THIS IS OUR SECOND ANNUAL RESEARCH FESTIVAL. I'M BILL RILEY, THE DIRECTOR OF THE OFFICE. ONE-DAY FESTIVAL WE DO EACH YEAR TO GATHER THE DIASPORA OF SCIENTISTS TO HIGHLIGHT RECENT RESEARCH WE HAD FUNDED, AND IN THIS WORLD OF VIRTUAL MEDIUM SYNCHRONOUS TO MEET ONCE A YEAR, AND EXCHANGE IDEAS AND CONSIDER STRATEGIES TO ADVANCE OUR SCIENCE. FOR OUR WELCOME IT'S MY PLEASURE TO INTRODUCE DR. LARRY TABAK, THE PRINCIPAL DEPUTY DIRECTOR OF NIH, SERVED IN THAT CAPACITY FOR NEARLY A DECADE WAS DIRECTOR OF THE NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH, LED EFFORTS INCLUDING ENHANCING PEER REVIEW, GUIDING AGENCY THROUGH THE AMERICAN COVERY AND REINVESTOR. ACT, SPEARHEADING EFFORTS IN RIGOR AND REPRODUCIBILITY, AND DEVELOPING NIH-WIDE STRATEGIC PLAN. FOR FOLKS WHO DON'T KNOW HE'S BEEN QUITE A CHAMPION, WORKFORCE DIVERSITY IN GENDER AND RACIAL, PARTLY OF THE RESULT OF A QUOTE I'VE HEARD HIM SAY A NUMBER OF TIMES, LET'S QUIT TALKING ABOUT IT AND LET'S DO SOMETHING ABOUT IT, WHICH ACTUALLY SPURS US ON QUITE OFTEN. I'M NOT SURE WHAT HE REALIZED WHAT "AND DUTIES" MEANT, BUT MANY POTENTIALLY BAD THINGS THAT COULD HAVE HAPPENED TO THE NIH HAVE NOT HAPPENED AS A RESULT OF HIS TIRELESS EFFORTS OVER THESE YEARS. SO JOIN ME IN WELCOMING DR. LARRY TABAK. [APPLAUSE] >> THANK YOU AND GOOD MORNING. YOU'RE ALL PART OF AN EXPERIMENT. DESPITE THE FACT THEY HAVE CORDONED OFFER THE BACK YOU'RE STILL SITTING AS FAR BACK AS POSSIBLE. I THOUGHT BEHAVIORAL AND SOCIAL SCIENTISTS WOULD HAVE OVERCOME THAT BUT I GUESS NOT. GOOD MORNING TO ALL OF YOU. BILL, THANK YOU VERY MUCH FOR ALLOWING ME TO PINCH HIT FOR JIM ANDERSON, WHO MAY HAVE BEEN PINCH HITTING FOR FRANCIS, I DON'T KNOW, BUT IT'S GOOD TO BE HERE. SO FIRST, LET ME CONGRATULATE THE OBSSR AND YOUR COORDINATING COMMITTEE FOR PUTTING TOGETHER WHAT LOOKS TO BE A REALLY OUTSTANDING AGENDA. AND ONLY IN THE SOPHOMORE YEAR. SO NO SOPHOMORE SLUMP FOR YOU FOLKS. YOU KNOW, THE LINEUP OF SPEAKERS AND PRESENTERS IS OUTSTANDING, AND I'M SURE THAT THIS FESTIVAL CREATES A GOOD DEAL OF MOMENTUM GOING FORWARD. LET ME JUST SPEND A COUPLE MOMENTS REITERATING HOW VITAL OBSSR IS TO NIH. SINCE ITS FOUNDING IN 1993, OBSSR HAS SOUGHT TO DEFINE, DEEPEN UNDERSTANDING OF AND MEASURE SOCIAL AND CULTURAL FACTORS THAT CONTRIBUTE TO HEALTH, WELLNESS AND DISEASE. THE TRUTH IS, MANY INTERVENTIONS, THERAPIES AND TREATMENTS WOULDN'T HAVE NEARLY AS MUCH IMPACT WITHOUT CONSIDERATION OF RESEARCH ON THE ASSOCIATED BEHAVIORS AND SOCIAL ELEMENTS NEEDED FOR IMPLEMENTATION. SOCIETY SO FOR 20 YEARS OBSSR HAS STRENGTHENED AND BOLSTERED THIS FIELD OF RESEARCH. OF COURSE, ALL SCIENTIFIC DISCIPLINES AND CERTAINLY OF COURSE ALL OF THE NIH, INSTITUTES AND CENTERS. THESE DAYS, WE ONCE AGAIN SEE BEHAVIORAL SCIENCE AT THE FOREFRONT OF HEALTH RESEARCH. YOU'RE CHARTING NEW PATHS IN mHEALTH. AT THIS POINT FRANCIS SHOWS HE'S WEARING A DEVICE. I'M WEARING A WATCH FROM 46 YEARS AGO, BUT YOU GET THE POINT, DISEASE MONITORING, REDUCING TOBACCO USE, LOWERING SUDDEN INFANT DEATH, PREVENTING DIABETES, INTEGRAL TO EVERYTHING. IT'S HARD TO BE AT THE PODIUM AND NOT MENTION A CRISIS THAT HAS OVERCOME THE NATION, AND THAT OF COURSE IS THE CRISIS OF OPIOID MISUSE. AS YOU KNOW, THIS IS RAVAGING THE COUNTRY. NIH WITH ALMOST EVERY OTHER FEDERAL AND STATE AGENCY HAS BEEN CALLED UPON TO ATTACK THIS. AND THE DEPARTMENT OF HEALTH AND HUMAN SERVICES HAS DEVELOPED THE HHS OPIOID INITIATIVE, FOR INSTANCE, AND THE EPIDEMIC HAS BEEN DESIGNATED AS AGENCY PRIORITY GOAL. THE FACTS MANY IF NOT ALL OF YOU ARE FAMILIAR ARE STAGGERING. 2016, 18 MILLION PEOPLE MISUSED PRESCRIPTION DRUGS, 940,000 USED OTHER. PROVISIONAL 2016 DEATHS VERSUS 2015, DEATH RATE FROM HEROIN WAS UP 17%, FROM PRESCRIPTION NON-SYNTHETICS UP 14%, AND SCARY ARE INFLUX OF SYNTHETICS, SUCH AS FENTANYL BECAUSE OF POTENCY, MISUSE FROM 12.5 TO 13%. OVERPRESCRIBING IS SEEN AS A BIG DRIVER OF THIS, AND I RECENTLY HAD -- I NEEDED A ROOT CANAL, QUITE INTERESTING. THE DENTIST KNEW THAT I'M ALSO A DENTIST, WHEN IT CAME TO THAT MOMENT, WHEN, OKAY, DO YOU -- WHAT DO YOU WANT TO DO ABOUT PAIN MEDICATION, YOU KNOW, WHEN YOU LEAVE THE OFFICE. AND I SAID, YOU KNOW, I'M QUITE SURE THREE IBUPROFEN WILL BE FINE. A SIGH OF RELIEF, MANY PATIENTS ARE PROGRAMMED FOR OPIOIDS, AND LOTS OF THEM. THE MANY YEARS I PRACTICED ENDODONTICS, I NEVER PRESCRIBED ONE, INTERESTINGLY ENOUGH. NEVERTHELESS, OVERDOSES HAVE CONTRIBUTED TO A DECREASE THE LIFE EXPECTANCY, THE WHOLE THING IS JUST ENTERING EVERY FABRIC OF OUR SOCIETY. NOW, THERE'S FEW PROMISING LIGHTS OF HOPE HERE IN THE SENSE THAT WE NOW HAVE AVAILABLE A NARCAN NASAL SPRAY WHICH FIRST RESPONDERS ARE MORE LIKELY TO TAKE ADVANTAGE OF, IMPLANTABLE BUPRENORPHINE IS AVAILABLE, AND NOW PRE-CLINICAL RESEARCH WHICH IS DISCOVERING HOW, YOU KNOW, YOU CAN LOWER THE RISK FOR ADDICTION. SO ALL OF THESE -- THESE ARE PHARMACOLOGICAL INVENTIONS, YOU KNOW, INTERVENTIONS, BUT AGAIN, WITHOUT WHAT YOU ALL DO, WITHOUT THE BEHAVIORAL AND SOCIAL SCIENCE OVERLAY, THOSE PHARMACEUTICALS DON'T MATTER, RIGHT? IF THE PATIENT DOESN'T TAKE ADVANTAGE OF THEM, IF THE PRESCRIBERS DON'T THINK THROUGH WHAT THEY ARE DOING, NONE OF THIS WILL MATTER. AND SO CERTAINLY, YOU KNOW, ADDITIONAL DEVELOPMENT OF BEHAVIORAL AND OTHER COMPLEMENTARY APPROACHES ARE CRUCIAL. FOR EXAMPLE, WE HAVE SOME DATA THAT COGNITIVE BEHAVIORAL THERAPY, TRAINING TO CHANGE PAIN-RELATED THOUGHTS AND BEHAVIOR, AND MINDFULNESS BASED STRESS REDUCTION AND YOGA ARE EFFECTIVE FOR CHRONIC LOW BACK PAIN, ONEOF THE MAJOR SOURCES OF CHRONIC PAIN IN THIS NATION. WE'VE SEEN THE LAUNCH OF THE NIH-DoD-V.A. COLLABORATORY AND PROJECTS WITH NON- NON-PHARMACEUTICAL PAIN MANAGEMENT FOR SERVICE MEMBERS AND VETERANS. TWELVE RESEARCH PROJECTS, $80 MILLION OVER THE NEXT SEVERAL YEARS WILL FOCUS ON DEVELOPING AND IMPLEMENTING REAL WORLD RESEARCH ON NON-DRUG APPROACHES FOR PAIN MANAGEMENT AND RELATED CONDITIONS IN MILITARY AND VETERANS. THIS COULD BE GAME CHANGING. AND OBVIOUSLY, YOUR FIELD IS AT THE FOREFRONT OF THIS. NOW, THE PRESIDENT ANNOUNCED A COMMISSION ON COMBATING DRUG ADDICTION AND OPIOID CRISIS. ON OCTOBER 4 NIH INITIATED A PUBLIC/PRIVATE PARTNERSHIP, SIX MEETINGS, COMPANIES ENGAGED, THE NATIONAL PAIN STRATEGY WAS RELEASED INCLUDING A NUMBER OF RESEARCH RECOMMENDATIONS, I UNDERSTAND OBSSR IS TEAMING UP WITH NIDA AND NICCH TO TAKE THIS ON AT A CONFERENCE IN MARCH AND WE'RE LOOKING FORWARD TO LEARNING THE RESULTS OF THAT MEETING. SO WE'RE TRYING EVERY FACET OF THIS, AND AS YOU ALL KNOW, I'M JUST SAYING THIS SO YOU REALIZE I KNOW IT, OBVIOUSLY BEHAVIORAL AND SOCIAL SCIENCE RESEARCH IS AT THE FOREFRONT OF HELPING US MEET THIS CRISIS. SO, BEFORE I ROLL OFF TO THE NEXT THING THAT I'M DOING, I JUST WANTED TO TELL YOU ABOUT AN ISSUE THAT FRANCIS AND I CURRENTLY ARE WORKING ON. AND THAT'S THE NEXT GENERATION OF RESEARCHERS INITIATIVE. WE CALL IT NEXT GEN, THAT MAKES FRANCIS UNCOMFORTABLE BECAUSE HE THINKS DNA SEQUENCING, BUT FOR THE REST OF US NEXT GEN SORT OF WORKS. WE USE NGRI IN HIS PRESENCE. SO I HOPE MOST OF YOU HEARD ABOUT NEXT GEN. THIS WAS INTRODUCED BACK IN JUNE. AND NEXT WEEK WE'LL BE HAVING A READOUT FROM A WORKING GROUP OF THE ADVISORY COMMITTEE TO THE DIRECTOR THAT I HAVE THE PRIVILEGE OF CO-CHAIRING ABOUT THIS INITIATIVE. WHAT SHE MEANS ABOUT THE WORKING GROUP, HERE'S A SOCIAL SCIENCE EXPERIMENT FOR YOU. INSTEAD OF THE COMMITTEE LOOKING LIKE ME, OKAY, MEANING REALLY OLD, GRAY HAIRED PEOPLE, WE HAVE GRADUATE STUDENTS, POSTDOCS, ASSISTANT PROFESSORS, AND INTERESTINGLY ENOUGH THEY ARE NOT BASHFUL WHEN GIVEN THE OPPORTUNITY TO SPEAK. THIS IS AN INTERESTING DYNAMIC RANGING FROM GRADUATE OPPORTUNITY TO A NOBEL LAUREATE AND EVERYTHING IN BETWEEN. ALSO BEEN A FASCINATING SET OF ACTIVITIES BUT BASICALLY WHAT THIS INITIATIVE IS BEING TO SEEK TO DO IS MAKE SURE THAT WE STABILIZE OUR BIOMEDICAL RESEARCH WORKFORCE. AND PART OF THAT IS, AS MY GENERATION FADES AWAY, I SEE SOME SMILES, PEOPLE ARE GOING, OH, FINALLY, GET RID OF ... IT'S GOING TO HAPPEN, I PROMISE! BUT AS OUR GENERATION FADES AWAY, WE ABSOLUTELY HAVE TO MAKE SURE THAT THE NEXT GENERATION GETS PUT ON BOARD AND IN A WAY THAT ENABLES THEM TO SUCCEED. YOU DON'T WANT TO GIVE PEOPLE JUST ENOUGH MONEY TO FAIL BUT YOU WANT TO MAKE SURE YOU GIVE THEM A STRONG FOUNDATION. AS YOU WATCH PEOPLE GO THROUGH THE METAPHORICAL PIPELINE, WHEN THEY FALL OUT OF THE SYSTEM, WE HAVE TO PAY PARTICULAR ATTENTION TO THAT AS WELL. BY TAKING SPECIAL STEPS REHOPE TO REDUCE HYPERCOMPETITION, STABILIZE THE WORK FORCE, ENSURE IT REMAINS HEALTHY GOING FORWARD. SO WITH THAT, I JUST WOULD AGAIN LIKE TO THANK YOU FOR PARACHUTING, ALLOWING ME TO PARACHUTE IN AND OUT. I WISH YOU A GREAT MEETING AND LOOK FORWARD TO HEARING FROM BILL ABOUT THE GREAT MEETING AND DELIBERATIONS. SO THANK YOU ALL VERY MUCH. [APPLAUSE] >> MANY THANKS TO LARRY AGAIN FOR DOING THAT WITH A LOT OF THINGS GOING ON IN HIS SCHEDULE OVER THE COURSE OF IT SEEMS LIKE EVERY DAY AT THIS POINT. AS USUAL, FOR US I LIKE TO START US OFF WITH A LITTLE BUILT OF A STATE OF THE SCIENCE OF THE NIH OVER THE LAST FISCAL YEAR, GIVE PEOPLE A SENSE OF WHAT WE'VE BEEN DOING AND WHAT'S GOING ON AND SPEAK MORE FROM THE PERSPECTIVE OF ASSOCIATE DIRECTOR REPRESENTING ALL OF YOU AT THE NIH LEADERSHIP. AS YOU KNOW, IT SEEMS A LONG TIME AGO, ONLY NOVEMBER OF LAST YEAR WE RELEASED OUR STRATEGIC PLAN WITH THREE SCIENTIFIC PRIORITIES, BASIC AND APPLIED RESEARCH SYNERGY, METHODS, MEASURES, AND THEN FOUNDATIONAL PROCESS OF PROGRAM COORDINATION, TRAINING, POLICY AND EVALUATION. WE THEN QUICKLY TRIED TO GET THE WORD OUT AS FAST AS WE COULD. A FEW COMMENTARIES CAME OUT ABOUT THAT TIME, SOON AFTERWARDS, FOR DESCRIBING EACH OF THE SCIENTIFIC PRIORITIES AND GETTING THEM OUT FOR THE COMMUNITY TO BE ABLE TO UNDERSTAND IN MORE DEPTH WHAT WE WERE TRYING TO ACHIEVE. I WANTED TODAY TO GIVE YOU SOME SENSE OF JUST A FEW EXAMPLES OF THE SORT OF THINGS WE'VE DONE AROUND THOSE FOUNDATIONAL PROCESSES. WE HAVE THE MATILDA WRIGHT RILEY EVENT, WE'LL DELVE MORE IN A BIT. WE HAVE A MONTHLY DIRECTOR'S WEBINAR THAT WE DO AT THE OBSSR AS WELL. ON THE COORDINATION FRONT, OBVIOUSLY THE BEHAVIORAL AND SOCIAL SCIENCE RESEARCH COORDINATING COMMITTEE, WHICH IS ACTUALLY THE PRIMARY SPONSOR OF THIS EVENT, AND MUCH APPRECIATED. I'LL TALK ABOUT THAT IN A SECOND. AS WELL AS TRYING TO WORK WITH TRANS-NIH INITIATIVES LIKE THE PRECISION MEDICINE INITIATIVE OR "ALL OF US," ECHO BRAIN AND ABCD AS EXAMPLES. PEOPLE MAY BE SURPRISED TO LEARN THE OBSSR FUNDS CURRENTLY 11 WEEK-LONG SUMMER TRAINING INSTITUTES OR AT SOME SEASON OF THE YEAR, MOST OF THEM THROUGH R25 MECHANISMS AND A STRONG EVALUATION COMPONENT TO THE OFFICE WORKING WITH THE OFFICE OF PORTFOLIO ANALYSIS NOW ON BETTER SUBCLUSTERRING THE TOPICS WITHIN BEHAVIORAL AND SOCIAL SCIENCE RESEARCH SO WE HAVE A BETTER SENSE OF WHAT THOSE ARE AS WELL AS ENSURING RELEVANCE OF CLINICAL TRIALS POLICIES TO SOCIAL AND BEHAVIORAL GRANTS AND THAT'S ALL I'M GOING TO SAY ABOUT CLINICAL TRIALS POLICIES TODAY. SO ON THE IMPROVING THE SYNERGY OF BASIC BEE AND APPLIED BEHAVIORAL, WE SUPPORT BENCH TO BEDSIDE AND YOU'LL HEAR FROM AN AWARDEE AT AN INTRAMURAL HIGHLIGHT. OUR CONTINUED SUPPORT FOR OP-NET AS A TRANS-NIH EFFORTE OPP-NET, I CAN SAY THE WORDS LIKE RESILIENCE WITH NOBODY BEING IN PROBLEMS OF COMPETITION. WORKING WITH THE BRAIN INITIATIVE ON TRYING TO PAIR SOME THINGS THAT GO ON WITH SOME TOOLS IN BRAIN WITH SOME TOOLS THAT WOULD ALSO ALLOW US TO UNDERSTAND BEHAVIORAL AT THAT LEVEL OF TEMPORAL PRECISION AND STRENGTHEN TOOLS TO UNDERSTAND THE PROCESS THAT GOES FROM VERY BASIC RESEARCH TO APPLIED, TO PRACTICE GUIDELINES, AND ON FROM THERE. IN SCIENTIFIC PRIORITY TWO, THESE ARE A FEW OF THE THINGS, INTENSIVE LONGITUDINAL ANALYSIS TO BEHAVIOR FOA IN REVIEW, WE CONDUCTED A WORKSHOP THIS SPRING ON COMPARISN GROUPS, THERE'S A PAPER THAT'S BEING WORKED ON IN THAT. EACH YEAR WE DO METHODOLOGY WORKSHOP FOR THE NIH STAFF ABOUT EMERGING METHODOLOGIES THAT WE THINK PEOPLE NEED TO HEAR MORE ABOUT. AND THIS YEAR IT WAS ON NON-TRADITIONAL SURVEY DATA COLLECTION APPROACHES. WE HAVE A COMPUTATIONAL MODEL IN BIG DATA WORKING GROUP, AND BEHAVIORAL AND SOCIAL SCIENCES, AND ONE OF THE THINGS THAT OUR OFFICE WILL SPEND A SIGNIFICANT AMOUNT OF TIME ON IS IMPROVING OUR BEHAVIORAL TERMINOLOGY, CATEGORIZATIONS WE USE TO USE THE SAME LANGUAGE BETTER THAN WE CURRENTLY ARE IN THE FIELD. PRIORITY THREE, MONTHLY RESEARCH HIGHLIGHTS EVERY MONTH, RECENT FINDINGS THAT HAVE COME OUT IN THE FIELD, LISTINGS OF ACCOMPLISHMENTS AND PAPERS WHEN THE WEBSITE COMES OUT, WORKING WITH NCIH ON EPOCKETS EMOTIONAL WELL BEING IN THE SPRING. YEAH, APRIL, THANK YOU. AND THEN NCI'S IMPLEMENTATION SCIENCE GROUP HAS BEEN A LEADER IN IMPLEMENTATION SCIENCE AREA SO WE'VE BEEN TRYING ASSIST AND SUPPORT AS WE CAN THE EFFORTS THAT THEY DO THERE. A LITTLE BIT NOW ON FUNDING FOR BEHAVIORAL AND SOCIAL SCIENCE RESEARCH AT THE NIH. WE'RE DOING OKAY. MAY NOT ALWAYS FEEL OKAY FROM DAY TO DAY AND WEEK TO WEEK, BUT OUR FUNDING HAS INCREASED, SOME IN 2016, SOME IN 2017. BASED ON RCDC CRITERIA OF BEHAVIORAL AND SOCIAL SCIENCE RESEARCH GRANT, INCLUDED INCREASE IN BASIC BEHAVIORAL AND SOCIAL SCIENCE RESEARCH AND OVERALL THERE'S BEEN SOME INCREASE. SOME OF THAT'S BEEN THE RESULT OF SOME SPECIALIZED FUNDING THAT WE'VE RECEIVED FROM THE NIH FOR AREAS LIKE ALZHEIMER'S TO "ALL OF US" INITIATIVE AND THOSE TYPES OF THINGS, FOR SOME INCREASES BUT IT'S BEEN NICE TO SEE INCREASES OCCURRING. I'LL REMIND YOU, THIS IS AN IMPORTANT THING A YOU LOOK AT RCDC CRITERIA, COUNTS OF THE NUMBER OF THE GRANTS THAT HAVE SOME BEHAVIORAL AND SOCIAL SCIENCE RESEARCH COMPONENT TO IT. THEY ALSO ARE COUNTED IN BY DETECTIVES AND HEART DISEASE AND ALL OTHER KINDS OF CONDITIONS, COUNTED IN OTHER CROSS-CUTTING CATEGORIES LIKE PREVENTION AS WELL. THEY ARE NOT, QUOTE, PURELY BEHAVIORAL AND SOCIAL SCIENCE RESEARCH RESEARCH BUT ALL HAVE SOME COMPONENT OF THAT IN THE WORK BEING DONE. THAT'S AN INTERESTING SPLIT AT THE TOP. SO WE HAD TO BREAK IT, IT WAS SO BIG, NIA HAD SO MUCH MONEY WE MOVED THEM FURTHER OUT. NO, IF YOU LOOK BY INSTITUTE, THE FUNDING PER INSTITUTE, YOU CAN SEE THAT NIA HAS THE HIGHEST AMOUNT OF FUNDING AT THE NIH IN THE BEHAVIORAL AND SOCIAL SCIENCE RESEARCH RESEARCH AT THIS POINT, AGAIN PROBABLY IN PART BECAUSE OF ALZHEIMER'S INITIATIVE AND INFUSION OF FUNDS IN THAT AREA FOR WORK IN COGNITIVE PROCESS, CHANGES AND TRAINING. NIMH ALSO AS WELL IS CUT OFF IN THAT PART. AND THEN YOU CAN SEE FROM THERE THE VARIOUS SORT OF GROUPS AND AMOUNT OF BEHAVIORAL AND SOCIAL SCIENCE RESEARCH FUNDING THAT THEY RECEIVE SO YOU CAN LOOK FOR YOUR OWN INSTITUTE. THIS IS NOT NECESSARILY AN INDICATION OF COMMITMENT TO BEHAVIORAL AND SOCIAL SCIENCE RESEARCH BUT RECOMMENDS THE FACT SOME ARE SMALLER INSTITUTES WITH SMALLER BUDGETS. SOME NEAR THE BOTTOM ARE SOME OF THE ONES THAT ARE QUITE COMMITMENTED TO BEHAVIORAL AND SOCIAL SCIENCE RESEARCH, THEY HAVE JUST A RELATIVELY SMALL BUDGET TO WORK WITH. COMMON THEMES IN THE BEHAVIORAL AND SOCIAL SCIENCE RESEARCH RESEARCH PORTFOLIO, I'LL JUST LET YOU LOOK AT A FEW OF THE GENERAL CONCEPTS HERE IN TERMS OF WHAT WE TYPICALLY HAVE FUNDED AND WHAT THE AREA IS BUT IMPORTANT IS THE BREADTH OF THE RESEARCH THAT GETS FUNDED IN THE BEHAVIORAL AND SOCIAL SCIENCES AT THE NIH. I DID THIS LAST YEAR, I'M GOING TO TAKE A FEW MINUTES TO ACTUALLY GIVE YOU A FEW EXAMPLES. LAST YEAR I GAVE YOU EXAMPLES FROM THE SMALLEST FUNDED BEHAVIORAL AND SOCIAL SCIENCE INSTITUTES AND CENTERS. THIS YEAR I THOUGHT I WOULD WITCH AND SWITCH AND DO THE TOP TEN ICs IN TERMS OF FUNDING TO GIVE YOU A SENSE. I PARTICULARLY LIKE TO DO THIS BECAUSE OTHERWISE I WANT THESE EXAMPLES IN YOUR MIND, WHEN YOU HEAR THE, QUOTE, WASTE OF FUNDING THAT MIGHT INCLUDE OFTEN INACCURATELY SOME BEHAVIORAL OR SOCIAL SCIENCE STUDY. THESE ARE JUST RANDOM LOOKING THROUGH WHAT ARE OVER 2800 GRANTS THAT THE NIH FUNDED IN THIS AREA THIS YEAR. THIS WAS ON SELF-REGULATION OF BRAIN AND COGNITIVE HEALTH IN OLDER ADULTS, A SMALL BUT LARGE IN TERMS OF LONGITUDINAL LENGTH STUDY LOOKING AT SELF REVELATION, EXECUTIVE COGNITIVE FUNCTION, HEART RATE VARIABILITY AND THOSE THINGS, MEASURED NEUROCOGNITIVE HEALTH ASSOCIATED WITH AGING AND RISK FOR NEUROLOGICAL DISEASE, A CONTINUED STUDY LOOKING AT THIS PROCESS OF SELF-REGULATION AND HOW IT AFFECT IT'S BRAIN AND COGNITIVE HEALTH IN OLDER ADULTS. THIS IS A STUDY FROM NATIONAL MENTAL HEALTH FOR ANOREXIA NERVOSA, A QUITE SERIOUS AND LIFE-THREATENING DISORDER THAT PEOPLE HAVE. AND FAMILY-BASED TREATMENTS HAVE BEEN USED FOR SOME YEARS, ARE SUCCESSFULLY TREATING 30 TO 40% BUT THERE ARE A NUMBER OF PEOPLE THAT FALL IN THE FAILURE CATEGORY, IDENTIFIED QUICKLY BECAUSE THERE'S A WEIGHT GAIN IN THE FIRST FEW WEEKS IN FAMILY-BASED TREATMENT USED IN THOSE SITUATIONS AND THAT CAN BE A QUICK PREDICTOR OF WHETHER YOU'RE GETTING A TREATMENT RESPONSE OR NOT AND WHETHER YOU SHOULD DO SOMETHING DIFFERENT. SO THIS STUDY IS A NICE ADAPTIVE TREATMENT-DESIGNED APPROACH, WHAT TO DO IN ADDITION ONCE A FAMILY-BASED THERAPY FAILS, WHAT ADDITIONAL THINGS TO ADD TO MOVE FORWARD. FROM NIDA I HAD TO DO SOMETHING ABOUT THE OPIOID EPIDEMIC, DIDN'T HAVE MUCH CHOICE THERE IN TERMS OF EXAMPLES. THIS IS I THINK A REALLY INNOVATIVE WAY TO THINK ABOUT THIS. THIS GROUP FROM BRITISH COLUMBIA CENTER HAS THREE MULTI-SITE LONGITUDINAL COHORT STUDIES GOING ON IN BRITISH COLUMBIA AND VANCOUVER IS DOING SOME REALLY INTERESTING THINGS RIGHT NOW IN TERMS OF SOCIAL APPROACHES TO THE OPIOID CRISIS. THEY HAVE INITIATED A NUMBER OF THINGS SUPERVISED INJECTION SERVICES, LOW THRESHOLD OPIOID AGONIST THERAPY, OPIOID MAINTENANCE THERAPY AND FENTANYL-BASED THERAPY AND MONITORING SERVICE, AND CLINICAL PRACTICE GUIDELINES FOR OPIOID DISORDER AMONGST RESIDENTIAL AND COMMUNITY CARE SYSTEMS AND OTHER CHANGES IN THE HEALTH CARE SYSTEMS. HAVING THAT ONGOING STUDY AND CHANGES ALLOWS THEM TO LOOK AT THE IMPACTS OF THOSE VARIOUS CHANGES IN THE HEALTHCARE SYSTEM AND OPIOID ABUSE RESPONSE TO THOSE TYPES OF PROBLEMS. OKAY. A REALLY INTERESTING STUDY FROM CHILD AND HUMAN HEALTH DEVELOPMENT, A STUDY OUR CONCERN FOR MANY YEARS HAS BEEN WHAT'S THE IMPACT OF HOUSEHOLD INCOME ON DEVELOPMENTAL CHANGES IN CHILDREN. THIS STUDY ACTUALLY DOES THAT WITH THE RANDOMIZED CONTROL TRIAL IN WHICH THEY DO BASICALLY UNCONDITIONED CASH PAYMENTS TO LOW INCOME FAMILIES AND COMPARE THAT TO PEOPLE GETTING A RELATIVELY SMALL AMOUNT OF SUPPORT TO SEE IF JUST THE ADDITIONAL RESOURCES ALONE, ADDITIONAL FINANCIAL RESOURCES ALONE WILL HAVE AN IMPACT ON EARLY DEVELOPMENT AND SOME OF THE SOCIAL AND EMOTIONAL DEVELOPMENT THAT GOES ON IN THE FIRST THREE YEARS OF LIFE. SO REALLY INTERESTING STUDY FROM THAT PERSPECTIVE. THIS IS ONE FROM OUR FRIENDS AT THE NATIONAL INSTITUTE OF ALCOHOL ABUSE, ALCOHOLISM, THIS IS -- I HAVE TO GIVE A BEHAVIORAL ECONOMIC EXAMPLE, RICHARD THALER WON THE PRIZE IN ECONOMICS FOR WORK IN BEHAVIORAL ECONOMICS, APPROACH APPROPRIATE WE HAVE ONE EXAMPLE IN THE GROUP I SHOW YOU TODAY. THIS IS LOOKING AT BEHAVIORAL ECONOMIC DOMAINS OF ALCOHOL DEMAND IN PROPORTION TO ALCOHOL-RELATED REINFORCEMENT AND IMPACT LONGITUDINALLY ON EARLY AGE DRINKERS FROM 20 TO 25 OVER A PERIOD OF TIME, ASSESSING THAT IN A LONGITUDINAL COHORT FASHION. THIS IS A STUDY FROM NIDDK, YOU THINK OF THE DIABETES INSTITUTES BUT IT'S KIDNEY, LOOK THIS IS END STAGE RENAL DISEASE AND QUALITY OF LIFE, AND END STAGE RENAL DIALYSIS, A WAY OF DELIVERING THOSE TYPES OF SUPPORT FOR A STEP COLLABORATIVE CARE MODEL TO INTERVENE OVER THE COURSE OF TIME. THIS IS FROM NINDS, EXCUSE ME, AND I WILL TELL YOU IN EACH OF THESE I HAD TO SHORTEN THE ABSTRACT A BIT SO IT WOULD FIT ON THE SLIDE. THIS IS ONE I DIDN'T WANT TO SHORTEN OUR TRUNCATE BECAUSE IT WAS SO WELL WRITTEN ABOUT DESCRIBING HOW WE THINK ABOUT MOTOR LEARNING AND MOTOR MEMORY, AND IT WAS PARTICULARLY INTERESTING I THOUGHT BECAUSE IT JUXTAPOSES, I THINK IT'S USEFUL ILLUSTRATION OF THE INTEGRATION WE'RE TRYING TO ACHIEVE BETWEEN BEHAVIORAL SCIENCE AND NEUROSCIENCE, NEUROSCIENCE ONE WOULD THINK WITH PRACTICE ASSOCIATION OF STIMULUS AND PROPER MOTOR COMMANDS SEEMS TO OCCUR BUT TWO THINGS HAPPEN FROM THE BEHAVIORAL SCIENCE IN THE WAY WE DO MOTOR LEARNING. ONE OF THEM IS THE CONCEPT OF SAVING. WHICH IS AFTER YOU THINK AFTER A LONG WASHOUT PERIOD THOSE MEMORIES WOULD BE GONE, THOSE WOULD NO LONGER BE THERE. BUT THERE'S A SAVINGS THAT OCCURS, MORE RAPIDLY RELEARN. EVEN IF YOU LEARN SOME OPPOSITE THAN THAT, THERE IS THE SORT OF PROCESS OF KIND OF A META LEARNING, THE PERSON CAN LEARN THE NEW THING FASTER BECAUSE THEY LEARNED SOME OLD MOTOR SKILL PREVIOUSLY EVEN THOUGH IT'S A DIFFERENT ONE. THIS IS A NICE STUDY LOOKING AT SOME OF THE NEURAL BIOLOGICAL BASES FOR THE LEARNING PROCESS, TRYING TO BETTER UNDERSTAND THAT PROCESS OVER TIME. FROM THE NATIONAL HEART, LUNG AND BLOOD INSURE TRUTH, A MULTI-CENTER TRIAL FOR PATIENTS WITH IMPLANTABLE DEFIBRILLATORS, PARTICULARLY SELECTED THIS ONE BECAUSE IT'S A NICE EXAMPLE OF AN EFFECTIVENESS IMPLEMENTATION HYBRID DESIGN, LOOKING EFFECTIVENESS OF DECISION SUPPORT TOOLS FOR SHARED DECISION MAKING IN ICD PATIENTS, BUT ALSO IN ADDITION WHY IT ALSO THAT EVEN THOUGH THERE'S PRETTY GOOD RESEARCH IN A COCHRANE REVIEW IT'S NOT PICKED UM IN ROUTINE CLINICAL PRACTICE AND WHAT NEEDS TO HAPPEN FOR THAT TO BE DONE IN THAT AREA. IN CANCER SPACE, WORK BY ABBY KING RECENTLY FUNDED INTERESTING FROM THE PERSPECTIVE OF TAKING A PROGRAM SHE'S IS FOR SOME TIME ACT ACTIVE LIVING EVERY DAY ADDING A CITIZEN SCIENCE COMPONENT IN WHICH THEY USE MOBILE PHONES TO BE ABLE TO IDENTIFY POTENTIAL BARRIERS IN THEIR COMMUNITY TO ACTIVE PHYSICAL ACTIVITY AND THEN COLLECTIVELY THEY SEND THAT DATA TO POLICYMAKERS AND SUPPORT SYSTEMS TO SEE IF THERE'S ADDITIONAL SUPPORT THAT HAPPENS AS A RESULT OF DOING THAT. THEN FROM THE NATIONAL INSTITUTE OF MINORITY HEALTH AND HEALTH DISPARITIES, NICE STUDY LOOKING AT SOME OF THE EPIGENETIC MEDIATIONS POSSIBLE IN TERMS OF GOING ON RELATED TO ADVERSE SEXUAL CONTACTS ON CENTRALS RESPONSE AND SOCIAL AND EMOTIONAL DEVELOPMENT AND HEALTH, A LARGE STUDY OF LARGE PERCENTAGE OF AFRICAN-AMERICAN AND HISPANIC POPULATION TO GET A SENSE WHETHER THERE'S EPIGENETIC MEDIATORS IN THAT PROCESS. THOSE ARE A FEW EXAMPLES. IT'S IMPORTANT TO SEE REAL EXAMPLES OF RESEARCH THAT'S BEEN FUNDED SO SOMEONE SAYS LOOK AT THIS, YOU CAN SAY, WELL, LOOK AT THIS, NICE RESEARCH AMONG TEN OF OVER 28 GRANTS FUNDED THIS YEAR. FUNDING ANNOUNCEMENT HIGHLIGHTS THAT I WANTED TO REMIND PEOPLE, ACTIVE IN FY17 SCIENCE OF BEHAVIOR CHANGE HAD A COUPLE OF FOAs, OPPNET HAD ONE ON MID-CAREER INVESTIGATORS FOR CLINICAL TRIALS, NIDDK HAD A NUMBER ON ANCILLARY STUDIES TO BEHAVIOR WITH OBESITY AND A NUMBER OF OTHERS YOU CAN SEE THERE. FOGARTY HAS AN ACTIVE ONE OUT ON MOBILE HEALTH AND TECHNOLOGY AND OUTCOMES IN LOW AND MIDDLE INCOME COUNTRIES. NCI HAS DISSEMINATION IMPLEMENTATION RESEARCH AND HEALTH AMONG THE MANY, THIS IS A SAMPLING OF THEM. NABIB WHICH MOST DON'T THINK AS BEING A BEHAVIORAL AND SOCIAL SCIENCE RESEARCH INSTITUTE HAS THIS ON PREDICTIVE MULTI-SCALE MODELS, SOME COMPUTATIONAL MODELING APPROACHES ARE ENDING UP THERE. NIDA HAS BEHAVIORAL INTEGRATIVE TREATMENT DEVELOPMENT PROGRAM, NIA HAS RESEARCH OF MECHANISMS, AND NICHD IS LEADING ONE IN HEALTH OF SEXUAL AND GENDER MINORITY, AND NINR HAS ONE A FUNCTION YAM FUNCTIONAL WELLNESS. I WANT TO MENTION A FEW OF THE FOAs THAT OBSSR HAS& PARTICULARLY LED. AND KEEP IN MIND THAT WE LEAD WHEN YOU CAN'T. OUR ROLE IS IN SITUATIONS IN WHICH ONE IC ISN'T IN A GOOD POSITION TO TAKE A LEAD ON A FOA, BUT THERE'S MANY WHO WOULD LIKE TO PARTICIPATE, THAT'S A GOOD EXAMPLE OF THE TYPE OF THING WE WANT TO BE ABLE TO HELP LEAD THOSE EFFORTS IN. THE INTENSIVE LONGITUDINAL ANALYSIS OF HEALTH BEHAVIORS USING TECHNOLOGY AND COMPUTATIONAL MODELING IS IN REVIEW. METHODOLOGY AND MEASUREMENT IN BEHAVIORAL AND SOCIAL SCIENCES, EDUCATION AND HEALTH NEW FRONTIERS, SYSTEMS SCIENCE AND HEALTH IN THE BEHAVIORAL AND SOCIAL SCIENCES, POPULATION HEALTH INTERVENTIONS TRYING TO INTEGRATE INDIVIDUAL AND GROUP LEVEL EFFORTS, REVISION APPLICATION ALSO ARE STILL OUT THERE FOR VALIDATION OF MOBILE AND WIRELESS HEALTH TOOLS FOR MEASUREMENT AND INTERVENTION. AND THEN ADVANCING INTERVENTIONS TO IMPROVE MEDICATION ADHERENCE WHICH WE DO ON BEHALF OF THE ADHERENCE NETWORK THAT WE HELP WORK WITH. SO A NUMBER OF ACTIVE OBSSR-LED FUNDING ANNOUNCEMENTS THAT ARE OUT THERE FOR THIS YEAR. OKAY. CO-FUNDING, WHAT EVERYBODY THINKS ABOUT WHEN THEY THINK ABOUT OBSSR, A FEW WORDS ABOUT THAT. WE CONTINUE TO USE ABOUT $20 MILLION OF OUR $27 MILLION FOR CO-FUNDING, AND MEETINGS AND CONTRACTS AND THAT SORT OF THING. WE HAD A LITTLE BIT OF A -- WE HAVEN'T EXPERIENCED IN INCREASE IN TOTAL AMOUNT BUT LOWER LEFT INCREASE IN NUMBER OF GRANTS WE CO-FUNDED OVER THE COURSE OF THE YEAR. YOU CAN, AGAIN, LOOK AT YOUR INSTITUTES AND CENTER AND WHERE YOU FALL AMONG ALL OF THESE. SOME HIGHER, SOME LOWER, AGAIN PARTLY RESULT OF HOW MUCH BEHAVIORAL AND SOCIAL SCIENCE RESEARCH THEY HAVE AND HOW MUCH GRANT FUNDING THEY DO BY SINCE TUT. I N STITUTE. IF YOU SEE SPIKES, THAT SPIKE IN 2016 WAS RESULT OF THE BRAIN INITIATIVE HAVING GRANTS IN LANGUAGE AND COMMUNICATION AND NEUROBIOLOGICAL PROCESSES RELATED, HAVING DIFFICULTY FUNDING AND WE PUT A SIGNIFICANT AMOUNT INTO THAT TO GET THAT GOING UNTIL THE BRAIN INITIATIVE GOT THE INFUSION OF FUNDING FROM THE 21ST CENTURY CURES ACT. EXAMPLES, IF YOU LOOK AT THE TOPICS OF THE TYPES OF THINGS, LOOKING ACROSS THE VARIOUS ASPECTS OF THAT, I'LL PUT THAT UP SO YOU HAVE A SENSE OF TYPES OF THINGS WE'RE LOOKING AT. AGAIN, A FAIRLY REASONABLE BREADTH I THINK, EVERYTHING FROM VERY BASIC BEHAVIORAL AND SOCIAL SCIENCE RESEARCH AND COGNITIVE AND BEHAVIORAL NEUROSCIENCE RESEARCH TO THE OTHER END OF THE SPECTRUM OF SOCIAL INFLUENCE ON HEALTH. I DID THOUGH WANT TO GIVE YOU EXAMPLES OF THE THINGS WE FUND QUITE A BIT. I TOOK THE ONES OFF THE TOP, THE ONCE WE PROVIDED THE MOST CO-FUNDING FOR, IN F.Y. 17. I WAS HESITANT TO SHOW YOU THIS BECAUSE EVERYBODY WILL NOW THINK, OH, WELL, I'LL ASK FOR $950,000, CO-FUNDING. OUR TYPICAL CO-FUNDING AMOUNT USUALLY RUNS IN $150 TO $250,000, FOR A GRANT IN TERMS OF WHAT WE FUND. MANY OF THESE LARGE ARE ONES WE'VE HAD REALLY CHARGE COMMITMENT TO THAT WE STARTED, LED, NEEDED TO PUT A FAIR AMOUNT OF MONEY INTO. I WILL NOTE THE ONE AT THE TOP, THE MOBILIZING RESEARCH INITIATIVE, IS BASICALLY A RESOURCE FOR MOBILE HEALTH RESEARCHERS, TO BE ABLE TO HAVE A TEST BENCH THEY CAN READILY AND QUICKLY BE ABLE TO GRAB PARTICIPANTS THAT HAVE CELL PHONE, SMARTPHONE, AND QUICKLY TEST AN INTERVENTION OR ASSESSMENT PROCEDURE. AND BE ABLE TO DO THAT RAPIDLY. AND MAKE THAT AVAILABLE TO RESEARCHERS SO THEY SHOULD HAVE THAT READY IN JANUARY OR FEBRUARY, CERTAINLY BY THE SPRING. YOU CAN SEE SOME THINGS WE FUND, PRETTY SIGNIFICANT WAYS. WE PUT HALF A MILLION INTO THE ABCD STUDY EVERY YEAR, VARIOUS COMPONENTS AS YOU LOOK AT THAT LIST TO GIVE YOU A SENSE OF SOME LARGER ONES WE CO-FUNDED. ONE OF THE THINGS THAT MAKES US PARTICULARLY FUNCTIONAL IN OBSSR, WE HAVE WONDERFUL PARTNERS AT THE ICs, AND EACH OF YOU IS REPRESENTED BY SOMEONE FROM YOUR INSTITUTE WHO IS A MEMBER OF THE COORDINATING COMMITTEE FOR US. WE HAVE A NUMBER OF WORKING GROUPS ONGOING RIGHT NOW, ONE ON THE CLINICAL TRIALS POLICY THAT'S BEEN ABLY LED BY MEMORIAL IS A RIDDLE AND BILL ELWOOD TO JUMPED IN TO HELP OUT IN LATER STAGES OF THAT. OUR BEHAVIORAL ONTOLOGY WORKING GROUP, BASIC AND BEYOND WORKING GROUP LOOKING AT BASIC TO APPLIED TRANSLATIONAL ASPECTS WITHIN THAT AREA, HEALTH BEHAVIOR THEORY AND FESTIVAL GROUP THAT HELPED PUT THIS TOGETHER AN EFFORT TO INTEGRATE IN THE LARGER ENTERPRISE OF THE NIH. IN TERMS OF EVENTS, THIS IS MATILDA WHITE RILEY FROM LAST YEAR, THESE ARE A COUPLE OF THE FOUR EARLY STAGE INVESTIGATORS WE AWARDED, IT'S BEEN TWO YEARS NOW, OUR THIRD COMING UP WHERE WE TAKE EARLY STAGE INVESTIGATORS, TEN YEARS SINCE TERMINAL DEGREE, ASK THEM TO SUBIT A PAPER, DO AWARDS AND PAPER COMPETITION FOR SOME OF THE MOST SORT OF IMPACTFUL AND CRITICAL RESEARCH THAT WE SEE FROM EARLY STAGE INVESTIGATORS AS WELL. AND THEN WE'VE HAD A LOT OF NEW FACES IN FY17, YOU MAY LOOK AT THIS AND WONDER WEREN'T YOU UNDER A HIRING FREEZE? WE WERE, BUT NOT UNTIL JANUARY. SINCE OBSSR, THE FISCAL YEAR STARTS IN OCTOBER FOR US, WE DID A FAIR AMOUNT OF HIRING THAT WAS PART OF THE TWO-YEAR RAMP BACK UP TO BEING AT FULL CAPACITY OR NEAR FULL CAPACITY. SO JUST A FEW FOLKS, TO LET YOU KNOW WHO PEOPLE ARE. KARA JOHNSON ADMIN STAFF, ERICA MOORE COMMUNICATION DIRECTOR, A FEW WHO HAVE SEEN PROMOTIONAL MATERIALS AND THINGS RELATED TO THIS EFFORT, THAT WAS ERICA'S WORK. GILLIAN AND ERIN, GILLIAN WAS HELPFUL WITH ANALYSES FOR THIS PRESENTATION AS WELL. LAURA CAME TO ALLS FROM NIA, KATE MCNEIL FROM NCI CONTRACTS AND BUDGET, AND OUR LATEST HIRE CHRISTINE HUNTER, DEPUTY DIRECTOR, WHICH HAS BEEN A WONDERFUL ADDITION TO WHAT IS ALREADY A GREAT GROUP OF PEOPLE THAT I THINK WE'VE AMASSED TOGETHER AT OBSS OBSSR TO SUPPORT THE BEHAVIORAL AND SOCIAL SCIENCES AT YOUR INSTITUTES AND CENTERS. LOOKING AHEAD, AND WRAPPING UP, THERE ARE A FEW THINGS TO REMIND YOU OF AS WE LOOK FORWARD. SOCIAL AND BEHAVIORAL SCIENCE CONTRIBUTIONS IN SUPPORT OF THE NIH RESPONSE TO OPIOID CRISIS MARCH 5 AND 6. OUR HOPE IS WE ACHIEVE THE ABILITY TO JUST BE MORE COMPREHENSIVE AND BALANCED RELATED TO PROVIDE CRISIS. SCREENING AND REFERRAL FOR SOCIAL DETERMINANTS OF HEALTH, NCI AND OBSSR SUPPORTED AN IOM REPORT ON INCORPORATING AND CAPTURING SOCIAL AND BEHAVIORAL PHENOMENA IN THE ELECTRONIC HEALTH RECORD. THIS IS A FOLLOW-UP MEETING FROM THAT TO SEE WHERE ARE WE, WHAT THINGS HAVE WE DONE, MOVE TO FORWARD. AND MATILDA WHITE RILEY HONORS MAY 31 IN WILSON HALL AS WELL. TERRY MOFFITT, WE'VE ALREADY SELECTED OUR EXCELLENT LECTURER FOR THIS YEAR COMING UP, TERRY MOFFITT WILL BE OUR LECTURER FOR THAT. EARLY STAGE INVESTIGATOR PAPER NOMINATIONS OR APPLICATIONS WILL BE STARTING IN JANUARY, SO KEEP YOUR EYES OPEN FOR THAT AND IF YOU HAVE EARLY STAGE INVESTIGATORS YOU WANT TO HAVE THEM CONTRIBUTE TO THAT PROCESS BY ALL MEANS DO. A FEW NEW THINGS COMING DOWN THE PIKE, WE'VE BEEN WORKING FURIOUSLY ON A NEW WEBSITE, STREAMLINED, CLEANER, EASY TO NAVIGATE, UP AND RUNNING FAIRLY SOON IN THE NEW YEAR. WE'RE CLOSE TO AN ELECTRONIC CO-FUNDING REQUEST SYSTEM SO ALL THAT PAPER YOU'VE HAD TO WRITE ON ALL THE TIME TO TELL US ABOUT YOUR CO-FUNDING REQUEST WILL BE ELECTRONIC AND ALSO MORE INTEGRATED ACROSS ALL THE DIVISION OF PROGRAM COORDINATION POLICY AND STRATEGIC INITIATIVE. AND THEN THIS WILL BE A JOKE FOR EVERYBODY WHO WORKS AT THE OBSSR. ONE DAY WE'RE GOING TO HAVE AN OPEN HOUSE FOR OUR RENOVATED OFFICE SPACE. I SAY ONE DAY, BECAUSE I THINK THIS TIME LAST YEAR WE THOUGHT IT WAS GOING TO NEARLY BE DONE. WE'RE STILL THIS YEAR, IT'S NOT QUITE DONE. BUT SOON AND AT SOME POINT. WHEN WE DO WE'LL INVITE ALL OF YOU OVER TO SEE IT AND HAVE MILK AND COOKIES, WHICH IS ABOUT ALL WE CAN SERVE AT THE NIH. AND THEN FINALLY THE RESEARCH FESTIVAL PLANNING COMMITTEE, THESE ARE THE FOLKS THAT HELP PUT THIS TOGETHER. TAKE YOUR NOMINATIONS FOR PANELS THAT WOULD RESPOND, AND DELIVER THE VARIOUS SORT OF PANEL PRESENTATIONS OVER THE COURSE OF THE DAY, ALL OF THEM, AMAZING WORK, MUCH APPRECIATED FROM ALL OF THEM FOR DOING THIS ABLY LED BY WENDY SMITH, ASSOCIATE DIRECTOR AT OBSSR FOR PULLING ALL OF THIS TOGETHER, SO THANK YOU VERY MUCH. AND WITH THAT, I THINK I AM DONE. AND I WILL NOW TURN THE PODIUM OVER TO BOB FREEMAN FROM NIAAA TO GET US STARTED WITH THE FIRST PANEL AND INTRODUCE THE PANEL PRESENTATIONS. SO, BOB, IT'S ALL YOURS. THANK YOU. THANK YOU ALL. >> I'M BOB FREEMAN, NIAAA, WE HAVE OUR INTERVENTION PANEL THIS MORNING. THREE EXCELLENT SPEAKERS. FIRST IS DR. ERIC LENZE, PROFESSOR IN DEPARTMENT OF PSYCHIATRY AT WASHINGTON UNIVERSITY MEDICAL SCHOOL OF MEDICINE, COMPLETED COLLEGE MEDICAL SCHOOL AND PSYCHIATRY WASHINGTON UNIVERSITY, THEN MOVED TO PITTSBURGH. 2007 RETURNED TO WASHINGTON UNIVERSITY DEPARTMENT OF PSYCHIATRY, DIRECTS HEALTHY MIND LAB. RESEARCH FOCUS ON TREATMENT FOR OLDER ADULTS WITH DEPRESSION, ANXIETY AND COGNITIVE DECLINE AND STUDIES HOW TO IMPROVE RECOVERY FROM DISABLING MEDICAL CONDITIONS SUCH AS HIP FRACTURES AND STROKE, AUTHOR ON 200 PEER REVIEWED ARTICLES, REVIEWS AND BOOK CHAPTERS, A PRACTICING GERIATRIC PSYCHIATRIST WHO SEES PATIENTS AND TEACHES YOUNG PHYSICIAN AND MEDICAL STUDENTS AT WASHINGTON UNIVERSITY, PRESENTATION IS "MINDFULNESS BASED STRESS REDUCTION FOR OLDER ADULTS." I'M GOING TO DO ALL THREE. SECOND SPEAKER IS SEBASTIAN LINNEMAYR, SENIOR ECONOMIST AT THE RAND CORPORATION, PROFESSOR AT THE RAND GRADUATE SCHOOL, RESEARCH ON USE OF APPLICATION OF INSIGHTS FROM BEHAVIORAL ECONOMICS TO IMPROVE CONFLICTS, CHRONIC HEALTH BEHAVIOR IN PARTICULAR RELATED TO HIV, TRAVELS TO UGANDA, PRESENTATION IS "BEHAVIORAL ECONOMIC APPROACHES TO IMPROVE ANTIRETROVIRAL THERAPY ADHERENCE." THE THIRD SPEAKER IS KELLI KOMRO, PROFESSOR BEHAVIORAL SCIENCES AND HEALTH EDUCATION ROLLINS SCHOOL OF PUBLIC HEALTH AT EMORY, SOCIAL AND BEHAVIORAL EPIDEMIOLOGIST, TWO DECADES EXPERIENCE OF P.I. OR CO-P.I. RANDOMIZED TRIALS, REDUCING HEALTH DISPARITIES FOCUSING ON UNDERSERVED POPULATION OF USE, LEADS AN NIMHD-FUNDED STUDY ON SECURITY POLICY EFFECT ON INFANT AND CHILD MORTALITY AND COMMUNITY TRIAL IN COLLABORATION WITH CHEROKEE NATION TO PREVENT ALCOHOL USE AND CONSEQUENCES AMONG YOUTH IN RURAL COMMUNITIES, PUBLISHED OVER 100 STUDIES, LEADING PUBLIC HEALTH PREVENTION SCIENCE, PREVENTIVE MEDICINE ADDICTION AND HEALTH BEHAVIOR JOURNALS, RECOGNIZED FOR TEACHING AND MENTORING, RECIPIENT OF THE UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE EXEMPLARY TEACHER AWARD, SOCIETY FOR PREVENTION RESEARCH MENTORING AWARD AND AMERICAN PUBLIC HEALTH ASSOCIATION STUDENT CAUCUS MENTOR OF THE YEAR AWARD, MEMBER OF DELTA OMEGA SOCIETY, HONORARY PUBLIC HEALTH SOCIETY, HELD ACADEMICS POSITIONS AT UNIVERSITY OF MINNESOTA AND UNIVERSITY OF FLORIDA, ASSOCIATE DIRECTOR EVER INSTITUTE FOR CHILD AND HEALTH POLICY, ALCOHOL USE AMONG NATIVE AMERICAN AND WHITE HIGH SCHOOL STUDENTS IN THE CHEROKEE NATION, SO WE'LL BEGIN WITH DR. LENZE. [APPLAUSE] >> THANK YOU FOR THE INTRODUCTION. THANK YOU FOR THE INVITATION TO THIS MEETING. I'M A GERIATRIC PSYCHIATRIST, I WANT TO GIVE THANKS TO THE NIH INSTITUTES FUNDING OUR RESEARCH. BACKGROUND OF DEMENTIA, SEVERE COGNITIVE DECLINE THAT WHICH ROBS OUR ABILITY TO LIVE AND FUNCTION INDEPENDENTLY. DEMENTIA IS CAUSED BY A NUMBER OF NEURODEGENERATIVE CONDITIONS, THE MOST COMMON OF WHICH IS ALZHEIMER'S DISEASE. WE HEARD A LITTLE BIT ABOUT THE OPIOID CRISIS, WHICH HAS TO SOME EXTENT TAKEN US BY SURPRIS, BUT DEMENTIA IS AN ONGOING AND LOOMING PUBLIC HEALTH CRISIS THAT WE'VE KNOWN IS COMING FOR DECADES NOW. THAT'S BECAUSE BY FAR THE STRONGEST RISK FACTOR FOR THESE NEURODEGENERATIVE DISEASES IS AGING, AND OUR POPULATION IS AGING. WHY IS THIS BECOMING A CRISIS? IN SPITE OF INCREASING CRISIS OF DEMENTIA, THERE EXISTS CURRENTLY NO EVIDENCE-BASED PREVENTION FOR DEMENTIA. I'LL SAY IT AGAIN. RECENTLY BOTH THE AHRQ AND NATIONAL ACADEMY OF SCIENCES RELEASED DOCUMENTS EXAMINING EVIDENCE FOR PREVENTING OR SLOWING DOWN COGNITIVE DECLINE AND DEMENTIA, AND HAVE CONCLUDED THAT WE HAVE AS YET NO EVIDENCE-BASED INTERVENTION. PSYCHOSOCIAL OR PHARMACOLOGIC OR OTHERWISE. SO WHAT DOES THIS MEAN FOR OUR SOCIETY? RIGHT NOW IN THE U.S. THERE ARE 5 MILLION ADULTS LIVING WITH DEMENTIA. IN THE VERY NEAR FUTURE, 2030 IS AS EYE BLINK BY NIH TERMS, WE'LL SEE A RISE TO OVER 8 MILLION CASES. THIS IS AS THE BABY BOOMER GENERATION ENTERS THE AGE OF HIGHEST RISK FOR DEMENTIA. AND ULTIMATELY WITHOUT AN EFFECTIVE PREVENTION TREATMENT THAT'S DISPERSED WIDELY IN OUR POPULATION WE'LL SEE 10 MILLION CASES BY 2050. AND THAT EVEN PALES TO WHAT DEMENTIA WILL BE WORLDWIDE BY 2050, OVER 100 MILLION CASES. FOR THOSE OF YOU, MANY IN THE ROOM WHO DEALT WITH EVEN ONE CASE OF DEMENTIA IN A FAMILY MEMBER, THESE NUMBERS ARE SOBERING. NOW, A LOT OF REALLY GOOD IS FOCUSED ON UNDERSTANDING AND TARGETING THE MOLECULAR PROCESSES. FOR EXAMPLE, IN ALZHEIMER'S DISEASE, AMYLOID DEPOSITION AND TAU PHOSPHORYLATION. HOWEVER, THOSE DISEASES THEMSELVES, THE BRAIN PATHOLOGY WE SEE IN OLDER ADULTS, EXPLAINS MAYBE ONLY 40% OF THE COGNITIVE DECLINE IN THAT POPULATION. THIS MEANS THERE'S A VERY LARGE ROLE POTENTIALLY FOR BEHAVIORAL AND SOCIAL SCIENCE RESEARCH FOR THAT OTHER 60% BY WHICH I MEAN INCREASING BRAIN AND COGNITIVE RESILIENCE TO PREVENT OR SLOW DOWN COGNITIVE DECLINE OF DEMENTIA. TWO I'LL TOUCH ON TODAY, BY NO MEANS AN EXHAUSTIVE LIST, STRESS REDUCTION AND EXERCISE. SO STARTING WITH STRESS AND AGING, HOW IS STRESS -- THIS IS A TERM THAT GETS USED RATHER BROADLY, BUT HERE I WOULD MEAN CHRONIC PSYCHOSOCIAL STRESS OR STRESS CONDITIONS LIKE MAJOR DEPRESSION OR ANXIETY DISORDERS. HOW IS THAT TOXIC TO THE BRAINS OF OLDER ADULTS? WELL, MANY OF YOU ARE PROBABLY AWARE OF A LONGSTANDING THEORY THAT I , THE GLUCOCORTICOID THEORY, I'M NO NEUROBIOLOGIST SO I SIMPLIFY FOR MY SAKE. THINK OF HOW DOES STRESS AFFECT THE BODY AND THEN THE BRAIN, STRESS CAUSES A HYPERACTIVATION OF WHAT WE CALL THE HPA PATHWAY. A BRAIN PATHWAY THAT PUTS OUT EXCESS CORTISOL, WHICH THEN COMES BACK INTO THE BRAIN, TRIGGERING EXCESS GLUCOCORTICOID RECEPTOR ACTIVATION PARTICULARLY WITHIN THE HIPPOCAMPUS AND PREFRONTAL CORTEX, STRESS LEADS TO MORE STRESS. INTERESTINGLY ENOUGH, THIS LONGSTANDING AND HIGHLY RESPECTED THEORY HAS YET TO LEAD TO ANY EVIDENCE-BASED INTERVENTIONS FOR THIS CONDITION OF COGNITIVE IMPAIRMENT. SO WE'VE BEEN LOOKING AT ONE, WHICH IS MINDFULNESS. MINDFULNESS PERHAPS THE OLDEST INTERVENTION TO REACH OUT FOR SINCE ITS EXISTED IN SOME FORM FOR ABOUT 5,000 YEARS. LET ME JUST DEFINE FOR THE AUDIENCE WHAT I'M TALKING ABOUT WHEN I REFER TO MINDFULNESS. WHICH IS A PROCESS OF BRINGING ONE'S COMPLETE ATTENTION TO THE PRESENT EXPERIENCE, PAYING ATTENTION BUT IN A SPECIFIC WAY. PAYING ATTENTION ON PURPOSE AND HOPEFULLY WITH THIS AUDIENCE NON-JUDGMENTALLY. ONE WAY I LIKE TO THINK OF MINDFULNESS, WHAT IT IS, IS JUST DESCRIBE INSTANCES WHEN IT ISN'T. SO IF YOU'RE SITTING HERE THINKING ABOUT YOUR TALK YOU'RE GOING TO GIVE IN THE FUTURE, YOU'RE NOT BEING PRESENT. ALTHOUGH I DON'T BLAME YOU. THAT'S WHAT I WOULD BE DOING IF I HAD A TALK COMING UP. [LAUGHTER] IF YOU'RE WORRYING ABOUT THE FUTURE, YOU'RE NOT BEING PRESENT. NOT BEING MINDFULNESS. IF YOU'RE RUMINATING ABOUT THE PAST YOU'RE NOT BEING MINDFUL. IF ON YOUR DRIVE IN HERE, YOU WERE INSTEAD OF FOCUSING ON THE ROAD, YOU WERE THINKING ABOUT EVERYTHING YOU HAD TO GET DONE THAT DAY, YOU PARKED AND THOUGHT, GEEZ, I WAS REALLY ON AUTO DRIVE, HOW DID I GET HERE, YOU WERE NOT BEING MINDFUL. NO BLAMES HERE, MOST OF US ARE NOT BEING MINDFUL FOR MOST OF OUR LIVES. AND THEN HOW DOES MINDFULNESS RELATE TO MEDITATION? MEDITATION IS A SERIES OF SIMPLE BUT FORMAL PRACTICES WHICH INCREASE THE SKILL OF MINDFULNESS. PROBABLY THE SIMPLEST MEDITATION IS JUST SITTING AND BREATHING AND FOCUSING ON YOUR BREATHING. SO, YOU'VE NO DOUBT SEEN MINDFULNESS RESEARCH ENTER INTO MANY DIFFERENT NIH-FUNDED REALMS. COULD IT IMPROVE AGING? ONE CASE REPORT, IF IT HELPED THIS GUY LIVE TO 900 YEARS MAYBE THIS IS REALLY A POTENTIAL INTERVENTION. BUT WHAT ABOUT OUR INDIVIDUALS IN THE REAL NON-FANTASY WORLD? I WANT TO DESCRIBE THE RESULTS OF A STUDY I CARRIED OUT WITH MY COLLEAGUE AND PARTNER IN CRIME, JULIE WEATHERELL, A PSYCHOLOGIST AT UCSD WHO URGEED ME TO GET INTO MINDFULNESS RESEARCH WITH HER. WE WERE AWARDED ONE OF THE LAST COLLABORATIVE R34s NIH GAVE OUT FUNDED BY WHAT WAS THEN NCCAM, NOW NCCIH. I'LL TALK MORE ABOUT WHAT MINDFULNESS-BASED RESEARCH IS BUT WE RANDOMIZE OVER 100 OLDER ADULTS TO ONE OF TWO INTERVENTIONS, EITHER ACTIVE INTERVENTION MINDFULNESS-BASED STRESS REDUCTION WHICH IS WITHIN GROUP MEDITATION AND MINDFULNESS PRACTICE, AND THEN AT-HOME PRACTICE AS WELL, OR WHAT YOU COULD CALL AN ATTENTION PLACEBO, HEALTH EDUCATION GROUP. ALL OF THESE OLDER ADULTS HAD NOT ONLY COGNITIVE COMPLAINTS, I SHOULD SAY SUBJECTIVE COGNITIVE COMPLAINTS AS OPPOSED TO OBJECTIVE IMPAIRMENTS, AND THEY ALSO HAD EITHER AN ANXIETY DISORDER OR DEPRESSION. SO REALLY PEOPLE WHO ARE IN OUR MINDS EXEMPLIFYING THE STRESS AND COGNITIVE IMPAIRMENT DYAD. I'M GOING TO GO RIGHT TO THE MAIN RESULTS. THIS IS THE CLIFF NOTES VERSION OF WHAT WE FOUND. THE MINDFULNESS TRAINING WAS THREE THINGS. ONE, GOOD FOR THE BRAIN, AND I'LL SHOW YOU THOSE FINDINGS. IT WAS ALSO GOOD FOR ANXIETY AND DEPRESSION. AND FINALLY, WE FOUND EVIDENCE THAT IT WAS A SUSTAINABLE INTERVENTION. I'LL JUST MAKE A COMMENT, ONE OF THE NICE THINGS ABOUT BEHAVIORAL AND SOCIAL INTERVENTIONS IS THAT YOU OFTEN GET A TWO-FER OR THREE-FER, INTERVENTION THAT MAY HELP THE BRAIN AND QUALITY OF WELL-BEING, FINISHED A WHILE AGO BUT JUST THIS YEAR PUBLISHED. NO FURTHER COMMENTS ABOUT THAT. SO WHAT IS MINDFULNESS-BASED STRESS REDUCTION? AN INTENSIVE AND HIGHLY PROTOCOLIZED INTRODUCTION TO MINDFUL MEDITATION. AS A CLINICAL TRIALIST, THE CHANCE TO STUDY MINDFULNESS WITHIN A HIGHLY PROTOCOLIZED INTERVENTION IS VERY ATTRACTIVE. THIS IS AN 8-WEEK CLASS, WHEREUPON PEOPLE COME TO 2 1/2-HOUR CLASSES THAT HAVE FAIRLY SPECIFIED CONTENT FOR EACH CLASS, AS WITH MANY MINDFULNESS PRACTICES THERE IS EMBEDDED WITHIN THE CLASS A DAY-LONG RETREAT, AND THEN THE OTHER MAJOR PART OF MINDFULNESS-BASED STRESS REDUCTION IS DAILY AT-HOME PRACTICE. SO WHAT YOU LEARN IN CLASS, THEN YOU PRACTICE AT HOME. SO, AS FAR AS THE FIRST RESULT, HOW DID WE FIND EVIDENCE THAT MINDFULNESS-BASED STRESS REDUCTION WAS GOOD FOR THE BRAIN? WE MEASURED OLD ADULTS MEMORY BEFORE AND AFTER. AS YOU CAN SEE MEMORY PERFORMANCE IMPROVED, IT INCREASED IN BOTH GROUPS POSSIBLY REFLECTING PRACTICE EFFECTS, BUT IMPROVED SIGNIFICANTLY MORE IN THE MINDFULNESS-BASED STRESS REDUCTION INTERVENTION GROUP. WHY? ONE POSSIBLE BIOLOGICAL EXPLANATION FOR THIS GOES BACK TO THE THEORY I SAID BEFORE, SO WE ALSO CONCURRENTLY FOUND A CORTISOL REDUCTION IN THE MINDFULNESS GROUP VERSUS NOT IN THE CONTROL GROUP. AND ADDITIONALLY WE FOUND THAT THE INDIVIDUALS WHO HAD THE LARGEST IMPROVEMENT IN MEMORY WITH MINDFULNESS WERE THE ONES WHO HAD THE HIGHEST CORTISOL AT BASELINE. SO, THIS IS ONE OF OUR THEORIES HOW MINDFULNESS MAY AFFECT BRAINS OF OLDER ADULTS, CONTROL AND REGULATION COMING WITH MINDFULNESS TRAINING REDUCES THIS HPAX, HYPERACTIVITY, REDUCING CORTISOL PRODUCTION, LESS HYPERACTIVATION OF THESE BRAIN REGIONS, IMPROVED COGNITION AND REDUCED DISTRESS. ALONG THE WAY, ANOTHER POSSIBLE CANDIDATE MECHANISM CAME UP, WHICH INVOLVED A MOLECULE CALLED REST. I GUESS I WOULD DESCRIBE AS A NON-NEUROBIOLOGIST, REST IS A NEUROPRESERVATION OR NEURORESILIENCE MOLECULE, REPRESSOR ELEMENT-1 SILENCING TRANSCRIPTION FACTOR AND THIS MOLECULE, REST, IS FOUND IN NEURONS WHERE IT'S BEEN FOUND TO BE ONE OF THE KEY REGULATORS OF THE BRAIN STRESS RESPONSE, IN HEALTHY OLDER ADULT POPULATIONS REST IS INCREASED AND APPEARS TO BE NEUROPROTECTIVE, PROTECTING NEURONS FROM OXIDATIVE STRESS AS WELL AS TOXICITY FROM AMYLOID. IT'S REDUCED IN BOTH STRESS CONDITIONS AND ALZHEIMER'S DISEASE IN INDIVIDUALS WHO WERE FOUND TO HAVE FASTER PROGRESSION TO DEMENTIA, HAD LOWER REST LEVELS. VERY NICELY, REST IS A NEURONAL MOLECULE BUT CAN BE MEASURED IN BLOOD BY MEASURED BY MEASURING NEURONALLY DERIVED EXOSOMES, NEURONS THAT BREAK OFF AND FLOAT INTO AND CAN BE COLLECTED AND MEASURED AND AND IN PERIPHERAL BLOOD. REST LEVELS INCREASE WITH MINDFULNESS-BASED STRESS REDUCTION AS YOU CAN SEE IN THE FIGURE ON THE LEFT, INCREASE IN MINDFULNESS GROUP VERSUS NO INCREASE IN THE CONTROL CONDITION. AND THEN THESE OTHER TWO FIGURES JUST SHOW SPAGHETTI PLOTS SHOWING NUMBER OF INDIVIDUALS WHO INCREASED OR DECREASED IN EACH GROUP AS YOU CAN SEE ON THE FAR RIGHT, ALMOST ALL OF THE INDIVIDUALS WHO RECEIVED MBSR SHOWED SOME INCREASE IN REST LEVEL. I DO WANT TO SAY THIS IS VERY PRELIMINARY RESEARCH, IN THAT AREA, BUT IT IDENTIFIES A COUPLE OF BRAIN PROTECTIVE MECHANISMS, BIOLOGIC MECHANISMS. MBSR WAS ALSO GOOD FOR ANXIETY AND DEPRESSION, REDUCING WORRY PATHOLOGY, WHAT YOU SEE HERE IS A REDUCTION IN A WORRY SCALE, WITH MINDFULNESS-BASED STRESS REDUCTION, FROM BEGINNING TO END. THREE AND SIX MONTHS LATER REALIZING THIS IS AFTER THE INTERVENTION WAS DONE, CONTINUED LOWER WORRY PATHOLOGY, AND THIS GREATER IMPROVEMENT OR EFFECTIVENESS WAS SEEN ON SEVERAL OTHER CLINICAL SCALES AS WELL. FINALLY ONE OF THE THINGS MOST PLEASANTLY DESCRIBED, WE CALLED PEOPLE THREE OR SIX MONTHS LATER, ARE YOU STILL PRACTICING MINDFULNESS, BASICALLY OUR RESPONSE WAS, WAIT, YOU ARE? AS AN INTERVENTION RESEARCHER I USUALLY SEE PEOPLE STOP DOING WHAT WE'VE HELPED THEM DO, AS SOON AS THE STUDY IS OVER. IN THIS CASE, EVERY SINGLE PARTICIPANT WHO COMPLETED, EVERY COMPLETER I SHOULD SAY, REPORTED CONTINUING TO ENGAGE IN AT LEAST SOME MINDFULNESS PRACTICE, ON A WEEKLY BASIS. AND I THINK THIS BODES WELL FOR THIS INTERVENTION AS A POTENTIAL PROVIDING SUSTAINED HEALTH BEHAVIOR CHANGE. THIS WAS PILOT WORK THAT LED TO A LARGE ONGOING STUDY FUNDED BY MULTIPLE NIH INSTITUTES AS WELL AS McKNIGHT BRAIN RESEARCH FOUNDATION, MEDEX, MINDFULNESS EDUCATION AND EXERCISE, BUT THIS IS A TEST OF MINDFULNESS-BASED STRESS REDUCTION AND EXERCISE FOR THE COGNITIVE BENEFITS. I'LL TOUCH ON EXERCISE, WHY ARE WE LOOKING AT BOTH OF THEM TOGETHER IN ONE STUDY? EXERCISE ALSO HAS MANY PUTATIVE BENEFITS FOR THE BRAIN, LISTED HERE, WHICH MAY COMPLEMENTARY TO OR SYNERGISTIC WITH THE PUTATIVE BENEFITS OF MBSR. THIS IS AN ONGOING STUDY, AS I SAID, A BEAST OF A STUDY AS WELL, HAPPY TO SAY THAT IT'S GOING WELL AND WITHIN ANOTHER TWO YEARS WE SHOULD HAVE OUR INITIAL RESULTS FROM IT. BUT IN THIS STUDY A LARGE POPULATION, 580 OLDER ADULTS RANDOMLY ASSIGNED TO GET EXERCISE OR NOT AND MINDFULNESS FOR ONE TO TWO YEARS AND MAINTENANCE PERIOD MEASURED WITH A VARIETY OF BATTERIES INCLUDING NEUROPSYCHOLOGICAL, PERIPHERAL BIOMARKERS INCLUDING ONES I DESCRIBED AND ALSO SOME MULTI-FACETED METABOLIC FITNESS PERFORMANCE BEHAVIORAL AND FUNCTIONAL OUTCOMES. WE THINK THAT THESE INTERVENTIONS WILL HELP IN MANY WAYS, WE WANT TO MEASURE EACH OF THEM. I'M JUST GOING TO FINISH WITH JUST SOME BROADER THOUGHTS ABOUT PREVENTING COGNITIVE DECLINE AND KEY ROLE OF BEHAVIORAL AND SOCIAL SCIENCE RESEARCH. THEY ARE ESSENTIAL STUDIES OF OLDER ADULTS, FOUND THESE STRONGEST, THE STRONGEST RISK OR RESILIENCE FACTORS, BRAIN RISK OR RESILIENCE FACTORS, ARE BEHAVIORAL AND SOCIAL INCLUDING BUT NOT LIMITED TO EDUCATION, SOCIAL AND COGNITIVE ENGAGEMENT, PERSONALITY TRAIT OF CONSCIENTIOUSNESS, SYMPTOMS OF DEPRESSION AND ANXIETY, STRESS, ONE'S PHYSICAL ACTIVITY AND DIET AND TOUCHED ON BEFORE THESE KINDS OF INTERVENTIONS HAVE POSITIVE SPILLOVER EFFECTS, IF YOU'RE AT NIA YOU MIGHT BE INTERESTED IN HOW THESE PREVENT COGNITIVE DECLINE OR POSSIBLY FALLS. BUT THEY CAN, FOR EXAMPLE, IMPROVING CONSCIENTIOUSNESS, ALSO IMPROVE TREATMENT ADHERENCE WHICH WOULD BE OF INTEREST TO SOMEONE AT NCI OR NHLBI. STRESS REDUCTION MAY HEALTH BRAIN HEALTH AND QUALITY OF WELL-BEING, REDUCE LOWER BACK PAIN. SO, WHAT KIND OF THOUGHTS DO I HAVE ABOUT RESEARCH, JUST TIME PREVENTS ME FROM FULLY GIVING YOU THOSE THOUGHTS BUT INCORPORATING BIOMARKERS INTO SOCIAL AND PSYCHOSOCIAL INTERVENTION STUDIES HAS BEEN REALLY PRODUCTIVE. I KNOW FOR OUR LAB, AND I THINK MORE OF THAT IS NEEDED. I GUESS I WOULD SAY THE CONVERSE, TO PUT PSYCHOSOCIAL MEASUREMENT ALSO IN BIOLOGICAL STUDIES. THE CLINICAL TRIALS, WE NEED RIGOROUS TESTS OF THE BEST CANDIDATES TO PREVENT COGNITIVE DECLINE. THEY NEED TO BE DONE IN HIGH RISK POPULATIONS, AND MOST IMPORTANTLY THEY NEED TO BE CARRIED OUT FOR A SUFFICIENT INTERVENTION. BELIEVE IT OR NOT, A OF 1 1/2-YEAR LONG INTERVENTION MAY BE SUFFICIENT TO SHOW A COGNITIVE BENEFIT, A BRAIN BENEFIT IN OLDER ADULTS, BUT IT'S PROBABLY NOWHERE NEAR LONG ENOUGH TO DEMONSTRATE DEMENTIA PREVENTION BENEFIT. SO SUFFICIENT DURATION CLINICAL TRIALS. AND THEN IN THE AREA OF DEMENTIA PREVENTION, DISSEMINATION AND IMPLEMENTATION RESEARCH, HOW DO WE GET THESE INTERVENTIONS WIDESPREAD? HOW DO WE GET THE ULTIMATELY 100 MILLION OLDER ADULTS IN THE U.S. AND ULTIMATELY 2 BILLION, BILLION WITH A B, WORLDWIDE, TO DO THE INTERVENTION. THANK YOU FOR YOUR ATTENTION. [APPLAUSE] DO WE TAKE QUESTIONS NOW OR LATER? NOW? OKAY. I'M HAPPY TO TAKE QUESTIONS ABOUT ANY OF THE -- OR IF YOU'D RATHER PRACTICE MINDFULNESS FOR A MINUTE, I CAN UNDERSTAND THAT AS WELL. ALL RIGHT. THANK YOU VERY MUCH. OH, I DO HAVE ONE. OKAY, THANK YOU. DIDN'T GIVE YOU A CHANCE TO GET TO THE MICROPHONE >> I WAS CURIOUS IF YOU LOOKED AT MRI STUDIES TO LOOK AT, YOU KNOW, THE ACTIVE -- BASICALLY REGIONS OF THE BRAIN AFFECTED BY MINDFULNESS AND IF YOU SAW ANY CHANGES IN THAT AT ALL. >> YEAH, GREAT QUESTION. THE SHORT ANSWER IS WE DIDN'T. WE ARE NOW. >> OKAY. >> WE'RE NOW CONDUCTING WHAT FRIGHTENINGLY TO ME IS PERHAPS ONE OF THE LARGEST NEUROIMAGING STUDIES CONDUCTED IN OLDER POPULATIONS WHICH IS THE MEDEX STUDY, AND SO WE WILL I THINK HAVE SOME REALLY GOOD ANSWERS TO THAT WHEN THE STUDY IS DONE. IF YOU IMAGE 580 PEOPLE AT THREE TIME POINTS UNDERGOING MINDFULNESS TRAINING OR NOT, IT SHOULD HAVE SOME GOOD ANSWERS BY THE END OF THAT STUDY. >> COOL. >> THANK YOU. >> HI, LIZ NEILSEN, NATIONAL INSTITUTE ON AGING. I'M INTERESTED IN YOUR THOUGHTS ON THIS IDEA THAT'S OUT THERE THAT MINDFULNESS AND EXERCISE BOTH ARE SORT OF PLASTICITY INDUCERS IN SOME SENSE, AND THAT MIGHT BE -- MIGHT LAY A NICE FOUNDATION FOR NEW LEARNING, HAVE YOU IN ANY OF YOUR SMALL STUDIES TRIED TO LOOK AT COMBINATION OF MINDFULNESS OR EXERCISE WITH, SAY, COGNITIVE TRAINING OR HABIT LEARNING, MAYBE IN CBT OR SOMETHING LIKE THAT AND SEEN BOOSTER EFFECTS OF HAVING THAT INITIAL MINDFULNESS OR EXERCISE MANIPULATION? >> WE HAVEN'T, BUT IT'S A REALLY DELICIOUS IDEA. THE IDEA THAT ONE INTERVENTION THAT ENHANCES NEUROPLASTICITY MIGHT MAKE A SECOND INTERVENTION WORK EVEN BETTER, OR THAT IN THAT WAY TWO INTERVENTIONS MAY HAVE NOT JUST ADDITIVE BUT SYNERGISTIC EFFECT, TO SOME EXTENT IMPLICIT IN THE MEDEX STUDY. I'VE NOT COMPLETED RESEARCH OF THAT SORT. WE HAVE SOME ONGOING PROJECTS OF THAT SORT, AND, BOY, THERE ARE A LOT OF CANDIDATES FOR THAT, RIGHT? YOU COULD GIVE SOMEONE A MEDICATION THAT MAY BOOST NEUROPLASTICITY TO SEE IF IT HELPS PSYCHOTHERAPY OR MINDFULNESS WORK BETTER, YOU COULD EXERCISE SOMEONE TO HOPEFULLY IMPROVE NEUROPLASTICITY AND SEE IF EXERCISE MAKES MINDFULNESS PSYCHOTHERAPY OR OTHER -- OSH A HEALTH BEHAVIOR CHANGE INTERVENTION WORK BETTER. YOU COULD USE COGNITIVE TRAINING TO DO SO, OR YOU COULD USE A DEVICE LIKE TRANSCRANIAL DIRECT CURRENT STIMULATION OR TRANSCRANIAL MAGNETIC STIMULATION. THE POSSIBILITIES ARE VIRTUALLY ENDLESS, I THINK IT'S A GREAT IDEA, AND I'M GLAD THE NIA IS INTERESTED IN THAT. >> THANK YOU. >> REALLY GOOD STUDY. THANK YOU FOR THE PRESENTATION. GOT A QUESTION ABOUT THE INTENSIVENESS OF THE MINDFULNESS TRAINING. YOU KNOW, IT SOUNDED LIKE YOU HAD EIGHT SESSIONS, 2 1/2 HOURS DO YOU THINK THAT MINDFULNESS MIGHT WORK BECAUSE IT SOUNDS AS IF DOING THAT AT A POPULATION WOULD PROBABLY BE DAUNTING. YOU'RE NOT GOING TO GET THIS IN THE OLD FOLKS HOMES. >> YEAH, IT'S A REALLY GOOD THOUGHT. I GUESS AT THIS STAGE OF THE RESEARCH, OUR GOAL IS TO SEE HOW WELL IT WORKS AT THIS INTENSITY AND AS YOU KNOW, THERE'S OFTEN A STRONG AND VERY REASONABLE PUSHBACK FROM PEOPLE WHO SAY, HEY, WHY DO YOU RESEARCHERS IMMEDIATELY WANT TO ADAPT AND SLIM DOWN OR DUMB DOWN OR SIMPLIFY AN INTERVENTION THAT'S ALREADY GOT A LOT OF BACKGROUND TO IT? SO WE FOR NOW HAVE STUCK WITH PROTOCOLIZED. I'LL SAY THIS ON A POPULATION LEVEL. MINDFULNESS TRAINING CAN BE DONE IN GROUPS, PROBABLY THE COST AT LEAST IN THE ST. LOUIS AREA TO UNDERGOING PER INDIVIDUAL TO UNDERGOING A GOOD COURSE OF MBSR WOULD BE A COUPLE, $200, $300 FOR THE WHOLE COURSE. LARGE COST, COMPARED TO EVEN LIKE GENERIC ANTI-DEPRESSANT AND PARTICULARLY COMPARED TO THE ENORMOUS COST OF COGNITIVE DECLINE AND AGING. BUT THAT PUSHBACK SAID, I TOTALLY AGREE WITH YOUR POINT. >> VERY QUICK QUESTION. SO HOW DOES PRAYER CONNECT TO MINDFULNESS? ARE THERE -- I MEAN SOMEBODY'S ENGAGED IN PRAYER, IS THAT CONSIDERED BEING PART OF MINDFULNESS OR ARE THERE ASPECTS THAT THERE'S SOMETHING THAT NEEDS TO BE ADJUSTED TO BE COMPLETELY -- >> IT'S A GREAT QUESTION. IF I COULD BROADEN IT, I'LL NOTE THAT, YOU KNOW, THE ORIGIN OF MINDFULNESS TRAINING IS RELIGION, AND ALL OF THE WORLD'S MAJOR RELIGIONS HAVE A COMPONENT OF MINDFULNESS AND MEDICATION TO THEM. WHAT WE'RE STUDYING IN THIS IS A COMPLETELY SECULARIZED VERSION OF WHAT WAS ORIGINALLY BUDDHIST MINDFULNESS MEDITATION. I AGREE WITH YOU WHOLEHEARTEDLY, THIS IS SOMETHING THAT MAY BE AN ACTIVE MECHANISM IN PRAYER, AND ITS HEALTH BENEFITS. I'LL STOP THERE AND ALLOW THE NEXT SPEAKER TO COME UP. THANK YOU FOR YOUR ATTENTION. [APPLAUSE] >> GOOD MORNING. THANKS FOR HAVING ME HERE. IT'S A GREAT PLEASURE BEING ABLE TO SHARE MY RESEARCH WITH YOU AND MORE IMPORTANTLY TRYING TO INFECT YOU WITH MY ENTHUSIASM FOR BEHAVIORAL ECONOMICS AS A WAY TO THINK ABOUT AND BETTER UNDERSTAND CHRONIC HEALTH BEHAVIORS. AND I WILL TALK A LITTLE BIT ABOUT CONCEPTUALLY TODAY ABOUT HOW WE CAN USE INSIGHT FROM BEHAVIORAL ECONOMIC TO ARE COST INCENTIVE CHRONIC HEALTH BEHAVIOR IN A GIVEN APPLICATION (INDISCERNIBLE). WHY BEHAVIORAL ECONOMIC? I'M SURE A LOT OF YOU HAVE HEARD ABOUT BEHAVIORAL ECONOMICS FIELD, A SHOUT OUT IN HIS INTRODUCTION, BEHAVIORAL ECONOMICS IS INTERVENTION OF ECONOMICS, PSYCHOLOGY, SOCIOLOGY, NEUROSCIENCE, AND RATHER THAN TRY TO SAY WHAT IT IS, LET ME CONTRAST WITH THE TRADITIONAL APPROACH THAT I WOULD SAY HAS INFLUENCED POLICY MAKING, TRADITIONALLY ECONOMICS HAS DISPROPORTION IMPACT ON POLICY MAKING. TRADITIONAL ECONOMICS WE'RE DEALING WITH A RATIONAL ACTOR WHO NEVER MAKES MISTAKES, ALWAYS DOES THE RIGHT THING. FROM POLICY PERSPECTIVE THAT'S A SCARY THING, THERE'S NOT MUCH YOU CAN DO. BEHAVIOR SUCH AS SMOKING, NOT USING CONDOMS DURING SEX, THERE'S AN INFORMATION GAP, I WOULD ARGUE BY NOW WE KNOW THAT INFORMATION OFTEN IS NOT THE GAP, WE'VE SEEN ALL THESE BILLBOARDS, SMOKING KILLS, HIV IS BAD FOR YOU, AND BOTH EMPIRICALLY MORE STUDIES SHOWS EDUCATION CAN ONLY DO SO MUCH, ALSO WHEN I WORKED IN RURAL AFRICA, IT'S REALLY HARD TO FIND SOMEONE WHO DOES NOT KNOW WHAT HIV IS OR YOU NEED TO TAKE MEDICATION. SECONDLY THE TRADITIONAL PARADIGM IF SOMEONE SHOWS UNHEALTHY BEHAVIOR THAT PERSON MUST HAVE A WEIRD PREFRONTAL PREFERENCE, INJECTING DRUGS, WE HAVE TO GET THE PERSON TO NOT ENGAGE, LEADING TO POLICIES SUCH AS CIGARETTE TAX OR SUGAR TAX OR SODA TAX, THESE SORT OF THINGS. THE FLIP SIDE ON THE INTERVENTION SIDE IS WE'VE SEEN A LOT OF CONTINGENCY MANAGEMENT TYPE OF INTERVENTIONS WHERE PEOPLE RELATIVELY -- OFTEN VERY LARGE AMOUNTS OF MONEY IN THE ORDER OF HUNDREDS OF DOLLARS COME TO THE CLINIC, I'LL GIVE YOU $50, PICK UP AN HIV TEST, I'LL GIVE YOU $100. THEY HAVE SEEN MIXED RESULTS OR LIMITED RESULTS, I WANT TO POINT OUT ONE OF THESE STUDIES WAS EXTREMELY WIDELY PUBLICIZED, THIS IS FROM THE "NEW YORK TIMES" AND THE TITLE IS STUDY THAT PAID PATIENTS TO TAKE HIV DRUG FAILS. AS A BEHAVIOR ECONOMIST, I STARTED WORKING WITH THIS, THE GOOD NEWS IS THERE INCREASING RECOGNITION BEHAVIOR MATTERS AND WE CAN DO THINGS TO INFLUENCE BEHAVIOR. THE NEGATIVE THING, WHAT WORRIES ME, IS THAT THESE SORT OF HIGHLY PUBLICIZED STUDIES MAY MAKE PEOPLE THINK, WELL, INCENTIVES DON'T WORK. CONCLUSION I DRAW IS VERY DIFFERENT. I WOULD ARGUE THAT INCENTIVES DO WORK BUT IT REALLY MATTERS HOW WE STRUCTURE THEM. SO FAR, TESTS THROW IN CASH AT PEOPLE IS PROBABLY NOT THE MOST EFFECTIVE THING WE CAN DO. SO I WOULD ARGUE THAT BEHAVIORAL ECONOMICS IS A REALLY GREAT TOOL TO THINK ABOUT INCENTIVE, BARRIERS TO BEHAVIOR, WHY DO THEY BEHAVIOR THE WAY THEY DO AND HOW CAN WE USE INSIGHTINGS TO CREATE MORE EFFECTIVE AND COST EFFECTIVE INCENTIVES. BEHAVIORAL ECONOMICS, ECONOMICS GOES BEYOND THE RATIONAL MODEL AS PEOPLE ARE NOT ALWAYS MINDFUL, THEY ARE IRRATIONAL. WE ALL STRUGGLE WITH SELF CONTROL. FOR HIV THAT'S PARTICULARLY DAMAGING. AND STARTING POINT, I FIND PEOPLE HAVE THE INFORMATION THEY NEED, THEY KNOW HIV IS A SERIOUS DISEASE. THEY HAVE GOOD INTENTIONS. THEY SAY I WANT TO BE HEALTHY, SEE MY KIDS GRADUATE. BUT SOMEHOW IN THE SHORT TERM THERE'S SOMETHING IN BETWEEN AND FAIL TO FOLLOW LONG-TERM PLAN. SECONDLY FOR THE DESIGN OF INCENTIVE WE FOCUS ALMOST EXCLUSIVELY ON MONEY AND VOUCHERS, THESE SORT OF THINGS SO FAR. CLEARLY THERE'S OTHER THINGS THAT DRIVE BEHAVIOR, SOCIAL STATUS, ACADEMIC RESEARCHERS THERE'S CERTAINTY, WE COME TO THE CONFERENCES, WITHOUT GETTING PAID, BECAUSE WE LIKE HAVING THE EXPOSURE AND PUBLISHING IN FANCY JOURNALS. WE LIKE TO FEEL GOOD ABOUT OURSELVES, WE HAVE A CERTAIN SELF IMAGE, WE WANT TO KEEP UP. THERE'S A LOT OF DRIVERS OF BEHAVIOR I WOULD ARGUE WE HAVEN'T REALLY USED AS ENTRY POINT FOR INCENTIVES YET. THERE'S MENTIONED ALSO, DIFFICULTY UNDERSTANDING PROBABILITIES WHICH HAS IMPLICATIONS FOR STRUCTURING MESSAGES AND INCENTIVES AS I WILL SHOW YOU IN A MOMENT. AND I CAN TELL YOU HOW MANY TIMES IN THE LAST COUPLE OF YEARS I'VE GOTTEN A CALL FROM SOMEONE WITH INCENTIVE-BASED INTERVENTION, VERY MUCH BEFORE THE INTERVENTION STARTS THEY SAY HOW MUCH SHOULD WE PAY? THEN I HAVE TO UNFORTUNATELY SAY IT'S NOT THAT EASY, TAKE A STEP BACK, FROM A BEHAVIORAL ECONOMICS POINT MUCH VIEW THE QUESTION IS NOT HOW MUCH, THE KEY, BUT IT'S REALLY MUCH BROADER QUESTION, HOW DO WE INCENTIVIZE BEHAVIOR? SO I TRY IN THIS TABLE HERE TO CONTRAST ON THE LEFT SIDE HOW TRADITIONALLY INCENTIVES HAVE BEEN STRUCTURED, ON THE RIGHT SIDE DIFFERENT IDEAS HOW THE INCENTIVES MIGHT BE MORE EFFECTIVE AND FOR THOSE WHO CAN'T BE MINDFUL THERE'S THE REFERENCE TO THE SHORT PAPER THIS IS BASED ON. SO TRADITIONAL INCENTIVES, PAY A COUPLE HUNDRED DOLLARS TO QUIT SMOKING, LOSE FIVE POUNDS, WE OVERRIDE WITH RELATIVELY LARGE AMOUNTS, THAT'S WHAT'S IMPORTANT, HOW MUCH DO WE NEED TO PAY TO DO THIS, RIGHT? BEHAVIORAL ECONOMICS TELLS US THIS IS KIND OF A LITTLE BIT OF BACKWARD WAY OF DOING THINGS, MOST PEOPLE ARE MOTIVATED TO DO THINGS, TO REMAIN HEALTHY, INTRINSIC MOTIVATION, LET'S TAG ON AND JUST USE SMALL INCENTIVES TO NUDGE PEOPLE IN THE RIGHT DIRECTION, SO THE BALL IS ALREADY ROLLING, LET'S MOVE IT IN THE RIGHT DIRECTION. IN TERMS OF TYPE OF INCENTIVE ALREADY MENTIONED TYPICALLY IT'S MONEY THAT IS GIVEN, BEHAVIORAL ECONOMICS TELLS US IN-KIND CAN WORK, MANY CAN OFTEN BACKFIRE. FOR SOME BEHAVIORS SUCH AS DONATING BLOOD OR WHEN WE HELP OUR FRIENDS MOVE APARTMENTS, SOCIAL ACTIVITIES, THERE HAVE BEEN STUDIES THAT SHOW IF YOU PAY PEOPLE FOR THESE ACTIVITIES, BLOOD DONATIONS GO DOWN, PEOPLE STOP HELPING FRIENDS BECAUSE THEN IT'S ALL ABOUT THE MONEY. THE SECOND I WANT TO TOUCH ON IN THE LAST TWO HERE IS IT REALLY ALSO MATTERS HOW YOU GIVE OUT INCENTIVES. IT REALLY MATTERS WHETHER YOU FOLD IT INTO A SALARY CHECK, FOR EXAMPLE, WHETHER YOU GIVE IT IN A FIXED AMOUNT OR SORT OF THE LOTTERY, AND ALSO HOW YOU FRAME THE INCENTIVE, PERCEIVED AS GAIN OR LOSS, CAN HAVE HUGE IMPACT. SO THIS ENDS THE CONCEPTUALLY INCENTIVE THAT I'VE TALKED ABOUT, TO GIVE WHAT THIS CAN LOOK LIKE IN PRACTICE I WOULD LIKE TO PRESENT THE RESULTS OF R34 STUDY LAST YEAR FUNDED BY NIMH IN UGANDA. YOU DON'T HAVE TO WRITE ANYTHING DOWN. THIS WAS PUBLISHED IN AIDS THIS YEAR I THINK IN FEBRUARY. THE STARTING POINT WAS THAT WE HAVE AN HIV CLINIC, EXTREMELY RESOURCE POOR SETTING. A LOT OF STIGMA. A LOT OF POVERTY. AND WE TRIED TO TARGET PEOPLE WHO HAD BEEN ON ART FOR TWO YEARS, ADHERENCE PROBLEMS, MOTIVATION IS FADING. WHAT CAN WE DO TO GET PEOPLE BACK ON TRACK TO TAKING MEDICATION? IN UGANDA, PEOPLE REALLY APPRECIATE THE OPPORTUNITY TO WIN SOMETHING, TO HAVE SOME FUNDING, SCRATCH CARDS SOLD EVERYWHERE, EVERY COKE BOTTLE A GAME OF CHANCE WHERE YOU CAN WIN A PRIZE, IPAD OR CAR OR SOMETHING. WHY NOT DO A LOTTERY WHERE PEOPLE DON'T HAVE TO PAY FOR THE TICKETS THEY GET BUT WHERE THEY HAVE TO BUY IT BY SHOWING HEALTHY BEHAVIOR. SO THIS LED TO AN INTERVENTION WHERE WE HAD A SMALL RCT WITH 50 PEOPLE IN EACH ARM, GAVE EVERYBODY ELECTRONIC PILL CAPS, AND TWO TEAM GROUPS, BASICALLY EVERY TIME THE PEOPLE CAME TO THE CLINIC, AVERAGE OF ABOUT EVERY TWO MONTHS OR SIX TIMES A YEAR, THEY HAD A CHANCE OF -- LET ME IF I CAN FIND IT. YEAH, DRAWING ONE OF THESE NUMBERS OUT OF THE BAG. IF THEY SHOWED 90% OR MORE ADHERENCE, AND IF THEY DRAW RED& NUMBERS, 6, THEY COULD WIN ONE OF THESE PRIZES IN THE MIDDLE. SO FAR THE INTERVENTION LOOKS LIKE CONTINGENCY MANAGEMENT BUT MIDDLE PICTURE SHOWS DIFFERENT, THE PRIZE VALUES WERE MINIMAL EVEN BY UGANDA STANDARDS. PRIZES COST AVERAGE OF $2, ON AVERAGE EVERY PERSON WINS A PRICE ONCE A YEAR, SO PRIZE VALUE IS $2 PER PERSON PER YEAR. AND EVEN BY UGANDAN STANDARDS IT'S VERY LOW. FOR EXAMPLE, IT COSTS $4 FOR MOST PEOPLE TO COME TO THE CLINIC, WE GIVE THEM ABOUT $6 OR OR $7, IT'S HARD TO ARGUE YOU'RE CHANGING PRIZES, THIS IS JUST TELLING THEM YOU CAN WIN SOMETHING. AND IN THE LAST PICTURE EVEN FIT OF EVEN IF IT DOESN'T LOOK LIKE, PEOPLE LIKE TO PARTICIPATE. THEY HAVE TO GET UP EARLY, TAKE THE BUS FOR HOURS, WAIT IN LINE FOR HOURS, THE DOCTOR IS OVERWORKED, I'M LOOKING FORWARD TO DRAWING A PRIZE. YOU SAY $2 PER PERSON, PER YEAR, WITH HIGHLY STIGMA STIGMATIZED IS NOT GOING TO TRICK BUT THAT'S NOT THE CASE. IN THIS GRAPH WE SEE CUMULATIVE ADHERENCE OVER NINE MONTHS, FURTHER OUT 80, 90, 100%. BLUE LINE IS CONTROL GROUP. WE SEE THAT'S RELATIVELY FLAT. INTERVENTION GROUPS ARE THE GREEN AND RED LINES. THEY REALLY, IF YOU LOOK AT IT, IT REALLY SEEMS LIKE WE PUSHED THOSE THAT OTHERWISE WOULD HAVE BEEN AROUND 60 OR 70% UP TO 90% ADHERENCE. AND FOR THOSE MATHEMATICALLY MINDED STATISTICALLY SIGNIFICANT NUMBER OF REGRESSIONS WE RAN, BASICALLY WHAT WE MANAGED TO DO IS WE IMPROVED THE NUMBER OF PEOPLE TAKING MEDICATION IN A CLINICALLY MEANINGFUL WAY SO HAVING AT LEAST 90% OF MEDICATION, INCREASED FRACTION FROM ABOUT 40% IN CONTROL GROUP TO 65% IN THE INTERVENTION GROUPS. SO THE OTHER NICE THING IS BECAUSE WE ARE ALL CONCERNED ABOUT THE SUSTAINABILITY, AT LEAST IN ONE OF THESE GROUPS THE INTERVENTION EFFECT LINGERED ON AFTER THE FULL INTERVENTION ENDED AT MONTH 20 AND ANOTHER SIX MONTHS FURTHER ON. THESE ARE PRELIMINARY ANALYSES BECAUSE ONLY LOOKED IN DETAIL AT THE FIRST YEAR, BUT THESE ARE VERY PROMISING RESULTS I WOULD ARGUE FOR A PRIZE OF LESS THAN $2 FOR PERSON TO SEE THIS LARGE INCREASE IN ADHERENCE AND SUSTAINED INCREASE AT THAT. WE THINK THAT INTERVENTION WORKS WELL BECAUSE ON THE ONE HAND WE TARGETED -- I MENTIONED SELF CONTROL ISSUES WHEN WE TRY TO HAVE LONG-TERM BEHAVIORS, TAKING HIV DOESN'T HELP YOU NOW, IT HELPS 10 OR 15 DOWN THE ROAD WITH HIGHER LIFE EXPECTANCY AND QUALITY. GIVING OUT SMALL PRIZEs IS BETTER THAN WAITING 15 YEARS. WE LEVERAGED OPTIMISM, DESPITE TREATMENT PROBLEMS THEY ALL WANTED TO PARTICIPATE AND WERE ALL 100% SURE THEY WOULD WIN. AND LASTLY, I THINK THE REAL IMPOTANT PART HERE WAS THAT WE FRAMED INCENTIVE AS A SMALL THING THAT HELPED, RATHER THAN PAYMENT. WE DIDN'T TELL THEM YOU DO 90% ADHERENCE, YOU GET $50. WE KNOW IT'S HARD FOR YOU, WE THOUGHT ABOUT SOMETHING, WE THINK YOU MIGHT ENJOY, AND HERE'S A LITTLE BASICALLY REWARD, A PRESENT FOR YOU THAT YOU DID WHAT YOU ACTUALLY WANTED TO DO YOURSELF ANYWAY. I WOULD ARGUE THAT WE'RE JUST STARTING TO BETTER UNDERSTAND HOW INCENTIVES WORK, THE TIP OF THE ICEBERG. I WANT TO SHOW YOU A COUPLE OTHER STUDIES I HAVE IN THE FIELD. THE FIRST STUDY IS R01 BASED ON THE STUDY I JUST PRESENTED, HERE THE INTERESTING THING IS THAT WE TEST OUT INCENTIVIZING BEHAVIOR OF ADHERENCE, MORE OR LESS EFFECTIVE THAN INCENTIVIZING THE OUTCOME OF INTEREST. SO SHOULD WE INCENTIVIZE EATING LESS OR LOSING WEIGHT, SMOKING, THERE'S NO LITERATURE. THE SECOND STUDY HERE, SECOND BULLET POINT, CURRENTLY INVESTIGATING WHETHER SETTING A FIXED INCENTIVE, 90% ADHERENCE OR LOSE 5 POUNDS OR SO, IS MORE OR LESS EFFECTIVE THAN SETTING A FLEXIBLE TARGET, SO TAKING STARTING CONDITIONS IN ACCOUNT. PEOPLE IN AFRICA ARE DEMOTIVATED QUICKLY BECAUSE IT'S HARD IF YOU SHOW 30% TO GET TO 90% ADHERENCE. THEN ANOTHER AREA WHERE I TRIED TO WORK ON IS COMBINING THE SMALL NOTCHES WITH MOBILE HEALTH, MOBILE TECHNOLOGIES, BY SMS, PRICES OUT IN A SMALL STUDY IN LOS ANGELES TRYING TO INCREASE HIV TESTING, AND THEN THE LAST STUDY ONE MINUTE ON BECAUSE I'M REAL EXCITED BECAUSE I MENTIONED BEFORE THAT CONTINGENCY MANAGEMENT TYPE OF TRADITIONAL INCENTIVES GIVE OUT LARGE AMOUNTS OF CASH, IN THE STUDY I PRESENTED I GAVE OUT VERY SMALL REWARDS IN-KIND, IN THIS LAST STUDY DOESN'T GIVE OUT PRIZES BUT STILL USES INCENTIVES. WE WORKED WITH YOUTH IN TWO HIV CLINICS IN UGANDA. WHEN YOU WORK WITH YOUTH IT'S IMMEDIATELY CLEAR VERY MUCH INFLUENCED BY WHAT PEERS ARE DOING, WHAT THEY WEAR, HOW THEY TALK, HOW THEY TALK ABOUT HIV CARE. AND OF COURSE YOUTH LIKE TO USE MOBILE TECHNOLOGIES, AND PLAY AROUND WITH CELL PHONES ALL THE TIME. WHAT WE DID IS WE GAVE PILL BOXES THAT SEND US INFORMATION REMOTELY AND IN REAL TIME AND EVERY SUNDAY WE SENT OUT ADHERENCE BACK TO THE INTERVENTION GROUPS. AND THE FIRST GROUP KIND OF TRADITIONAL ADHERENCE FEEDBACK INTERVENTION, IMPLEMENTED USING MOBILE HEALTH, TOLD EVERYONE 70% THIS WEEK, FOR EXAMPLE. THE INTERESTING PROGRESS THE SECOND GROUP, WE WROTE CONGRATULATIONS, YOU'RE AT 70% BUT DID YOU KNOW YOUR FRIENDS ARE 80 OR 85%? PEER PRESSURE. IT LOOKS AT IN PARTICULAR THOSE THAT SHOW 50, 60, OR RELATIVELY LOW ADHERENCE GO UP TO 90% THRESHOLD WE INDICATE IN WEEKLY MESSAGES. I'M EXCITED BECAUSE THIS USES INCENTIVE, CLEARLY AN INCENTIVE BECAUSE PEOPLE WANT TO DO BETTER THAN FRIENDS. WE DID QUALITATIVE DATA, PEOPLE SAID THEY WERE SO ANGRY, I TOOK MY MEDICATION, I WAS BETTER THAN THEM. IT DRIVES PEOPLE'S BEHAVIOR. WE DON'T HAVE TO GIVE OUT PRIZES AND SPEND MONEY. ONCE THIS INTERVENTION IS UP AND RUNNING IT'S COMPLETELY AUTOMATIC, DATA COMES IN AUTOMATIC, WE SEND SMS AUTOMATIC, ENHANCE QUICKLY, SCALABLE AND ALMOST ZERO COST, ZERO RUNNING COST AT LEAST ONE IT'S UP AND RUNNING. TRYING TO CONVINCE YOU IN THE LAST 15 MINUTES BEHAVIORAL ECONOMICS IS REALLY -- HAS GROWN TO THE EXTENT THAT NOW IT'S STARTING TO INFILTRATE DIFFERENT FIELDS. I'M TRYING TO DO THIS WITH HIV. I WOULD ARGUE BEHAVIORAL ECONOMICS PROVIDES MUCH RICHER POLICY TOOL SET MOVING AWAY FROM GIVING OUT INFORMATION OR CHANGING PRIZES OR PENALIZING PEOPLE WITH TAXES TO CHANGE BEHAVIOR. I ARGUE INCENTIVES CAN BE SMALL VALUE, SO THE NUDGES EVERYBODY HEARD OF, AND CAN EVEN BE NON-MONETARY, THE EXAMPLE OF SOCIAL PRESTIGE OR PEER PRESSURE IS ONE INCENTIVE TO DOESN'T RELY ON MONETARY PAYMENTS. THAT'S VERY GOOD NEWS FOR COST EFFECTIVENESS AND SCALEUP. THE QUESTIONS WE HAVE TO THINK ABOUT FOR CHRONIC DISEASES, LONG-TERM DISEASE HOW DO WE DO THESE IN THE LONG TERM AND TREAT PEOPLE, COMBINE WITH DIFFERENT APPROACHES BECAUSE WITH HIV LUCKILY IF A CHILD IS BORN WITH HIV TODAY HAS A RELATIVELY NORMAL LIFESPAN AND CERTAINLY GIVING INCENTIVES FOR 70 YEARS WON'T WORK. WE CLEARLY HAVE TO FIND DIFFERENT INTERVENTIONS. I THANK NIH FOR THE INVITATION, NIMH FOR FUNDING AND PARTICIPANTS AND COLLEAGUES FOR THEIR PARTICIPATION. THANK YOU AND I LOOK FORWARD TO YOUR QUESTIONS. [APPLAUSE] NO QUESTIONS? I THINK THERE'S ONE QUESTION. >> VERY INTERESTING. THANK YOU. I WAS THINKING ABOUT BEING IN THE WORKPLACE, INCENTIVES OFFERED TO EMPLOYEES LIKE AWARDS AND RAISES OR WHATEVER IT MIGHT BE. I'M JUST WONDERING HOW YOU MIGHT APPLY BEHAVIORAL ECONOMICS, THINKING WHEN IT'S PART OF YOUR ACTUAL FORMAL RESPONSIBILITY AS OPPOSED TO SOMETHING ABOUT YOUR HEALTH, OR VOLUNTEERING, SOMETHING FOR SOCIAL GOOD. >> SHOW PRODUCTIVITY THAT'S NOT DIRECTLY BENEFICIAL TO YOU ONLY LIKE HEALTH? FOR YOUR WORK? >> WELL, IT IS FOR YOU PERSONALLY BECAUSE IT'S YOUR WORK. YOU CAN BENEFIT FROM IT. BUT IT'S NOT BECAUSE YOU'RE TRYING TO IMPROVE YOUR HEALTH OR CONTRIBUTE TO SOCIETY OR SOMETHING LIKE THAT >> VERY RELATED STUDIES TO MINE, FOR EXAMPLE, TARGET PROVIDER BEHAVIOR WHICH MAYBE GETS AT THE POINT YOU'RE ASKING ABOUT. WE'VE HEARD ABOUT OPIOID OVERPRESCRIPTION. YOUR SOCIAL STATUS OR SOCIAL RANKING MECHANISMS SEEM TO INDUCE PROVIDERS TO PRESCRIBE FEWER ANTIBIOTICS, FOR EXAMPLE. YOU HAVE A LIST, FOR EXAMPLE, PEOPLE SIGN, I'M A PROVIDER, I WILL NOT OVERPRESCRIBE ANTIBIOTICS, HUNG IN THE WAITING ROOM, EVERY MONTH THE E-MAIL WITH HIGHEST AND LOWEST PRESCRIBED IN THE HOSPITAL, AGAIN NON-MONETARY BUT VERY EFFECTIVE BECAUSE IT GETS AT THE CORE OF WHAT A PROVIDER DOES AND A LOT OF PEOPLE ARE NOT AWARE THEY ARE DOING THIS SORT OF IS SORT OF THING. >> THANK YOU. >> (INAUDIBLE) (OFF MICROPHONE). >> FOR ME THE BEAUTY OF BEHAVIORAL ECONOMICS IS REALLY THAT THESE BASIC SYSTEMATIC DECISION MAKING ERRORS SUCH THAT WE VALUE LONG-TERM HEALTH BUT IN THE SHORT TERM GO FOR THE HAMBURGER, THAT'S UNIVERSAL, I WOULD ARGUE. OR MY EXPERIENCE IN AFRICA, OTHER COUNTRIES, YOU SEE THE SAME THINGS OVER AND OVER AGAIN. EVERYBODY LIKES BEATING THEIR FRIENDS AT GAMES. EVERYBODY WANTS TO BE REWARDED, SEES THEMSELVES AS A GOOD PERSON. I THINK THE UNDERLYING BIASES ARE ALMOST UNIVERSAL I THINK WHERE YOU HAVE TO THINK ABOUT CULTURAL ADAPTATION, WHAT SORT OF PRIZES TO GIVE OUT AND WE DID INFORMATIVE WORK, ASKED WHAT SORT OF PRIZES THEY WANT. OF COURSE THE FIRST ANSWER IS ALWAYS A CAR, A HOUSE, A WASHING MACHINE. BUT IF YOU DIG DEEP ENOUGH YOU GET PRIZES THEY LIKE AND PEOPLE, FOR EXAMPLE, LOVE THE UMBRELLA, COMMON ACTIVITY IN UGANDA IS HAVING TO SIT AT THE MARKET FOR 12, 14 HOURS, SELLING SOMETHING. SO WHEN WHO WON PRIZES THE UMBRELLA, WOMEN WHO SAT AT THE MARKET. UGANDA, IT WASN'T THE MONEY BUT SOMETHING THAT THEY COULD PASS OUT TO THEIR WIFE, THE WIFE WAS HAPPY TO HAVE THAT AND REALLY THAT'S WHAT THE CULTURAL ADAPTATION IS REALLY IMPORTANT. >> HI. THANK YOU FOR THE PRESENTATION. FOR THIS SESSION AND THE LAST ONE, PSYCHOLOGY ONE, THINKING THAT WE ARE TALKING ABOUT POSITIVE, YOU GET SOMETHING BENEFIT, BUT WE STUDY A NEGATIVE THING, THEY WOULD GO OPPOSITE, ADVERSE IMPACT. WE HAVE STUDY OF THE NEGATIVE THINGS LIKE PSYCHOLOGY, IF SOMEBODY TAKING AWAY THEIR PRIVILEGE, THEIR RIGHTS, AND THEN BENEFIT, ADVERSE, SAME ECONOMIC SENSE, YOU DO SOMETHING, TAKE AWAY THEIR BENEFIT, SOCIAL PROGRAM BENEFIT, THEY WILL BE OPEN TO SOLUTION. DO WE HAVE STUDY OF THIS TYPE OF ADVERSE IMPACT, HOW MUCH IS SUFFERING INDIVIDUALS SAY AND ALSO ON THE SOCIETY OF ALL LOSS OR DAMAGES? >> UH-HUH >> DO WE HAVE THIS TYPE OF STUDY OR CAN YOU SAY SOME IMPACT ABOUT IT? >> FIRST OF ALL, THERE'S A LOT WE CAN LEARN FROM PSYCHOLOGY. I DON'T SEE BEHAVIORAL ECONOMICS, REPLACE IT, IT'S REALLY GETTING INSIGHT FROM PSYCHOLOGY. MAYBE ONE IS LOSS AVERSION, PEOPLE PERCEIVE LOSING SOMETHING AS MORE EMOTIONALLY HURTING THEM THAN GAINING SOMETHING. AND HOW WE USE THIS, FOR EXAMPLE, IN THE -- WHEN WE DECIDE INCENTIVES, A VERY GOOD OR EFFECTIVE, FIRST GIVE PEOPLE $20 WHEN YOU WANT THEM TO DO SOMETHING, PUT IT IN AN ENVELOPE, WRITE DOWN WHAT THEY WANT TO DO WITH $20, GO FOR DINNER WITH THEIR GIRLFRIEND OR SOMETHING. AFTER THEY HAVE TESTING, THEY HAVE TO ACHIEVE A CERTAIN POINT, FOR EXAMPLE. AFTERWARDS YOU GIVE THEM THE ENVELOPE BACK AND THAT'S THE TYPICAL REWARD. FOR THOSE WHO DON'T DO IT, IT HURTS THEM A LOT NOT TO GET THE ENVELOPE BECAUSE ARE DECIDE, HAD EMOTION ATTACHED BECAUSE THEY WROTE WHAT THEY WANTED TO DO WITH THAT MONEY. THAT WAY YOU CAN POTENTIALLY INCREASE MOTIVATION FOR ACHIEVING A TASK DRAMATICALLY. IN GENERAL I WOULD LOVE TO HEAR ABOUT YOUR WORK AND HOW TO BETTER INTEGRATE THAT INTO THE INCENTIVES. >> WE HAVE TO MOVE ON. THANK YOU SO MUCH. [APPLAUSE] >> OKAY, GOOD MORNING, EVERYONE. I'M HAPPY TO BE HERE TO SHARE MY RESEARCH, FUNDED BY NIAAA WITH CO-FUNDING FROM NIDA. THESE ARE A COUPLE MAIN PUBLICATIONS FROM THE TRIAL. PLEASE E-MAIL ME IF YOU WANT MORE DETAIL OF THE STUDIES AND WE HAVE A COUPLE OF NEW EXCITING PAPERS FROM THE TRIAL IN THE NEXT COUPLE MONTHS. SO I REALIZE THAT EVERYONE IN THE ROOM HAS NOT DEDICATED 20 OR MORE YEARS OF THEIR LIFE TO PREVENTING ALCOHOL USE AMONG ADOLESCENTS, SO I WANTED TO DO A QUICK SNAPSHOT WHY I'VE DEDICATED SO MUCH OF MY CAREER TO THIS ISSUE. SO IF YOU'RE CONCERNED ABOUT CHILD AND ADOLESCENT HEALTH ALCOHOL IS THE THE TOP OF THE ISSUES, LEADING CAUSE OF ADOLESCENTS, MOTOR VEHICLE CRASH, HOMICIDE AND SUICIDE, ALCOHOL SIGNIFICANTLY CONTRIBUTES TO THOSE. ALCOHOL IMPAIRMENT PUTS YOUNG PEOPLE AT RISK FOR, OF HIGH RISK SEXUAL ACTIVITY, VICTIMIZATION AND AGGRESSION. WE'VE LEARNED A GREAT DEAL ABOUT THE ADOLESCENT BRAIN DEVELOPMENT, AND HOW ALCOHOL AND OTHER DRUG USE REALLY IMPACTS BOTH THE FUNCTION AND STRUCTURE OF THE DEVELOPING BRAIN. AND IMPORTANTLY, WE KNOW THAT IT'S IMPORTANT EVERY YEAR THAT WE CAN DELAY OR PREVENT ALCOHOL USE, THAT IT'S BENEFICIAL. BECAUSE WE SEE INCREASED RISKS FOR ADDICTION AND ALCOHOL-RELATED PROBLEMS, THE EARLIER ONE BEGINS TO DRINK. THIS IS A FIGURE THAT DEPICTS THIS, SO YOU SEE THE AGE OF STARTING TO DRINK, AND THE PERCENT OF ALCOHOL DEPENDENT, YOU SEE QUITE A LINEAR RELATIONSHIP. SO THE GOAL REALLY IS TO DELAY THE ONSET OF DRINKING. AND THIS TRIAL THAT I'LL BE DESCRIBING TODAY IS REALLY IMPORTANT BECAUSE IT'S FOCUSED ON A COUPLE OF DIFFERENT HEALTH DISPARITIES, WE SEE THAT RURAL USE, ESPECIALLY MINORITY -- ETHNIC MINORITY RURAL USE AT INCREASE FOR ALCOHOL AND ALCOHOL-RELATED RISKS. WE ALSO SEE STAGGERING STATISTICS AMONG AMERICAN INDIAN POPULATION, BEING AT HIGH RISK FOR ALCOHOL-RELATED CONSEQUENCES THIS TRIAL TARGETS BOTH RURAL AND AMERICAN INDIAN POPULATIONS. THEY TRIAL WAS A PARTNERSHIP WITH MY COLLEAGUES AND I, UNIVERSITY-BASED PREVENTION SCIENTISTS, WITH THE LEADERSHIP OF THE CHEROKEE NATION, BEHAVIORAL HEALTH, PSYCHOLOGISTS RUNNING CHEROKEE NATION BEHAVIORAL HEALTH SERVICES. WE CAME TOGETHER AND WROTE THE PROPOSAL TOGETHER AND HAVE DESIGN AND RUN THE STUDY TOGETHER, GOAL TO PREVENT AND REDUCE COLLABORATIVE REDUCE ALCOHOL USE AMONG HIGH SCHOOL STUDENTS LIVING IN THE NORTHEASTERN CORNER OF OKLAHOMA, WHICH IS THE CAPITAL OF THE CHEROKEE NATION, NOT A RESERVATION LAND; CHEROKEES WERE FORCIBLY MOVED FROM ORIGINAL HOMELAND IN SOUTHEAST U.S. TO INDIAN TERRITORY, AND COMMUNAL LAND WAS TAKEN AWAY, THIS IS NOT RESERVATION LAND BECAUSE OF THE HISTORY MOVING TRIBES TO THE AREA, THEY REPRESENT HIGH PROPORTION OF POPULATION AND IN THIS REGION PARTICULARLY CHEROKEE, CAPITAL IN TALLEQUA, SECOND LARGEST TRIBE IN THE U.S., DEMOCRATLY ELECTED GOVERNMENT, THEY HAVE CAPITAL IN TALLEQUA AND JURISDICTION 14 COUNTY REGION, NORTHEASTER OKLAHOMA. 60% LIVE IN THIS AREA. SO WHAT WE DID WAS -- THAT WAS THE REGION WE WERE INTERESTED IN WITHIN THE JURISDICTIONAL SERVICE AREA OF THE CHEROKEE NATION. WE HAD A SELECTION CRITERIA OF COMMUNITIES, AND THEN FROM THE COMMUNITIES THAT FIT THOSE CRITERIA WE SELECTED THE HIGHEST RISK AND DID RANDOM ASSIGNMENT INTO STUDY CONDITION. WE DID A FACTORIAL DESIGN, IMPLEMENT AND COMPARED TWO INTERVENTION STRATEGIES AND COMBINATION OF THE TWO, FACTORIAL DESIGN. BECAUSE OF THE CONSTRAINTS OF BUDGETS, WE HAD -- WE WERE ONLY ABLE TO ALLOCATE ONE TO TWO COMMUNITIES IN EACH STUDY CONDITION, SO TO INCREASE CAUSAL INFERENCE WE COMBINED THIS WITH INTENSIVE LONGITUDINAL DESIGN, AND ALSO HAVE MULTIPLE OUTCOME MEASURES. THIS IS A SIMPLIFIED VERSION OF CONCEPTUAL MODEL. WE HAVE THE TWO INTERVENTIONS, ONE AT THE COMMUNITY LEVEL, ONE AT THE INDIVIDUAL LEVEL. SO A COMMUNITY ENVIRONMENTAL CHANGE INTERVENTION THAT WAS TARGETED AT REDUCING ACCESS TO ALCOHOL, THE USE PERCEPTION OF ENFORCEMENT OF UNDERAGE DRINKING LAWS, AND DRINKING NORMS, SO INTERVENTION WAS TARGETING THESE PROXIMAL OUTCOMES, HYPOTHESIZED TO LEAD TO REDUCTION OF ALCOHOL USE AND ALCOHOL-RELATED CONSEQUENCES. SECOND INTERVENTION WAS AT THE INDIVIDUAL LEVEL, A UNIVERSALLY IMPLEMENTED SCREENING AND BRIEF INTERVENTION WHICH WAS TARGETING ALCOHOL COGNITION, SOCIAL SUPPORT AND DRINKING NORMS. SO THIS IS OUR INDIVIDUAL LEVEL INTERVENTION WHICH WE CALLED CONNECT. THE UNIQUENESS, SCIENCE-BASED APPROACH THAT WE WERE TAKING TO THE SCHOOLS, SO OFTENTIMES SCREENING, INTERVENTIONS ARE IMPLEMENTED WITHIN CLINIC SETTINGS, SO WE WERE TAKING IT TO WHERE THE KIDS ARE, IN THESE RURAL AREAS WITHIN THE SCHOOLS, AND WE ALSO IMPLEMENTED IT UNIVERSALLY, NOT TO STIGMATIZE ANY RACIAL OR ETHNIC GROUP, OR EVEN THE DRINKERS. SO IT WAS IMPLEMENTED EVEN FOR THE YOUNG PEOPLE WHO WERE NOT DRINKING AND WAS REINFORCING NON-DRINKING NORM. SO I MENTIONED THE GOALS OF THIS UNIVERSALLY IMPLEMENTED SCREENING, BRIEF INTERVENTION WITHIN THE SCHOOLS, AND HOW WE DID THAT WAS THAT WE PARTNERED WITH THE OKLAHOMA DEPARTMENT OF HUMAN SERVICES, HAD A PROGRAM AT THE THE TIME WHERE IF A SCHOOL WAS ABLE TO COVER 50% OF A SCHOOL-BASED SOCIAL WORKER, THE STATE WOULD PAY FOR THE OTHER HALF. SO WE USED THE GRANT FUNDING TO SUPPORT THE SCHOOL'S PORTION AND PUT A FULL-TIME SOCIAL WORKERS INTO THESE SCHOOLS. 50% OF THE TIME WAS DEDICATED TO THE INTERVENTION, THE OTHER 50% OF THE TIME DEDICATED TO THEIR USUAL SCHOOL-BASED SOCIAL WORK ACTIVITIES, CONNECTING YOUNG PEOPLE TO COMMUNITY RESOURCES. THE COACHES WERE HIRED AND TRAINED INTENSIVELY IN CONDUCTING BRIEF INTERVENTIONS, USING MOTIVATIONAL INTERVIEWING TECHNIQUES, WHICH WE FELT WERE THE MOST APPROPRIATE FOR THIS MULTI-RACIAL STUDENT BODY. WE SUPPLEMENTED THIS SCREENING AND BRIEF INTERVENTION WITHIN THE SCHOOLS WITH A MEDIA CAMPAIGN TO REINFORCE THE MESSAGE OF IMPORTANCE OF STAYING CONNECTED WITH YOUNG PEOPLE, COMMUNICATING WITH YOUNG PEOPLE. SO THE MOTIVATIONAL INTERVIEWING WAS A REALLY CRITICAL PIECE OF SCREENING AND BRIEF INTERVENTION, THIS IS REALLY A CLIENT-CENTERED IN THIS CASE YOUTH-CENTERED APPROACH, WHERE WE FELT THAT IT WAS VERY WELL SUITED, NOT ONLY FOR TEENAGERS, BUT AMERICAN INDIAN TEENAGERS IN PARTICULAR. IT'S REALLY NON-CONFRONTATIONAL STYLE, A COLLABORATIVE NATURE, EMPHASIS ON RESPECT AND EMPOWERMENT AND ENCOURAGING THE YOUNG PEOPLE LIKE TAKING THE YOUNG PEOPLE THROUGH A PROCESS WHERE THEY UNDERSTAND ALCOHOL DOES NOT COINCIDE WITH THEIR LIFE GOALS. THIS IS JUST AN EXAMPLE OF THE MEDIA WE SENT POSTCARDS HOME TO FAMILY MEMBERS, AND THEN HAD POSTERS AROUND THE COMMUNITY JUST WITH SUPPLEMENTING IN-SCHOOL PROGRAM WITH MESSAGING OF STAYING CONNECTED AND WITH YOUNG PEOPLE. SO WE WERE SUCCESSFUL IN UNIVERSAL IMPLEMENTATION, CONNECT COACHES SAW 73 TO 100% OF THE ELIGIBLE STUDENTS. ONCE A SEMESTER OVER THE 2 1/2-YEAR INTERVENTION PERIOD. AND WE ALSO IMPLEMENTED THE MEDIA CAMPAIGN. THE SECOND INTERVENTION WAS DIFFERENT, COMMUNITY LEVEL INTERVENTION TARGETING REDUCTION OF ACCESS TO ALCOHOL FOR THE YOUNG PEOPLE. STRATEGIES WE USE IN THIS INTERVENTION, WE HIRED SOMEONE FROM THE LOCAL COMMUNITIES AND TRAINED THEM IN DIRECTION ACTION COMMUNITY ORGANIZING TECHNIQUES, AND PROVIDED THEM WITH EVIDENCE-BASED GUIDES, STRATEGIES FROM PREVIOUS SCIENCE ARE EFFECTIVE IN REDUCING YOUNG PEOPLE'S ACCESS TO ALCOHOL, REDUCING ALCOHOL USE, THAT WE'RE TARGETING COMMERCIAL SOURCES, SOCIAL SOURCES, OR ENFORCEMENT. THE COMMUNITY ORGANIZING APPROACH WAS ALSO A STRATEGY THAT WE FELT THAT WAS VERY APPROPRIATE FOR THESE COMMUNITIES THAT ARE MIXED NATIVE AMERICAN AND WHITE, IT'S A STRATEGY THAT'S REALLY COMMUNITY DRIVEN, THERE'S A LEADERSHIP DEVELOPMENT AMONG COMMUNITY MEMBERS, AND THIS REALLY ENGAGING AND EMPOWERING LOCAL CITIZENS TO TAKE ACTION IN THEIR COMMUNITIES. THESE ARE EXAMPLES OF SOME OF THE -- WHAT WAS IMPLEMENTED IN THE -- BY THE COMMUNITY ACTION TEAMS, SO LOTS OF MEDIA EFFORTS, ESPECIALLY AROUND SOCIAL MEDIA, TO REINFORCE THE ACTIONS THAT THEY WERE TAKING, GOOD PARTNERSHIPS WITH LAW ENFORCEMENT, BETWEEN THE COMMUNITIES AND INITIATED FROM THE ACTION TEAMS. SOME OF THE COMMUNITIES ACTUALLY PASSED ORDINANCES TO INCREASE -- TO INCREASE ENFORCEMENT OF SOME OF THE EXISTING LAWS, AND THEN THERE WERE TRAINING OF OUTLETS THAT SELL ALCOHOL. SO, THE MAIN OUTCOMES WERE SELF REPORTED ALCOHOL USE AMONG THE YOUNG PEOPLE AND WE MEASURED ALCOHOL USE USING STANDARDIZED ITEMS FROM THE YOUTH BEHAVIOR SURREY, MEASURING IN THE PAST MONTH, HEAVY USE IN THE PAST MONTH, FIVE OR MORE DRINKS IN A ROW. WE HAVE MEASURES OF ALCOHOL-RELATED CONSEQUENCE AND OTHER DRUG USE. WITH THE INTENSIVE LONGITUDINAL DESIGN WE CONDUCTED 12 SURVEYS, SO 4 A YEAR, ACROSS 3 YEARS. WE FOLLOWED A COHORT OF 9th AND 10th GREAT STUDENTS OVER 3 YEARS. THIS IS WHAT OUR -- THE POPULATION, OUR STUDY POPULATION LOOKED LIKE, OVER 1600 HIGH SCHOOL STUDENTS FOLLOWED OVER THOSE 3 YEARS. EQUAL GENDER SPLIT. AVERAGE AGE AT BASELINE 15 FOLLOWED OVER THREE YEARS. PRETTY EQUALLY SPLIT NATIVE AMERICAN AND WHITE. THESE COMMUNITIES OF COURSE HAVE BEEN LIVING TOGETHER FOR GENERATIONS, SO WE HAVE THIS REALLY, YOU KNOW, INTERESTING SPLIT. OF THE 46% OF HIGH SCHOOL STUDENTS WHO REPORTED TO BE NATIVE AMERICAN, HALF OF THEM REPORTED BEING NATIVE AMERICAN ONLY, THE OTHER HALF REPORTED BEING NATIVE AMERICAN AND OTHER, MOSTLY WHITE. AND AS YOU CAN SEE, THE MAJORITY OF THE NATIVE AMERICAN USE IN THIS REGION WERE CHEROKEE. SO, THIS IS A GRAPH OF THE OUTCOMES ON PAST MONTH HEAVY USE. THIS IS NUMBER OF STUDENTS REPORTING 5 OR MORE DRINKS IN A ROW IN THE PAST MONTH. THE TOP LINE IS OUR CONTROL COMMUNITIES. AND THIS IS OVER TIME. SO THIS IS THE 9th AND 10th GREATEST, 10th AND 11th, AND 11th AND 12th GRADERS. AND WE HAD TWO BASELINE SURVEYS. AND THEN THE FOLLOW-UP SURVEYS. SO FIRST, YOU CAN SEE IF YOU LOOK AT THE CONTROL COMMUNITY, THE NORMATIVE TRAJECTORY IN THE U.S. FOR INCREASING ALCOHOL USE IN THE DEVELOPMENTAL PHASE. AND THEN WE HAVE OUR THREE INTERVENTION CONDITIONS, AND YOU SEE THERE WAS A SIGNIFICANT EFFECT FOR ALL THREE OF THE INTERVENTION CONDITIONS, SO THIS DARK LINE IS THE COMBINED CONDITION, AND THEN WE HAD THE CONNECT IS THE DOTTED LINE, OR DASHED LINE I SHOULD SAY, AND THEN THE CMCA IS THIS DOTTED LINE. SO YOU SEE WE -- YOU KNOW, ALL THE TRENDS WERE SIGNIFICANT FOR ALL THREE. ALL THREE OF THE INTERVENTIONS WERE SIGNIFICANTLY LOWER THAN THE CONTROL CONDITION. YOU SEE, YOU KNOW, THE EFFECT VARIES OVER THE PERIOD WHERE WE HAVE VERY LARGE INTERVENTION EFFECTS DURING THE SECOND YEAR THAT SEEM TO DISSIPATE, ALTHOUGH THERE SEEMS TO HAVE BEEN SOME DIFFUSION. WE DID ASK THE CONTROL COMMUNITIES WHAT WAS -- WHAT PREVENTION ACTIVITIES WERE GOING ON IN SCHOOLS AND COMMUNITIES AND THERE WERE REPORTS OF SOME PREVENTION ACTIVITIES SIMILAR TO WHAT WE WERE IMPLEMENTING GOING ON. WE ALSO -- I MEAN, WE ALSO KNOW THIS IS THE CHALLENGING TIME OF YEAR WITH PROM AND GRADUATION. THIS IS A REALLY SIMILAR PATTERN AND I'M NOT SHOWING ALL THREE OF THE MAIN OUTCOMES WHICH IS PAST MONTH ALCOHOL USE, THIS IS ONE IS HEAVY USE, AND THEN ALCOHOL-RELATED CONSEQUENCES BECAUSE THEY ALL LOOK VERY SIMILAR TO THIS. THESE REDUCTIONS REPRESENT ABOUT 15 TO 25% REDUCTIONS IN ALCOHOL USE AMONG INTERVENTION CONDITIONS. SO, THIS IS THE EFFECT OF THE COMMUNITY INTERVENTION, REPRESENTED ABOUT 25% REDUCTION IN BOTH 30-DAY AND HEAVY USE AS I JUST SHOWED. WE ALSO JUST RECENTLY LOOKED AT OUR OTHER DRUG USE ITEMS, AND WE ARE SEEING THAT WE HAD WHAT WE CALL SPILLOVER EFFECTS, WHICH MAKES CONCEPTUAL SENSE, A LOT OF DRUG USE BEHAVIORS CO-VARY AND HAPPEN AT THE SAME TIME. SO FOR BOTH THE CMCA AND THE CONNECT INTERVENTION, WE WERE SEEING SIGNIFICANT REDUCTIONS IN OTHER DRUG USE, CHEWING TOBACCO, MARIJUANA USE AND PRESCRIPTION DRUG MISUSE. WE ALSO MEASURED -- THOSE WERE THE MAIN OUTCOME MEASURES TARGETED, AND WE ALSO MEASURED INTERMEDIATE OUTCOMES. I WANTED TO SHARE ONE OF THE OBJECTIVE MEASURES WHERE WE ACTUALLY ASSESSED ABILITY OF YOUNG PEOPLE TO PURCHASE ALCOHOL WITHOUT USING AN AGE IDENTIFICATION. AND THIS IS THE GRAPH OF THE OUTCOMES FROM THAT. SO THE DARK LINE IS THE CONTROL COMMUNITIES. WE ACTUALLY ASSESS THIS MONTHLY SO THIS IS REALLY INTENSIVE LONGITUDINAL. THIS IS THE ONSET OF THE INTERVENTION PERIOD. AND THEN YOU SEE THE REDUCTION. WE HAD A REDUCTION IN THE ABILITY OF YOUNG PEOPLE TO PURCHASE ALCOHOL WHICH WAS ONE OF OUR KEY INTERMEDIATE TARGETS OF THE INTERVENTION. SO, WE DEMONSTRATED A SUCCESS IN REDUCING ALCOHOL USE WITH THE BOTH INTERVENTION STRATEGIES. WE ARE PROUD OF THE TRUE TRIBAL COMMUNITY AND UNIVERSITY COLLABORATION THAT WAS EFFECTIVE IN IMPLEMENTING THIS COMPLEX COMMUNITY RANDOMZED INTERVENTION TRIAL. AND WE ARE IN THE PROCESS OF DISSEMINATION, CMCA HAS BEEN REVIEWED AND IS LISTED AS A PROMISING PROGRAM ON THE NATIONAL REGISTRY OF EVIDENCE-BASED PROGRAMS AND PRACTICES. AND THEY ARE CURRENTLY REVIEWING THE CONNECT INTERVENTION. WE ALSO THANKS TO DR. ROSS HANGSON INVITES US EACH YEAR TO PRESENT TO CADCO MEETINGS, AND CMCS BEING INTERVENTIONED THROUGH YOUTH LEADERSHIP INSTITUTES WHICH PROVIDES TRAINING ACROSS THE COUNTRY AND PLEASE E-MAIL IF YOU WOULD LIKE COPIES OF ANY OF THE PAPERS. THANK YOU. [APPLAUSE] QUESTIONS? ONE QUESTION? ALL RIGHT. SURE. >> (INAUDIBLE) >> OKAY, GOOD. THANK YOU. >> THANK YOU SO MUCH, DR. KOMRO. TO YOU, DISTINGUISHED SPEAKERS, WELCOME VISITORS, COLLEAGUES, I'M BILL ELWOOD FROM OBSSR, ON BEHALF OF ALL OF US WE'RE GLAD YOU'RE HERE. WE'RE COMING UP TO THE BREAK. YOU CAN SEE THE LOCATIONS OF THE TOWN HALLS. IF YOU ARE -- THE TWO TOWN HALLS, IF YOU WANT TO KNOW WHERE YOU'RE SUPPOSED TO GO, LOOK AT YOUR NAME TAG. IF YOU HAVE A DOT, YOU WILL BE IN THE OBSSR SERVING THE RESEARCH COMMUNITY. THAT LOCATION IS OUTSIDE THE DOORS DOWN THESE TWO HALLWAYS, TOWARD THE BACK. NO? >> GNAWED GNAWED >> (INAUDIBLE). >> OH, THANK YOU. IF YOU HAVE A DOT, EXCEPT ME, YOU'RE IN BALCONY B. THAT'S UP THE TWO STAIRCASES, DIRECTLY BEHIND YOU IN THE MIDDLE OF THAT BALCONY. UNLESS-- I'M THE ONLY ONE WITH THE DOT WHO IS GOING DOWNSTAIRS IN ROOM F. REGARDLESS OF WHETHER YOU ARE DOT OR DOTLESS, RESTROOMS IF YOU'VE NEVER BEEN TO ON NATCHER ON THESE TWO CORRIDORS, MEN'S AND LADIES ROOMS. UPSTAIRS TO THE LEFT ACROSS THE BIG HALL WITH TERRAZZO FLOORS IS CONVENIENCE STORY AROUND CAFETERIA, IF YOU'D LIKE A REFRESHMENT FOR YOUR 15-MINUTE BREAK. 10:45, FIND YOURSELF WITH ME, IF YOU DON'T HAVE A DOT, IN ROOM F. OR ALL THE DOTTED OTHER PEOPLE WILL BE UPSTAIRS IN BALCONY B. SEE YOU THERE. THANK YOU. [APPLAUSE] WELCOME BACK FROM LUNCH AND FROM WHAT I HEAR WERE VERY USEFUL TOWN HALL MEETINGS WITH GREAT FEEDBACK FOR OUR STAFF ABOUT THINGS WE CAN DO MOVING FORWARD. I HAD THE OPPORTUNITY NOW TO INTRODUCE TO YOU ELISEO PEREZ-STABLE, DIRECTOR OF THE NATIONAL INSTITUTE OF MINORITY HEALTH AND HEALTH DISPARITIES. THIS IS A FIRST YEAR WE HAVE ADDED A DIRECTOR OF PERSPECTIVE TO OUR RESEARCH FESTIVAL AND I THINK IT WILL BE ONE OF OUR ANNUAL TRADITIONS MOVING FORWARD TO HAVE ONE OF THE NIH DIRECTORS TALK TO US ABOUT THE VISION FOR THEIR PARTICULAR INSTITUTE AND SOME OF THE BEHAVIORAL AND SOCIAL SCIENCE RESEARCH THEY PRIORITIZE THERE. SO PRIOR TO COMING TO NIMHD DR. PEREZ-STABLE WAS PROFESSOR OF MEDICINE AT UCSF. HE LED THE CENTER OF AGING AND DIVERSE COMMUNITIES AND SERVED ON NIA ADVISE SRI COUNCIL SO MANY PEOPLE AT NIA KNOW HIM WELL. GIVEN MY RESEARCH BACKGROUND I BEST KNOW HIS 30 YEARS OF RESEARCH IN TOBACCO CESSATION AND TOBACCO CONTROL IN THE LATINO COMMUNITIES. SINCE TAKING THE HELM AT NICHD HE'S TAKEN THAT VISION AND DEVELOPING A STRATEGIC PLAN. JOIN ME IN WELCOMING THIS YEAR'S DIRECTOR'S PERSPECTIVE PRESENTER, DR. ELISEO PEREZ-STABLE. [APPLAUSE] >> THANK YOU VERY MUCH, BILL. I LOOK FORWARD TO THIS TALK. I ANTICIPATE IT WILL EXACTLY WHAT WAS ASKED OF ME AND WHAT WOULD I DO AND AS OPPOSED TO SORT OF JUST PULL OUT SOMETHING FROM THE CAN. HOPEFULLY WE'LL HAVE GOOD CONVERSATION. I WANT TO START WITH DEFINING A LITTLE BIT OF OUR PERSPECTIVE FROM NIMHD AND CRITICAL PILLARS OF RESEARCH, PRESENT OUR RESEARCH FRAMEWORK ON OUR WEBSITE, SHOW EXAMPLE OF NIMHD RESEARCH IN THESE TOPICS, THEN FINISH WITH EMPHASIS OWN PATIENT CLINICIAN COMMUNICATION, DEEPER DIVE IN THOSE CONSTRUCTS AROUND DISCRIMINATION RACISM AND A LITTLE BIT ON WORK WE DID IN LIMITING THIS PROFICIENCY AND SOME SPECULATION ON FUTURE DIRECTION. MINORITY HEALTH IN OUR PERSPECTIVE IS EVERYTHING THAT HAS DO WITH MINORITY GROUPS IN THE US. AS DEFINED BY THE OFFICE OF MANAGEMENT AND BUDGET. WHETHER OUTCOMES ARE GOOD OR NOT GOOD SO DOESN'T HAVE TO BE A DISPARITY. WE'RE INTERESTED IN MECHANISMS AND OUTCOMES AND WELL BEING, EVERYTHING RELATED TO THE MAJOR -- MINORITY GROUPS IN THE US. WE PUT OUT THE IDEA THAT ALL RACIAL ETHNIC MINORITY GROUPS HAVE A SOCIAL DISADVANTAGE BUILT ON THE BEING SUBJECT TO DISCRIMINATION. HISTORICALLY OR CURRENTLY. AND DISPARITY, SLAVERY OBVIOUSLY IS VERY UNIQUE LEGACY AS WHAT THE AMERICAN INDIAN POPULATION WENT THROUGH. ALL MINORITY GROUPS HAVE TO SOME EXTENT BEEN VICTIMS OF DISCRIMINATION. WE ALSO THE INSTITUTE ON HEALTH DISPARITIES AND THOSE POPULATIONS INCLUDE NOT JUST MINORITY GROUPS BUT ALSO POOR PEOPLE SO LESS PRIVILEGE SOCIO ECONOMIC STATUS, ANYONE UNDERSERVED RURAL RESIDENTS, THIS IS MANDATED VERY STRATEGIC AT THIS TIME AND THEN LAST YEAR WE DECLARED SEXUAL GENDER MINORITY AS A DISPARITY POPULATION. WE GOT THE -- I GOT THE CREDIT AS A DIRECTOR OF N ISHMHD THOUGH THE WORK HAD BEEN DONE BY OTHERS PRIMARILY LARRY TABAK FROM OFFICE OF DIRECTOR AND HHS AGREED SO IT IS ONE OF OUR DISPARITY POPULATIONS. IN THESE POPULATIONS WHEN OUTCOME IS WORSE, THAT'S HEALTH DISPARITY. IF A WHITE MAN HAS MORE HEART ATTACK, IT'S NOT A HEALTH DISPARITY, IT'S DIFFERENCE. SO TO CLARIFY THAT FOR MAYBE FOR ALL OF YOU SORT OF WELL KNOWN BUT TO MAKE SURE WE'RE ON THE SAME PAGE N. OUR INSTITUTES PERSPECTIVE, ALL SCIENCE THAT WE LOOK AT IS THROUGH THE LENS OF RACE ETHNICITY AND SOCIO ECONOMIC STATUS. THAT IS WHAT WE BRING TO TABLE. SO I ASKED BEHAVIORAL SCIENTIST, THAT'S SOMETHING I THINK ALL OF YOU SHOULD AT LEAST HAVE ON YOUR CHECKLIST IF NOT CENTRAL. THIS IS OUR FRAMEWORK THAT WE CREATED, BUILT ON STUFF THAT I DID WITH CARL HILL, MARIE BERNARD AND NORMAN CAP PLAN AND OUR SCIENCE TOOK IT TO A MORE SOPHISTICATED LEVEL. YOU CAN GRASP FROM IT INCORPORATES ALL ASPECTS OF BEHAVIORAL SOCIAL SCIENCE RELATED TO BOTH INDIVIDUALS, INTERPERSONAL, COMMUNITY AND SOCIETAL LEVELS OF INFLUENCE, THE BIOLOGY, BUILT ENVIRONMENT AND SOCIAL CULTURAL ENVIRONMENT RELATED TO HOW PEOPLE INTERACT. I THINK IF THIS IS ON OUR WEBSITE, WE'RE -- WE PLAN TO CONTINUE TO TWEAK IT AS NEEDED BUT CERTAINLY IT IS A GUIDE FOR US, NOT MEANT TO BE COMPREHENSIVE NOR CAUSAL, WE'RE NOT SHOWING ARROWS HERE, JUST REALLY A FRAMEWORK, NOT A CONCEPTUAL MODEL IN THAT REGARDS. LET ME SHARE SOME RESEARCH WE HAVE FUNDED THAT I THINK IS IMPORTANT IN THE BEHAVIORAL SOCIAL SCIENCE WORLD SO THIS IS A STUDY THAT ELSIE DID AND MATT GILMAN WAS THE SENIOR AUTHOR ON IT. THE CORED STUDY LOOKING AT OBESITY RISK FACTORS DURING PREGNANCY INFANCY AND EARLY CHILDHOOD. 1100 MOTHER CHILD PAIRS, MOSTLY BLACK AND LATINA, INFANCY RISK FACTOR, INTRODUCTION OF SOLID FOODS BEFORE FOUR MONTHS AND EARLY CHILDHOOD RISK FACTORS HAVING TV IN YOUR ROOM AT AGE 4. LARGELY EXPLAINED OBESITY DISPARITIES AT SEVEN SO OTHER THINGS PEOPLE ARE TALKING ABOUT, BYE-BYE IN BED -- BABY IN BED OR BOTTLE FEEDING UNTIL WHAT AGE, ALL THESE DIFFERENT THINGS THAT PEOPLE POSTULATED DID NOT PAN OUT IN THIS PERSPECTIVE COHORT STUDY. CAUSAL INFERENCE IS CAUTIOUS BUT CERTAINLY CAN BE DERIVED. FROM PROVEN SUBSEQUENTLY. AND PREGNANCY RISK FACTORS SIGNIFICANT WERE GESTATIONAL DIABETES AND MATERNAL DEPRESSION SO NOT WEIGHT GAIN OR WEIGHT RETAINED WHICH HAD BEEN ALSO CONSIDERED POPULAR OR AGE OF PREGNANCY OR NUMBER. THIS IS LOOKING AT OBESITY AGE 7 SO PRESUMABLY AT CHILDHOOD AGE 7 YOU HAVE MORE TIME TO HAVE SORTED THINGS THROUGH SO I THINK IT'S IMPORTANT OBSERVATIONAL STUDY. THIS IS A MORE RECENT PAPER FROM IMMUNITY ACADEMIC PARTNERSHIP, AN R-24 GRANT, OTHER WAS, RO1, CLUSTER RANDOMIZE TRIAL IN MIDDLE SCHOOLS IN LOS ANGELES LOOKING AT LOW SES MINORITY PUBLIC SCHOOLS. AND IT WAS A MULTI-LEVEL INTERVENTION LOOKING AT BOTH THE STRUCTURAL INTERVENTION, SCHOOL WIDE ACCESS TO CHILLED WATER, SEEMS PRETTY SIMPLE BUT THAT WE USED TO HAVE WATER FOUND TEARS IN SCHOOL, THOSE WENT AWAY IN CALIFORNIA AT LEAST. HEALTHY FOOD OPTIONS IN THE CAFETERIA AND BEHAVIORAL THINGS ENCOURAGING KIDS TO EAT THESE, EDUCATION, PEER LEVEL EDUCATION, IN TWO YEARS NO CHANGE IN BMI BY SCHOOL ASSIGNMENT SO NEGATIVE TRIAL BY INTENT TO TREAT. HOWEVER, IF ONE DOES SUBGROUP ANALYSIS WHICH IS ALWAYS DONE CAUTIOUSLY, THE OBESE STUDENTS AT BASELINE IN THE INTERVENTION SCHOOLS HAVE BMI REDUCTION AND LOST UP TO NINE POUNDS. MORE THAN EXPECTED. AND I THINK INVESTIGATORS CONCLUDED THAT THE STRUCTURAL CHANGE OF ACCESS TO CHILLED WATER WAS THE PREDOMINANT INTERVENTION. SO INTERESTING THAT THE BEHAVIORAL COMPONENTS WE TRY TO TEACH WERE A, WHAT, MAYBE IT WASN'T POWERED ENOUGH OR THEY GET DILUTED BUT A STRUCTURAL CHANGE LED TO BEHAVIORAL CHANGE. THIS IS A LESSON I HAVE LEARNED OVER THE YEARS. THIS CAME OUT OUR INTRAMURAL PROGRAM, CALVIN TROY AND OTHER LOOKING AT DIRECT MAIL MARKETING TOBACCO USE BEHAVIOR, ANALYSIS OF PAP, A VERY LAUNCHER CORE STUDY -- LARGE CORE STUDY FUNDED BY -- THROUGH TOBACCO LEGISLATION AND I THINK IT'S FDA/NIH/NIDA SUPPORT. NIDA MANAGES IT SO LOOK WHETHER DIRECT MAIL MARKETING AFFECTED SMOKING BEHAVIORS IN INDIVIDUALS OF LESS EDUCATION AND INCOME LOW SES REGARDLESS OF SMOKING STATUS MORE LIKELY WITH MORE EDUCATION TO BE EXPOSED TO MARKETING OR THAT MEANS WE'RE CALLING OR REMEMBERING THEY WERE EXPOSE. EXPOSURE WAS ASSOCIATED WITH PROGRESSION OF SMOKING AMONG NON-SMOKERS AND DIFFICULTY IN SMOKING CESSATION AMONG SMOKERS. SO IS THERE SELF-SELECTION, PEOPLE LIKELY MORE LIKELY TO SMOKE FOR OTHER REASONS WE'RE NOT MEASURING, REMEMBER THAT THEY GOT THE MARKETING OR NOT, WE DON'T KNOW BUT AGAIN, THE CAUSAL INFERENCE HERE BASED ON OTHER LITERATURE HOW TOBACCO INDUSTRY MARKETED AGGRESSIVE WILL I TO POPULATION AND ASSOCIATED WITH TOBACCO USE AND SUBSEQUENTLY DECREASE IN TOBACCO USE AS MARKETING HAS BEEN RESTRICTED OR MAYBE LEGAL. THE UNKNOWN JUNGLE IN THIS WORLD IS WHAT'S GOING ON IN THE INTERNET OR SOCIAL MEDIA. THIS DOES NOT INCLUDE THAT. AND THERE'S NO REGULATION IN THOSE AREAS. THIS IS ANOTHER STUDY THAT'S MORE BASED IN A CLINICAL SETTING, AGAIN FUNDED BY NIMHD, EXTRAMURAL. AND IT WAS HIV INFORMATION EXCHANGE IN CLINICAL SETTING. PATIENTS IN HIV NOWADAYS, AS YOU ARE AWARE, BEHAVIORAL COMPONENT TAKE YOUR MEDICINE, SO THAT YOU SUPPRESS THE VIRUS. AND IF YOU DO THAT YOU CAN LIVE WITH CHRONIC DISEASE WHICH IS A GOOD THING FOR PATIENTS WHO INFECTED WITH HIV. WE KNOW MINORITIES ARE LESS LIKELY TO TAKE ANTIRETROVIRAL THERAPY AND BE VIRALLY SUPPRESSED IN THIS STUDY OVER 1100 PATIENTS IN SOUTHERN CALIFORNIA FOLLOWED OVER THREE YEARS AND THE IMPACT OR THE AFFECT OF LABORATORY HEALTH INFORMATION EXCHANGE. THE SIGNIFICANT BLACK WHITE DISPARITIES IN USE OF ANTIRETROVIRAL THERAPY AND VIRAL SUPPRESSION EXISTED BASELINE AND THE INTERVENTION IN A TIME SERIES BEFORE AND AFTER DESIGN, DECREASE DISPARITIES AFTER ADJUSTED FOR DEMOGRAPHICS AND HIV CARE VISITS. LATINOS HAVE GREATER ODDS THAN WHITES. IN TAKING ANTIRETROVIRAL THERAPY AND BEING SUPPRESSED VIRALLY. HAVING VIRAL SUPPRESSION. NOW, THIS IS ANOTHER STUDY FUNDED BY NIMHD LOOKED AT STRESS MANAGEMENT PATIENTS WITH DIABETES IN THE CASE LATINO. IT USES A MODEL INCREASINGLY RELEVANT TO IMPLEMENT A VARIETY OF SETTINGS SO IT STARTED OUT YEARS AGO WITH -- (SPEAKING NON-ENGLISH) OR PEER WORKERS TO HELP THEM TEACH THEM ABOUT GO GET SCREENED FOR CANCER, THIS WAS THE WORK I WAS INVOLVED WITH AT ONE POINT SO THE COMMUNITY HEALTH WORKER THEN ELEVATE THEM A LITTLE BIT, YOU GIVE THEM TRAINING AND THEN THEY BECOME PEER DELIVERERS OF INTERVENTIONS. THERE'S ONE THAT A COLLEAGUE DID IN THE BAY AREA MANAGING DEPRESSION IN RECENT IMMIGRANTS, THIS IS A STRESS MANAGEMENT INTERVENTION AND PEOPLE WITH DIABETES. IN THE CLINICAL SETTING WE'RE USING IT MORE AND MORE, IN WHAT IS CARE MANAGER OR INDIVIDUALS ARE HELPING MANAGE MORE COMPLE PATIENTS. AGAIN THAT'S PROBABLY ANOTHER LEVEL NOTCHING UP A LITTLE BIT IN TERMS OF THE INTERVENTION PERSON HAVING MORE SKILLS. BUT THAT'S -- THIS IS A FUNDAMENTALLY BASED IN BEHAVIORAL RESEARCH AND USING INTERMEDIARIES TO IMPROVE OUTCOMES OF PATIENTS. IN THIS INTERVENTION STRESS MANAGEMENT DID IMPROVE DEPRESSION ANXIETY AND SELF-REPORTED HEALTH STATUS IN THE LATINOS WITH DIABETES. THERE WASN'T MUCH OF IMPACT IN THE HEMOGLOBIN A 1C THOUGH WITH AGAIN SUBGROUP ANALYSIS OF DOSE EXPOSURE YOU CAN SEE AFFECTS ON A 1C AND DIABETES AND STRESS, SOME WAYS SO MUCH GOES INTO DETERMINING HEMOGLOBIN A 1C LEVELS PRIMARILY TYPE AND MEDICINE INDIVIDUALS TAKE AND ADHERENCE TO THERAPY THAT MAY NOT EXPECT THIS KIND OF INTERVENTION TO HAVE AN IMPACT ON THAT UNLESS IT IMPROVES ADHERENCE IN OTHERWISE POORLY ADHERENT PATIENT. SO LET ME VEER NOW FOCUS ON PATIENT DOCTOR OR CLINICIAN PATIENT, LABORATORY IF YOU WISH. I THINK THIS IS A RICH AREA FOR BEHAVIORAL RESEARCH THAT AT NIH WE HAVE NOT ACTUALLY TAKEN ADVANTAGE OF ENOUGH. HOPEFULLY THROUGH INTRAMURAL PROGRAM WE WILL IN THE FUTURE AND HIGHLIGHT SOME POINTS AND EMPHASIZE DISCRIMINATION. SO FIRST OF ALL THERE'S A GIVEN THERE'S SOCIAL DISTANCE OR DIFFERENCE IN POWER LEVELS, CLINICIANS HAVE GRADUATE DEGREES, WE ALL DO BY DEFINITION , MOST PATIENTS ARE NOT IN THE ONE PERCENT SO TAKE CARE OF 1% SOCIAL BUSINESS MAY GO THE OTHER WAY BUT MAJORITY OF US TOOK CARE OF REGULAR PEOPLE IN BROAD SPECTRUM OF REGULAR PEOPLE. HEALTH LITERACY IS UBIQUITOUS PROBLEM IN THIS COUNTRY, IT'S SOME ESTIMATES ARE 50% OF THE POPULATION IS SUB-- INADEQUATE HEALTH LITERACY. THIS IS RELATED TO BUT NOT EXCLUSIVELY EXPLAINED BY THE YEARS OF FORMAL EDUCATION. WE KNOW IT'S RELATED TO HEALTH OUTCOMES, IN A VARIETY OF CLINICAL SETTINGS WITHOUT GOING INTO DETAIL SO IT'S SOMETHING ROUTINELY WE SHOULD BE LOOKING AT AND EVALUATING IN CLINICAL CARE. WE DON'T DO ENOUGH OF IT. MORE RECENT CONSTRUCT PEOPLE PAID ATTENTION TO IS NUMERACY, WE TELL PATIENTS OFTEN WELL YOUR RISK OF CANCER OR HEART ATTACK, IS BLANK. YOU CAN SAY RISK IS 10 OR 12% THEREFORE TAKE THIS DRUG EVERY DAY FOR THE REST OF YOUR LIFE OR 20 YEARS, A STATIN TO LOWER CHOLESTEROL. YOU ASK PEOPLE WHAT IS HIGH RISK. THEY WILL SAY 50%. SO NUMERACY CONSTRUCTS ARE SOMETHING SIMPLE PROPORTIONS IN ARITHMETICS. WE'RE NOT TALK CALCULUS HERE. BETTER OR WORSE NO ONE HAS STUDIED THIS BUT CLINICIANS ARE ALSO NOT REALLY THAT GOOD AT NUMERACY EITHER. TRUST IN THE DOCTORS OR CLINICSES ARE IMPORTANT, IT'S LINKED TO DISCRIMINATION. OFTEN PEOPLE THINK THEY CAN'T GAIN THE TRUST OF PATIENT WHOSE ARE DIFFERENT THAN THEY ARE BUT I DON'T THINK THAT'S NOT TRUE. INDIVIDUAL CLINICIANS CAN, IT'S INSTITUTIONAL MISTRUST YOU CANNOT CHANGE THAT BUT YOU CAN OVERCOME IT. DISCRIMINATION IS REAL, I WILL GET INTO THAT MORE. LIMITED PROFICIENCY IS A TOPIC WE ARE INTERESTED IN, I WILL GO OVER THAT. AND THAN THE SHARE DECISION MAKING, THIS PARTICIPATION IN IT HAS BECOME THE GOLD STANDARD MANTRA OF CLINICAL DECISION AND YET WE REALLY DON'T FULLY UNDERSTAND WHAT PATIENTS WANT OR HOW TO DO IT RIGHT. SO I THINK THIS IS ANOTHER AREA OF RIPE FOR MORE RIGOROUS RESEARCH. IT COMES IN PART FROM ANNE GLOW AMERICAN PREDOMINANT PARADIGM INDIVIDUAL AUTONOMY. AND THE INDIVIDUAL IS THE DOMINANT INDIVIDUAL IS THE PREDOMINANT PARADIGM HERE. I CAN SHARE WHEN I STARTED WORKING IN TOBACCO SINCE BILL MENTIONED IT, ONE OF THE THINGS THAT WE DID THAT WAS BASED ON OUR QUALITATIVE DATA THAT WAS DIFFERENT AT THAT TIME WAS THAT WE PUT IN OUR FIRST CESSATION GUIDE WE PUT THE FAMILY ON THE COVER, AT THE SAME TIME THE AMERICAN LUNG ASSOCIATION PUBLISHED A TERRIFIC SMOKING CESSATION GUIDE ALL ABOUT INDIVIDUALS. IT WAS VERY DIVERSE, LOTS OF TYPES OF PEOPLE BUT IT WAS VERY MUCH QUIT FOR YOUR OWN GOOD OPPOSED TO THE ELECTIVE INTEREST -- COLLECTIVE INTEREST. I THINK A LOT OF NON-WHITE CULTURE OR IMMIGRANT CULTURE C COLLECTIVIST IN THEIR APPROACH. WE HAVEN'T FULLY -- PEOPLE ARE AWARE OF THIS BUT THEY HAVEN'T FULLY INCORPORATED THAT INTO THEIR WORK. MENT AND CONCORDANCE IS ANOTHER AREA OF RESEARCH. LANGUAGE IS OBVIOUS BUT ALSO RACE ETHNICITY MATTER, THERE'S GENDER CONCORDANCE MANNER, ALL RIPE FOR RESEARCH. QUICKLY SHOW YOU SOME DATA ON DISCRIMINATION. THIS IS FROM THE KEISER FAMILY FOUNDATION, SURVEY OF AMERICANS FROM COUPLE OF YEARS AGO. 53% OF AFRICAN AMERICANS SAID THEY WERE TREATED UNFAIRLY IN -- AND 12% HEALTHCARE SO WE DO BETTER IN HEALTHCARE, I HAVE READ OR HEARD OF SURVEYS THAT HAVE BEEN AS HIGH AS 30% IN HEALTHCARE. LATINOS WERE 36% AND 14% HEALTHCARE YOU CAN SEE THE BACKGROUND FOR WHITES. SO THIS IS REAL. THIS IS NOT SOMETHING THAT PEOPLE ARE MAKING UP. I THINK WE'RE IF I REMEMBER IN 2009 I WAS ASKED THE QUESTION YOU ELECTED A BLACK PRESIDENT, AREN'T WE OVER THIS? AND THE ANSWER I THINK DOESN'T NEED TO BE EXPANDED ON. DAVID WILLIAMS, AMONG OTHERS, HELPED THINK ABOUT HOW DO WE STRUCTURE OR THINK ABOUT RACISM. MOST OF WHAT PEOPLE KNOW AND WHAT WE HAVE DONE RESEARCH ON IS INTERPERSONAL SO YOU ASK PEOPLE HAVE YOU HAD DISCRIMINATION. AND GOOD SCALES, EVERY DAY DISCRIMINATION SCALE, OTHERS THAT CAN BE USED, RELIABLE, REASONABLE FACE VALIDITY AND LINKED TO SOME PROCESS VARIABLES. STRUCTURAL RACISM IS NOR CHALLENGING -- MORE CHALLENGING ONE. WE HAD A SCIENTIFIC WORKSHOP THIS YEAR EARLIER ON THIS TOPIC. I THINK HOW TO CONCEPTUALIZE THIS AS RESEARCH CONSTRUCT IS A CHALLENGE. WE WANT TO SEE AND PURSUE THIS MORE. AND WE HAD SOME PLANS ON THAT. BUT HISTORY CULTURE INSTITUTIONS CODIFIED PRACTICE SO THE IDEA IS YOU WALK INTO A PLACE AND YOU SAY THIS IS NOT A FRIENDLY PLACE, STRUCTURAL RACISM, NOT JUST AGGRAVATED NEIGHBORHOODS OR THE -- AGGREGATED NEIGHBORHOODS OR LAWS THAT EXIST THAT BAN PEOPLE FROM CERTAIN INSTITUTIONS, ET CETERA, THAT'S PART OF IT AND SPECIALIZED RACISM IS HARDER. PEOPLE WHO SAY NO, I'M FINE, NEVER DISCRIMINATED BUT INTERNALIZED IT. SUPPOSABLYMATION HOW IT AFFECT -- SUBLIMATION AFFECTS THEM NEEDS TO BE MORE MICRORESEARCH AND MORE CONTROLLED ENVIRONMENTS TO BE ABLE TO FIND MECHANISMS. THESE ARE SOME OF THE MEASURES IN LINKING BEHAVIOR AND BIOLOGY, SURE YOU ARE FAMILIAR WITH ALL OF THESE ARE HAPPENING IN MINORITY HEALTH, HEALTH DISPARITIES. I WAS ON THE RADIO YESTERDAY LISTENING TO ARLENE, TALK ABOUT THE WEATHERING HYPOTHESIS SO THE ALLO STATIC LOAD THAT'S AROUND INFLAMMATION, THE TELOMERE LENGTH USUALLY IN WHITE CELLS, THEN SLEEP IS RELATIVELY NEW. WE HAVE A FUNDING OPPORTUNITY ANNOUNCEMENT ON THIS, IT'S AN IMPORTANT ONE. TO QUANTIFY, WE HAVE TOOLS THAT QUANTIFY BOTH IN TERMS OF QUANTITY AND QUALITY BETTER. BRAIN IMAGING IS A NEW FRONT THAT I KEEP BRINGING UP BECAUSE WE NEED TO LOOK AT DIFFERENCES BY GENDER RACE ETHNICITY AND SES. SO RACIAL INEQUITY HARMING HEALTH, THE DATA ON HOW PEOPLE SELF-PERCEIVE THEIR HEALTH AS A CONSEQUENCE OF DISCRIMINATION IS FAIRLY GOOD, MOSTLY PHYSICAL AND MENTAL HEALTH, PRIMARILY AFRICAN AMERICANS MEN MORE THAN WOMEN, BUT ALSO INCLUDES DATA ON LATINOS AND ASIAN, SO THIS IS WHERE THE BEST DATA BUT IT'S A SELF-REPORTED HEALTH SO HOW DOES IT AFFECT PHYSIOLOGIC MEASURES, MOST HAVE BEEN ON CARDIOVASCULAR MEASURES SO RELATED TO SYSTOLIC BLOOD PRESSURE OR INFLAMMATORY MARKERS. AGAIN, THERE'S DATA ON THAT, THIS IS PROCESS INTERMEDIARY VARIABLES. THERE'S LINKS ON MENTAL HEALTH HOW IT AFFECTS HEART DISEASE SO WHERE PEOPLE ARE MAKING CONNECTS. THEN THERE IS FAIRLY GOOD DATA ON SMOKING. WE DID A STUDY ON THAT IN AFRICA AND INDIGENOUS GROUPS IN NORTHERN ARGENTINA. PROBLEM DRINKING SUBSTANCE USE. THE -- THIS IS AN OPPORTUNITY FOR FURTHER RESEARCH. THIS IS AN EXAMPLE OF A RECENT PAPER, THAT CAME OUT OF CARDIA, LINKING RACE RESIDENTIAL SEGREGATION TO CHANGES IN SYSTOLIC BLOOD PRESSURE. TRYING TO GET FINITE WITH RACIAL SEGREGATION SCORE AND PERSONS WHO LIVE IN THESE HIGH RESIDENTIAL SEGREGATION AREAS VERSUS THOSE THAT DIDN'T AND LOOK AT DIFFERENCES IN BLOOD PRESSURE. 1 TO 2-MILLIMETERS OF MERCURY IS IT WAS STATISTICALLY SIGNIFICANT AND CONTINUOUS VARIABLE. OVERPOPULATION, COUPLE OF MILLIMETERS MERCURY IN SYSTOLIC BLOOD PRESSURE CAN BE A RELEVANT CHANGE. THIS IS ANOTHER ONE TRYING TO GET INTERNALIZE RACIAL ATTITUDES AND NATIONAL SURVEY OF MESH LIFE AND AFRICAN AMERICAN MEN. NO MANUFACTURED DISCRIMINATION IN PREDICTING CARDIOVASCULAR HISTORY, MEN WHO ENDORSE NEGATIVE BELIEFS ABOUT BLACKS. BLACK MEN WHO HAVE NEGATIVE BELIEFS ABOUT BLACKS AND PRESUMABLY INTERNALIZED THIS AT HIGHEST RISK OF EVENT. HISTORY. AGAIN, BASED ON HISTORY, NOT -- AND P TENDED TO BE A YOUNGER GROUP SO WE STUDIED MEN OVER 60 PERHAPS YOU WOULD SEE A MORE ROBUST RELATIONSHIP HERE. I THINK THIS IS AN AREA VERY LIMITED RESEARCH IN THISSIC. THIS -- THIS TOPIC. IN INDIANAPOLIS, NEW SCIENTIFIC DIRECTOR. SHE HIGHLIGHTED WHEN I SAID I WAS GOING TO DO THIS TALK DO YOU HAVE SUGGESTIONS, SHE SENT ME A PAPER THAT DAVID WILLIAMS AS SENIOR AUTHOR IS IN -- AVAILABLE ON LION RIGHT NOW. IT'S DISPARITIES AMONG NON-PORE. MINORITY HEALTH, HEALTH DISPARITIES IS PEOPLE BRING THE TWO TOGETHER AND SAY THE YOU'RE MINORITY YOU'RE POOR. THERE'S VERY LITTLE RESEARCH ON NON-POOR MINORITY. THAT IS ANOTHER AREA THAT NEEDS WORK. NOT THAT MANY DATABASES HAVE NUMBERS HERE SO THE NATIONAL LONGITUDINAL SURVEY OF YOUTH BACK TO 1979 AND HAVING 33 YEARS OF FOLLOW-UP, SO PARENTS AND CHILDREN, YOU CAN SEE THE DIVERSITY OF THE SAMPLE, PRETTY GOOD. 24% LATINO. THE METHODS ARE COMPLICATED BECAUSE THE SAMPLE SIZE WAS 4 TO 5,000 RANGE BUT DIFFERENT FOR DIFFERENT MEASURES. YOU'LL LET YOU ENJOY THAT READING. BUT ESSENTIALLY AS WHITES GOT HIGHER ON THE SES SCALE, THEY REPORTED LESS DISCRIMINATION, ACUTE AND CHRONIC. FOR BLACKS AND LATINOS IT WAS THE OPPOSITE SO AWKWARD NO -- UPWARD MOBILITY LED TO GREATER REPORTING OF DISCRIMINATION. IT HELPED EXPLAIN SOME OF THE BLACK WHITE GAP IN SELF-RATED HEALTH, NOT LATINOS UNDERRATE THEIR HEALTH ANYWAY IN THE SELF-REPORT MEASURE SO THIS IS VERY INTERESTING AREA, IMPORTANT, I GUESS THE LESSON IS WE HAVE TO STUDY NON-POOR MINORITIES IN PARTICULAR AFRICAN AMERICANS AND LATINOS. SO THIS IS TO BUILD INTO THE JAMES JACKSON AFFORDANCE MODEL, CHRONIC STRESS LEADING TO MENTAL HEALTH ISSUES AND UNHEALTHY BEHAVIORS, WE HAVE BEEN INTERESTED IN THIS AND WITH ERIC RODRIGUEZ WORKED ON THIS USING OTHER DATA SETS BUT JAMES PUBLISHED THIS NUMBER OF YEARS AGO BASICALLY SAYING MADE THE OBSERVATION THAT WHITES HAVE HIGHER RATES OF SUICIDE AND HIGHER RATES OF DEPRESSION THAN BLACKS. THIS IS CONSISTENT. ALL THE DATA SHOW THE SAME THING. DIFFERENCE IN SUICIDE RATES ARE ALMOST TRIPLE, DIFFERENCE IN DEPRESSION ARE SIGNIFICANT. DIAGNOSE DEPRESSION USING STANDARDIZED INTERVIEWS. HE POSTULATED THAT WAS RELATED -- THE WAY DIFFERENT RACIAL GROUPS RESPOND TO CHRONIC STRESS ANALYZING DATA FROM THE AMERICA CHANGING LIFE SURVEY FROM THE LATE 1980s, THIS IS A LIMITATION, THE WHITES HAD UNHEALTHY BEHAVIORS, STRENGTHINGENS STRESSORS LEADING TO MORE DEPRESSION. SO WHILE BLACKS WHO DID UN HEALTHY BEHAVIOR AND USED SMOKING ALCOHOL AND UNHEALTHY FOOD WAS PROTECTIVE FOR MENTAL HEALTH CONDITION SO THE IDEA WAS THAT THAT'S O COPING, UNHEALTHY COPING MECHANISM FOR -- AND LENGTH THE NUMBER OF CHRONIC CONDITION INCREASED. NOT LOT OF OTHER SUPPORT FOR THIS HYPOTHESIS THOUGH JAIL STILL HAS THAT AS A FLAG BUT IT'S AN INTERESTING WAY OF ANALYZING AND THINKING ABOUT WHAT WE OBSERVE. I'M GOING TO SKIP THIS. FOR THE SAKE OF FEW MINUTES LEFT TO MENTION UNCONSCIOUS BIAS, A HAS BEEN DONE ON THIS FROM SYSTEMS PERSPECTIVE, AWARENESS PERSPECTIVE. LIMITED RESEARCH THAT IS ANYTHING THAT WOULD STAND RIGOR. LOTS OF DATA SHOWING DOCTORS DID NOT ALWAYS PRESCRIBE WHAT WAS THOUGHT STATE-OF-THE-ART THERAPY FOR BLACK PATIENTS OR LATINO PATIENTS. MOSTLY WITH AFRICAN AMERICANS AROUND CARDIAC AND TECHNICAL PROCEDURES. MEDICAL STUDENT BIAS DOING SCENARIOS IN OBESE PATIENT VERSUS NON-OBESE VIRTUAL PATIENT. REFERRAL MINORITY PATIENT FOR OBTAINING OTHER TECHNICAL PROCEDURES IN LUNG CANCER SURGERY, RENAL TRANSPLANT BUT USING CLINICAL VIGNETTE TO STUDIES FOUND FAVORING TREATMENT OF WHITES, NOT A LOT OF EMPIRICAL BASES THOUGH FOR IMPLICIT BIAS. SO IS IT MODIFIABLE? THIS IS ONE OF THE MORE RECENT THINGS I THOUGHT WAS GOOD. IT EVALUATED CHANGE IMPLICIT RACIAL BIAS TOWARDS AFRICAN AMERICAN MEDICAL STUDENTS IN 49 SCHOOLS THROUGH A WEB-BASED QUESTIONNAIRE AND FIRST AND LAST SEMESTER MEDICAL SCHOOL. THE CHANGE IN IMPLICIT BIAS BASED ON THE BLACK, WHITE, IAT METHOD IF YOU HAVE NOT TAKEN IT YOU CAN DIAL INTHE ANY CATEGORY YOU WOULD LIKE. IF YOU COMPLETE IT YOU'RE MORE LIKELY TO CHANGE SO IT WASN'T SELF-AWARENESS, THE SELF-ASSESS SKILLS CARING FOR LACK PATIENTS IF YOU THOUGHT YOU WERE BETTER TAKING CARE OF AFRICAN AMERICAN PATIENTS YOU DID BETTER AT END OF MEDAL SCHOOL. IF YOU HEARD NEGATIVE COMMENTS FROM SUPERVISOR ABOUT AFRICAN AMERICAN PATIENTS YOU DID WORSE SO THIS IS A RELEVANCE ROLE MODELING AND NATURE OF CONTACT WITH AFRICAN AMERICAN PHYSICIANS SO IF THEY HAD GOOD CONTACT WITH AFRICAN AMERICAN PHYSICIANS THEY DID BETTER. CONTACT WITH AFRICAN AMERICAN DECISION WAS PERCEIVED NOT GOOD, THEN THEY DID WORTHS. UNLIMITED ENGLISH PROFICIENCY, ALE SUMMARIZE FROM THIS SLIDE, IT'S A NO BRAINER IF YOU SIT WITH SOMEONE IN THE SAME ROOM TALKING ABOUT YOUR HEALTH AND YOU DON'T SPEAK THE SAME LANGUAGE THERE'S SOME LIMITATION OF COMMUNICATION, RIGHT? FROM AMAZINGLY WE LET THIS GO ON EVERY DAY IN HEALTHCARE AUTISM THE TIME. ALL TIME. SPANISH IS PREDOMINANT KNOCK ENGLISH LANGUAGE SPOKEN BY HOUSEHOLDS THAT DO NOT SPEAK ENGLISH AT HOME, SOMETHING LIKE 65% OF ADULTS WHO DO NOT SPEAK ENGLISH SPEAK SPANISH. A LITANY OTHER LANGUAGE, I THINK CHINESE THE SECOND. CONCORDANCE OF THE SAME LANGUAGE LEADS TO LOWER A 1Cs IN PATIENTS WITH DEKES, MOSTLY GOOD DATA FROM THE KEISER SYSTEM, MORE PATIENT CENTERED, IT'S PATIENTS HAVE BETTER HEALTH OUTLOOK WITH QUALITATIVE STUDIES. THE LANGUAGE IS COMMON, INTERPRETERS ARE OFTEN NOT AVAILABLE, THEIR USE -- UNDERUTILIZED, SAY I'LL GET BY, WE DO VETERINARY MEDICINE HERE. THAT'S OKAY. INTERPRETERS ARE OFTEN UNTRAINED SO INSISTENCE WHO IS IN THE OFFICE WHO HAPPENS TO SPEAK SPANISH. NO ONE TESTED HIM OR HER TO SEE IF THEY SPEAK ADEQUATE MEDICAL SPANISH. AND THEN THERE'S LOTS OF ERRORS, WE DID A IMPAIRED STUDY IN SAN FRANCISCO BAY AREA LOOKING AT HOSPITALS, IT WAS QUALITATIVE STUDY, I DON'T HAVE TIME TO GO OVER ALL THE DETAILS BUT BOTTOM LINE, WE HAD 27 ERRORS ON AVERAGE PER SRI IS IT, THE WHOLE INTERCHANGE WAS ANALYZED USING TEXT UNITS AND THERE WERE CLINICALLY SIGNIFICANT ERRORS THAT OCCURRED IN 7% OF TEXT UNITS. INCLUDING ONE A PATIENT WAS TOLD TO TAKE ACETAMINOPHEN DOSE IF THEY DID IT WAS RISK FOR OVERDOSE AND MISMANAGEMENT OF CHEST PAIN WHICH SHOULD HAVE BEEN MANAGED AS CONCERN FOR CARDIAC ISCHEMIA GONE DOWN ANOTHER ROUTE COMPLETELY. SO WE DO HAVE A WAY, PROFESSIONAL INTERPRETERS DO BETTER AND SOMETHING THANES TO BE CONSIDERED ISSUE OF QUALITY. NULL STUDY FROM WENDY LEVINSON FROM 2005 SHOWED THAT HALF OF PEOPLE PREFER THE PHYSICIAN TO MAKE A DECISION, THOUGH EVERYONE WANTS INFORMATION. I DON'T THINK THERE'S A LOT BEEN DONE ON THIS, FIND OUT HAS THESE CHANGED SINCE THEN? I DON'T KNOW IF THIS IS -- THIS DOESN'T FEEL LIKE IT WOULD BE A FIXED ATTITUDE. IT WASN'T VERY DIVERSE. SO I'LL FINISH WITH A CUP OF THOUGHTS. I WOULD IMPLORE YOU SOCIAL BEHAVIORAL SCIENTISTS THINK ABOUT DISPARITIES IN YOUR RESEARCH. YOU MAY NOT FOCUS ON IT BUT THINK ABOUT IT. THERE'S ADAPTING VERSUS FIDELITY, ADAPTING INTERVENTION REQUIRE CHANGES. VERSUS JUST STICKING WITH THE PROTOCOL. THERE'S SOME PUBLISHED EXPERIENCES ON THAT. EFFICACY IS IMPORTANT AND THEN YOU IMPLEMENT AND HOW DO YOU SUSTAIN, THESE ARE ALL CRITICAL ISSUES. THE WHOLE WORLD OF HEALTH IT AND HOW TO INFLUENCE PREFERENCES FOR INVOLVING DECISION MAKING OR PROMOTING BEHAVIOR CHANGE IS AN AREA THAT CAN BE EXPLORED FURTHER. COMMUNICATION STRATEGY. I SAID ABOUT CHILLED WATER MAKING CHANGE BUT STRUCTURAL CHANGE DOES A LOT MORE THAN YOU THINK IN CHANGING BEHAVIOR. INCLUDING SMOKING INDOORS WE THOUGHT WE -- PEOPLE THOUGHT THEY DID THAT TO GET SMOKERS TO QUIT AND WHAT IT LED TO LESS HEART ATTACKS. HOW IS THAT FOR GETTING BANG FOR YOUR CHANGE. THESE ARE SOME FUNDING OPPORTUNITY ANNOUNCEMENTS NIMHD HAS, ALL ON THE WEBSITE IF PEEP ARE INTERESTED IN THIS, THIS IS NOT COMPLETE LIST FOR THOSE THAT RELATE TO RESEARCH. THANK YOU FOR YOUR ATTENTION AND I HAVE A FEW MINUTES FOR QUESTIONS. [APPLAUSE] >> SO CHILLED WATER WHAT'S THE DIFFERENCE BETWEEN CHILLED WATER SEARCH AND SEIZURE REGULAR WATER? IS THERE A SIGNIFICANT MEANING BEHIND CHILL WATER VERSUS >> CALIFORNIA. IT'S ALWAYS 80-DEGREES. IT'S 100 IN THE SUMMER. >> GOT YOU. >> SO THE PEOPLE LIKE TO DRINK COLD WATER. >> >> ALL RIGHT. I DON'T KNOW. WE CAN CONTACT INVESTIGATOR. >> COUPLE OF QUESTIONS ACTUALLY. THE OTHER THING, I'M CURIOUS GOOGLE TRANSLATE HAS MADE BIG CHANGES ESPECIALLY TOURIST TO DIFFERENT COUNTRIES. HAS ANYONE LOOKED AT TECHNOLOGIES TO HELP TRANSLATION BARRIER? ESPECIALLY OBVIOUSLY THERE'S MEDICAL TERMINOLOGY BEING PASSED THROUGH. SURE SOMETHING LIKE IBM OR WATSON CAN HELP LOOK AT A WAY OF FACILITATING ESPECIALLY WHEN INTERPRETER IS NOT THERE. >> YOU BRING UP A GOOD POINT, COULD BE IN TEN YEARS THIS WILL BE A MOOT ISSUE. THE TECHNOLOGY HAS IMPROVED, THERE WAS ONE COUPLE OF PEOPLE WHO TRIED TO DO SOMETHING WITH THIS, AT UCSF WHEN I WAS THERE. I WASN'T INVOLVED IN IT. IT WAS INTERESTING. IT DOESN'T PASS THE INITIAL SMELL TEST RIGHT NOW IN TERMS OF COMMUNICATING WITH YOUR CLINICIAN. BUT WITHOUT BEING DOGMATIC ABOUT IT, IT'S LIKE DRIVERLESS CARS. MAYBE IN THE FUTURE NO ONE HAVE TO LEARN HOW TO DRIVE BECAUSE THEY'LL ALL HAVE SELF-DRIVING CARS. SO I THINK THIS COULD BE A WAY OUT OF THIS ISSUE, AT LEAST IN THE -- CAN BE IMMEDIATELY THERE ON THE SCREEN AND PEOPLE CAN INTERACT THAT WAY. SO I WOULDN'T -- I THINK IT'S SOMETHING TO EXPLORE. THANK YOU. >> MY NAME IS LI YOUNG. I THINK THERE ARE SOME OTHER ASPECT MAYBE WE CAN INVESTIGATE, MINORITY, BLACK AND LATINO, RACIAL PROFILING HIGHER THAN WHITE AND THEY ARE MASS INCARCERATION, WHICH HAD TO PAY A LOT OF BAIL, INCOME NORMALLY IS LOW AND (INAUDIBLE) EVEN WORSE. IF YOU DON'T HAVE MONEY, OBVIOUSLY YOU HAVE LESS POSSIBILITY TO HAVE A GOOD HEALTHCARE. NOT ONLY EDUCATION BACKGROUND BUT ALSO TREATMENT, IMPROVE THE HEALTH STATUS. I'M THINKING NOT THEY ARE IMPOSSIBLE TO HAVE GOOD HEALTHCARE, I THINK THERE'S SOMETHING SOCIETY SYSTEM IS WRONG, THEY HAVE SOME KIND OF MEDICAL TREATMENT INFORMATION BUT THEY ARE REALLY UNDER NEGATIVE TREATMENT. THEY ARE NOT REALLY RECEIVE BENEFIT BUT THEY ARE VICTIMIZED IN SUCH A WAY THEIR SOCIAL BENEFIT, OF HEALTH OCCUPATION OR HOSPITAL OR REHAB CENTER THEMSELVES RATHER THAN PAY ATTENTION TO HEALTHCARE SO WONDER, A LOT OF THIS TYPE OF THINGS SHOULD BE TAKEN INTO ACCOUNT, WITH STUDIES, GOVERNMENT AND HEALTHCARE CAUSE THROUGH GOOD BENEFIT POPULATION RATHER THAN PAID INCLUDING PSYCHOLOGISTS OR SOCIAL SERVICE WORKERS. THEY'RE ALWAYS -- THE FORCE FALSE TESTIMONY AGAINST MINORITIES. THEY HAVE A FALSE IMPRISON, FALSE DETENTION AND NOW THEY USE HOSPITAL AND REHAPPEN CENTER AS A ALTERNATIVE TO DETENTION CENTER, PRISON. THING WE HAVE TO INVESTIGATE IS TO HAVE A REAL GOOD SENSE -- >> DO YOU HAVE A QUESTION?& >> MY QUESTION IS THOSE PROBLEM SYSTEMIC PROBLEM IS AGAINST MINORITY, SO YOU MIGHT HAVE -- GOVERNMENT MIGHT HAVE HIGH COST OF HEALTHCARE BUT THEY DON'T BENEFIT MINORITIES. >> I THINK I HEARD YOU TALK MOSTLY ABOUT THE IMPORTANCE OF CONSIDERING INCARCERATION IN MINORITY HEALTH AND HEALTH DISPARITY. THERE'S A LOT OF ISSUE AROUND THAT. I DIDN'T PRETEND TO BE COMPREHENSIVE IN MY PRESENTATION. SO MANY TALKED ABOUT HIPSRY OF INCARCERATION AS SOCIAL DETERMINANT GIVEN PREVALENCE OF PARTICULARLY AMONG MEN OF COLOR. IN THIS COUNTRY. AND I THINK THAT -- BECAUSE THAT IMPACTS YOUR ABILITY TO GET A JOB, YOUR ABILITY TO DO A NUMBER OF THINGS IN SOCIETY. ONCE YOU ARE OUT OF PRISON. I ALSO THINK IT HAS BEEN USED IN VARIETY OF WAY SOCIALLY SO THAT'S IMPORTANT. ALL PEOPLE INCARCERATED ARE NOT INCLUDED IN EVERY NATIONAL SURVEY BECAUSE IT NOT INSTITUTIONALIZED IN ANY SURVEYS THAT WE DO, N HAYNES, ET CETERA, NIEHS OR ANY POPULATION BASED SURVEYS. THE HEALTHCARE OF PEOPLE WHO ARE INCARCERATED VARY BY STATES. AND IT CAN BE ACTUALLY BETTER THAN THEY WOULD GET IN THE COMMUNITY IN SOME CASES. BUT IT OBVIOUSLY THEY HAVE -- IT IS -- DOES REPRESENT A SIGNIFICANT CHALLENGE FOR BOTH STATE GOVERNMENT AND PUBLIC HEALTH. MOST RECENT EXAMPLE HEPATITIS C TREATMENT IN THE OPTIONS TO TREAT AND CURE HEPATITIS C FOR INCARCERATED POPULATIONS IN WHAT STATE HEALTH DEPARTMENTS WERE GOING THROUGH IN TERMS OF HOW WERE THEY GOING TO AFFORD IT. AND HAVING TALKED TO AT LEAST A COUPLE OF THEM, AND HEARING THEM REPORT ON THAT I THINK IS ONE EXAMPLE OF A SYSTEM ISSUES THAT AFFECTS HEALTHCARE THAT WOULD AFFECT LONG TERM HEALTH OF HE IS INDIVIDUALS DURING THE TIME THEY ARE IN PRISON AS WELL AS IF AND WHEN THEY'RE RELEASED. [APPLAUSE] JANINE SIMMONS WILL BE THE MODERATOR FOR THE NEXT PANEL. JANINE. >> I'M NOT GOING SO MUCH MODERATE BUT INTRODUCE, I'M JANINE FROM NATIONAL INSTITUTE OF MENTAL HEALTH, MY PLEASURE IS TO INTRODUCE THE THREE SPEAKER ON THE PANEL OF BEHAVIORAL NEUROSCIENCE, I'LL INTRODUCE THEM AT ONCE SO YOU HAVE TO REMEMBER ALL THIS INFORMATION TO ACTIVATE YOUR WORKING MEMORY CIRCUIT. SO DR. KENNY, FIRST SPEAKER IS DR. PAUL ANYONENY, -- KENNY, THE CHAIR MAN OF THE DEPARTMENT OF NEUROSCIENCE AT ICON SCHOOL OF MEDICINE MOUNT SINAI. HIS RESEARCH IS TO US CUSSED ON UNDERSTANDING MOLECULAR NEUROBIOLOGY OF DRUG ADDICTION OBESITY AND SCHIZOPHRENIA. RECEIVED NUMEROUS AWARDS, INCLUDING THE MEMORIAL AWARD FOR SOCIETY OF NEUROSCIENCE AND DISTINGUISHED INVESTIGATOR AWARD FROM NARSA. HE ALSO SERVEDS AS MEMBER. NATIONAL ADVISORY COUNCIL FOR NIAAA, THE NATIONAL INSTITUTE OF ALCOHOL ABUSE AND ALCOHOLISM. TODAY HIS PRESENTATION IS GOING TO BE TITLED BRAIN AVOIDANCE CIRCUITS AND ADDICTION. AFTER DR. KENNY WE HAVE DR. SHANNON GOURLEY, WHO COMES TO US FROM THE EMORY SCHOOL OF MEDICINE AND HER RESEARCH FOCUSES ON ISSUES OF DEPRESSION AND ADDICTION WITH PARTICULAR FOCUS ON ADOLESCENT. SHE'S PARTICULARLY INTERESTED IN HOW ADVERSE OUTCOMES MAY RELATE TO THE MANNER PATHOLOGICAL STIMULI SUCH AS STRESSORS, SOCIAL ISOLATION AND DRUGS OF ABUSE IMPACT THE ADOLESCENT PRE-FRONTAL CORTEX AND SHE USES VARIETY OF METHODS INCLUDING BEHAVIORAL PHARMACO LOGICAL BIOCHEMICAL AND GENETIC AND CELLULAR TO THERAPEUTICS INTERVENTIONS FOR VULNERABLE ADOLESCENT POPULATION. HER LAB IS SUPPORTED BY NIMH AND SHE'S RECEIVED EARLY STAGE INVESTIGATOR AWARD CALL BRAIN BIOBEHAVIORAL RESEARCH AWAR FOR NEW SCIENTIST AS PROGRAM WHICH NIMH IS VERY PROUD AND ALSO SUPPORTED BY THE NATIONAL INSTITUTE ON DRUG ABUSE AND HER PRESENTATION IS GOING TO BE TITLED, ACTION CONSEQUENCE, DECISION MAKING AND AFFECTS OF COCAINE. FINALLY, WE'LL HAVE DR. RUSS FERNALD, HE IS THE BENJAMIN SCOTT CROCKER PROFESSOR OF HUMAN BIOLOGY AT STANFORD UNIVERSITY. HIS RESEARCH IS FOCUSED HOW SOCIAL BEHAVIOR INFLUENCES THE BRAIN AND SPECIFICALLY ANALYZING THE CELLULAR AND MOLECULAR CONSEQUENCES OF SOCIAL INTERACTIONS ON THE NERVOUS SYSTEM HE RECEIVED THE NEUROSCIENCE INVESTIGATOR AWARD AND WAS NAMED TRIPLE AS FELLOW. HE'S ALSO RECEIVED SEVERAL AWARDS FOR HIS WORK ON CONTRIBUTIONS TO UNDERGRADUATE EDUCATION AT STANFORD. HIS PRESENTATION IS TITLED HOW DOES SOCIAL BEHAVIOR CHANGE THE BRAIN. SO WE'LL START WITH DR. KENNY. PLUS PLUS [APPLAUSE] >> THANK YOU, JANINE FOR THE INTRODUCTION AND ALSO THANKS TO ORGANIZER FOR THE INVITATION TO BE HERE TODAY. I'M GO THE TALK ABOUT PUBLISHED A LITTLE BIT OF PUBLISHED WORK THEN UNPUBLISH WORK HOPEFULLY TO LINK ADDICTIVE PROPERTIES OF NICOTINE WITH BROADER HEALTH IMPLICATIONS OF THE USE OF THE DRUG. SOME HOPEFULLY TO BE OF INTEREST TO YOU. WE FOCUS IN LAB MAY SEEM STRANGE WHEN YOU WORK IN ADDICTIVE DRUGS WHICH ARE KNOWN TO BE REWARDING, PLEASANT, THAT'S THE REASON WHY THEY USE BUT WE WORK IN AVERSION CIRCUIT. WHY WOULD YOU DO THAT FOR DRUGS INTRINSICALLY REWARDING? TURNS OUT LIKE MOST THINGS, THERE'S A YANG TO THAT YIN SO THERE'S AN OPPOSITE SIDE AND DRUGS ARE PERHAPS AS AVERSE AS THEY ARE REWARDING WHICH DEPENDS ON WHICH GOES YOU USE, AS YOU WILL SEE IN A FEW MINUTES TURNS THAT THOSE DIVERSESIVE COMPONENTS OR ASPECTS OF ADDICTIVE DRUGS ARE PRETTY IMPORTANT IN TERMS OF WHETHER YOU ACQUIRE A HABIT, SUSTAIN THE HABIT AND DIFFICULTY QUITTING THE HABIT. SO ONE OF THE REASONS WE GOT INTERESTED IN AVERSIVE PROPERTIES OF NICOTINE CAME FROM HUMANS HUMAN GENETICS TO BEGIN WITH, WHEN PEEP LOOK AT GENETICS OF TOBACCO DEPENDENCE IN GENES ASSOCIATEDDED WITH VULNERABILITY OF TOBACCO USE, IT'S PERHAPS NOT SURPRISING SOME OF THOSE GENES RESIDED IN HICK TINNIC RECEPTOR GENES THE NICOTINIC RECEPTORS THAT RESPOND TO NICOTINE CONTAINED IN TOBACCO SMOKE SO ALLELIC VARIATION IN SOME OF THOSE SUBUNITS, GENES ENCODE THE SUBUNITS, THE DEGREE WHICH YOU SMOKE, AFT THE TIME IT WAS ALLELIC VARIATION IS NOT IN THE POPULATION OF NICOTINIC RECEPTORS WE KNOW AND LOVE. ALPHA 4 BETA 4 TICK ANYONE I CAN RECEPTORS RESPONSIBLE FOR ACTS OF NICOTINE IN THE BRAIN AND THOUGHT CENTRAL TO REWARDING PROPERTIES OF THE DRUG. AND IN FACT CHAN TICKS VERANACLIN THE MAJOR SMOKING CESSATION ON THE MARKET WAS DESIGNED TO BE AGONIST OF THESE ALPHA 4 BETA 2 RECEPTORS. WHEN YOU LOOK AT GENETICS, ALLELIC VARIATION INFLUENCES THE TOBACCO DEPENDENCE RESIDES IN IN A SEPARATE SET OF GENES THE ALPHA 5 ALPHA 4 AND ALPHA 3 BETA 4 NICOTINIC RECEPTOR GENES. THAT WAS OF INTEREST BECAUSE THESE ARE LESS PREVALENT IN THE BRAIN, FAR LESS DENSELY EXPRESSED, FACTOR PRIMARILY CONSIDERED GANGLIONIC NICOTINICS SO IT WAS CONSEQUENCE NOT MANY WERE HAD BEEN LOOKING AT SUBUNITS AND YET THIS FINDING OF GENETIC VARIATION INFLUENCING DEPENDENCE VULNERABILITY IS REPLICATED OVER AND OVER AND EXTENTED TO OTHER DRUGS OF ABUSE LIKE ALCOHOL WHICH ALLELIC VARIATION INFLUENCES VULNERABILITY, ASSOCIATION WITH COCAINE DEPENDENCE THOUGH STRANGE IN THE OPPOSITE DIRECTION SO THIS SEEMS AN IMPORTANT LOCUST. AS I SAID, THE SUBUNITS ARE NOT PREVALENT IN TERMS OF WIDESPREAD DISTRIBUTION BUT THERE ARE CERTAIN AREAS OF THE BRAIN THEY'RE CONCENTRATE AND TEND TO BE AREAS WE WE HAVEN'T IN THE PAST FOCUS ON MECHANISM OF ADDICTION IN TERMS OF CONTRIBUTION OF THESE BRAIN REGIONS SO TWO OF THESE REINVENTORY GENERALS WHAT YOU SEE -- REGIONS DENSE CONCENTRATION OF THIS SUBUNIT WHICH COMES UP EVERY ON THE OTHER HAND IN TERMS OF TOBACCO DEPENDENCE VULNERABILITY ARE SHOWN HERE THIS IS ARE THE MESSENGER RNA IN THE BRAIN THAT REFLECTS EXPRESSION OF SUBUNITS ONE CIRCUIT THAT RICH IN THE GNAW COLLIEIUS PATHWAY, AN AREA OF REAL INTEREST TO US AND OTHERS NOW, NOT NECESSARILY THE MEDIAL WHICH IS WHERE WE FOCUS ON BUT THE LATERAL CONSIDERABLE INTEREST TO THOSE INTERESTED IN DEPRESSION, AN AREA OF THE BRAIN INVOLVED IN NEGATIVE REWARD SIGNALS AND SOMETIMES CALLED DISAPPOINTMENT CENTER OF THE BRAIN. SO MEDIAL IS RIGHT BESIDE THAT AREA. AND IT'S INCREDIBLY ENRICHED IN ALPHA 5 NICOTINIC RECEPTORS YET ITS FUNCTION IS STILL UNCLEAR. BUT IMPORTANT POINT, ONE MAJOR CONVECTION CENTERS IN THE BRAIN, ONE OF THE MAJOR TWO DESCENDING PATHWAYS THAT CONNECTS WITH FOREBRAIN WITH MID BRAIN IN TERMS OF COMMUNICATING INFORMATION YET STILL DON'T KNOW WHAT TYPE OF INFORMATION IS TRANSMITTED. ANOTHER AREA OF THE BRAIN IS THE NUCLEUS SOLITARY TRACT WHICH IS INTERESTING, PEOPLE WHO ARE CONCERN ISED WHAT APPETITE REGULATION OR INFORMATION FLOW INTO THE BRAIN FROM THE PERIPHERY, THIS IS THE SIZE WHICH THE VAGUS NERVE PROVIDES INFORMATION TO THE BRAIN WHICH THEN TRANSMIT FORWARD SO IT'S IMPORTANT LOCUST BETWEEN GUT FOR EXAMPLE AND BRAIN OR OTHER VISCERAL ORGAN AND BRAIN COMMUNICATION. AND A LOT OF ALPHA 5 IN THERE SO BASED ON EXPRESSION PATTERNS WE WERE INTERESTED IN TWO CIRCUITS TO SEE IF THEY PLAY A ROLE IN REGULATING MOTIVATIONAL PROPERTIES OF NICOTINE. SO THE FIRST THING WE DID IS LOOK AT ALPHA 5 SUBUNIT KNOCK OUT MOUSE. WHAT DID IT HAVE NICOTINE TAKING PHENOTYPE AND YOU EXPECT SO BECAUSE HUMANS WITH ALLELIC VARIATION IN THE GENE SEEM TO TAKE A LOT MORE NICOTINE, THEY SMOKE MORE. WHAT WE FOUND WHICH WAS SURPRISING TO US AT THE TIME BUT NOW MAKES MORE SENSE, LOOK HERE AT THE KNOCK OUTS, THESE ARE THE SHOWN HERE IN BLACK ARE THE WILD TYPE. AND THE KNOCK OUTS SEEM TO TAKE MORE NICOTINE BUT THAT IS MOST PREVALENT OR MARKED IF YOU WILL, WHEN THIS DOSE OF NICOTINE IS AVAILABLE, .4 MG PER KB PROFUSION. YOU CAN SEE A STRIKING DIFFERENCE IN INTAKE. WHY IS THAT IMPORTANT? THIS IS CONSIDERED A MAXIMALLY REWARDING AND WE HAVE DONE THESE MANY TIMES, TENDS TO BE A HINT THAT THE ALPHA 5 KNOCK OUTS WILL TAKE MORE NICOTINE AT THE MAXIMUM AWARDING DOSE, IT'S NEVER REALLY COMING TRUE. TYPES OF 10 TO 12 PER GROUP GENERALLY THERE BUT THIS AFFECT ALWAYS IS WHICH YOU CAN SEE HOPEFULLY THE ANIMALS WILD TYPE LIKE TO USE NICOTINE AT CERTAIN DOSE BUT AS HIGHER THEY AVIED THE DRUG BECAUSE IT'S NOXIOUS, THE ALPHA 5 WILL USE NICOTINE AND DON'T RESPOND TO NOXIOUS PROPERTIES THE SAME WAY. SO THIS GENE THAT INFLUENCES TOBACCO USE IN HUMANS IS NOT INFLUENCING REWARDING PROPERTIES OF NICOTINE BUT THE DEGREE WHICH YOU ABIDE THE DRUG BECAUSE OF NOXIOUS PROPERTIES. IF WE TAKE MISSING SUBUNIT INTO AERS VIEW, PUT THAT VIRUS SPECIFICALLY BACK INTO THE PATHWAY OVER HERE SO WE RESCUE SUBUNIT EXPRESSION BUT ONLY IN THIS PART OF THE BRAIN, THE KNOCKOUT MICE TAKE A LOT OF NICOTINE WHEN HIGH DOSE AVAILABLE LOOK NORMAL. SO LOOKS LIKE ABSENT ALPHA 5 SIGNALING IN THIS PARTICULAR CIRCUIT THAT SEEMS TO DIMINISH SENSITIVITY TO THE AVERSIVE PROPERTIES OF THE DRUG AND CONSEQUENTLY USE MORE SO PRESUMABLY MORE SINCETIVE TO WANTING TO DEVELOP BONA FIDE ADDICTION. SO THAT THEN PROMPTED US TO LOOK AT OTHER CIRCUMSTANCES OF THE BRAIN RICH IN ALPHA 5 AND THE OTHER SIDE THAT HAS DENSE EXPRESSION IS THE HIND BRAIN CALLED THE NTS, THE CIRCUIT I TOLD YOU THAT'S INVOLVED IN THIS KIND OF INFORMATION FLOW FROM THE PERIPHERY INTO THE BRAIN AND THAT INFORMATION BEING STORED TO MID BRAIN PRIMARILY BY FOREBRAIN SITES SO WE LOOK TO SEE IF NICOTINE WAS EVEN ABLE TO ACTK INVESTIGATE NEURONS IN THIS PART OF THE BRAIN AND IF SO, WAS THE ACTIVATION CONTINGENT UPON EXPRESSION OF ALPHA 5 NICOTINIC RECEPTOR SUBUNIT. SO WE INJECTED WITH NICOTINE AND USED REACTIVITY AS MEASURE OF NEURAL ACTIVATION SO A QUICK DIRTY MEASURE TO SEE IF MIC TEEN IS ABLE TO ACTIVATE PART OF THE BRAIN AND IF SO WHAT IT WAS DOING. YOU CAN SEE THE LITTLE RED DOTS HERE, NICOTINE IS TURNING NEURONS ON, WE SEE LOTS OF THESE RED DOTS IN RESPONSE TO NICOTINE. BUT WHAT WE FOUND SURPRISING WAS THERE'S A MAJOR POPULATION OF NEURONS IN THIS PART OF THE BRAIN, CATECHOLAMINEERGIC NEURONS, A SOURCE OF NOREPINEPHRINE TO THE MEMBRANE, TWO THAT PROVIDE NOREPINEPHRINE TO MID BRAIN AND FOREBRAIN. NEURONS TURNED ON BY NICOTINE WERE NOT WELL KNOWN POPULATION OF CELLS, AT LEAST THOSE WORKING IN THIS PART OF THE BRAIN SO NICOTINE TURN THIS AREA ON BUT NOT THE CELLS YOU MIGHT EXPECT. SO OF COURSE YOU ARE HOPING TO SEE WHICH CELLS THEY MIGHT BE ACTING ON, AND TURN THIS UTTER INTERESTING POPULATION OF CELLS TO PRODUCE A NEURAL PEPTIDE CALLED GLC 1, WHICH IS ALSO PRODUCED IN THE GUT, IN THE BRAIN, THESE ARE THE ONLY NEURONS THAT WILL DO THAT, NICOTINE LOOKS LIKE IT'S ABLE TO TURN THOSE CELLS ON. THIS IMPORTANT, WE WANT TO MANIPULATE GLP MOTOR RECEPTOR TRANSMISSION, WE ACTIVATE RECEPTOR SIMPLY BY GIVING THE ANIMAL A DIRECT AGONIST, AND EXAMPLE OF THAT IS -- A DIRECT GLP RECEPTOR AGONIST, WE TREAT ABLE TO BLOCK THE BREAKDOWN OF THE PEPTIDE ITSELF DRUGGED CALLED -- SO EITHER ONE OF THESE BOOST RECEPTOR TRANSMISSION AND WE DID IT IN BOTH CASES DECREASED SELECTIVELY NICOTINE USE BY THE ANIMAL BUS NOT FOOD CONSUMPTION SO LOOKS LIKE A SELECTIVE REDUCTION AND MOTIVATIONAL PROPERTY OF NICOTINE. AND CONVERSELY IF WE DELETE KNOCK DOWN GLP 1 RECEPTORS IN ANIMALS, THEY USE MORE NICOTINE. SO LOOKS LIKE GLP IS PLAYING A ROLE CONTROLLING NICOTINE INTAKE, BUT I TOLD YOU GLP PRODUCE IN BRAIN, THESE ARE ALL GLOBAL MANIPULATIONS, IT SCUZZN'T SPEAK TO WHETHER THE BRAIN INVOLVED SO WE WENT THEN DIRECTLY AND MANIPULATED THE NEURONS IN THE NTS TO SEE IF THAT WOULD DO ANYTHING. WE DID THAT A COUPLE OF DIFFERENT WAY USING A COUPLE OF DIFFERENT CRE EXPRESSING MICE RECOMBINATION IN THESE GLP INURN AND TURN AN OR OFF USING CHEMOGENETICS. IF WE TURN THEM ON, ANNALS STOP USING NICOTINE. TURN THEM OFF, ANIMALS WILL USE MORE NICOTINE. SO LOOKS LIKE THIS IS AN IMPORTANT GROUP OF CELLS IN THE HIND BRAIN THAT SEEM TO BE ABLE TO CONTROL THE MOTIVATIONAL PROPERTIES OF NICOTINE AND THE DATA I WON'T SHOW YOU ALSO EXPRESS ALPHA 5 NICOTIIC RESEMITORRS. SO HUMAN -- RECEPTORS. THE HUMAN GENETICS DROVE THE TWO CIRCUITS WOULDN'T HAVE LOOK AT OTHERWISE AND THOSE TWO CIRCUITS DISAPPEARED WHICH IS GREAT. I GUESS I'M UP. THAT ME? DO I GET THE SLIDES BACK? THERE YOU GO. I GUESS WE JUMPED FORWARD A FEW SLIDES. SO I'LL TAKE IT FROM HERE. SAKE OF FILE I WON'T GO BACK. -- TIME I WON'T GO BACK. I WAS GOING TO SHOW YOU PRETTY ELECTROPHYSIOLOGY, BLAH, BLAH, BLAH, HOW IS THIS WORKING. THESE GLP NEURONS PROJECT TO THE SAME CIRCUIT I SHOWED YOU EARLIER ALPHA FIVE IS WORKING IN. SO I TOLD YOU THERE WAS A LOT OF ALPHA FIVE NICOTINIC RECEPTORS AND I SAID ALSO ALPHA 5 DOWN HERE IN THE HIND BRAIN, TURNS OUT THOSE HYPED BRAIN GLP 1 NEURONS SEND PROJECTION INTO THE HABINULA AND IPN CIRCUIT, ACTIVATE THE NEURONS THEY ENHANCE THE IPN CIRCUIT. HOPEFULLY THAT MAKES SENSE. NICOTINE ACTS IN CIRCUIT TO ALPHA 5 AND ALSO ACTS IN THE HIND BRAIN CIRCUIT THIS CIRCUIT ITSELF ACTUALLY PROJECTS THE IPN SO LOOKS LIKE THE IPN IS A KEY CIRCUIT INVOLVED IN CONTROLLING NICOTINE UNTAKE AND IF IT ACTS DIRECTLY ON ALPHA 5 OR TRUE GLP 1 IT LOOK LIKE ABLE MODIFY INTAKE AND THAT'S SHOWN HERE, SO WE KNOCKED IN THE RECEPTOR DENSELY EXPRESSED IN THIS PART OF THE BRAIN, AND IF WE KNOCK IT DOWN USING INTERFERONS ANIMALS USE NOR NICOTINE, IF WE STIMULATE USING A GLP RECEPTOR AGONIST ANIMALS, IT WAS REALLY STRIKING AFFECT, ANIMALS WENT OVER USED THE VERY FIRST INFUSION OF NICOTINE, FIRST INFUSION LIKE THAT DO, SOON AS THEY TOO TOOK THE FIRST INFUSION THEY WOULD NOT TOUCH THE LEVER AGAIN SO PERFECTLY NORMAL UNTIL THEY GET THE DRUG. IT'S SENSITIZING THIS AVERSION CIRCUIT. THE ANIMAL EXPERIENCES NICOTINE, SUPER AVERSIVE AND ACTIVELY WANTS THE DRUG. SO WHAT'S GOING ON IS THESE ARE CIRCUIT CONTAINING ALPHA 5, WHERE AS THE IPN THERE'S GLP # INPUT, SMOKE CIGARETTE STIMULATES THE RECEPTORS RELEASING THE GLUTAMATE WHICH ACTIVATES THE IPN, THAT STILLS YOU IS TO STOP SMOKING IF THIS IS NOT WORKING YOU SMOKE MORE. NICOTINE STIMULATES THE OTHER POPULATION OF CELLS THAT RELEASES G HEALTHCAREP LOCALLY THAT SEEMS TO BOOST TRANSMISSION IN THE CIRCUIT AND THAT WILL ENHANCE THAT RESPONSE EVEN MORE. SO THESE TWO PARTS OF THE BRAIN ARE ACTING IN CONCERT, NOT TO USE NICOTINE BUT TELL IT TO STOP. IF YOU DAMAGE IT GENETICALLY SO TO SPEAK IF YOU CARRY ALLELE, THAT MEANS THIS CIRCUIT ISN'T SENSITIVE, YOU USE MORE AND MORE LIKELY TO BE A SMOKER. SO RUNNING SHORT ON TIME BUT GOT INTERESTED TRYING TO UNDERSTAND HOW THE CIRCUIT MAYBE WORKING FROM A MOLECULAR PERSPECTIVE BECAUSE WE WANT TO TAKE ADVANTAGE OF IT. AS I SAID, IF WE ENHANCE ACTIVITY AT CIRCUIT BIGGEST EFFECT WE HAVE SEEN IN THE LACK IN TERMS OF NOT USING NICOTINE, GLP 1 IS AN INTERESTING TARGET THE DRUG WE USE TO MANIPULATE GLP 1 ARE IN MARKET FOR TREATMENT OF DIABETES. HOWEVER, TO GET DIABETES DRUGS INTO BRAIN AT EFFECTIVE LEVELS LIKELY IMPACT BLOOD SUGAR AND UNINTENDS CONSEQUENCES THAT ARE UNDESPIRED. SO CAN WE UNDERSTAND HOW GLP IS WORKING IN THE BRAIN, DIRECTLY MANIPULATE THAT CIRCUIT IN A MANNER THAT DOESN'T HAVE THESE COMPROMISING BLOOD SUGAR AFFECTS SO HOW DOES GLP # WORK? RECEPTORS ESSENTIALLY STEALS IF YOU WILL, INTRACELLULAR MACHINES USED FOR OTHER SIGNALING CASCADES, PRIMARILY WINT SKIINGNALLING CASCADE KNOWN IN DEVELOPMENT, IT HELPS PATTERN AND FORM THE BRAIN AND BY THE TIME OF ADULT YOU DON'T NEED WINT SIGNAL BECAUSE YOU HAVE A BRAIN. FOR GLP # IT TAPS TO THE CIRCUIT BY ACTIVATING ATYPICAL MANNER PROTEIN CALLED BETA CATENIN, ABLE THE TRANSLATE INTO THE NUCLEUS AN DIMERIZE PROTEIN. SO THIS IS WHAT HAPPENS IN PANCREATIC BETA CELL SEW WE THOUGHT MAYBE THE SAME THING HAPPENING IN THE BRAIN. SO THIS IS CONSIDERED MOST POOR COMPONENT OF WINT SIGNALING AND PANCREATIC BETA CELL IS CORE COMPONENT GLP SO WE THOUGHT TCF ALSO ACTIVE IN THE BRAIN AND WE MAY FIND NEW CIRCUITRIES WHICH GLP 1 RECEPTORS ARE WORKING AND MODIFY IT IN INTERESTING WAYS SO WE LOVE TO SEE IF TCF IN THE BRAIN, NO JUST PANCREAS BUT BRAIN. LOOK IN THE OUTER BRAIN ATLAS, DENSE EXPRESSION WHERE WE HOPE SEE IT IN THE MEDIAL -- LOOK FOR PROTEIN DOING IMMUNOSTAIN, THIS IS A MOUSE SHOWING WHERE THE CELLS ARE, THEY WERE RED. STAIN FOR TCF 7L 2 IN GREEN YOU CAN SEE BEAUTIFULLY DENSE EXPRESSION THAT OVERLAPS THE CELLS. TCF IS IN THE LABINULA WHEN CELLS ARE ACTIVE, CELLS GO BLUE, WE THOUGHT WE TREAT WITH NICOTINE AND DIFFERENT PROCEDURES TO TURN THE SIGNALING OEN, IF WE TAKE THE BRAINS AND SLICE THEM, IT'S CONSTITUTIVELY ACTENING THE -- TCF IS A CORE COMPONENT OF WINT SIGNALING CASCADE THOUGHT ESSENTIALLY INERT IN BRAIN BUT NOT IN THE HA BIN LA, TCF IS TUSHED ON AND FUNCTIONAL IN THE ADULT HA BIN LA SO THAT SUGGESTS IT'S IMPORTANT SO IN COLLABORATION WITH AARON GETS WE DEVELOPED THE KNOCK OUT RAT. WE HAD TO USE A RAT BECAUSE THE KNOCK OUT DIE SOON AFTER BIRTH, WON'T GO INTO DETAIL BUT THE RATS SURVIVE THIS EARLY EVENT THAT DRIVES THE DEATH, THEY TURN OVER TO BE PERFECTLY NORMAL LATER IN ADULTHOOD, EXCEPT WHEN NICOTINE THEY TAKEN TOES OF THE DRUG SO THE SIGNALING REALLY INCREASES NICOTINE CONSUMPTION AND IS THIS RELATED TO DISREGULATION? YES INDEED IF WE KNOCK DOWN TCF IN LA BIN LA, WE GET THE SAME AFFECT. HOW IS THIS, WORK SOMETHING IT TURNED INTO AN INTERESTING MECHANISM, WHAT TCF IS DOING IS CONTROLLING THE ACTIVITY OR FUNCTIONALITY OF NICOTINIC REACCEPT TOTORS IN THE LA BIN LA. SO RECEPTOR CURRENT HERE, IF YOU DESENSITIZE CURRENT USING FREQUENT PULSES OF NICOTINE, TURNS OFF, WILD TYPE ANIMAL NICOTINIC RECEPTOR COVERS, TCF KNOCK OUT IT DOESN'T SO SPECIFIC RELATIVELY INTERESTING MECHANISM BY WHICH TCF IS WORKING. 'S CONTROLLING RECOVERY FROM DESENSITIZATION OF NICOTINIC RECEPTORS. COUPLE MORE PIECES OF DATA, AT THE MECHANSIM BECAUSE OF COURSE WE WANT NOVEL THERAPEUTIC, HOW IS TCF WORKING SO WE TOOK THE KNOCK OUT RATS, IT'S A TRANSCRIPTION FACTOR SO WE SEQUENCED WHICH GENES ARE DISREGULATED, IN THESE ANIMALS, TURNS OUT WHEN YOU DO BIOINFORMATIC ANALYSIS THERE'S A PREPONDERANCE OF GENES THAT RECK LATE CYCLIC AMP SIGNALING SO KNOCK OUT RATS AND STIMULATE THOSE CELLS WHICH EXAMINE GLP 1 AGONIST IN WILD TYPES, NICE INCREASE IN CYCLIC AMP, THAT'S ABSENT IN KNOCK OUT RATS SO LOOK LIKE CYCLIC AMP DIMINISHED THE ABILITY TO RESPOND TO THAT PART OF THE BRAIN. RESCUE CYCLIC AMP THE NICOTINIC RECEPTORS WORK. IF WE CAN BOOST CYCLIC SIGNALING IN THE HA BIN LA, LOCALIZED PHOSPHODIE ESTERASES WE MAYBE ABLE TO DEVELOP A NOVEL SMOKE THERAPEUTIC. I'LL LEAVE YOU WITH A COUPLE OF PIECES OF DATA BECAUSE I WANT TO BE ON TIME. TCF, THIS IS NOT THE FIRST TIME IT'S BEEN LOCKED DOWN, IT'S QUITE FAMOUS BUT NOT IN ADDICTION, IN DIABETES. TCF RISK ALLELES ARE DEALLELES IN MOST ASSOCIATED WITH TYPE 2 DIABETES SO THIS IS ALMOST LIKE ALPHA 5 GENE ASSOCIATED WITH THE BACK, PCF RISK ALLELES ARE ASSOCIATED WITH TYPE 2 DIABETES. IN FACT GLP 1 RECEPTOR AGONIST, THINGS THAT BOOST IT ARE ALSO ON THE MARKET FOR TREATMENT OF DIABETES. THIS STRUCK US AS BEING PERHAPS COINCIDENCE BUT SOMETHING TO LOOK AT, ONE OR TWO DIABETES RELEVANT A GENE AND RECEPTOR IN THE HA BIN LA, IS NATURE CONSERVING AND USING SOMEWHERE ELSE OR MIGHT THEY BE INVOLVED IN REGULATING BLOOD SUGAR, THIS IS IMPORTANT BECAUSE SMOKING IS THE SECOND LEADING CAUSE OF TYPE 2 DIABETES. SO BLOOD SUGAR IN RATS AN MICE IF WE INAPOLOGETIC RATS WITH NICOTINE WE GET A HUGE SEARCH IN BLOOD SUGAR IN RESPONSE TO NICOTINE WE HAVE NEVER SEEN BEFORE, WE NEVER LOOKED. WE SEE THE DOSE IS MOST PREVALENT TO ACTIVATE THE HA BIN LA. IF ANIMALS SELF-ADMINISTER, THE DOSES FOR A LONG PERIOD OF TIME THEY BECOME DIABETIC SO NICOTINE DRIVE DIABETES IF YOU ACTIVATE THE HA BIN LA AND THAT IS QUITE MARKED. IF WE KNOCK DOWN SPECIFICALLY AND ABLATE THE HYPERGLYCEMIC EFFECT AND DIABETES INDUCING AFFECTS OF NICOTINE SO SEEMS TCF SIGNALING IS A LOCUST ABLE TO CONTROL OR LINK I GUESS THE REWARD ENHANCING OR THE ADDICTIVE PROPERTIES OF NICOTINE, IF YOU WILL, AND DIABETIC EFFECTS SO A LOCUST THAT CONTROL THESE TWO DISEASE RELEVANT ASPECTS OF NICOTINE. WHY THAT'S THE CASE WE DON KNOW. WHY SHOULD GLAD SUGAR BE REGULATE BY HA BIN LA, WE DON'T KNOW BUT SEE IF IT'S POTENTIAL ODDER GRAND A THAT CAN BE MA -- ORGAN THAT CAN BE MANIPULATED. I WOULD LIKE TO THANK EVERYBODY IN THE LAB AND OF COURSE NIH FOR THE SUPPORT. I'M SORRY FOR GOING OVER. [APPLAUSE] >> MY NAME IS SHANNON GOURLEY, COMING TO YOU FROM EMORY UNIVERSITY IN ATLANTA. WE'RE FUN FACT IT'S SNOWING NOW. MY STUDENTS HAVE BEEN EXCITEDLY REPORTING ALL DAY THAT EVERYONE IS GOING BANANAS. I MEAN OBVIOUSLY NOT THEM, THEY'RE PLAYING IT COOL. EVERYONE ELSE IS GOING NUTS. SO TODAY I WOULD LIKE TO TALK ABOUT ONE OF THE PROJECTS IN MY LAB THAT'S FUNDED BY NIDA, BUT I'M GOING TO TOUCH ON MY NIMH AWARD PROJECT AS WELL REGARDING ACTION CONSEQUENCE DECISION MAKING AND IN THIS CASE EFFECTS OF COCAINE. SO THIS PROJECT IS GENERALLY MOTIVATED BY INTEREST IN THE LONG TERM CONSEQUENCES OF COCAINE EXPOSURE. AND THIS ISSUE IS REALLY IMPORTANT BECAUSE WE KNOW FROM EPIDEMIOLOGICAL STUDIES THAT INDIVIDUAL WHOSE ARE EXPOSED TO COCAINE DURING ADOLESCENCE HAVE BAD LONG TERM OUTCOMES. AND ONE IN PARTICULAR THAT ALWAYS STICKS WITH ME IS THAT INDIVIDUALS EXPOSED TO COCAINE DURING ADOLESCENCE ARE LESS LIKELY TO SEEK TREATMENT THAN ANY POINT IN THE LIFE SPAN THAN AN INDIVIDUAL WHO WAS FIRST EXPOSED TO THE DRUG AS AN ADULT. SO COCAINE PARTICULARLY DEVELOPMENTAL COCAINE IS AFFECTING DECISION MAKING. SO WHEN WE THINK ABOUT DECISION MAKING IN MY LAB, WE THINK ABOUT THE ORBITAL PREPROBLEM TALL CORTEX, THOSE PREFRONTAL CORTEX,THE ORBITAL CORTEX IS SITTING RIGHT HERE. MUCH LIKE IT IS IN THE HUMAN. SO IT'S CALLEDDED THE ORBITAL CORTEX BECAUSE IT SITS ABOVE THE EYE ORBITS AN HELPS US CHOOSE THE BEST BEHAVIORAL STRATEGIES AMONG MANY SO IT HELPS TO PERSPECTIVELY EVALUATE THE POSSIBLE CONSEQUENCES OF OUR ACTIONS. AND HOPEFULLY CHOOSE THE BEST ACTION. P P P SO IS IT'S PROBABLY INVOLVED IN ADDICTION, IT'S APPRECIATED COCAINE CAUSES A I TROPHY OF THE ORBITAL CORTEX AND IF YOU'RE A RAT OR MOUSE AND I GIVE YOU COCAINE I CAN CAUSE LOSS OF SYNAPTIC CONTEXT WITHIN THE ORBITAL CORTEX. IF YOU'RE AD LESS ISN'T MOUSE AND I GIVE YOU COCAINE YOU SEE LOSS OF DEXTERITY IN THE NEURONS. SO WE THINK IT HA Z TO DO WITH THE ABILITY OF INDIVIDUAL WITH COCAINE TO TOGGLE BACK AND FORTH BETWEEN ACTS AND HABITS. I WILL DEFINE THAT IN A MOMENT BUT JUST TO GIVE YOU A SPOILER ALERT WHAT I'M GOING TO TRY TO DO IS UNDERSTAND THE WAYS OF THE BRAIN ALLOWS TO COORDINATE ACTIONS AND HABIT, GOING TO FOCUS ON PROTEIN CALLED BRAIN DERIVED BDNF AND HI RECEPTOR TRACK B AND TAKE WHAT WE LEARNED ABOUT THE BIOLOGY AND BLOCK HABITS INDUCED IN THIS CASE BY COCAINE EXPOSURE. SO MY LAB IS REALLY EXCITED ABOUT THIS THIS ORBITAL CORTEX BECAUSE IT'S NICELY POSITIONED IN THE BRAIN TO TALK TO OTHER STRUCTURES THAT ARE IMPORTANT FOR COMPLEX DECISION MAKING. THESE ARE GRADE TRACING STUDIES WE TRACER WITHIN THE ORBITAL CORTEX OF MOUSE AND LOOK AT AXONAL PROJECTIONS YOU CAN SEE A NICE TERMINAL PATTERN, WHOA, SORRY, MY OWN HABITS ARE GOING AWRY. YOU CAN SEE PROJECTION PATTERNS IN THE DORSAL STRIATUM AND AMYGDALA. THIS IS EXCITING BECAUSE REGIONS ARE KNOWN TO BE IMPORTANT IN HUMANS AN RODENTS IN DIRECTED BEHAVIOR VERSUS ACTION TYPE VERSUS HABIT BEHAVIOR. SO I MENTIONED THESE TERMS A COUPLE OF TIMES SO LET'S DEFINE THEM. AN ACTION GOAL DIRECTED ACTION IS WHAT IT SOUNDS LIKE, YOU CAME EXPECTATION THAT THAT BEHAVIOR WOULD BE A REAP FORCED WITH THE ACHIEVEMENT OF YOUR GOAL. THAT IS YOUR GOAL IS HOPEFULLY HEARING SOME HALFWAY DECENT TALKS. I USUALLY GET A LAUGH THERE. APPRECIATE THAT. SO BY CONTRAST, A HABIT IS A BEHAVIOR CONCEPTUALIZE AS HAVING ENGAGE SOD MANY TIMES IT BECOMES STIMULUS ELICITED, YOU OR I MIGHT DRIVE A FAMILIAR DRIVE HOME THAT IT BECOMES HABITUAL, WE ALSO ENGAGE IN HABITS WHEN WE FAIL TO LEARN NEW RESPONSE STRATEGIES STRATEGIES SO WE MIGHT REFER BACK IF WE FAIL TO LEARN A NEW BEHAVIOR IS BETTER FOR US. SO YOU CAN IMAGINE THAT IN OUR DAILY LIVES DEVELOPING HABITS CAN BE ADVANTAGEOUS, THAT U ALLOW US TO FLEE UP ATTENTIONAL RESOURCES WHEN ENGAGING IN BEHAVIOR STRATEGIES THAT HAVE BEEN SUCCESSFUL MANY TIME BEFORE, HOWEVER, MANY MODELS OF ADDICTION ARGUE THAT HABITS PLAY A MAL ADAPTIVE THE ROLE. SO FOR EXAMPLE AN INDIVIDUAL MIGHT FIRST CASUALLY USE DRUGS THEN DRUG TAKING AND DRUG SEEKING MIGHT BECOME HABITUAL AND IN SOME CASES UNDER SOME CIRCUMSTANCES ENVIRONMENTAL OR GENETIC, THAT HABITUAL DRUG USE PROCEED INTO COMPULSIVE DRUG USE. SEW I CAN ASK MY IF THEY'RE ENGAGING IN STRATEGYTOR HABIT USING CONDITIONAL CHAMBERS. THERE'S A GUY ROARING UP AGAINST THE WALL. THIS WALL HAS THREE NOSE POKE PORTS THAT HE CAN ENTER HIS NOSE IN AND IF HE ENGAGE IT IS BEHAVIOR I WOULD LIKE HE CAN BE REINFORCED WITH A FOOD PELLET SO THE PELLET LIVE HERE, DRIVERRED THROUGH THIS TUBE -- DELIVERED FOR IN THIS TUBE AND THERE'S HIM WAITING FOR THE FOOD REINFORCER. ALL THESE ARE USING FOOD REINFORCEMENT BUT WE CAN REINFORCE ANIMALS WITH DRUGS OF ABUSE. AND IN MY LAB OFTEN THAT MEANS COCAINE. SO IF WE ZOOM IN ON OUR NOSE POKE PANEL, THIS FANCY GRAPHIC IS MEANT TO REMIND ME TO TELL YOU WE TRAIN OUR ANIMAL FIRST TO PERFORM RESPONSES ON TWO NOSE POKE PORTS SO ENGAGE IN BEHAVIOR EQUALLY, ONE SCHEDULE REINFORCEMENT AN OVER COURSE OF THE WEEK CAN ACQUIRE THE SAME NUMBER OF PELLETS, ASSOCIATED WITH EACH LEFT AND RIGHT NOSE POKE RESPONSE. THEN WE WANT TO ASK THEM WHETHER THEY'RE ENGAGING IN BEHAVIOR BASED ON ACTION OUTCOME OR GOAL DIRECTED RESPONSE STRATEGYTOR HABIT. AND I CAN DO THIS USING A TASK CALLED INSTRUMENTAL CONTINGENCY DEGRADATION, THIS IS WHERE I MAKE A JOKE, THIS IS A FANCY TASK -- TERM FOR A VERY SIMPLE TASK, BUT I WAS NOT GOING THE MAKE THE JOKE BECAUSE I THINK A LOT OF YOU PROBABLY KNOW WHAT THIS IS. UNUSUAL FOR ME TOE HAVE THAT AUDIENCE SO FOR THOSE WHO DONE, INSTRUMENTAL CONTINGENCY DEGRADATION MEANS WE'RE GOING TO VIOLATE THE PREDICTIVE RELATIONSHIP BETWEEN ACTION AND OUTCOME AND ASK THE ANIMAL HOW HE OR SHE RESPONSE, THIS IS A THREE DAY PROCEDURE. WE'RE GOING TO BLOCK ONE NOSE POKE RECESS, BRING TO CONDITIONING CHAMBER AB HE CAN RESPOND LIKE ALWAYS AND THE RESPONDING IS REINFORCED. TAKE BECAME HOME TO THE COLONY, BACK IN THE NEXT DAY AND TODAY WE WILL PLAY A LITTLE TRICK ON THE MOUSE, WE BRING BACK INTO THE CONDITIONING CHAMBER AND NOW HIS RESPONSE IS NOT EXPLICITLY REINFORCED SO HE'S GOING TO BANG ON THAT NOSE POKE RECESS, HE'S GOING TO GET FREE PELLETS BUT THE PELLETS ARE UNCOUPLED FROM HIS RESPONDING SO HE CAN RESPOND NOW AND THAT PELLET COMES 15 SECONDS LATER. SO IF YOU ALLOW ME TO FOR A MINUTE, I'M A GOAL DIRECTED MOUSE, WHAT I SHOULD BE LEARNING HERE IS WAIT A MINUTE, MY NOSE POKE NO LONGER MAKES A DIFFERENCE, ANY NOSE POKE IS NOT REINFORCED. INSTEAD WHEN THIS PELLET OR PORT IS AVAILABLE I GET FREE LUNCH. SO TO ASK THE ANIMAL IF HE'S LEARNED THIS NEW CONTINGENCY WE CAN BRING BACK TO THE CONDITIONING CHAMBER FOR A BRIEF PROBE TEST CONDUCTED IN EXTINCTION AND WHEN A TYPICAL MOUSE SELF-RESPECTING MOUSE WILL DO IS DIRECT HIS RESPONSE TOWARD BEHAVIOR LIKELY REINFORCED SO IN OTHER WORDS HE WILL GENERATE MOST OF HIS NOSE POKE RESPONSES OVER HERE BECAUSE THAT RESPONSE OUT CONTINGENCY WAS INTACT BY CONTRAST WE'LL NEGLECT THE OTHER RESPONSE. SO WE CAN TRAIN MICE VERY EASILY TO GENERATE A RESPONSE PROFILE THAT LOOKS LIKE HISTOGRAM ON A SCREEN, WE CAN ALSO TRAIN MICE PRETTY EXTENSIVELY USING LOTS AND LOTS OF TRAINING AND LIKE YOU AND I MIGHT DEVELOP A HABIT THE MICE WILL DEVELOP HABITS AS WELL. THAT LOOKS LIKE IS THIS. THEY RUN INTO THE CONDITIONING CHAMBERS AND BANG ON BOTH NOSE POKE PORTS LIKE ALWAYS INSENSITIVE TO CONTINGENCY DEGRADATION. IN ADDITION TO EXTENT OF TRAINING WE CAN EXPOSE ANIMALS TO LOTS OF COCAINE, OR AMPHETAMINE AND THIS INDUCES HABIT BASED RESPONSE BIASES EVEN WHEN REINFORCER IS FOOD NOT JUST DRUG. WE CAN ABLATE THE ORBITAL CORTEX OR INACTIVATE USING INDUCIBLE TECHNIQUES AN CAUSE ANIMALS TO DEFER TO HABIT THESE BEHAVIORS AT THE RESPONSE OF GOAL DIRECTED ACTIONS SO WHEN I WAS TRAINING WITH JANE TAYLOR AT YALE I WANTED TO KNOW WHY THE ORBITAL CORTEX DO THIS. ONE OF THE POSSIBILITIES WAS THAT THIS PROTEIN CALLED BDNF WHICH IS IMPORTANT FOR NEUROPLASTICITY IN THE STRUCTURAL STABILITY OF YOUR DENDRITES, IS VERY NICELY EXPRESSED IN THE ORBITAL CORTEX AND I THOUGHT MAYBE THIS IS A KEY MECHANISM SO I GOT MY HANDS ON HOMOZYGOUS MICE OR MICE THAT WERE HOMOZYGOUS FOR PHLOX PNF GENE, BILATERALLY IN OFC AND INDEED IF I TAKE THE MICE AN TRAIN THEM TO PERFORM IN NOSE POKE RESPONSES WE CAN SEE THAT OUR KNOCK DOWN MICE LACKK BDNF WITHIN THE ORBITAL CORTEX HAVE LOWER RESPONSE RATES WHICH IS TYPICAL OF ORBITAL DAMAGE BUT THEY CAN LEARN TO NOSE POKE WHICH IS IMPORTANT. BUT WHAT WAS MORE INTERESTING TO ME OF COURSE WAS THAT WHEN MODIFY THOSE RESPONSE STRATEGIES OUR MICE WITH KNOCK DOWN COULDN'T KEEP UP SO OUR CONTROL MICE ARE GENERATING THEIR RESPONSES MOST LIKELY REINFORCED BUT ARE KNOCK DOWN MICE ARE UNAUTOMOBILE TO DO THAT. SO THEN I MOVED TO EMORY. I HAD A STUDENT INTERESTED IN FOLLOWING THIS LINE OF RESEARCH AND I ASKED HER TO REPLICATE MY FIND SO IS WE USE A DIFFERENT STRAIN OF MICE, A DIFFERENT VIRAL VECTOR, THE HANDS ARE KELSEY'S. SHE WAS ABLE TO REPLICATE FINDING. AND THAT IS OUR MICE HAVE LACK OF BDNF IF ORBITAL CORTEX UNABLE TO MODIFY BEHAVIOR WHEN ACTION OUTCOME CONTINGENCIES CHANGE SO UNABLE TO SELECT ACTS BASED ON EXPECTED OUTCOMES. LAST COUPLE OF MINUTES I WANT TO SHOW THE WORK WE HAVE BEEN DOING TO UNDERSTAND CIRCUITS AND TO UNDERSTAND WHETHER WE CAN USE WHAT WORE LEARNING BY BIOLOGY OF ACTIONS AND HABITS TO BLOCK HABITS THAT ARE MAL ADAPTIVE THE. SO KELSEY AND I HYPOTHESIZE FOR A NUMBER OF REASONS THE ORBITAL CORTEX AND ABILITY TO TALK TO THE AMYGDALA WERE IMPORTANT IN ITS ABILITY TO COORDINATE ACTIONS AND HABITS. SO FORTUNATELY FOR US THE OR BIRTHAL CORTEX AND IN PARTICULAR THE VENTRAL ORBITAL CORTEX WE CARE ABOUT, IS CHECKED BY PROJECTIONS, THE CORTEX IS TALKING TO THE LEFT AMYGDALA, THE RIGHT IS TALKING TO THE AMYGDALA. THIS ALLOWS US TO USE DISCONNECTION TRAGEDIES THIS MEANS WE CAN YEN RATE A SELECTIVE BDNF KNOCK DOWN WITH ONE HEMISPHERE OF THE ORBITAL CONTEXT AND CONTRALATERAL WE CAN INACTIVATE AMYGDALA. SO WHEN WE INACTIVATE THE AMYGDALA WHAT HAPPENS HERE IS OUR BDNF DEFURTHER CORTEX IS TRYING TO TALK TO INTACT AMYGDALA WHILE HEALTHY ORBITAL CORTEX IS TRYING TO TALK TO INACTIVATED AMYGDALA. IF THIS CIRCUIT IS ABDNF DEPENDENT AND NECESSARY FOR THE BEHAVIOR I CARE ABOUT THAT BEHAVIOR WILL BE DISRUPTED. WE ALSO HAVE MICE THAT CARRY THE REQUISITE VIRAL VECTOR CONTROLS BUT ADDITIONALLY WE CAN PLACE THE SAME DAMAGE IN ONE HEMISPHERE OF THE BRAIN AND ALLOWS US TO LEAVE ANOTHER NETWORK INTACT. WHAT HAPPEN? WE HYPOTHESIZE BDNF DEPENDENT INTERACTIONS BETWEEN CORTEX AND AMYGDALA IS IMPORTANT FOR LAYING DOWN NEW MEMORY. WE TOOK THROUGH THE PROCEDURE I JUST EXPLAINED AND THEN ON THAT DAY WHEN THEY ARE SUPPOSED TO BE LEARNING WAIT A MINUTE MY RESPONSE NO LONGER PREDICTS OUTCOME, WE PULL THEM OUT OF THE CONDITIONING CHAMBER AND CHEMOGENETICLY INACTIVATE THE BLA. BASAL LATERAL AMYGDALA. WHAT WE TRY TO DO IS DISRUPT ABILITY OF THE MICE TO LAY DOWN NEW MEMORY. SO TO TEST IF WE WERE SUCCESSFUL BRING THEM BACK TO THE CONDITIONING CHAMBER THE NEXT DAY AND WE LOOK AT THE RESPONSE PATTERNS. WHAT I HOPE YOU CAN SEE IS THAT THE CONTROL MICE AND THE IPSILATERAL GROUPS CAN REDIRECT TO SELECT RESPONSE LIKELY REINFORCED BY CONTRAST OUR MICE WITH THIS DISCONNECTION ARE UNABLE TO SELECTIVELY GENERATE THE NEW RESPONSE. AND THEY DEFER TO THESE HABIT BASED STRATEGIES. SO EVERYTHING I HAVE SHOWN YOU SO FAR HAS BEEN GENERATED USING MALE MICE BUT WE HAVE GREAT AND GREATER APPRECIATION FOR THE USE OF FEMALES IN OUR RESEARCH RECENTLY. SO WE HAVE BEGUN TO CONDUCT ALL OF OUR EXPERIMENTS IN BOTH SEXES AND WHAT YOU CAN SEE HERE IS IN OUR FEMALE MICE THE SAME PRINCIPLES HOLD TRUE. SO IF WE DISCONNECT THE ORBITAL CORTEX FROM THE AMYGDALA BDNF OUR MICE CANNOT MAKE SELECTION BASED ON CONSEQUENCES. SO I'LL SKIP OVER THE SLIDE IN THE INTEREST OF TIME. WHAT WE REALLY AT THE END OF THE DAY WHAT WE WANT TO DO IS TO APPLY THIS TO CLINICALLY RELEVANT QUESTIONS IN MY WORLD THAT MEANS DEVELOPMENTALLY RELEVANT QUESTIONS AS WELL. SO AS I MENTIONED AT THE BEGINNING OF MY TALK WE'RE INTERESTED IN THE LONG TERM CONSEQUENCES OF STRESS OR COCAINE EXPOSURE. WE'RE INTERESTED IN THE CONSEQUENCES BECAUSE WE KNOW NEUROBIOLOGICALLY COCAINE EXPOSURE DURING A BRIEF TIME EARLY IN ADOLESCENCE CAN HAVE LONG TERM CONSEQUENCES. IF WE EXPOTION ADOLESCENT MICE, DAY 31 TO 35, EARLY ADOLESCENCE IN A HUMAN. AGES 12 TO 13. IF WE EXPOSE MICE TO CONSIDERED A LOW DOSE OF COCAINE, SUBCHRONIC DOSING PROCEDURE, THEN ALLOW THEM TO GROW WITHOUT ANY MORE DRUG, WE EUTHANIZE AS ADULTS AND LOOK AT ORBITAL CORTEY SEIZE AND THE NEURONS ARE SIMPLIFIED SOD THEY HAVE SHORTER BASAL ARTERIES AND THOSE ARE SIMPLIFIED WHICH IS WHAT THAT ANALYSIS IS SHOWING YOU. WE ALSO SEE THAT IF WE ENUMERATE DENDRITIC SPINES ON THESE HARBORS WE SEE FEWER DENDRITIC SPEANS, THIS IS A DENSITY MEASUREMENT, NOT JUST DUE TO LOSS OF THE ARBOR, IT'S IN ADDITION TO THE LOSS OF THE ARBOR. WE ALSO KNOW THIS PROCEDURE, EXPOSURE PROTOCOL INDUCE HABIT BIASES IN AIT WILL HOOD SO WE'RE EXPOSING IN ADOLESCENCE AND SEEING BIASES IN ADULTHOOD. I'LL SHOW YOU WHAT THAT LOOKS LIKE. IN MY LAST SLIDE I WANT TO BLEND ALL THE STUFF I HAVE SHOWN YOU SO WHAT HAVE I SHOW YOU? BDNF KNOCK DOWN OR DEFICIENCY IN THE ORBITAL CORTEX CAN CAUSE HABIT BIASES,. SO CAN WE STIMULATE BDNF SYSTEMS WITHIN THE ORBITAL CORTEX AND TRY TO RESCUE OR REVERSE THESE COCAINE INDUCED HABITS. UNTIL RECENTLY THIS HAD BEEN A DIFFICULT QUESTION, HOWEVER THERE ARE DRUGS BEING DEVELOPED THAT CAN STIMULATE HIGH AFFINITY BDNF RECEPTOR. ONE IS CALLED THF SO I MY STUDENT LIZ WANTED TO DETERMINE WHETHER SHE COULD STIMULATE BDNF TRACK B SYSTEMS IN MICE WITH HISTORY OF COCAINE EXEXPOSURE AND QUESTIONS QUEUE ACTION CONSEQUENCE DECISION MAKING. SO FIRST AS ADOLESCENCE AND YOU CAN SEE DEVELOP HABIT BIASES IN ADULTHOOD LIKE PROMISED. SHE THEN TAKES THE MALLS THROUGH THE -- ANIMALS THROUGH THE CONTINGENCY DEGRADATION, PULLS THEM OUT ANOTHER OF THE CAME BEFORE AND GIVE IT IS TRACK THE AGONIST 78 DHF DURING THAT PERIOD NEW MEMORY AND CODING AND BRINGS BACK TO THE CHAMBERS THE NEXT DAY DRUG FREEK SHE CAN SEE SHE'S ABLE TO RESCUE THAT MEMORY. SOAR HOOK SEE THESE ARE MICE THAT ARE EXPOSED TO COCAINE, DESPITE EXPOSURE THEY ARE ABLE TO SELECT ACTIONS BASED ON ANTICIPATED CONSEQUENCES. SO SHE'S ABLE TO RESCUE DECISION MAKING ABNORMALITIES CAUSED BY COCAINE EXPOSURE. SO 78 DHF IS A NEW RELATIVELY NEW DRUG, IT'S A LITTLE BIT CONTROVERSIAL BECAUSE SOME BRAIN REGIONS YOU DON'T SEE TRACK ACTIVATION, THAT IS OCCURING IN OUR HANDS AS WELL SO I SHOW YOU LIZ INAPOLOGETICKED THE DRUGS DHS SYSTEMICALLY AND PUNCHED OUT MEDIAL PREFRONTAL CORTEX AND ORBITAL. AND TO OUR SATISFACTION WE SAW IN THE ORBITAL CORTEX WE SEE NICE ACTIVATION OF THE TRACK RECEPTOR SO FEW LIKE WE SHOULD, THAT'S REALLY IMPORTANT FOR HER MODEL. HOWEVER, INTERESTINGLY WITHIN THE MEDIAL PREFRONTAL CORTEX WHICH IS CLOSE AND SIMILAR, WE DON'T SEE ACTIVATION OF TRACK V. SO WHY THIS IS, WE DON'T KNOW. IT'S SOMETHING THAT WE'RE TRYING TO INVESTIGATE FURTHER. BUT IT MAYBE ADVANCE TAIGAS IN TERMS OF THINKING ABOUT DRUGS THAT HAVE OFF TARGET EFFECTS, MIGHT THINK ABOUT DRUGS THAT AFFECT CERTAIN BRAIN REGIONS AND NOT OTHERS. I SHOWED YOU BDNF TRACK B IS IMPORTANT IN THE ORBITAL CORTEX FOR THE MOUSE ABILITY TO SELECT ACTS BASED ON CONSEQUENCES, VIA INTERACTIONS WITH THE AMYGDALA, COCAINE WEAKENS MEMORY FOR CONSEQUENCES CAUSING HABIT BASED BEHAVIOR AND 78 DHF RESTORES ACTION CONSEQUENCE DECISION MAKING. IN A SERIES OF EXPERIMENTS THAT I DIDN'T TALK ABOUT TODAY BUT THAT WAS FUNDED BY THE BRAINS MECHANISM WE SHOWED THIS IS ALSO TRUE FOLLOWING DEVELOPMENTAL STRESS HORMONE EXPOSURE, WHICH IS SIMILAR EFFECTS WITHIN THE OR WITHAL CORTEX RELATIVE TO COCAINE. SO WE THINK A LOT OF THIS IS DUE TO EFFECTS ON DENDRITIC SPINE DENSITY AND MORPHOLOGY AS YOU CAN SEE IN A HIGH RES PICTURE THERE OUR SPINES WE CAN IMAGE IN RODENTS AND WE WILL INVESTIGATE IN THIS MODEL. I WILL STOP THERE AND THANK NIMH AND NIDA AND YOU AND MY TEAM AT EMORY. [APPLAUSE] >> SO I WOULD LIKE THE THANK THE ORGANIZE RECOGNIZER FOR A CHANCE TO TALK TODAY. I WILL SHOW YOU SOMETHING DIFFERENT TO TALK ABOUT THE ROLE OF SOCIAL STATUS IN OUR LIVES. SO ALL SOCIAL ANIMALS HAVE THESE SOCIAL HIERARCHIES WE'RE AWARE OF YOU HEARD ABOUT THEM OBLIQUELY BUT THEY'RE PRESENT IN ALL ORGANISMS. THEY'RE ESTABLISHED BY AGGRESSION, TWO GIRAFFES FIGHTING BY HITTING THE OTHER GIRAFFE IN THIS AXIS WITH THEY HEAD WHICH IS 400 POUNDS AND KNOCKING THE BREATH OUT OF THEM, QUITE A SIGHT TO SEE, MAINTAIN THE SOCIAL STATUS BY GROOMING OR -- WHY DO THESE EVOLVE? PRIMARILY BECAUSE IT REDUCES THE NUMBER OF CONFLICTS THE DOMINANCE TO RESOURCES LIKE FOOD AND FEMALES AND YOU CAN SEE SOCIAL DOMINANTS IN ALL ANIMALS HERE, DOMINANT DOG AND NON-DOMINANT DOG, PORTRAYED BY DARWIN NOT DOMINANT DOG HERE. SO SOCIAL STATUS IN HUMAN IS EVIDENT AND WIDESPREAD, IT'S RELATED TO POWER PRESTIGE WEALTH ET CETERA. AND INCOME. IT'S IMPOSSIBLE TO THINK ABOUT HUMAN SOCIETIES WITHOUT THINKING SOCIAL STATUS. IT IS EVERYWHERE AND WHETHER BECAUSE IT'S A DOT ON YOUR NAME TAG OR WHETHER IT'S SOMETHING ELSE BUT FUNDAMENTALLY IT'S PRESENT. IT'S SUMMARIZED IN HUMANS, SES BUT ALSO DEEPER THAN THAT. HERE IS AN INTERESTING FACT WE CAN SOLVE PROBLEMS BY GIVING PEOPLE OSCARS BECAUSE IF YOU WIN OS OSCAR YOU HAVE 3.6 YEARS ADDED TO YOUR LIFE. NO NIH PROGRAM TO PASS THOSE OUT WE KNOW THIS WOULDN'T WORK. WE COULDN'T JUST GIVE THEM OSCARS THEY WON THEM. BUT HOW DOES THIS INFORMATION ABOUT STATUS GET UNDER YOUR SKIN, CHANGE THE LIKELIHOOD THAT YOU WILL LIVE LONGER? BASICALLY, WE REALLY WANT TO KNOW HOW THIS HAPPENS. BUT TO DO THAT, I'M GOING TO TALK ABOUT SOCIAL STATUS AND SOCIAL SYSTEM WORKING ON FOR SOME TIME, IT'S A DRUG IN FORCE EVOLUTION AND TELL YOU ABOUT A STORY ABOUT A FISH THAT I WORK ON HOW THESE NEURAL MECHANISMS ARE REGULATED AND HOW SOCIAL STATUS GETS UNDER THE UNDER THE FIN IN CIRCUMSTANCE. HOW UNDERSTOOD BY THE BRAIN. I USE SOCIAL INTERACTIONS FOCUSED ON FOOD AND SECOND. THIS ALSO EXPLAINS WHY UNDERGRADUATES WORK IN ANY LAB BECAUSE THEY DON'T JUST STUDY THIS BUT ADMIRE THIS FISH. SINGLE MINDED ADHERENCE TO THESE GOALS. WE WANT TO BE ABLE TO ANALYZE SEVERAL ANIMALS AT ONCE BECAUSE WE THINK THAT LOOKING AT SOCIAL INTERACTIONS IS REALLY THE BASIS OF EVOLUTIONARY CHANGE, WANT TO KNOW HOW THAT WORKS. WE WANT TO MEASURE IT ALL LEVELS OF ACTIVITY, SOME EXAMPLES BEHAVIOR PHYSIOLOGY, GENE EXPRESSION SO HERE THE PLAYERS, THESE FISH CALLED (INDISCERNIBLE) HERE TWO MALES FIGHTING. WHAT DO THEY DO, WHAT DO THEY LOOK LIKE? HERE YOU CAN SEE A DOMINANT MALE, MAKE A NOTE OF THIS BACK EYE BROW TURN OFF NEURALLY AND THREATEN OTHER ANIMALS. THESE WILL PLAY A ROLE IN A MINUTE. THIS MIGHT BE A FEMALE BUT MIGHT BE A NON-TERRITORIAL MALE, NOT LUCKY ENOUGH TO HAVE THESE CASH FLOWS AN HENCE LOTS OF CONSEQUENCES FOR BEING LOW STATUS INDIVIDUAL. THEY LIVE IN AFRICA AND WHEN THE EUROPEANS WERE PILLAGING AFRICA THEY SENT SCIENTISTS TO SEE WHAT THEY COULD FIND IN THESE VARIOUS RICH AREAS. AND SCIENTISTS WERE COMPLY SIT IN WHAT THEY COULD STEAL AND SCIENTISTS WENT, SHOWN HERE WITH MAJOR ONLY RESEARCH TOOL THE DEPTH CHARGE SO HE WENT AROUND AND BLUE UP LARGE VOLUMES OF WATER, WROTE FOUR BOOKS ABOUT WHAT HE FOUND AND SO WHEN I WAS THE FIRST PERSON AFTER HIM TO GO AND STUDY HE IS ANIMALS IN THE WILD, LOTS OF PICTURES OF THESE FISH BUT THERE WAS NO REAL BEHAVIORAL DATA FROM THESE EXPERIMENTS SO WEPT THERE AND HAD TO LOOK FOR THEM AND BUILT UNDERWATER REPORT, WENT TO THIS BEAUTIFUL LAKE. MY FIRST DIVE ACTUALLY SAW A COBRA EAT A FISH UNDERWATER AND WHEN I CAME UP THERE WAS A 6-METER LONG CROCODILE 120 FEET AWAY. I'M HERE TODAY WE WERE FORTUNATE WE FOUND THEM IN THESE POOLS ON THE EDGE OF THE LAKE. SO BASICALLY GO TO THESE POOLS, I PUT BAMBOO STAKES IN IN SO YOU CAN SEE WHAT I THATK LOCK LIKE, WHERE THEY LIVE AND THEY LIVE IN THESE PITTS THEY HAVE DUG HERE AND THIS IS THE FOOD, BOTTOM FEEDERS AND WHEN THEY ARE IN THIS AREA, THE MALES HERE ARE GUARDING TERRITORY. SO EACH CIRCLE REPRESENTS DOMINANT MALE, HE'S DIGGING THE PIT AND TRYING TO KEEP FEMALES IN AND OTHER MALES OUT. HIS GOAL THERE ARE 1200 FISH IN THIS PARTICULAR POOL AND OF THEM 600 MALE 600 FEMALES SO THE MALES WHICH ARE ABOUT 540 HAVE A REAL BIG CHALLENGE THEY HAVE TO GET IN THERE AND GET SOME FOOD SO THEY PRETEND THEY'RE FEMALES, THEY SWIM IN, LET THEMSELVES BE SOLICITED BY THE MALE, LED INTO THEIR TERRITORY, THEY EAT VIGOROUSLY AND THEN THE DOMINANT MALE SAYS LET'S GO INTO MY -- AND THEY SAY I HAVE OTHER PLANS THIS AFTERNOON SO I'LL GO SOMEWHERE ELSE. THE FEMALES ARE COMPLETELY IN CHARGE THEY CAN GO AND CHOOSE THE MALE BECAUSE BEAUTIFUL COLORS OR NICE TEAR TORE, LOT OF FOOD, GOOD MOVES AND SPAWN WITH THE MALE IN HIS TERRITORY. SO THIS ALL LOOKS LIKE THIS, THIS IS A DOMINANT TERRITORIAL MALE ABOUT TO LOSE HIS DOMINANCE. THIS GUY RIGHT HERE IS BEING CHALLENGED BY THIS NON-DOMINANT MALE YOU CAN SEE THEY'RE FIGHTING BY BITING EACH OTHER HITTING EACH OTHER AND THIS IS A FIGHT THAT WAS REALLY ABOUT THIS LITTLE GUY GETTING A CHANCE TO HAVE TERRITORY. IT'S DOMINANT MALE SLOWLY LOSING, AND SO THEY THEN HAD A DECISION MADE WHICH IS NEW TERRITORY HERE, THIS GUY GETS THIS SIDE SO HE NOW HAS A SPACE TO ATTRACT FEMALES THIS IS IMPORTANT FOR HIS FUTURE YOU WILL SEE IN MINUTE. SO THEN IF WE LOOK AT THE PROBLEM, THESE MEALS -- THIS AREA IS VERY WINDY SO THERE'S NO WAY TO LAY THEIR EGGS SO THEY LAY IT IN SUBSTRATE AND FEMALE PICKS THEM UP IN THEIR MOUTH WHICH POSES A PROBLEM EVOLUTIONARILY HOW THEY FILL UP THOSE EGGS. THAT'S SOLVED NEATLY BY -- THIS IS A VIDEO CALLED FISH SEX AND VIDEOTAPE. IN WHICH SHE WILL LAY HER EGGS AND THEN PICK THEM UP IN HER MOUTH AND HE WILL THEN YOU WILL SEE -- PICK UP THE EGGS, LAY THEM, THIS IS MADE BY NATIONAL GEOGRAPHIC SO HE WILL SWIM OFF AND SHOW HIMSELF OFF, HE DOESN'T DO THAT IN THE WILD. HE KEEPS BUGGING HER BUT NOW HE'LL -- YOU'LL SEE HIM PUT HIS ANAL FIN DOWN AND SHE'LL PICK THEM UP AND FERTILIZE THE EGGS IN HER MOUTH. SHE THEN SAY HOW ABOUT LAYING MORE EGGS AND SHE SAY I DON'T THINK SO. SO SHE CARRY THESE EGGS FOR ABOUT TWO WEEKS IN HER MOUTH. AND THESE ANIMALS ARE EXTREME AGGRESSIVE IN DEFENSE OF THEIR TERRITORIES FOR REASONS IT'S WHAT GIVES THEM ACCESS TO BEING ABLE TO BASICALLY MATE. THEY'RE SO AGGRESSIVE, COMPARED TO ANY OTHER ANIMAL YOU WILL SEE THE NON-MALES ARE NOT AGGRESSIVE AT ALL AND THE DOMINANT MEALS ARE QUITE -- MALES ARE QUITE AGGRESSIVE. THESE COMPARED TO OTHER ANIMALS BABOONS OR FRUIT FLIES OR ZEBRAFISH OR THIS GUY WHO IS MORE AGGRESSIVE BUT NOT FOR THE FULL TIME ACTIVITY THAT DOMINANT TERRITORIAL MEALS DO. SO -- MALES DO. WHAT DO NONE THEY MIMIC FEMALE BEHAVIOR TO EAT AND AVOID PREDATOR AND WATCH FOR A CHANCE TO BECOME DOMINANT AND ASCEND. SO THERE'S TWO SOCIALLY REGULATED MALE TYPES, DOMINANT MALES WHO HAVE THESE TERRITORIES THIS, 17 BEHAVIORS AND NON-DOMINANT MALES WHO ARE ACTIVE IN SCHOOL. ENTIRELY UNDER SOCIAL CONTROL. SO WE DID THE FIRST EXPERIMENT WHEN I BROUGHT THEM BACK FROM AFRICA AND RAISED AS DOMINANT OR NON-DOMINANT MALES AND YOU COMPARE THE SIZE OF MATCHED BROTHERS, THIS IS A POP QUIZ, WHO GREW UP AS A DOMINANT MALE. THE FISH DON'T ANSWER ME BUT THIS IS WHAT THEY LOOK LIKE. AND IF YOU GUESS THAT WAS A NON-DOMINANT AND DOMINANT MALE YOU'RE RIGHT. NOT ONLY DO THESE GONADS BIGGER BUT FILLEDDED WITH MATURE SPERM, THIS HAS NONE AS ALL, THOUGH THE BODY SIZE ARE THE BRAIN. THE VERTEBRA BRAIN CONTROLS THE GONADS, LOOK IN THE BRAIN HOW THIS IS CONTROLLED. THE ONLY EXCEPTION IS WHITE POLITICIANS WHO END UP ANOTHER ORGAN HAS TAKEN OVER IN THIS CASE FOR REASONS THAT WE'RE NOT ENTIRELY CLEAR. SO NORMALLY THE HPG AXIS YOU ALL KNOW ABOUT, THAT IS REGULATES THE GONADS. SO THIS IS NORMALLY HAPPENS IF YOU'RE NOT A WHITE POLITICIAN. THEN YOU SEE THIS IS A PLACE WE SHOULD LOOK IN THE BRAIN. TAKES CARE OF THIS THROUGH RELEASE OF GONADOTROPIN, STICK OF PEPTIDE THESE FISH IN ALL ANIMALS LAB RACE HUMANS HAVE IN CONSERVED PEPTIDE. AND WE DISCOVERED WHEN YOU LOOK IN THE BRAIN THAT THESE NON-DOMINANT MEALS HAD CELLS THAT WERE 1/8 SIZE OF DOMINANT MALES. SAME NUMBER OF CELLS BUT ONLY FRACTION OF THE SIZE IN THESE NON-DOMINANT MALES SO THAT'S PUZZLING NEUROBIOLOGICALLY BECAUSE MOST CELL DON'T CHANGE SIDES. WE WANT TO SEE HOW MUCH IS SOCIALLY CONTROLLED SO CONVERTED DOMINANT TO NON-DOMINANT MALES, THE SAME DATA YOU SAW OF THE GONADS WHERE THIS IS NOW STOMA SIZE. AND IF YOU HAVE NON-DOMINANT MALE THEY'RE HERE, DOMINANT MALE HERE. MAKE A DON DOMINANT MALE ODOM FANTASTIC MALE NON-DOMINANT, GONADS SHRINK AND IF YOU ALLOW NON-DOMINANT BECOME DOMINANT, THE GONADS GROW AGAIN, IT'S LIKE REPEATED PUBERTY. THIS IS BASICALLY THEY CAN GO BACK AND FORTH AND IT'S ENTIRELY UNDER SOCIAL CONTROL SO THEY LOSE TERRITORIES THEY WILL SHRINK AND GROW. CHANGING THE SOCIAL STATUS CHANGING THE BRAIN AND I HAVE ONLY TOLD YOU COUPLE OF CASES, THIS IS GNRH NEURONS ARE ALSO THE GONADS AND THERE'S NUMEROUS RECEPTORS AND OTHER PARTS OF THE BRAIN THAT ARE ACTUALLY CHANGED AS WELL THIS IS ALL JUST THROUGH SOCIAL AWARENESS OF THEIR SITUATION OF THEIR OWN IS THE THUS. SO WHAT ELSE CHANGES IN THESE CELLS? INTERESTINGLY, WE ARE ABLE TO SHOW THAT THE DENDRITES CHANGE. SO SURPRISINGLY THIS IS A NEURON, THIS IS IN DOMINANT MALE AND LOW AND BEHOLD WHAT HAPPENS IS THAT THESE ARE CHANGING IN SIZE. WE WONDER WHAT WAS GOING ON, WE MADE A TRANSGENIC FISH, THIS IS BOTTOM OF FISH BRAIN AND THAT'S A TRANSGENIC PART OF THE CELLS, WE THEN RECORDED FROM THE THESE CELLS AND SHOWED THAT AS THE MEMORY BECOMES DOMINANT THEY CAN NOW PRODUCE THIS PRODUCTION OF GNRH NEEDED IN ORDER TOP BE REPRODUCTIVELY ACTIVE. SO BECOMING DOMINANT REACHES INTO THE BRAIN AND CHANGES THE SIZE OF THESE CELLS, CONNECTS WHEN DOMINANT DISCONNECT WHEN NOT SO INCREDIBLE OUTCOME OF SOCIAL STATUS. COULD CORTISOL REGULATE THIS? HERE IS AN INTERESTING CASE WE PUT ANIMALS TOGETHER, THEY'RE FOR A WHILE THEY DON'T KNOW EACH OTHER, THEY DON'T KNOW WHAT THEY'RE DOING THEN THEY DOMINANT MALE BECOME EXTREMELY HIGH IN CORTISOL AND DOMINANT MALES DROP THE CORTISOL EXTREMELY LOW SO A CLOSE FRIEND OF MINE AND COLLEAGUE, SAID THESE SHOULD HAVE LIQUID BRAIN BECAUSE IT'S SO BAD FOR THEM SO WE CLONED SEQUENCED THE RECEPTORS FOR CORTISOL AND THREE RECEPTOR TYPE ONE HAS RAY ZINC FINGER WHERE IT'S BINDING WITH CORTISOL SO WE MEASURED THE EFFICACY AND SHOWED THIS RECEPTOR IS NOT AS GOOD AS THIS LISTENING TO CORTISOL SO MEDITATE NON-DOMINANT MEALS INSERT DIFFERENT CORTISOL RECEPTOR, WHEN NON-DOMINANT THEY TURN OFF THE VOLUME TO LISTEN TO THE CORTISOL THEMSELVES SO THIS IS AN ALTERNATIVE MEDITATION UNTIL I CAN TEACH THEM HOW TO DO IT THEY USE THIS METHOD. SO WHAT DO THESE FISH ACTUALLY KNOW? ONE THING INTERESTING THAT BEHAVIOR IS CON CONTINGENT ON OTHER ANIMALS. HERE IS THE DON MA'AM MALE, WHEN HE'S IN HIS SHELTER HE CAN'T DO ANYTHING BUT WHEN HE COMES OUT HE WILL ATTACK WHOMEVER IS AROUND. THAT'S WHAT THE DOMINANT MALE DOES, INTERMEDIATE MALES NOTICE ONLY COME OUT AND ATTACK ANOTHER ANIMAL WHEN HE CAN'T SEE THEM, WHEN HE CAN'T SEE THEM THEY ACT AND THEY'RE ACTUALLY AN ATTENTION HIERARCHY SHOWS THEY'RE ATTENDING TO THE DOMINANT MALE AS YOU KNOW FROM KINDERGARTEN, CHILDREN FROM ALL KINDS OF ISSUES WHERE PEOPLE DO ATEN TV HIERARCHY BASED ON WHO IS MORE DOMINANT. SOMETHING THAT PUZZLED ME IS HOW TO DEAL WITH LARGE LIFE DECIDING WHO TO ATTACK. SO WE THEN ASKED COULD THEY INFER DOMINANCE RANK FOR OBSERVATION BECAUSE IF HE WERE SWIMMING A POOL OF 540 MALE WHOM DO YOU CHOOSE TO FIGHT? SO WE TESTED THEM TO SEE IF FOR DOMINANCE RANK HAVING THEM FIGHT SEQUENTIALLY IN CBD AND DBE OR NOT AND THEN ASK THEM COULD THEY KNOW THAT B WOULD BE D. HAVING NEVER SEEN THAT BY ITSELF. SOMETHING YOU COULD DO WHEN YOU WERE THREE, SO WE TESTED AND THEY CAN TELL B WOULD BE D NEVER HAVING SEEN THAT SO FIRST INDICATION THAT THEY CAN DO TRANSFER INFERENCE LIKE WE KNOW BIRDS AN PRIMATES AND HUMANS CAN DO. NOW TURN ON TO SOMETHING ELSE HOW DO YOU TEST WHAT HAPPENS WHEN THEY BECOME SOCIALLY DOMINANT, THIS SOCIAL ENVIRONMENT INDUCE AS PHENOTYPE AND THIS PHENOTYPE IS THEN CHANGES REPRODUCTIVE CAPACITY SO THESE HAPPEN SO WE WANTED THEM TO PERFORM WHAT I CALL A BULLYECTOMY WHICH IS TO REMOVE A DOMINANT MALE AND SEE WHAT HAPPENS AS THE NON-DOMINANT MALE ASCENDS SO HOW DOES HE CHANGE FROM NON-DOMINANT TO DOMINANT. WE HAVE A SOCIAL GROUP, THESE ANIMALS IN THE MIDDLE AND AT NIGHT COME INFRARED GOGGLE AND REMOVE THE DOMINANT MALE, NEXT DAY AT SUNRISE THIS GUY WAKES UP AND IS ALONE THERE. SO THIS IS QUITE INTERESTING TO SEE. MAYBE. THIS IS DOMINANT MALE, THIS THE NON-DOMINANT MALE HERE, GOING BACK TO HIS SHELTER TRYING TO COURT FEMALE, BRING HER BACK TO HIS SHELTER SHE IS NOT FOLLOWING HIM SO HE GOES BACK AND CLEANS UP AND MAYBE HE'S MESSIER SOMETHING AND FIGHT THROUGH THE GLASS OF ANOTHER NEIGHBOR HERE TO TRY TO LURE HER BACK AGAIN, SHE'S NOT FOLLOWING. THEY MEANWHILE LOOKING OUT THE WINDOW HOPING HE DOESN'T NOTICE THEY'RE STILL AROUND AND HE'S FIGHTING THE NEIGHBOR IS FULL TIME BULLY AS HE IS ALL TIME. SO THEN HERE IS ANIMAL THAT'S JUST THE CAMERA WENT ON JUST AS HE WOKE UP. YOU CAN SEE HE'S ACTING DIFFERENTLY. IN A MATTER OF A FEW SECONDS, HE WILL TURN ON THE EYE BAR, WE KNOW HE DOESN'T HAVE GONADS BUT WILL TRY TO COURT FEMALES FIGHT THROUGH THE WINDOW, BECOME BEHAVIORALLY ACTIVE THOUGH HE CAN'T DO ANYTHING. WHAT WAS AMAZING ABOUT THIS IS YOU CAN WATCH THE SOCIAL ASSENT, TRACK NEUROBIOLOGICALLY WHAT'S HAPPENING AND DISCOVER THAT BASICALLY IT'S UPREGULATED IN 20 MINUTES SO HERE IS A TRANSDUCTIONS OF THIS SOCIAL INFORMATION, SOCIAL OPPORTUNITY TURNING TO BEHAVIORAL CHANGE TURNING TO MOLECULAR CHANGE AND WE TRACK NUMEROUS OTHER THINGS CHANGING AS WELL. SO THE NEURAL POPULATION THAT CONTROLS THAT ARE THE VENTRAL MEDIA HYPOTHALAMUS. WON'T DESCRIBE? GREAT DETAIL BUT FINAL STORY THEY ACTUALLY HAVE TWO PATHWAYS SOCIAL ASSENT FROM NON-DOMINANT TO DOMINANCE TAKES PLACE IN TWO TIME FRAMES. IN MINUTES THEY CAN TURN ON ALL THESE COLORS, DATA DIDN'T SHOW YOU REVEALS WITH OXYTOCIN AND VASOPRESS SIN CAUSING THAT ACTION. AND THEN IN THREE OR FOUR DAY THEY REWIRE THE GNRH CELLS AND PRODUCE NEW ROBUST PHYSIOLOGY. SO WE HAVE THIS PATHWAY OF SOCIAL INFORMATION, YOU HAVE NOW DONE OXYTOCIN VASOPRESS SIN KNOCK OUTS TO TEST AND WE CAN DO THAT NOW IN THESE FISH. SO SUM VISE WITH A FEW CONCLUSIONS. STATUS THE IN THIS CASE REGULATED DIRECTLY BY AGGRESSION IS PRETTY IMPORTANT, IMPORTANT IN ALL SPECIES, IT MAYBE AMELIORATED BY NOT USING AGGRESSION DIRECTLY BUT MEASURE OF STATUS THAT YOU CAN TELL. HOW IS THIS INDO THE SKIN? ONE THING, THE BRAIN CHANGES IN REAL TIME IN THESE ANIMALS BECAUSE THEY'RE WATCHING WHAT OTHER ANIMAL ARE DOING AND ACTUALLY ABLE TO RESPOND AND PREPARE THEIR BODY TO BECOME A DOMINANT MALE IN ANTICIPATION OF CHANGING. I DIDN'T TELL YOU BUT WE HAVE SHOWN NUMEROUS REACCEPT TOKERS AND OTHER PATHWAYS ARE INK CHAIING AS WELL. -- CHANGING AS WELL. ANOTHER THING THAT'S IMPORTANT FOR US IN PARTICULAR IS THIS IS DONE THROUGH COLLECTING INFORMATION. SO WHEN YOU GO INTO A ROOM, YOU WILL LOOK AROUND YOU, KNOW WHO IS HIGH STATUS, LOW STATUS, WHO IS OLE, WHO IS YOUNG, MALE, FEMALE, COLLECT THAT INFORMATION, INTUITIVELY AND YOU MAY OR MAY NOT USE IT BUT IT IS PART OF YOUR DETERMINING WHERE YOU FIT IN THE STATUS OF THAT SITUATION. THAT TURNS OUT TO BE REALLY IMPORTANT. IN HUMANS WE KNOW SOCIAL STATUS IS PRETTY PREDOMINANT FEATURE. YOU HEARD IT IN MANY TALKS TODAY, MAJOR FEATURE IN HOW HEALTH OUTCOMES ARE DETERMINED. YOU CAN BE PLEA STATUS IN WORK BUT HIGH IN YOUR CHURCH SO WE HAVE A VARIETY OF PLACES WHERE WE HAVE STATUS DIFFERENCES, THEY'RE NOT QUITE AS OVERT, EASY TO SEE HERE, WHAT WE HAVE HERE IS WAY TO LOOK AT HOW IT WORKS AND CIRCUITS INVOLVED. HOW DOES SOCIAL INFORMATION GET TRANSDUCED INTO WAY OF UNDERSTANDING SOCIAL STATUS ITSELF. SO THEY -- WE'RE NOW DOING CUMULATIVE INFORMATION AND I THINK THAT ANIMAL PERCEPTIONS ARE ALWAYS CHANGING THE WAY FOR NEW STATUS AND THEY'RE HAVING -- WE'RE UNWILLING TO CALL THEM CONSCIOUS, I CERTAINLY WOULDN'T DO THAT BUT THEY HAVE A SOCIAL CALCULUS, THEY'RE DOING THESE THINGS WITH THE BRAIN THAT DOESN'T HAVE A CORTEX BUT DOING ESSENTIALLY ALL THE THINGS THAT WE CAN DO AND HAVE THIS BEHAVIORAL REPERTOIRE THAT'S GUIDING THEIR LIVES IN A NATURAL SETTING. SO I WANT TO THANK NIH, NINDS AND NIMH FOR SUPPORTING THE AND THE PEOPLE WHO DO THE WORK. AND I'LL BE GLAD TO TAKE QUESTIONS. I MAY HAVE HAVE A FEW SECONDS LEFT. [APPLAUSE] THANK YOU AGAIN, SORRY WE DIDN'T HAVE TIME FOR QUESTIONS, HOPEFULLY YOU GOT A CHANCE TO MEET WITH THE THREE PRESENTER, I THOUGHT THEY WERE ALL THREE EXCELLENT PRESENTATIONS ABOUT -- AND ACTUALLY WELL DESCRIBED IN TERMS OF RESEARCH FOR PEOPLE LIKE ME WHO DON'T UNDERSTAND THAT RESEARCH SO WELL SO I THOUGHT THOSE WERE ALL WELL DONE. THIS IS OUR FIRST YEAR OF ADDING AN INTRAMURAL HIGHLIGHT TO OUR RESEARCH FESTIVAL, WE'RE ONLY IN OUR SECOND YEAR SO WE CAN BE FORGIVEN FOR MESSING UP WITH FIRST YEAR AND KEEP DOING THIS MOVING FORWARD SO A NICE ASPECT TO HAVE. TO INTRODUCE OUR PRESENTER FOR THE HIGHLIGHT THIS YEAR, I'M PLEASED TO INTRODUCE DR. JOHN GALLIN, CHIEF SCIENTIFIC OFFICER FOR THE CLINICAL CENTER. YOU KNOW JOHN HAS BEEN SCIENTIFIC DIRECTOR FOR INTRAMURAL RESEARCH AT NIAID BACK IN 1985. I THINK '71? YOU WERE 12 WHEN YOU STARTED. FROM '94 TO 2017 SERVE AS DIRECTOR OF THE NIH CLINICAL CENTER AND MANY OF THE ACCOMPLISHMENTS OF THAT CLINICAL CENTER ARE RESULT OF JOHN'S EXCELLENT LEADERSHIP OVER THE YEARS SO WELCOME DR. JOHN GALLIN. [APPLAUSE] >> THANK YOU, BILL. IT'S FUN TO HAVE AN OPPORTUNITY TO CELEBRATE. AND THIS IS A GREAT OPPORTUNITY. I THINK TITLE OF TODAY'S FESTIVAL CONNECTING PEOPLE TO ADVANCE HEALTH, FITS IN WITH WHAT -- YOU WILL HEAR THE NEXT SESSION. LET ME TELL YOU A LITTLE BIT WHERE THE PROGRAM WE CALL BENCH TO BEDSIDE AWARDS CAME FROM. PERHAPS WE WILL MAYBE EXCITE SOME OF YOU TO TRY AND BECOME PARTNERS IN THIS. GOING FORWARD. SO IN 1999 WHEN I HAD BEEN DIRECTOR OF CLINICAL CENTER FOR ABOUT FIVE YEARS A LITTLE LEFT OVER MONEY AT END OF THE YEAR, I WENT TO THE THEN DIRECTOR OF NIH HAROLD VARMUS AND I SAID WE GOT A LITTLE MONEY, HOW ABOUT STARTING THIS NEW PROGRAM, DESIGNED TO BRING TOGETHER A BASIC SCIENTIST AND CLINICAL PERSON SOME NEW PROJECT MA MIGHT IMPROVE HEALTH. HE SAID GREAT, DO IT. SO WE STARTED IT, THAT WAS GREAT, THEN AFTER THE FIRST YEAR I RAN OUT OF MONEY. SO I WENT WITH A TIN CUP TO NIH OFFICE AND SAID HEY, HOW WOULD YOU LIKE TO SUPPORT THIS? AND MUCH TO MY PLEASURE AND AMAZEMENT PEOPLE SAID SURE, LET'S SEE WHAT WE CAN DO. THE OFFICE OF BEHAVIORAL AND SOCIAL SCIENCES RESEARCH FESTIVAL IS A GREAT CHAMPION OF THIS AWARD NOW FOR NINE CYCLES. AND EIGHT AWARD HAVE BEEN GIVEN OUT, OVER THE HISTORY OF THIS PROGRAM, WE HAVE GIVEN OUT $55 MILLION OF YOUR TAXPAYER DOLLARS. AND RESULTED IN GOOD PROJECTS. BUT STARTING IN 2006 WE CHANGED THE PROGRAM FROM BEING INTRAMURAL TO BEING PARTNERSHIP BETWEEN INTRAMURAL AND EXTRA MURAL. AND SINCE THEN ABOUT 93% OF THE AWARDS HAVE BEEN TRUE PARTNERSHIP. THEY'RE SMALL AWARDS, RELATIVELY. THEY STARTED AT $130,000 A YEAR FOR TWO YEARS, NOW $150,000 FOR TWO YEARS. THE IDEA IS THEY SEED A PROJECT AND HOPEFULLY THAT PROJECT WILL RESULT IN SOMETHING BIGGER AND BETTER, THERE'S A BUNCH OF PATENT, LICENSES AND WONDERFUL THINGS THAT I THINK WE'RE PROUD OF THAT HAVE COME FROM THAT. SO ONE OF THE PEOPLE WHO HAS BEEN REMARKABLY SUCCESSFUL T A KEY PARTICIPANT IS THE SPEAKER TODAY, JACK YANOVSKI, IN HIS ROLE RUNNING A KEY SECTION ON GROWTH AND OBESITY IN THE CHILD HEALTH INSTITUTE, HERE AT NIH, HAS MADE I THINK REMARKABLE CONTRIBUTIONS TO OUR UNDERSTANDING OF THE BEHAVIORAL ABNORMALITIES AND BIOCHEMICAL ABNORMALITIES IN THAT SETTING. SO JACK HAS RECEIVED I THINK TOO MANY AWARDS TO COUNT. HE'S RECEIVED THREE OR FOUR AWARDS AND THEY REALLY HAVE DONE WELL. TODAY WE WILL SHARE WITH YOU HIS RECENT WORK ON DEPRESSION, I'M SORRY LYNN RESISTANCE IN ADOLESCENT GIRLS, INTRAMURAL BENCH TO BEDSIDE INVESTIGATION. HE CHAIREDDED THE REVIEW COMMITTEE THAT REVIEWS ALL THE APPLICATIONS WHEN THEY COME IN, JACK, THANK YOU FOR WHAT YOU DO AND WELCOME. [APPLAUSE] >> THANKS FOR THE KIND INTRODUCTION. THE TITLE ON THE SLIDE HERE, DEPRESSION AND INSULIN RESISTANCE IN ADOLESCENT GIRLS AND PUT UP OUR VERY GRATEFUL FUNDER OBSSR AND THE SIGNATURE OF THE BENCH TO BEDSIDE PROGRAM THAT I FOUND ON THE INTERNET SO I HOPE THAT'S THE ONE JOHN LIKES. MY GROUP AT THE NICHD IS CALLED SECTION GROWTH AND OBESITY AND WE'RE INTERESTED IN HOW GENETICS AND ENVIRONMENT AFFECT BEHAVIOR AND PHYSIOLOGY TO IMPACT THE DEVELOPMENT OF PEDIATRIC OBESITY AND COMORBIDITY AND THE IDEA IS THAT TOGETHER FULL UNOF THESE COMPONENTS ALLOW US TO DEVELOP RATIONALE PREVENTION AND TREATMENT STRATEGIES. ONE IMPORTANT OBESITY RELATED COMORBIDITIES THIS PROJECT IS REALLY ABOUT IS DEVELOPMENT OF TYPE 2 DIABETES AND AS YOU KNOW IT'S OBESITY RELATED ILLNESS THAT CAUSES SEVERE HEALTH COMPLICATIONS SO THESE ARE DATA FROM ADULTS THAT SHOW EVEN WITHIN NORMAL RANGE BMI, AGE ADJUSTED RISK OF DEVELOPING DIABETES INCREASES DRAMATICALLY SO BY THE TIME YOU REACHED A LEVEL OF OBESITY, THERE'S A 25 FOLD INCREASE RISK OF TYPE 2 DIABETES, THAT SKYROCKETS WHEN INDIVIDUALS ARE HEAVIER SO THIS IS A CONDITION WE'RE INTERESTED IN, IN PART BECAUSE DIABETES IS TIED TO GREATER MORTALITY RATE AMONG PEOPLE IN THE UNITED STATES. A DISPROPORTIONALLY AFFECT MINORITY AS LESSENS SO AS PERCENTAGE OF DIABETES, THE PERCENT THAN AFFECT TYPE 2 DIABETES IS MARKEDLY INCREASED FORKER ETHNIC AND RACIAL MINORITY GROUPS COMPARED TO NON-HISPANIC WHITES AMERICAN INDIAN PARTICULARLY AFFECTED BUT OTHER GROUPS NON-HISPANIC BLACK ASIAN PACIFIC ISLANDERS AND HISPANIC INDIVIDUALS SO THIS IS A SERIOUS CONDITION WHICH IS NEEDS GREATER AMOUNT OF OUR ATTENTION TO TREAT. AN PREVENT. A KEY PRECURSOR OF TYPE TWO DIABETES IS INSULIN RESISTANCE. MANY OF YOU KNOW INSULIN IS SECRETED, PROMOTES UTILIZATION OF GLUCOSE BY BODY CELLS AND THE TERM INSULAR RESISTANCE MEAN TARGET TISSUES DEVELOPED DECREASED SENSITIVITY TO INSULIN ACTIONS TAKE UP LESS SUGAR IN RESPONSE TO INSULIN. IS ARE INSULIN RESISTANCE TOGETHER WITH EVENTUALLY THE DEVELOP OF INSUFFICIENT INSULIN SECRETION SUGAR TO CELLS IS THE ULTIMATE TRIGGER 2 DIABETES. THERE ARE MANY GENETIC ENVIRONMENTAL INFLUENCES IN INSULIN RESISTANCE. I HAVE SHOWN YOU OBESITY IS LINKED TO THE PRESENCE OF TYPE 2 DIABETES AND ACTUALLY THAT'S RIGHT THROUGH THE INSULIN RESISTANCE PATHWA. BUT THERE ARE OTHER CONDITIONS THAT WE FIND RELATED TO TYPE 2 DIABETES AND INSULIN RESISTANCE AND INCLUDE CHANGES IN DIET LIFESTYLE PRESENCE OF PUBERTY AND DURING PREGNANCY THESE CHANGE INSULIN RESISTANCE AND LEAD TO DEVELOP OF TYPE 2 DIABETES. IN ADDITION TO FACTORS HERE I WILL SPEND MOST TIME CONVINCING YOU THAT DEPRESSIVE SYMPTOMS ARE LINKED TO INSULIN RESISTANCE AND TYPE 2 DIABETES AND THEREFORE THIS IS AN INTERESTING AREA TO STUDY AND PERHAPS FOR THE PREVENTION OF TREATMENT OF TYPE 2 DIABETES. FIRST A LITTLE DATA FROM ADULTS. DEPRESSION IS ASSOCIATED WITH INSULIN RESISTANCE IN ADULT WOMEN EVEN AFTER ACCOUNTING FOR DEGREE OF OBESITY SO INDEPENDENT PRETICKTOR OF PRESENCE OF INSULIN RESISTANCE AND ADULT DEPRESSION PREDICT ONSET OF TYPE 2 DIABETES AGAIN AFTER ADJUSTING FOR BODY WEIGHT. ACTUALLY META ANALYSIS ADULTS DEPRESSION HAVE ABOUT 37% GREATER RISK OF DEVELOPING TYPE 2 DIABETES SO DEPRESSION SEEMS TO BE A VERY IMPORTANT RISK FACTOR FOR THE DEVELOPMENT OF TYPE 2 DIABETES IN ADULTS. NOW, WE THINK IT'S ALSO IMPORTANT TO INCREASE UNDERSTANDING OF THE DEPRESSION INSULIN RESISTANCE RELATIONSHIP IN YOUTH. FIRST, AS MANY OF YOU KNOW RATES OF DEPRESSION RISE DRAMATICALLY IN TRANSITION TO ADOLESCENCE AND OVER 20% GIRLS HAVE ONE POINT DURING ADOLESCENCE MAJOR DEPRESSIVE DISORDER DIAGNOSE. DEPRESSION OF COURSE IS ASSOCIATED WITH SIGNIFICANT IMPAIRMENT AND SERIOUS COMORBIDITY AND IF I'M TREATED ASSOCIATED WITH RECURRENT EPISODES OF DEPRESSIVE ILLNESS IN ADULTHOOD SO CLEARLY THIS IS A TIME OF SENSITIVITY CONCERN FOR THE DEVELOPMENT OF DEPRESSION AND ADOLESCENCE, IT'S ALSO INTERESTING TIME FOR THE DEVELOPMENT OF INSULIN RESISTANCE BECAUSE DURING ADOLESCENCE THE ONSET OF PUBERTY ACTUALLY INCREASES INSULIN RESISTANCE AND THEREFORE THE NORMATIVE RISE IN INSULIN RESISTANCE DURING PUBERTY INCREASES RISK FOR THE ONSET OF TUBE 2 DYE. TOGETHER WITH MY COLLEAGUES, PROFESSOR OF PSYCHOLOGY AT THE -- ACROSS THE STREET FROM US, AND LAWRENCE SHOEMAKER, WHO WAS A TO POST-DOCTORAL FELLOW WITH ME AT THE TIME WE STARTED THESE STUDIES NOW ASSISTANT PROFESSOR OF PSYCHOLOGY COLORADO STATE UNIVERSITY, TRIED TO EXAMINE THIS ISSUE IN YOUTH DEPRESSIVE SYMPTOMS CONNECTED TO INSULIN RESISTANCE IN YOUTH AND OF COURSE FOR PURPOSES OF DECIDING IF IT WAS IMPORTANT TO STUDY SEPARATE FROM OBESITY, ARE THESE RELATIONSHIPS INDEPENDENT OF BODY COMPOSITION. SO FIRST, WE EXAMINED EXTENT DATA IN OUR SECTION, FINDING THAT SYMPTOMS OF DEPRESSION IN THIS CASE BY QUESTIONNAIRE, WERE INDEED RELATED TO INSULIN RESISTANCE, IN THIS CASE ADJUSTED FOR BODY COMPOSITION AND FACTORS THAT MIGHT BE PLAUSIBLY EXPECTED TO IMPACT INSULIN RESISTANCE SO THIS POSITIVE RELATIONSHIP IS CONSISTENT WITH THE ADULT LITERATURE AND BUT THAT WASN'T ENOUGH TO SAY ASSOCIATED CROSS SECTIONALLY SO WE ASK DO CHILDREN'S PREDICT WORSENING INSULIN RESISTANCE OVER TIME, INDEPENDENT OF BODY COMPOSITION. WE USED A LONG TERM PROSPECTIVE LONGITUDINAL STUDY IN 1996, WHERE WE ACCRUED CHILDREN WHO WERE 8 TO 12 YEARS BELIEVE AT RISK FOR ADULT OBESITY BECAUSE THEY WERE ALREADY OVERWEIGHT OR OBESE OR HAD PARENTS WITH OVERWEIGHT OR OBESITY, STUDIED BASELINE FOR DEPRESSIVE MEASURED NAYSING INSULIN AND FOLLOWED 15 YEARS OF FOLLOW-UP THROUGH ADOLESCENCE INTO ADULTHOOD AND EXAMINE WHAT HAPPENS TO INSULIN RHESUS RESISTANCE. I'M GOING TO CONCENTRATE ON THE INSULIN RESISTANCE STORY. PUNCH LINE. LOOK AT THOSE WHO HAD LOWER DEGREE OF BASELINE DEPRESSIVE SYMPTOMS COMPARED TO ELEVATED BASELINE DEPRESSIVE SYSTEMS, GREATER AT FOLLOW-UP ADJUSTED FOR ALL THESE NECESSARY CO-VARIANTS. SO LOOKS LIKE PROSPECT TVLY DEPRESSIVE SYMPTOM WAS PREDICTOR OF WORSENING INSULINS RESISTANCE THROUGHOUT LONG TERM FOLLOW-UP SO MIGHT BE A LONG TERM TO EXAMINE. PART OF THE INSULIN RESISTANCE STORY, IT WAS -- FOUND GLUCOSE WAS HIGHER IN THESE CHILDREN THOSE WHO HAD HIGHER BASELINE DEPRESSIVE SYMPTOMS THAT SUGGESTS THEY WERE ON THE WAY TO DEVELOPING TYPE 2 DIABETES, THOSE WHO ARE FOLLOWING GLUCOSE LITERATURE CONSIDR VALUE OVER A HUNDRED TO BE CONSISTENT WITH IMPAIRED FASTING GLUCOSE, AND REALLY ANYTHING OVER 90 IS SIGNIFICANT IN TERMS OF GREATER PREVALENCE OF DEVELOPING IMPAIRED GLUCOSE TOLERANCE. SO THIS CROSS SECTIONAL PROSPECTIVE LONGITUDINAL ASSOCIATIONS BETWEEN DEPRESSIVE SYMPTOMS AND UNDERSTAND LINTS ARE SUSTAINS IS ALL VERY NICE, BUT THAT ALSO LEADS TO THE CONTRALATERAL HYPOTHESIS IF WORSENING SYMPTOM OF DEPRESSION ARE LEADING TO WORSENING INSULIN RESISTANCE, IT SHOULD BE THE CASE REDUCING DEPRESS RECEIVE -- TEST THE HYPOTHESIS OF HOW IMPORTANT INSULIN RESISTANCE IN DEPRESSION IS. THAT LED TO THE RANDOMIZED CONTROL TRIAL THAT WAS FUNDEDDED BY THE BENCH TO BEDSIDE PROGRAM, IN A FEW YEARS AGO. WE ASKED DOES REDUCE ELEVATED SYMPTOMS IMPROVE RESISTANCE IN ADOLESCENT GIRLS AT RISK FOR TYPE 2 DIABETES? TO ANSWER THE QUESTION WE RECRUITED SUBJECTS AT RISK FOR BOTH CONDITIONS, HIGH RISK TYPE 2 DIABETES BECAUSE OF OVERWEIGHT OR OBESITY AND CLOSE FAMILY MEMBER WHO DEVELOPED TYPE 2 DIABETES A PARENT, OR GRANDPARENT OR AUNT OR UNCLE. THEY ALSO HAD TO HAVE ELEVATED SYMPTOMS AT BASELINE, THIS CASE IT'S A SCALE SCORE IN THE MILD OR MODERATE RANGE,, I WILL TELL YOU MORE ABOUT MODERATE DEPRESSIVE SYMPTOMS BECAUSE THOSE INDIVIDUALS AS YOU SEE BETTER IMPROVEMENTS TO APPROACHES TO TREAT IT. WE EXCLUDED THOSE AT THE TIME OF EVALUATION REQUIRED ACUTE INTERVENTION LIKE MAJOR DEPRESSIVE ILLNESS OR DIABETES OR OTHER SERIOUS MEDICAL CONDITIONS. AND TO STUDY THIS QUESTION, WE RANDOMIZED TO A COGNITIVE BEHAVIORAL DEPRESSION PREVENTION PROGRAM WHICH HAD BEEN SHOWN TO HAVE LONG TERM EFFECTS IN ADOLESCENTS OR A CONTROL HEALTH EDUCATION PROGRAM DESIGNED TO BE A CONTACT CONTROL SO ALL INDIVIDUALS SEEING SAME NUMBER OF TIMES FOR SAME NUMBER OF HOURS AND WE CROSSED OVER PEOPLE WHO DELIVERED THE PROGRAMS SO WE CAN ALSO VARY BY LEADER. THEN WE KNOWED THEM ON GLUCOSE TOLERANCE TESTS. IN TERMS OF BASELINE ASSESSMENT THE GROUPS WERE COMPLETELY EQUIVALENT IN TERMS OF MANUFACTURERS. ABOUT 61 CHILDREN IN COGNITIVE BEHAVIORAL THERAPY GROUP AND SAME IN HEALTH EDUCATION GROUP. A CUP OF THE SALIENT DETAILS HERE, RISK IS MORE COMMON IN MINORITY POPULATIONS. IT'S HOYLY ENRICHED FOR THOSE WHO HAVE OBESITY DEFINE AS BMI OVER 950% -- 95% TILE. AND MAJORITY HAD MODERATELY ELEVATED DEPRESS RECEIVE SYMPTOMS SO HIGH LEVEL OF SCORES ON THIS CENTER FOR EPIDEMIOLOGICAL STUDIES DEPRESSION SCALE. IN TERMS OF FLOW WE RANDOMIZED 120 KIDS, MOST MADE THROUGH THE ENTIRE GROUP, ALMOST 90% ON BOTH GROUPS. WHAT IS INTERESTING ABOUT TREATING AD LESS ISN'TS AND EXAMINING DEPRESSION, WHEN KIDS DON'T HAVE MAJOR DEPRESSIVE ILLNESS IF YOU ENGAGE YOU IMPROVE DEPRESSIVE SYMPTOM SHORT TERM NO MATTER WHAT YOU DO, SAME ISSUE TO HELP SYMPTOMS ACUTELY SO EVERYBODY IMPROVES DEPRESSIVE SYMPTOMS DURING THE PROGRAM. THOSE WITH MODERATE DEPRESSIVE SYSTEMS TO BETTER IN THE COGNITIVE BEHAVIORAL THERAPY PROGRAM AND HEALTH ED AND IF WE LOOK OVERALL, IT'S SAME KIND OF BUT NOT SIGNIFICANT. BUT EVEN IN THE FIRST SIX WEEKS OF TREATMENT, IF WE LOOK AT THE CHANGES IN INSULIN SENSITIVITY, THOSE WHO DECREASE DEPRESSIVE SYMPTOM, ONES DOWN HERE, ACTUALLY IMPROVE THEIR INSULIN SENSITIVITY, BY CONTRAST WORSENING DID WORSE IN TERMS OF THEIR INSULIN SENSITIVITY SO PROOF OF THE IDEA OF DEPRESSIVE SYMPTOMS BUT THERE WERE -- IN INSULIN SENSITIVITY. HOWEVER, WE ALSO THOUGHT THERE MIGHT BE GREATER AFFECTS IF WE EXAMINE KIDS LATER ON AT TIME WHEN PREVENTION OF DEPRESSION PROGRAM OUGHT TO BE MORE POTENT ATIER'S FOLLOW UP WHEN THE GROUP WAS GONE. IN THIS CASE CASE SHOW MODERATELY DEPRESSED GROUP INSULIN SENSITIVITY MEASURES SO HERE IS FASTING INSULIN, THE GROUP THAT RECEIVED COGNITIVE BEHAVIORAL THERAPY HAS IMPROVEMENT IN FASTING INSULIN, THE GROUP WITH CONTROL HEALTH ED GROUP DOES WORSE. SIMILARLY FOR THE TWO HOUR INSULIN DURING GLUE DOSE TOLERANCE TEST IS IMPROVEMENT IN THE CBT GROUP, WORSENING IN THE HEALTH EDUCATION GROUP. THIS IS CONTROL FOR ALL RELEVANT VARIANT LIKE FAT MASS, ET CETERA. SO THESE SUPPORT IDEA THAT IMPROVING DEPRESSIVE SYMPTOMS IMPROVE INSULIN RESISTANCE MEASURES. GLUCOSE FOR INSULIN TOGETHER THERE'S TREEN FOR IMPROVEMENT IN -- IT'S NOT SIGNIFICANT. ARE THERE DECREASES IN DEPRESSIVE SYSTEMS IN EXPLANATORY MEDIATOR OF EFFECT ON INSULIN OUTCOMES IS A RELEVANT QUESTION. THERE'S A LOT OF THINGS HAPPENING TO AD LESS ISN'TS ADS THEY LIVE ANOTHER YEAR. IN THIS CASE WE USE MEDIATION MODELS TO EXAMINE BETWEEN CBT THROUGH CHANGE AND DEPRESSION ON INSULIN RESISTANCE. YOU CAN SEE THERE ARE SIGNIFICANT CONNECTIONS BETWEEN CBT AND CHANGES IN DEPRESSIVE SCORES AND CHANGES IN INSULIN RESISTANCE AND WE CAN SEE THIS FOR HOMOIR AND INDIRECT EFFECT SIGNIFICANCE THROUGH DEPRESSION& FOR FASTING INSULIN ALL SIGNIFICANT EFFECTS THROUGH CHANGES IN DEPRESSIVE SCORES SO PLAUSIBLE SET OF DATA SUGGESTS HOW CHANGES IN DEPRESSION HOW CBT IMPROVES VALUE. THE SECONDARY AIM WHICH IS WHAT MAKES A BENCH TO BEDSIDE PROGRAM WHAT ARE THE MEDIATORS THAT UNDERLIE DECREASES IN DEPRESSIVE SYMPTOM AND IMPROVEMENTS IN INSULIN RESISTANCE THAT WE OBSERVE. SO THEY CAN MECHANISMS REMAIN TO BE EXPLORED IN THE STUDIES THAT WERE CARRYING ON NOW, WE THINK HOW DEPRESSIVE SYMPTOMS IMPROVE INSULIN RHESUS STAINS, WE PUT A QUESTION MARK HERE, THE AMOUNT OF DEATH THAT REALLY DEMONSTRATE HOW THIS IS DONE IS LIMITED. WE THINK THAT STRESS WHICH IS REDUCED WHEN DEPRESSIVE SYMPTOM REDUCE MAY PLAY IMPORTANT ROLE AND STRESS ITSELF MAY AFFECT BEHAVIOR AND PHYSIOLOGY. IN TERMS OF BEHAVIORAL MEASURES, WE CAN CHANGE PHYSICAL ACTIVITIES, DEPRESSIVE SYMPTOMS REDUCE PHYSICAL ACTIVITY AND WE HAVE SOME DATA FINDING A LINK BETWEEN THOSE. DEPRESSIVE SYMPTOMS SEEM TO ALTER EATING BEHAVIOR, WE HAVE DATA AS WELL SUPPORTING THE NOTION THAT DEPRESSIVE SYMPTOM CHANGE HOW PEOPLE EAT IN THE LAB SETTING. WE'LL EXPLORE THOSE. IN TERMS OF PHYSIOLOGICAL MEASURE THERE'S INTERESTING DATA HOW CORTISOL AND NEUROPEPTIDE Y ALTER EATING BEHAVIOR AND MAY DIRECTLY AFFECT INSULIN RESISTANCE. THESE ARE ALL SECONDARY AIMES OF THE CLINICAL TRIAL THAT ARE STILL BEING FULLY EXPLORED SO I CAN'T SHOW YOU ANY DATA ON THAT. IN ADDITION THE GENETIC VULNERABILITY TO ALL OF THESE POTENTIALLY SHOW INTERACTIONS BUT IN SIZE OF STUDY WE CARRY OUT WE DON'T HAVE THE POWER TO LOOK AT GENETIC VARIABILITIES. LET ME STOP BY ACKNOWLEDGING IF MULTIPLE GROUPS THAT PARTICIPATED IN THIS WORK. THE DIABETES INSTITUTE, WE HAVE COLLABORATORS WHO HELP WITH BODY ASSESSMENT AND NIMH, ASSESSMENTS RELATED TO AFFECT. THE CLINICAL NUTRITION TEAM WORK CLOSE BY TO ASSESS FOOD INTAKE, RAID I DON'T GO, COLLABORATORS EXTRAMURAL, NOW OUT OF STATE, OREGON RESEARCH INSTITUTE, DEVELOP PSYCHOLOGICAL PROGRAM FOR INTERVENTION AND NVCU WHO HELPED WITH THESE PROGRAMS, PEOPLE WHO WORK WITH ME BENCH TO BEDSIDE AND OBSSR PROGRAMS. THANK YOU VERY MUCH FOR YOUR ATTENTION. [APPLAUSE] >> YOU ARE BASED ON THE RESEARCH ININ THIS AREA BUT IN REAL WORLD A LOT OF PEOPLE PROBABLY MISS DIABETES LABEL MENTALLY ILL BUT THEY'RE REALLY NOT MENTAL LITTLE I WILL, SEND THEM TO JAIL OR REHAB AND TAKE AWAY THEIR RESOURCES AND THE REAL HEALTH -- VICIOUS CYCLE AND FAMILY'S LIFE,'S ALL TAKEN APART. SO WE HAVE RESEARCH STUDY SO WE CAN RESTORE FAMILY LIFE AND SOCIETY IN GOOD HEALTH IN REAL WORLD PROBABLY NOT ACCORDING TO THE RESEARCH YOU IDENTIFY PEOPLE WHO HAVE DIABETES 2 OR WHATEVER, THE WAY THEY LABEL PEOPLE MENTALLY ILL OR DIABETES TO GIVE THEM ALL KIND OF FORCE MEDICATION AND EVENTUAL CAUSE OF DEATH AND MAYBE LABELED MENTALLY -- BUT NOT. ARE WE HAVING STUDY ALSO FROM RE STORE SOCIETY ETHICAL VALUE AND MAINTAIN PEEP FAMILY LIFE AND ACTIVITIES? >> I'M AFRAID I DON'T DO THAT KIND OF RESEARCH, NOT SURE I'M RIGHT ONE TO ANSWER THE QUESTION. YOU'RE CERTAINLY RIGHT. >> NIH MAKE THIS RESEARCH. IN PROTOCOL SENSE IN SCIENTIFIC SENSE, GOOD TO KNOW HOW CAUSE AND CONSEQUENCES. BUT REAL WORLD IS VICTIMIZE PEEP BY ALL KIND OF FALSE EXCUSES. >> THANK YOU FOR THAT COMMENT. >> KING COMMENT, CAN YOU TALK ABOUT HOW YOU FOUND YOUR EXTRAMURAL COLLABORATORS? WE HAD QUESTIONS ABOUT HOW -- >> VERY GOOD QUESTION. WHAT'S WONDERFUL ABOUT THE BENCH TO BEDSIDE PROGRAM, IS THAT THE IMPETUS FOR RESEARCH QUESTION CAN COME EITHER FROM AN INTRAMURAL INVESTIGATOR OR DIRECTLY FROM EXTRA MURAL INVESTIGATOR BUT KEY THING IS TRY TO FIND LIKE MINED PEOPLE WHO WANT TO WORK TOGETHER SO THAT'S OFTEN RESULT OF PRIOR CONVERSATION AND DISCUSSION SO I ENCOURAGE INTRAMURAL AND EXTRAMURAL PEOPLE TO SEEK OUT EACH OTHER AT MEETINGS AND OTHER VENUES TO MAKE SURE YOU COME TO FULL UNDERSTANDING WHAT IS POSSIBLE TO BE DONE AND DIFFERENT INSTITUTIONS AND WHERE THERE MIGHT BE COMMONALITY OF INTEREST THAT COULD LEAD TO THESE KIND OF DEVELOPMENTS. IN THIS CASE BECAUSE THE GROUP IS ACROSS THE STREET WE HAVE ONGOING COLLABORATION FOR VARIETY OF SORTS REGARDING PSYCH LOGICAL QUESTIONS BEHAVIORAL QUESTIONS RELATED TO OBESITY. WHEN WE UNCOVER THIS DEPRESSION CONNECT FOR US, WHICH IS NOT A PRIMARY AIM OF MY GROUP, WE THOUGHT IT WAS A PERFECT OPPORTUNITY TO WORK TOGETHER TO TRY TO DEVELOP GOOD CLINICAL PROJECT AND MAKE SOME PROGRESS THAT MIGHT HOPEFULLY HELP PEEP IN THE FUTURE. >> GREAT ANSWER, NUMBER OF PEOPLE EMAIL ME OR CALL MY UP AND SAY HEY, I HAVE THIS IDEA CAN YOU CONNECT ME WITH SOMEONE. WE DO OUR BEST TO MAKE THOSE CONNECTIONS. MY LAST COMMENT IS IF YOU NOTICE THE SYMBOL IN THE BENCH TO BEDSIDE AWARD, THERE'S A FUNNY ARROW THAT SORT OF HAD A FUNNY SHAPE TO SIGNIFY WE'RE TALK ABOUT BENCH TO BEDSIDE AND BACK. REALIZING THAT LABORATORY BENCH RESEARCH CAN LEAD TO CLINICAL OBSERVATION BUT CAN GO THE TORE WAY. WE ENCOURAGE BOTH PARTS OF THAT CYCLE. IN THIS PROGRAM. >> MOST PROJECTS GREATER VERY CLEARLY DEFINED BENCH COMPONENT THAT WOULD BE FOR INSTANCE IN ANIMAL STUDY OR EVEN MUCH MORE WAY SICK BIOLOGY. THANK YOU. >> HELLO. MY NAME IS MELISSA RIDDLE FROM NATIONAL INSTITUTE ON DENTAL AND CRANIOFACIAL RESEARCH. I HAVE THE GREAT HONOR INTRODUCING A PANEL DEER TO MY HEART WHICH IS SOCIAL FACTORS AND HEALTH. SO I KNOW THAT SOME OF YOU FEEL AS STRONG AS I DO THAT SOCIAL FACTTOR AFFECT HEALTH AND HEALTH AND HEALTH DECISIONS HAPPEN IN CONTEXT OF SOCIAL RELATIONSHIPS. SO I'M VERY EXCITED THIS IS INCLUDED IN THE PROGRAM. LIKE THE OTHER PANELS I'M GOING TO INTRODUCE ALL THREE SPEAKERS AT ONCE. AFTER THEIR PRESENTATIONS, WILL ASK EACH SPEAKER TO FIELD A FEW QUESTIONS WE'LL MOVE TO THE NEXT SPEAKER. OUR FIRST SPEAKER IS DR. MONNAT. I CHECKED AHEAD OF TIME AND FORGOT. DR. SHANNON NONGNAT IS LEARNER CHAIR OF PUBLIC HEALTH PROMOTION AND ASSOCIATE PROFESSOR OF SOCIOLOGY IN THE MAXWELL SCHOOL OF CITIZENSHIP AND PUBLIC AFFAIRS AT SYRACUSE UNIVERSITY. SHE'S ALSO A SENIOR RESEARCH ASSOCIATE IN THENT ISER FOR -- CENTER FOR POLICY RESEARCH AT SYRACUSE AND FELLOW AT THE CAR SHY SCHOOL OF PUBLIC POLICY UNIVERSITY OF NEW HAMPSHIRE. DR. NONGNAT'S RESEARCH -- MONNAT'S RESEARCH INCLUDES EPIDEMIOLOGICAL STUDIES SOCIAL PREDICTORS AND VARIATION IN OPIOID ABUSE AND WHAT SHE CALLS DISEASE Z AN DEATHS OF DESPAIR. HEALTH INSURANCE COVERAGE HEALTHCARE ACCESS AND UTILIZATION AND POLICY AFFECTS ON HEALTH AND WELL BEING. MUCH RESEARCH FOCUSES ON RURAL PEOPLE AND PLACES, PUBLISHED OVER 50 PEER REVIEWED ACADEMIC ARTICLES BOOK JOURNAL RESEARCH BRIEF AND REPORTS AND PRESENTED 90 PSYCHOPAPERS TO NATIONAL AND INTERNATIONAL ACADEMIC POLICY MAKER IN PUBLIC AUDIENCES. RESEARCH FUNDED BY PROBLEM WOOD JOHNSON FOUNDATION AND USDA NATIONAL INSTITUTE OF JUSTICE AND INSTITUTE FOR NEW ECONOMIC THINKING. SHE WAS ALSO A RECIPIENT OF AN NIMHD LOAN REPAYMENT PROGRAM AWARD. DR. MONNAT'S PRESENTATION IS TITLED OPIOID USE AN MORTALITY IN RURAL AND SMALL TOWN AMERICA. LACK FORWARD TO THAT. OUR NEXT SPEAKER IS DR. CLAIRE YANG, DEPARTMENT PROFESSOR OF SOCIOLOGY AT LINDBERGER COMPREHENSIVE CANCER SENT AND FACULTY FELLOW AT THE CAROLINA POPULATION SEPTEMBER AT THE UNIVERSITY NORTH CAROLINA ADS CHAPEL HILL. DR. YANG RECEIVED A BA IN CHINESE LANGUAGE AND LITERATURE IN 1998 FROM BEIJING UNIVERSITY, MASTER OF ARTS AND SOCIOLOGY IN 2000 FROM OHIO STATE UNIVERSITY. GO BUCK EYES. MASTERS IN STATISTICS IN 2004 AND Ph.D. IN SOCIOLOGY IN 2005 FROM DUKE UNIVERSITY. SHE STARTED HER ACADEMIC CAREER AS ASSISTANT PROFESSOR IN SOCIOLOGY DEPARTMENT, POPULATION RESEARCH CENTER AND SENT ON AGING AT THE UNIVERSITY OF CHICAGO. DR. YANG IS BIODEMOGRAPHER MEDICAL SOCIOLOGIST SOCIAL STATISTICIAN, INTERESTED IN HEALTH AGING AND QUANTITATIVE METHODOLOGY. SHE CONDUCTS DISCIPLINARY RESEARCH THAT AIMS TO LIFE COURSE PROCESS BY WHICH SOCIAL FORCES AND BIOLOGICAL FACTOR JOINTLY CONTRIBUTE TO HELP DISPARITIES AND TO UNCOVER HOW IT IS THAT EXPOSURES AND EXPERIENCES GET UNDER THE SKIN TO MANIFEST IN HEALTH DIFFERENCES. HER GENERAL APPROACHES ARE TO INTEGRATE SOCIO DEMOGRAPHIC AND BIOLOGICAL THEORIES OF DATA, TO DEVELOP NEW STATISTICAL MODELS AND METHOD FOR ANALYSIS TIME RELATED CHANGE AND CONSTRUCT MULTI-SYSTEM EXPLANATORY FRAMEWORK FOR IDENTIFYING PATHOGENIC MECHANISMS OF AGE RELATED DISEASES. SHE'S PUBLISHED EXTENSIVELY ON NEW STATISTICAL METHODOLOGIES OF COHORT ANALYSIS AND SOCIAL DIFFERENTIALS OF HEALTH AND AGING. ACROSS DISCIPLINES. SHE'S PI OF A KO 1 PROJECT FOR UNDERSTANDING SEX DIFFERENCES IN HEALTH AND LONGEVITY AND ON GOING RO1 PROJECT ON SEX DISPARITIES AND ALZHEIMERS DISEASE AND COGNITIVE DECLINE. SHE'S ALSO A ONGOING AD HEALTH WAVE 5 STUDY ON DEVELOPMENTAL ORIGIN OF ADULT HEALTH, DR. YANG'S PRESENTATION IS TITLED SOCIAL STRESS AND CHRONIC DISEASES OF AGING, NEW LIFE COURSE APPROACH, TO BIOSOCIAL LINKAGES. THEN OUR THIRD SPEAKER, IS DR. STEVEN GILMAN, CURRENTLY INVESTIGATOR AND ACT CHIEF OF THE HEALTH BEHAVIORAL BRANCH IN THE NICHD DIVISION OF INTRAMURAL POPULATION HEALTH RESEARCH. AND IS APPOINTED AS ADJUNCT PROFESSOR IN THE DEPARTMENT OF MENTAL HEALTH AT JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH. DR. GILMAN RECEIVED DOCKER TO HAVE SCIENCE DEGREE FROM HARVARD SCHOOL OF PUB LINK HEALTH AND RECEIVED POST-DOCTORAL TRAINING IN BEHAVIORAL MEDICINE AT BROWN MEDICAL SCHOOL. PRIOR TO JOINING THE INTRAMURAL RESEARCH PROGRAM DR. GILMAN SERVED ON THE FACULTY OF THE HARVARD TH CHAN SCHOOL OF PUBLIC HEALTH. DR. GILMAN IS SOCIAL EPIDEMIOLOGIST FOCUSING ON INEQUALITIES AND MAJOR MENTAL DISORDERS TRYING TO UNDERSTAND HOW THEY EMERGE AND PERSIST OVER LIFE COURSE. HIS RESEARCH SEEKS TO UNDERSTAND -- TO ADDRESS THE PROBLEM OF SOCIAL INEQUALITIES BY INVESTIGATING THE EARLY CHILDHOOD DETERMINANTS OF COMMON MENTAL DISORDERS. DR. GILMAN'S RESEARCH IS FUNDED BY THE NATIONAL INSTITUTE OF MENTAL HEALTH, INSTITUTE ON AGING AND THE CANADIAN INSTITUTE OF HEALTH RESEARCH. DR. GILMAN'S PRESENTATION IS TITLED SOCIO ECONOMIC DISADVANTAGE GESTATIONAL IMMUNE ACTIVITY AND CHILDREN'S NEUROCOGNITIVE DEVELOPMENT. SO PLEASE HELP ME IN WELCOMING OUR SPEAKERS AND FIRST DR. NONNOT. -- MON NOT. -- DR. MONNAT. >> GOOD AFTERNOON, EVERYBODY, I WOULD LIKE TO THANK OBBSSR FOR BRINGING ME HERE, VERY EXCITING, LOTS OF BRAIN STIMULATION GOING ON ESPECIALLY AFTER THE LAST GROUP OF PRESENTATIONS REALLY ABOUT NEURONS AND THESE INDIVIDUALIZED BRAIN CELLS. I'M ABOUT TO TAKE US AS FAR FROM THAT AS POSSIBLE. MY PRESENTATION IS MUCH MORE MACRO LEVEL FOCUS AS SOCIOLOGIST AND DEMOGRAPHER. AND I HAVE THREE GOALS WITH THIS PRESENTATION. THE FIRST GOAL IS RELATED TO WHY THE TITLE IS DIFFERENT THAN WHAT'S IN YOUR PROGRAM. MY FIRST GOAL IS TO CAUTION AGAINST FOCUS OR OVERFOCUS OR OBSESSION WITH OPIOIDS AT THE RISK OF IGNORING RELATED BEHAVIORAL HEALTH OUTCOMESES THAT HAVE CONNECTIONS AS WELL TO DISPAIR. OPIOIDSES ARE HERE IN OUR FACE EVER DAY, THE CURRENT CANARY CRY IN THE COLE MINE BUT REFLECTIVE OF MUCH LARGER ISSUES AND PROBLEMS. I'M GOING TO GET TO THOSE. THE SECOND GOAL IS TO DISPEL THE MYTH THAT RURAL AREAS ARE ALL BEING HEAVILY AFFECTED BY THE OPIOID EPIDEMIC AND THAT RURAL IS SOMEHOW MONOLITHIC. THIRD GOAL TO MOVE FOCUS ON OPIOID ISSUE BEYOND ONE THAT IS ON THE INDIVIDUAL TO ONE THAT IS PLACE BASED AND CONTEXTUAL SO THAT'S IN REFERENCE BOTH OPIOID EPIDEMIC AND DEPTH OF DESPAIR MORE BROADLY. SO I WILL GIVE A BACKGROUND OF THE GEOGRAPHIC CONTEXT OF THE OPIOID EPIDEMC DRUGS MORE BROADLY AND THEN ALCOHOL AND SUICIDE ADS WELL AND DISCUSS THE UPSTREAM DRIVERS AS I SEE THEM IN MY RESEARCH, THE WAY UPSTREAM DRIVERS OF THE GEOGRAPHIC PATTERNS WE'RE SEEING. SO THIS SHOWS A MAP OF DRUG RELATED MORTALITY RATES AT THE COUNTY LEVEL. THE ORANGE AND RED WITH COUNTIES WITH HIGHER DRUG MORTALITY RATES AND BLUE ARE COUNTIES WITH THE LOWEST. SO THEN USING THIS TERM LANDSCAPES OF DISPAIR A LOT DURING MY PRESENTATION REFLECT THE IDEA THERE'S SIGNIFICANT SPATIAL VARIATION IN THIS DRUG PROBLEM BUT ALSO A LOT OF SPATIAL CLUSTERING. BUT THE OVERDOSE CRISIS IS NOT HAPPENING BY ITS OWN, THERE'S SIMILAR CLUSTERING AT ALCOHOL RELATED DEATH AND WHEN YOU LOOK AT SUICIDE THAT ARE CAUSED BY THINGS OTHER THAN DRUGS. WHEN WE LOOK AT THIS MAP WHAT I SEE AND SHOW YOU WITH THE DATA IS THESE ARE LARGELY PLACES THE RED PLACES ARE LARGELY PLACES OF EXPERIENCE SIGNIFICANT ECONOMIC DECLINE AND GOING THROUGH A LOT OF ECONOMIC DISTRESS AS WELL AS DECLINE IN SOCIAL CONDITIONS AND FAMILY CONDITIONS. ULTIMATELY I THINK THE OPIOID PROBLEM IS WE'RE EXPERIENCING IT NOW IS A 30 TO 40 YEAR BUILDING PROBLEM. WHAT WE SEE ON THE MANIFESTATION OF SOCIAL CONDITIONS THAT HAVE BEEN PRESENT FOR SEVERAL DECADES. IS THIS A RURAL PROBLEM? ON THE ONE HAND YOU CAN MAKE THE CASE THAT YES, THE STATES WITH THE HIGHEST DRUG OVERDOSE MORTALITY RATES ARE VERY RURAL. WEST VIRGINIA, NEW HAMPSHIRE, KENTUCKY. ON THE OTHER HAND, THE STATES WITH THE THREE LOWEST DRUGS OVERDOSE MORTALITY RATES ARE ALSO RURAL. NORTH DAKOTA SOUTH DAKOTA AND NEBRASKA. YOU SEE DICHOTOMY BIFURCATION BETWEEN RURAL AREAS EXPERIENCING HIGH RATES DRUG OVERDOSE AND RURAL AREAS NOT AS HEAVILY AFFECTED BY THE PROBLEM. THIS IS A MAP OF DRUG OVERDOSE MORTALITY RATES ACROSS RACIAL GROUPS, ALL COMBINED. BUT I CAN TELL YOU THAT WHEN I DRAW OUT JUST NON-HISPANIC WHITES AND MAP OVER DOSE DEATH AMONG THEM, SPATIAL TRENDS LOOK NEARLY IDENTICAL. THAT BIG RED BLOB IN OKLAHOMA WAS DUE TO AMERICAN INDIAN DEATH. THEY'RE DUE TO WHITE DEATH. SO WHEN I BREAK THIS DOWN TO JUST LOOK AT WHITES YOU WILL SEE A SIMILAR DEMOGRAPHIC PATTERN GOING ON. SO USING THIS DATA YOU CAN COMPARE PAST YEAR PRESCRIPTION OPIOID MISUSE ACROSS LARGE METRO MALL METRO AND RURAL AREAS. THAT'S ONE OF THE CHALLENGES WITH USING CURRENTLY PUBLICLY AVAILABLE SECONDARY DATA TO DO NATIONAL ANALYSES, IS THAT YOU END UP HAVING TO COLLAPSE ALL RURAL PEOPLE TO ONE CATEGORY WHEN WE KNOW THAT RURAL VARIES QUITE DRAMATICALLY SO WHEN YOU DO THIS AND YOU COMPARE PAST YAR PRESCRIPTION OPIOID MISUSE ACROSS THESE GROUPS YOU SEE THEY'RE COMPARABLE, PRETTY SIMILAR, THEY'RE NOT MASSIVE DIFFERENCES IN PRESCRIPTION OPIOID MISUSE ACROSS CATEGORIES METROPOLITAN STATUS, THE CASE FOR YOUNG ADULTS AND OLDER ADULTS. HEROIN USE IS SO LOW PREVALENCE SO LOW THE TREND LINES FOR THOSE LOOK COMPARABLE AS WELL. I JUST DIDN'T INCLUDE THEM. SO NOW WHEN WE ARE ABLE TO DRILL DOWN INTO FINER GRAINED URBAN RURAL CATEGORIES WE START TO SEE PRONOUNCED DIFFERENCES IN MORTALITY RATES THAT ARE MASSED WHEN WE LOOK METRO AND NON-METRO DICHOTOMY, YOU SEE DRUG MORTALITY RATES WERE HIGHEST IN THE LARGE CENTRAL METRO AREAS BUT BY MID 2000s THAT TREND REVERSED. AND LARGE CENTRAL METRO AREAS THOUGH CONTINUE TO HAVE HIGHER DRUG OVERDOSE RATES THAN THEY DID IN THE EARLY 2000s, THEY NOW HAVE LOWEST DRUG OVERDOSE RATES OF ALL DIFFERENT METROPOLITAN STATUS CATEGORIES. YOU CAN ALSO SEE IF THE YOU LOOK AT THE GREEN LINES AND THE BLUE LINES, THE GREEN ARE NON-METRO, BLUE ARE SMALL MEDIUM METRO, THAT DRUG OVERDOSE MORTALITY RATES ARE COMPARABLE ACROSS NON-METRO AREAS AND SMALL AND MEDIUM METRO AREAS SO IT'S THE LARGEST METROPOLITAN AREAS THAT SEEM TO NOT INCREASE AS MUCH AS OTHER PLACES. BUT THAT EVEN STILL WHEN YOU BRAKE DOWN LIKE THAT DOESN'T COME CLOSE TO TELLING THE WHOLE STORE I ARE ABOUT THE GEOGRAPHIC DISTRIBUTION OF THIS. SO NOW WHEN YOU COMPARE COUNTY MEAN DRUG MORTALITY RATES, ACROSS THE USDA DIFFERENT ECONOMIC RESOURCE DEPENDENCY CATEGORIES, WHAT YOU SEE IS THAT DRUG OVERDOSE RATES ARE INCREDIBLY HIGH AND MINING DEPENDENT RURAL COUNTIES BUT LOW IN FARMING DEPENDENT RURAL COUNTIES. WHAT THIS MEANS IS WITHIN RURAL DIFFERENCES IN THE OPIOID PROBLEM SPECIFICALLY IN THE DRUG PROBLEM MORE GENERALLY, WITHIN RURAL DIFFERENCES ARE ACTUALLY LARGER THAN RURAL URBAN DIFFERENCES ARE. SO THERE'S DRAMATIC VARIATION AGAIN RURAL IS NOT MONTHLITHIC AND TREATING IT AS THOUGH IT IS, RESOURCES DISTRIBUTED INEFFICIENTLY AND INEFFECTIVELY. NONETHELESS GIVEN DATA CHALLENGES SOMETIMES WE HAVE TO USE THESE LARGE BINARY CATEGORY GROUPS, THAT'S ALL WE HAVE SO HERE COMPARING THE CONTRIBUTORS F PRESCRIPTION OPIOIDS, HEROIN, SYNTHETIC OPIOIDS WHICH ARE FENTANOL AND BENZODIAZEPINES THEIR CONTRIBUTION TO ALL DRUG RELATED DEATH AND NON-METRO AND METRO AREAS. WHAT WE SEE HERE ARE THAT PRESCRIPTION OPIOIDS ARE CONTRIBUTING TO A LARGER PERCENTAGE OF DRUG RELATED DEATH IN RURAL AREAS HER LOW NGUYEN IS CONTRIBUTE -- HEROIN IS CONTRIBUTING TO >> LARPER DEATHS IN URBAN AREAS. FENTANOL IS SURGED TO LARGER CONTRIBUTOR TO DRUG RELATED DEATH. IF WE HAD DATA FROM 2016 AND 2017 FENTANOL WOULD HAVE TAKEN OVER PRESCRIPTION OPIOIDS AT LEAST IN METROPOLITAN AREAS. WE ALSO HAVE TO REMEMBER THAT MANY TIMES DRUGS ARE NOT IDENTIFIED ON THE DEATH CERTIFICATE, SO A DRUG RELATED DEATH MIGHT BE CODED ADS DRUG RELATED DEATH BUT MEDICAL EXAMINER DOESN'T IDENTIFY WHAT TYPE OF DRUG WAS INVOLVED SO THERE'S RESEARCH SUGGESTING THAT OPIOID DEATHS MIGHT BE UNDERCOUNTED BECAUSE NOT SHOWING UP ON MEDICAL EXAMINER CERTIFICATE. AS I SAID FROM THE BEGINNING THE STORY FOR ME IS MORE THAN OPIOIDS AND MORE ABOUT DRUGS IN GENERAL. EVEN THOUGH IT'S BEEN THE DRUG OVERDOSE RATES INCREASE THE MOST, ALCOHOL RELATED DEATH HAVE ALSO INCREASED AS HAVE SUICIDES FROM CAUSES OTHER THAN ALCOHOL. SO WE CAN'T LOSE OTHER THAN DRUGS. SO WE CAN'T LOSE SIGHT OF THOSE OTHER MORTALITY RATES INCREASING ESPECIALLY WITHIN THE CONTEXT WITHIN WHICH OTHER MAJOR CAUSES OF DEATH HAVE DECLINED. ACROSS MOST POPULATION GROUPS, IT'S STRIKING THAT THESE THREE HAVE INCREASED WHILE OTHER MAJOR CAUSES OF DEATH DECLINED. IN ADDITION TO THAT, IT'S REALLY HARD TO DISENTANGLE WHICH DEATHS ARE SPECIFICALLY DRUG RELATED OR ALCOHOL RELATED OR SUICIDE, WE KNOW FROM PAST RESEARCH THAT VERY LARGE PERCENTAGE OF SUICIDE HAVE ALCOHOL INVOLVED AT THE TIME WITH THE PERSON HAVING JUST CONSUMED ALCOHOL OR EVEN BEING INTOXICATED. AND A LARGE NUMBER OF DRUG RELATED DEATHS, ACCIDENTAL DRUG OVERDOSES INVOLVE ALCOHOL AS WELL SO THERE'S COMORBIDITY IN USE OF THESE SUBSTANCES, FOCUSING ON ONLY OPIOIDS MASKS THAT MORBIDITY AND SUGGESTS ALL WE HAVE TO DO IS SOLVE THE OPIOID PROBLEM THEN FIX MORTALITY AND MENTAL HEALTH PROBLEMS THAT GO WITH IT. COUNTLESS TIMES I HEARD THAT ADDICTION DOES NOT DISCRIMINATE. I HEAR AT LEAST ON A WEEKLY BASIS. THAT'S TECHNICALLY TRUE. BUT THE REPETITION OF THAT PHRASE MASK IT IS REALITY THAT NOT ONLY ARE MORTALITY RATES DRUG MORTALITY RATES FAR DIFFERENT ACROSS DIFFERENT DEMOGRAPHIC GROUPS, BUT THEY'RE ALSO DIFFERENT ACROSS DIFFERENT GEOGRAPHIC LOCATIONS. SO WHAT THIS SHOWS ARE AGE ADJUSTED DRUG INDUCED ALCOHOL INDUCED SUICIDE MORTALITY RATES. BY SEX AND RACE FOR NON-HISPANIC BLACK AND WHITE AND HISPANIC. WHAT YOU SEE IS THAT RATES INCREASE THE MOST AMONG WHITES, FASCINATING THAT THEY DECREASED AMONG NON-HISPANIC BLACKS. YOU DON'T SEE THESE TRENDS WHERE DISEASE INCREASES AMONG WHITES BUT DECLINES AMONG VULNERABLE GROUP LIKE NON-HISPANIC BLACK MEN. POINT OUT AMERICAN INDIANS ARE NOT ON HERE, THEY HAVE THE HIGHEST ALCOHOL AND SUICIDE RELATED MORTALITY RATES. SO WHEN I INITIALLY PUT THEM ON THIS CHART FOR THIS REPORT THAT I DID, THE CHART WENT OFF THE ENDS IT WAS SO HIGH. SO REALLY MINIMIZE OTHER GROUP DIFFERENCES IF YOU INCOLLIDE INDIANS ON THIS CHART. QUESTION IS WHAT THE HECK IS GOING ON WITH WHITES? WHAT'S THE DEAL WITH WHITES THESE DAYS? THIS IS MOSTLY I SHOULD SAY BEING DRIVEN BY WHITES WITHOUT A FOUR YEAR COLLEGE DEGREE. WHAT I THINK IS GOING ON IS REFERENCE GROUP THEORY AND GROUPS WE COMPARE OURSELVES AND WE TENDMENT COMPARE OURSELVES TO OUR PARENTS AND GRANDPARENTS, GENERATION BEFORE US TO ASELL HOW WELL WE'RE DOING. KNOP HISPANIC WHITES WITHOUT A FOUR YEAR COLLEGE DEGREE FEEL LIKE THINGS ARE WORSE NOW. THAN THEY WERE 20 OR 30 YEARS AGO. THE PEW RESEARCH CENTER DOES A SURVEY ASKING PEOPLE ABOUT HOW THEY THINK THEIR LIVES ARE GOING COMPARED TO PARENTS' GENERATION AND WHAT THEY FOUND IS AMONG THOSE WITHOUT A FOUR YEAR COLLEGE DEGREE, NON-HISPANIC WHITES NOT ONLY HAVE VERY LOW OPTIMISM OR SAY THEY'RE DOING BETTER THAN THEIR PARENTS, BUT THAN OTHER RACIAL GROUPS BUT THOSE LINES HAVE BEEN TRENDING DOWNWARD. SO THE REPORT ARGUES THERE IS NO GROUP OF AMERICAN WHOSE ARE MORE PESSIMISTIC THAN NON-HISPANIC WHITES WITHOUT A FOUR YEAR COLLEGE DEGREE. GETS AT THAT DESPAIR IDEA. THERE'S SOMETHING TO DO WITH THAT INDIVIDUALISM PARADIGM THAT DR. PEREZ-STABLE TALKED ABOUT EARLIER, THAT NON-HISPANIC WHITES EMBRACE INDIVIDUALISM RATHER THAN COLLECTIVITY AND THAT'S NOT USEFUL WHEN THINGS ARE GOING WRONG IN YOUR LIFE. SO NOW WE'RE WELL VERSED IN THIS PART OF THE OPIOID STORY, THIS IS NOT WHERE I'LL SPEND MY TIME, THIS IS THE FIFTH VITAL SIGN, DRUG COMPANIES MISLEADING PHYSICIANS THE HEAVY MARKET PRACTICES PILL MILLS, YOU HAVE SEEN PRESENTATIONS ON THIS STORY COUNTLESS TIMES. THE STAGE IS SET FOR A WHILE TO MAKE US VULNERABLE TO DRUG LIKE OPIOIDS, WE LIKELY WOULD HAVE SEEN INCREASE IN SUICIDE DEATH AND ALCOHOL DEATH EVEN WITHOUT THE EMERGENCE OF OPIOIDS. OF COURSE, WIDESPREAD DRUG AVAILABILITY ESPECIALLY THE WIDESPREAD EMERGENCE OF THE POWERFUL AND POTENT OXYCONTIN WAS REALLY THE SPARK THAT STARTED THE FIRE WE'RE TALKING ABOUT NOW. BUT YOU CAN'T START A FIRE WITH A SPARK, YOU NEED KINDLING. SO OPIOIDS HAVE BEEN GETTING A LOT OF ATTENTION. THAT'S OTHER DRUGS LIKE BENZODIAZEPINE IS INCREASING DEATHS BY ALCOHOL AND DEATHS BY DRUGS IS INCREASING SO OPIOIDS CAN'T BE THE ONLY ANSWER. DRUGS ALCOHOL SUICIDE, THEY'RE NOT A RANDOM COLLECTION, THOSE TYPES OF DEATH DERIVE FROM DEPRESSION AND HOPELESSNESS, CHRONIC PAIN, ESPECIALLY STRIKING IS THREE THREE CAUSES OF DEATH INCREASE DURING PERIODS OF DECLINING MORTALITY FROM OTHER CAUSES SO WHILE OPIOIDS HAVE BEEN THE SPARK, I SUGGEST THAT SOCIAL AND ECONOMIC FACTORS BUILDING THE PAST THREE OR FOUR DECADES ARE THE UNDERLYING KINDLING. SO WE SAW THIS MAP IN THE BEGINNING IN THESE CLEAR SPATIAL PATTERNS WHERE HIGHER RATES, THIS MAP SHOWS CHANGE IN ECONOMIC DISTRESS, MEASURED WITH THE VARIETY OF INDICATORS THAT A PHARMA COMMON CONSTRUCT OF STRESS, PRIME AGE NOT WORKING RATE, MEDIAN HOUSEHOLD IN THE COUNTY RELATED TO THE STATE. PUBLIC ASSISTANCE HOUSING CHALLENGES SO THE RED COUNTIES ARE COUNTIES THAT ARE DOING MUCH WORSE ECONOMICALLY NOW, THAN THEY WERE DOING IN 2000. THESE COUNTIES EXPERIENCE ECONOMIC DECLINE SINCE 2000. IF I SHOW YOU IN MAP I CAN GO BACK TO 1980 AND SHOW YOU SAME PLACES ON THIS MAP NOW IS IN THE MAP SHOWED ECONOMIC DECLINE SINCE 1980. SO THESE ARE PLACES LIKE INDUSTRIAL MIDWEST THAT EXPERIENCE SIGNIFICANT DECLINES IN MANUFACTURING OR NEW ENGLAND THAT IS EXPERIENCED DECLINES IN THE PAPER MILL INDUSTRY AND LOGGING INDUSTRY. AND NORTHWEST WHERE THERE ARE ALSO DECLINE IN LOGGING AND MANUFACTURING. SO THERE'S TREMENDOUS OVERLAP STATISTICALLY BETWEEN THESE TWO MAPS. I WILL SHOW YOU WHAT THOSE PREDICTOR OR INDICATORS OF ECONOMIC DISTRESS LOOK LIKE IN RELATIONSHIP TO DRUG ALCOHOL AND SUICIDE MORTALITY RATES. SO WHAT THIS SHOWS THESE BARS, MEAN COUNTY LEVEL DRUG ALCOHOL SUICIDE MORTALITY RATE. FOR COUNTIES IN LOWEST QUARTILE DOING THE BEST ON THAT PARTICULAR ECONOMIC INDICATOR, COMPARED COUNTIES DOING THE WORSE, THEY'RE IN THE TOP 25th PERCENTILE ECONOMIC INDICATOR. FOR EXAMPLE THE POVERTY RATE, COUNTIES IN THE LOWEST QUARTILE POVERTY HAVE A AVERAGE MORTALITY RATE OF ABOUT 36 PER 100,000. COUNTIES IN HIGHEST QUARTILE OF POVERTY, HAVE DRUG ALCOHOL AND SUICIDE RATE, ABOUT 46, 47 PER 100,000. THESE BIG GAPS IN AVERAGE DRUG ALCOHOL SUICIDE MORTALITY RATES BETWEEN COUNTIES AT LOWEST LEVELS OF DISTRESS VERSUS HIGHEST LEVELS OF ECONOMIC DISTRESS. SHOWING YOU THE QUARTILES INSTEAD OF FULL THREE TOP AND BOTTOM INSTEAD OF FULL GAMUT OF WORK BECAUSE IT TAXES TOO MUCH ROOM. POVERTY DISABILITY RATE, PERCENT UNEMPLOYED SING PARENTS FAMILIES, WITHOUT A FOUR YEAR DEGREE, COUNTIES DOING THE WORST ON THOSE INDICATORS HAVE SIGNIFICANTLY HIGHER DRUG ALCOHOL AND SUICIDE MORTALITY RATES. I CAN SHOW YOU BROKEN DOWN BY SPECIFIC INDICATORS THE END OF GOING INTO AN INDEX THAT I USE IN REGRESSION MODELS. SO THE RED BARS ARE SHOWING PERCENT INCREASES, SO LARGER HIGHER DRUG MORTALITY RATES. THE BLUE ARE NEGATIVE ASSOCIATIONS SO INDICATORS THAT ARE PROTECTIVE IF WE USE CAUSAL LANGUAGE HERE. LOWER MORTALITY RATES, SO YOU CAN SEE INTERESTING INDICATORS ON HERE THAT AREN'T JUST ABOUT ECONOMIC ISSUES. THEY'RE FAMILY ISSUES AS WELL SO COUNTIESES THAT HAVE A HIGHER DIVORCE OR SEPARATION RATE HAVE SIGNIFICANTLY HIGHER DRUG OVERDOSE MORTALITY RATES. MANUFACTURING JOB LOSS, MEDIAN HOUSEHOLD INCOME JOB LOSS, THESE ARE THINGS ASSOCIATED WITH HIGHER MORTALITY RATES. CONVERSELY TO THAT, REALLY INTERESTED IN VARIABLES AT THE BOTTOM, THE SOCIAL CAPITAL VARIABLES SO COUNTIES WITH HIGHER PRESENCE OF SOCIAL CAPITAL PROMOTING INSTITUTIONS HAVE SIGNIFICANTLY LOWER DRUG ALCOHOL AND SUICIDE MORTALITY RATES. I'M GOING TO SUMMARIZE BUT SAM KIN SON GETS THIS RIGHT IN HIS BOOK DREAM LAND, IT'S NOT NEW, BUT BUILDING FOR A LONG TIME AND JUST LIKE NOBODY PAID ATTENTION WHEN POOR BLACK WERE DYING OF CRACK IN THE 1980s AND WE WERE LOCKING THEM UP, NOBODY WAS PAYING ATTENTION WHEN OPIOID PROBLEM WAS UNFOLDING IN APPROXIMATE LA SHAH. PEOPLE WERE DYING THERE, BEING LOCKED UP, THESE WERE POOR WHITES THAT WERE BEING IGNORED UNTIL THIS PROBLEM SPREAD ACROSS THE REST OF THE COUNTRY. APPALACHIA. SO THE TAKE AWAYS FOR ME FROM THE RESEARCH I HAVE DONE THE OPIOID PROBLEM LOOK DIFFERENT IN DIFFERENT PLACES DESPAIR MAYBE MANIFESTING DIFFERENTLY AMONG DIFFERENT GROUPS AND PLACES, WE NEED TO ASK OURSELVES WHAT PROBLEM ARE WE TRYING TO FIX? ARE WE ONLY INTERESTED IN SAVING LIVES RIGHT NOW OR DO WE WANT TO MAKE SURE THAT WE ARE NOT VULNERABLE TO THE NEXT DRUG EPIDEMIC THAT COMES ALONG? WE TRIED THE SAME THING WE'RE TRYING NOW WITH CRACK IN THE '80s AND METH IN THE 2000s AND IN 1990s. AND NOW WE HAVE ANOTHER PROBLEM OPIOID. ANOTHER ONE THAT COMES AFTER THIS. SO WE DEAL WITH THESE UNDERLYING DRIVERS OF ECONOMIC DISTRESS AND DESPAIR AND SOCIAL DECLINE. I THINK WE WILL REMAIN VULNERABLE. THIS ISN'T TO SAY TREATMENT ISN'T IMPORTANT. OF COURSE IT IS. BUT WE'RE NOT GOING TO NARCAN OUR WAY OUT OF THIS, NOT GOING TO TREAT OUR WAY OUT BECAUSE THE PROBLEM IS BIGGER THAN OPIOIDS, BIGGER THAN DRUGS ALL TOGETHER. ANYONE PAYING AWE TENSION CAN SEE THERE'S SOMETHING BIGGER THAN DRUGS GOINGEN. SO WE START DEALING WITH THOSE -- IF WE DON'T START DEALING WITH THOSE ISSUE WELLS BE IN BIG TROUBLE SO LEAF YOU WITH THIS TO SAY TREATMENT IS IMPORTANT BUT WE CAN'T IGNORE WHAT'S GOING ON UPSTREAM SO THIS IS SOMETHING I REGULARLY SHOW MY UNDERGRADS. I'M STANDING BY THE SHORE OF THE RIVER AND I HEAR THE CRY OF A DROWNING MAN SOY JUMP THE RIVER PUT MY ARMS AROUND HIT PULL HIM TO SHOW AND APPLY ARTIFICIAL RESPIRATION, ENHE BREATHES ANOTHER CRY FOR HELP, AS HE BEGINS TO BREATHE ANOTHER CRY FOR HELP SO BACK IN THE RIVER AGAIN REACHING PULLING APPLYING BREATHING ANOTHER YELL AGAIN AND AGAIN WITHOUT END GOES THE SEQUENCE. I'M SO BUSY JUMPING AND PULLING THEM TO SHOW, APPLYING ARTIFICIAL RESPIRATION I HAVE NO TIME TO SEE WHO IS UPSTREAM PUSH THEM ALL IN. THANK YOU. [APPLAUSE] IS THERE TIME FOR A QUESTION OR DO WE NEED TO MOVE -- >> ANYBODY HAS A QUESTION? >> JIM GRIFFIN, NICHD, THANK YOU. GREAT TALK. I KNOW ONE THING FROM THE FAMILY LIFE PROJECT STUDY RURAL FAMILIES IN NORTH CAROLINA, PENNSYLVANIA, THE WORD MORALITY. I JUST ASSUME THE MORE RURAL, THE WORSE WHAT THEY FOUND THE MOST ISOLATED PROTECTIVE FACTORS SOME PEOPLE -- NORTH CAROLINA FARMED SINCE THE CIVIL WAR, IT WAS THOSE WITH THE LITTLE BIT MORE OFTEN GOVERNMENT HOUSING BECAUSE IT'S ALSO WHERE GANGS WERE, WHERE DRUGS WERE, THINGS OF THAT NATURE. WONDER IF YOU CAN COMMENT A LITTLE BIT ON THOSE THINGS AND SOME WE KNOW IN TERMS OF SOME OF THE SOCIAL STRUCTURE AND FACTORS AND HOW THOSE MIGHT CONTRIBUTE TO SOME OF THE PROBLEMS AND MIGHT LEAD TO SOME OF THE SOLUTIONS. >> THAT'S A GREAT QUESTION. SO WHEN YOU DO LOOK AT JUST THE MOST REMOTE RURAL AREAS, THOUGH FARMING DEPENDENT COUNTIES AND THEY HAVE LOW RATES OF THESE PROBLEMS SO I THINK THERE ARE A LOT OF UNTAPPED MEASURES THAT WE CAN GET AT INCLUDING THINGS LIKE RELIGIOUSTY AND SOCIAL COHESION AND SOCIAL CAPITAL THAT YOU CAN'T NECESSARILY GET OUT WITH TYPE OF DATA I'M USING, THOSE ARE VERY PROTECTIVE. WE ALSO HAVE TO KEEP IN MIND THAT THERE IS A LOT TO HAVE OVERLAP AND INTERSECTION BETWEEN RURAL AND URBAN AREAS, THEY'RE NOT COMPLETELY INDEPENDENT, DRUG DISTRIBUTION DOESN'T JUST STOP AT BORDER. THERE'S OVERLAP AND CO-MINGLING SO RURAL PLACES THAT HAVE GREATER DEGREE OF INTEGRATION WITH URBAN PLACES ARE GOING TO BE VULNERABLE TO THE DRUGS THAT ARE AVAILABLE THERE AS WELL. SO YEAH, I THINK THAT'S AN IMPORTANT REASON FOR ME TO SPLIT UP RURAL PLACE AN DIFFERENCE TYPES OF URBAN PLACES. WE SEE IT IN URBAN BUT SEEM TO NOT RECOGNIZE IT IN RURAL. THANK YOU. [APPLAUSE] >> HELLO. THANK YOU, VERY MUCH, MELISSA, FOR THE NICE INTRODUCTION AND THANK YOU ALL ALSO FOR STICKING AROUND, IT'S BEEN A LONG AND PROBABLY COGNITIVELY DEMANDING DAY. THANKS OBSSR FOR HAVING ME HERE MAKING ME HAPPY TO COME AND SHARE WITH YOU SOME OF THE THINGS THAT WE HAVE BEEN DOING. SO I AM VERY HAPPY TO SEE CONNECTION AND OVERLAP OF MY TALK WITH A NUMBER OF PRECEDING TALKS. ESPECIALLY COMING FROM A COMPLETELY DIFFERENT PLANET OF POPULATION HEALTH SCIENCE AS A DEMOGRAPHER WORKING AT THE INTERFACE BETWEEN SOCIAL AND BIOLOGICAL DETERMINANTS OF POPULATION HEALTH. SO MY LONG-TERM INTEREST IS IN MODELING THE LIFE COURSE PROCESSES OF CHRONIC DISEASES OF AGING AND ASSOCIATED MORTALITY, FOCUSING ON SOCIAL DISPARITIES AND BIOLOGICAL AND BEHAVIORAL MECHANISMS UNDERLYING THESE DISPARITIES. A NUMBER OF NIH IN PARTICULAR NIA AWARDS HAVE BEEN INSTRUMENTAL IN MY RESEARCH USING CONSORTIUM OF POPULATION BASE STUDY INTEGRATING SOCIAL ENVIRONMENTAL DATA AND BIOMARKERS TO EXAMINE KEY HYPOTHESIS ABOUT THE EARLY LIFE ORIGINS OF LATER LIFE HEALTH DISPARITIES. AND SO WHAT I HAVE ALREADY SEEN FROM THIS EMERGING BODY OF RESEARCH IS PROMISED TO TRANSFORM OUR KNOWLEDGE ABOUT THE DIVERSE INTERACTIVE PATHWAYS LEADING TO HEALTH AND I BELIEVE WHAT'S UNDERWAY IS EVEN MORE EXCITING AND WILL CONTINUE TO ENRICH OUR UNDERSTANDING OF THESE PATHWAYS AND DIRECT US MORE TOWARD TARGETED EFFECTIVE INTERVENTIONS, SPECIFIC TO EACH LIFE STAGE. I WILL GIVE SPECIFIC EXAMPLES BUT BEFORE THAT START WITH A GENERAL CONCEPTUAL MODEL THAT GUIDES MY WORK. ACROSS DIVERSE SPECTRUMS OF HEALTH OUTCOMES AND AS WELL AS EXPOSURES. THIS MODEL DESCRIBE IT IS PROCESS SOCIAL FACTORS, IN PARTICULAR SOCIAL CONDITIONS COME TO EFFECT INDIVIDUAL DISEASE SUSCEPTIBILITIES AND LONGEVITY, ACROSS THE LIFE COURSE AND THE MODEL ACTUALLY HAS FOUR COMPONENTS. I'M SHOWING ONLY TWO HERE BECAUSE THESE ARE RELATIVELY FAMILIAR. SO PATH A IS WELL DOCUMENTED LINKING SOCIAL FACTORS AND DISEASE AND LONGEVITY ESPECIALLY IN THE LITERATURE AND SOCIAL EPIDEMIOLOGY AND DEMOGRAPHY. THERE'S ALSO RESEARCH DOCUMENTS PATH B BIOLOGICAL RESEARCH THAT SHOWS BIOPHYSIOLOGICAL PLAYS A KEY ROLE IN MANY CHRONIC DISEASE MORBIDITY OUTCOMES. WHAT'S MUCH LESS UNDERSTOOD IS HOW PATH A AND B ARE RELATED TO EACH OTHER OR LINKED THROUGH PATH C THAT IS WHAT IS ROLE OF BIOPHYSIOLOGICAL REGULATION IN EXPLAINING THE SOCIAL IMPACTS ON HEALTH OUTCOMES. MORE IMPORTANTLY, HOW DO THESE LINKS UNFOLD OVER TIME ADS INDIVIDUALS AGE FROM CHILDHOOD TO LATE ADULTHOOD SO AS REPRESENTED BY THE TRAJECTORY LIFE COURSE TRAJECTORY D. THIS GENERAL LIFE COURSE MODEL CAN BE USED TO BEAR TO ADDRESS MAJOR REMINDING QUESTIONS GAPS AND CHALLENGES CONFRONTING OUR FIELDS. SO WHY DO SOCIAL FACTORS HAVE HEALTH EFFECTS WHICH CONCERN MECHANISMS. AND WHEN DO THESE EFFECTS EMERGE AND HOW LONG DO THEY LAST? WHICH CONCERNS TEMPORAL PROPERTIES OF THESE EFFECTS. AND PREVIOUS RESEARCH, THERE'S A HUGE UNIVERSE. BUT IT'S RELATIVELY CONFINED TO CORRELATIONAL STUDIES LOOKS AND ASSOCIATIONS BETWEEN FACTORS, INDIVIDUAL FACTORS BASED ON CROSS SECTIONAL DATA AT POINT IN TIME AND CONFINE WITHIN A SINGLE DEVELOPMENTAL PERIOD SUCH AS CHILDHOOD OR OLD AGE. SO THERE'S SIMPLY A LACK OF KNOWLEDGE OF HOW ASSOCIATIONS UNFOLD OR CHANGE, OVER LIFE COURSE. OUR GOALS FOR COLLABORATIVE WORK ACROSS MULTIPLE DISCIPLINES INCLUDING BIODEMOGRAPHY, CHRONIC DISEASE EPIDEMIOLOGY, DEVELOPMENTAL BIOLOGY, NEUROCOGNITIVE SCIENCE AND QUANTITATIVE METHODOLOGY, IS TO CONDUCT TRANSDISCIPLINARY RESEARCH TO UNDERSTAND HOW SOCIAL FACTORS GET UNDER THE SKIN TO AFFECT HEALTH ACROSS THE HUMAN LIFE SPAN BY FOCUSING ON THE LINKS SHOWN IN PATH C BETWEEN SOCIAL STRESS AND BIOMARKERS OF PHYSIOLOGICAL FUNCTIONING MORE IMPORTANTLY BREAK NEW GROUND BY ARTICULATING FOR THE FIRST TIME THE LIFE COURSE CONTEXT AND TEMPORAL DYNAMICS SHOWN IN TRAJECTORY D IN WHICH THESE LINKS UNFOLD AND EVENT WAIT IN SOCIAL DISPARITIES AND HEALTH SO OUR CONTRIBUTIONS TWO FOLD, ONER FIRST TO DEVELOP THE INTERCONSTITUTION NATURAL RESEARCH DESIGNS BY JOINING LARGE SCALE PERSPECTIVE COHORT STUDIES THAT COLLECTIVELY COVER THE LIFE SPAN FROM CHILDHOOD THROUGH OLD AGE. AND IT CAN SERVE AS FOUNDATION FOR A FUTURE RESEARCH OF A MULTITUDE OF HEALTH OUTCOMES AND ALSO MODEL BUILDING AND MORE CUMULATIVE SCIENCE OF POPULATION HEALTH. SO THIS INITIAL IMPLEMENTATION OF THIS-DESIGN HAS GIVEN US NEW MECHANISTIC KNOWLEDGE OF HEALTH IMPACTS OF SOCIAL FACTORS THAT SHOWS HOW SOCIAL DISADVANTAGE AND BIOLOGICAL RESPONSE TO STRESS COMBINE TO PRODUCE HEALTH DISPARITIES AS AGING PROGRESSES. AND THIS KNOWLEDGE IS QUITE CRITICAL FOR IDENTIFYING THE LIFE STAGES IN WHICH INTERVENTION IS MOST EFFECT EFFECTIVE. TARGETING PREVENTION AND TREATMENT IN HIGH RISK POPULATION SUBGROUPS SO MEN AND WOMEN, LOW, HIGH, SES GROUPS. SO NOW I WILL GIVE THREE ILLUSTRATED EXAMPLES BY RECENT AND ONGOING RESEARCH FUNDED BY THE NIH. FIRST IS CONCERNED WITH SOCIAL RELATIONSHIPS AND THEIR HEALTH IMPACTS. WE HAVE DONE A NUMBER OF STUDIES ON THIS TOPIC IN WHICH COULDNATED IN RECENT PUBLICATION IN PNAS, THE FOCUS OF MY TALK TODAY. SO BEGINNING WITH THE BACKGROUND THAT WE ALL KNOW THAT SOCIAL ISOLATION KILLS. WE KNOW FROM STUDIES OF MODEL ANIMALS IN RATS FOR INSTANCE, SOCIAL ISOLATION AND HYPERVIGILANCE ACCELERATES AGING AND SHORTENS LIFE SPAN. FOR EXAMPLE THE TOP PANEL HERE SHOWS IN FEMALE RATS THAT ARE SOCIALLY ISOLATED, THEY TEND TO DEVELOP MAMMARY TUMORS WHICH CORRESPOND TO BREATH CANCER IN HUMANS -- BREAST CANCER IN RELATIVELY YOUNGER AGES COMPARED TO THOSE ASSIGNED TO LIVE IN GROUPS. SAME DAY OF AGE THE RAT WHO IS SOCIAL ISOLATED HAS DEVELOPED MULTIPLE MAMMARY TUMORS COMPARED TO THE GROUP HOUSE ONE SO IN OUR OWN STUDIES OF HUMANS, THIS IS BASED ON THE U.S. POPULATION FROM THE N HAYNES DATA WE FOUND SIMILAR STRONG DETRIMENTAL SURVIVAL EFFECTS, SOCIAL ISOLATION, SO THE HAZARDS OF DEATH IS VASTLY ELEVATED FOR THOSE WHO ARE SOCIALLY ISOLATED BY ABOUT 80% FOR THE OVERALL MORTALITY AND EFFECTS ARE HIGHLY CONSISTENT ACROSS MAJOR CAUSES OF DEATH SUCH AS CARDIOVASCULAR DISEASE AND CANCER AND EFFECTS ALSO TEND TO BE LARGER FOR OLDER ADULTS, AND AS WELL AS FOR MEN. SO WHY? WHAT IS GOING ON? SO WE CONSIDER BIOPHYSIOLOGICAL PROCESSES IN UNDERLYING THIS LINK THAT'S MUCH LESS EXAMINED THAN THE PSYCHOSOCIAL BEHAVIORAL MECHANISMS IN SOCIAL POPULATION SCIENCE. SO WE BEGIN WITH FACT THAT RESEARCH ACROSS THE AREAS OF PSYCHONEURAL IMMUNONOLOGY CHRONIC BREAST EXPOSURE PROMOTE CHRONIC ACT VISION OF PHYSIOLOGICAL STRESS RESPONSE THAT INDUCE A CASCADE OF IMMUNE NEUROENDOCRINE AN METABOLIC CHANGES SO THE GRAPH ON THE LEFT SHOWS HOW CHRONIC SOCIAL STRESS SUCH AS LOW SOCIO ECONOMIC STATUS, SOCIAL DEPRIVATION RELATIONSHIP PROBLEMS, ALL THOSE SORTS OF EXPOSURES CAN INDUCE CHANGES IN THE HPA AND SNS, THAT MODULATE INFLAMMATORY PROCESSES AND UPREGULATE PRODUCTION OF PRO-INFLAMMATORY PSYCHKINES AND HAVE VARIOUS SORTS OF MORBIDITY CONSEQUENCES. SO THIS REGULATION IN THE IMMUNE CORD CARD YOU METABOLIC FUNCTIONS HAVE MAJOR RAMIFICATIONS FOR AGE RELATED DISEASE, STRONGLY PREDICT MORTALITY AND THEIR DIRECTLY EFFECTED BY SOCIAL FACTORS. SO WE FOCUS ON IN CRUCIAL BIOSOCIAL LINKAGE BETWEEN EXPERIENCE OF SOCIAL STRESS AND THE MORBIDITY CONSEQUENCES OF INFLAMMATION, METABOLIC SYNDROME AND THEIR COMPONENTS. SO BEUSE THIS EXTENSIVE LONGITUDINAL DESIGN TO DOCUMENT THE ASSOCIATION REMITTEDNAL PATH C AS THEY UNFOLD ACROSS MULTIPLE DEVELOPMENTAL STAGES FROM ADOLESCENCE, EARLY ADULTHOOD ALL WAY TO LATE ADULTHOOD BY SIMULTANEOUSLY ANALYZING LONGITUDINAL DATA SET ACROSS LIFE SPAN FOR ADOLESCENTS, WE HAVE NATIONAL LONGITUDE -- ADULT HEALTH OR AD HEALTH AND YOUNG TO MIDDLE ADULT WHO HAVE NATIONAL SURVEY OF MID LIFE DEVELOPMENT AT THE U.S. OR MIDAS AND LATE ADULTHOOD WE HAVE TWO LARGE DATA SETS, ONE HEALTH AND RETIREMENT STUDY AND OTHER FROM NATIONAL SOCIAL LIFE HEALTH AND AGING PROJECT. SO USING THESE DATA SETS WE HAVE COMPILED COMPREHENSIVE SET OF MEASURES OF RELATIONSHIP CHARACTERISTICS THAT ENCOMPASS THOSE QUANTITATIVE AND QUALITATIVE ME OF RELATIONSHIPS SUCH AS SOCIAL INTEGRATION AND SUPPORT AND HARMONIZE THEM ACROSS STUDY AND ALSO STUDY THEIR ASSOCIATION WITH MULTIPLE BIOMARKERS THAT ARE COMMON TO STUDIES, MANY MARKERS WHAT WE HAVE IN COMMON ARE THESE FOUR. THEN I HAVE MAJOR FINDINGS HERE FIRST SOCIAL INTEGRATION, THE DEGREE OF SOCIAL CONNECTEDNESS, THE DENSITY OF SOCIAL NETWORK WAS FOUND TO PREDICT BETTER PHYSIOLOGICAL FUNCTIONING AND LOWER RISK OF INFLAMMATION METABOLIC SYNDROME IN THE LINEAR OR DOSE RESPONSE FASHION. ACROSS LIFE STAGE STUDY SAMPLE SO HIGHER DEGREE OF SOCIAL CONNECTEDNESS AT PRIOR POINT IN TIME SHOW LOWER PREDICTED LEVELS OF PROTEIN INFLAMMATION AND SYSTOLIC BROOD PRESSURE BODY MASS INDEX AT THE FOLLOW-UP. THESE ASOUTHERN YEAR AGOS ARE HIGHLY SIGNIFICANT ACROSS ALL LIFE COURSE SAMPLES FOR EUROPEAN BLOOD PRESSURE AND ALSO SIGNIFICANT FOR ADOLESCENTS IN WITH CENTRAL BODY MASS INDEX. THE FINDINGS ON THE QUALITATIVE MEASURES OF SOCIAL RELATIONSHIPS SUCH AS PERCEIVED SOCIAL SUPPORT SHOW SIMILAR PATTERNS WITH THEIR ASSOCIATION WITH PHYSIOLOGICAL MARKERS THOUGH THESE ASSOCIATES TEND TO BE NOT LINEAR, MORE MODEST AND PARTICULARLY SALIENT FOR MIDDLE ADULTHOOD. FOR INSTANCE, COMPARED TO THOSE WHO HAVE LOW SOCIAL STRAIN, THOSE WITH HIGH LEVELS SOCIAL STRAIN PRIOR POINT IN TIME SHOW SIGNIFICANTLY HIGHER LEVELS OF CRP AT FOLLOW-UP, ENOUGH MID ADULTHOOD AND ALSO HIGHER BMI AND WASTE CIRCUMFERENCE IN BOTH MID TO LATE ADULTHOOD. TO SUM UP THIS BODY OF RESEARCH WHAT WE KNOW IS THAT WE HAVE CONSISTENT SPORT FOR PATH C. WE HAVE SHOWN THAT SOCIAL INTEGRATION PROTECTS HEALTHY REGULATION OF BIOLOGICAL SYSTEMS AND PHYSICAL HEALTH TO SOME EXTENT THAT APPLIES TO SOCIAL SUPPORT AND STRAIN OR LACK OF SOCIAL STRAIN. WE ALSO FIND IMPORTANT OF THE ROLE OF TRAJECTORY D. SO WE SEE THE MER GENERALS OF ASSOCIATION EARLY ON, AS EARLY AS ADOLESCENCE WE HAVE DATA WE SEE ASSOCIATION OF FOR INSTANCE SOCIAL ISOLATION AND INFLAMMATION COMPARABLE TO THAT OF PHYSICAL INACTIVITY AND INFLAMMATION WHICH IS HUGE. WE FOUND LONG TERM IMPACTS IT HAS LONG ARM OF EARLY LIFE INFLUENCE, TO LATE ADULTHOOD ADULTHOOD, WE SEE SOCIAL ISOLATION HYPERTENSION EXCEEDS THAT OF DIABETES IN LATE ADULT HOOD. IT'S QUALITY RA THE THAN QUANTITY FOR MENTAL HEALTH. THE SECOND EXAMPLE, WE -- I NOW TALK ABOUT SOMETHING THAT HAS BEEN TALKED ABOUT QUITE FREQUENTLY AND WE'LL COME UP IN THE NEXT TALK THAT IS ABOUT SES. THERE HAS BEEN SOME GROWING INTEREST IN EARLY LIFE ORIGINS OF HEALTH DISPARITY BY SES GROUPS, WE USE THE LIFE COUNSELOR PERSPECTIVE TO EXAMINE THE BIOLOGICAL MECHANISMS LINKING EARLY LIFE SES AND LATER LIFE HEALTH. SO HERE WE HAVE SOME MORE SPECIFIC THEORETICAL EXAMPLES TO APLAIN ASSOCIATIONS BETWEEN LIFE COURSE SES AN HEALTH CHANGE WITH AGE. THE FIRST WHICH IS RELATIVELY FAMILIAR TO YOU IN LIFE SCIENCES IS THE SENSE TV PERIOD. HYPOTHESIS WHICH MEANS EARLY LIFE SES HAS DIRECT EFFECT ON LATER LIFE HEALTH THROUGH BIOLOGICAL PROGRAMMING IRREVERSIBLE UNMODIFIABLE INDEPENDENT OF ADULT, ISES. THE SECOND IS ACCUMULATION OF RISK MODEL WHICH POSTULATES EARLY LIFE, BOTH EARLY AND ADULT SES ACCUMULATE IN THEIR EFFECTS TO AFFECT HEALTH SO WE SEE ADDED TO EFFECTS OF THE TWO. THIRD IS THE PATHWAY MODEL, EARLY LIFE SES INDIRECT AFFECT ADULT HEALTH H THEIR EFFECT ON ADULT SES ACT AS A PATHWAY LINKING EARLY TO LATER CONDITION. THE RESULTS OF SOCIAL MOBILITY MODEL WHICH TALKS MOVEMENT OR CHANGE IN EARLY LIFE AND ADULT SES AND INDEPENDENT IMPACT ON HEALTH. THESE LIFE COURSE PROCESSES HYPOTHESIZE BY THESE MODELS ARE NOT MUTUALLY EXCLUSIVE BUT INTERINTERRELATED AND COMPLIMENTARY SO WE EXAMINE THIS S EBBS PHYSIOLOGICAL FUNCTION LINKAGES AS THEY UNFOLD ACROSS LIFE SPAN FROM CHILDHOOD TO YOUNG ADULTHOOD TO MIDDLE ADULTHOOD AND LATE ADULTHOOD. SO WHAT WE DO IS TO CONSTRUCT COMPILE MEASURES OF EARLY LIFE SES USING PRETTY COMMON AND OVERLAPPING MEASURES IN EARLY LIFE. AS WELL AS ADULT SES MEASURES AND HARMONIZE USING ADVANCE QUANTITATIVE METHODS ACROSS STUDIES SUCH THAT WE CAN ENTER THEM INTO THE REGRESSION MODEL TO STUDY. THEN HERE IS SOME INTERESTING RESULTS SO IN YOUNG ADULTHOOD, BOTH EARLY LIFE SES AND CURRENT OR ADULT SES SHOWS SIGNIFICANT AND NEGATIVE EFFECTS ON INFLAMMATION AND OTHER METABOLIC INDICATORS SO THE LIGHT GRAY BAR AND BARS HERE CORRESPOND TO EARLY LIFE AND OCCUR IN SES EFFECTS OF CORRESPONDINGLY. THE -- LATE LIFE SO FOR YOUNG ADULTHOOD WE SEE EVIDENCE OF ACCUMULATION OF RISKS. IN LATE ADULTHOOD IT'S SLIGHTLY DIFFERENT SO THE CURRENT OR ADULT SES DOMINATES IN THEIR EFFECT SHOWN BY THE BARS HERE. SO WITH CURRENT SES PRESENT EARLY LIFE SES RECEDED IN ITS EFFECT, WILL BE ABSORBED OR MEDIATED BY ADULT SES SO HERE WE SEE MORE OR LESS EVIDENCE OF PATHWAY MODELS. THERE'S ALSO EVIDENCE FOR SOCIAL MOBILITY, PROCESS WHICH MEANS THE MOVEMENT BETWEEN LOWEST QUARTILE IN SES DISTRIBUTION TO HIGHER QUARTILES OR VICE VERSA HAVE INDEPENDENT EFFECT ON HEALTH AS WELL SO WE SEE COMPARED TO THOSE WHO ARE IN -- WHO ARE PERSISTENTLY IN THE -- CONSTANTLY STAY IN THE TOP THREE QUARTILE OF THE SES DISTRIBUTION DOWNWARD MOBILITY EXPERIENCE PERSISTENT DISADVANTAGES WHO STAY LOW, THEY ALL COMPARE TO THE REFERENCE GROUP SHOW HIGHER INFLAMMATION AND HIGHER PROBABILITY OF METABOLIC SYNDROME, IN ADULTHOOD. SO PRETTY MUCH WHAT IT MEANS IS SOCIAL SES DISADVANTAGE IN ANY POINT IN TIME HURT. SO IN SUM, WE FOUND THAT THE RELATIVE IMPORTANCE OF EARLY LIFE AND ADULT SES VARIES ACROSS THE LIFE COURSE SO TIMING DOES MATTER. THE SPECIFIC DIRECTION HOW IT MATTER IS THAT WE SEE ADULT ACCUMULATION MODEL IN YOUNG ADULTHOOD TRANSITIONING OR WEAKENING OF EARLY LIFE BUT STILL PRESENT IN MID ADULTHOOD TRANSITION AND THEN IN LATE ADULTHOOD WE SEE PATHWAY. SOCIAL MOBILITY OR IMMOBILITY IN SOME CASE BETWEEN EARLY AND ADULT SES ALSO MATTERS. SO MOVING ON TO I DON'T KNOW HOW MUCH TIME WE HAVE, BUT QUICKLY I'LL TALK ABOUT THE THIRD EXAMPLE, SO BUILDING ON THE RESEARCH INFORMED BY THE USE OF MULTIPLE DATA SETS, I HAVE TALKED ABOUT, WE NOW EXTEND LONGITUDINAL RESEARCH DESIGN TO STUDY THE LIFE COURSE PROCESS OF ALZHEIMERS DISEASE AND COGNITIVE CHANGE. NEWLY AWARDED PROJECT. WE WILL ADDRESS TWO FUNDAMENTAL PROBLEMS IN DISEASE HERE, FIRST IS SEX DISPARITIES IN COGNITIVE DECLINE WITH AGING, SECOND IS INTERPLACE BETWEEN SOCIAL AND BIOLOGICAL MECHANISMS OR PATHWAYS THAT GENERATE AND SUSTAIN SUCH DISPARITIES. SO HERE IS CONCEPTUAL MODEL THAT DESCRIBES HOW WE THINK THAT SEX/GENDER SOCIAL STRESS AND BIOLOGICAL PATHWAYS COMBINE TO SHAPE THE COGNITIVE TRAJECTORIES IN LATE LIFE, THE PRECEDING PATHWAY TO ONSET OF AD RISK. REFERS TO AIM TO IDENTIFY THE AGE TRAJECTORY SO CHANGE IN COGNITIVE FUNCTION FROM AD LESS ISN'T TO LATE ADULTHOOD IN RELATIONSHIP TO THE ONSET OF AGENING LATE ADULTHOOD AND THEN TO TEST THE SEX DIFFERENCES IN THE AGE PROFILES WITH COGNITIVE DECLINE, WE THEN AIM TO EXAMINE THE LIFE COURSE MECHANISMS BY WHICH SOCIAL STRESS ASSOCIATE WITH LOW SES AND SOCIAL DEFICITS SHAPE AGE PROFILES OF COGNITIVE DECLINE. WE AIM TO EXPLICATE THE BIOLOGICAL PATHWAYS THAT UNDERLIE THE LET REGENEITY -- HETEROGENEITY IN THE PROFILE FILLS OF COGNITIVE DECLINE AND INTERRELATIONSHIP WITH SOCIAL STRESS OVER THE LIFE COURSE SO HERE IN ORDER TO IMPLEMENT THIS MODEL WE EXTEND ON THE PREVIOUS RESEARCH TO MOVE ON TO A MORE INNOVATIVE LIFE COURSE RESEARCH DESIGN BY STAGING TOGETHER FIVE NIH STUDIES AT HEALTH I TALKED ABOUT ALREADY, MYDAS AND ACL WHICH IS THE AMERICAN CHANGING LIVES STUDY, THAT GIVES MORE DATA FOR MID ADULTHOOD AND LATE ADULTHOOD WE HAVE HRS AND ATOM STUDY. SO WHAT'S NEW HERE, COMPARED TO THE PREVIOUS EXAMPLES, WE ANALYZED SIMULTANEOUSLY MULTIPLE DATA SETS, WE CONDUCTED PARALLEL ANALYSIS WITHIN STUDIES AND COMPARE FINANCE ACROSS QUALITATIVELY. HERE WE IN THIS NEW STAGE OF RESEARCH WE FULLY INTEGRATE ALL INDIVIDUAL STUDIES BY COMBINING INTO ONE SAMPLE AND CREATING NEW DATABASE USING THE METHODOLOGY OF IDA OR INTEGRATIVE DATA ANALYSIS SO WE POOLED THEM TO CREATE A NEW DATABASE WITHIN AGE RANGE OF 12 TO 85 PLUS. WITH A MASSIVE NUMBER OF PERSON YEARS CLOSE TO 200,000. WELL IN ORDER TO COMBINE THESE INDIVIDUALS STUDIES WE APPLY METHOD DODGECAL GUIDELINES OF IDA TO ACCOUNT FOR HETEROGENEITY ACROSS INDEPENDENT STUDIES DUE TO MEASUREMENT SAMPLING DESIGN AND HISTORICAL TIME. SO THIS INNOVATIVE APPLICATION OF IDA TO COGNITIVE AGING RESEARCH, CANNOT FOR US A NUMBER OF ADVANTAGES NOT AVAILABLE TO CONVENTIONAL STUDIES. FIRST HAS TO DO WITH ECONOMY. SO WE USE EXISTING DATA WITH QUITE A BIT OF OVERLAPPING VARIABLES AND MEASURES BOTH EXPOSURES AND OUTCOMES AND SECOND, INCREASE POWER. NOW WE HAVE BOOSTED POWER, MORE IMPORTANTLY ALLOWS US TO HAVE THIS ABILITY TO ADDRESS NEW QUESTIONS WITH REGARD TO TEMPORAL DYNAMICS THAT CAN COVER A FAR MORE EXTENSIVE PERIOD OF LIFE THAN ANY BENEFIT CAN ALLOW. ULTIMATELY GIVES US THIS OPPORTUNITY TO SUPPORT DATA SHARING AND BUILD A MORE CUMULATIVE SCIENCE BY GIVING US REPLICATION EFFECTS ASSOCIATIONS ACROSS STUDIES OR DETECTING INCONSISTENCIES OR DESIMILARITIES AMONG THE STUDIES. AND I'LL CONCLUDE MY TALK. THANK YOU, VERY MUCH. [APPLAUSE] Q. QUESTION. (OFF MIC) >> THANK YOU VERY MUCH. THIS IS A TREMENDOUSLY IMPORTANT DAY. NOT ONLY FOR THE EXCITING RESEARCH BUT IT IS REALLY IMPORTANT FOR THE NIH TO CELEBRATE AND RECOGNIZE THE SOCIAL AND BEHAVIORAL SCIENCE RESEARCH. WE TEND TO SEE THINK OF NIH AS A PREDOMINANTLY BIOMEDICAL INSTITUTION BUT WHAT THE RESEARCH TODAY HAS SHOWN IS THE IMPACT THIS WORK HAS NOT ONLY ON DISEASE TREATMENT BUT ON PREVENTION. SO THE WORK THAT I WILL BE PRESENTING TO YOU TODAY IS TEAM STUDIES ON EARLY ORIGINS OF HEALTH DISPARITIES. SO YOU HAVE SEEN A MAP ALREADY. BUT THIS MAP IS LIFE EXPECTANCY AT BIRTH ACROSS THE UNITED STATES. WE SAW THIS PUBLISHED THIS PAST SUMMER IN JAMA INTERNAL MEDICINE, WHAT I WANT TO HIGHLIGHT IS NOT ONLY THE MAP, BUT THE LEGEND AT THE BOTTOM. WHICH I -- WHICH IS INCREDIBLY STRIKING. YOU OFTEN FOCUS JUST ON WHICH AREAS HAVE HIGHEST MORTALITY RATES, LIFE EXPECTANCY AT BIRTH BUT HERE LOOK CAREFULLY AT THE LEGEND AT THE BOTTOM, THE DIFFERENCE IN LIFE EXPECTANCY ACROSS PLACES IN THE U.S. IS OVER 20 YEARS. THIS LIFE EXPECTANCY AT BIRTH. LOOK AT WHAT'S GOING ON OVER TIME IN THE UNITED STATES, THIS IS A MEASURE OF GEOGRAPHIC INEQUALITY AND LIFE EXPECTANCY AT BIRTH AND WE SEE MEASURE OF INEQUALITY SINCE 1980s HAS BEEN INCREASING. WHAT EXPLAINS THIS? AND THE WORK THAT I'LL PRESENT WILL LEAD TO ARRIVE AT THESE THREE CONCLUSIONS. SOCIAL CONDITIONS DURING PREGNANCY ARE ASSOCIATED WITH NEURODEVELOPMENTAL PROBLEMS IN EARLY CHILDHOOD AND IN PART THIS COULD BE DUE TO IMMUNE FUNCTION DURING PREGNANCY AND IMMUNE FUNCTION IN PREGNANCY AND NEURODEVELOPMENTAL PROBLEMS HAVE VERY LONG TERM CONSEQUENCES FOR ADULT HEALTH. I WILL BE FOCUSING ON MENTAL HEALTH. SO THE WORK I WILL PRESENT TODAY IS BASED ON MANY YEARS OF RESEARCH WITH U.S. COLLABORATIVE PERINATAL PROJECT IN FOLLOW-UP STUDY. CPP COLLABORATIVE PERINATAL PROJECT WAS LAND MARK STUDY CONDUCTED IN 1950s -- '60s AND '70s WHICH RECRUITED OVER -- UPWARDS OF 50,000 PREGNANCIES. AND FOLLOWED THEIR CHILDREN THROUGH SEVEN YEARS OF LIFE. THESE ARE THE ACADEMIC SITES AROUND THE COUNTRY AND I HAVE HIGHLIGHTED BOSTON AND PROVIDENCE WHERE WE HAVE BEEN FOLLOWING UP CHILDREN BORN IN THE COHORT FOR THE LAST 20 YEARS. THE STUDY DESIGN OF THE ORIGINAL CPP IS UPWARDS OF ALMOST 50,000 PREGNANCIES ENROLLED IN 1960s FOLLOWED THROUGH AGE 87. MEASURES ARE MEASURE OF SOCIO ECONOMIC DISADVANTAGE SUCH AS IN DEPTH HISTORY ENTERRUES DURING PREGNANCY, WE HAVE CONSTRUCTED A COMPOSITE MEASURE OF SOCIO ECONOMIC DISADVANTAGE BASED ON FAMILIES EDUCATION, INCOME, AND FAMILY STRUCTURE. OCCASION. WHAT'S INCREDILY RICH ABOUT THE CPT IS THAT INTENSIVE DEVELOPMENTAL ASSESSMENTS THAT WERE CONDUCTED WHEN DURING CHILDHOOD, MENTAL MOTOR NEUROLOGIC DEVELOPMENT BY TRAINED PEDIATRICS NEUROLOGIST. IN ADULTHOOD WE HAVE ADMINISTERED STRUCTURED PSYCHIATRIC DIAGNOSTIC INTERVIEWS TO ASSESS DISORDERS, SUBSTANCE USE DISORDERS AND OTHERS SUCH ADS SCHIZOPHRENIA. SO TO SET THE STAGE, WHEN WE LOOKED BACK AT ARCHIVAL LAB PROJECT DATA, AT THE NEUROLOGIC DEVELOPMENT OF CHILDREN ACCORDING TOP THE SOCIO ECONOMIC DISADVANTAGE IN THEIR HOUSEHOLD WHAT WE FIND AS EARLY AS FOUR MONTHS OF AGE THOSE CHILDREN IN THE HIGHEST DISADVANTAGED HOUSEHOLDS HAVE A HIGHER RISK OF NEUROLOGIC ABNORMALITIES. THESE PERSIST THROUGH ONE YEAR, AND SEVEN YEARS AND YOU HAVE ALSO NOTED ABNORMALITIES IN DOMAIN OF AUTONOMIC NERVOUS SYSTEM FUNCTIONING. HOW MIGHT SOCIO ECONOMIC DISADVANTAGE IMPAIR DEVELOPMENT? WE FOCUSED ON INFLAMMATION IN PART BECAUSE PRENATAL STRESSORS THAT ARE OFTEN ASSOCIATED WITH CHRONIC SOCIO ECONOMIC DISADVANTAGE ARE LINKED WITH INFLAMMATORY RESPONSES DURING PREGNANCY WHICH WE KNOW FROM HUMAN AND ANIMAL STUDIES HAS CONSEQUENCES FOR NEURAL DEVELOPMENT. SO THE QUESTION I'M ASKING NOW IS DOES SOCIO ECONOMIC DISADVANTAGE DISRUPT MATERNAL IMMUNE ACTIVITY DURING PREGNANCY AND IS THIS DISRUPTION TRANSMITTEDDED TO THE DEVELOPING INFANT? INFLAMMATION? WE KNOW THE BALANCE OF DIFFERENT TYPES OF INFLAMMATORY MOLECULE SHIFTS DURING THE COURSE OF HEALTHY PREGNANCY, THIS IS IMPORTANT FOR FETAL SURVIVAL BUT WHEN THE BALANCE IS ABNORMAL IT CAN HAVE ADVERSE PREGNANCY COMPLICATIONS AND ADVERSE PREGNANCY OUTCOMES. INFLAMMATION CAN BE PART OF IMMUNE RESPONSE TO INFECTION BUT CONCENTRATIONS OF INFLAMMATORY MOLECULES ALSO CAN BE LINKED TO SOCIAL STRESSORS. THIS IS IMPORTANT BECAUSE INFLAMMATION CAN HAVE ADVERSE EFFECTS ON NEURODEVELOPMENT PARTICULARLY DEVELOPMENT OF FETAL HPA AXIS INVOLVED IN STRESS RESPONSE. SO WE HAVE GONE BACK TO THE BIO REPOSITORY PROJECT NICHD, WE HAVE GONE BACK TO 60-YEAR-OLD STORED PRENATAL SERUM TO CONDUCT ASSAYS OF SMALL PANEL OF INFLAMMATORY CYTOKINES. AND LOOPED THOSE WITH SOCIO ECONOMIC DISADVANTAGE DURING PREGNANCY SO FIRST I'LL SHOW YOU RESULTS ON INFLAMMATORY MOLECULES, ASSOCIATED WITH SOCIO ECONOMIC ADVANTAGE AND ASK THE QUESTION DOES INFLAMMATION MEDIATE ASSOCIATION BETWEEN SOCIO ECONOMIC ADVANTAGE AND NEURAL DEVELOPMENT. OUR FINDINGS WITH RESPECT TO INFLAMMATION DURING PREGNANCY ARE THAT MOTHERS, PREGNANCIES IN THE HIGHEST SOCIO ECONOMIC DISADVANTAGE CATEGORY HAD SUBSTANTIALLY LOWER CONCENTRATION CONCENTRATIONS OF THE PRO-INFLAMMATORY CYTOKINE INTERLEUKIN 8, WAY TO UNDERSTAND THIS GRAPH, IT PRESENCE THE REGRESSION CO-EFFICIENTS FROM REGRESSION MODEL THAT LOOKS AT IL 8 CONCENTRATIONS ACROSS THE ENTIRE DISTRIBUTION. IF YOU FOCUS ON THE 50th QUANTILE, THIS IS THE MEDIAN, SO JUST IGNORE EVERYTHING ELSE FOR NOW AND LOOK AT WHAT'S HAPPEN WITH THE MEDIAN. AT THE MEDIAN OF THE DISTRIBUTION OF IL 8 THE SOCIO ECONOMICALLY DISADVANTAGED PREGNANCIES HAVE LOWER CONCENTRATIONS. BUT THE MEDIAN DOESN'T TELL STORY BECAUSE THESE BIOMARKERS ARE HIGHLY SKEWED. SO THEN WE LOOK AT THE UPPER END OF THE DISTRIBUTION, WE SEE EVEN LARGER DIFFERENCES IN IL 8 BETWEEN SOCIO ECONOMIC DISADVANTAGED PREGNANCIES AND LESS DISADVANTAGE PREGNANCY. SO DOES THIS MATTER FOR INFANT DEVELOPMENT, NEURAL DEVELOPMENT? THESE ARE RESULTS OF STATISTICAL MEDIATION ANALYSIS. SO LOOK AT THIS PATHWAY HERE. AND THE ODDS RATIOS IN THIS TABLE SHOW YOU INDIRECT EFFECT ODDS RATIOS. SO IN OTHER WORDS THESE QUANTIFY HOW MUCH ASSOCIATION BETWEEN SOCIAL ECONOMIC DISADVANTAGE AN NEURODEVELOPMENT IS LINKED WITH GESTATIONAL IMMUNE ACTIVITY. THESE ODDS RATIOS HERE FOR EXAMPLE, AT FOUR MONTHS OF AGE INFANTS BORN TO HIGHLY DISADVANTAGED PREGNANCIES HAVE A 36% HIGHER ODDS OF NEUROLOGIC ABNORMALITIES BECAUSE OF SOCIO ECONOMICALLY DRIVEN VARIATION IN MATERNAL IMMUNE FUNCTION. I'M GOING TO SHIFT AND TALK FOR THE REMAINING FEW DATA SLIDES ON IMPLICATIONS INTO ADULTHOOD. IMPLICATIONS IN IMMUNE ACTIVITY DURING PREGNANCY, AND EARLY NEURODEVELOP MENTAL DEFICITS TO UNDERSTAND LONG TERM REACH OF EARLY SOCIAL CONDITIONS. WE HAVE CONDUCTED SEVERAL STUDIES ON 60-YEAR-OLD SERUM COLLECTED IN 1960s, 40-YEAR-OLD COLLECTION IN THE 1960s MAKING IMMUNE FUNCTION AND MOLECULES DURING PREGNANCY AND ADULT NEUROPSYCHIATRIC DISORDERS AND THE FIRST THING YOU WILL NOTICE HERE, THIS IS TRUE FOR MANY OF OUR STUDIES IS THERE ARE SEX DIFFERENCES AND THINGS WORK DIFFERENTLY FOR MEALS AND FEMALES. WHAT WE FIND IS FOR THE MALES IN OUR STUDY, THOSE WITH HIGHER LEVELS OF PRO-INFLAMMATORY CYTOKINES DURING PREGNANCY HAD HIGHER RISK OF MAJOR DEPRESSIVE DISORDER AND HIGHER RISK FOR PSYCHOSIS. LINKING THIS BACK TO THE FIRST SLIDE ON LIFE EXPECTANCY, BOTH OF THESE CONDITIONS ARE KNOWN TO BE ASSOCIATED WITH SHORTENED LIFE EXPECTANCY. FOR FEMALES WE FOUND OPPOSITE, HIGHER LEVEL OF PRO-INFLAMMATORY CYTOKINES DURING PREGNANCY ASSOCIATED WITH LOWER RISK THAN THESE DISORDERS SO'S MATERNAL FETAL INTERACTION WITH RESPECT TO ROLE OF MATERNAL IMMUNE ACTIVITY IN OFFSPRING MENTAL HEALTH. THE CHILDHOOD NEURODEVELOPMENTAL PROBLEMS HAVE LONG TERM CONSEQUENCES. WHEN WE FOLLOW-UP CHILDREN FROM THE COHORDE INTO ADULTHOOD, WE FIND THAT THE NEUROLOGIC ABNORMALITIES HERE I'M SHOWING DATA ON -- THESE CHILDREN HAVE HIGH HER RISK FOR ATTENTION DEFICIT HYPERACTIVITY DISORDER, LOOK AT SUBTYPES AND FIND HIGHER RISK ACROSS SUBTYPES. WE ALSO LOOK AT ADULT OUTCOME OF COGNITIVE PERFORMANCE AND NEUROCOGNITIVE DEVELOPMENT AND WE FIND THIS IS THE RISK BEING HOSPITALIZED FOR MAJOR DEPRESSIVE EPISODE. THOSE CHILDREN WITH LOWEST COGNITIVE PERFORMANCE SCORES, SEVEN YEARS OF LIFE, HAVE UPWARDS OF 15% HIGHER RISK OF BEING HOSPITALIZED FOR MAJOR DEPRESSIVE DISORDER IN ADULTHOOD. FIRST WORD HOW TO INTERPRET HOW WE HAVE BEEN INTERPRETING THE IMMUNE FINDINGS. PARTICULARLY WITH RESPECT TO IL 8. IT WAS PERHAPS SURPRISING TO US WE FOUND LOWER CONCENTRATIONS IN THE MOST DISADVANTAGED PREGNANCIES WE MIGHT HAVE HYPOTHESIZED THE OPPOSITE BUT BACK TO THE LITERATURE IT BECAME CLEAR THIS IS HIGHLY CONSISTENT WITH WHAT WE KNOW ABOUT IMMUNE SUPPRESSION IN CONTEXT OF EXCESS GLUE DOE CORTICOIDS. WHAT DOES IT DO? MANY THINGS, IT'S AN ANGIOGENIC FACTOR, THAT PLAYS A CRITICAL ROLE IN NEURODEVELOPMENT. WHERE IS THIS GOING IN SHORT TERM IN REGARDS TO SPECIFIC STUDIES? WORK IS FOCUSING ON BROADER PANEL IMMUNE MARKERS MORE FREQUENTLY DURING PREGNANCY, ALONGSIDE MARKERS OF GLUE CO-CORTICOIDS TO BETTER UNDERSTAND ASSOCIATIONS CONSEQUENCES FOR NEURAL DEVELOPMENT AND LONG TERM EFFECTS. MORE BROADLY WHERE OUR RESEARCH IS GOING IS TO TRY AND BETTERED UNDERSTAND DEVELOPMENTAL MECHANISMS UNDERLIE HEALTH DISPARITIES AND NOT ONLY IN PHYSIOLOGIC SYSTEMS BUT IN FAMILY ENVIRONMENT, NEIGHBORHOOD ENVIRONMENT AND HOW FACTORS EARLY ON HAVE LONG TERM EFFECTS BECAUSE WHAT WE KNOW IS HEALTH DISPARITIES ARE IN LARGE PART I WOULD ARGUE PROBLEM OF CHILD DEVELOPMENT. I WANT TO ACKNOWLEDGE A LIFE COURSE FUNDING. FROM MAINLY NIH AND INTRAMURAL RESEARCH PROGRAM, COLLABORATORS AT MANY PLACES AND TRAINEES. HEALTH BEHAVIOR BRANCH AT NICHED. THANK YOU VERY MUCH. [APPLAUSE] >> (OFF MIC) >> I CAN HEAR YOU, I'LL REPEAT YOUR QUESTION. (OFF MIC) >> SEE THESE TYPES OF CONSEQUENCES? >> I CAN -- SO THE QUESTION IS, DID WE LOOK WITHIN PREGNANCIES, WITHIN FAMILIES, WITHIN MOTHERS WHO HAD EITHER HIGHER LOW SOCIO ECONOMIC ADVANTAGE AND VARIATION WITHIN THOSE GROUPS WAS IN THE VARIOUS IMMUNE BIOMARKERS AND WHAT IMPLICATIONS WERE FOR OFFSPRING? THAT'S AN EXCELLENT IDEA. WE HAVEN'T DONE THAT. >> THANKS. THAT QUESTION SPEAKS TO RESELL YENS OR OTHER PATHWAYS THAT CAN BE INVOLVED. THANK YOU FOR THAT COMMENT. >> OKAY. THANK YOU VERY MUCH. >> I'M CHRISTINE HUNTER, NEW DEPUTY DIRECTOR FOR OBSSR. I'M ACUTELY AWARE THAT I'M WHAT'S BETWEEN YOU AND THE START OF YOUR WEEKEND. I THINK I HAVE TEN MINUTES ON THE SCHEDULE, I PROMISE I WON'T USE THOSE TEN MINUTES. I HAVE THREE POINTS THAT I WANT TO MAKE. ONE IS REALLY ENJOYED THE PRESENTATIONS WE HAD TODAY. I WAS VERY IMPRESSED. [APPLAUSE] I THINK IT ALSO REFLECT IT IS RICH NATURE OF OUR FIELD, EVERYTHING FROM BEHAVIORAL NEUROSCIENCE TO APPLIED INTERVENTION TO THINKING ABOUT SOCIAL AND ECONOMIC INFLUENCES ON HEALTH AND REALLY DONE IN A THOUGHTFUL WAY. AND SO VERY PLEASED WITH THAT. ALSO PLEASED THAT WE HAVE REPRESENTATION OF BOTH OUR EXTRAMURAL AND INTRAMURAL COMMUNITY IN TERMS OF OUR SPARES AND HOPE YOU ENJOY THE NETWORKING AND TOWN HALL OPPORTUNITIES. I ALSO WANT TO THANK ALL OF YOU WHO MADE THIS DAY GREAT. THE ATTENDEES, EVERYBODY THAT HERE STAYED LISTENED AND ASKED INTERESTING QUESTIONS THAT PARTICIPATED IN THE NETWORKING, THAT'S WHAT MAKES THIS DAY GREAT. AGAIN, THE SPEAKER WERE REALLY OUTSTANDING, I WANT YOU TO KNOW THEY WERE SELECTD FROM A LARGE NUMBER OF SUBMITS AND SO WE WISH WE COULD HAVE HIGHLIGHTED EVERYBODY, I THINK WE HIGHLIGHTED SOME EXCELLENT SPEAKERS AND PRESENTATIONS BUT THE FULL LIST OF THOSE THAT WERE NOMINATED WILL BE IN THE FESTIVAL SUMMARY THAT WILL BE POSTED ON OUR WEBSITE SOON SO YOU'RE INTERESTED YOU CAN LOOK AT THAT. ALSO THE VIDEOS OF EACH OF THESE PRESENTATIONS WILL BE POSTED, SO IF YOU WANT TO SHARE THIS WITH COLLEAGUES OR WATCH IT AGAIN, THAT WILL BE AN OPPORTUNITY FOR YOU AS WELL. I ALSO WANT TO THANK THE MODERATORS AND TOWN HALL FACILITATORS FOR DOING SUCH A GOOD JOB AND THE OBSSR STAFF AND COORDINATING COMMITTEE WHO DID ALL THE WORK IN THOUGHTFULLY PLANNING THIS AND PULLING OFF THIS EXCELLENT DAY. FINALLY BEFORE YOU START YOUR WEEKEND, I WANT TO SAY WE REALLY LOOK FORWARD TO HEARING FROM YOU OVER THE NEXT YEAR, WE'RE COMMITTED TO CONTINUING THIS CONVERSATION, WE WANT TO KNOW ABOUT YOUR PRIORITIES. WE WANT TO KNOW IDEAS FOR HOW OUR OFFICE CAN FACILITATE AND SUPPORT AND ADVANCE BEHAVIORAL AND SOCIAL SCIENCES. SO AGAIN, THANK YOU VERY MUCH. I THINK IT WAS AN EXCELLENT DAY, I HOPE YOU AGREE. HAVE WOUND OF WEEKEND. -- HAVE A WONDERFUL WEEKEND. [APPLAUSE]