGENATOR IN A LONG-TERM PRETERM ANIMAL MODEL, WHICH WILL BE THE FOCUS OF A FUTURE R-AWARD.

FIREFIGHTER AND FIRST RESPONDER AWARENESS & OUTREACH

NOTIFICATION OF FIREFIGHTER & FIRST RESPONDER DEATHS

HOUSING COUNSELING ASSISTANCE PROGRAM

IDENTIFY CELL SURFACE PROTEIN LIGAND CANDIDATES FOR UNDERSTUDIED ADHESION GPCRS USING A SENSITIVE CELL-BASED APPROACH - PROJECT SUMMARY/ABSTRACT ADHESION G PROTEIN-COUPLED RECEPTORS (AGPCRS) ARE A GROUP OF 33 POORLY CHARACTERIZED NON-OLFACTORY GPCRS WITH DISTINCT FEATURES INCLUDING AUTOCATALYTIC PROCESSING AND LARGE EXTRACELLULAR REGIONS. AGPCRS ARE INVOLVED IN A MYRIAD OF BIOLOGICAL PROCESSES AND SOME OF THEM ARE ASSOCIATED WITH DISEASES, ESPECIALLY A WIDE RANGE OF CANCERS. THE EXTRACELLULAR REGIONS OF MANY OF THE AGPCRS CONTAIN DOMAINS THAT ARE KNOWN TO BE INVOLVED IN PROTEIN-PROTEIN INTERACTIONS, SUGGESTING THAT BINDING TO CELL SURFACE PROTEIN LIGANDS MAY PLAY AN IMPORTANT ROLE IN THEIR MECHANISMS OF ACTION. THE MAJORITY OF AGPCRS, HOWEVER, ARE ORPHAN RECEPTORS WITHOUT KNOWN LIGANDS. IDENTIFICATION OF LIGANDS FOR THESE AGPCRS SHOULD HELP UNDERSTAND THEIR PHYSIOLOGICAL FUNCTIONS AND ROLES IN CANCER DEVELOPMENT. A MAJOR CHALLENGE FOR IDENTIFYING LIGANDS INVOLVED IN LIGAND-RECEPTOR INTERACTIONS AT THE CELL-CELL INTERFACE IS THAT THEY TEND TO BIND THEIR RECEPTORS VERY WEAKLY AND CURRENTLY AVAILABLE METHODS DO NOT HAVE ENOUGH SENSITIVITY. TO OVERCOME THIS, WE PROPOSE TO EMPLOY A NOVEL AND HIGHLY SENSITIVE CELL-BASED APPROACH TO IDENTIFY PROTEIN LIGANDS FOR 17 UNDERSTUDIED ORPHAN AGPCRS. THE FEASIBILITY OF THE APPROACH HAS BEEN TESTED USING MODEL LIGANDS AND RECEPTORS THAT ARE KNOWN BIND TO EACH OTHER WITH LOW AFFINITIES. WE WILL USE THE CELL-BASED APPROACH TO SCREEN A COLLECTION OF TRANSMEMBRANE PROTEINS TO IDENTIFY LIGAND CANDIDATES FOR THE AGPCRS. LIGAND CANDIDATES IDENTIFIED IN THIS STUDY WILL PAVE THE WAY FOR MORE IN-DEPTH CHARACTERIZATION OF THEIR BINDINGS TO RESPECTIVE AGPCRS AND THE FUNCTIONAL CONSEQUENCES OF THE BINDINGS IN FUTURE STUDIES.

FIREFIGHTER & FIRST RESPONDER PREREQUISITE CERTIFICATION/BENEFITS

HOUSING COUNSELING ASSISTANCE PROGRAM

AN EHEALTH PSYCHOSOCIAL INTERVENTION FOR CAREGIVERS OF CHILDREN WITH CANCER

HOUSING COUNSELING ASSISTANCE PROGRAM

REAL-TIME USE OF CGM IN ADOLESCENTS WITH POORLY-CONTROLLED TYPE 1 DIABETES

HOUSING COUNSELING ASSISTANCE PROGRAM

SIMULATION STUDIES OF PARENTAL PERMISSION AND CHILDRENS ASSENT FOR RESEARCH

NATURALISTIC STUDIES OF PARENTAL PERMISSION AND CHILDREN?S ASSENT FOR RESEARCH

A NEW STRATEGY TO INCREASE PROTEOTOXIC CELL DEATH IN HEPATOCELLULAR CARCINOMA - INHIBITORS OF THE UBIQUITIN PROTEASOME SYSTEM (UPS, THE MAJOR PATHWAY THAT DEGRADES UNFOLDED PROTEINS) INCREASE PROTEOTOXIC STRESS AND HAVE CLINICAL SUCCESS FOR MULTIPLE MYELOMA BUT NOT FOR SOLID CANCERS SUCH AS HEPATOCELLULAR CARCINOMA (HCC). CURRENT CLINICAL STRATEGIES TO FURTHER ENHANCE PROTEOTOXIC STRESS IN SOLID TUMORS BY COMBINING PAN-HISTONE DEACETYLASE (HDAC) + UPS INHIBITORS HAS SOME SUCCESS BUT COMES WITH HIGH TOXICITY TO NORMAL TISSUES. WE PROPOSE AN ALTERNATIVE STRATEGY TO ENHANCE PROTEOTOXIC STRESS IN HCC BUT WITH LESS TOXICITY TO NON-CANCER CELLS BY COMBINING A NEW PAN-CYCLOPHILIN INHIBITOR CRV431 (CRV) AND A SECOND-GENERATION UPS INHIBITOR IXAZOMIB (IXZ). SINCE CYCLOPHILINS ARE IMPORTANT IN PROTEIN FOLDING, COMBINING A PAN-CYCLOPHILIN INHIBITOR SUCH AS CRV TO INCREASE MISFOLDED PROTEINS AND BLOCKING THEIR DEGRADATION WITH A UPS INHIBITOR SUCH AS IXZ AMPLIFIES PROTEOTOXIC STRESS AND FORCES APOPTOTIC CELL DEATH. OUR PRELIMINARY DATA SUPPORTS THE USE OF CRV + IXZ AS A NEW STRATEGY FOR TREATMENT OF HCC WITHOUT CAUSING TOXICITY TO NON-CANCER CELLS. WE PROPOSE THAT MAINTENANCE OF ELEVATED LEVELS OF PRO-SURVIVAL RESPONSE MEDIATOR XBP1S (UNFOLDED PROTEIN RESPONSE) AND LOW CYCLOPHILIN EXPRESSION/ACTIVITY TRIGGERS CELL DEATH IN HCC CELLS. NOTABLY, CRV + IXZ IS NOT TOXIC IN A NON-CANCER COMPARED TO HCC CELLS WHEREAS A CURRENT PROTEOTOXIC STRESS COMBINATION PANOBINOSTAT (CLINICALLY RELEVANT PAN-HDAC INHIBITOR) + IXZ IS EQUALLY TOXIC IN NON-CANCER AND HCC CELLS. THE HYPOTHESIS OF THIS PROPOSAL IS THAT CRV + IXZ MAINTENANCE OF HIGH XBP1S AND LOW CYCLOPHILIN EXPRESSION/ACTIVITY OVERWHELMS PRO-SURVIVAL PATHWAYS AND FORCES HCC CELLS TOWARD APOPTOTIC CELL DEATH WITHOUT HARMING NORMAL CELLS. THE RATIONALE IS THAT IF THIS NEW COMBINATION KILLS HCC CELLS WITHOUT HARMING NORMAL CELLS IN PRECLINICAL MODELS, THE CHANCES FOR SUCCESS IN CLINICAL SETTINGS WILL INCREASE. AIM 1: IDENTIFY MEDIATORS THAT LINK ACTIVATION OF APOPTOTIC CELL DEATH IN CRV + IXZ TREATED HCC BUT NOT IN NON- CANCER CELLS. AIM 2: INVESTIGATE THE EFFICACY OF THE ORALLY BIOAVAILABLE CRV + IXZ COMBINATION IN MOUSE MODELS OF HCC. IN ADVANCED HCC, THERE HAS BEEN LITTLE PROGRESS IN DISCOVERING NEW CHEMOTHERAPY STRATEGIES. WE PROPOSE THAT TARGETING THE ESSENTIAL PROTEOTOXIC STRESS RESPONSE SURVIVAL PATHWAY BY COMBINING ORALLY BIOAVAILABLE PAN-CYCLOPHILIN AND UPS INHIBITORS WILL BE A USEFUL STRATEGY TO SELECTIVELY KILL HCC WITHOUT CAUSING EXCESSIVE SIDE EFFECTS TO NORMAL TISSUES. CURRENTLY, CRV IS BEING INVESTIGATED AS AN ANTI-VIRAL AND ANTI-LIVER FIBROSIS AGENT AND WE ARE THE FIRST TO PROPOSE ITS USE IN HCC COMBINATION THERAPY. THE LONG-TERM GOAL WILL BE TO USE CRV + IXZ TO TREAT HCC PATIENTS WITH THE HOPE THAT PROTEOTOXIC STRESS CELL DEATH SPECIFICALLY IN HCC CELLS WITHOUT CAUSING TOXICITY TO NORMAL TISSUES WILL INCREASE OVERALL SURVIVAL AND IMPROVE QUALITY OF LIFE.

PILOT TESTING AND IMPLEMENTATION EVALUATION OF RAILROAD CRITICAL INCIDENT STRESS PLAN

3RD NATIONAL FIRE SERVICE RESEARCH AGENDA SYMPOSIUM

HOUSING COUNSELING ASSISTANCE PROGRAM

PURPOSE: THE PURPOSE OF HUD’S COMPREHENSIVE HOUSING COUNSELING (CHC) GRANT IS TO PROVIDE DIRECT FUNDING SUPPORT TO HUD’S NATION-WIDE NETWORK OF APPROVED HOUSING COUNSELING AGENCIES. FOR MORE INFORMATION ABOUT THE COMPREHENSIVE HOUSING COUNSELING GRANT PROGRAM, SEE HTTPS://WWW.HUD.GOV/PROGRAM_OFFICES/HOUSING/SFH/HCC.; ACTIVITIES TO BE PERFORMED: HOUSING COUNSELING ACTIVITIES INCLUDE PROVIDING INFORMATION, ADVICE, AND TOOLS FOR CONSUMERS SEEKING, FINANCING, MAINTAINING, RENTING, OR OWNING A HOME. AGENCIES ALSO ASSIST THOSE FACING HOMELESSNESS AND HOMEOWNERS IN NEED OF FORECLOSURE ASSISTANCE. THE HOUSING COUNSELING ACTIVITY TYPES THAT CAN BE REIMBURSED BY THE CHC GRANT INCLUDE ALL APPROVED HOUSING COUNSELING, EDUCATION, AND OUTREACH TOPICS LISTED IN THE CURRENT. HTTPS://WWW.HUD.GOV/PROGRAM_OFFICES/ADMINISTRATION/HUDCLIPS/HANDBOOKS/HSGH/7610.1. THIS INCLUDES, BUT IS NOT LIMITED TO, PRE-PURCHASE/HOME BUYING COUNSELING, RESOLVING, OR PREVENTING FORWARD OR REVERSE MORTGAGE DELINQUENCY OR DEFAULT COUNSELING, AND NON-DELINQUENCY POST-PURCHASE COUNSELING. GRANTEES ARE REQUIRED TO DEMONSTRATE, THROUGH THE CURRENT FORM HTTPS://WWW.HUD.GOV/PROGRAM_OFFICES/ADMINISTRATION/HUDCLIPS/FORMS/HUD9, HOUSING COUNSELING AGENCY ACTIVITY REPORT, THE NUMBER OF HOUSEHOLDS THAT WERE COUNSELED BY ACTIVITY TYPE AND NUMBER OF HOUSEHOLDS THAT ATTENDED WORKSHOPS BY ACTIVITY TYPE DURING THE APPLICABLE FISCAL YEAR. HOUSING COUNSELING AGENCIES MAY ALSO BE SPECIFICALLY AWARDED TO PARTNER WITH A MINORITY-SERVING INSTITUTION (MSI) TO PROVIDE HOUSING COUNSELING TO THE MSI INSTITUTIONS’ COMMUNITIES AND EXPAND THESE INSTITUTIONS’ PARTNERSHIPS WITH HOUSING COUNSELING AGENCIES. OUTPUTS AND DELIVERABLES FOR THIS GRANT AWARD IS THE SAME AS THE PARAGRAPH DESCRIBED ABOVE, HOWEVER, GRANTEES ARE REQUIRED TO PARTNER WITH A MSI TO PROVIDE THOSE ACTIVITIES. ; EXPECTED OUTCOMES: THE QUANTIFIABLE OUTCOMES FOR THE CHC GRANT INCLUDE, BUT ARE NOT LIMITED TO, THE NUMBER OF HOUSEHOLDS THAT GAINED ACCESS TO HOUSING RESOURCES; RECEIVED INFORMATION ON FAIR HOUSING, FAIR LENDING, AND/OR ACCESSIBILITY RIGHTS; IMPROVED CURRENT LIVING CONDITIONS; PURCHASED HOUSING; RECEIVED A REVERSE MORTGAGE; PREVENTED OR RESOLVED A MORTGAGE DEFAULT; AND RECEIVED A LOAN MODIFICATION. ALL POSSIBLE OUTCOMES ARE LISTED IN SECTION 10 OF THE CURRENT FORM HTTPS://WWW.HUD.GOV/PROGRAM_OFFICES/ADMINISTRATION/HUDCLIPS/FORMS/HUD9, HOUSING COUNSELING AGENCY ACTIVITY REPORT.; INTENDED BENEFICIARIES: INDIVIDUALS, GROUPS OF INDIVIDUALS, AND FAMILIES WHO ARE RENTERS, TENANTS, HOMEOWNERS, AND HOME BUYERS UNDER HUD, CONVENTIONAL, AND OTHER GOVERNMENT PROGRAMS.; SUBRECIPIENT ACTIVITIES: THE SUBRECIPIENT ACTIVITIES ARE UNKNOWN AT THE TIME OF AWARD.

GRANT OF FUNDS PROVIDED TO THE THOMSON REUTERS FOUNDATION TO ENHANCE THE ROLE OF MEDIA IN UPCOMING EGYPTIAN ELECTIONS THROUGH 2 MECHANISM 1ST BY CREA

DEVELOPING DISSEMINATION STRATEGIES FOR HEALTHCARE PROVIDERS TO ADVANCE THE REACH OF T1D PSYCHOSOCIAL CARE - PROJECT SUMMARY YOUTH WITH TYPE 1 DIABETES (T1D) EXPERIENCE WORSE T1D HEALTH OUTCOMES (HIGHER GLYCEMIC LEVELS, GREATER PSYCHOLOGICAL DISTRESS) COMPARED TO ADULTS. EVIDENCE-BASED PEDIATRIC T1D PSYCHOSOCIAL CARE HAS THE POTENTIAL TO IMPROVE DIABETES DISTRESS, HIGH GLYCEMIC LEVELS, AND FAMILY CONFLICT. HOWEVER, FEW FAMILIES ARE AWARE OF OR RECEIVE THIS NEEDED CARE. THIS GAP IS DUE TO LIMITED INTEGRATION OF RESEARCH INTO PRACTICE (IMPLEMENTATION) AND INSUFFICIENT AWARENESS OF EVIDENCE-BASED PSYCHOSOCIAL CARE BY T1D PROVIDERS, WHO ARE THE TRUSTED, PREFERRED SOURCE OF T1D HEALTHCARE INFORMATION AND REFERRALS AMONG FAMILIES (DISSEMINATION). TO INCREASE THE REACH OF THIS CARE REQUIRES BOTH IMPLEMENTATION STRATEGIES TO ENSURE WHAT IS DELIVERED IN STANDARD CARE IS EVIDENCE-BASED (FOCUS OF THE PIS K23DK125666), AS WELL AS DISSEMINATION STRATEGIES TO INCREASE T1D PROVIDER KNOWLEDGE AND UTILIZATION OF THIS CARE. DISSEMINATION EFFORTS MUST CENTER VIEWPOINTS OF T1D PROVIDERS TO EFFECTIVELY TAILOR STRATEGIES TO THIS TARGET AUDIENCE. THE PROPOSED STUDY IS THE FIRST TO DEVELOP PROVIDER-FOCUSED DISSEMINATION STRATEGIES FOR EVIDENCE-BASED T1D PSYCHOSOCIAL CARE. GUIDED BY DESIGNING FOR DISSEMINATION (D4D), THE CURRENT COMMUNITY-ENGAGED STUDY WILL BE CONDUCTED WITH THE PIS EXISTING T1D PROVIDER PARTNERS (REACH PILOT; P20GM144270) WHO WILL GUIDE REFINEMENT AND EXECUTION OF THE PROPOSED RESEARCH PLAN FROM STUDY DESIGN THROUGH DISSEMINATION. CONTENT EXPERTS ON DISSEMINATION SCIENCE (BECKER), MIXED METHODS (DEATRICK) AND PEDIATRIC BEHAVIORAL INTERVENTION IN MEDICAL SETTING (KAZAK), AS WELL AS NEMOURS AND BREAKTHROUGH T1D SOCIAL MEDIA SPECIALISTS WILL SUPPORT THE EXECUTION OF THIS RESEARCH. LEVERAGING HER BENCHMARKING STUDY ON PSYCHOSOCIAL STAFFING AND CARE IN PEDIATRIC DIABETES CLINICS, DR. PRICE WILL USE SURVEY METHODOLOGIES TO GATHER PERSPECTIVES FROM T1D PROVIDERS (ENDOCRINOLOGISTS, ADVANCED PRACTICE PROVIDERS) NATIONALLY ON PREFERENCES RELATED TO (1) WHAT SHOULD BE DISSEMINATED, (2) BY WHOM, AND (3) WHERE, AS WELL AS IDENTIFY (4) BARRIERS AND (5) FACILITATORS OF ACCESSING AND USING RESEARCH FINDINGS (AIM 1). INDIVIDUAL INTERVIEWS WITH T1D PROVIDERS WILL BE USED TO REFINE QUANTITATIVE DATA FROM AIM 1 AND TO SELECT AND TAILOR DISSEMINATION TOOLS (AIM 2). AFTER VIEWING NEWLY CREATED DISSEMINATION TOOLS AND CONTENT, T1D PROVIDERS WILL COMPLETE SURVEYS ON THE CLARITY, REACH, INFLUENCE, AND TRUSTWORTHINESS OF THESE TOOLS AND STRATEGIES (AIM 3). THIS FOUNDATIONAL STUDY WILL RESULT IN PROVIDER- CENTERED, READY-TO-TEST DISSEMINATION STRATEGIES, WHICH WILL BOLSTER AN R01 APPLICATION TO CONDUCT A MULTI-SITE RANDOMIZED TRIAL TESTING DISSEMINATION STRATEGY EFFECTIVENESS ON INCREASING T1D PROVIDERS’ KNOWLEDGE AND UTILIZATION OF EVIDENCE-BASED T1D PSYCHOSOCIAL CARE. THIS RESEARCH COMPLEMENTS DR. PRICE’S ONGOING RESEARCH ON IMPLEMENTATION SCIENCE (K23 FROM NIDDK). WITH HER COMMUNITY PARTNERSHIPS AND COMPLEMENTARY IMPLEMENTATION DATA, THE PROPOSED DISSEMINATION PROJECT WILL ADVANCE HER GOALS TO BECOME AN INDEPENDENT INVESTIGATOR AND IMPROVE T1D HEALTHCARE AND OUTCOMES AMONG YOUTH WITH T1D.

CHS: SMALL: COMPOUNDING DIVIDENDS ON VOICE BANKING