I'M WELCOMING YOU TO THE 150TH MEETING OF THE NATIONAL ADVISORY COUNCIL ON ALCOHOL ABUSE AND ALCOHOLISM. FIRST WE'RE GOING TO INTRODUC NEW MEMBERS. AND THEY ARE -- I'M GOING TO LIST THEM AND THEN I'LL GO THROUGH EACH ONE INDIVIDUALLY AND TELL YOU ABOUT THEM. SO DR. CHRISTOPHER CARPENTER, CHRIS, DO YOU WANT TO RAISE YOUR HAND? THERE YOU ARE. BETH KANE-DAVIDSON. BETH, RAISE YOUR HAND. CHARLES LANG. MARY LARIMER. I LIKE THE MER PART. LAURA NAGY, AND LAURA O'DELL. OH, THERE YOU ARE, LAURA. AND THEN -- I'LL GO THROUGH AND TELL YOU WHERE THEY'RE FROM AND WHY THEY'RE FAMOUS, BUT BEFORE WE DO THAT, WE'LL GO AROUND AND INTRODUCE OURSELVES. SO I'M OBVIOUSLY THE DIRECTOR OF NIAAA. >> GOOD MORNING, I'M TRISH COULD LIN, THE DEPUTY DIRECTOR OF NIAAA. >> AMEDI SULLIVAN, PROFESSOR IN PSYCHIATRY AT STANFORD UNIVERSITY, AND NEUROIMAGING AND NEUROPSYCHOLOGY. >> I'M SUSAN SMITH, I'M AT THE NUTRITION RESEARCH INSTITUTE AT UNIVERSITY OF NORTH NORTH CAROLINA CLA PEL HIM, ALL THINGS FETAL ALCOHOL EXPOSURE. >> VIJAY SHAH, ALCOHOL-LY LATED LIVER DISEASE. >> SCOTT RUSSO, PROFESSOR OF NEUROSCIENCE AT MOUNT SINAI. WE WORK ON STRESS AND AGGRESSION AND THE NEUROBIOLOGY OF THOSE CONDITIONS. >> MY NAME IS LAURA O'DELL AND I'M A PROFESSOR AT THE UNIVERSITY OF TEXAS AT EL PASO, AND MY RESEARCH FOCUSES ON THE NEUROBIOLOGY OF DRUGS OF ABUSE WITH A FOCUS ON NICOTINE. >> LAURA NAGY, CLEVELAND CLINIC, AND I WORK ON ALCOHOL-ASSOCIATED LIVER DISEASE AN TISSUE INJURY. >> MARY LARIMER, DEPARTMENTS OF PSYCHIATRY, BEHAVIORAL SCIENCE AND PSYCHOLOGY UNIVERSITY OF WASHINGTON, AND I WORK ON ETIOLOGY PREVENTION AND TREATMENT OF ALCOHOL USE DISORDERS AND RELATED CO-MORBID CONDITIONS. >> I'M CHUCK LANG, PROFESSOR AT PENN STATE COLLEGE OF MEDICINE IN HERSHEY, PENNSYLVANIA, RESEARCH INTERESTS ARE IN CARDIAC AND SKELETAL MUSCLE WASTING AND EFFECTS OF ALCOHOL. >> HI, IKE VICKIE BUCKLEY, EXECUTIVE OFFICER OF NIAAA. >> I'M -- ACTING DIRECTOR DIVISION OF MEDICATIONS DEVELOPMENT, ACTING DIRECTOR DIVISION OF TREATMENT AND RECOVERY RESEARCH AT NIAAA. >> GOOD MORNING. I'M ANTONIO NURONA, DIVISION DIRECTOR OF NEUROSCIENCE AND BEHAVIOR AT NIAAA. >> I'M MEGAN RYAN, THE SBIR STTR PROGRAM COORDINATOR. >> GEORGE -- DIRECTOR OF THE INTRAMURAL PROGRAM. MY RESEARCH FOCUSES ON THE BIOLOGY OF ENDOCANNABINOIDS AND METABOLIC REGULATION. >> I'M CHARLES MILLIKEN, COLONEL, RETIRED U.S. ARMY, CLINICAL DIRECTOR OF SUD CLINICAL CARE FOR THE ARMY AND SOON TO MOVE OVER TO DOD, THEY'RE ACTUALLY CONSOLIDATING ARMY AND NAVY AND AIR FORCE MEDICINE UNDER A SINGLE DOD HEALTH AGENCY. >> GOOD MORNING. MY NAME IS CATHY YOUNG, AND HERE AT NIAA I'M DIRECTOR OF THE DIVISION OF METABOLISM AND HEALTH EFFECTS. >> GOOD MORNING. I'M BRIDGET WILLIAMSON, DIRECTOR OF THE OFFICE OF SCIENCE POLICY COMMUNICATIONS, NIAAA. >> GOOD MORNING, I'M RALPH HENKSON, NIAAA. >> GOOD MORNING, BETH KANE-DAVIDSON, CLINICAL DIRECTOR OF INTUR BAB HOSPITALS ADDICTION TREATMENT CENTER. >> GOOD MORNING, I'M CONNIE HORGAN, PROFESSOR AND DIRECTOR OF THE INSTITUTE FOR BEHAVIORAL HEALTH AT BRANDEIS UNIVERSITY AND A HEALTH SERVICES RESEARCHER FOCUSED IN THE MENTAL HEALTH AND ADDICTION AREA. >> GOOD MORNING, BOB HITZEMNN, OREGON HEALTH SCIENCE UNIVERSITY, WORK FOCUSES MAINLY ON BEHAVIORAL GENETICS. >> GOOD MORNING. THIS IS ALEX DOPEY DOPICO. >> I'M CHRISTOPHER CARPENTER, PROFESSOR OF ECONOMICS AT VANDERBILT. I'M A HEALTH ECONOMIST, I STUDY PUBLIC POLICIES FOR YOUTH ALCOHOL CONSUMPTION AND LGBT HEALTH. >> GOOD MORNING, MY NAME IS DANICA DAN CALAC, CALIFORNIA. >> I'M JILL BECKER, I'M A PROFESSOR OF PSYCHOLOGY AT THE MICHIGAN NEUROSCIENCE INSTITUTE AT THE UNIVERSITY OF MICHIGAN. I STUDY SEX DIFFERENCES IN MOTIVATION AND ADDICTION. >> I'M DR. LOU BAXTER. I'M THE EXECUTIVE MEDICAL DIRECTOR FOR THE PROFESSIONAL ASSISTANCE PROGRAM OF NEW JERSEY. WE TAKE CARE OF HEALTHCARE PROFESSIONALS ALSO AND A MEMO BRER OF BER OF THE AMERICAN COLLEGE OF ADDICTION MEDICINE, PAST PRESIDENT OF ASAM AND THE CO-FOUNDER OF THE HOWARD UNIVERSITY ADDICTION MEDICINE FELLOWSHIP PROGRAM. >> I'M ABE BAUTISTA, EXECUTIVE SECRETARY OF COUNCIL. >> OKAY. SO I'D LIKE TO TELL YOU ABOUT OUR NEW COUNCILMEMBERS. IT WON'T BE TOO LONG HOPEFULLY, HOPE YOU ALL WILL WELCOME THEM AT THE BREAKS. AND EVERYBODY GET TO KNOW EACH OTHER. SO DR. CHRISTOPHER CARPENTER IS THE E BRONSON INGRAM PROFESSOR OF ECONOMICS DIRECTOR OF THE PROGRAM IN PUBLIC POLICY STUDIES, PROFESSOR OF LAW, PROFESSOR OF LEADERSHIP POLICY AND ORGANIZATIONS, PROFESSOR OF MEDICINE HEALTH AND SOCIETY, PROFESSOR OF WOMEN'S AND GENDER STUDIES AT THE COLLEGE OF ARTS AND SCIENCES VANDERBILT UNIVERSITY. HE RECEIVED HIS PH.D. IN ECONOMICS FROM THE UNIVERSITY OF CALIFORNIA BERKLEY, HE'S A HEALTH AND LABOR ECONOMIST WHO STUDIES THE EFFECTS OF PUBLIC POLICIES ON HEALTH AND FAMILY OUTCOMES AT AT VANDER BELT, TRANS INSTITUTIONAL PROGRAMS SUPPORTED VANDERBILT LGBT POLICY LAB. DR. CARPENTER HAS PUBLISHED EXTENSIVELY ON THE CAUSES AND CONSEQUENCES OF SUBSTANCE USE ON OTHER HEALTH BEHAVIORS SUCH AS BICYCLE HELMET USE, SEAT BELT USE, CANCER SCREENING AND VACCINATION. HIS RESEARCH HAS BEEN TANSLY SUPPORTED BY NIAAA, THE NATIONAL INSTITUTE ON AGING, THE NATIONAL INSTITUTE ON CHILD HEALTH, THE ROBERT WOOD JOHNSON FOUNDATION, AND THE AMERICAN CANCER SOCIETY. HE IS A RESEARCH ASSOCIATE AT THE NATIONAL BUREAU OF ECONOMIC RESEARCH AND EDITOR AT THE JOURNAL OF HEALTH ECONOMICS. HE SERVES ON THE EDITORIAL BOARDS OF THE AMERICAN JOURNAL OF HEALTH ECONOMICS AND THE JOURNAL OF POLICY ANALYSIS AND MANAGEMENT. SO WELCOME. BETH KANE-DAVIDSON IS AN M.D. -- THERE SHE IS AGAIN -- IS THE DIRECTOR OF SUBURBAN HOSPITAL ADDICTION TREATMENT CENTER, RIGHT ACROSS FROM NIH. SHE HOLDS A MASTER'S DEGREE IN EDUCATION FROM VIRGINIA TECH, A B.A. AND ADVANCED GRADUATE STUDIES CERTIFICATE IN ADDICTION FROM JOHNS HOPKINS UNIVERSITY. SHE'S A LICENSED CLINICAL ALCOHOL AND COUNSELOR. THAT DOESN'T MAKE SENSE, A LICENSED CLINICAL ALCOHOL COUNSELOR WHO HAS MORE THAN 30 YEARS OF EXPERIENCE IN THE ADDICTION TREATMENT FIELD. SHE'S RECOGNIZED THROUGHOUT THE REGION. HER EXPERTISE AND LEADERSHIP IN THIS AREA. MS. DAVIDSON IS THE FOUNDER OF FIRST CONCERNS, A PRIVATE PRACTICE IN BETHESDA, WHERE SHE AND HER STAFF PROVIDE EXPERT SUBSTANCE ABUSE ASSESSMENT, EDUCATION, GUIDANCE COUNSELING AND RELAPSE PREVENTION FOR ADOLESCENTS AND ADULTS. IN ADDITION, FIRST CONCERNS PROVIDE SUBSTANCE ABUSE ASSESSMENT AND CONSULTATION TO INDEPENDENT SCHOOLS THROUGHOUT THE WASHINGTON, D.C. MET METROPOLITAN AREA AND HAS FOSTERED THE FOUNDING OF SUOL, SOUL, SURVIVING OUR ULTIMATE LOSS, A SUPPORT GROUP FOR MOTHERS WHO HAVE LOST CHILDREN TO OVERDOSE. SHE HAS SERVED AS A CONSULTANT AT THE COMMUNITY OF CONCERNS INCORPORATED AND COUNSELOR AT PRIMA VAIR A CULPEPER, VIRGINIA. SO WELCOME. DR. CHARLES LANG IS A DISTINGUISHED PROFESSOR AND ASSOCIATE DEAN FOR GRADUATE STUDENTS PENN STATE UNIVERSITY COLLEGE OF MEDICINE, HERSHEY, PENNSYLVANIA. HE RECEIVED HIS PH.D. IN PHYSIOLOGY AND BIOCHEMISTRY FROM THE HANAMAN MEDICAL COLLEGE. SINCE 1987, DR. LANG HAS BEEN FUNDED BY NIAAA, NIGMS, NHLBI, LBI IS HEART, LUNG AND BLOOD, AND NIDDK. DIGESTIVE AND KIDNEY DISEASES. ON A NUMBER OF RESEARCH PROGRAMS THAT COVER METABOLIC AND NUTRITIONAL PHYSIOLOGY, LIVER PATHOPHYSIOLOGY, MUSCLE WASTING, ALCOHOLIC CARDIOMYOPATHY, TRAUMA, AND SEPSIS. HE IS LIST ALSO DIRECTOR OF THE NIGMS FUNDED T32 TRAINING PROGRAM IN ORGAN INJURY. HE'S CURRENTLY THE EDITOR-IN-CHIEF OF THE AMERICAN JOURNAL OF PHYSIOLOGY, THE ENDOCRINOLOGY AND METABOLISM PART OF THAT JOURNAL. HE SERVES AS FIELD EDITOR OF ALCOHOLISM IN CLINICAL AND EXPERIMENTAL RESEARCH AND SITS ON THE EDITORIAL BOARD FOR "SHOCK." THAT'S A JOURNAL. DR. LANG WAS THE PRESIDENT OF THE SHOCK SOCIETY IN 2014 HE SERVED AS CHAIR OF NIAAA'S BIOMEDICAL RESEARCH REVIEW SUBCOMMITTEE AA1 AND WAS A STANDING MEMBER OF SURGERY ANESTHESIOLOGY AND TRAUMA STUDY SECTION AT CSR. HE IS AN NIAAA MERIT AWARDEE. DR. MARY LARIMER IS THE ASSOCIATE DIRECTOR, MARY, WAVE YOUR HAND -- IS THE ASSOCIATE DIRECTOR ADDICTIVE BEHAVIORS RESEARCH CENTER PROFESSOR PSYCHOLOGY PSYCHIATRY AT THE UNIVERSITY OF WASHINGTON. SHE RECEIVED HER PH.D. IN CLINICAL PSYCHOLOGY FROM THE UNIVERSITY OF WASHINGTON. DR. LARIMER'S RESEARCH AND CLINICAL INTERESTS INCLUDE PREVENTION AND TREATMENT -- DISSEMINATION OF EVIDENCE-BASED PREVENTION AND TREATMENT APPROACHES INTO CLINICAL SCHOOL AND WORK SITE SETTINGS. SHE'S BEEN FUNDED BY NAR.IAAA AND NIMH SINCE 1996. SHE IS THE PAST PRESIDENT OF THE RESEARCH SOCIETY ON ALCOHOLISM. SHE IS AN AUTHOR AND CO-AUTHOR OF NUMEROUS ALCOHOL RELATED TOPIC, SHE IS THE ASSOCIATE EDITOR OF PSYCHOLOGY OF ADDICTIVE BEHAVIOR AND A MEMBER OF THE EDITORIAL ADVISORY BOARD OF ALCOHOL RESEARCH IN HEALTH, AND DR. LARIMER IS ALSO A RECIPIENT OF AN NIAAA MERIT AWARD. DR. LAURA NAGY IS PROFESSOR OF MOLECULAR MEDICINE PATHOBIOLOGY AND GASTROENTEROLOGY. LAURA, CAN YOU WAVE? RESEARCH INSTITUTE AT THE CLEVELAND CLINIC. SHE'S ALSO PROFESSOR OF PEDIATRIC NEUROLOGY AT THE CARVER COLLEGE OF MEDICINE OF IOWA HEALTHCARE. SHE RECEIVED HER PH.D. IN NUTRITION IN 1986 FROM THE UNIVERSITY OF CALIFORNIA BERKLEY. SHE'S CURRENTLY A PROFESSOR OF MOLECULAR MEDICINE AS I ALREADY SAID IN PATHOBIOLOGY AND GASTROENTEROLOGY AT THE CLEVELAND CLINIC, DIRECTOR OF THE LIVER DISEASE RESEARCH CENTER AND VICE CHAIR FOR EXTERNAL AFFAIRS IN THE LERNER RESEARCH INSTITUTE. SHE'S INTERNATIONALLY RENOWNED FOR HER WORK IN THE AREA OF SIGNAL TRANSDUCTION AND INNATE IMMUNITY IN NON-ALCOHOLIC AND ALCOHOLIC LIVER DISEASES. HER RESEARCH HAS BEEN CONTINUOUSLY FUNDED BY NIAAA SINCE 1998 AND ALSO THE DEPARTMENT OF DEFENSE. SHE IS A PRINCIPAL INVESTIGATOR OF THE NORTHEAST OHIO ALCOHOL RESEARCH CENTER, WHICH IS A P50. SHE HAS SERVED AS PRESIDENT OF THE RESEARCH SOCIETY ON ALCOHOL IMAS ALCOHOLISM AS WELL, CHAIR -- FOR THE ALCOHOL BEVERIDGE MEDICAL RESEARCH FOUNDATION AND CHAIR OF THE NIAAA BOARD OF SCIENTIFIC COUNSELORS AS YOU HEARD EARLIER. ASSOCIATE EDITOR OF THE JOURNAL ALCOHOLISM CLINICAL AND EXPERIMENTAL RESEARCH. AND FORMER CHAIR OF THE NIAAA BIOMEDICAL RESEARH SUBCOMMITTEE AA1. DR. NAGY IS ALSO AN NIAAA MERIT AWARDEE AND WE RECENTLY CELEBRATED HER WINNING THE NIAAA MARK TELLER HONORARY LECTURE AWARD, SHE GAVE AN OUTSTANDING LECTURE ABOUT A WEEK AGO, SO LAURA HAS BEEN AROUND A LOT, I THINK. HAPPILY. DR. LAURA O'DELL IS PROFESSOR IN THE DEPARTMENT OF PSYCHOLOGY AT THE UNIVERSITY OF TEXAS IN EL PASO. BEFORE JOINING UTEP AS ASSISTANT PROFESSOR, SHE WAS A STAFF SCIENTIST AT THE SCRIPS RESEARCH INSTITUTE. SHE RAN MY LAB. QUITE EXCELLENTLY, I MIGHT ADD. DR. O'DELL RECEIVED HER PH.D. IN BEHAVIORAL NEUROSCIENCE FROM ARIZONA STATE UNIVERSITY AND POSTDOCTORAL FELLOW AT AMIS TECHNOLOGIES, INCORPORATED. DR. O'DELL'S RESEARCH PROGRAM IS FOCUSED ON THE NEUROMECHANISMS THAT MEDIATE ADDICTION TO DRUGS OF ABUSE, FACTORS THAT PROMOTE TOBACCO USE IN VULNERABLE POPULATIONS SUCH AS ADOLESCENTS, FEMALES AND PERSONS WITH DIABETES. SHE ALSO EXAMINES MECHANISMS THAT MODULATE THE NEUROCHEMICAL EFFECTS OF NICOTINE AND CHEMICAL WITHDRAWAL FROM THIS DRUG AND THE BIOLOGICAL UNDERPINNINGS FROM DRUGS OF ABUSE SUCH AT METHAMPHETAMINE. HER RESEARCH PROJECTS HAVE BEEN CONTINUOUSLY FUNDED AND SUPPORTED BY NIDA SINCE 2007. LAURA ALSO DID A POSTDOCTORAL FELLOWSHIP WITH LARRY PARSONS AT THE SCRIPS RESEARCH INSTITUTE. MANY OF YOU KNOW HE PASSED AWAY TWO YEARS AGO. WAY TOO EARLY. DR. O'DELL RECEIVED SEVERAL AWARDS INCLUDING THE PCASE AWARD FROM THE NATIONAL SCIENCE AND TECHNOLOGY COUNCIL, OFFICE OF THE PRESIDENT OF THE UNITED STATES, AND SHE ALSO WON THE EXCELLENCE IN MENTORING AWARD FROM THE NATIONAL HISPANIC SCIENCE NETWORK ON DRUGS OF ABUSE. SHE'S A MEMBER OF THE NIAA ADVISORY COUNCIL WORKING GROUP ON DIVERSITY AND HEALTH DISPARITIES IN THE BIOMEDICAL WORKFORCE. SO LET'S WELCOME EVERYBODY TO COUNCIL AND AS I SAID BEFORE, YOU KNOW, I THINK ABE DOES AN EXCELLENT JOB IN RECRUITING INDIVIDUALS FOR COUNCIL FROM DIVERSE BACKGROUNDS, DIVERSE GEOGRAPHICAL AREAS AND WE TRY TO MAINTAIN A GOOD PERCENTAGE IN THE GENDER DOMAIN AS WELL, AND YOU KNOW, SO -- I THINK THE THEME THAT I'VE LEARNED THROUGH NIH'S FOCUS ON DIVERSITY IS THAT IT REALLY IMPROVES OUR RESEARCH BECAUSE WE START THINKING IN DIFFERENT WAYS AND BETTER WAYS AND OUT OF THE BOX WAYS WHEN WE HAVE A DIVERSE GROUP OF INDIVIDUALS. SO THAT'S WHY WE EVEN EMBRACE PEOPLE THAT WERE FUNDED CONTINUOUSLY BY NIDA. [LAUGHTER] HAD TO SAY THAT. DO I GIVE MY TALK NOW? JUST FOR THE RECORD, WE LOVE NIDA. THEY'RE OUR SISTER INSTITUTE, WE LIKE TO CALL THEM. SO THIS IS THE DIRECTOR'S REPORT OF THE ACTIVITIES FOR THE 153 MEETING OF THE NATIONAL ADVISORY COUNCIL OF THE NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM. SO SO THIS IS OUR 50TH ANNIVERSARY IF YOU HAVEN'T FIGURED THIS OUT BY ALL THE SIGNS AND POSTERS AND SO FORTH, AND THERE'S GOING TO BE A LOT OF ACTIVITIES SURROUNDING THE 50TH ANNIVERSARY, BUT WE WERE BASICALLY FOUNDED IN 1970. THERE WILL BE SOME DISCUSSIONS IN SOME OF THESE PLACES ON OUR WEBSITE OF EXACTLY HOW NIAAA CAME ABOUT. IT WASN'T A MAGIC WAND THAT POINTED IT, IT CAME THROUGH A WHOLE SEARS EASE SERIES OF ACTIONS. THAT WAS BEFORE MY TIME, I WAS A FIRST YEAR GRADUATE STUDENT IN 1970. MY FIRST GRANT WAS ACTUALLY FROM NIMH. AN R21, AS I REMEMBER. AND I WAS TRAINED ON A HEART LUNG TRAINING GRANT. MOST OF YOU DON'T KNOW THAT I WAS TRAINED ON A T32 FOR MY PH. D IN THE PHYSIOLOGY DEPARTMENT ON A HEART LUNG TRAINING GRANT. I'M ACTUALLY VERY PROUD OF THAT, I TELL GARY GIBBONS THAT ALL THE TIME. SOME OF THE SPECIAL EVENT FRED AND EVERYBODY IN THEIR GROUP HAS STARTED TO ORGANIZE ARE AS FOLLOWS. WE'RE GOING TO HAVE AN ALCOHOL RESEARCH SYMPOSIUM ON THE NIH MAIN CAMPUS ON MARCH 31ST. YOU'RE ALL WELCOME TO LISTEN IN, COME BY IF YOU'RE LOCAL OR FLY IN IF YOU WANT TO. WE'RE ALSO ON THE NIH MAIN CAMPUS GOING TO SCREEN A DOCUMENTARY WE DID WITH H BSM O CALLED "RISKY DRINKING." YOU REMEMBER THIS WAS A COLLABORATIVE EFFORT AND I THINK IT'S A REALLY GOOD FILM THAT SHOWS THE SPECTRUM OF ALCOHOL USE DISORDER ACROSS SOCIETY AND HOW IT TRANSITIONS. AND ACTUALLY SOME OF THE BIOLOGY AND SOME OF THE TREATMENT AND SOME OF THE PREVENTION THAT GOES INTO ALCOHOL USE DISORDER IN A LAY WAY OF EXPLANATION. AND THEN THERE'S GOING TO BE A SPECIAL PRESENTATION AT RSA/ISBRA MEETINGS IN NEW ORLEANS ON JUNE 21ST. THIS IS STILL BEING WORKED ON. SO, YOU KNOW, TELL EVERYBODY YOU KNOW, HELP US CELEBRATE. I THINK THERE ARE ALREADY BANNERS ON A NUMBER OF THE LIGHT POSTS ON THE MAIN CAMPUS. I THINK FRED MANAGED TO GET ONE OF THEM RIGHT IN FRONT OF BUILDING 1, RIGHT? SO I THINK WE'RE GOOD. BUT YOU KNOW, WE'RE VERY PROUD OF THIS ANNIVERSARY AND I THINK IT'S A WAY WE CAN MAKE OUR FOOTPRINT A LITTLE BIGGER IN THE NIH COMMUNITY. SPEAKING OF THAT, ONE OF THE THINGS I'VE DEDICATED THIS YEAR TO DOING, AND EVERYONE ON OUR STAFF IS HELPING, AND YOU'LL SEE EVIDENCE OF THIS AS WE MOVE THROUGH TODAY, WE'RE DOING A LOT MORE COLLABORATION WITH OTHER NIH INSTITUTES, AND THESE INCLUDE THE NATIONAL INSTITUTE ON AGING, THE NATIONAL INSTITUTE ON MENTAL HEALTH, OF COURSE OUR SISTER INSTITUTE, THE NATIONAL INSTITUTE ON DRUG ABUSE, NIDDK, JUST RECENTLY WE JOINED THE MOSAIC PROGRAM WITH NIGMS, SO THAT'S A LOT OF OUTREACH, WE'RE WORKING WITH THE NATIONAL INSTITUTE ON CHILD HEALTH, SO THERE'S A WHOLE BUNCH OF COLLABORATIVE WORK THAT WE'RE DOING, AND, YOU KNOW, ONE OF THE COUNCILS, MAYBE NEXT COUNCIL, BECAUSE WE'RE WORKING UP ALL OUR INTERACTIONS WITH THE REST OF NIH, MAYBE WE'LL HAVE A SLIDE ON THAT. SO THAT'S SOMETHING TO THINK ABOUT. I'M REALLY SAD TO TELL YOU THAT LAST WEEK WE LOST ONE OF OUR MOST DISTINGUISHED AND SENIOR SCIENTISTS IN THE INTRAMURAL PROGRAM. RICHARD KNOWN AT "BUD" VEECH PASSED AWAY SUDDENLY, CHIEF OF NIH'S INTRAMURAL LABORATORY OF METABOLIC CONTROL, WORLD RENOWNED SCIENTIST ON CELLULAR ENERGY METABOLISM, ALSO KNOWN FOR HIS WORK THAT CHARACTERIZED THERAPEUTIC BENEFITS OF A KETONE-RICH DIET AND SERVED AS A SCIENTIST IN THE FEDERAL GOVERNMENT FOR OVER 50 YEARS. THE KETONE -- INCLUDING ALCOHOL DISORDER. SO WE'RE REALLY SAD THAT HE'S NOT WITH US ANYMORE. GEORGE CAN TELL YOU MORE OF THE DETAILS. THERE'S A FUNERAL, I BELIEVE, ON SATURDAY, THIS COMING WEEKEND. GEORGE WILL REPRESNT US THERE. THERE IS AN OWE OBITUARY THAT'S BEING SENT OR WAS SENT THIS MORNING TO MICHAEL GOTTESMAN, WHO'S HEAD OF ALL OF INTRAMURAL, SO THERE WILL BE ANNOUNCEMENTS THROUGHOUT NIH. SO WE HAVE SOME NEW STAFF. IF THEY'RE HERE, I'M GOING TO ASK THEM TO RAISE THEIR HAND. EMILY BREWER, ARE YOU HERE, EMILY? SHE JOINED THE OFFICE OF DIRECTOR AS A PROGRAM SPECIALIST. SHE'LL BE SUPPORTING THE OFFICE OF THE DIRECTOR, THAT'S MY OFFICE, STAFF MEMBERS. PRY ARE TO PRIOR TO JOINING NIAAA, SHE WAS A PROGRAM ANALYST AT THE U.S. DEPARTMENT OF AGRICULTURE. DR. LUIS ESPINOZA HAS JOINED THE EXTRAMURAL PROJECT REVIEW BRANCH OF THE OFFICE OF EXTRAMURAL ACTIVITIES AS THE SCIENTIFIC REVIEW OFFICER OF THE CLINICAL, TREATMENT AND HEALTH SERVICES RESEARCH REVIEW SUBCOMMITTEE. WOW! THAT'S A LOT OF WORDS. BUT ANYWAY, HE'S THE SRO FOR AA-3. THAT'S A SHORTER WAY OF SAYING IT. HE PREVIOUSLY SERVED AS SRO AT THE CENTER FOR SCIENTIFIC REVIEW. WE'RE REALLY HAPPY TO HAVE HIM JOIN US. DEBORAH LANGER JOINED THE COMMUNICATIONS AND PUBLIC LIAISON BRANCH FROM THE NIH OD OFFICE OF DISEASE PREVENTION. SHE WILL BE SERVING AS COMMUNICATIONS LEAD FOR OUTREACH ACTIVITIES TO ADVANCE AND ENHANCE NIAAA'S STAKEHOLDER ENGAGEMENT, HAPPY TO HAVE YOU JOIN US. THEN WE HAVE KAREN HARRINGTON, TRANSITIONED FROM HER ROLE AS THE INTRAMURAL SECTION CHIEF IN THE ADMINISTRATIVE SERVICES BRANCH TO CLEAVE OF THE ADMINISTRATIVE SERVICES BRANCH. SO CONGRATULATIONS, KAREN. WE LOST A NUMBER OF PEOPLE. MOST OF THEM MOVED TO OTHER POSITIONS THAT WERE, YOU KNOW, NEW CHALLENGES FOR THEM, AND SOME RETIRED. SO ANITA BECHTHOLT, FORMER HEALTH SCIENCE ADMINISTRATOR, TRAN TRANSFERRED TO THE NATIONAL INSTITUTE OF MENTAL HEALTH WHERE SHE NOW SERVES AT THE ASSOCIATE DIRECTOR FOR RESEARCH TRAINING AND CAREER DEVELOPMENT IN THE DIVISION OF TRANSLATIONAL RESEARCH. BO FLEE ELLIS, FORMER ADMINISTRATIVE SERVICES BRANCH CHIEF ACCEPTED A NEW POSITION AS EXECUTIVE OFFICER WITH THE NIH CENTER FOR SCIENTIFIC REVIEW. DR. MEHDI FAROKHNIA, RESEARCH FELLOW IN THE LABORATORY ON CLINICAL PSYCHONEUROENDOCRINOLOGY AND NEUROPSYCHOPHARMACOLOGY HAS ACCEPTED A POSITION AS STAFF SCIENTIST AT THE NATIONAL INSTITUTE ON DRUG ABUSE. BRIDGETTE GREEN LEFT HER POSITION TO JOIN THE NURSING DEPARTMENT AT THE NIH CLINICAL CENTER AS LEAD EXTRAMURAL ASSISTANT IN SEPTEMBER. DR. DALE HERELD RETIRED IN SEPTEMBER AFTER 11 YEARS AS A HEALTH SCIENCE ADMINISTRATOR IN THE DIVISION OF METABOLISM AND HEALTH EFFECTS. BILL DUNTY HAS CONTINUED IN OUR FETAL ALCOHOL DISORDER PORTFOLIO AND DALE IS VERY MUCH MISSED BUT IT WAS TIME THAT HE WANTED TO RETIRE AND I THINK HE'S GOING TO BE HAPPY IN THAT ROLE. MINOO McFARLAND, A NURSE PRACTITIONER WITH THE LABORATORY OF NEUROIMAGING, DEPARTED NIH TO SPEND TIME WITH HER FAMILY. AND MY BELOVED ALESIA WILBUR LEFT ME AFTER 30 YEARS OF FEDERAL SERVICE, AND I'M STILL NOT OVER IT. [LAUGHTER] MANY OF YOU KNOW ALESIA RAN MY OFFICE, LITERALLY KEPT ME IN LINE, KEPT ME HONEST, KEPT ME ALIVE, AND WE REALLY MISS HER. DURING HER TIME AT NIAAA, SHE WORKED CLOSELY WITH ME, THE NIAAA DIRECTOR, AND MANAGED AS ADMINISTRATIVE STAFF AND FUNCTIONS WITHIN THE OFFICE THE DIRECTOR. HAPPILY, EMILY BREWER IS WITH US AND AURELIA HAS STAYED ON SO WE'RE MUDDLING THROUGH VERY BRAVELY BUT WE DO MISS ALESIA. BUDGET. MOSTLY GOOD NEWS. WE ACTUALLY HAVE A BUDGET. IT WAS ENACTED, NIAAA HAS AN INCREASE IN OUR BUDGET TO $526 MILLION. WE ESTIMATE FUNDING 760 RESEARCH PROJECT GRANTS WHICH IS ABOVE WHAT WE DID THE PREVIOUS YEAR. THE TOTAL COMPETING AWARDS IS 159, OTHER RESEARCH GRANTS 182, RESEARCH CENTERS STILL AT 21. AND TRAINING POSITIONS 326. I HAVE TO SAY OVER MY TIME AT NIH, WE HAVE, I THINK, SIGNIFICANTLY INCREASED OUR RESEARCH PROGRAM GRANTS AND WE HAVE SIGNIFICANTLY INCREASED OUR TRAINING POSITIONS. FOR THOSE OF YOU WHO WANT THE DETAILS PROBABLY AT RSA, I'LL SHOW A GRAPH OF THINGS OVER THE LAST SIX YEARS, BUT IT'S& GENERALLY BEEN IN THE RIGHT DIRECTION. SO THE F YEAR 20 BUDGET, WE RECEIVED $41.6 BILLION AT NIH, WHICH IS A $2.3 BILLION INCREASE FROM FISCAL YEAR '19. THIS FUNDING INCLUDES ALLOCATIONS FOR THE HEAL INITIATIVE, WHICH MANY OF YOU KNOW IS THE HELPING TO END ADDICTION LONG TERM INITIATIVE. THE 21ST CENTURY CURES ACT, THE BRAIN INITIATIVE, WHICH I THINK YOU'RE ALL FAMILIAR WITH, AND RESEARCH ON INFLUENZA. AND IT CONTINUES SUPPORT FOR THE GABRIELLA MILLER KIDS FIRST ACT PEDIATRIC RESEARCH INITIATIVE. WHAT YOU WANT TO KNOW IS NIAAA RECEIVED $545 MILLION, THAT'S A $19.8 MILLION INCREASE FROM FISCAL YEAR '19, WHICH I JUST SHOWED YOU THE DATA. FISCAL YEAR 21 BUDGET IS UNDER DEVELOPMENT. I CAN'T TELL YOU WHAT THIS INCREASE IS GOING TO TRANSLATE TO BECAUSE THERE ARE A LOT OF TAPS ON THE BUDGET, AND THEY COME AND GO. SO I'LL GIVE YOU AN EXAMPLE, THERE MAY BE A NEED THAT NIH PROVIDE EMERGENCY FUNDS FOR CORONAVIRUS, FOR EXAMPLE, SO I DON'T LIKE TO MAKE PREDICTIONS ABOUT WHAT EXACTLY THIS MEANS, BUT IT'S MUCH, MUCH BETTER THAN A DECREASE. I THINK THAT'S THE TAKE HOME MESSAGE. SO WE HAVE A LOT OF FUNDING OPPORTUNITY ANNOUNCEMENTS. THEY COME WITH EVERY COUNCIL MEETING. THESE ARE LISTED IN YOUR DIRECTOR'S REPORT. I'M NOT GOING TO GO THROUGH EACH ONE OF THESE, BUT THEY RANGE FROM THE NADIA CONSORTIUM, THE NEUROBIOLOGY OF ADOLESCENT DRINKING IN ADULTHOOD, TO MEDICATIONS DEVELOPMENT FOR TREATMENT OF ALCOHOL USE DISORDER, AND THEN WE'RE DOING A LOT MORE NOTICES THAN WE ARE NECESSARILY WITH FOAs. AND THESE INCLUDE ADMINISTRATIVE SUPPLEMENTS FOR REGULATORY SUPPORT FOR SBIRs. AND A NUMBER OF OTHERS THAT WE ARE PARTICIPATING IN FROM NEURAL CIRCUITS RELATED TO MENTAL ILLNESS IN NON-HUMAN PRIMATES TO A NUMBER OF FOAs IN SUPPORT OF CAREER DEVELOPMENT AND DIVERSITY IN RESEARCH TRAINING. WE PARTICIPATE IN A GREAT NUMBER OF THESE. I MENTIONED THAT WE JUST JOINED MOSAIC. AND THEN THERE ARE MULTIPLE FUNDING OPPORTUNITY ANNOUNCEMENTS RELATED TO SEX AND GENDER INFLUENCES, AND SO I REFER YOU TO THE DIRECTOR'S REPORT FOR THE DETAILS. WHY IS THIS IMPORTANT? WELL, WHEN YOU GO BACK TO YOUR HOME INSTITUTIONS, YOU KNOW, WE CERTAINLY HOPE THAT YOU WOULD ENCOURAGE PEOPLE TO LOOK AT THESE ANNOUNCEMENTS, ESPECIALLY YOUNG, BRIGHT PEOPLE WHO WE WOULD LIKE TO HAVE IN THE ALCOHOL FIELD. THESE ARE OPPORTUNITIES FOR RESEARCH, AND YOU KNOW, AND THEN THE ONE THING I WOULD LIKE TO SAY IS, WHEN YOU DO THIS ENCOURAGEMENT OF YOUNG PEOPLE, REMIND THEM TO NOT SEND IN A GRANT TO NIAAA WITHOUT CALLING ONE OF OUR PROGRAM OFFICERS FIRST. PLEASE DO THAT BECAUSE YOU KNOW, THEY CAN HELP OUT PARTICULARLY A YOUNG PERSON ON HOW YOU CROSS ALL THE Ts AND DOT ALL THE Is, SO ON AND SO FORTH. SO THERE'S SOME THINGS THAT I WANTED TO MENTION ABOUT NIAAA BEING IN THE NEWS. THERE WAS A STUDY THAT WAS JUST PUBLISHED BY AARON WHITE, THERE'S AARON, JEN CASSEL. JEN IS HERE. AND RALPH INGSTON. "USING DEATH CERTIFICATES TO EXPLORE CHANGES IN ALCOHOL-RELATED MORTALITY IN UNITED STATES 1999 TO 2017." IT REVEALED THAT ALCOHOL RELATED MORTALITY HAS DOUBLED FROM 1999 TO 2017. THE DEATH RATES WERE HIGHEST AMONG MEN AND MIDDLE AGED AND OLDER ADULTS, 45 TO 74. THE DEATH RATES INCREASED OVER TIME ACROSS ALL AGE GROUPS EXCEPT FOR THE 16 TO 20-YEAR-OLDS, AND THE 75 AND OLDER GROUP. THESE STATISTICS ALIGN WITH OTHER REPORTS THAT HAVE HIGHLIGHTED CHANGING TRENDS IN DRINKING PATTERNS AND INCREASED CONSEQUENCES OF ALCOHOL IN WOMEN IN THE AGING POPULATION, BOTH OF WHICH ARE FOCUSES OF OUR AND THE MORTALITY DATA LINKED TO ALCOHOL USE IS ALSO LINKED TO THE "DEATHS OF DESPAIR" AND PROBABLY INVOLVES CONTRIBUTIONS FROM SUICIDE, DRUG OVERDOSE, AND LIVER DISEASE. AND ALCOHOL ACCOUNTS FOR ABOUT 50% OF LIVER DISEASE IN THIS COUNTRY, FOR YOU INDIVIDUALS WHO ARE NEW TO OUR PATHOPHYSICIAN PATHOPHYSIOL OGY ASSOCIATED WITH ALCOHOL. I THINK THIS IS A DRAMATIC EXAMPLE OF HOW ALCOHOL GETS INVOLVED IN SO MANY DISEASE PROCESSES. IT'S ESTIMATED THAT THERE'S SOMETHING LIKE 200 DISEASES THAT ALCOHOL CAN EXACERBATE, CAN MAKE WORSE OR ACTUALLY CAUSE. AND YOU KNOW, I THINK WE OFTEN FORGET ABOUT THIS, AND PROBABLY SOME OF THIS IS ACTUALLY AN UNDER -- AARON LIKES TO SAY IS PROBABLY AN UNDERESTIMATION BECAUSE NOT EVERYONE LISTS ALCOHOL AS A CONTRIBUTOR ON DEATH CERTIFICATES. AND WE ALSO KNOW, THOSE OF YOU CONCERNED ABOUT THE OPIOID OVERDOSES, ALCOHOL PROBABLY CONTRIBUTES TO 15 TO 20% OF THOSE AS WELL. COMING UP, WE HAVE THE NATIONAL DRUGS AND ALCOHOL CHAT DAY. WE DO THIS WITH NIDA EVERY YEAR. IT'S AN ANNUAL LIVE ONLINE CHAT HELD BETWEEN HIGH SCHOOL STUDENTS AND THE NIH SCIENTISTS. STUDENTS FROM AROUND THE COUNTRY ASK QUESTIONS THAT THEY MOST WANT ANSWERS TO ABOUT DRUGS AND ALCOHOL MISUSE, INCLUDING DRUG EFFECTS, HOW TO HELP FRIENDS OR FAMILY THAT ARE USING DRUGS AND WHAT CAUSES ADDICTION. EXPERT SCIENTISTS GIVE THEM THE FACTS. SO I ALWAYS PARTICIPATE, NORA VOLKOW ALWAYS PARTICIPANTS, JOSH GORDON HAS BEEN PARTICIPATING. IT'S A HOOT BECAUSE THEY ASK THE DAMNEDEST QUESTIONS, WE GO ON FOR SEVERAL HOURS DOING THIS. THEN ONE THING I WANTED TO MENTION TO Y'ALL, ARE WE EXPERIENCING A CHUL TEURL SHIFT IN ATTITUDES CULTURAL SHIFT IN ATTITUDES ABOUT ALCOHOL USE? SOME OF US TALKED ABOUT THIS LAST NIGHT. WE GOT A LOT OF INTERES PARTIALLY BECAUSE FRED RAISED THE INTEREST WITH THIS MARATHON SERIES OF INTERVIEWS I DID THAT WE DO ONCE A YEAR, HE RAISED THE ISSUE ABOUT DRY JANUARY AND THE PRESS PICKED IT UP, BUT THIS IS A PHENOMENON THAT STARTED IN THE UNITED KINGDOM A COUPLE YEARS AGO, WHERE YOU BASICALLY DON'T DRINK FOR A MONTH. AND YOU KNOW, I THINK IT'S GAINING IN POPULARITY IN THE UNITED STATES. IT THERE WAS A GREAT DEAL OF INTEREST IN THIS AND I THINK IT'S VALUABLE FOR MULTIPLE REASONS BUT ONE IS, YOU KNOW, IT ALLOWS A PERSON TO RE-EVALUATE OR EVALUATE THEIR RELATIONSHIP WITH ALCOHOL. YOU KNOW, IF YOU START FEELING BETTER, YOU'RE SLEEPING BETTER, YOUR DIGESTIVE SYSTEM IS BETTER, YOU'RE BRIGHT EYED AND BUSHY TAILED GETTING TO WORK MONDAY MORNING, YOUR BODY IS TRYING TO TELL YOU SOMETHING. THAT IS, IF THIS OCCURS WHEN YOU'RE NOT DRINKING. THE OTHER REASON I THINK IT'S REALLY VALUABLE IS BECAUSE IT REALLY CUTS DOWN ON THE STIGMA OF NOT DRINKING. AND THERE IS A STIGMA ASSOCIATED WITH PARTICULARLY IN YOUNG PEOPLE IF YOU'RE NOT PART OF THE CROWD THAT'S DRINKING. BUT YOU CAN SAY I'M DOING DRY JANUARY OR I'M PART OF SOBER-CURIOUS OR WHATEVER PARTICULAR TREND, YOU KNOW, THAT IS POPULAR IN YOUR AREA OR THAT YOU'VE EMBRACED. YOU KNOW, THERE ARE DRY BARS POPPING UP IN SOME MAJOR CITIES LIKE NEW YORK, WHERE YOU CAN GO AND HAVE A GOOD TIME AND ALCOHOL IS NOT BEING SERVED. SO YOU KNOW, WE'VE KIND OF BEEN GOING WITH FLOW WITH THIS, BUT I THINK YOU'RE STARTING TO SEE A SHIFT. AND YOU KNOW, I WANT TO NOTE SOMETHING THAT WE'VE SEEN A STEADY DECLINE IN UNDERAGED DRINKING IN THE UNITED STATES OVER THE LAST 15 YEARS. THIS IS THE GOOD NEWS. WE'VE SEEN A DECLINE NOW IN BINGE DRINKING IN COLLEGE STUDENTS OVER THE LAST 10 YEARS. AND EVEN THOUGH I'M NOT SUPPOSED TO MAKE A BIG DEAL OF IT, BUT SINCE COLLEGE AIM CAME OUT, IT'S PRETTY MUCH A STRAIGHT LINE DOWN, AND YOU'LL NOTE FROM THAT PREVIOUS SLIDE I JUST SHOWED YOU ABOUT THE DEATHS AND MORTALITY, THAT THE 16 TO 20-YEAR-OLD GROUP IS THE ONE THAT WAS NOT SHOWING THIS INCREASED MORTALITY. SO MY HOPE IS THAT WE ARE ACTUALLY SEEING POSSIBLY AN AGE-RELATED SHIFT IN RELATIONSHIP WITH ALCOHOL. AND THE THIRD REASON I THINK THIS IS REALLY GOOD, THESE THINGS LIKE DRY JANUARY AND SOBER-CURIOUS IS, I SAID THIS TO THE PRESS, YOU KNOW, YOU KNOW WHAT AGE GROUP I'M IN, ALL RIGHT? IT TOOK US A LONG TIME IN MY AGE GROUP TO FIND A GOOD RELATIONSHIP WITH ALCOHOL. IF WE CAN HELP MILLENNIALS DO THIS IN A FASTER, QUICKER WAY BY THINGS LIKE SOBER-CURIOUS OR DRY JANUARY, SO MUCH THE BETTER. AND ON THAT SOBERING NOTE, I WANT TO MAKE ANOTHER SOBER POINT, THAT WE'VE NOW EMBRACED, WE ALWAYS EMBRACE THE U.S. DIETARY GUIDELINES BUT THAT'S GOING TO BE OUR METRIC FROM NOW ON. WE'VE YOU PUT IT IN ALL THE WEBSITES, WE'VE CHANGED RE-THINKING DRINKING. WE'RE NOT GOING TO BE PARSING THE BUSINESS ABOUT HOW MANY DRINKS DOES IT TAKE BEFORE YOU'RE VULNERABLE FOR AN ALCOHOL DISORDER. WE'RE SIMPLY GOING TO GO WITH THE U.S. DIETARY GUIDELINES, NO MORE THAN TWO DRINKS A DAY FOR MEN, NO MORE THAN ONE DRINK A DAY FOR WOMEN AND NO INDIVIDUALS UNDER 21 SHOULD BE DRINKING. THERE ARE ALSO OTHERS THAT SHOULD AVOID ALCOHOL COMPLETELY, INCLUDING PEOPLE WHO PLAN TO DRIVE OR OPERATE MACHINERY OR PARTICIPATE IN ACTIVITIES THAT REQUIRE SKILL, COORDINATION AND ALERTNESS, PEOPLE WITH CERTAIN MEDICAL CONDITIONS OR WHO TAKE CERTAIN MEDICATIONS, PEOPLE THAT ARE RECOVERING FROM ALCOHOL USE DISORDER OR ARE UNABLE TO CONTROL THE AMOUNT THEY DRINK, PEOPLE THAT ARE PREGNANT OR TRYING TO BECOME PREGNANT. AND TO BE HONEST, SOME OF YOU, YOU KNOW, WHO ARE MAYBE MISSING THE ALLELE FOR -- HYDROGENASE, YOU DON'T WANT TO DRINK AND MAYBE YOU SHOULDN'T DRINK. AS ONE OF MY COLLEAGUES, I WON'T MENTION HIS NAME SAID, IF I DRINK, GEORGE, IT DOESN'T TAKE A .08 TO GET ME DANGEROUS BEHIND THE WHEEL, IF I EVEN HAVE A COUPLE SIPS OF ALCOHOL, I GET DIZZY, I GET RED-FACED, I GET A REACTION, I GET NAUSEOUS AND YOU DON'T WANT ME BEHIND THE WHEEL OF A CAR EITHER. SO I JUST WANT TO EMPHASIZE, THIS IS THE METRIC THAT WE'RE EMBRACING AT NIAAA. CANCER INSTITUTE HAS FOR A LONG TIME HAD ON THEIR WEBSITE THAT EVEN ONE DRINK A DAY CAN CONVEY A VULNERABILITY TO BREAST CANCER IN WOMEN, AND WE HAVE ADDED THOSE KIND OF METRICS TO OUR WEBSITE AS WELL. OKAY. SO THAT'S KIND OF THE GENERAL PIECES THAT I WANTED TO TELL YOU A LITTLE BIT ABOUT, SOME OF THE SHIFTS IN THINKING THAT WE'RE DOING, SOME OF THE SHIFT IN HOW WE'RE PRESENTING, YOU KNOW, GUIDELINES FOR THE PUBLIC. YOU KNOW, BEFORE I LAUNCH INTO THE RESEARCH HIGHLIGHTS, SOME OF THE THINGS WE HAVE THAT WE'RE WORK ON AND HOPEFULLY MAYBE EVEN BY NEXT COUNCIL, WE'LL HAVE SOME TANGIBLE PROGRESS, BUT WE'RE WORKING ON A CORE PREVENTION RESOURCE TO GET WHAT PREVENTIONS ARE EFFECTIVE OUT FOR MIDDLE SCHOOLS AND HIGH SCHOOLS OUT TO THE GENERAL POPULATION, AND THEN A CORE CLINICIAN RESOURCE WHERE WE HOPE TO HAVE BASIC INFORMATION THAT CLINICIANS COULD USE IN UNDERSTANDING ALCOHOL IN THEIR PRACTICES. WHEN I SAY CLINICIAN, I MEAN EVERYONE FROM A PHARMACIST TO A NURSE PRACTITIONER TO A CLINICAL PSYCHOLOGIST TO A PRIMARY CARE DOC TO A BOARD CERTIFIED ADDICTION MEDICINE SPECIALIST. OKAY? SO THOSE ARE THE TWO THINGS THAT ARE A HIGH PRIORITY FOR ME CURRENTLY. I WANT TO TELL YOU ABOUT SOME RESEARCH HIGHLIGHTS. THIS ROUND IT'S GOING TO BE LARGELY LIVER SO I'M GOING TO DO THE BEST I CAN ON THE LIVER. I'VE CERTAINLY LEARNED A LOT BY READING SOME OF THESE PAPERS. I THINK RACHEL ANDERSON, WHO HELPED ME WITH THE SLIDES, HAS LEARNED A LOT ABOUT THE LIVER AS WELL. AND I'M SORRY TO SAY, BUT NEUROSCIENCE GOT THE SHORT SHRIFT THIS TIME. AND I WANT TO SAY THAT A NUMBER OF THESE CONTRIBUTIONS ACTUALLY COME FROM OUR INTRAMURAL PROGRAM. SO THIS PARTICULAR STUDY IS REALLY PRESS WORTHY IN THE SENSE THAT IT'S MAKING THE CASE THAT CANNABINOIDS EXACERBATE ALCOHOL TERATOGEN CYST AND THEY DO IT VIA A CANNABINOID 1 HEDGE HOG REACTION. THIS STUDY DEMONSTRATED THAT A SINGLE EXPOSURE TO KA IN ADDITION CANNABINOIDS PRENATALLY CAUSED CRANIOFACIAL AND BRAIN MALL FOR MAKES SIMILAR TO THOSE CAUSED BY PRENATAL ALCOHOL EXPOSURE. THIS DRUG IS A CANNABINOID 1 AGONIST, IT'S FAMOUS TO ME BECAUSE I KNEW IT WHEN THEY FIRST IDENTIFIED BINDING TO CANNABINOIDS IN THE BRAIN. THIS WAS THE LIGAND THAT WAS USED TO BIND TO THE RECEPTOR. IT'S A VERY POTENT CANNABINOID 1 AGONIST. SO THIS DRUG WAS USED AT DOSES UP TO .25 MILLIGRAMS PER KILOGRAM, AND THEN THE ALCOHOL WAS IN 2.8 GRAMS PER KILOGRAM AT THE HIGHEST DOSE. YOU CAN SEE ON THE LEFT-HAND SIDE OF THE PANEL FROM ALCOHOL ALONE, BUT WHEN YOU ADD THE CANNABINOID, YOU SEE MORE PUPS WITH AN EYE DEFECT. YOU CAN SEE IN THE PICTURE DOWN AT THE BOTTOM THAT SHOWS, YOU KNOW, A CRANIOFACIAL MALFORMATION FOLLOWING EXPOSURE TO ALCOHOL AND THIS CANNABINOID 1 AGONIST. SO MECHANISTIC STUDIES, THEY FOLLOWED THROUGH IN THIS REPORT ON, INDICATED THAT BOTH ALCOHOL AND THIS CANNABINOID AGONIST CONVERGE TO INHIBIT THE SONIC HEDGEHOG PATHWAY, THIS COULD BE ETIOLOGICAL. THIS SHEDS LIGHT ON THE MECHANISM OF ALCOHOL AND KA NEIGHBOR NOID INDUCED BIRTH DEFECTS AND FURTHER HIGHLIGHT THE DANGER OF COBIRTH COULD-SUBSTANCE USE DURING PREGNANCY. THEY WERE ACTUALLY RECOMMENDING THAT PREGNANT WOMEN USE CANNABINOIDS TO TREAT MORNING SICKNESS, AND, YOU KNOW, THERE'S NOT A GREAT HISTORY OF DRUGS BEING USED TO TREAT MORNING SICKNESS. SOME OF YOU REMEMBER THALIDOMIDE. I DON'T WANT TO GO SO FAR AS TO SAY THAT CANNABINOIDS ARE AS BAD AS THALIDOMIDE, BUT WHAT THIS STUDY SHOWS IS THAT IF YOU ARE ALSO DRINKING AND TAKING CANNABINOIDS, THEY CAN POTENTIATE EACH OTHER POSSIBLY. AND MUCH, MUCH MORE WORK SHOULD BE DONE IN THIS AREA AND I CERTAINLY HOPE THAT PEOPLE WILL START SENDING IN PROPOSALS TO FOLLOW UP ON THIS KIND OF WORK. THIS IS A MICROBIOME STUDY THAT ARGUES THAT BACTERIOPHAGE TARGETING -- THIS WAS A MOUSE MODEL OF ETHANOL INDUCED LIVER DISEASE. THEY USED A CHRONIC BINGE ETHANOL DIET. AND THEY BASICALLY SHOWED THAT THE PRESENCE OF CYTOLYSIN-POSITIVE E-FAECALIS CORRELATED WITH THE SEVERITY OF LIVER DISEASE AND MORTALITY IN PATIENTS WITH ALCOHOLIC HEPATITIS. AND FURTHERMORE, USING THIS MOUSE MODEL OF ALCOHOL-ASSOCIATED LIVER DISEASE, THEY DEMONSTRATED THAT THE BACTERIOPHAGES THAT SPECIFICALLY TARGET THIS CYTOLYSIN-POSITIVE E-FAECALIS ARE EFFECTIVE IN REDUCING LIVER INJURY SUGGESTING A POTENTIAL THERAPEUTIC TARGET FOR THE TREATMENT OF ALCOHOLIC HEPATITIS. SO WHAT THESE GRAPHS SHOW ARE DECREASES IN THE CHEMOKINES AND DECREASES IN A COLLAGEN-TYPE 1 ALPHA-1 MEASURE IN THE RIGHT-HAND SIDE GRAPH WHERE THEY USE THE PHAGE THERAPY AGAINST CYTOLYTIC E-FAECALIS AND IT REVERSES SOME OF THESE MEASURES OF LIVER DAMAGE. TO DO THIS ORIGINAL EXPERIMENT, WHICH IS ON THE LEFT SIDE IN THE PANELS, THEY ACTUALLY TOOK GERM-FREE MICE AND THEY INJECTED THEM -- THEY COLONIZED THEM WITH THE FECES FROM TWO CYTOLYSIN-POSITIVE PATIENTS, HUMANS WITH ALCOHOL LINKED HEPATITIS. THEY'RE ACTUALLY TAKING THIS BACTERIUM FROM PEOPLE WITH HEPATITIS, INJECTED IT INTO MICE, COLONIZING THE MICE, AND THEN BEING ABLE TO IDENTIFY THE TARGET, THIS CYTOLYSIN, AND USE THAT TARGET TO ACTUALLY REVERSE ELEMENTS OF ALCOHOLIC LIVER DAMAGE. SO ANOTHER PLAYER IN LIVER DAMAGE ASSOCIATED WITH CHRONIC ALCOHOL. THIS TIME FROM THE MICROBIOME. IN THE SAME VEIN, THIS STUDY SHOWED THAT GLUTAMATE SIGNALING -- BY THE WAY, THE PREVIOUS AUTHORS WERE FROM UCSD, AND THE FIRST I SHOWED YOU WAS FROM UNC. THIS PARTICULAR STUDY WAS INTRAMURAL WITH DR. CHOI AND GEORGE KOONOS'S GROUP, SOME OF THE ACTIONS OF GLUTAMATE ARE METABOTROPIC GLUTAMATE RECEPTORS. THE CURRENT STUDY DEMONSTRATED THAT GLUTAMATE SIGNALING VIA THESE RECEPTORS IS ALSO INVOLVED IN MEDIATING ALCOHOL-ASSOCIATED LIVER DISEASE. SO THE BASIC SCHEME HERE SHOWN IN THE CARTOON DIAGRAM IS THAT ALCOHOL INCREASES THE ACTIVITY OF THE CYSTINE GLUTAMATE ANTIPORTER OR WHAT I CALL EXCHANGER, THIS EXCHANGES GLUTAMATE RELEASE AND ON THE HEPATIC STELLATE CELLS WHICH HITS THE METABOTROPIC GLUTAMATE RECEPTOR ON THESE CELLS. THAT TIM LATES T-AG PRODUCTION PRODUCTION -- HEPATOLIPOGE NIC GENE AND THAT CAUSES STEATOSIS IN LIVER, WHICH IS FATTY LIVER. THE RESULTS SUGGEST INHIBITION OF A SINGLE PHARMACOLOGICAL TARGET MAY HAVE THERAPEUTIC VALUE IN THE TREATMENT OF BOTH ALCOHOL USE DISORDER AND ALCOHOL-INDUCED LIVER DAMAGE. IF IT'S TRUE, YOU CAN TAKE TO THE BANK. BUT I MEAN, I THINK, YOU KNOW, WE ARE GETTING INCREASINGLY INTERESTED IN THE INSTITUTE IN THE CROSSTALK BETWEEN WHAT HAPPENS IN THE LIVER, WHAT HAPPENS IN THE BRAIN, AND NOT JUST CROSSTALK, BUT PARALLEL ACTIVITIES. AND I THINK THERE'S A LOT OF HOPE THAT THROUGH THIS INTERACTION AND THROUGH KIND OF A COUNCIL WHERE WE HAVE PEOPLE WHO WORK ON THE LIVER AND WE HAVE PEOPLE WHO WORK ON THE BRAIN, SOME OF THESE THINGS CAN BE BROUGHT TO FRUITION. I THINK THIS PAPER WAS A GOOD EXAMPLE OF THAT, AND THAT'S ONE OF THE REASONS WE CHOSE IT. THIS ONE IS A LITTLE PAROCHIAL BECAUSE I WAS ON THIS STUDY WITH FOLKLOF AND HIS GROUP AND LEE. OUR CONTRIBUTION WAS THAT IT WAS OUR RATS' LIVERS THAT WE SENT. BURR BASICALLY WHAT BUT BASICALLY WHAT HE FOUND WAS THAT EPIGENOME-WIDE ASSOCIATION OF ALCOHOL USE DISORDER WITH A COMPOUND KNOWN AS PRO PROTEIN CONVERTASE SUBTILISIN/KEXIN WHICH IN SHORT IS THIS THING ON HERE CALLED PCS K-9. ANYWAY, THIS COMPOUND WAS A TARGET THAT IS EPGENICLY REGULATED BY ALCOHOL CONSUMPTION IN AN EARLIER STUDY BY LOHOFF AND COLLABORATORS. SO IN THIS PARTICULAR STUDY, HE WANTED TO SEE WHETHER IT HAD ANYTHING TO DO WITH ALCOHOL USE DISORDER AND ALCOHOL RELATED LIVER DISEASE AND SO HE FOUND A COMPOUND THAT'S ON THE, IT'S CALLED ALIROCUMAB, AND THIS COMPOUND TRADE NAME -- SOME OF YOU MAY KNOW OF IT BECAUSE IT'S ACTUALLY A SECOND TIER TREATMENT FOR SEVERE HYPERCHOLESTEREMIA. SO IF YOU HAVE HIGH CHOLESTEROL, THIS DRUG, YOU CAN GET INJECTIONS OF THIS DRUG AT A SMALL FORTUNE, IT RUNS ABOUT $4,000 TO $8,000 A YEAR, BUT IT'S OUT ON THE MARKET FOR TREATING HYPERCHOLESTEREMIA. AND I THOUGHT FALK CLEVERLY KNEW THAT IT ALSO INHIBITED PCS K-9. SO HE ADMINISTERED TO RATS WHO HAD BEEN MADE DEPENDENT ON ALCOHOL WITH A LIQUID DIET CONTAINING 12% ALCOHOL FROM MY LAB AND WE SENT THE RATS OR THEIR LIVERS DOWN TO FALK. IN ANY EVENT, WHAT HE SHOWS IN THIS PARTICULAR STUDY IS THERE'S A DECREASE IN ALT AND AST, WHICH REFLECT LIVERRER LIVER INJURY. HE ALSO SEES A DECREASE IN THE MRNA FOR PCS K-9 AND HE SEES DECREASES IN THE LDL -- INCREASES IN THE LDL RECEPTOR, WHICH IS THE LOW DENSITY LIPOPROTEIN RECEPTOR, BUT HE SEES DECREASES IN TRANSCRIPTION FACTOR THAT CONTROLS CHOLESTEROL HOMEOSTASIS. SO THESE ARE INTRIGUING RESULTS. YOU HEARD ABOUT FALK, SOME OF YOU IN THE BSC REVIEW AND THIS IS ONE OF THE EXCITING AREAS THAT HE'S WORKING ON THAT HE'S PLANNING ON EXPANDING IN HIS FUTURE RESEARCH, AND AGAIN I LIKE THE IDEA THAT WE HAVE A LINK BETWEEN WHAT THE LIVER DOSES AND OTHER PHYSIOLOGICAL EFFECTS, AND WHO KNOW, MAYBE YOU CAN TREAT YOUR HIGH CHOLESTEROL AND REVERSE SOME OF YOUR LIVER DAMAGE AT THE SAME TIME. THEN CATHY YOUNG'S DIVISION PUT THIS ONE IN AS A HIGH PROFILE PAPER, AND THIS GROUP IS FROM THE GEORGIA STATE UNIVERSITY, AND IT DOESN'T REALLY HAVE A WHOLE LOT TO DO WITH ALCOHOL, BUT THEY USED -- ONE OF THE MODELS THEY USED WAS A WAY OF PRODUCING ALCOHOLIC LIVER DISEASE IN RATS, THEY USE THIO THIOACETAMIDE, THIS MARKER FOR COLLAGEN DISTRIBUTION IS A MODEL FOR FIBROSIS. THIS PARTICULAR NEW ASSAY CAN PICK THIS UP. IN THESE ANIMALS BY IMAGING, USING A MAGNETIC RESONANCE IMAGING. THEY CAN ALSO PICK UP A NON-ALCOHOLIC STEATO HEPATITIS DIET. I THOUGHT THIS WAS KIND OF COOL, THEY GET WHAT'S CALLED A WESTERN DIET. I GUESS THAT MEANS MCDONALD'S, YOU KNOW? AND FRUCTOSE IN THEIR DRINKING WATER. SO THAT'S THE DIET THAT CAUSES NASH. ANYWAY, I THOUGHT IT WAS PRETTY COOL THAT WITH THE IMAGING, THIS IS THE SCHEME OVER HERE ON THE RIGHT SHOWING YOU, YOU KNOW, HOW THEY DEVELOP THIS MOLECULE AND WHAT CHANGES OCCUR THAT INDICATE EARLY FIBROSIS AND SEVERE FIBROSIS. SO I THINK THIS COULD BE OF GREAT USE FOR THE ALCOHOL COMMUNITY, AND I DON'T KNOW WHAT JIJAY THINKS ABOUT VIJAY THRINGS ABOUT IT THINKS ABOUT IT -- THUMBS UP. IF WE'RE GOING TO HAVE THIS CROSSTALK AND DO AN EARLY AN INTERVENTION AS POSSIBLE FOR LIVER DISEASE BUT ALSO ALCOHOL USE DISORDER. AND THEN ANOTHER ONE THAT I HELPED WITH A LITTLE BIT BASICALLY WITH ADRIENNE GUILLOT AND BEN GAU'S GROUP WITH INTRAMURAL WAS A STUDY -- BEN IS REALLY OBSESSED WITH FIGURING OUT WHERE IN THE BODY ALDEHYDE DEHYDROGENASE IS ACTUALLY DOING ITS METABOLIC EFFECTS, WHICH IS TO BREAK DOWN ACID ALDEHYDE. MOST OF YOU KNOW, THIS IS THE SECOND LIVER IN THE METABOLISM OF ALCOHOL. FIRST THERE'S ALCOHOL DEHYDROGENASE, THEN THERE'S -- IF YOU BLOCK IT, MOST OF YOU KNOW YOU RAISE ACET TALDEHYDE. THE DRUG HAS BEEN OUT THERE FOR YEARS BUT WHAT BEN AND ADRIENNE HYPOTHESIZED WAS THAT MAYBE THEY COULD JUST REDUCE ALDEHYDE DEHYDROGENASE IN THE LIVER AND ALSO ALTER ALCOHOL INTAKE. AND BASICALLY WHAT THIS STUDY SHOWS IS THAT IF YOU USE THE DID MODEL, YOU SEE A DECREASE, A DOSE-DEPENDENT DECREASE, DEPENDING ON IF YOU HAVE A GLOBAL KNOCKOUT, WHICH IS THE MINUS MINUS THERE, OR YOU HAVE ONLY THE LIVER KNOCKOUT. AND YOU ALSO DECREASE ALCOHOL PREFERENCE, PARTICULARLY AT THE HIGH DOSES OF ALCOHOL INTAKE. AND THIS GRAPH OVER HERE ON THE LEFT SHOWS THAT, YOU KNOW, ALDEHYDE DEHYDROGENASE IS METABOLIZED -- ADL, ALDEHYDE DEHYDROGENASE IS ALSO LOCATED IN OTHER ORGANS OF THE BODY AND CONTRIBUTES TO ASSET ALDEHYDE METABOLISM. THERE'S STILL A HERD OF OTHER ORGANS THAT CONTAIN THIS ENZYME AND CONTRIBUTE TO METABOLISM. WE JUST GOT A LETTER FROM A CHAP IN ENGLAND WHO'S RETIRED BUT HE WANTED US TO MENTION -- I DIDN'T KNOW THIS, THAT SIGH AN MIGHT MIGHT IS APPARENTLY A SECOND LINE DRUG THAT ACTS LIKE DIE DISULFIRAM. IT ACTUALLY PRODUCES A LITTLE MORE LIVER TOXICITY THAN DISULFIRAM BUT IT'S BEEN USED IN THE SAME WAY, SO WE ALREADY HAVE GENERATED SOME INTEREST IN THE FIELD ON THIS PARTICULAR GENETIC MANIPULATION. WHO KNOW, THERE MIGHT BE A WAY DOWN THE LINE THAT THIS COULD CONTRIBUTE AS ANOTHER POTENTIAL TREATMENT FOR ALCOHOL USE DISOR DISORDER. BY THE WAY, SOME OF YOU MAY WONDER, WHY DON'T WE JUST USE DISULFIRAM FOR EVERYBODY? WELL, THE REASON IS BECAUSE PEOPLE DON'T TAKE IT. THAT'S THE ISSUE. THERE ARE A NUMBER OF STUDIES, SOME CHAMPIONED BY A GROUP IN SCOTLAND WHERE THEY ACTUALLY MONITORED PEOPLE TAKING THE DISULFIRAM. IF YOU MONITOR THE SUBJECTS AND MAKE SURE THAT SIGNIFICANT OTHER IS THERE WITH A BASEBALL BAT, YOU KNOW, MAKING SURE THAT THE OTHER SIGNIFICANT OTHER IS TAKING THEIR DIE DISULFIRAM, IT ACTUALLY WORKS VERY WELL, BUT THAT'S THE ISSUE. SO I DID PAY SOME HOMAGE TO THE BRAIN. THIS IS ACTUALLY A VERY NICE STUDY BY MIRIAM BOCARSKY AND GROUP IN THE INTRAMURAL PROGRAM, AND BASICALLY IT'S PRETTY WELL DIAGRAMMED HERE ON THE RIGHT-HAND SIDE, BUT WHAT THEY CAN DO WITH NOW THESE MOLECULAR GENETIC MANIPULATIONS IS REMOVE THE DOPAMINE D2 RECEPTOR SELECTIVELY IN THE STRIATUM. NOW JUST AGAIN A LITTLE BIT OF BACKGROUND, D2 RECEPTORS, NOR A VOLKOW HAS SHOWN IN HER SEMINOLE WORK THAT D2 RECEPTORS IN MOST DRUGS OF ABUSE ARE DECREASED, AND THERE'S BEEN AN ARGUMENT THAT THAT IS CAUSED BY CHRONIC ADMINISTRATION OF THE DRUG BUT IT'S ALSO -- THERE'S AN ARGUMENT THAT IT CAN BE A VULNERABILITY FACTOR FOR INCREASED SELF ADMINISTRATION OF DRUGS, INCLUDING ALCOHOL. SOME OF HER MOST ROBUST STUDIES, NORA VOLKOW, IN HUMANS, USING PET SCANS IS WITH ALCOHOL DEPENDENT INDIVIDUALS. ALL RIGHT? AND SO WHAT VERONICA ALVAREZ' GROUP HAS BEEN DOING IS TRYING TO FIGURE OUT HOW THESE DIRECT AND INDIRECT PATHWAYS IN THE STRIATUM WORK, AND BASICALLY WHAT THEY SHOW IS THAT ON MEDIUM SPINY NEURONS, IF YOU PRODUCE A SELECTIVE LOSS OF THE D2 RECEPTORS, YOU INCREASE ALCOHOL STIMULATION MEASURED BY LOCAL MOTOR ACTIVITY AND YOU DECREASE ALCOHOL SEDATION. THE ALCOHOL STIMULATION REQUIRES THE D1 RECEPTOR, SO IF YOU TAKE THAT OUT, YOU LOSE THE STIMULATION REGARDLESS, BUT WHEN YOU TAKE OUT THE D2 RECEPTOR, YOU ALSO POTENTIATE THE EFFECTS OF D1 ACTIVATION ON LOCAL MOTOR ACTIVITY. SO LOW D2s EQUALS A D1 HYPERSENSITIVITY, AND THEIR ARGUMENT IS THIS COULD LEAD TO COMPULSIVE DRINKING. SO BASICALLY, YOU KNOW, WHAT WE WROTE HERE, WHAT RACHEL AND I WROTE WAS HEIGHTENED SENSITIVITY TO ALCOHOL STIMULATING EFFECTS HAS PREDICTIVE VALUE FOR ALCOHOL MISUSE USING TRANSGENIC MICE AND OTHER GENETIC MANIPULATIONS, THIS STUDY PROVIDED DIRECT EVIDENCE THAT LOWERING LEVELS OF D2 RECEPTORS ON STRIATAL PROJECTION NEURONS HEIGHTENS ALCOHOL RELATED STIM TRI EFFECTS AND ESCALATION OF ALCOHOL INTAKE. THEY SHOW AN ANTI -- THAT DESPITE PUNISHMENT, THE ANIMALS WILL KEEP DRINKING. SO THIS REALLY SUGGESTS THAT THE LOW D2 RECEPTOR COULD BE CONTRIBUTING TO THE ETIOLOGY AND BEGINNING OF COMPULSIVE DRINKING. THIS IS KIND OF COOL BECAUSE IT DOVETAILS REALLY WELL WITH THE HUMAN DATA THAT PRECEDED IT. I'M CITING MYSELF, THIS WHOLE RESEARCH HIGHLIGHTS IN SOME LEVEL BECAUSE THIS PARTICULAR STUDY REVIEW ARTICLE IS WRITTEN BY SCOTT EDWARDS WHO'S AT LSU, HE WAS A FORMER POSTDOC OF MINE, SO IS NICK GILPIN WHO'S ON THIS PAPER, BUT SCOTT IS A VERY SCHOLARLY PERSON AND HE THINKS REALLY DEEPLY AND THIS IS A REALLY, REALLY GOOD REVIEW. SO IF YOU'RE INTERESTED IN ALCOHOL AND PAIN, THIS IS A REALLY NICE REVIEW OF IT AND A TRANSLATIONAL REVIEW OF CLINICAL AND PRE-CLINICAL FINDINGS TO INFORM FUTURE TREATMENT STRATEGIES. I WANT TO MENTION TWO THINGS OFFLINE. ONE IS THAT I'VE PRESENTED BEFORE AT COUNCIL. WE KNOW THAT ALCOHOL IS A GREAT PAIN RELIEVER. BUT WE ALSO KNOW FROM THE META-ANALYSIS I HIGHLIGHTED AT COUNCIL A COUPLE YEARS AGO, THAT THE THRESHOLD FOR GOOD PAIN RELIEF FOR ALCOHOL IS .08. AND .08 IS THE LEVEL OF A BINGE. RIGHT? AND THE SECOND THING WE KNOW IS THAT ALCOHOL WITHDRAWAL IN HUMANS CAUSES HYPERALGESIA, CAUSES INCREASED PAIN SENSITIVITY, AND THIS CORRELATES WITH MOOD. SO THE WORSE YOUR AFFECT, THE WORSE THE PAIN SENSITIVITY FROM ALCOHOL WITHDRAWAL. SO WHAT I REALLY LIKE ABOUT THIS REVIEW IS THEY GO THROUGH ALL THAT, BUT THEY ALSO TALK ABOUT THE ANIMAL MODELS, THEY TALK ABOUT ALL THE GAPS, AND THEY COME UP WITH RECOMMENDATIONS, AND SO THEY PROVIDE UPDATES ON RECENT MODELS IN RESEARCH, THEY DESCRIBE OVERLAPPING BEHAVIORAL, SOCIAL AND BIOLOGICAL MECHANISMS, THEY ASSESS EVIDENCE FOR INFORMING TREATMENT RECOMMENDATIONS AND FUTURE RESEARCH THAT INTERSECT WITH PAIN AND ALCOHOL USE DISORDER, AND THEN THEIR RECOMMENDATIONS WHICH MAY BE HARD TO SEE IN THE BACK, BUT BASICALLY THEY ARGUE WE SHOULD BE FOCUSING ON MOTIVATIONAL AND EFFECTIVE COMPONENTS ON KNOWS NOCICEPTIN AND -- CLINICAL RESEARCH STUDIES AND I COULDN'T AGREE MORE. PHYSICAL PAIN CAUSES EMOTIONAL PAIN, EMOTIONAL PAIN CAUSES PHYSICAL PAIN, AND THAT'S LONG BEEN NEGLECTED IN THIS DOMAIN. NOT ONLY WITH ALCOHOL BUT WITH OPIATES. AND THEN THEY ARGUE WE SHOULD BE DISCRIMINATING HYPERSENSITIVITY VERSUS ANALGESIC EFFECTS IN ALCOHOL CHRONIC PAIN PATIENTS WITH CO-MORBID ALCOHOL USE DISORDER. WE'VE HAD CLINICIANS CALLING US UP AND TELLING US THAT THEIR PATIENTS NOW, THESE ARE CLINICIANS WHO TREAT PAIN PATIENTS, THEIR PATIENTS NOW ARE DRINKING MORE AND MORE. THIS IS A RESTRICTION ON OPIATE USE, SO ONE OF THE THINGS THEY'RE FALLING BACK ON IS ALCOHOL. AND THESE ARE PAIN DOCS, NOT ADDICTION DOCS. AND THEN NEW MEDICATION TARGETS, THEY ARGUED FOR SOME OUT OF THE BOX TARGETS LIKE METHOTPRISTONE, CANNABIS-BASED MEDICATION. ANYWAY, IT'S A GREAT REVIEW ARTICLE AND I THINK IT FORMS A GREAT TEMPLATE FOR SOME OF THE EFFORTS THAT MARK EGLEY IS CHAMPIONING. ARE YOU HERE, MARK? ANYWAY, HE'S CHAMPIONING OUR PAIN PORTFOLIO AND WORKING DOGGEDLY WITH THE HEAL INITIATIVE FOR WHICH HE DESERVES A MEDAL. ALL RIGHT. AND THEN FINALLY, I GOT TWO LAST ONES I WANT TO TALK ABOUT. THIS IS A STUDY FROM THE UNIVERSITY OF NEW MEXICO. IT'S BY STEIN AND WICKIEWTITZ. THEY ARGUE THAT TRAIT SELF CONTROL PREDICTS DRINKING PATTERNS DURING TREATMENT FOR ALCOHOL USE DISORDER AND RECOVERY UP TO THREE YEARS FOLLOWING TREATMENT. SO PREVIOUS RESEARCH THEY SAY HAS IDENTIFIED DEMOGRAPHIC AND CLINICAL IND CORES RELATED TO RECOVERY OUTCOMES AND -- HAVE RECEIVED LESS ATTENTION. SO THEY CONFIRMED THAT SEVEN CLASSES OF DRINKING PATTERNS AMONG PARTICIPANTS IN TREATMENT HAVE BEEN IDENTIFIED IN PREVIOUS RESEARCH AND THEY COMPARED THEIR BASELINE SELF CONTROL ACROSS THESE SEVEN CLASSES. WHAT THEY FOUND, WHICH IS ILLUSTRATED IN THE BOX, HIGHLIGHTED HERE, THE CONSISTENT LOW RISK DRINKING GROUP HAD SIGNIFICANTLY HIGHER SELF CONTROL THAN THOSE PERSISTENT HEAVY DRINKING AND CONSISTENT ABSTINENCE GROUPS. SO IF YOU'RE REALLY TRYING TO RETURN TO LOW RISK DRINKING, OR KEEP AT LOW RISK DRINKING, IT TURNS OUT THAT YOU HAVE TO WORK HARD AT SELF CONTROL AND APPARENTLY IT PAYS OFF. THESE WERE ACTUALLY A SECONDARY ANALYSIS OF BELIEVE IT OR NOT PROJECT MATCH DATA. MOST OF YOU YOUNG PEOPLE HAVE NEVER HEARD OF PROJECT MATCH, BUT IT WAS THIS ENORMOUS STUDY DONE LONG BEFORE MY TIME AT NIAAA THAT WAS FLISHLY DEEMED INITIALLY D EEMED A FAILURE, THEY DID DOUBLE BLIND PLACEBO CONTROLLED TRIAL OF BEHAVIORAL TREATMENTS, COGNITIVE BEHAVIORAL THERAPY AND A 12 STEP PROGRAM SIMILAR TO AA BUT NOT AA AND WHAT THEY FOUND IS EVERYBODY RECOVERED TO THE SAME EXTENT. SO IT WAS SOUGHT TO BE A NEGATIVE TRIAL BECAUSE THERE WAS NO CONTROL GROUP THAT GOT NOTHING. ON THE OTHER HAND, IT'S TURNED OUT TO BE A GOLD MINE OF INFORMATION THAT'S STILL BEING ANALYZED AND THIS IS A GOOD EXAMPLE OF THAT. FURTHERMORE, I THINK THE MESSAGE THAT ALL THREE BEHAVIORAL TREATMENTS WORK VERY WELL IS AN IMPORTANT MESSAGE SO I'VE ALWAYS BEEN A CUP HALF FULL MENTIONED WITH PROJECT MATCH. I WON'T MENTIO WHO ARE THE CUP HALF EMPTY PEOPLE. AND SELF CONTROL IS BASICALLY SELF REGULATION. SELF REGULATION IS A KEY PART OF SOME OF THE MECHANISMS OF BEHAVIORAL CHANGE THAT HAVE BEEN STUDIED AND LOOKED AT BY A LOT OF OUR GRANTEES. AND THEY ARE A KEY PART OF MOST OF THESE BEHAVIORAL TREATMENTS. AND THEY APPROACH THE SELF REGULATION IN A VERY RIGHT OF DIFFERENT WAYS, AND I CAN GIVE YOU A LECTURE ON SELF REGULATION LIKE I DID THE UNDERGRADUATES AT USSD UCSD BUT I'LL DECLINE AND I'M PROBABLY NOT A GOOD MODEL FOR SELF REGULATION. AND FINALLY, THIS ONE IS A LITTLE CONTROVERSIAL IN SOME SENSE. NOARND, WE ON THE OTHER HAND, WE THOUGHT ABOUT IT FOR A LONG TIME AND DECIDED THIS IS AN IMPORTANT ISSUE. SO THIS IS A REALLY KIND OF COOL STUDY THAT SHOWS THAT ASSOCIATION OF PRIOR CONVICTIONS FOR DRIVING UNDER THE INFLUENCE PRODUCE AN INCREASED RISK -- SHOW AN INCREASED RISK OF SUBSTANCE ARREST FOR VIOLENCE CRIMES AMONG HANDGUN PURCHASERS. SO THE WHAT THEY DID, THIS IS UC DAVIS, THEY TOOK 21 TO 49-YEAR-OLDS, QUITE A LOT OF THEM, 80,000 INDIVIDUALS, AND THEY DID A RETROSPECTIVE LONGITUDINAL COHORT AND THEY FOLLOWED THEM UP FROM THEIR FIRST GUN PURCHASE, WHICH WOULD HAVE BEEN IN 2001, THEY WERE FOLLOWED FROM 2001 TO 2013. AND HISTORY OF DUI CONVICTION AT THE TIME OF PURCHASE WAS ASSOCIATED WITH A SIGNIFICANT INCREASE IN THE RISK OF A SUBSEQUENT ARREST FOR VIOLENT CRIME. BOTH FIREARM-RELATED VIOLENT CRIME INDEX LISTED VIOLENT CRIME OR ANY VIOLENT CRIME. PURCHASERS WITH A PREVIOUS DUI CONVICTION AND OTHER NON-DUI ARREST OR CONVICTIONS WERE AT GREATEST RISK FOR SUBSEQUENT ARREST FOR VIOLENT CRIME. THAT'S NOT SHOWN IN THE GRAPH BUT IT'S IN THE TABLE WHEN THEY DO THE RATIO OF LIKELIHOOD OF AN ARREST. SO THIS FINDING, THEY ARGUE, EXTENDS PREVIOUS LINKS BETWEEN ALCOHOL USE AND VIE LESS TO LEGAL PURCHASERS THE -- THIS IS THE BIT OF THE CONTROVERSIAL CONCLUSION BUT THIS IS THEIR CONCLUSION, THAT ALCOHOL RELATED PROHIBITIONS ON FIREARM PURCHASE BASED ON DUI CONVICTIONS MAY REDUCE FIREARM-RELATED INJURY AND DEATH. THERE WAS INCREASED INTEREST IN VIOLENCE, YOU KNOW, AND THERE IS MONEY BEEN ALLOCATED BY CONGRESS FOR STUDYING VIOLENCE, AND YOU KNOW, ALCOHOL PROBABLY CONTRIBUTES TO SOME OF THE INCREASED VIOLENCE WE SEE IN THE UNITED STATES. AND SO I THOUGHT IT WAS WORTH HIGHLIGHTING THIS PAPER IN LIEU OF THE FACT THAT YOU'LL BE HEARING MORE ABOUT FUNDING OPPORTUNITIES IN STUDYING VIOLENCE. TRUTHFULLY, WE'VE HAD A FEW GRANTS BUT WE'VE HAD VERY LITTLE PRE-CLINICAL WORK IN THIS AREA WITH THE EXCEPTION OF OUR STAR RESEARCHER WHO HAS BASICALLY HELD UP THE WHOLE FIELD OF DRUG INTERACTIONS WITH VIOLENCE IN PRE-CLINICAL STUDIES, BUT THERE'S LITTLE KNOWN ABOUT THE NEURAL CIRCUITRY AND HOW IT'S ENGAGED, AND HOW ALCOHOL ASSOCIATED WITH VIOLENCE AND HOW ALCOHOL MIGHT EXACERBATE OR FACILITATE THAT PATHOPHYSIOLOGY. SO I WANT TO REALLY THANK ALL THE PEOPLE ON THIS SLIDE WHO HAVE HELPED ME WITH THIS PRESENTATION. I PARTICULARLY WANT TO THANK RACHEL ANDERSON WHO'S BECOME INCREDIBLY SKILLED AT MAKING MY SLIDES PALATABLE TO ME AND HOPEFULLY TO YOU. BUT THE TEAM UP THERE HS BEEN VERY HELPFUL, WITH BRIDGET WILLIAM SIMMONS AND AARON WHITE AND TRISH POWELL ARE MY REVIEWERS. SO THANK YOU VERY MUCH. [APPLAUSE] HOW AM I ON TIME? WAY OVER? >> WAY OVER. WE CAN TAKE A BREAK FOR 5 MINUTES. I'VE BEEN REALLY LOOKING FORWARD TO THIS TALK. SO JILL BECKER IS THE -- AS YOU KNOW ALREADY BECAUSE WE MENTIONED THIS ONCE BEFORE, BIOPSYCHOLOGY CHAIR ON THE PATRICIA -- COLLEGIATE PROFESSOR OF PSYCHOLOGY AT THE UNIVESITY OF MICHIGAN. SHE RECEIVED HER PH.D. DEGREE IN NEUROSCIENCE FROM THE UNIVERSITY OF ILLINOIS IN URBANA. RENOWNED EXPERT ON INVESTIGATING SEX DIFFERENCES IN AND SEXUAL DIFFERENTIATION OF THE NEURAL SYSTEMS MEDIATING DRUG ABUSE AND MOTIVATION. SHE'S BEEN DOING THIS FOR 30 YEARS. WAY BEFORE EVERYBODY ELSE. HER EARLY RESEARCH LAID THE GROUNDWORK FOR THESE STUDIES BY DEMONSTRATING THAT THERE IS A SEX DIFFERENCE IN DOPAMINE RELEASE FROM THE STRIE A TUM. THIS SEX DIFFERENCE IS AFFECTED BY NEONATAL AND ADOLESCENT HORMONE MANIPULATIONS AND SHE'S SHOWN THAT ESTRADIOL -- HER RESEARCH HAS BEEN FUNDED BY THE NATIONAL SCIENCE FOUNDATION, HEREDITARY DISEASE FOUNDATION, UNIVERSITY OF MICHIGAN, THE DIAMOND M CUBED IN SOCIAL SCIENCES ANNUAL INSTITUTE, AND SINCE 1980, BY NICHD, THAT'S CHILD HEALTH, NEUROLOGICAL DISEASES, MENTAL HEALTH AND NATIONAL INSTITUTE ON DRUG ABUSE. SHE'S CHAIRED THE ISIS FUND NETWORK ON SEX GENDER AND DRUGS ON THE BRAIN FOR THE SOCIETY OF WOMEN'S HEALTH RESEARCH FROM 2002 TO 2007, SHE'S RECEIVED SEVERAL AWARDS INCLUDING WINTER CONFERENCE ON BRAIN RESEARCH BRAIN AWARD, THE LEE AWARD -- ENDOWMENT FOR THE BASIC SCIENCES FACULTY RECOGNITION AWARD, AND THE HANSON SPECIAL RECOGNITION AWARD FROM THE SOCIETY FOR NEUROSCIENCE. SO JILL IS GOING TO TALK ABOUT SEX DIFFERENCES IN ADDICTION, LESSONS FROM ANIMAL MODELS. IT'S ALL YOURS, JILL. >> SO THANK YOU FOR THAT INTRODUCTION AND I'M LOOKING FORWARD TO TELLING YOU ABOUT MY ROW SECH. I HAVE BEEN STUDYING SEX DIFFERENCES SINCE MY DISSERTATION, WHICH GEORGE IS KIND ENOUGH NOT TO SAY WAS IN 1980. JUST SO YOU KNOW, I'VE BEEN STUDYING SEX DITCHES SEX DIFFERENCES FROM WAY BEFORE THEY WERE POPULAR OR MANDATED AND I STUDY ANIMAL MODELS, I'M HOPING TO MAKE THIS RELEVANT TO THOSE OF YOU THAT DON'T STUDY ANIMALS THAT STUDY PEOPLE BECAUSE WE'RE USING THE ANIMALS TO INFORM ON PEOPLE AND HOW WE CAN IMPROVE TREATMENT. I ALSO WANT TO MENTION IF YOU'RE INTERESTED IN SEX DIFFERENCES, THE ORGANIZATION FOR THE STUDY OF SEX DIFFERENCES IS FOR ALL SPECIES, ALL ORGANS, IT'S REALLY A COMPREHENSIVE LOOK AT SEX DIFFERENCES IN THE BODY, BRAIN AND ACROSS INDIVIDUALS. SO IT'S A GREAT GROUP TO LEARN FROM. I'M GOING TO START OFF BY TALKING TO YOU ABOUT WHAT SEX DIFFERENCES ARE, EVERYBODY THIPTION THEY KNOW IT BECAUSE YOU HEAR THE WORDS AND UNDERSTAND THEM BUT THEY'RE NOT ACTUALLY CLEAR. THEN I'LL GIVE YOU SOME IDEA ABOUT SOME OF THE MECHANISTIC WORK THAT I'VE DONE, TRYING NOT TO GO INTO TOO MUCH DETAIL, AND THEN TALK ABOUT HOW THESE SEX DIFFERENCES IN THE BRAIN CAN BE IMPLEMENTED TO LOOK AT THE MECHANISMS OF SEX DIFFERENCES IN ADDICTION AND HOW WE CAN BEGIN TO TEASE APART WHAT'S GOING ON IN THE BRAIN. SO AS I'M SURE YOU KNOW, IF YOU GET TWO X CHROMOSOMES, THEN THE BIPOTENTIAL GONAD BECOMES AN OVARY, YOU GET A FEMALE BRAIN. IN THE MALE, YOU HAVE XY CHROMOSOMES, THEN THE SRY GENE TELLS THE GONAD TO BECOME A TESTES, WHICH THEN RESULTS IN MASCULINIZATION IN THE BRAIN. SO TESTOSTERONE CONVERTED -- IN HUMANS IT LOOKS LIKE BOTH TESTOSTERONE AND ESTRADIE OLE ARE PLAYING A ROLE IN SEXUAL DIFFERENTIATION. NOW, PART OF WHAT IS SOMETIMES DIFFICULT TO TEASE APART WHEN YOU'RE STUDYING SEX DIFFERENCES IS THAT THERE ARE THESE ORGANIZATIONAL EFFECTS OF HORMONES DURING CRITICAL PERIODS OF DEVELOPMENT. IN THE HUMAN, IT'S DURING THE SECOND TRIMESTER IN UTERO, AND THEN AGAIN AT PUBERTY. SO YOU HAVE DEVELOPMENTAL EFFECTS WHICH PERMANENTLY CHANGE THE BRAIN AND THE BODY, AND THEN ON TOP OF THAT, ONCE YOU HAVE PUBERTY ENACTED, THE HORMONES PRODUCED BY THE OVARIES AND THE TESTES ARE DIFFERENT, SO YOU'RE ACTING ON SUBSTRATES THAT ARE DIFFERENT IN MALES AND FEMALES TO PRODUCE CHANGES IN BEHAVIOR THAT CAN BE DEPENDENT ON THE PRESENCE OF THE HORMONES. SO YOU HAVE THE ACTIVATION OF HORMONES -- YOU HAVE ACTIVATION OF NEURAL ACTIVITY THAT CAN CAUSE DIFFERENCES IN BEHAVIOR AS WELL AS THESE DEVELOPMENTAL EVENTS THAT RESULT IN A SUBSTRATE THAT'S ACTING ON -- SO IF YOU GIVE ESTRADIOL, THE BODY IS DIFFERENT AND HAS DIFFERENT RESPONSES TO THESE HORMONES. SO YOU CAN HAVE BOTH ACTIVATIONAL DIFFERENCES AS WELL AS THESE BASIC SUBSTRATE DIFFERENCES. WHAT THAT MEANS IS THAT YOU DON'T NECESSARILY HAVE A BIMODAL DISTRIBUTION OF SEX DIFFERENCES. SO MOST PEOPLE THINK THAT IF YOU HAVE A SEX DIFFERENCE, MALES ARE BLUE AND FEMALES ARE PINK AND THEY'RE COMPLETELY DISASSOCIATED. THAT IS PRETTY RARE. OTHER THAN REPRODUCTIVE FUNCTION, FEMALES GET PREGNANT AND MALES DON'T, MALES MAKE SPERM AND FEMALES DON'T, OTHER THAN THESE BASIC REPRODUCTIVE FUNCTIONS, MOST SEX DIFFERENCES ARE MUCH MORE NUANCED. AND THIS IS FROM AN ARTICLE I WROTE WITH DR. KOOB A FEW YEARS AGO THAT DESCRIBES THESE DIFFERENCES IN MORE DETAIL. YOU CAN ALSO HAVE DIFFERENCES WHERE BASICALLY THE BIOLOGICAL SUBSTRATE, THE BRAIN OF MALES AND FEMALES ARE THE SAME, BUT ONE SEX EXHIBITS A QUANTITATIVE DIFFERENCE. SO IF YOU GIVE A DRUG LIKE AMPHETAMINE, WHICH IS A STIMULANT, TO MALES AND FEMALES, FEMALES RUN AROUND MORE. SO YOU HAVE A QUANTITATIVE DIFFERENCE IN THE BEHAVIOR PRODUCED BY THE SAME DOSE OF A DRUG. YOU CAN ALSO HAVE DIFFERENCES THAT I THINK ARE MORE LIKE POPULATION DIFFERENCES, AND THESE ARE USUALLY THE RESULT OF SOMETHING THAT HAPPENS DURING DEVELOPMENT, AN ENVIRONMENTAL STRESS, FOR EXAMPLE, THAT ACTS ON MALES AND FEMALES IN A DIFFERENT WAY, RESULTING IN A SHIFT OF THE DISTRIBUTION OF ONE SEX, SO IN ONE EXAMPLE I'LL SHOW YOU, FEMALES TEND TO ESCALATE DRUG TAKING MORE RAPIDLY. BUT I ACTUALLY THINK THAT THIS IS A POPULATION DIFFERENCE. SOME MALES ESCALATE RAPIDLY AS WELL, IT'S JUST THAT MORE FEMALES ESCALATE COCAINE-TAKING IN MY LABORATORY MORE RAPIDLY THAN MALES DO. AND THEN YOU HAVE EXAMPLES WHERE THE TRAIT IS IDENTICAL IN MALES AND FEMALES. THEY LOOK PERFECTLY THE SAME, BUT THEN WHEN YOU DIG DOWN INTO THE NEURAL CIRCUITRY OR THE MESSENGER SYSTEMS ACTING TO MEDIATE THE RESPONSE TO CRF, FOR EXAMPLE, YOU SEE THAT IN MALES AND FEMALES, THE MECHANISMS ARE DIFFERENT. SO I'M ENCOURAGING PEOPLE TO TRY TO THINK ABOUT SEX DIFFERENCES AS BEING MORE NUANCED RATHER THAN ALL GIRLS DO THIS AND ALL BOYS DO THAT. SO I STUDIED THE BRAIN AND I STUDY RATS, AND WHAT WE KNOW IS THAT THE NEURAL SYSTEMS THAT MEDIATE MOTIVATION AND ADDICTION DEPEND UPON THE REWARD SYSTEM. I TEND TO FOCUS ON THE DOPAMINE SYSTEMS IN THE BRAIN, BUT ACKNOWLEDGE THAT GLUTAMATE, GABA AND OTHER NEURAL SYSTEMS ARE ALSO ACTING. I'M GOING TO BE FOCUSING TODAY ON THE STRIATUM AND NUCLEUS I NCUMBENS PRIMARILY BUT I AM AWARE THAT OTHER AREAS OF THE BRAIN ARE INVOLVED. SO THIS IS A RAT BRAIN. SO OVER THE COURSE OF MY -- SO THIS IS WHERE I STARTED, AS I DISCOVERED THAT IF YOU TAKE THE STRIATUM OF MALES AND FEMALES AND YOU PUT THEM IN A TEST TUBE AFTER CASTRATING THEM, THAT YOU GOT A SEX DIFFERENCE IN THE RESPONSE TO AMPHETAMINE, AND THIS WAS HORMONE-DEPENDENT IN FEMALES. SO YOU TAKE AWAY THE TESTES OF MALES, YOU GET THE SAME RESPONSE TO PSYCHOMOTOR STIMULANTS AS YOU DO IN THE INTACT ANIMAL. IF FEMALE, YOU TAKE AWAY ESTRO DIE OL -- YOU GIVE THEM ESTRO DIE OL BACK, WE'VE SHOWN IT IN VIVO USING A TECHNIQUE CALLED IN VIVO MICRO DIALYSIS WHICH ALLOWS US TO SAMPLE FROM THE BRAIN AS ANIMALS ARE FREELY MOVING AND WE'VE USED -- ANOTHER WAY TO SHOW THAT DOPAMINE IS RAPIDLY INFLUENCED BY ESTRODIOL. SO DOPAMINE RELEASED IN -- AND DORSAL STRIATUM IS BEING MODULATED BY ESTRADIOL. THAT IS THE CHEMICAL NAME THAT THE HORMONE -- THE PRIMARY HORMONE PRODUCED BY THE OVARY, BUT I'M TRYING TO BE CORRECT IN TERMS OF MY CHEMICAL STRUCTURES. MOST OF YOU WILL HAVE BEEN TAUGHT IN MEDICAL SCHOOL AND OTHER TYPES OF SCHOOLS THAT THE RECEPTORS FOREST TRA FOR ESTRADIOL ARE IN THE NUCLEUS AND THAT'S PART OF WHAT THEY ARE SO YOU HAVE SLOW ACTING ESTRADIOL RECEPTORS. YOU ALSO HAVE RAPIDLY ACTING ESTRADIE OL RECEPTORS IN THE MEMBRANE. IT'S TRUE IN THE BRAIN, IT'S TRUE IN THE HEART, IT'S TRUE IN BONE. YOU HAVE BOTH RAPID EFFECTS OF ESTRADIOL AND YOU HAVE MORE LONG TERM SLOWLY ACTING EFFECTS OF ESTRADIOL, AND THESE TWO EFFECTS OF THE HORMONE INTERACT TO PRODUCE CHANGES IN NEURAL ACTIVITY AND OTHER TYPES OF CELLULAR ACTIVITY. SO IF I TAKE THIS, 250 MICRONS IN DIAMETER, I CAN PUT IT INTO THE SPECIFIC AREA OF THE BRAIN AND SAMPLE THE NEUROCHEMISTRY THAT'S GOING ON IN THE EXTRACELLULAR SPACE AROUND THIS PROBE. AND WHEN I DO THAT, I CAN ACTUALLY PUT DRK INTO THE PROBE, I CAN PUT A CONCENTRATION OF ESTRADIOL SO I CAN DELIVER IT DIRECTLY TO THE BRAIN, AND THEN I CAN SAMPLE DOPAMINE THAT'S PRESENT EXTRACELLULARLY, SO IF I PUT ESTRADIOL INTO THE PROBE AND THEN ABOUT AN HOUR LATER, GIVE THE ANIMALS AMPHETAMINE, WHAT YOU SEE IS THAT THIS IS THE RESPONSE TO AMPHETAMINE IN THE ABSENCE OF ESTRADIOL, AND WHEN YOU GIVE ESTRADIOL, YOU ENHANCE AM FET AMPHETAMINE -- TO INCREASE DOPAMINE RELEASE IN THE BRAIN. AND IF I GIVE ESTRADIOL 30 MINUTE LATER, YOU ACTUALLY SEE A DOWN REGULATION OF D2 DOPAMINE RECEPTORS. THIS IS NOT THE RIGHT SLIDE, THIS IS A HORIZONTAL SECTION OF THE RAT BRAIN. AS DR. KOOB WAS TALKING ABOUT EARLIER, D2 DOPAMINE RECEPTOR ACTIVATION IS THOUGHT TO BE RELATED TO INCREASED DRUG TAKING BEHAVIOR. SO BY INACTIVATING DOPAMINE RECEPTORS, YOU GET INCREASED DRUG TAKE BEING SO THE EFFECTS OF ESTRADIOL ARE ENHANCING DOPAMINE RELEASE, AT THE SAME TIME YOU'RE DOWNREGULATING D2 DOPAMINE RECEPTORS TO HAVE SORT OF A DOUBLE EFFECT IN FEMALES. SO AS I MENTIONED, ESTRADIOL IS ACTING ON SPECIFIC RECEPTORS IN THE BRAIN TO INFLUENCE NEURAL ACTIVITY, AND THEY'RE ER-ALPHA, ER-BETA AND THERE'S A NEW RECEPTOR I'M GOING TO TELL YOU ABOUT TODAY CALLED GPER #, WHICHR1, WHICH IS ANOTHER RAPID ACTING G PROTEIN COUPLED RECEPTOR. ALL OF THESE RECEPTORS ARE FOUND THROUGHOUT THE BODY, AND SO THE EFFECTS OF ESTRADIOL, FOR EXAMPLE, ON THESE RECEPTORS IS BEING -- IN BREAST, FOR EXAMPLE, THE MEMBRANE RECEPTORS ARE THOUGHT TO EXACERBATE THE EFFECTS OF THE INTRACELLULAR RECEPTORS AS PART OF TARGETS FOR BREAST CANCER THESE DAYS. SO THIS IS JUST A SCHEMATIC SHOWING ESTRADAY OL -- TO INDUCE THE INTRACELLULAR SIGNALING, THAT'S PART OF THE MECHANISM HERE WHICH THE ER-ALPHA AND ER-BETA KNOWN TO BE ACTIVE IN THE NUCLEUS ALSO ARE ACTIVE EXTRACELLULARLY. GPER1 IS ALSO FOUND ON THE MEMBRANE IN THE STRIATUM, IT LOOKS LIKE THE GLUTAMATE RECEPTOR 5 IS THE KEY RECEPTOR MEDIATING THE EFFECTS OF ESTRADIOL. SO THIS SHOWS MY MODEL OF HOW I THINK ESTRADIOL IS ACTING IN DORSAL STRIATUM TO AFFECT DOPAMINE RELEASE. SO IT'S ACTING ON MEMBRANE RECEPTORS TO DOWNREGULATE D2 DOPAMINE RECEPTORS, AND THAT RESULT -- THERE'S ALSO A SIMULTANEOUS DECREASE IN GABA RELEASE, WHICH RESULTS IN ENHANCED DOPAMINE RELEASE. SO YOU HAVE SIMULTANEOUSLY ENHANCED DOPAMINE RELEASE AND DECREASE D2 DOPAMINE RECEPTORS, RESULTING IN GREATER D1 ACTIVATION THAT RESULTS IN ENHANCED DRUG-TAKING BEHAVIOR. SO WHICH HAVE WE HAVE RAPID EFFECTS OF ESTRADIOL IN THE DORSAL STRIE A TUM SPECIFICALLY IN FEMALES. IF WE LOOK AT MALES IN ALL OF THE TESTS I JUST TOLD YOU ABOUT, WE DO NOT SEE AN EFFECT OF ESTRADIOL, SO WE THINK THESE ARE SPECIFIC EFFECTS TO FEMALES THAT ARE SEXUALLY DIFFERENTIATED DURING CRITICAL PERIODS OF DEVELOPMENT. SO THESE EFFECTS OF ESTRADIOL INFLUENCE MOTIVATION AND DRUG TAKING BEHAVIOR. NOW, I ALWAYS TRY TO THINK ABOUT WHY IN THE WORLD WOULD THERE BE A SEX DIFFERENCE IN MOTIVATION? WHY WOULD ESTRADIOL BE REGULATING NEURAL ACTIVITY IN SUCH A WAY THAT FEMALES ARE MORE AFFECTED BY OVARIAN HORMONES? AND ONE OF THE THINGS THAT I BELIEVE IS HAPPENING, BECAUSE THE SAME HORMONAL EVENTS INFLUENCE THE ONSET OF MATERNAL BEHAVIOR. AND AFTER ESTRADIOL PRIMING, FEMALE RATS BECOME MATERNAL IMMEDIATELY UPON PARTURITION. THE NEURAL SYSTEMS FOR ATTACHMENT HAVE TO BE DIFFERENT IN FEMALES, THEY HAVE TO BE READY TO FORM THIS RAPID ATTACHMENT TO THEIR OFFSPRING PAUSE IT'S BECAUSE IT'S REALLY CRITICAL IN MAMMALS THAT YOU HAVE AN IMMEDIATE ATTACHMENT AND YOU HAVE THE MOTHER LACTATING AND PROVIDING NUTRIENTS TO HER OFFSPRING. SO THE NEURAL SYSTEMS FOR MOTIVATION WERE DESIGNED IN FEMALES TO HAVE THIS RAPID ATTACHMENT. THERE'S ALSO SEX DIFFERENCES IN MOTIVATION FOR REPRODUCTIVE BEHAVIORS IN RATS THAT WE'VE STUDIED. I WON'T TELL YU ABOUT THAT. AND THEN ESTRADIOL INCREASES FEEDING BEHAVIOR AT THE SAME TIME IT'S INCREASING MOTIVATION FOR A MATE. SO THESE HORMONES ARE ALL DESIGNED TO OPTIMIZE ACTUALLY MATERNAL BEHAVIOR AND CARE FOR THE OFFSPRING. SO WHAT WE KNOW FROM EPIDEMIOLOGY AND FOR STUDIES OF HUMANS IS THAT THE TIME FROM FIRST EXPOSURE TO DRUGS OF ABUSE TO CHRONIC DRUG USE IS SHORTER FOR WOMEN THAN IT IS FOR MEN. AND THIS IS TRUE FOR ALCOHOL AND FOR COCAINE AND FOR HEROIN. FEMALES PRESENT WHEN THEY GO IN TO A CLINIC FOR HELP TAKING MORE COCAINE, AND THEY REPORT THEIR TIME OF USE IS SHORTER. NOW SOME OF THE E.R. DOCS I'VE TALKED TO SAID, WELL, THEY ALWAYS ASSUMED THAT THE WOMEN WERE LYING. BECAUSE THEY COULDN'T POSSIBLY ONLY BE USING THAT LONG AND COME IN WITH THIS REALLY HIGH BLOOD CONTENT, BUT FOLLOW-UP STUDIES HAVE SHOWN THAT IT IS A SHORTER TIME. AND THEN WOMEN REPORT SELF-MEDICATING FOR DEPRESSION AND ANXIETY WHILE MEN TEND TO REPORT TAKING DRUGS AT LEAST INITIALLY TO ENGAGE IN RISKY BEHAVIORS AND TO BE PART OF THE GROUP. SO THE REASONS FOR TAKING DRUGS OF ABUSE ARE ALSO DIFFERENT. THIS IS FROM THE REVIEW THAT DR. KOOB AND I WROTE AND I'M NOT GOING TO GO THROUGH IT IN DETAIL, BUT THE POINT HERE IS THAT AT ALL STAGES OF THE ADDICTION CYCLE, THERE ARE SEX DIFFERENCES IN DRUG USE AND THIS IS TRUE FOR ALCOHOL AND COCAINE AND OTHER CLASSES OF DRUGS, AND SOME OF THEM ARE QUALITATIVE AND SOME OF THEM ARE QUANTITATIVE. AND OTHERS ARE POPULATION DIFFERENCES. AND YOU BASICALLY SEE THE SAME TRENDS IN RODENT RESEARCH AS WELL. SO THAT RODENTS ARE A GOOD MODEL FOR STUDYING DRUG ABUSE IN HUMANS AND FOR STUDYING SEX DIFFERENCES IN ADDICTION. SO ONE OF THE STUDIES -- I'M JUST GOING TO TELL YOU A LITTLE SNPPETS OF RESEARCH FROM MY LAB. ONE OF THE THINGS WE'VE BEEN TRYING TO DO IS COME UP WITH PARADIGMS THAT ARE MORE SIMILAR TO WHAT'S GOING ON IN THE HUMAN PARADIGM, BECAUSE YOU NEVER HAVE HUMANS BEING PUT INTO A LITTLE BOX AND IF YOU PUSH THIS BAR, YOU GET DRUG AND IF YOU DON'T PUSH A BAR, NOTHING HAPPENS, BECAUSE THAT'S TOTALLY BORING. SO WE GIVE OUR RATS A CHOICE BETWEEN TASTY BANANA FLAVORED PELLETS OR COCAINE, SO ONE OF THE NOSE POKES GIVES COCAINE AND THE OTHER NOSE POKE GIVES BANANA FLAVORED PELLETS AND THEY'RE TRAINED OVER A PERIOD OF TIME, WHICH ONE IS GOING TO DELIVER WHICH, AND THEY HAVE A NUMBER OF DIFFERENT PERIODS DURING WHICH THEY CAN SELECT ONE OR THE OTHER. AND AT THE BEGINNING, THEY'RE GIVEN A CHOICE, THEY ALL LIKE THE BANANA FLAVORED PELLETS. BASICALLY. SO YOU CAN SEE HERE THE ONES WHO END UP PREFERRING COCAINE ARE THE CLOSED CIRCLES, THE ONES THAT END UP PREFERRING PELLETS ARE THE OPEN CIRCLES. AT THE BEGINNING, EVERYBODY'S CHOOSING THE PELLETS. AFTER SEVEN WEEKS TAKING COCAINE, SOME OF THEM SWITCH OVER AND START PREFERRING THE PELLETS, SOME KEEP PREFERRING COCAINE. I MEAN PELLETS. SO THAT IT'S ACTUALLY A FAIRLY LARGE PERCENTAGE THAT CONTINUE TO TAKE THE BANANA FLAVORED PELLETS. AND IF YOU LOOK AT THE SURVIVAL CURVES IF TERMS OF THE NUMBER OF ANIMALS WHO GO OVER TO COCAINE, AND ONCE THEY GO OVER TO COCAINE, THEY DON'T GO BACK. WE HAVE A -- IT'S PRETTY MUCH A WIN-WAY STREET. WHAT YOU SEE IS THAT ABOUT 50% OF THE FEMALES CHOOSE COCAINE AND THEY CHOOSE COCAINE MORE RAPIDLY THAN THE MALES, ALTHOUGH SOME MALES CHOOSE COCAINE PRETTY RAPIDLY AS WELL, IT ONLY ABOUT 20% OF THE MALES THAT END UP CHOOSING COCAINEMENT IF WE LOOK AT WHAT HAPPENS IN THE BLAINE DURING THE CHOICE FOR COCAINE, THIS IS IN THE NUCLEUS -- THOSE ANIMALS THAT CHOOSE COCAINE, THIS IS EARLY DEURNLG DURING SELF ADMINISTRATION AT WEEK 2 AND THIS IS AT WEEK 7, THOSE ANIMALS THAT ARE COCAINE PREFERRING HAVE A DECREASE IN DOPAMINE RELEASE WHILE THE ANIMALS WHO ENDED UP CHOOSING PELLETS OR NOT TAKING ANY COCAINE AT ALL HAD THE SAME AMOUNT OF DOPAMINE RELEASE THROUGHOUT THEIR DRUG TAKING AND WE DID NOT SEE A SEX DIFFERENCE. SO IT LOOKS LIKE A POPULATION DIFFERENCE IN THAT MORE FEMALES WENT OVER TO CHOOTION COKEAN BUT THE NEURAL SYSTEMS THAT ARE MEDIATING IT AT LEAST IN TERMS OF CHANGES IN DOPAMINE RELEASE APPEAR TO BE THE SAME FOR MALES AND FEMALES AND WE DID NOT SEE AN EFFECT OF ESTRACYCLE. SO THE RECEPTORS ARE PRESENT IN THESE TARGET AREAS IN THE NUCLEUS ACUMBENS AND THE -- AREA SO WE CAN LOOK AT HOW THESE RECEPTORS ARE AIFNGHTING PREFERENCE FOR COCAINE AND WE DECIDED TO USE A CONDITION PLACE PREFERENCE, SO THIS IS AN EXAMPLE OF WHY IT'S GOOD TO ALWAYS STUDY BOTH SEXES. WE ARE INCLUDING MALES, BUT WE REALLY EXPECTED THE EFFECT TO BE IN FEMALES. WE ARE GIVING AN ANTAGONIST TO ERA FA AND BETA AND ALPHA AND BETA AND TH EN LOOKED AT WHETHER THEY LIKED AN AREA ASSOCIATED WITH COCAINE MORE. SO THIS IS CONDITION PLACE PREFERENCE, IN ONE COMPARTMENT, THEY GET COCAINE AND THEN THEY'RE PUT IN THERE FOR 30 MINUTES AND THE OTHER, THEY GET SALINE, AND THEN WE COME BACK AFTER MULTIPLE EXPOSURES AND ASK THE RAT, WHICH ONE DO YOU LIKE BETTER. IF THEY PREFER ONE, THEY'LL HANG OUT THERE MORE. SO THE AMOUNT OF TIME THEY SPEND INCREASES IN THE AREA PAIRED WITH COCAINE. AND TO OUR SURPRISE, WE HAD NO EFFECT WHATSOEVER IN FEMALES. SO THE ICI WHICH WAS BLOCKING ER-ALPHA AND ER-BETA DID NOTHING IN FEMALES, BUT IN THE DORSO LATERAL STRIATUM, IT BLOCKED CONDITION PLACE PREFERENCE IN THE MALES. SO THAT WAS REALLY CURIOUS TO US BECAUSE WE HAVE NEVER SEEN AN EFFECT OF GIVING ESTRADIOL ON DRUG-TAKING BEHAVIOR, ON THE BEHAVIORAL RESPONSE TO COCAINE OR AM FET AMPHETAMINE, AND THEN WE REALIZED THAT ICI IS ALSO AN AGONIST TO THIS NEW RECEPTOR, GPER1, AND SO WE GAVE AN AGONIST TO GPER1 TO MALES AND FEE MAILT AND FEMALES. AND IT DOESN'T DO ANYTHING TO FEMALES, BUT IT ALSO BLOCKS PREFERENCE FOR COCAINE IN MALES. SO NOW WE'RE REALLY INTERESTED IN TRYING -- IN INVESTIGATING THE EEFNGHTS OF EFFECTS OF GPER1 IN MALES IN TERMS OF A POTENTIAL TO DECREASE DRUG TAKING BEHAVIOR. WE ALSO HAVE SHOWN THAT IF YOU GIVE THE ANTAGONIST TO GPER1, YOU CAN INCREASE COCAINE PREFERENCE SO THIS IS JUST A LITTLE MODEL, SO YOU INHIBIT GPER1, IT INCREASES COCAINE PREFERENCE, IN MALES, NOT FEMALES, AND THE ANTAGONIST DECREASES IT -- AGONIST DECREASES IT IN MALES. FINALLY WE'VE BEEN TRYING TO LOOK AT THE EFFECTS OF SOCIAL SUPPORT. IN HUMANS, IT'S BEEN SHOWN THAT OXYTOCIN IS ALSO A POTENTIAL TREATMENT AND ATTENUATES REACTIVITY DURING CONFLICT, AND IS A POTENTIAL TREATMENT FOR ALCOHOL ABUSE IN SEVERELY ALCOHOLIC INDIVIDUALS. SO WE'RE NOW DOING THIS IN BOTH MALES AND FEMALES BUT IN THIS STUDY WE STUDIED ONLY FEMALES, AND WE ASKED THE RATS, HOW MUCH DO YOU LIKE METHAMPHETAMINE? AND THEY ANSWER BY NOSE POKING FOR METHAMPHETAMINE, AND THEN AFTER THEIR FIRST DOSE, THEY HAVE TO POKE MORE, AND THEN THEY HAVE TO POKE EVEN MORE AND WHEN THEY FINALLY SAY, THAT'S ENOUGH, THAT'S WHAT WE CALL THEIR BREAKING POINT. SO HOW HARD ARE THESE RATS WILLING TO WORK FOR METHAMPHETAMINE. AND WHAT YOU CAN SEE IS THAT IF THEY'RE INDIVIDUALLY HOUSED, THEY WORK HARDER THAN IF THEY HAVE A FRIEND IN THEIR HOME CAGE. SO THEY BASICALLY ARE PAIR HOUSED AND THEY ONLY COME OUT TO SELF-ADMINISTER METHAMPHETAMINE. SO YOU CAN SEE BOTH GROUPS INCREASE BREAKING POINT FOR METHAMPHETAMINE OVER TIME, THE INDIVIDUALLY HOUSED ANIMALS WORK HARDER FOR COCAINE, FOR METHAMPHETAMINE. SO THIS IS THE SAME DATA BROKEN DOWN BY ANIMALS THAT THEN GET EITHER OXYTOCIN PERIPHERALLY OR ARE GIVEN VEHICLE. WHAT YOU SEE IS THE ONES WHO ARE GIVEN THE VEHICLE, EITHER INDIVIDUALLY HOUSED OR SOCIALLY HOUSED, CONTINUE TO WORK HARDER FOR METHAMPHETAMINE THAN ANIMALS THAT ARE GIVEN OXYTOCIN. SO OVER A PERIOD OF TWO WEEKS, THERE'S A DECREASE IN RESPONDING FOR OXYTOCIN AFTER TREATMENT FOR OXYTOCIN. IF WE LOOKED AT THE INDIVIDUAL VARIABILITY IN THE ANIMALS HERE, ANIMALS WHO HAD VERY LOW MOTIVATION FOR METHAMPHETAMINE. SO SOCIAL HOUSING WAS A GOOD TREATMENT UP FRONT, AND OUR ANIMAL MODEL FOR SOCIAL SUPPORT IN FEMALE RATS. IF YOU LOOK THEN BASED ON HOW HARD THEY WERE MOTIVATED FOR METHAMPHETAMINE, THIS IS ANIMALS NOT BROKEN DOWN BY SOCIAL HOUSING BUT BY THEIR BREAKING POINT, WHAT YOU SEE IS THAT THIS IS THE FIRST WEEK OF OXYTOCIN TREATMENT. THESE ANIMALS GET -- HAD HIGH LEVELS OF RESPONDING AND ALSO RECEIVED OXYTOCIN, AND WHAT YOU SEE IS THAT BY THE SEVENTH WEEK, THE ANIMALS THAT ARE RESPONDING TO THE OXYTOCIN ARE THOSE WITH THE GREATEST MOTIVATION FOR METHAMPHETAMINE. SO THERE'S AN INTERACTION BETWEEN THE ABILITY OF OXYTOCIN TO DECREASE MOTIVATION AND ITS EFFECTIVENESS. SO IT COULD BE THAT THOSE ANIMALS WHO HAD HIGH MOTIVATION FOR METH AND WERE SOCIALLY HOUSED SIMPLY DIDN'T HAVE A GOOD PARTNER, AND THAT'S ONE OF THE THINGS THAT WE'RE LOOKING AT NOW. WE'RE LOOKING AT WAYS TO MEASURE THE QUALITY OF THE SOCIAL INTERACTION IN OUR ANIMALS. SO WHAT I'VE TOLD YOU IS THAT THERE ARE A NUMBER OF DIFFERENT WAYS OF THINKING ABOUT SEX DIFFERENCES IN ANIMALS AND HUMANS, AND THAT IF YOU LOOK AT THE EFFECTS OF DRUGS AND ES HORMONES, WHAT YOU SEE IS THAT ESTRADIOL HAS A QUALITATIVE DIFFERENCE IN A WAY IN THAT IT ACTS IN FEMALES AND NOT IN MALES, BUT THERE ARE ALSO QUANTITATIVE DIFFERENCES, INITIAL RESPONSE TO COCAINE OR METHAMPHETAMINE IS GREATER IN FEMALES THAN IN MALES, AND THERE ARE ALSO POPULATION DIFFERENCES WHICH I BELIEVE IS REFLECTED IN THE VULNERABILITY FOR ADDICTION. SO YOU HAVE DIFFERENT UNDERLYING NEURAL MECHANISMS AS WELL AS THESE POPULATION DIFFERENCES IN THE RESPONSE TO DRUGS OF ABUSE. SO WHAT I'VE TOLD YOU IS THAT THERE ARE SEX DIFFERENCES IN THE VULNERABILITY FOR ADDICTION, THESE ARE AFFECTED BY ESTRADIOL IN TERMS OF ENHANCING ESCALATION IN DRUG TAKING, THE RECEPTORS INVOLVED MAY BE MORE THAN JUST ALPHA-1 -- SOCIAL HOUSING AND OTHER TYPES OF SOCIAL CONDITIONS CAN ATTENUATE MOTIVATION FOR METHAMPHETAMINE, AT LEAST IN FEMALES, AND WE'LL FIND OUT ABOUT MALES SOON, AND THAT OXYTOCIN MAY BE A TREATMENT TO AMELIORATE MOTIVATION FOR METHAMPHETAMINE IN FEMALES, AND WE'RE HOPING TO FIND OUT ABOUT MALES AS WELL. AND WAS RECENTLY FUNDED BY NIDA TO DO THAT. SO WHAT I HOPE I'VE CONVINCED YOU IS THAT BY STUDYING FEMALES, YOU CAN ACTUALLY DISCOVER IMPORTANT INSIGHTS THAT ARE RELEVANT FOR ADDICTION IN BOTH FEMALES AND MALES, AND THESE SEX DIFFERENCES IN THE BRAIN ARE REALLY FUNDAMENTAL. THEY'RE NOT JUST ADD-ONS, THEY'RE NOT JUST -- THEY'RE REALLY IMPORTANT FOR UNDERSTANDING HOW THE BRAIN WORKS, AND AS WE BEGIN TO STUDY BOTH MALES AND FEMALES, WE REALLY ARE GOING TO UNDERSTAND HOW THE BRAIN WORKS IN BOTH SEXES. SO THANK YOU. [APPLAUSE] >> WE HAVE TIME FOR QUESTIONS IF ANYBODY HAS QUESTIONS. BOB? >> A COMMENT. WE'RE ABOUT TO PUBLISH -- SENT OUT REVIEW FOR A PAPER THAT SHOWS THAT THE ESCALATION OF ALCOHOL USE IS MUCH STRONGER IN HETEROGENEOUS STOCK MICE THAN IT IS IN INBRED MICE, AND SO EVERYBODY USES B6 IN THE ALCOHOL FIELD MORE OR LESS. THEY DON'T ESCALATE PRETTY MUCH, BUT THE -- MICE ESCALATE A LOT AND THEY SUSTAIN THE HIGH LEVEL MUCH BETTER THAN MALES. SO I THINK IN YOUR SLIDE, THERE'S THE GENETIC PART THAT IS THERE AS WELL. >> RIGHT. SO INDIVIDUAL DIFFERENCES CAN BE GENETIC OR HORMONAL AND THERE ARE LOTS OF DIFFERENT FACTORS CONTRIBUTING TO INDIVIDUAL DIFFERENCES. SEX IS A REALLY IMPORTANT PIECE OF THAT. >> I'D LIKE TO THANK YOU SO MUCH FOR THAT PRESENTATION BECAUSE FROM A CLINICAL STANDPOINT, WE SEE THOSE TYPES OF THINGS. I'VE WORKED IN THE VARIOUS LEVELS OF TREATMENT IN DETOXIFICATION, I'VE WORKED IN REHABILITATION AND NOW I DO SOME OF THE OFFICE-BASED WORK. A LOT OF MY COLLEAGUES DON'T UNDERSTAND HOW SOME 25-YEAR-OLD WOMAN CAN DRINK A CASE OF BEER, AND THEY CAN'T UNDERSTAND WHY THERE ARE THE DIFFERENCES WHEN WE SEE THEM GOING THROUGH WITHDRAWAL MANAGEMENT. AND SO THESE ARE THINGS THAT WE HAVE OBSERVED CLINICALLY, AND SOME OF US, ESPECIALLY THE ADDICTION MEDICINE SPECIALISTS, WE UNDER AND UNDERSTAND THIS A LOT BETTER . BUT WHEN I HEARD YOU TALK ABOUT THE REACTION FROM EMERGENCY PHYSICIANS OR OTHER NON-ADDICTION PHYSICIANS, IT STILL BOTHERS ME THAT THEY HAVEN'T LEARNED THOSE TYPES OF THINGS. THOSE OF US IN ADDICTION MED SIRNTION WE HAVE MEDICINE, WE'VE LEARNED THOSE TYPES OF THINGS BECAUSE WE'VE SEEN THEM, BUT YOUR WORK IS GIVING US SOME FOUNDATION UNDER WHICH WE CAN EXPLAIN THESE DIFFERENCES THAT WE HAVE SEEN CLINICALLY. SO THANK YOU SO MUCH. >> THANK YOU. >> JILL, I HAVE HERDS OF QUESTIONS BUT I'M ONLY GOING TO ASK ONE. WHAT DOES OXYTOCIN DO FOR MALES? I MEAN, I KNOW THERE ARE EFFECTS OF OXYTOCIN IN MALES BECAUSE WE'VE SEEN IT IN MY OWN LAB, BUT WHAT IS THE NATURAL ROLE OF OXYTOCIN IN MALES? IS IT KNOWN? OTHER THAN BEING A TRANSMITTER IN THE BRAIN PRESUMABLY. >> SO PERIPHERALLY, IT'S IMPORTANT FOR EJACULATION, AND IT'S PART OF WHAT HAPPENS DURING EJACULATION. BUT IN THE BRAIN, WE KNOW FROM THE -- IT'S IMPORTANT FOR PAIR BONDING, AND SO IT'S ALSO PLAYING A ROLE IN THE FORMATION OF BONDS, IT'S JUST PAIR BONDING IN MOST MALES IS LESS STRUCTURED THAN THE MOTHER-INFANT BOND. SO I WOULD ASSUME THAT THAT WOULD BE PART OF THE REASON, IF WE SEE A SEX DIFFERENCE IN THE EFFICACY OF OXYTOCIN THAT I WOULD PREDICT IT WOULD BE SLIGHTLY LESS EFFICACIOUS IN MALES SIMPLY BECAUSE IT'S ACTING PRIMARILY IN VENTRAL PALIDOM RATHER THAN NUCLEUS ACCUMBENS IN MALES, AND THE PROJECTIONS ARE LESS ROBUST IN MALES TO THE NUCLEUS ACCUMBENS. >> WHILE I HAVE THE FLOOR, A PRACTICAL QUESTION FOR ALL THOSE RESEARCHERS OUT THERE AND THOSE THAT MIGHT BE LISTENING IN, PARTICULARLY RELEVANT TO THE DATA YOU SHOWED ON THE SOCIAL INTERACTION, WHAT ABOUT HOUSING? IS IT IMPORTANT HOW YOU HOUSE THE MALES VERSUS THE FEMALES AND IN THE RAT WORLD VERSUS THE MOUSE WORLD? >> SO OF COURSE IT'S -- I MEAN, PART OF THE BIGGEST PROBLEM IN THE MOUSE WORLD IS THAT MALE MICE CAN -- UNLESS YOU'RE REALLY DESIGN YOUR CONDITIONS SO THAT YOU'VE GOT YOUR MALES HOUSED TOGETHER PRIOR TO PUBERTY, AND EVEN THEN YOU START GETTING MORE FIGHTING THAT YOU HAVE TO SEPARATE MALES. MALE RATS, IF YOU -- WE HOUSE THEM POST PUBERTAL BUT PRE -- ABOUT DAY 45, SO THEY ACTUALLY FORM BONDS TOGETHER FOR THE MOST PART, BUT THEIR SOCIAL BEHAVIOR IS REALLY DIFFERENT THAN THE SOCIAL BEHAVIOR OF THE FEMALES TOGETHER. THE MALES DO A LOT MORE ACTIVE PLAY BEHAVIOR AND DOMINANCE DETERMINING, WHILE FEMALES USUALLY TEND TO HUDDLE AND NOT DO AS MUCH PLAYING. SO PART OF WHAT'S MAYBE GOING ON IS THAT THEY'RE DOING DIFFERENT TYPES OF SUPPORT BEHAVIORS. >> [OFF MICROPHONE] >> IT'S A PROBLEM TO STUDY SOCIAL SUPPORTS IN MALES UNLESS YOU GIVE THEM A FEMALE. THAT WOULD BE THE OTHER WAY TO TRY TO DO IT. >> I HAVE ONE QUICK QUESTION AFTER THAT BEAUTIFUL TALK. HAVE YOU LOOKED AT THE FEMALES WHO ARE NOW POSTPARTUM AND HAVE HAD -- YOU KNOW, HAVE HAD PUPS AND DO THEY DIFFER IN THEIR RESPONSES TO DRUGS AND ALCOHOL IN ADDICTIVE ABILITIES/DESIRES? >> SO WE HAVE DONE THAT, AND WE DIDN'T EXACTLY FIND WHAT WE WERE EXPECTING. WE WERE ACTUALLY EXPECTING THAT THE POSTPARTUM FEMALES WOULD BE LESS VULNERABLE FOR COCAINE TAKING AND IT TURNED OUT THERE WASN'T MUCH OF AN EFFECT UNTIL YOU STRESSED THEM, GIVE THEM A LITTLE FOOT SHOCK ONE DAY, THEN THEY ESCALATED MUCH MORE RAPIDLY THAN THE NELLYPARUS FEMALES. AND THEIR DOPAMINE RELEASE INDUCED BY COCAINE IN THE NUCLEUS ACCUMBENS WAS GREATER POSTPARTUM THAN IT WAS THE VIRGIN FEMALES. SO IT WASN'T WHAT WE PREDICTED. I DIDN'T KNOW HOW TO FOLLOW THAT ONE UP. >> THAT'S REALLY EXCITING BECAUSE THERE'S THIS CULTURE OUT THERE OF MOTHERS IN PARTICULAR SELF MEDICATING. I THINK -- I'VE THOUGHT OF IT IN PART BECAUSE THE CULTURE EMPHASIZES THIS TOTAL MOMMY-DEDICATED THING AND WOMEN AREN'T ENCOURAGED AND REWARDED FOR TAKING TIME FOR THEMSELVES. I'VE ALWAYS THOUGHT OF THAT AS A SOCIAL CONSTRUCT AND MAYBE IT'S NOT SO SOCIAL. THAT'S VERY EXCITING. >> WE KNOW THAT THE BRAIN IS PERMANENT WILL I CHANGED BY HAVING HAD A LITTER OF PUPS AND OF BEING A MOM AS A HUMAN, THERE'S A LOT OF WORK ON THAT, SO I THINK IT'S SOMETHING WE REALLY NEED TO STUDY. WE'RE ALWAYS STUDYING THESE ANIMALS WHO HAVE NEVER HAD SEX OR HAVE HAD A LITTER OR PUPS. AND I'M TALKING ABOUT RATS. IN THE HUMAN LITERATURE ALSO, WE DON'T TEND TO DISASSOCIATE, YOU KNOW, MOTHERS VERSUS NON-MOTHERS, SO I THINK IT SHOULD BE AN IMPORTANT CONSIDERATION. >> SO THANK YOU AGAIN, JILL, FOR A WONDERFUL TALK, AND I'M SURE EVERYBODY WILL HAVE OTHER QUESTIONS AT BREAKS AND SO FORTH, SO WE'RE GOING TO MOVE ON NOW. CORRECT? >> YES. >> SO IT'S A PLEASURE TO INTRODUCE CONNIE HORGAN, A PROFESSOR AT THE HELLER SCHOOL FOR SOCIAL POLICY AND MANAGEMENT AT BRANDEIS UNIVERSITY AND IS FOUNDING DIRECTOR OF ITS INSTITUTE FOR BEHAVIORAL HEALTH. DR. HORGAN RECEIVES HER DOCTORATE IN HEALTH POLICY AN œUNIVERSITY.ROM JOHNS HOPKINS SHE'S A NATIONAL EXPERT ON THE ORGANIZATION FINANCING AND QUALITY OF BEHAVIORAL HEALTHCARE. HER RESEARCH IS FOCUSED ON HOW ALCOHOL, DRUG AND MENTAL HEALTH SERVICES FINANCED, ORGANIZED AND DELIVERED IN PUBLIC AND PRIVATE SECTORS, AND WHAT -- TO IMPROVE THE QUALITY AND EFFECTIVENESS OF THE DELIVERY SYSTEM DR. HORGAN HAS LED STUDIES FOR A RANGE OF ORGANIZATIONS INCLUDING THE NATIONAL INSTITUTES OF HEALTH, NIAA, NIDA AND NIMH, THE AGENCY FOR HEALTHCARE RESEARCH AND QUALITY, AHRQ, THE CENTER FOR MEDICARE AND MEDICAID SERVICES, SOME OF YOU KNOW THIS AS CMS, THE SUBSTANCE ABUSE AND MENTAL HEALTH ADMINISTRATION, SAMHSA, STATE GOVERNMENTS FOUNDATION INCLUDING THE ROBBED WOOD JOHNSON FOUNDATION. SHE HAS LED FOUR MAJOR NATIONAL SURVEYS FUNDED BY NIAAA AND NIDA WHICH PROVIDE AN ONGOING PICTURE OF THE COMPLEX AND CHANGING ORGANIZATION OF DRUG AND MENTAL HEALTH SERVICES IN PRIVATE HEALTH PLANS, PRIMARY CARE AND ACCESS TO SPECIALTY TREATMENT. DR. HORGAN IS THE DIRECTOR OF THE BRAN DICE HARVARD CENTER TO IMPROVE SYSTEM PERFORMANCE OF SUBSTANCE USE DISORDER TREATMENT FUNDED BY NIDA AND THE NIAAA BRANDEIST32 ALCOHOL AND RELATED -- RESEARCH. SHE HAS RECEIVED A LIFETIME ACHIEVEMENT AWARD AND THE 2010 ANDERSON AWARD FROM THE NATIONAL ASSOCIATION OF STATE ALCOHOL AN DRUG ABUSE DIRECTORS FOR HER DISTINGUISHED CONTRIBUTIONS IN THE FIELD OF ADDICTION RESEARCH AND TRAINING AND EVALUATION. SO CONNIE IS GOING TO TALK ABOUT USING HEALTH SERVICES RESEARCH TO IMPROVE THE DELIVERY OF ALCOHOL SERVICES. IT'S ALL YOURS. >> THANK YOU. GOOD MORNING. GOOD AFTERNOON, EVERYONE. THANK YOU, DR. KOOB AND ALL OF THE NIAAA STAFF THAT ARE HERE AND MY FELLOW COUNCILMEMBERS. IT IS TRULY A PLEASURE AND AN OPPORTUNITY TO BE HERE TO TALK ABOUT THIS TOPIC TODAY. I WAS TRAINED AS A HEALTH SERVICES RESEARCHER AND WAS FOCUSED SQUARE LE IN THE HEALTH SYSTEM. EARLY IN MY CAREER, I BECAME INTRIGUED AS TO WHY SO LITTLE WAS BEING DONE WITH THE TOOLS OF HEALTH SERVICES RESEARCH FOR THE QUALITY OF THE DELIVERY OF ALCOHOL SERVICES. THIS HAS BECOME MY PASSION. OVERVIEW, JUST A QUICK LITTLE PRIMER ON WHAT IS HEALTH SERVICES RESEARCH. SOMETIMES I THINK THAT WE ARE NOT ALL ON THE SAME PAGE AS TO WHAT HEALTH SERVICES RESEARCH IS AND WHAT IT DID DO TO LINK WITH SOME OF THE CLINICAL WRORK THAT HAS BEEN DONE. I ALSO WOULD LIKE TO SPEND SOME TIME TALKING ABOUT THE HEALTHCARE SYSTEM ITSELF AND HOW IT IS CHANGING. THEN DRILL DOWN AND TALK ABOUT WHAT DOES THIS MEAN FOR THE DELIVERY OF ALCOHOL SERVICES. AND THEN I'M GOING TO DO A FURTHER DRILLDOWN ON TWO EXAMPLES FROM HEALTH SERVICES RESEARCH. THAT WE TALK ABOUT A LOT, ENCOURAGING THE INTEGRATION OF SERVICES BECAUSE IT'S GOING TO MAKE EVERYTHING BETTER AND WE'RE GOING TO HAVE A BETTER DELIVERY SYSTEM, AND SOMETHING THAT I TRULY BELIEVE IN IS PAYMENT. HOW DO YOU PAY FOR SOMETHING IS GOING TO DRIVE WHAT YOU GET. SO HOW CAN WE USE PAYMENT TO IMPROVE THE QUALITY OF SERVICES. HEALTH SERVICES RESEARCH. THIS SIMPLY: HOW DO PEOPLE GET ACCESS TO HEALTHCARE? HOW IS THE SERVICE? IS IT OF A HIGH QUALITY? HOW MUCH DOES IT COST, AND WHAT IS THE OUTCOME OR RESULT OF THE CARE? THAT'S SIMPLE. BUT WHAT ARE THE TOOLS OF HEALTH SERVICES RESEARH? MOST OF THE PEOPLE IN THIS ROOM ARE USING CLINICAL TOOLS TO IMPROVE THINGS. THAT'S -- WE NEED TO WORK WITH PEOPLE WHEN WE'RE USING CLINICAL TOOLS. WHAT WE'RE ASKING IS, WHAT IS THE MOST EFFECTIVE WAY TO ORGANIZE, TO MANAGE, AND TO FINANCE HIGH QUALITY CARE BASED ON THE EVIDENCE. HOW DO YOU MAKE IT HAPPEN. HEALTH SERVICES RESEARCH WORKS FOR THE FULL CONTINUUM OF CARE. IT GOES FROM PREVENTION, RECOGNITION AND IDENTIFICATION, TO TREATMENT, AND MAINTENANCE AND RECOVERY. SOMETIMES I THINK WE'RE FOCUSED ON JUST THE MIDDLE PART, THE TREATMENT OR THE RECOGNITION PART. BUT IT IS THE FULL CONTINUUM OF CARE. NOW, YOU'RE EITHER GOING TO LOVE OR HATE THIS SLIDE. I BET YOU'VE NEVER HAD A MUSTANG ON THE SLIDE SHOW FOR NIAAA, BUT I'D LIKE TO USE THIS AS AN ANALOGY OF HEALTH SYSTEM CHANGE. SOME PEOPLE WOULD SAY THAT WE HAVE BEEN IN A PROFOUND PERIOD OF CHANGE IN THE HEALTH SYSTEM FOR THE LAST 50 YEARS. I POSE THE QUESTION, HAS IT REALLY CHANGED THAT MUCH OR HAS THE CHANGE BEEN REALLY MARGINAL? I'D LIKE TO COMPARE THIS BRIEFLY TO CARS, TO MUSTANGS IN PARTICULAR. LET'S LOOK AT THE 1970 MUSTANG. IT LOOKS, I THINK, REMARKABLY SIMILAR TO THE 2020 MUSTANG. I MEAN, 2020 IS JAZZIER, BUT THE REAL QUESTION IS NOT WHAT'S HAPPENING EXTERNALLY, WHAT IT LOOKS LIKE. IT STILL HAS FOUR WHEELS AND A CHASSIS AND THE GOAL IS TO GET IN ONE PLACE TO ANOTHER. THAT'S STILL THE MAIN PURPOSE. BUT WHEN WE LOOK INTERNALLY, WHAT'S REALLY HAPPENING UNDER THE HOOD TO DRIVE THIS CHANGE? IN 2020, I KNOW THAT'S AN ELECTRIC CAR, THERE'S A GPS, PEOPLE IN THIS ROOM WHO KNOW A LOT MORE ABOUT CARS CAN PROBABLY GIVE YOU 50 OTHER THINGS THAT ARE NOW IN THE 2020 MUSTANG THAT DIDN'T EXIST 20 YEARS AGO. SO KEEP THAT ANALOGY IN MIND. I'M JUST GOING TO GIVE ONE BECAUSE I KNOW WE'RE VERY SHORT ON TIME SO I'M JUST GOING TO GIVE YOU ONE BIG ONE THINKING BACK TO HOW THE HEALTH SYSTEM HAS CHANGED. BACK IN 1970, WHERE DID YOU GET YOUR CARE? MANY PEOPLE, MOST PEOPLE WENT TO A SOLO PRACTITIONER. IN 2020, WHERE ARE YOU GETTING YOUR CARE? MANY OF YOU ARE GETTING IT IN A HEALTH SYSTEM, GOING TO AN ORGANIZATION. BUT YOU KNOW WHAT? AS OF LAST WEEK, THIS WEEK, IT'S BEEN ALL OVER THE PAPERS, WAL-MART IS GOING TO HAVE HEALTH CLINICS IN THEIR STORES. SO I WOULD ARGUE THAT THERE ARE DIFFERENCES IN DELIVERING SERVICES AS A SOLO PRACTITIONER VERSUS GOING TO WAL-MART, AND YOU KNOW WHAT, WAL-MART IS NOT EVEN THE END OF THE CONTINUUM AS TO WHAT'S AFFECTING WHERE SERVICES ARE DELIVERED. SO THE QUESTION IS, HOW DO CLINICAL SERVICES GET INCORPORATED IN THIS IN A WAY THAT IS GOING TO MAKE A DIFFERENCE? I'M GOING TO BRIEFLY TOUCH ON A COUPLE OF THINGS IN HEALTHCARE THAT HAVE BEEN MAKING PROFOUND CHANGES IN THE HEALTH SYSTEM. HEALTHCARE REFORM AND PARITY, TWO MAJOR PIECES OF FEDERAL LEGISLATION THAT HAVE AFFECTED HEALTHCARE REA FORM HAVE REFOM HAS AFFECT ED COVERAGE EXPANSION, WHICH MEANS THERE ARE A LOT MORE PEOPLE WHO HAVE COVERAGE NOW, WHETHER IT'S THROUGH MEDICAID OR PRIVATE INSURANCE. THERE ARE MORE PEOPLE WHO NOW HAVE ACCESS TO SERVICES. THE OTHER THING THAT'S EXPANDED ARE SERVICES. THEY ARE NOW ESSENTIAL BENEFITS, AND THERE ARE FAR MORE SERVICES -- ARRAY OF SERVICES THAT ARE NOW PAID FOR BECAUSE, YOU KNOW, THE NAME OF THE GAME IS PARITY. THERE WAS LEGISLATION, ADDICTION AND MENTAL HEALTH SERVICES MUST BE TREATED AT PARITY WITH MEDICAL CARE. IT HAS A BIG IMPACT. YOUR CO-PAYS ARE THE SAME FOR ADDICTION TREATMENT AS FOR MEDICAL SERVICES NOW, IF YOU'VE NOTICED. IT USED TO BE A LOT HIGHER. THESE ARE IMPORTANT CHANGES AND THERE'S BEEN RESEARCH THAT SHOWED WHAT THAT MEANT. ANOTHER THING THAT HAPPENS IS A NEED TO MEASURE CARE, MEASURE THROUGH PERFORMANCE MEASURE. YOU CAN'T CHANGE WHAT YOU DON'T MEASURE. YOU HAVE TO KNOW WHERE YOU ARE. SO PERFORMANCE MEASURE IS WELL ESTABLISHED IN THE MEDICAL AREA, AND THEY'RE USED TO REWARD PERFORMANCE. I'LL BE SPEAKING A LITTLE BIT MORE IN DEPTH ON THIS LATER, BUT THE IDEA OF REWARDING OUTCOMES, REWARDING PERFORMANCE IS ABSOLUTELY KEY IN HEALTH SERVICES RESEARCH RIGHT NOW. INFORMATION TECHNOLOGY, WE ALL KNOW THE IMPORTANCE OF ELECTRONIC HEALTH RECORDS, CLINICAL REGISTRIES, PATIENT PORTALS. THERE ARE ALL THESE WAYS THAT INFORMATION TECHNOLOGY IS IMPACTING THE DELIVERY AND WHAT CAN BE DONE. AND THERE IS A MOVEMENT TOWARDS INTEGRATING CARE. I WAS FASCINATED WHEN YOU TALKED ABOUT HOUSING IN THE LAST PRESENTATION, BECAUSE THAT'S A LOT OF WHAT'S BEING TALKED ABOUT WITH HOW DO YOU INCORPORATE SOME WRAPAROUND SERVICES INTO HEALTH SERVICES RESEARCH. SO THE IDEA F INTEGRATED CARE IS THAT THERE IS NO WRONG DOOR, HOW DO YOU GET PEOPLE INTEGRATED WITH THE ADDITIONAL SERVICES THAT THEY NEED AS PART OF HEALTHCARE. THIS IS A CONCEPTUAL FRAMEWORK THAT IS WIDELY USED IN HEALTH SERVICES RESEARCH TALKING ABOUT THE KEY PLAYERS IN HEALTH SERVICES RESEARCH. I'M JUST GOING TO STICK TO THE THREE KEY PAIRS. UP AT THE TOP IS THE PAYER. WHAT IS THE PAYER DOING? THAT'S THE INSURER, WHETHER IT'S A PRIVATE HEALTH PLAN, PUBLIC MEDICAID PLANS, THAT IS THE PAYER. THE PAYER RELATES TO BOTH THE CLINICIAN AND THE PATIENT. IT USED TO BE THE PAYER PAYED THE CLINICIAN, THE CLINICIAN DELIVERED CARE TO THE PATIENT, BUT IT'S ALL INTERTWINED. I WILL SAY THE MAJOR THING THAT HAS HAPPENED IN HEALTH SERVICES OVER THE LAST 5 YEARS IS THAT PROVIDER ORGANIZATION IN THE MIDDLE THERE, I WILL NOT GO INTO IT IN ANY DEPTH, BUT THERE'S ANOTHER PLAYER IN THERE THAT IS IN BETWEEN WHAT THE RELATING THE PAYER AND THE CLINICIAN. THE CLINICIAN IS NOT REALLY DEALING DIRECTLY WITH THE PAYER ANYMORE. I WANT TO GIVE TWO EXAMPLES IN ALCOHOL TO MAKE THIS REAL SO THAT YOU CAN SEE HOW IT AFFECTS THE DELIVERY OF CARE. LET'S LOOK AT THE DIRECT RELATIONSHIP BETWEEN A PAYER, THE INSURER, AND A PATIENT. WELL, THERE'S BEEN A LOT OF TALK AT THIS MEETING ABOUT MEDICATIONS AND WHAT'S HAPPENING WITH MEDICATIONS. WELL, HOW YOUR BENEFIT IS DESIGNED IMPACTS WHETHER YOU WILL EVEN HAVE ACCESS TO THE MEDICATION. IS IT ON THE FORMULARY? WHAT TIER IS IT ON? ARE YOU GOING TO PAY A $10 CO-PAY OR ARE YOU GOING TO PAY A $50 CO-PAY? ARE YOU GOING TO HAVE TO GO THROUGH A FAIL-FIRST PROCESS TO EVEN BE ABLE TO BEGIN IT. THESE ARE ALL QUESTIONS THAT HEALTH SERVICES RESEARCH EXAMINES. ANOTHER QUICK EXAMPLE. LET'S JUST TAKE THE CLINICIAN AND THE PATIENT RELATIONSHIP. SCREENING. HOW OFTEN IS SCREENING DELIVERED IN AN EVIDENCE-BASED MANNER? WE ALL KNOW IT'S AN EVIDENCE-BASED PRACTICE. HOW DO YOU GET IT IMPLEMENTED? WHAT ARE THE TOOLS OF HEALTH SERVICES RESEARCH THAT CAN HELP WHAT WE KNOW IS AN EVIDENCE-BASED PRACTICE TO GET IMPLEMENTED PROPERLY SO THAT IT AFFECTS THE QUALITY OF CARE. THIS IS A SLIDE THAT I'VE ADAPTED FROM CONNIE WISENER. IN THE FIRST COLUMN, IT'S THE PAST, HOW ARE ALCOHOL SERVICES DELIVERED. ON THE RIGHT SIDE, IT SORT OF THE CURRENT, THE FUTURE, IT'S THE VERY FUTURE FOR SOME PLACES, AND KAISER, I HAVE TO SAY, IS ONE OF THE LEADING ORGANIZATIONS, AND THEY'RE SO DOING A LOT OF THIS. YOU HAVE THE SLIDES IN YOUR BOOK, I KNOW WE'RE SHORT ON TIME. I'M ONLY GOING IT PICK OUT JUST A COUPLE TO MENTION. IN THE PAST, ALCOHOL SERVICES, MENTAL HEALTH SERVICES WERE LARGELY IGNORED IN PRIMARY CARE. THERE HAS BEEN A HUGE EMPHASIS ON SCREENING AND MONITORING IN PRIMARY CARE. HOW CAN WE MAKE THAT MORE WIDESPREAD AND HOW CAN WE HAVE IT MAKE A DIFFERENCE. LET'S STIP DOWN TO THREE, PAPER CHARTS. OKAY. WELL, DOES ANYONE HAVE PAPER CHARTS ANYMORE? SOME PROVIDERS DO. BUT WE ARE CERTAINLY MOVING TO A MUCH MORE ELECTRONIC SYSTEM. AND FIVE, FOCUS ON HEALTH ISSUES. THERE IS AN INCREASING RECOGNITION THAT YOU CANNOT LOOK AT EACH DISEASE, EACH BODY PART IN ISOLATION, YOU HAVE TO LOOK AT THE WHOLE PERSON. THERE ARE INTERSECTIONS BETWEEN ALCOHOL AND EVERYTHING ELSE IN YOUR BODY, WE KNOW THAT THERE ARE SYSTEMS THAT ARE AFFECTED BUT IT SHOULD BE IN THE DELIVERY SYSTEM AS WELL, SO THE PURPOSE IS TO LOOK AT THE PERSON AS A WHOLE AND GET PEOPLE CONNECTED WITH THE RIGHT CARE. AND I WILL BE SPEAKING ABOUT THE LAST ONE, FEE FOR SERVICE PAYMENT, WHICH IS GOING BY THE WAYSIDE WHERE YOU PAY FOR A UNIT OF SERVICE, AND THERE ARE ALL KINDS OF ALTERNATIVE PAYMENT MODELS. I WILL SAY THAT ALCOHOL, DRUGS AND MENTAL HEALTH ARE NOT WHERE THE HEALTH FIELD HAS BEEN. THEY'RE BEHIND, AND NOT -- I'M JUST SAYING THAT THAT'S WHERE IT'S AT. SOME OF THESE THINGS THAT I'M SAYING ARE LIKE, JEEZ, THAT'S SO BASIC, BUT IN BEHAVIORAL HEALTH SERVICES, THEY'RE NOT AS BASIC AS THEY ARE IN HEALTH. MY FIRST OF TWO EXAMPLES. HOW AM I DOING ON TIME? I'LL GO QUICKLY THROUGH THE EXAMPLES. EXAMPLE ONE, HOW DO WE ENCOURAGE THE INTEGRATION OF SERVICES? I THOUGHT THIS WAS CUTE, THE DANCE OF INTEGRATION. EVERYONE IS TALKING ABOUT HOW WE'VE GOT TO INTEGRATE, COLLABORATE, COORDINATE. GEORGE, YOU EVEN TALKED ABOUT COLLABORATION AMONG THE INSTITUTES AND I THINK YOU KNOW THAT'S PROBABLY PRETTY HARD. BUT THIS IS WHAT'S HAPPENING IN HEALTHCARE. I WOULD ARC ARGUE THAT IT'S -- I'D SAY WE'RE DATING, AND WE'RE MOVING TOWARDS A MORE INTEGRATED SYSTEM. SOME PEOPLE THINK IT'S BETTER, SOME PEOPLE THINK IT'S WORSE, BUT ARE WE REALLY, REALLY HEADED TOWARDS, I DON'T KNOW, LOVE AT VALENTINE'S DAY IS COMING UP, MAYBE WE ARE HEADED THAT WAY. LET'S GET SOMETHING THAT'S A LITTLE MORE FOCUSED ON THE DELIVERY SYSTEM. WHAT ARE WE TALKING ABOUT WHEN WE'RE INTEGRATING SUBSTANCE ABUSE AND HEALTHCARE? THIS IS A SIMPLE DIAGRAM. IT JUST HAS PRIMARY CARE AND SPECIALTY CARE. I DON'T HAVE ON THE DIAGRAM THE OTHER THINGS THAT ARE PART OF THE SYSTEM. WHAT ABOUT THE E.R.? WHAT ABOUT THE COMMUNITY SUPPORTS THAT ARE NEEDED? SO LET'S JUST TAKE THE VERY SIMPLE NOTION OF PRIMARY CARE AND SPECIALTY CARE. A PERSON CAN GO BACK AND FORTH BETWEEN THESE SYSTEMS AND THERE SHOULD BE COMMUNICATION BETWEEN THEM. SCREENING IN PRIMARY CARE, TREATMENT IN PRIMARY CARE IF THE CONDITION IS MODERATE, BRIEF INTERVENTION. IF SPECIALTY CARE IS NEEDED IT GOES TO THE SPECIALTY SECTOR AND THEN DEPOSE BACK TO THE GOES BACK TO THE PRIMARY CARE FOR MONITORING AND RECOVERY SUPPORT, IT'S A MONITORING AND BACK AND FORTH BETWEEN THE SYSTEM. INTEGRATION, I'LL ZOOM THROUGH THIS, IT CAN BE COORDINATED AT THE MINIMAL END, CO-LOCATED, AND FULLY INTEGRATED WITH TEAM BASED APPROACHES WHERE THERE'S FREQUENT COMMUNICATION. I HAVE SEVERAL SLIDES I COULD TALK ABOUT ON THIS, I WON'T. THIS IS ONE OF MY FAVORITE SLIDES. THIS IS ABOUT HOW THINGS CAN WORK TOGETHER. YOU'LL SEE THAT THE BIG COG THERE IS CLINICAL. HOW CAN WE USE THE COGS OF FINANCIAL AND STRUCTURAL ISSUES TO HELP IMPROVE AND MAKE EVERYTHING WORK TOGETHER. IT MAKES A DIFFERENCE IN HOW THINGS ARE PAID FOR TO SUPPORT THE CLINICAL INTEGRATION. AND WHAT IS THE INFRASTRUCTURE? THE STRUCTURE OF TECHNOLOGY AND TRAINING AND COMMUNICATIONS. ALL OF THESE HAVE TO BE IN PLACE TO ACTUALLY MAKE THE CLINICAL INTEGRATION TAKE PLACE. PAYMENT. PAYMENT CAN HELP. DO THEY PAY FOR THINGS OTHER THAN FACE TO FACE? WHAT ABOUT IT? WE'RE TALKING ABOUT TELEMEDICINE. IS IT PAID FOR, IS IT PART OF THE SYSTEM. DO THE BILLING REGULATIONS SUPPORT COORDINATED CARE. THESE ARE ALL RESEARCHABLE SSUES. SUPPORT. IS COMMUNICATION AND TEAM-BASED CARE PAID FOR? IS IT REIMBURSED? IS THE WHOLE TEAM REIMBURSED IN THE SYSTEM? IS INVESTMENT IN THE INFRASTRUCTURE SUPPORTED AND PAID FOR? I WILL JUST ZOOM ON. SO THE QUESTION IS, OKAY, DOES INTEGRATION WORK? SUMMARY OF THE RESEARCH STUDIES TODAY. CLINICAL INTEGRATION HAS BEEN FOUND TO WORK TO IMPROVE CERTAIN TREATMENT OUTCOMES, PATIENTS LIKE IT, IMPROVES PATIENT EXPERIENCES AND HAS SHOWN TO REDUCE CONSTANT SERVICES FOR SOME POPULATIONS. BUT WHEN YOU GET TO HEALTH SERVICES RESEARCH, THERE IS NO CLEAR EVIDENCE ABOUT WHICH CARE PROCESSES, WHICH MODELS OF INTEGRATION AND WHICH PAYMENT STRUCTURES ARE MOST EFFECTIVE. SUMMARY. I'D SAY THERE'S LOTS OF OPPORTUNITIES FOR INTEGRATION. EVIDENCE SHOWS INTEGRATION CAN IMPROVE CARE AND IT'S REALLY COMMITTED TO THE CONCEPT, THERE IS NO WRONG DOOR FOR CONSUMERS TO GET INTO THE SYSTEM. IT CAN BE THROUGH THE ER DEPARTMENT, IT CAN BE THROUGH THE POLICE. IT'S LIKE HOW DO YOU GET IN TO THE SYSTEM? AND THAT IS WHAT INTEGRATION IS ALL ABOUT. THE SECOND EXAMPLE I WILL FOCUS ON SOME PAYMENT STRATEGIES. VERY FAMOUS SEMINOLE STUDY IN ALCOHOL RESEARCH, TWO STUDIES, THAT CAME FROM THE INSTITUTE OF MEDICINE. 2001, EVERYONE REFERS TO IT. IT'S CALLED CROSSING THE QUALITY CHASM. IT'S 2001, IT STILL IS DRIVING THE QUALITY AREA IN HEALTH SERVICES RESEARCH. THERE IS A GROWING CHASM BETWEEN THE ACTUAL HEALTHCARE DELIVERY SYSTEM AND THE QUALITY OF CARE THAT PEOPLE GET. AS AN ASIDE, AT THE TIME THAT THIS STUDY WAS DONE, THERE WAS A VERY FAMOUS STUDY DONE BY RAND, THEY LOOKED AT 25 SERVICES, HOW THEY WERE BEING DELIVERED AND WERE THEY BEING PRODUCED IN A QUALITY MANNER. 25. WON'T GO INTO WHAT THEY WERE, BUT OF THE 25, WHAT CAME IN DEAD LAST? ALCOHOL. AND ALCOHOL SERVICES WERE DLIFFED IN DELIVERED IN A QUALITY MANNER ONLY 10% OF THE TIME. NO ONE GOT 100% BUT THERE WERE SOME TYPES OF SERVICES THAT WERE UP IN THE 80s AND 90 PERCENTS. ANOTHER VERY WELL-KNOWN STUDY FROM THE IOM WAS ON THE USE OF INCENTIVES TO DRIVE QUALITY CARE. THIS HAS BEEN AROUND A LONG TIME, 2007, WIDELY USED IN HEALTH SERVICES RIGHT NOW IN AFFECTING CARE. DRILLING IN A LITTLE MORE ON THIS IDEA OF USING INCENTIVES, THE CONTEXT OF PAY FOR PERFORMANCE. HISTORICALLY HEALTHCARE DIDN'T OFFER FINANCIAL OR NON-FINANCIAL REWARDS RELATED TO QUALITY OR OUTCOMES, JUST PAID FOR IT. HIGH QUALITY AND LOW QUALITY PROVIDERS EARN THE SAME. DIDN'T MATTER WHAT WOULD HAPPEN IF THIS WERE HOTELS? YOU DON'T PAY THE SAME PRICE TO STAY AT THE RITZ THAN THAN MOTEL 6. ONE OF THE TWO PIECES OF INCENTIVES, HOW DO YOU MEASURE THINGS, HOW DO YOU HAVE A MEASURE, WHAT ARE THE MEASURES TO USE AND HOW DO YOU PAY WITH A MEASURE -- PAY FOR IMPROVEMENT. THESE ARE BASICALLY WHAT PAY FOR PERFORMANCE IS ALL ABOUT. THERE ARE SOME VERY WELL ESTABLISHED PERFORMANCE MEASURES IN THE ADDICTION AREA. AND THERE ARE FAR FEWER THAN THERE ARE IN THE GENERAL MEDICAL AREA. THESE ARE FOR I WOULD SAY THE GRANDPARENTS OF -- SCREENING AND BRIEF INTERVENTION, YES, THERE IS AN AREA FOR IT. IDENTIFICATION IN A HEALTH PLAN, HEALTH SYSTEM, DO YOU INITIATE TREATMENT, IF YOU INITIATE TREATMENT, DO YOU ENGAGE IN TREATMENT. THESE ARE CORE MEASURES. ARE PEOPLE BEING MONITORED TO SEE HOW THIS IS HAPPENING? WE'RE TALKING ABOUT ALL THESE WONDERFUL INTERVENTIONS, ARE WE MEASURING WHAT DIFFERENCE THAT THEY MAY MAKE IN THE REAL WORLD DELIVERY SYSTEM. I WILL CERTAINLY -- A PREMISE OF THE CHANGING DELIVERY SYSTEM IS CHANGING HOW WE'RE PAYING PROVIDERS, PAYING THE PROVIDER ORGANIZATION. FEE FOR SERVICE IS BECOMING JUST NOT VERY COMMON ANYMORE WITH THE INSURER AND HOW THEY PAY THE ORGANIZATION. AND WE'RE MOVING TO THESE ALTERNATIVE PAYMENT STRATEGIES. THEY'RE LISTED OUT THERE, PAY FOR PERFORMANCE, BUNDLED PAYMENTS, GLOBAL PAYMENTS. I KNOW WE'VE TALKED ABOUT CMS AND MEDICARE/MEDICAID HAVE THESE INHERENTLY BUILT IN TO HOW THEY'RE TRACKING THE SYSTEM AND MANY HEALTH INSURERS -- MOST HEALTH INSURERS ARE AS WELL. IS THERE REASON TO BE CONCERNED? YES. I KNOW I'M STANDING BETWEEN YOU AND LUNCH SO IF ANYONE WANTS TO KNOW ABOUT ALL THESE CONCERNS, I WILL BE HAPPY TO TALK ABOUT THEM BECAUSE THERE ARE PROBLEMS AND HOW DO YOU BUILD IN A SYSTEM, THAT'S WHAT HEALTH SERVICES RESEARCH CAN DO, TO DEAL WITH SOME OF THESE CONCERNS ABOUT WHAT IS THE RIGHT LEVEL OF PAYMENT. DO YOU WANT TO SEE IMPROVEMENT IN SCORES OVER TIME OR DO YOU JUST WANT TO ATTAIN A CERTAIN BASE LEVEL. IS THERE GAMING, ARE PROVIDERS SORT OF TRYING TO NOT HAVE SOME OF THE SICKER PATIENTS STAY IN THE SYSTEM. I WILL SKIP THAT BECAUSE OF TIME. THERE'S BEEN A LOT OF RESEARCH IN THIS AREA IN MENTAL HEALTH AND ADDICTION, LARGELY AT STATE LEVELS. THESE ARE STUDIES THAT MY GROUP HAS DONE OVER TIME. I WON'T GO THROUGH THEM, SEVERAL STATES ACROSS THE COUNTRY, MAINE, WASHINGTON, CONNECTICUT, DELAWARE. OKAY. WHAT DO THEY SHOW? QUICKLY, THE RESULTS, THAT IMPROVEMENTS DO HAPPEN IN LOTS OF AREAS, WAITING TIME, UTILIZATION, BUT THERE IS EVIDENCE OF UNINTENDED CONSEQUENCES IN MANY AREAS. BUT THE BOTTOM LINE I'LL SHOW YOU DOWN THERE, THE BOTTOM LINE IS ABOUT MEDICAL CARE, THE RESULTS OF THE FEW STUDIES THAT HAVE BEEN DONE IN THIS AREA ARE VERY SIMILAR TO THE BROADER MEDICAL CARE SYSTEM. SO IN SUMMARY, P4P, PAY FOR PERFORMANCE, USING INNOCENCE TIFS -- THE RIGOROUS STUDIES EXIST ARE NOT AS MANY AS YOU WANT, THE EVIDENCE IS MIXED. BUT THERE HAVE BEEN MODEST IMPROVEMENTS IN SOME MEASURES. WE'RE STILL LEARNING HOW TO USE PAY FOR PERFORMANCE AND INCENTIVES EFFECTIVELY. THERE'S CONSIDERABLE PROMISE AND FORMIDABLE CHALLENGES. LOOKING TO THE FUTURE, SOME KEY ISSUES FOR ALCOHOL SERVICES ARE REALLY ADAPTING TRULY IN A MEANINGFUL WAY TO THE CONCEPT OF A WHOLE PERSON. THAT MEANS CO-OCCURRING MEDICAL, CO-OCCURRING MENTAL HEALTH AND OTHER SUD. IDENTIFYING OPPORTUNITIES, BECAUSE MEDICAL CARE IS BECOMING FAR LESS SILOED. IN THE MEDICAL ENVIRONMENT, WHAT ARE THE OPPORTUNITIES WITH PRIMARY CARE SPECIALTY MEDICAL, WE'VE BEEN TALKING ABOUT SPECIALTY ADDICTION SERVICES, WHAT ABOUT SPECIALTY MEDICAL? THE EMERGENCY DEPARTMENT. THERE'S SO MUCH BEING DONE IN THE EMERGENCY DEPARTMENTS NOW TO BETTER LINK PEOPLE DIRECTLY TO THE COMMUNITY. THAT'S PART OF HEALTH SERVICES RESEARCH, THAT'S PART OF LOOKING AT THE SYSTEM. I WILL SAY, I'LL THROW OUT A NUMBER OF A STUDY THAT JUST CAME OUT THIS WEEK IN THE ANNALS OF INTERNAL MEDICINE BETWEEN 2008 AND 2016, THERE HAS BEEN A 25% DECLINE IN THE USE -- IN THE VISITS TO PRIMARY CARE. THERE HAS BEEN A 46% INCREASE IN PRIMARY CARE AND USING ALTERNATIVE VENUES. SO IN TERMS OF THE SYSTEM CHANGING, IT IS CHANGING OUT THERE FOR HEALTHCARE. WHERE IS ALCOHOL IN ALL OF THIS AND TAKING ADVANTAGE OF THE FACT THAT THE SYSTEM CHANGING AND CAN WE BE THERE. AND AGAIN, I'D LIKE TO END WITH THE IMPORTANCE OF LOOKING AT THE FULL CONTINUUM, AND WE'RE PARTICULARLY IN NEED OF A FOCUS IN THE AREA OF RECOVERY. SO GETTING BACK TO MY CAR ANALOGY, SO WHERE ARE WE? THE SYSTEM HAS CHANGED A LOT, I WOULD ARGUE. WE ARE AT A CHASM, BUT I LIKE TO BELIEVE THAT WE HAVE THE TOOLS IN HAND SO THAT THAT CAR THAT'S GOING OFF THE CLIFF IS NOT FALLING INTO THE CHASM, THAT WE CAN WORK TOGETHER, AND GET SAFELY TO THE OTHER SIDE AND IMPROVE THE DELIVERY AND QUALITY OF ALCOHOL SERVICES, AND ALL HEALTH SERVICES FOR THAT MATTER. I'VE GOT A WHOLE TEAM BACK AT BARNDEIS WORKING IN THIS AREA, WONDERFUL COLLEAGUES, AND THANK YOU. LUNCHTIME. [APPLAUSE] >> THAT WAS GREAT AND A REAL GREAT OVERVIEW OF WHERE THE CHALLENGES AND THE FUTURE CHALLENGES ARE. YOU KNOW, FOR ME WHEN LISTENING TO THIS, IT ALL HARKENS BACK TO THIS ISSUE OF PARITY FOR MENTAL HEALTH AND ALCOHOL IN PARTICULAR. DO YOU THINK AS PARITY MOVES FORWARD, SOME OF THESE THINGS WILL RESOLVE BECAUSE THEY'RE ALREADY BEING RESOLVED IN, YOU KNOW, OTHER DOMAINS OF HEALTHCARE? >> I THINK IF YOU THINK OF PARITY AND THAT PEOPLE HAVE MORE ACCESS TO SERVICES, THERE ARE ALL KINDS OF PROBLEMS WITH IMPLEMENTING THE FEDERAL PARITY. THERE ARE LAWSUITS. SO IT'S ALWAYS CHALLENGING. I THINK THAT BEYOND PARITY, HOW ARE YOU GOING TO GET THE BASICS INTO GETTING THE DELIVERY SYSTEM OR GETTING THE PROVIDER ORGANIZATION AND THE CLINICIANS TO PUT SYSTEMS IN PLACE SO THAT THE WONDERFUL THINGS THAT WE'VE BEEN HEARING ABOUT HERE ARE ACTUALLY PUT INTO PRACTICE. BECAUSE IT'S NOT THAT THE KNOWLEDGE ISN'T OUT THERE. ILTS JUST THAT IT'S NOT BEING IMPLEMENTED IN A MEANINGFUL WAY. I WILL TELL YOU, I GUESS IT'S SORT OF A FUNNY STORY. I HAVE MY MEDICAL RECORD IS FOREVERMARKED, AND IN THE NOTES SECTION ON MY MEDICAL RECORD, THERE'S, I GUESS BIG LETTERS, "ALWAYS ASK HER ABOUT ALCOHOL SCREENING." WHY IS THIS -- THEN THEY GO INTO, DO YOU DRINK TOO MUCH? COMPLETELY DON'T GO INTO WHAT IS AN INSTRUMENT THAT HAS BEEN VALIDATED SO -- BUT YOU KNOW, THAT'S MAKING CHANGE, AT LEAST PEOPLE ARE SAYING, I DON'T HAVE TIME TO DO THIS, IT'S NOT IMPORTANT, AND LET'S JUST ZIP THROUGH IT. BUT HOW DO YOU KNOW THAT IT'S BEING DONE, HOW DO YOU BUILT IN THE SYSTEMS NOT JUST TO MONITOR, HOW DO YOU USE THE SYSTEM NOT TO JUST HOLD PEOPLE ACCOUNTABLE, HOW DO YOU USE TO LEAD TO IMPROVEMENT SO THAT YOU GET TO A BETTER PLACE THROUGH ALL OF THIS. >> ANY OTHER COUNCILMEMBERS? DAN? >> THANKS, CONNIE. QUICKLY, IT'S RIGHT THERE ON THE CUSP, AND I'M JUST GOING TO USE AN EXAMPLE FROM I THINK IT'S SINGAPORE, I'M NOT QUITE SURE, WHERE YOU HAVE THAT HEALTH PORTABILITY, SO YOU NEED TO HAVE SOME MICRO CHIP, YOUR DRIVER'S LICENSE, SOME KIND OF INTERCONNECTIVITY WHERE CHARTS CAN ACTUALLY TALK TO EACH OTHER, AND YOU HAVE THAT CHIP WITH YOU, SO EVERYONE KNOWS HOW YOU'RE DOING AND WHAT YOU NEED BASICALLY, AND YOU CARRY THAT ALONG WITH YOU. ALONG WITH SINGAPORE, HONG KONG, THE 5G TECHNOLOGY, YOU CAN PAY FOR ANYTHING ON THE STREET, THERE'S NOT AS MUCH OBSTACLES -- >> INTERNATIONAL STUDIES HERE, I DIDN'T SHOW THEM, BUT WE LIKE TO THINK THAT THE HEALTHCARE IS THE BEST IN THE WORLD, IN THE U.S. IN TERMS OF QUALITY AND MOST QUALITY MEASURES, THE U.S. IS NOT AT THE TOP, WE'RE NOT GETTING WHAT WE PAID FOR. SO IT'S REALLY AN ECONOMIC VALUE ARGUMENT, AND YOU GIVE A GOOD EXAMPLE OF A PLACE OR COUNTRY THAT ARE TRYING NEW TECHNIQUES. WE ARE VERY GOOD AT SOMETHING ELSE, THOUGH. WE ARE THE MOST EXPENSIVE SO -- SO THAT RELATES TO THE QUESTION OF VALUE, WHAT IS THE VALUE AND HOW DO YOU IMPROVE IT. IF WE'RE PAYING THE MOST AND WE'RE NOT THE HIGHEST QUALITY, WE'RE AT VERY HIGH QUALITY FOR SOME POPULATIONS. SO THE ISSUE OF DISPARITIES AND EQUITIES AND WHO HAS ACCESS TO WHAT IS A KEY PART OF THIS WHOLE DISCUSSION. >> SO I'M ASSUMING ALL OF YOU CERTAINLY HAVE THOUGHTS AND QUESTIONS ABOUT THE THINGS THAT CONNIE HAS COVERED. I CERTAINLY CAN THINK OF IN MY OWN LIFE AND FAMILIES ALL THESE ISSUES THAT HAVE COME UP. BUT WE ARE RUNNING LATE, SO I'M GOING TO LET YOU ASK SOME OF THOSE QUESTIONS, WE'LL HAVE SOME DISCUSSION LATER SO WE CAN ASK QUESTIONS OF CONNIE AND JILL LATER AS WELL. SO WE'RE GOING TO BREAK UNTIL 1:15, THEN WE NEED TO COME BACK. SO WE'VE GOT TO MOVE WITH VIGOR TO GET LUNCHES AND EVERYTHING. WELCOME BACK FROM LUNCH. SUCH AS IT IS. ABE IS GOING TO PRESENT FOR COUNCIL APPROVAL OF THE SEPTEMBER 12TH MEETING MINUTES, AND HE'S GOING TO TELL YOU ABOUT FUTURE MEETING DATES. >> DO YOU HAVE ANY COMMENTS ABOUT THE COUNCIL MEETING MINUTES? OKAY, HEARING NONE, I'D LIKE TO ENTERTAIN A MOTION TO APPROVE, FIRST. SECOND? APPROVE, DI APPROVE, ABSTAIN? THANK YOU. NOW I'D LIKE TO ANNOUNCE THE MEETING DATES FOR 2020. IT WILL BE ON MAY 12TH, AND FOR THE COMBINED COUNCIL MEETING, THAT WILL BE THE FOLLOWING DAY, MAY 13, AND THEN THE LAST MEETING FOR 2020 IS SEPTEMBER 10. FOR 2021, IT WILL BE FEBRUARY 4, FOR THE JANUARY COUNCIL. FOR THE MAY COUNCIL, IT WILL BE ON MAY 11 FOR NIAAA, AND MAY 12 FOR THE JOINT COUNCILS. AND SEPTEMBER 9, THE LAST MEETING OF 2021. FOR 2022, IT WILL BE FEBRUARY 10, MAY 10, MAY 11, AND SEPTEMBER 8. FOR 2023, FEBRUARY 9, MAY 9, MAY 10, AND SEPTEMBER 7. 2024, FEBRUARY 8, MAY 14, 15, AND 12.& PLEASE NOTE THAT THE COUNCIL MEETING FOR NIAAA USUALLY FALLS ON A THURSDAY, AND FOR THE JOINT COUNCIL, IT'S ON A WEDNESDAY, AND IF WE HAVE A JOINT MEETING WITH NIDA AND NCI, OUR COUNCIL BECOMES TUESDAY. THANK YOU. >> OKAY. SO NOW WE'RE GOING TO HAVE A COUNCIL OF COUNCILS REPORT BY DR. PAUL KENNY. HE'S THE PROFESSOR AND CHAIR OF THE NASH FAMILY DEPARTMENT OF NEUROSCIENCE AT THE ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI. HE ALSO SERVES AS THE DIRECTOR OF THE DRUG DISCOVERY INSTITUTE THERE. HIS MULTIDISCIPLINARY RESEARCH INVOLVES THE STUDY OF BEHAVIORAL PARADIGMS AND THE MOLECULAR UNDERPINNINGS OF BEHAVIORAL DISORDERS. INVESTIGATING THE BRAINS OF RODENTS TO UNCOVER NEW SIGNALING CASE KAIDZ THAT MAY PLAY A ROLE IN ADDICTION-LIKE BEHAVIORS. YOU REMEMBER PAUL WAS ON COUNCIL AND GAVE A REALLY GOOD TALK ABOUT HIS WORK ON NICOTINE AND ITS INTERACTION ULTIMATELY WITH THE PANCREAS, AND THAT PAPER JUST CAME OUT IN "NATURE," RIGHT? I THINK IT WAS THE COVER FOR "NATURE," RIGHT? YEAH. SO THOSE OF YOU WHO REMEMBER THE TALK MAY WANT TO LOOK UP THE PAPER. BECAUSE FOR ME, IT SUGGESTS THAT EVEN VAPING NICOTINE COULD LEAD TO VULNERABILITY FOR DIABETES, SO THERE'S SOME PRETTY HEAVY IMPLICATIONS OF THAT STUDY. BUT THAT'S NOT WHAT WE'RE HERE ABOUT. PAUL IS GOING TO TELL US ABOUT THE NIH COUNCIL OF COUNCILS. THE NIH COUNCIL OF COUNCILS ADVISES THE NIH DIRECTOR, THAT'S COLLINS, FRANCIS CLONS, ENCLOSE FRANCIS C OULD COLLINS, FONDLY KNOWN IN BUILDING 1 AS DPCPSI. I ALWAYS WONDERED WHAT THAT STOOD FOR. IT ACTS AS AN EXTERNAL ADVISORY PANEL TO THE IC DIRECTORS DURING THE CONCEPT APPROVAL, QUOTE-UNQUOTE, STAGE OF THE NIH ROAD MAP INITIATIVE REVIEW PROCESS. THE CONCEPT APPROVAL STAGE INVOLVES THE CONSIDERATION OF A LIST OF POTENTIAL TRANS-NIH INITIATIVES DEVELOPED BY DPCPSI STAFF AFTER RECEIVING INPUT FROM MULTIPLE SOURCES. SO WITH THAT INTRODUCTION, PAUL, YOU CAN TAKE IT AWAY. >> THANKS, GEORGE. IT'S NICE TO BE HOME AGAIN, SO TO SPEAK. I WAS ON NIAAA COUNCIL FOR ABOUT THREE YEARS, I ROTATED OFF, I GUESS ABOUT 18 MONTHS AGO, A YEAR AND A HALF AGO NOW, AND FOR ABOUT THE PAST YEAR, I'VE BEEN ON COUNCIL OF COUNCILS. I THINK THAT TIMING IS RIGHT. AND SO COUNCIL OF COUNCILS AS YOU JUST HEARD IS THE ADVISORY COUNCIL FOR D DPCPSI WHICH THEN REPORTS TO FRANCIS COLLINS. LET'S SEE IF I CAN GET THIS WORKING. OKAY. SO THIS IS A COUNCIL OF COUNCILS. YOU MAY KNOW IT WAS ONE OBVIOUS EXCEPTION IN THIS PICTURE, I'M NOT IN IT, AND THE REASON IS IEMED I'M STANDING RIGHT HERE. SO I'LL HAVE TO HAVE WORDS WITH THE PHOTOGRAPHER THAT I WAS CUT OFF. WE DISCUSS A WIDE RANGE OF TOPICS, THERE'S BEEN A LOT COVERED SINCE I'VE BEEN ON THE COMMITTEE SO WHAT I WOULD DO IS JUST CAPTURE A FEW OF THE VIGNETTES, SOME OF THE THINGS THAT HAVE COME UP IN TERMS OF DISCUSSIONS THAT WE'VE HAD, SOME REPORTS FROM FRANCIS COLLINS TO THE COMMITTEE, AND ALSO SOME OF THESE INITIATIVES THAT WERE PROPOSED IN THE PAST COUNCIL. SO THIS IS THE OVERVIEW OF WHAT I WAS HOPING TO GET THROUGH PRETTY QUICKLY. I'LL FIRST TALK ABOUT AN UPDATE THAT WE RECENTLY HEARD FROM FRANCIS COLLINS. THIS IS AN ISSUE THAT CAME UP AT COUNCIL OF COUNCILS IN TERMS OF SEXUAL AND GENERAL DI MINORITY AND GENDER MINORITY WORKING GROUP. THERE WERE A FEW THINGS I THOUGHT WOULD BE WORTHWHILE BRINGING BACK TO YOU TO HEAR, STUFF THAT I FOUND TO BE REALLY IMPORTANT AND TO BE MINDFUL. THERE'S A NEW INITIATIVE ON DOWN'S SYNDROME, AGAIN SOMETHING I THOUGHT WAS REALLY INTERESTING, BEYOND THE FACT THAT THIS IS A RELATIVELY UNDERREPRESENTED GROUP IN TERMS OF RESEARCH BUT ALSO THE VALUE THAT RESEARCH IN THE POPULATION CAN PROVIDE TO VARIOUS DISEASES IN TERMS OF INSIGHTS. A PROGRAM THAT I AM VERY KEEN ON, I THINK IT'S A WONDERFUL INITIATIVE AND IT'S BEEN EXPANDING AND HAS BEEN EXPANDED, SO I'LL TALK A LITTLE BIT ABOUT THAT, AND THEN AN UPDATE THAT WE RECEIVED RECENTLY ON THE USE OF PRIMATES ACROSS NIH INSTITUTES. SO AGAIN, I'LL TRY AND GO THROUGH PRETTY QUICKLY. SO FRANCIS COLLINS GAVE US A TALK A FEW MONTHS AGO ABOUT WHERE HE WAS THINKING NIH WAS GOING, SO I CAPTURED A FEW OF THOSE SLIDES AND I WANTED TO PRESENT SOME OF THEM HERE. SOME OF THE THINGS THAT THE FOCUSES FOR HIM CURRENTLY NIH-WIDE. OF COURSE A MAJOR CONCERN FOR HIM AND NIH IS THE OPIOID ADDICTION EPIDEMIC. I GUESS IT'S A CONCERN TO ALL OF US. WITH THIS BEING A NUMBER OF INITIATIVES THAT HAVE BEEN IMPLEMENTED, OF COURSE THE MAJOR ONE IS THE HEAL INITIATIVE, WHICH IS THE MAJOR SOURCE OF FUNDING FOCUSED ON UNDERSTANDING OPIOID ADDICTION, OF COURSE, DEVELOPING NEW THERAPEUTICS, NEW INTERVENTIONS. REALLY ACROSS THE BOARD. SO BASIC UNDERSTANDING ALL THE WAY THROUGH TO REALLY HOW WE IMPLEMENT AVAILABLE MEDICATIONS, INTERVENTIONS AND WE DEVELOP NEW INTERVENTIONS. SO WITH REGARD TO DPCPSI, THERE'S A FEW AREAS OR I GUESS COUNCIL OF COUNCILS THAT WE WERE ASKED TO CONSIDER THAT CAME UP DURING THIS MEETING, SO THIS IS REALLY WHERE THE HEAL INITIATIVE IS FOCUSED IN TERMS OF ENHANCING PAIN MANAGEMENT. OF COURSE MISMANAGED OR UNMANAGED PAIN IS A MAJOR DRIVER FOR OPIOID USE AND ULTIMATELY MISUSE, SO HOW DO WE MANAGE PAIN IN A BETTER MANNER AND HOW DO WE IMPROVE TREATMENTS FOR NOT JUST PAIN BUT ALSO FOR ADDICTION ONCE MISUSE OF OPIOIDS FOR PAIN HAS RESULTED IN DEPENDENCE AND ULTIMATELY ADDICTION. SO TWO OF THE AREAS THAT WE'VE BEEN LOOKING AT ARE REALLY AROUND PRELIN PRE-CLINICAL RESEARCH IN PAIN MANAGEMENT. COMMON FUND ADMINISTERED THROUGH COUNCIL OF COUNCILS HAS SOME AREAS THAT IT'S LOOKING TO SUPPORT WITH REGARD TO PRE-CLINICAL RESEARCH IN TERMS OF PAIN MANAGEMENT, AN ALSO TO EXPAND THERAPEUTIC OPTIONS. THE SPARC PROGRAM I JUST ALLUDED TO A FEW MOMENTS AGO IS AN AREA THAT'S -- MAINLY THIS ONE HERE IS MORE ADVANCED. SO THE TWO MAIN INITIATIVES THAT COUNCIL OF COUNCILS WERE CONSIDERING AND ARE GOING TO BE THE FOCUS OF INTENSE ACTIVITY UNDER THE HEAL INITIATIVE IS -- THE FIRST IS TO IDENTIFY BIOMARKERS OR SOME PREDICTIVE CAPABILITY TO DETERMINE SOMEONE WHO'S SUFFERING FROM ACUTE PAIN WILL TRANSITION INTO A STATE OF CHRONIC PAIN. THE UNDERLYING MECHANISMS ARE STILL VERY POORLY UNSTOOD. SO THE IDEA HERE IS, ARE THERE SOME KIND OF PHYSIOLOGICAL EVEN BLOOD BASED BIOMARKERS THAT MAY BE ABLE TO PREDICT THOSE WHO ARE MOST VULNERABLE AND IF SO, POTENTIALLY SUCH BIOMARKERS MAY EVEN BE INVOLVED IN THE PROCESS WHEREBY ACUTE PAIN TURNS INTO A STATE OF CHRONIC PAIN. SO TO MY MIND, THIS IS A VERY WORTHY INITIATIVE, PROBABLY SOMETHING THAT SHOULD HAVE BEEN DONE A LONG TIME AGO TO TRY AND UNDERSTAND THAT TRANSITION AND IT'S FANTASTIC THAT IT'S BEING DONE NOW. ANOTHER INITIATIVE I'LL AGAIN BRIEFLY MENTION IS THE SPARC INITIATIVE, STIMULATING PERIPHERAL ACTIVITY TO RELIEVE CONDITIONS. UNDERSTANDING HOW THE BRAIN INTERACTS WITH THE BODY AND HOW THE BODY INTERACTSZ WITH THE BRAIN. SO IF YOU STIMULATE THE VAGAL NEVER, IT MAY HAVE THERAPEUTIC EFFECTS IN TERMS OF DRUG USE SO& HOW DOES THAT WORK? HOW ARE THESE PERIPHERAL NEURONS THAT ARE PROVIDING INFORMATION TO THE BRAIN PROVIDE THAT INFORMATION AND HOW IS THAT INFORMATION USED AND CAN WE TAKE ADVANTAGE OF THAT UNDERSTANDING IF WE CAN FIGURE OUT HOW THAT WORKS. AND CONVERSELY, HOW IS THE BRAIN COMMUNICATING WITH PERIPHERAL ORGAN, AND IS THE BRAIN INVOLVED IN WHAT WE'D OTHERWISE CONSIDER TO BE PERIPHERAL ORGAN DISEASE, AND THIS GETS BACK ACTUALLY TO A PAPER FROM MY LAB THAT GEORGE JUST MENTIONED WHERE WE FOUND A LINK IN THE BLAINE THAT SEEMS BRAIN THAT SEEMS TO BE DRIVING DIABETES, SOMETHING THAT YOU WOULD NOT EXPECT, ALMOST A PANCREATIC-TYPE DISORDER, I KNOW THAT'S SOMETHING LAURA WORKS ON AS WELL, FAR MORE GOES ON IN THE BRAIN THAN WE PREVIOUSLY RECOGNIZED, NICOTINE-INDUCED DIABETES IS THE BASIS FOR MANY DISORDERS WE DON'T NORMALLY THINK. SO SPARC IS TRYING TO ADDRESS THAT TYPE OF DYNAMIC. SO IN THE CONTEXT OF OPIOID ADDICTION, THERE'S NOW AN INITIATIVE TO REALLY MAP CENTRAL COMMUNICATION WITH PERIPHERAL SITES INVOLVED IN PAIN PERCEPTION, WHICH YOU WOULD THINK WOULD HAVE BEEN KNOCKED OUT MANY, MANY YEARS AGO, BUT CONSIDERING THE TYPES OF TOOLS THAT ARE CURRENTLY AVAILABLE, THAT WEREN'T AVAILABLE BEFORE, AND NEW TOOLS ARE EMERGING, THERE'S A REALLY GOOD OPPORTUNITY TO HOPEFULLY GET MORE REFINED UNDERSTANDING OF HOW THE BRAIN IS INTERACTING WITH THESE NOCICEPTIVE-TYPE TISSUES. SO THOSE ARE TWO KIND OF INITIATIVES THAT WE WERE LOOKING AT, COUNCIL OF COUNCILS IS CONSIDERING. ANOTHER TOPIC THAT WAS RAISED BY FRANCIS COLLINS IS ARTIFICIAL INTELLIGENCE. ALL DOMAINS SCIENCE, NEUROSCIENCE, I WOULDN'T SAY IN PARTICULAR BUT CERTAINLY NEUROSCIENCE, IS SUBJECT TO BIG DATA. I THINK OUR EXPERIMENTS ARE GETTING BIGGER, THE DATASETS ARE GETTING BIGGER AND HOW DO WE HANDLE THAT. IT'S A CHALLENGE, PARTICULARLY IF YOU'RE TRAINED LIKE MANY OF US IN THE ROOM ARE, LIKE I WAS, WHICH IS YOU'RE NOT TRAINED TO HANDLE BIG DATA, YOU'RE TRAINED TO DO BENCH WORK-TYPE OF EXPERIMENTS AND YOU RUN EVERYTHING ON AN EXCEL FILE, MAYBE A PRISSMM FILE, YOU -- AND YOU'RE DONE. THAT'S NOT GULF GOING TO CUT IT ANYMORE WITH THE DATA WE'RE COLLECTING SO WHAT DO YOU DO. A WORKING GROUP HAS BEEN ASSEMBLED TO REALLY TRY AND MAKE RECOMMENDATIONS TO FRANCIS COLLINS ABOUT WHERE THE FUTURE LIES AND HOW WE CAN TRY AND GET AHEAD OF THAT. SO YOU CAN SEE IT'S A REALLY HIGH POWERED WORKING GROUP OF PEOPLE INTERESTED IN ARTIFICIAL INTELLIGENCE AROUND THIS TYPE OF BIG DATA, THESE BIG DATASETS THAT ARE BEING GENERATED. SO WE HAVE SOME EARLY STAGE RECOMMENDATIONS THAT WE JUST CONSIDERED RECENTLY, AN THEY'RE VERY INTUITIVE TYPE OF RECOMMENDATIONS, BUT IT'S IMPORTANT THAT THEY'RE MADE. THE FIRST IS WE SHOULD BEGIN TO CATALOG DATA SUCH THAT IT'S USABLE. IF WE'RE ALL GENERATING BIG DATASETS OR BEGIN TO GENERATE THOSE DATASETS, IF YOU GO THROUGH THE PEOPLE WHO REALLY UNDERSTAND AND USE THOSE DATASETS WHO'VE CAPTURED THEM AND USED THEM AS YOU WILL AND BENEFIT FROM THE TYPES OF DATA WE'RE GENERATING. SO BEING ABLE TO CAT LOCK AND USE EXISTING DATA AND GENERATE NEW DATA IS IMPORTANT. ANOTHER INITIATIVE, TO TRAIN THE PEOPLE TO DO THE TYPES OF SCIENCE THAT WE DO BUT ALSO UNDERSTAND THE COMPUTATIONAL APPROACHES THAT ARE REQUIRED, THE STATISTICAL APPROACHES THAT ARE REQUIRED TO HANDLE BIG DATA, SO WE NEED A NEW TYPE OF SCIENTIST, SOMEONE WHO CAN SPEAK BOTH LANGUAGES. SO HOPEFULLY THAT WILL BE THE CASE. I THINK IT HAS TO BE KERRED HOW WE CONSIDERED HOW WE DO SCIENCE NOW. THE INITIATIVE WAS TO TRY TO HIGHLIGHT WHEN THIS WORKS, WHEN BIG DATA HAS ACTUALLY PROVIDED BREAKTHROUGHS THAT YOU WOULDN'T HAVE HAD IF IT WEREN'T FOR THESE TYPES OF ARTIFICIAL INTELLIGENCE TYPE OF APPROACHES. SO IT WAS REALLY JUST TO ADVERTISE THAT THIS IS THE FUTURE. ANOTHER AREA DR. COLLINS HIGHLIGHTED WAS GENOME EDITING, TREMENDOUS AMOUNT OF EXCITEMENT AROUND, BASIC SCIENCE UTILITY TO 345 NIP LATE GENES, CELLS, ANIMALS EVEN, DISEASE INTERVENTION, CAN YOU USE CRISPR, CAS NINE, NEW GENOME EDITORS TO BE ABLE TO CRACK THOSE FAULTY GENES. ALREADY WE'RE BEGINNING TO SEE THIS HAPPEN. SO THIS SCIENCE FICTION IS BECOMING REALITY WHERE GENOME EDITING IS NOW BECOMING AN INTERVENTION FOR DISEASES, INCLUDING SICKLE CELL DISEASE. SO THIS IS FANTASTIC. IT JUST WORKS, IT'S ABSOLUTELY WONDERFUL, A WHOLE NEW APPROACH TO MEDICINE. OF COURSE ANOTHER TOPIC THAT CAME UP IS, WELL, THAT'S SOMATIC CELL MUTATION, BUT WHAT IF YOU BEGIN TO TACKLE GERMLINE MUTATION? WHAT IF PEOPLE BEGIN TO SAY, LET'S DIAL OUT MUTATIONS IN THE GERMLINE TO ERADICATE DISEASE ENTIRELY. SO IN OTHER WORDS THE MUTATION YOU MAKE ISN'T SOMETHING THAT YOU CARRY AND YOU DON'T PASS ON TO YOUR OFFSPRING. THE MUTATION THAT'S MADE IN YOU OR YOUR OFFSPRING IS SOMETHING THAT'S CARRIED FORWARD TO GENERATIONS. I THINK WE'VE ALL HEARD ABOUT THE THE NEWS COMING FROM CHINA WHERE THESE TYPES OF GERM CELL MUTATIONS HAVE BEEN CARRIED OUT AND THAT'S AN ETHICAL QUANDARY, SHALL WE SAY. SO AS YOU CAN SEE HERE, THERE'S A MORATORIUM THAT'S NOW BEING PROPOSED BY FRANCIS COLLINS -- TO SUGGEST TO SAY THAT THIS IS SOMETHING THAT WE SHOULDN'T DO NOW. MAYBE THERE IS BENEFIT TO THIS TYPE OF GERM CELL INTERVENTION, BUT WE'RE NOT AT THE STAGE YET WHERE WE UNDERSTAND THE TECHNOLOGY AND ITS CONSEQUENCES, EITHER SCIENTIFICALLY, BIOLOGICALLY, CLINICALLY OR PHILOSOPHICALLY, WHERE WE'RE ABLE TO MAKE THOSE DECISIONS SO A MORATORIUM IS PROBABLY THE RIGHT THING. SO SOMATIC MUTATIONS, ABSOLUTELY THEY WORK, THE GERM CELL, WE HAVE TO TREAD LIGHTLY. SO I JUST WANTED TO TOUCH UPON THIS BECAUSE I FOUND THIS NEXT TOPIC VERY -- ACTUALLY -- THERE'S A WORKING GROUP THAT REPORTS TO COUNCIL OF COUNCILS ON SEXUAL AND GENDER MINORITY, AND REALLY HOW WE CAPTURE THAT POPULATION OF PEOPLE IN THE NIH, IN TERMS OF WHETHER THEY'RE STUDENTS OR SUPPORTED BY THE NIH, OR FACULTY SUPPORTED BY THE NIH OR THEY'RE ENROLLED IN HUMAN CLINICAL TRIALS. SO THESE ARE FEMALES, FEMALE SCIENTISTS, GRADUATE STUDENTS, THEY'RE GAY PEOPLE, THEY'RE TRANSGENDER INDIVIDUALS, SO IT'S REALLY ANYONE WHO'S A SEXUAL OR GENDER MINORITY. SO THE WORKING GROUP HAS BEEN DEVELOPING RECOMMEDATIONS IN TERMS OF HOW THE NIH NEEDS TO LOOK AT ISSUES AROUND SEX AND GENDER. AND SO WE HAD AN INTERIM REPORT AND I SHOULD SAY THAT A FELLOW COUNCIL OF COUNCILS MEMBER, SCOUT, PRESENTED THIS REPORT. AS A CONSEQUENCE, WE PRESENTED SCOUT TO MOUNT SINAI AND BASED ON HIS RECOMMENDATIONS, WE BEGAN TO IMPLEMENT SOME OF THE CHANGES THAT CAME THROUGH THIS REPORT. SO I WOULD ENCOURAGE YOU TO HUNT DOWN THIS REPORT IF YOU CAN ONLINE AND TAKE A LOOK AT IT. I DON'T HAVE TIME TO GO THROUGH IT, BUT I JUST WANTED TO PRESENT JUST ONE PINT THAT CAME UP DURING WHAT WAS AN EXTENSIVE DISCUSSION, YOU DON'T EVEN NEED TO READ THIS, IF YOU THINK OF TRANSGENDER INDIVIDUALS, THERE'S A WHOLE POPULATION OUT THERE WHO ARE TRANSGENDER AND WE KNOW BASICALLY NOTHING ABOUT THEIR HEALTH ISSUES. THEY'RE NOT CAPTURES IN ANY CLINICAL TRIALS AND THEIR POPULATION IS INCREDIBLY VULNERABLE, THEY'VE GOT PERHAPS THE HIGHEST RATE OF SUICIDE IN ANY GROUP AND WE REALLY KNOW NOTHING ABOUT THE HEALTH DISPARITIES THAT THEY SUFFER FROM. IT'S AMAZING, WE'RE SCIENTISTS, WE TRACK DATA, WE USE DATA TO INFORM DECISIONS AND YET HERE IS A GROUP OF INDIVIDUALS THAT WE KNOW BASICALLY NOTHING ABOUT, WE HAVE NO DATA. SO I THOUGHT THAT THAT WAS REALLY IMPACTFUL, I FOUND IT VERY GRATIFYING TO BE ON A COMMITTEE THAT DEALS WITH THESE REAL WORRELL ISSUES THAT IMPACT HOW GROUPS THAT COULD BENEFIT FROM RESEARCH HOPEFULLY WILL BENEFIT FROM THAT RESEARCH. SO MOVING ON, ANOTHER ISSUE THAT CAME UP RECENTLY THAT WAS PRESENTED BY DR. TABAK WAS THE INITIATIVE FOCUSED ON -- JUST LISTEN TO THIS FOR A SECOND. >> SERIOUSLY, I DON'T FEEL I SHOULD HAVE TO JUSTIFY MY EXISTENCE. BUT TO THOSE WHO QUESTION THE VALUE OF PEOPLE WITH DOWN SYNDROME -- >> I'M SORRY, THE VIDEO STALLED. BASICALLY THIS INDIVIDUAL WAS SAYING THAT DOWN SYNDROME, QUITE OFTEN IT'S LOOKED UPON AS IT'S A HANDICAP BUT AS A HANDICAP AND IT DOESN'T HAVE TO BE. THAT PEOPLE WITH DOWN SYNDROME SHOULD BE INCLUDED IN RESEARCH. WE NEED TO UNDERSTAND WHERE THEIR HEALTH DISPARITIES ARE. QUITE OFTEN WE DON'T KNOW HOW THEY RESPOND TO MEDICATIONS. BUT IN ADDITION TO THAT, THEY CAN BRING A LOT TO THE TABLE. SO IF YOU LOOK AT THE HEALTH ISSUES THAT WE KNOW WITH THAT POPULATION OF INDIVIDUALS, QUITE OFTEN THEY'RE MORE VULNERABLE TO ALZHEIMER'S DISEASE, LEUKEMIA, HEART DEFECTS, AUTISM AND OTHER DISORDERS. SO THEY'RE MORE VULNERABLE IN THAT RESPECT. HOWEVER, CONVERSELY THEY'RE QUITE PROTECTED FROM CANCERS, HEART DISEASE, HEART ATTACKS. WE DON'T UNDERSTAND WHY. SO HERE IS A POTENTIAL WINDOW INTO VULNERABILITY AND RESILIENCE OF THESE DIFFERENT TYPES OF DISORDERS. SO THIS INITIATIVE THAT WA PRESENTED BY DR. TABAK WAS THAT WE NEED TO DO MORE RESEARCH FOCUSED ON THIS POPULATION. IT'S GOOD FOR THEM, AND IT'S GOOD FOR US. SO THIS INITIATIVE IS GOING TO INCREASE FUNDING FOR DOWN SYNDROME, THOSE LABS THAT ARE INTERESTED IN THAT, AND LABS THAT PERHAPS AREN'T WILL HAVE TOOLS THAT COULD BE RELEVANT AND TRY AND EXPAND DOWN SYNDROME TYPE RESEARCH, I THOUGHT WAS A WONDERFUL INITIATIVE. JUST TO MOVE BACK TO THE SPARC PROGRAM, THIS IS SOMETHING THAT AS I'VE MENTIONED PREVIOUSLY, I THINK IS A REALLY FANTASTIC INITIATIVE, ONE OF THESE KIND OF TRANS-NIH INITIATIVES WHERE IT TOUCHES ON THE ADMISSION OF MANY DIFFERENT INSTITUTES, NIAAA OF COURSE WILL BENEFIT TREMENDOUSLY FROM THIS TYPE OF RESEARCH, AND REALLY AS I SAID, IT'S TO UNDERSTAND HOW THE BRAIN AND THE BODY COMMUNICATE. AND IDEALLY TO DEVELOP NEW TOOLS TO MANIPULATE THAT COMMUNICATION IN THE CONTEXT OF THERAPEUTICS. SO DISEASE CONTEXT. IF WE CAN MA MANIPULATE BRAIN-DO DEINTERACTIONS SPECIFICALLY, THERE'S LIKELY TO BE UNEXPECTED BENEFITS. YET CURRENTLY WE REALLY CAN'T DO THAT. SO VAGAL STIMULATION IS REALLY DIRTY FOR LACK OF A BETTER WORD, YOU CAPTURE ALL THE NEURONS PROVIDING INFORMATION TO THE BRAIN AND ALL THE NEURONS ARE DESCENDING, PROVIDING CENTRA INFORMATION DOWN INTO PERIPHERAL ORGANS, SO YOU'RE HITTING EVERYTHING. IT WOULD BE NICE TO BE ABLE TO BE A LITTLE BIT MORE REFINED AND SPECIFIC AND OPTIMIZE THIS TYPE OF APPROACH. AND ULTIMATELY THAT'S THE GOAL WITH SPARC. SO I WOULD HOPE THAT AS THIS PROGRAM GATHERS STEAM, IT'S BEEN THERE WILL BE A LOT OF NOW, THAT- SERENDIPITY THAT WE WILL FIND THINGS WE DID NOT EXPECT TO FIND THAT WILL HAVE THERAPEUTIC IMPLICATIONS. SO WE START OUT WITH THE BASICS TO TRY AND DEFINE ANATOMICAL AND REALLY THE MAPPING OF THE BRAIN AND ORGANS, AND AS THAT MAPPING IS PROCEEDED, CAN WE DEVELOP TOOLS, THESE TOOLS ARE ABSOLUTELY QUIT CAL, IS THERE A WAY OF INTERVENING SO WE CAN TARGET -- AND DELIVER CENTRAL -- TO THE PANCREAS IN DIABETES, TO THE GUT IN TERMS OF IRRITABLE BOWEL SYNDROME OR WHEREVER IT MAY BE, AND BACK TO THE BRAIN, THAT'S INVOLVED WITH VARIOUS DISEASES. CAN WE MODEL THAT IN CELLS AND IDEALLY IN LABORATORY ANIMALS AND MANIPULATE THAT TYPE OF BACK AND FORTH BETWEEN BRAIN AND BODY, AND THE TOOLS REALLY HAVE BEEN MADE AVAILABLE, SO IF WE CAN UNDERSTAND HOW THIS OCCURS AND HAVE THE TOOLS, WE CAN BEGIN TO INTERVENE. AS WE'RE BEGINNING TO CAN PE MOVE TOWARDS HUMAN, A LOT OF DATA IS ALREADY BEING GENERATED, HOW DO WE HANDLE THAT DATA AND THE MOST RECENT ITERATION IS, CAN WE USE THIS TYPE OF APPROACH IN THE CONTEXT OF THE OPIOID ADDICTION EPIDEMIC. AGAIN, THE CONTEXT OF HEAL. SO CAN WE UNDERSTAND HOW PAIN SENSING ORGANS ARE RECEIVING INFORMATION FROM THE BRAIN AND SENDING INFORMATION BACK TO THE BRAIN AND ARE THERE NOVEL WAYS OF INTERVENING IN THAT TYPE OF COMMUNICATION FOR NOVEL ANALGESICS. SO I THINK THIS IS AN ABSOLUTELY WONDERFUL PROGRAM, IT'S A PLEASURE TO BE INVOLVED IN THOSE TYPES OF DISCUSSIONS WHEN THIS PROGRAM IS DISCUSSED IN COUNCIL OF COUNCILS. I JUST THOUGHT I'D SHOW SOME OF THE GRANTS THAT HAVE BEEN FUNDED RECENTLY BY SPARC. YOU CAN SEE, THEY LOOK REALLY EXCITING, REALLY INNOVATIVE TYPE WORK. BUT PERHAPS NOT THE TYPE OF WORK THAT AN INDIVIDUAL AGENCY AT THE NIH TYPICALLY WOULD HAVE FUNDED. SO IT'S KIND OF NICE TO HAVE THIS KIND OF PROGRAM THAT CAN FOCUS -- IT'S REALLY A CRITICAL AREA OF RESEARCH. AND LASTLY, I JUST WANTED TO HIGHLIGHT THE TYPES OF CONVERSATIONS THAT HAVE BEEN GOING ON AT COUNCIL OF COUNCILS AROUND THE USE OF PRIMATES. SO THERE'S REALLY TWO CONVERSATIONS, I'M PROBABLY OUT OF TIME SO I'LL GO REALLY QUICKLY. AND THE FIRST IS THE NATIONAL PRIMATE RESEARCH CENTERS, WHICH ARE AN INCREDIBLE RESOURCE. THEY PROVIDE PRIMATES FOR RESEARCH ACROSS ALL NIH AGENCIES. THERE'S TREMENDOUS WORK THAT COMES FROM THESE PRIMATE CENTERS. AND THEY'VE NOW BEEN SUPPORTED AGAIN, SO THIS IS ONE OF THESE CONCEPT CLEARANCES TO, AGAIN, SUPPORT THESE PRIMATE CENTERS TO MAKE SURE THEY STAY IN BUSINESS. HOPEFULLY THAT WILL BE THE CASE. ON THE FLIP SIDE OF THE COIN, FRANCIS COLLINS RECENTLY, I GUESS LESS THAN A YEAR AGO, MADE AN UPDATE, PROVIDED AN UPDATE ON THE USE OF CHIMPANZEES FROM THE NIH, AND AS YOU PROBABLY KNOW, THE NIH NOW DOES NOT USE CHIMPANZEES BUT HAS GOT A SUBSTANTIAL COLONY OF CHM CHIMPANZEES THAT WERE USED IN RESEARCH, IF I REMEMBER CORRECTLY, AROUND 250 MONKEYS. THE IDEA WAS THAT THESE MONKEYS WOULD BE TRANSFERRED TO BASICALLY A HAVEN, CALLED CHIMP HAVEN WHERE THEY CAN LIVE OUT THE END OF THEIR DAYS IN GRACE. THEY'VE DONE THEIR TOUR OF DUTY AND NOW IT'S FINISHED, AND THEY CAN MOVE FROM THE LAB INTO A PLACE WHERE THEY CAN BE HAPPY. BUT THE ISSUE IS, OF COURSE, THAT THIS IS AN AGING POPULATION, MANY OF THESE MONKEYS ARE GERIATRIC AND IT'S VERY DIFFICULT TO MOVE THEM FROM WHERE THEY CURRENTLY ARE INTO CHIMP HAVEN AND OTHER SUITABLE NEW HOMES WITHOUT IT BEING DETRIMENTAL TO THE MONKEYS. SO COUNCIL OF COUNCILS HAVE PUT TOGETHER A WORKING GROUP TO MAKE RECOMMENDATIONS ABOUT HOW TO HANDLE THIS REALLY SENSITIVE ISSUE. AND THERE ARE VERY REASONABLE RECOMMENDATIONS THAT ARE PUT FORTH, THIS IS LED BITTER EE MAG BY TERRY MAG SON FROM CHAPEL HIP, TO DO OUR VERY BEST TO MAKE SURE THAT AS MANY OF THESE CHIMPANZEES CAN TRANSITION TO WHERE THEY NEED TO BE. SO THAT'S ONGOING RIGHT NOW. AND I THINK THAT'S IT. THANK YOU. I'M HAPPY TO TAKE ANY QUESTIONS YOU MAY HAVE THAT I MAY BE ABLE TO ANSWER. [APPLAUSE] >> THANKS, PAUL. I JUST WANT TO MAKE A COUPLE OF QUICK COMMENTS. IT'S NOT UNUSUAL THAT THE NIAAA REPRESENTATIVE IS CUT OUT OF THE PICTURE. [LAUGHTER] WE'LL TALK ABOUT THAT LATER. BUT TWO THINGS. THE BLUEPRINT HAS AN INTERCEPTION PROGRAM THAT'S KIND OF LIKE AN EXTENSION OF SPARC ONLY MORE CENTRAL AS I UNDERSTAND IT, CENTRAL NERVOUS SYSTEM CONTROL OVER THE PERIPHERY AND HOW DO WE FEEL THINGS, SO SPARC IS SPARKING SOME OTHER INTERACTIVE PROGRAMS. I JUST THOUGHT I'D MENTION THAT. IT'S NOT OUT YET, BUT THE TIN CUPPING HAS STARTED FOR FUNDING IT. >> THAT'S FANTASTIC. >> YEAH. AND THIN -- AND YOU PERSONALLY MIGHT BE INTERESTED IN THAT. AND THEN THE PRIMATE PART, I JUST DID GET ASKED BY JIM ANDERSON TO PARTICIPATE IN THAT, AND WE DO HAVE QUITE A BIT OF PRIMATE RESEARCH AT NIAAA AND ONE OF THE IMPETUSES FOR THIS IS THE FACT THAT YOU CAN NOW DO GENETIC MODIFICATIONS OF PARTICULARLY MARMOSETS, AND SO THERE IS GENE EDITING BEING DONE IN MARMOSETS, TRANSGENIC MARMOSETS ARE BEING MADE, AND MARMOSETS HAVE A VERY WELL DEVELOPED FRONTAL CORTEX, AMONG OTHER THINGS, SO YOU KNOW, I THINK THERE'S SOME REAL OPPORTUNITIES FOR NIAAA IN THE PRIMATE ZONE. SO I'LL SHUT UP. BUT PAUL, IT MIGHT BE GOOD IF YOU AND I AND TRISH HAD A PHONE CALL WHENEVER IT'S CONVENIENT FOR YOU SO WE CAN KIND OF CATCH UP ON -- >> YEAH, THAT WOULD BE FANTASTIC. >> -- WHAT OUR INTERESTS ARE FOR THE COUNCIL OF COUNCILS. >> ABSOLUTELY. I'D BE HAPPY TO CONVEY THEM. >> THAT WAS REALLY GOOD COVERAGE, BUT THERE'S A LOT OF AREAS THERE THAT WE HAVE SOME INTEREST IN. QUESTION? >> PAUL, I HAD A COMMENT AND A QUESTION. I WAS THRILLED AT THE DOWN SYNDROME INITIATIVE. THAT'S FABULOUS. FOR CONTEXT, DOWN SYNDROME INCIDENCE IN THE U.S. IS 1 OF 700 BIRTHS, PRENATAL ALCOHOL EXPOSURE IS BETWEEN 3 TO 5% OF BIRTHS. IT DOESN'T DISAPPEAR EITHER AS YOU GET OLDER. MY QUESTION IS ABOUT THE A.I. INITIATIVE, AND WAS THERE DISCUSSION IN THERE ABOUT THE REPRODUCIBILITY PROBLEMS IN THOSE DATASETS. WE'VE PLAYED WITH IT AS WELL, AND THAT IS SO CRUCIAL BECAUSE PEOPLE ARE OFTEN USING THEIR DATASETS TO ACTUALLY TEST, AND THEN ALGORITHMS AND THE LIKE AREN'T BEING BLOCKED OUT. WAS THERE DISCUSSION? >> EXTENSIVE. I MOVED THROUGH THAT SO QUICKLY. IT'S SUCH A COMPLICATED AND FAST MOVING AREA SO I APOLOGIZE I DIDN'T CAPTURE EVEN A FRACTION OF THE DISCUSSION. WE HAD AT LEAST TWO PRESENTATIONS ON EXACTLY THAT AND RELATED ISSUES. SO THEY'RE TRYING TO COME UP WITH BEST PRACTICES AROUND EXACTLY THOSE TYPES OF ISSUES RIGHT NOW. >> ANY OTHER QUESTIONS FOR PAUL? PAUL, THANK YOU FOR DOING THIS. I MEAN, YET ANOTHER TRIP FROM NEW YORK DOWN HERE TO WASHINGTON ON MULTIPLE OCCASIONS, AND I REALLY AM GRATEFUL FOR PAUL TAKING THIS ON FOR US. SO THANKS A LOT. GREAT SUMMARY. OKAY. NEXT, YOU'RE GOING TO LOVE THIS ONE. MAYBE I SHOULD REPHRASE THAT. KOOB IS GOING TO LOVE THIS ONE. SO WE'RE GOING TO HAVE A CONCEPT CLEARANCE ON A WORD THAT MANY OF YOU HAVE NEVER HEARD OF BEFORE CALLED HYPERKATIFEIA, AND IT'S A WORD THAT I MADE UP. SO BETTER GET USED TO IT. IT'S IN WIKI NOW. SO DR. JENICA PATTERSON IS PROGRAM DIRECTOR IN THE DIVISION OF NEUROSCIENCE AND BEHAVIOR, DR. RACHEL ANDERSON, OFFICE OF SCIENCE POLICY AND COMMUNICATION. AND I JUST WANT TO SAY AHEAD OF TIME THAT I CHARGED THEM WITH DOING THIS FOR MULTIPLE REASONS. ONE OF WHICH WAS TO SEE WHAT WE WERE DOING IN THIS SPACE, WHICH WAS OF INTEREST TO US AT NIAAA, BUT THE OTHER REASON IS TO SET UP A PARADIGM, KIND OF A FRAMEWORK WHERE WE COULD DO THIS FOR YOUR FAVORITE WORD OR DOMAIN OF INTEREST. AND SO I'M GOING TO STOP TALKING AND LET THEM TELL YOU HOW THEY PULLED THIS OFF AND WHAT CAME OUT OF IT, AND WE WELCOME YOUR FEEDBACK. >> THANK YOU. FIRST OF ALL, I WANTED TO MAKE THE COMMENT, THIS IS NOT A FORMAL CONCEPT CLEARANCE. AND IT'S NOT A SCIENTIFIC TALK. BUT IT IS A DEMONSTRATION OF HOW WE CAN USE PORTFOLIO ANALYSIS TOOLS TO EXPLORE EMERGING AREAS OF RESEARCH. SO I'LL START BY SAYING THAT HERE AT NIH, PORTFOLIO ANALYSIS IS ONE WAY TO SYSTEMATICALLY EXAMINE CURRENTLY FUNDED RESEARCH PROJECTS. AND THESE ANALYSES CAN REVEAL TRENDS AND GAPS IN RESEARCH AND IDENTIFY DIFFERENT OUTPUTTINGS SUCH AS PUBLICATIONS OF GRANTS THAT WE HAVE FUNDED. NIH HAS A WHOLE OFFICE OF PORTFOLIO ANALYSIS THAT DEVELOS SEARCH AND ANALYSIS TOOLS TO HELP US ACCOMPLISH THIS. SO THROUGHOUT THE PRESENTATION TODAY, JENICA AND I WILL CALL OUT AND BRING YOUR ATTENTION TO A FEW OF THESE TOOLS AND TRY TO HIGHLIGHT WHAT WE CAN LEARN FROM THEM AND SOMETIMES POINT OUT WHAT THEIR LIMITATIONS ARE. SO JUST BRIEFLY, ON THIS SLIDE, YOU CAN SEE A COUPLE OF EXAMPLES NIH ANALYSES THAT WERE ACTUALLY PUBLISHED. ONE OF THEM LOOKS AT CHANGES IN DIVERSITY OF NIH FUNDED GRANTEES OVER TIME, AND THE SECOND ONE IS A DIFFERENT EXAMPLE OF USING TAXONOMY TO CATEGORIZE A BROAD PORTFOLIO OF PREVENTION RESEARCH. SO YOU CAN USE THESE TOOLS FOR A VARIETY OF DIFFERENT TASKS, AND WHAT JENICA AND I WERE HOPING TO DO IS TO USE THIS APPROACH AND THESE TOOLS TO LOOK AT A RELATIVELY NEW CONCEPT IN THE ADDICTION RESEARCH FIELD, AND THAT IS HYPERKATIFEIA. SO NOW WHAT SOME OF YOU HAVE BEEN WONDERING, WHAT IS HYPERKATIFEIA? SO THE WORD KATIFEIA IS FROM THE GREEK WORD THAT MEANS SADNESS OR NEGATIVE EMOTIONAL STATE, SO HYPER OBVIOUSLY MEANING EXCESSIVE. HYPERKATIFEIA IS A TERM PROPOSED TO CAPTURE THE EXACERBATED NEGATIVE EMOTIONAL STATE THAT OCCURS DURING WITHDRAWAL FROM ALCOHOL OR DRUG USE. AND THE STATE IS CHARACTERIZED BY EMOTIONAL DISTRESS OR EMOTIONAL PAIN, AND INDIVIDUALS WHO ARE EXPERIENCING HYPERKATIFEIA ARE VULNERABLE TO RELAPSE AS THEY MAY RETURN TO DRINKING TO MITIGATE THESE NEGATIVE AFFECTIVE SYMPTOMS. SO IT'S IMPORTANT TO UNDERSTAND BOTH THE NEUROBIOLOGICAL AND BEHAVIORAL PROCESSES THAT MEDIATE HYPERKATIFEIA IN ORDER TO BETTER INFORM NOVEL TREATMENT STRATEGIES. SO THIS SLIDE MIGHT LOOK FAMILIAR TO SOME OF YOU. WITHIN THE CONTEXT OF THIS THREE-STAGE ADDICTION CYCLE, HYPERKATIFEIA CORRESPONDS WITH THE NEGATIVE AFFECT AND WITHDRAWAL STATE. AND IT LIKELY INVOLVES MUCH OF THE SAME NEUROCIRCUITRY INVOLVING THE EXTENDED AMYGDALA. SO HYPERKATIFEIA IS ADMITTEDLY KIND OF A BROAD CONCEPT AND IT'S STILL BEING REFINED, BUT OUR GOAL WITH THIS CURRENT PROJECT WAS TO INITIATE A PORTFOLIO ANALYSIS OF NIAAA RESEARCH RELATED TO THIS CONCEPT AND TODAY WE WILL SHARE WITH YOU SOME OF OUR EARLY FINDINGS IN KIND OF A CONDENSED PRESENTATION OF WHAT WE'VE BEEN WORKING ON. SO HERE'S AN OUTLINE OF OUR PROCESS. WE STARTED OUT BY DEVELOPING A SEARCH STRATEGY TO GENERATE A LIST OF GRANTS. WE USED A SEARCH TOOL FROM THE OFFICE OF PORTFOLIO ANALYSIS CALLED ISEARCH THAT ALLOWS YOU TO PUT IN SOME PRETTY SOPHISTICATED SEARCH SYNTAX AND IT ALLOWS YOU TO SEARCH THROUGH AND ORGANIZE GRANTS IN A WAY THAT CAN BE VERY HELPFUL FOR ANALYSIS. SO OUR FIRST STEP WAS TO IDENTIFY GRANTS POTENTIALLY RELATED TO HYPERKATIFEIA SO THAT WAS OUR STARTING POINT. TO BEGIN WITH, WE PULLED GRANTS FROM FISCAL YEAR '17. WE STARTED THIS PROJECT IN 2018, SO WE JUST STARTED WITH THE MOST RECENT YEAR OF AVAILABLE DATA, WHICH WAS '17, AND SINCE THEN, WE'VE GONE BACK AND ADDED '18 AND '19 DATA TO OUR ANALYSIS, SO NOW WE HAVE THREE YEARS OF DATA. SO AFTER GENERATING THIS POSSIBLE LIST OF GRANTS, WE THEN DID THE HARD PART, WHICH WAS MANUALLY CODING EACH PROJECT. SO THIS INVOLVED READING THE ABSTRACT IN AIMS FOR EVERY GRANT AND CODING IT AS YES FOR RELATED TO HYPERKATIFEIA OR NO FOR NOT RELATED. SO REFINED OUR LIST AND CATEGORIZED AND ANALYZED THE GRANTS ON OUR FINALIST. I'M GOING TO TALK YOU THROUGH OUR INITIAL SERVE STRATEGY. THIS WAS A LITTLE BIT TRICKY BECAUSE THERE'S NO SIMPLE SEARCH TERMS TO CAPTURE THE CONCEPT. WE KIND OF NECESSARILY NEEDED TO CAST A WIDER NET THAN WE ULTIMATELY NEEDED BECAUSE WE WANTED TO CAPTURE AS MANY GRANTS AS POSSIBLE THAT MIGHT BE STUDYING THIS TOPIC. SO INITIALLY, WE USED PAIRS OF TERMS TO IDENTIFY GRANTS THAT FOCUSED ON THE NEGATIVE AFFECT AND WITHDRAWAL STAGE OF THE ADDICTION CYCLE. YOU CAN SEE HERE I'VE GOT TWO COLUMNS OF SEARCH TERMS, AND BASICALLY WE USE THESE WORDS TO KIND OF GENERATE A STARTING POOL OF GRANTS TO THEN GO THROUGH AND CODE. I MENTIONED BEFORE THAT OUTPUT FOR THIS PRESENTATION IS LIMITED TO FISCAL YEAR '17 THROUGH '18 ACTIVELY FUNDED AWARDS AND WE ALSO FOCUSED OUR SEARCH ONLY ON R AND U MECHANISMS AND P GRANTS, WE DID CODE INDIVIDUAL COMPONENTS OF THOSE P50 AND P60 GRANTS, AND I THINK WE HAD A FEW K-9 9s IN THERE AS WELL. SO THIS SEARCH STRATEGY GENERATED 198 GRANT PROJECTS, SO AGAIN, THESE PROJECTS INCLUDED AT LEAST ONE WORD FROM THIS COLUMN TO CAPTURE THE TIMING AND THE STAGE OF ALCOHOL USE DISORDER, AND AT LEAST ONE TERM OR VERSION OF THE TERM FROM THE SECOND LIST TO CAPTURE THE AFFECTIVE COMPONENT OF HYPERKATIFEIA. SO AFTER WE READ THROUGH THESE 200-ISH PROJECTS AND CODED THEM, WE ENDED UP WITH A LIST OF 73 PROJECTS. SO WE THEN TOOK THIS LIST OF 73 PROJECTS AND KIND OF DID A BACKWARDS ANALYSIS TO SEE WHICH OF OUR INITIAL SEARCH TERMS APPEARED MOST FREQUENTLY IN THE ABSTRACT OF IN AIMS THAT ULTIMATELY ENDED UP ON OUR LIST AS RELATED TO HYPERKATIFEIA. SO THESE RESULTS ARE PROBABLY NOT SURPRISING TO YOU, BUT THE TERMS ABSTINENCE AND WITHDRAWAL WERE USED VERY COMMONLY MANY TIMES RESEARCHERS USED BOTH TERMS, AND RELAPSE AND DEPENDENCE WAS ANOTHER CATEGORY THAT WE ADDED IN THERE WAS TO CAPTURE THOSE RESEARCHERS WHO DANCED AROUND SAYING ABSTINENCE AND WITHDRAWAL BUT ACTUALLY DO STUDY THOSE TIMES. AND THEN THE FIGURE OVER HERE IS SHOWING YOU THAT THE SEARCH TERMS THAT WE USE TO CAPTURE THE AFFECTIVE FEATURES OF HYPERKATIFEIA THAT APPEARED MOST COMMONLY, AGAIN, NOT SURPRISINGLY WERE ANXIETY, NEGATIVE AFFECT, DEPRESSION, STRESS, NEGATIVE EMOTION, AND NEGATIVE REINFORCEMENT. ONE OF THE TOOLS OFFERED TO US BY THE OFFICE OF PORTFOLIO ANALYSIS IS THIS TEXT CLUSTERING TOOL, SO WE BASICALLY FED OUR LIST OF 73 GRANTS INTO THIS PORTFOLIO ANALYSIS TOOL, AND IT USED A CLUSTERING ALGORITHM TO IDENTIFY TOPIC CLUSTERS FROM THE TITLE ABSTRACT IN AIMS OF THESE GRANTS AND IT GENERATES THIS FIGURE THAT GIVES YOU AN IDEA OF THE PREDOMINANT CONCEPTS THAT WERE COVERED IN THE GRANTS THAT FED INTO THIS ANALYSIS. SO EACH CLUSTER VISUALLY REPRESENTS THE RELATIVE PREVALENCE OF THESE PREDOMINANT CONCEPTS AND THE TOP CLUSTERS HERE ARE NOT SURPRISING. I WILL DRAW YOUR ATTENTION TO THE EXTENDED AMYGDALA, AS I POINTED OUT, THE BRAIN CIRCUITRY IS OVERLAPPING WITH THE STAGE OF THE ADDICTION CYCLE. THE TOOL ALSO HAS SOME INTERACTIVE FEATURES THAT I CAN'T REALLY DEMONSTRATE HERE, BUT WE DO HAVE THE ABILITY TO DIG IN TO THESE TOPICS AND CLICK ON THE WORDS AND SEE WHICH GRANTS THEY APPEARED IN, AND SOME OF THESE CLUSTERS ALSO IS SUBCATEGORIES, AND THEY'RE GROUPED TOGETHER BECAUSE THOSE WORDS IN THE SUBCATEGORIES ALL APPEARED TOGETHER IN THE SAME GRANTS. SO UNLIKE THE PREVIOUS DIAGRAM, THIS ONE IS NOT BIASED BY OUR OWN SEARCH TERMS SO IT WAS KIND OF A NICE CONFIRMATION THAT WE CAPTURED THE CONCEPTS AND THE FEATURES IN THESE GRANTS THAT WE WERE EXPECTING TO SEE EMERGE BASED ON OUR SEARCH STRATEGY. SO FROM HERE, I'M GOING TO LET JENICA GIVE YOU SOME MORE DETAILED INFORMATION ABOUT THE GRANTS THAT WE IDENTIFIED AS RELATED TO HYPERKATIFEIA. >> GREAT. THANK YOU, RACHEL. SO NOW I'M GOING TO DISCUSS THE CATEGORIZATION APPROACH THAT WE USED AS WELL AS THE DESCRIPTIVE ANALYSIS OF VARIOUS TOPICS AND OUTPUTS IN THE GRANTS. SO OF THE 73 HYPERKATIFEIA GRANTS THAT WE CODED, WE MANUALLY CHARACTERIZED THE GRANTS AND WHAT WE DID HERE IS WE WENT THROUGH ALL OF THE ABSTRACTS IN AIMS TO IDENTIFY UNDERLYING THEMES WITHIN THE GRANTS TO SEE IF THERE'S SOME COMMONALITY BETWEEN THEM. SO HERE WE DEVELOPED FIVE CATEGORIES, AND ON THIS SLIDE, IT'S REPRESENTATIVE OF ONLY THE PRE-CLINICAL STUDIES THAT WE TERMED ANIMAL ONLY. SO SORRY THE TEXT IS A LITTLE SMALL, BUT I'LL WALK YOU THROUGH SOME EXAMPLES HERE. SO THE FIVE CATEGORIES THAT WE DEVELOPED WERE NEUROCIRCUITRY, NEUROTRANSMISSION SIGNALING, PHARMACOLOGY MEDICATIONS DEVELOPMENT, GENETICS, AND THEN AN "OTHER" CATEGORY. SO NEUROCIRCUITRY IS ON THE TOP, SO HOW WE DEFINE NEUROCIRCUITRY IS THE INTERACTION OF TWO -- TWO OR MORE BRAIN REGIONS. SO JUST TO GIVE YOU AN EXAMPLE HERE, WE IDENTIFIED 13 GRANTS THAT FELL WITHIN THIS CATEGORY. AN EXAMPLE HERE IS A GRANT BY JEFL GRANT IS JEFF WEINER, ALCOHOL WITHDRAWAL INDUCED ANXIETY. SO THE NEXT CATEGORY WE DEVELOPED WAS NEUROTRANSMISSION SIGNALING. HERE WE IDENTIFIED 17 GRANTS. AND WE DEFINE NEUROTRANSMISSION SIGNALING AS THE TRANSMISSION WITHIN ONE BRAIN REGION. SO JUST TO GIVE YOU AN EXAMPLE HERE, .82, BRIAN'S GRANT THAT IS LOOKING AT DOPAMINE SIGNALING SPECIFICALLY IN THE BAY SEW LATERAL AMYGDALA. THE NEXT CATEGORY IS PHARMACOLOGY MEDICATIONS DEVELOPMENT, SO WE'RE WE DEFINED THIS CATEGORY AS REALLY INVESTIGATING A SPECIFIC PHARMACOLOGICAL TARGET OR TESTING A PHARMACOTHERAPY. SO WE HAD FIVE GRANTS IN THIS CATEGORY AND A GOOD EXAMPLE HERE IS THE -- AND WALKER GRANTS LOOKING AT THE KAPPA OPIOID SYSTEM. WE ALSO HAD A GENETICS CATEGORY WHERE WE HAD TWO GRANTS FOCUSING MAINLY ON THE EPIGENETIC AND GENETIC MECHANISMS, AND JUST A GOOD EXAMPLE HERE IS THE AMY LASIK GRANT LOOKING AT EPIGENETIC MECHANISMS OF GLIAL AND NEURAL INTERACTIONS IN AUD. AND THEN WE ALSO HAD AN "OTHER" CATEGORY WHICH WAS WHERE THESE GRANTS WERE UNIQUE FROM THE OTHER CATEGORIES THAT WE DEVELOPED SO WE COULDN'T REALLY FIT THEM IN THERE. SO WE KEPT THEM ON THEIR OWN. AND JUST TO GIVE YOU AN EXAMPLE OF WHAT AN OTHER CATEGORY REPRESENTED WAS LOOKING AT CYTOKINES, NEUROGENESIS, AND MICRO TUBULES. SO WE ALSO DID THIS FOR THE HUMAN GRANTS THAT WE IDENTIFIED, AND THAT WAS GRANTS THAT WERE MAINLY DOING CLINICAL RESEARCH. WE IDENTIFIED SIMILAR CATEGORIES HERE EXCEPT FOR ONE. WE'VE REMOVED THE NEUROTRANSMISSION CATEGORY, BUT WE ADDED THE TREATMENT NON-PHARMA CATEGORY. SO THE CATEGORIES ARE DEFINED VERY SIMILARLY EXCEPT FOR THE TREATMENT NON-PHARMA. SO FOR NEUROCIRCUITRY, WE IDENTIFIED THREE GRANTS, PHARMACOLOGY MEDICATION DEVELOPMENT, HERE BECAUSE IT'S HUMAN, IT WAS SPECIFICALLY LOOKING AT A MEDICATION THAT CAN TREAT ALCOHOL USE DISORDER. WE IDENTIFIED 17 GRANTS. FOR TREATMENT NON-PHARMA, WE DEFINED MAINLY AS TREATMENT OUTSIDE OF A PHARMACOLOGY APPROACH. SO A GOOD EXAMPLE HERE IS JANE METRICS GRANT RIGHT HERE LOOKING AT COGNITIVE BEHAVIORAL THERAPY APPROACHES OR CLAIRE WILCOX' GRANT HERE LOOKING AT TRANS MAGNETIC STIMULATION. I BELIEVE WE HAD EIGHT GRANTS IN THIS CATEGORY. GENETICS, WE HAD ONE GRANT, AND THEN OUR "OTHER" CATEGORY WHERE THERE WERE FOUR GRANTS FOCUSED MAINLY ON IMAGING AS WELL AS BEHAVIOR CHANGE OUTSIDE OF TREATMENT. SO NICKS NEXT WE WANTED TO IDENTIFY WHAT WERE THE MOST COMMON TARGETS AND BRAIN REGIONS -- THIS IS A COMPILATION OF BOTH THE HUMAN AND ANIMAL. ON THE LEFT SIDE OF THE SLIDE, YOU CAN SEE THE MOST COMMONLY STUDIED BRAIN REGION GRAPH. THE X AXIS IS THE NUMBER FUNDED RESEARCH PROJECTS AND THE Y AXIS CONTAINS THE BRAIN REGIONS OF INTEREST. AND HERE AS RACHEL POINTED OUT, WE IDENTIFIED A LOT OF THE BRAIN REGIONS THAT ARE IN THE ADDICTION CYCLE AS WELL AS MORE SPECIFICALLY IN THE NEGATIVE AFFECT PART OF THE ADDICTION CYCLE. INCLUDING THE AMYGDALA AND ITS SUBREGIONS, THE PREFRONTAL IDENTIFIED OTHER BRAIN REGIONS EMERGING IN ALCOHOL DISORDER LITERATURE. ON THE RIGHT SIDE OF THE SLIDE, YOU'LL SEE THE MOST COMMONLY STUDIED TARGETS, AND WE DEFINE TARGET AS EITHER A LIGAND, A RECEPTOR OR A SYSTEM OF ITSELF. AGAIN IT'S LAID OUT THE SAME WAY AS THE OTHER GRAPH. WE HAVE THE NUMBER OF FUNDED RESEARCH PROJECTS ON THE X AXIS AND THE TARGETS ON THE Y AXIS. NOT SURPRISINGLY, WE ARE SEEING MANY TARGETS THAT ARE COMMONLY FOUND IN THE ALCOHOL LITERATURE SUCH ASSIGNOR EPINEPHRINE AND CRF, ET CETERA. SO THE REGIONS THAT WE DID IDENTIFY DO STUDY CO-OCCURRING DISORDERS. SO TWO WERE STUDYING CO-OCCURRING DEPRESSION IN AUD AND FIVE GRANTS WERE STUDYING CO-OCCURRING PTSD IN AUD. AND 10 OF THE 73 PROJECTS INCLUDED BRAIN IMAGING, AND THAT INCLUDES FMRI, PET, AS WELL AS DTI, AND IT WAS MAINLY IN THE CLINICAL COHORT. SO NEXT WHAT WE DID IS WE TOOK THE GRANTS AND BROKE THEM DOWN IN TERMS OF THE TOTAL COST BETWEEN FISCAL YEAR '17 AND '19, AS WELL AS THEIR ACTIVITY CODE OR THE MECHANISM THAT THEY FALL UNDER. SO ON THE LEFT SIDE IS ANIMAL AND ON THE RIGHT SIDE IS HUMAN, AND YOU CAN SEE HERE, NIAAA INVESTED APPROXIMATELY $29.5 MILLION BETWEEN FISCAL YEAR '17 AND '19 FOR THE ANIMAL STUDIES, MAINLY FOCUSING ON NEUROCIRCUITRY AND NEUROTRANSMISSION. ON THE RIGHT SIDE IN HUMAN, INVESTED ABOUT $34.5 MILLION, MAINLY IN PHARMACOLOGY AND MEDICATIONS DEVELOPMENT. FOR THE ANIMAL STUDIES, WE MAINLY INVESTED IN THE P COMPONENTS OF THE P60 MECHANISM, AS WELL AS AN R01 MECHANISM, AND FOR HUMAN, IT WAS R01 AND R21 MECHANISMS. SO WE ALSO WANTED TO LOOK AT HOW THIS BROKE DOWN PER YEAR WITHIN OUR ANALYSIS, SO THIS GRAPH IS BREAKDOWN PER FISCAL YEAR FY 17 AND '19. ANIMAL IS ON THE LEFT SIDE, HUMAN IS REPRESENTED ON THE RIGHT SIDE AND THEIR RESPECTIVE CATEGORIES WE DEVELOPED. THIS IS JUST GIVING A PERSPECTIVE ON WHAT TRENDS ARE EMERGING IN THE FUNDING LANDSCAPE, SO JUST TO SHOW YOU BRIEFLY, ON THE ANIMAL SIDE, WE SEE A SLIGHT INCREASE IN FUNDING FOR NEUROTRANSMISSION, WHERE ON THE THE HUMAN STUDIES, WE SAW A SLIGHT DECREASE IN OUR NEUROCIRCUITRY CATEGORY. SO ONCE WE START COLLECTING MORE DATA AND MORE YEARS, I THINK WE'LL REALLY START SEEING REALLY STRONG TRENDS EMERGE FROM OUR DATA. SO AS RACHEL MENTIONED BEFORE, THERE ARE A SUITE OF OFFICE OF PORTFOLIO ANALYSIS TOOLS THAT WE CAN USE TO HELP -- THAT PROVIDE OUTPUTS, BRAIN OUTPUTS THAT CAN HELP QUANTIFY BRAIN ACTIVITY. SO THINK PUBLICATIONS, CLINICAL TRIALS, APPROVED DRUGS AND THINGS LIKE THAT. SO WHAT WE DID HERE IS WE TOOK THE OFFICE OF PORTFOLIO ANALYSIS TOOLS AND WE ANALYZE THE DATA FROM THE 73 GRANTS. HOWEVER, I DO WANT TO POINT OUT A CAVEAT HERE IS THAT MANY OF THESE GRANTS HAVE FUNDING PREDATING FISCAL YEAR 17 AND 19, SO, THEREFORE, IT'S VERY DIFFICULT TO TAKE THAT TOOL AND MANUALLY EXTRACT OUT THE INFORMATION JUST ON THE FISCAL YEAR 17 AND 19 THAT WE LOOKED, SO WE LOOKED ACROSS THE BOARD FOR HOW LONG THAT GRANT WAS FUNDED. SO, THEREFORE, THE NEXT SET OF SIDES IS GOING TO SHOW DATA FOR ALL YEARS OF THOSE GRANTS THAT WERE ALL CYCLES OF THE YEARS OF THE GRANTS THAT WERE FUNDED, DATING BACK ALL THE WAY TO THE 80s, JUST TO GIVE YOU AN EXAMPLE. SO WE FEEL THIS MAY BE A LIMITATION TO THE APPROACH THAT WE USED BECAUSE THE EARLIER FUNDING CYCLES MAY NOT DIRECTLY BE RELEVANT TO THE HYPERKATIFEIA STATE, MAY OR MAY NOT, BUT WE DO FEEL THAT THESE TOOLS WERE POWERFUL BECAUSE THEY CAN REFLECT THE PRODUCTIVITY OF THE GRANT. SO, THEREFORE, THE OUT IT OUTPUTS THAT WE LOOKED AT WERE PUBLICATIONS, PATENTS, CLINICAL TRIALS AND APPROVED DRUGS. SO FIRST WE LOOKED AT PUBLICATIONS. SO THIS IS JUST SHOWING THE NUMBER OF PUBLICATIONS THAT WERE GENERATED FOR ALL OF THE 73 GRANTS OVER THE COURSE OF THEIR LIFETIME. SO IN THE MIDDLE YOU CAN SEE THERE'S AN EXPONENTIAL INCREASE IN THE AMOUNT OF FUNDING OVER THE COURSE -- FROM 1980 TO 2020, AND YOU CAN SEE THAT A MAJORITY OF THEM ARE SHOWING UP DURING THE FISCAL YEAR 17 AND 19, WHERE WE DID OUR ANALYSIS. HAD MAJORITY OF THEIR PUBLICATIONS COME OUT OF THE P60 COMPONENTS AS WELL AS THE R01, AND ANIMAL ALSO HAD A ONE UO1 THAT ACTUALLY WAS RUNNING FOR OVER 28 YEARS THAT PUBLISHED A LOT OF PAPERS, SO ABOUT 300. SO THERE'S AN OFFICE OF PORTFOLIO ANALYSIS TOOL CALLED ITRANS. ITRANS IS PRETTY UNIQUE IN THE FACT THAT IT'S ABLE TO PROVIDE INFORMATION ABOUT THE CONTENTS OF PUBLICATION THAT COULD POTENTIALLY GIVE US INFORMATION ABOUT BENCH TO BEDSIDE TRANSLATION. SO THE WAY IT DOES THAT IS IT TAKES MEDICAL SUBJECT HEADING TERMS FROM PUBMED AND CAN TAKE THAT INFORMATION AND CLASSIFY THE PAPERS INTO HUMAN, ANIMAL OR MOLECULAR CELLULAR. SO DISPLAYED HERE IS THE TEMPORAL TRY PARTATE GRAPH IT PRO DAWES AND ON THE TOP PART OF THE GRAPH IS ALL OF THE HUMAN STUDIES, ON THE BOTTOM RIGHT IS ALL THE ANIMAL STUDIES, ON THE BOTTOM LEFT IS ALL THE MOLECULAR/CELLULAR STUDIES, AND IN THIS SPACE RIGHT HERE, YOU'LL SEE WE TERM AS KIND OF THE TRANSLATION PART OF THE GRAPH. AND AS I'LL SHOW YOU, THERE IS AN ANIMATION, YOU'LL SEE OVER TIME IT'S A HEAT MAP, AND THERE'S -- THE DENSITY OF THE ARTICLES WILL SHOW UP ON THE GRAPH IN AND A LOW ARTICLE DENSITY IS IN BLUE AND A HIGH ARTICLE DENSITY IS IN WHITE OR PINK. SO HERE WE'RE STARTING BACK IN THE 80s, AND YOU CAN START SEEING THE POPULATION OF ANIMAL STUDIES AS WELL AS HUMAN STUDIES AND A COMBINATION OF SOME MOLECULAR, CELLULAR AND ANIMAL STUDIES COMING INTO THE LATE '90S. AND IN THE EARLY 2000s, YOU'LL SEE KINE OF A PICKUP KIND OF A PICKUP IN ANIMAL AND HUMAN STUDY, AND LATER IN THE 2000s IS REALLY WHEN WE DID OUR ANALYSIS, REALLY MORE -- IT STOPPED. BACK UP, I'LL TRY THAT AGAIN. HERE WE GO. YOU'LL SEE IN THE LATE 2000s, THAT THERE'S A NICE TRANSLATION HERE BETWEEN THE HUMAN AND ANIMAL STUDIES. WE'RE HITTING THE 2000s, AND THEN HERE IS WHERE YOU REALLY SEE ANIMALS -- THE ANIMAL STUDIES POPPING UP, THE HUMAN STUDIES POPPING UP IN THAT LIGHT BLUE FOR TRANSLATION THERE. SO OTHER OUTPUTS WE LOOKED AT WERE CLINICAL TRIALS, PATENTS AND APPROVED DRUGS IN THE 70s FOR APPROVED GRANTS. SO CLINICAL TRIALS, WE FOUND 30. THIS WAS IN MORE THE HUMAN-ONLY GRANTS, BUT ALSO THAT IT WAS FOCUSING MAINLY ON THE CATEGORIES OF PHARMACOLOGY, MEDICATIONS DEVELOPMENT AND TREATMENT NON-PHARMA. MAJORITY OF THESE CLINICAL TRIALS WERE IN PHASE 1 AND PHASE 2. AND THEY FOCUSED ON A MEDICATIONS TARGET OR A BEHAVIORAL TREATMENT FOR ALCOHOL USE DISORDER. PATENTS, WE IDENTIFIED FOUR. A COUPLE OF THESE WERE ON A CRF SMALL MOLECULE AS WELL AS A CRF1 OVEREXPRE SSING MOUSE, SO THESE ARE PRODUCTS THAT ARE DEVELOPED THAT COULD POTENTIALLY BE USED TO ASSESS BEHAVIORAL PHENOTYPES OF HYPERKATIFEIA. AND WE DID NOT IDENTIFY ANY APPROVED DRUGS. SO HERE'S A SUMMARY OF OUR ANALYSIS. RACHEL AND I IDENTIFIED 73 GRANTS RELATED TO HYPERKATIFEIA CLASSIFIED INTO OUR SIX CATEGORIES. NIAAA INVESTED ABOUT $64 MILLION IN TOTAL INTO THE CONCEPTS THAT WE DEFINED AS HYPERKATIFEIA BETWEEN 2017 AND 19. AND WE IDENTIFIED 2500 PUBLICATIONS PRODUCED BETWEEN '84 AND 2020 FOR ALL OF THE 73 GRANTS THAT MAY OR MAY NOT BE DIRECTLY RELATED TO HYPERKATIFEIA. AS WELL AS 30 CLINICAL TRIALS AND FOUR PATENTS DEVELOPED FROM THE 73 GRANTS. SO IN CONCLUSION, WE FEEL AFTER OUR ANALYSIS THAT HYPERKATIFEIA IS AN EMERGING THEME IN ALCOHOL RESEARCH, AND ALTHOUGH WE SAW THAT LITTLE BIT OF TRANSLATION AT THE END IN THE TRIPARTITE GRAPH, WE FEEL TRANSLATION IN HYPERKATIFEIA RESEARCH CAN PROVIDE MORE INFORMATION, MORE TOOLS DEVELOPED IN THE BRAIN INITIATIVE, NEW BEHAVIORAL ANALYSIS, COMPUTATIONAL METHODS CAN PROVIDE A BETTER PERSPECTIVE OF THE HYPERKATIFEIA STATE. WE ALSO FELT' WF RAN OUR PORTFOLIO ANALYSIS, IT REALLY DID PROVIDE A BETTER VIEW OF THE LANDSCAPE. OUR NEXT STEPS ARE REALLY TO EXPAND THE ANALYSIS TO PRIOR YEARS TO LOOK FOR BETTER TRENDS. TO DEEP DIVE IN THOSE PUBLICATION OUTPUTS AS WELL AS THE CLINICAL TRIAL OUTPUTS TO SEE WHAT IS DIRECTLY RELATED TO HYPERKATIFEIA. IN THE END, WE FEEL THAT THIS KIND OF PORTFOLIO ANALYSIS MAY BENEFIT FROM OTHER RESEARCH AREAS WITHIN OUR INSTITUTE AS WELL AS ACROSS NIH. SO WITH THAT, I'D LIKE TO THANK YOU FOR YOUR ATTENTION. [APPLAUSE] >> SO IT MAKES ME FEEL WARM AND FUZZY INSIDE TO KNOW THAT HYPERKATIFEIA IS ALIVE AND WELL IN THE NIAAA PORTFOLIO. DOES ANYONE HAVE ANY QUESTIONS OR COMMENTS ABOUT THIS KIND OF AN APPROACH? I THINK IT MAY BE USEFUL FOR YOUR FAVORITE ORGAN OR CONSTRUCT. >> WELL, IN YOUR ANIMATION, I DIDN'T SEE A LOT OF CELLULAR/MOLECULAR BIOLOGY RESEARCH THAT WAS DONE BETWEEN THE 80s AND NOW. >> YEP, I THINK THE REASON THAT IS IS BECAUSE A MAJORITY OF THE GRANTS THAT WE CHOSE HAD SOME TYPE OF BEHAVIORAL OUTPUT, SO WHEN THEY CLASSIFY IT INTO THOSE THREE COMPONENTS, I THINK THEY WOULD MAINLY FALL INTO THE ANIMAL OR HUMAN. >> I WAS IMPRESSED, FIRST OF ALL, BUT I'M WONDERING WHY WHEN YOU DID YOUR SEARCH WORDS THAT YOU DID NOT USE DETOXIFICATION, BECAUSE THAT WAS WHAT EVERYONE WAS SAYING, IT'S ONLY BEEN OVER THE LAST COUPLE OF YEARS THAT WE'RE TALKING ABOUT WITHDRAWAL AND WITHDRAWAL MANAGEMENT. >> I GUESS I WOULD ANSWER THAT BY SAYING I THINK OF THAT AS KIND OF A SEPARATE STEP. INDIVIDUALS GOING THROUGH THE PHASES OF THE ADDICTION CYCLE, THEY MAY OR MAY NOT GO THROUGH DETOXIFICATION IN A FORMAL MEDICAL ENVIRONMENT, SO WE WERE JUST TRYING TO CAPTURE THE FACT THAT THEY WERE ADMINISTERING ALCOHOL OR ANOTHER DRUG IN THEORY AND THEN THEY STOPPED. >> I HAVE A QUESTION. >> YOU COULD ADD DETOXIFICATION TO IT AND SEE IF IT PULLS IN SOME OTHER CLINICAL STUDIES. I THINK IT MIGHT BE USEFUL AS AN EXERCISE. >> I WAS JUST WONDERING, GREAT JOB, GUYS, AND IS THERE ANY POSSIBILITY OF CREATING THIS INTO AN RCDC FINGERPRINT? I KNOW THE CLASSIFICATIONS ARE KIND OF DIFFICULT TO CAPTURE, BUT DID YOU FEEL LIKE THAT COULD POSSIBLY LEAD TO SOMETHING THAT COULD BE READILY USED BY THE INSTITUTE? >> THAT'S A GREAT QUESTION. I KNOW THAT I ACTUALLY ATTENDED THE -- THERE WAS AN OFFICE -- WORKSHOP ON IT SO IT'S SOMETHING THAT WE CAN DO, I JUST HAVE TO GET MORE INFORMATION ON EXACTLY HOW TO DO IT, BUT YES, WE COULD DO THAT. IT WOULD BE A GOOD NEXT STEP FOR US THAT WOULD INCREASE THE EFFICIENCY OF THIS ANALYSIS PROCESS. >> DID YOU GUYS HAVE -- THERE'S A LOT MORE WORK TO DO, OF COURSE YOU GUYS MENTIONED LOOKING AT OUTYEARS AND EVERYTHING, BUT YOU MENTIONED PUBLICATIONS AND THAT ON HYPERKATIFEIA. ARE THERE ANY PLANS OF POSSIBLY LOOKING -- I NO HE I KNOW IT'S A LOT OF WORK -- OF LOOKING AT THE PUBLICATIONS TO SEE IF THEY WOULD STILL FIT THE CRITERIA FOR WORD CLASSIFICATIONS AND TO SEE HOW MANY OF THOSE GRANTS ARE ACTUALLY PRODUCING WHAT YOU WOULD CALL, LIKE, HYPERKATIFEIA RESEARCH? >> RIGHT. YEAH, THAT WOULD BE A GREAT NEXT STEP. WE WILL HAVE TO GO THROUGH 2500 PUBLICATIONS SO IT WILL TAKE US SOME TIME, BUT YEAH, THAT'S SOMETHING THAT WE CAN DO. >> I WAS TOLD TO INTRODUCE MYSELF. I'M PAMELA WARNETT WITH NIAAA. >> ANY OTHER COMMENTS, THOUGHTS, QUESTIONS? ARE YOU READY TO TAKE THIS TO THE COUNCIL OF COUNCILS, PAUL? [LAUGHTER] >> THERE YOU GO. HIDE UNDER THE TABLE. WELL, THANK YOU BOTH. I THINK THAT WAS REALLY INTERESTING. AND AGAIN, I WANT COUNCILMEMBERS TO THINK ABOUT -- I MEAN, THIS IS -- THEY HAVE OTHER THINGS TO DO FOR THEIR DAY JOBS, BUT I THINK, YOU KNOW, I REALLY THINK THAT HAVING OUR STAFF ENGAGE IN SOME OF THESE EXERCISES, THINKING OUT OF THE BOX AND LOOKING AT DIFFERENT WAYS THAT WE CAN ANALYZE WHERE WE'RE GOING AND WA WE'VE BEEN DOING, WHERE WE SHOULD BE GOING. SO FOR THE REST OF THE STAFF, MORE OF THIS WOULD BE WELCOME, NOT JUST FOR OKAY. NOBODY THREW ANY TOMATOES. SO IT REMINDS ME OF A STORY, BY THE WAY. I GET A CHANCE NOR A STORY EVEN THOUGH WE'RE BEHIND AND ABE IS HAVING A FIT OVER HERE. SO I INTRODUCED HYPERKATIFEIA AT THE COLLEGE ON THE PROBLEMS OF DRUG DEPENDENCE LAST YEAR, WHICH IS NIDA'S MEETING, NOT NIAAA'S, BUT THEY ALWAYS KINDLY INVITE ME TO GIVE AN NIAAA UPDATE SO I INTRODUCED IT, AND I DIDN'T GET ANY GRIEF ABOUT IT, BUT MONTHS LATER, THE PERSON WHO'S LIKE THE EXECUTIVE OFFICER AND I GUESS IN CHARGE OF I.T. FOR CPDD SENT ME AN EMAIL AND HE SAID, DR. KOOB, I JUST THOUGHT YOU'D LIKE TO KNOW THAT THERE WAS ONE ABSTRACT AT THE MEETING THAT USED HYPERKATIFEIA IN THE TITLE, AND HE SAID, I'M PRETTY SURE WHEN GOOGLE CORRECT STARTS CORRECTING THE SPELLING, YOU'LL BE IN THERE. [LAUGHTER] OKAY. SO NOW WE ARE DOING A CLEARANCE. I ALWAYS MIX UP THESE TERMS, AND I'VE BEEN HERE FOREVER AND I STILL CAN'T GET THINGS STRAIGHT, BUT THAT WAS AN ANALYSIS YOU JUST SAW. WHAT WE ARE NOW DOING IS A CONCEPT CLEARANCE. THIS IS ON FETAL ALCOHOL SPECTRUM DISORDER. AND CATHY YOUNG, OUR DIVISION DIRECTOR FOR THE DIVISION OF METABOLISM AND HEALTH EFFECTS, IS GOING TO PRESENT THE CONCEPT ON DEVELOPMENTAL PROJECTS FOR CIFD. >> COLLABORATIVE INITIATIVE -- >> THERE IT IS, COLLABORATIVE INITIATIVE ON FETAL ALCOHOL SPECTRUM DISORDER. >> THANKS, EVERYBODY. FIRST OF ALL, JOE WANG WOULD LIKE TO BE HERE. HE SENDS HIS REGARDS AND HIS REGRETS. HE IS VOLUNTARILY OUT OF CONSIDERATION FOR ALL OF YOU SELF QUARANTINING BECAUSE HIS WIFE JUST RETURNED FROM A VISIT WITH HER FAMILY IN CHINA. SO THEY ARE WORKING AT HOME FOR TWO WEEKS SINCE THE INCUBATION PERIOD FOR THE CORONAVIRUS IS NOT ENTIRELY CERTAIN. SO I'M GOING TO GO THROUGH JOE'S TALK FOR YOU. SO AS GEORGE JUST SAID, IT'S FOR YOUR CONSIDERATION, A REQUEST FOR APPLICATIONS FOR THE DEVELOPMENTAL PROJECTS FOR THE COLLABORATIVE INITIATIVE ON FETAL ALCOHOL SPECTRUM DISORDERS. IT'S VERY IMPORTANT TO KNOW THAT FETAL ALCOHOL SYNDROME AND FETAL ALCOHOL SPECTRUM DISORDERS ARE REALLY A HORRIBLE THING THAT RESULT WHEN THE FETUS IS EXPOSED TO ALCOHOL DURING GESTATION. AND IN EXTREME CASE, THEY SUFFER FACIAL ANOMALIES AND GROWTH RETARDATION, AND THROUGHOUT THE WHOLE SPECTRUM, THERE ARE NEUROLOGICAL ABNORMALITIES AND COGNITIVE DEFICITS. THESE ARE LIFELONG AND THEY HAVE SIGNIFICANT IMPACT ON THE QUALITY OF LIFE OF THE CHILD AND AS THEY GROW INTO AN ADULT. THE COGNITIVE DEFICITS MEAN THEY'RE ALWAYS GOING TO HAVE TROUBLE IN SCHOOL AND TROUBLE IN LEARNING, TRUBLE WITH JOBS, AND VERY OFTEN THEY HAVE BEHAVIORAL CHALLENGES AS WELL. AND IT'S NOT A MINOR PROBLEM. AS SUSAN POINTED OUT, IT'S ACTUALLY QUITE PREVALENT. A RECENT STUDY FUNDED BY NIAAA SHOWED THAT THE ESTIMATED PREVALENCE RANGES FROM 1 TO 5% IN THE FOUR COMMUNITIES IN THE UNITED STATES THAT WERE STUDIED AMONG FIRST GRADERS. WHAT'S QUITE DISTURBING IS THAT THE STUDY PANEL RECOGNIZED THAT SO MANY CASES BUT OF THOSE, ONLY 1% HAD ACTUALLY BEEN DIAGNOSED BY THEIR PEDIATRICIAN OR BY THEIR PRIMARY CARE PERSON. FASD IS ONE OF OUR MAJOR FOCUSES OR AN IMPORTANT FOCUS FOR NIAAA, WE'RE THE ONLY INSTITUTE THAT ACTUALLY FUNDS RESEARCH ON FASD AND THERE ARE OVER 100 GRANTS ACROSS ALL THE DIVISIONS WITHIN NIAAA, BUT IT WAS DETERMINED THAT IN ORDER TO SPEED THINGS FORWARD, BACK IN 2003, THE COLLABORATIVE INITIATIVE ON FETAL ALCOHOL SPECTRUM DISORDER, CFASD, WAS FORMED IN ORDER TO MAKE IT MORE POSSIBLE TO HAVE MULTIDISCIPLINARY REEF SECH TO RESEARCH FORWARD AND ALSO TO MAKE TRANSLATIONAL APPROACHES POSSIBLE. THE CURRENT VERSION OF CFASD IS IN ITS FOURTH ITERATION AND IT CONSISTS OF NINE UO1s ADDRESSING 3D IMAGING -- ADDRESSING MORE GENERALLY, THE MAJOR TOPICS, I'LL TRY THIS, OF DIAGNOSIS AND SCREENING, THE MECHANISMS, INTERVENTIONS, AND SO THE MECHANISMS IN GENETICS ARE TO TRY TO FIGURE OUT WHAT GENETICALLY, IS THERE A CERTAIN SET OF FACTORS THAT PREDISPOSES CHILDREN TO DANGER OR PROTECTIVE, AND THE DIAGNOSIS AND THE SCREENING IS CURRENTLY THE MOST IMPORTANT BECAUSE AS CHILDREN ARE BORN, THE EARLIER FASD CAN BE IDENTIFIED, THE MORE POTENTIAL THERE IS FOR SUCCESSFUL INTERVENTION. SO IN TERMS OF SCREENING AND DIAGNOSIS, OF THE NINE UO1s, SOME ARE LOOKING AT 3D IMAGING AND NEUROIMAGING, NEUROBEHAVIORAL ANALYSES TO TRY TO DIAGNOSE BIOMARKERS AND 'TIL MEDICINE. TELEMEDICINE IS IMPORTANT BECAUSE THERE ARE A FEW EXPERTS IN THE WORLD WHO ARE VERY GOOD AT DIAGNOSING BUT TO GET THAT INFORMATION OUT IF TELEMEDICINE COULD BE USED, IT WOULD BE -- PEOPLE IN THE REMOTE AREAS OF THE WORLD COULD BE DIAGNOSED AND HELPED. ANOTHER ADVANTAGE OF THE CIFASD WELL, YOU NEED A LARGE COHORT OF STUDY SUBJECTS IN ORDER TO WORK AROUND THE CONFOUNDING FACTORS. AND CIFASD ACTUALLY SHARES COHORTS FROM THE U.S., SEVERAL CITIES IN THE U.S. AND CANADA AND ENGLAND AND THE UKRAINE. SO WITH THAT BACKGROUND ON CIFASD, I WANT TO TALK ABOUT WHY WE NEED THESE DEVELOPMENTAL PROJECTS. SO ALL ALONG, THERE HAVE BEEN THESE DEVELOPMENTAL PROJECTS THAT ARE UH2s. AND A UH2 MECHANISM IS A GRANT THAT'S VERY SIMILAR TO AN R21 IN SCOPE, SO IT'S A TWO-YEAR GRANT AND THE AMOUNT OF FUND SOMETHING ABOUT THE SAME, AND THIS ARE HIGH RISK, HIGH REWARD. JUST TO GIVE YOU SOME EXAMPLE OF THE -- SO CIFASD WAS GOING FROM 2017 TO 222, THE FIRST PROJECTS WERE ON BIOMARKERS FOR INTELLECTUAL DISABILITY, STUDYING PERIPHERAL SINGLE CELL RNAs TO FIND OUT WHETHER THEY WOULD PREDICT NEUROBEHAVIORAL DEFICITS FOLLOWING PRENATAL ALCOHOL EXPOSURE, AND DOES IT ALTER THE MICROBIOME AND IMMUNE RESPONSE IN EXPOSED OFFSPRING. WHAT I CAN TELL YOU IS FROM PREVIOUS ITERATIONS OF , THE DEVELOPMENTAL PROJECTS HAVE BEEN VERY SUCCESSFUL. SO IN CIFASD, 3 -- FOR UO1s, R01s OR R21s. FOR EXAMPLE, EVERHART'S IS A GOOD EXAMPLE. HIS DEVELOPMENTAL PROJECT WENT ON TO -- HE GOT R01 FUNDING TO CONTINUE THE SCREENING OF GENETIC RISK FACTORS FOR ALCOHOL INDUCED BIRTH DEFECTS USING ZEBRA ZEBRAFISH. A COUPLE OTHERS FROM THE PREVIOUS ITERATION, DEVELOPMENTAL PROJECTS ACTUALLY BECAME INCORPORATED INTO CIFASD BY THE IDENTIFICATION OF MATERNAL MICRO -- AND MATERNAL CYTOKINE MARKERS OF EXPOSURE AND EFFECT. SO WHAT WE'RE ASKING YOU TO CONSIDER TODAY IS THE FACT THAT SINCE AS YOU SEE AT THE BOTTOM, SINCE WE'RE IN THE MIDDLE OF A FIVE-YEAR PLAN AND THE FIRST SET OF DEVELOPMENTAL PROJECTS IS DONE, PERMISSION TO SOLICIT ANOTHER SET OF DEVELOPMENTAL PROJECTS FOR THE NEXT TWO YEARS, AND THE ADVANTAGE OF THESE AS I SAID LIKE AN R21 IS HIGH RISK OR HIGH REWARD, IT'S JUST A GREAT IDEA TO BE ABLE TO BRING IN NEW BLOOD, NEW IDEAS, NEW UNIQUE PERSPECTIVINGS, POSSIBLY NEW TECHNOLOGIES, AND SO I'M NOT GOING TO SAY THAT THE FIVE-YEAR ONE IS GOING TO BECOME PLATEAUED BUT IT REALLY JUST KEEPS THINGS MOVING, IT ALLOWS THINGS TO GO FORWARD. SO SHOULD WE GO FORWARD WITH THIS RAF, FA, THE GOALS WILL BE TO EXPLORE -- WE'RE GOING TO ENCOURAGE THE FUNDED RECIPIENTS TO ESTABLISH A COLLABORATIVE RELATIONSHIP WITH THE CIFASD CONSORTIUM. SO MUCH ADVANTAGE IN LEVERAGING THE INTELLECTUAL WEALTH WITHIN CIFASD AND ALSO THE PHYSICAL RE SOURCES THAT WOULD MAXIMIZE THE IMPACT OF THESE NEW DEVELOPMENTAL PROJECTS. SO WHAT THE RFA WOULD LOOK LIKE WOULD BE IN A UH2 COOPERATIVE AGREEMENT MECHANISM. AS I MENTIONED, IT'S LIKE AN R21, 2 YEARS LONG, BUM THERE'S AN NIAAA PROJECT SCIENTIST INVOLVED, WHICH WE FIND USEFUL. IT'S AN OPEN COMPETITION. ANYONE WHO IS QUALIFIED WOULD BE INVITED TO SUBMIT AN APPLICATION, AND THE RESEARCH TOPICS ARE OPEN. I THINK YOU'VE PROBABLY SEEN THIS LANGUAGE IN NIH LITERATURE AND MAY INCLUDE BUT NOT BE LIMITED TO DIAGNOSIS AND SCREENING. STUDIES ON THE ETIOLOGY AND MECHANISMS OF ALCOHOL'S DAMAGE DURING DEVELOPMENT, PREVENTION APPROACHES, AND INTERVENTIONS FOR THOSE WHO ARE BORN WITH FASD. AND AS WE SAY, THEY'LL BE ENCOURAGED TO COLLABORATE WITH CIFASD. SO I ASK FOR YOUR CONSIDERATION. IF THERE ARE ANY QUESTIONS OR COMMENTS, I'D BE DELIGHTED TO HEAR THEM. THANK YOU. [APPLAUSE] >> CATHY, I FIRST HAVE TO APOLOGIZE TO YOU AN JOE FOR NOT GIVING YOU FEEDBACK IN ADVANCE. WE HAD A DEATH IN THE FAMILY TWO WEEKS AGO SO I'VE BEEN PREOCCUPIED WITH THAT, BUT I THINK THIS LOOKS TERRIFIC. THE CIFASD PILOTS HAVE MADE TERRIFIC PROGRESS IN PAST CYCLES AND SO I WOULD ENDORSE THAT. I'M ALSO REALLY PLEASED THAT THERE'S BEEN KIND OF A SHIFT IN THE REVIEW PROCESS SO THAT THE REVIEW ON THESE PILOTS IS BEING DONE EXTERNALLY IN A COMPETITIVE MANNER, AND I THINK THAT'S REALLY CRUCIAL IN TERMS OF BRINGING NEW VOICES AND NEW THOUGHTS AND NEW IDEAS INTO WHAT IS AN ALREADY SUCCESSFUL COMPONENT. SO I'M FULLY SUPPORTIVE. >> THANK YOU. >> CATHY, I AGREE, I THINK IT'S A GREAT IDEA, BUT I'M WONDERING WHETHER PART OF THE REVIEW WOULD BE THEIR ABILITY TO COLLABORATE WITH THE REST OF THE CONSORTIUM OR WHETHER THEY'LL JUST BE ENCOURAGED TO -- YOU KNOW, THE WAY YOU DESCRIBED IT IS THE AWARDEES WOULD BE ENCOURAGED LATER, BUT WOULD THEY BE ENCOURAGED AHEAD OF TIME TO SET UP USE OF THE CURRENT RESOURCES WITHIN THE CONSORTIUM AS PART OF THE PROPOSAL? DOES THAT MAKE SENSE? >> I'M ABE BAUTISTA AND THAT'S ASSOCIATED WITH THE REVIEW CRITERIA. WE WILL CONSIDER YOUR SUGGESTION WHEN WE DEVELOP THE RFA. >> IF I COULD ADD, LAURA, THIS MAY BE HELPFUL, THE CIFAS D-DAY TACET IS ACTUALLY OPEN TO ANYONE, SO EVERYBODY HAS ACCESS TO THE INFORMATION THAT'S ALREADY THERE. >> AND I THINK LAURA'S QUESTION IS WHETHER THERE'S GOING TO BE A SCORABLE CRITERION IF THEY COLLABORATE OR NOT COLLABORATE, AND I THINK THAT'S REALLY A VERY IMPORTANT QUESTION THAT WE SHOULD CONSIDER IN DEVELOPING THE RFA. >> I THINK THUMBS UP FOR ACTUALLY MOVING AHEAD QUICKLY ON SOMETHING LIKE THIS. OF COURSE THE OTHER COMPONENTS, WITH THE OTHER PARTNERS IN UKRAINE AND SOME OF THE OTHER AREAS OF CONCERN, I'M WONDERING, WAS THERE ANY TALK ABOUT DOING ANYTHING WITH AUSTRALIA AND SOME OF THE ABORIGINAL POPULATIONS IN AUSTRALIA IN IS BECAUSE THEY HAVE A HUGE ONGOING ISSUE WITH THINGS SINCE ALCOHOL HAS A DIFFERENT STORY IN AUSTRALIA THAN IT DOES HERE IN THE AMERICAS. >> YOU KNOW, THAT'S AN EXCELLENT QUESTION AND I'M GOING TO DEFER TO OUR -- TO BILL DUNTY, WHO IS THE -- OF FASD, PROJECT COORDINATOR. >> >> THAT'S A GREAT SUGGESTION. CIFASD HAS HAD COLLABORATIONS WITH INTERNATIONAL INVESTIGATORS FROM AROUND THE WORLD. UNFORTUNATELY AUSTRALIA HAS NOT BEEN ONE OF THOSE SITES, BUT AUSTRALIA DOES HAVE SEVERAL ACTIVE RESEARCHERS TREEING TRYING TO UNDERSTAND THE KIND OF QUESTIONS THAT YOU'RE ASKING. >> AS YOU SAW, THERE ARE INVESTIGATORS INTERESTED, WE DO FUND FOREIGN GRANTS IF IT'S A UNIQUE SITUATION, AND IT SOUNDS LIKE IT WOULD BE. WE HAD SOME STUDIES IN SOUTH AFRICA SIMPLY FOR THE SIMILAR REASON THAT THERE'S A HIGH CONCENTRATION OF THE SYNDROME AND IT MAKES IT -- THE DATA COME IN MUCH QUICKER AND WITH MUCH MORE IMPACT. WE'RE GOING TO KEEP MOVING BECAUSE WE'RE SORT OF ALMOST ON TIME. DESPITE MY JABBER MOUTHING. SO NEXT CONCEPT CLEARANCE IS SECONDARY ANALYSIS FROM THE DIVISION OF EPIDEMIOLOGICAL AND PREVENTION RESEARCH AND THE DIVISION OF NEUROSCIENCE AND BEHAVIOR. DR. WENXING ZHA AND DR. ABBAS PARSIAN ARE PROGRAM DIRECTORS RESPECTIVELY FOR DEP R AND D NB, AND THEY'RE GOING TO PRESENT THE CONCEPT ON SECONDARY ANALYSES OF EXISTING ALCOHOL RESEARCH DATA. IT'S ALL YOURS. >> GOOD AFTERNOON. THE CONCEPT I'M PRESENTING IS SECONDARY ANALYSIS OF EXISTING ALCOHOL RESEARCH DATA. THIS IS A REASSURANCE OF OUR CURRENT PROGRAM ANNOUNCEMENT WITH -- THIS IS A REISSUANCE OF OUR CURRENT PROGRAM ANNOUNCEMENT WITH THE FUNDING MECHANISM OF R01, R03, WHICH WILL BE EXPIRED IN DECEMBER -- NO, IN SEPTEMBER OF THIS YEAR. THE FUTURE SOLICITATION WILL BE IN THE FORM OF NOTICE OF SPECIAL INTERESTS, AND IT ENCOURAGES A SUBMISSION OF APPLICATIONS OF SECONDARY DATA ANALYSIS TO ENHANCE OUR UNDERSTANDING OF PATTERNS IN THE TRAJECTORIES OF ALCOHOL CONSUMPTION, THE ETIOLOGY OF GENETICS -- ALCOHOL RELATED PROBLEMS AND DISORDERS. THE THREE TYPES OF GRANT APPLICATIONS THAT ARE ACCEPTABLE, INNOVATIVE ANALYSES OF EXISTING ALCOHOL RESEARCH DATA, THE NEXT IS ANSWER NOVEL RESEARCH HYPOTHESES AND QUESTIONS, DEVELOP AND TEST ADVANCED ANALYTICAL METHODOLOGIES. SOME BACKGROUND INFORMATION. FOR THE PAST DECADES, WE'VE BEEN SEEING INCREASING COST OF DATA COLLECTION ON HUMAN SUBJECTS. WHILE THE RICH EXISTING DATA RESOURCES YET TO BE FULLY UTILIZED. AND THE SECOND IS A COST-EFFICIENT WAY TO CONDUCT THE RESEARCH, AND SENSIBLE USE OF EXISTING SCIENTIFIC RESEARCH. ALSO THERE'S A LINKAGE COMBINATION CAN INCREASE STATISTICAL POWER EXPANDS THE SCOPE AND IMPACTS RESEARCH. THIS IS ESPECIALLY TRUE FOR THE STUDY OF RATIO RACIAL, ETHNIC GENDER SEXUAL MINORITIES WHERE THE DATA IS NOT LARGE ENOUGH. I WANT TO TALK ABOUT A LITTLE BIT OF HISTORY OF THIS PROGRAM ANNOUNCEMENT. NIAAA HAS ISSUED THE PROGRAM ANNOUNCEMENT ON SECONDARY DATA ANALYSES SINCE 2001, IF I CAN TRACE BACK ON THE INNET. INTERNET. FOR THE CURRENT CYCLE WHICH STARTED IN 2017, WE HAVE RECEIVED MORE THAN 30 APPLICATIONS. THE SCOPE AND THE RESEARCH COSTS -- NOT LIMITED TO THE FOLLOWING RESEARCH TOPICS. THE FIRST ONE IS DEVELOP IMPROVE VALIDATING MEASUREMENT OF UNDERIJ DRINKING, HIGH INTENSITY BINGE DRINKING, DRINKING DURING PREGNANCY, ADULT ALCOHOL MISUSE AND ALCOHOL USE DISORDERS. SUCH MEASUREMENT WILL HELP US BETTER UNDERSTAND THE LEVEL AND PATTERNS OF ALCOHOL INVOLVEMENT THAT ARE ASSOCIATED WITH THE SPECIFIC CONSEQUENCES ACROSS THE LIFESPAN. WE ENCOURAGE YOU TO DEVELOP A BIG DATA PURCHASE TO INTEGRATE AND HARMONIZE QUANTITATIVE AND QUALITATIVE MEASUREMENTS FROM VARIED STUDY DESIGNS AND SOURCES, AND ALSO THE DEVELOP COMPREHENSIVE ANALYTICAL METHODS FOR THE STUDY OF MISUSE AND PROGRESSION TO ALCOHOL USE DISORDER FROM DISWITH USING DATA FROM DIFFERENT SOURCES. WE ENCOURAGE DEVELOPING EFFECTIVE DATA ANALYTICAL APPROACHES FOR REALTIME ASSESSMENT OF ALCOHOL CONSUMPTION AND RELATED BEHAVIORS, MOBILE AND BIOSENSORS TECHNOLOGIES. DEVELOP A MACHINE LEARNING AND OTHER ARTIFICIAL INTELLIGENCE TO STUDY DRINKING PATTERNS, IDENTIFY AND PREDICT RISK DRINKING BEHAVIORS TARGETED PREVENTIVE INTERVENTIONS. THESE FOUR BULLETS ARE RELATED TO THE GENETICS RESEARCH. DEVELOP A COULD MON METRIC OF PHENOTYPIC AND ENVIRONMENTAL MEASURES ACROSS STUDY DESIGNS. DEVELOP AND ENGAGE NEW GENETIC ANALYSIS METHODS SUCH AS PATHWAY, NETWORK AT THE ME THAT OMICS ANALYSIS. USE NEW -- WITH BRAIN EXPRESSION DATA TO ESTABLISH THEIR RELATIONSHIPS. USE NOVEL BIOINFORMATIC TOOLS TO PERFORM CROSS SPEES SHEETION GENOMICS OR COMPARATIVE GENOMICS TO DETECT NEW EQTL RELATED TO AUD. THE DATA SOURCES FOR THIS ANNOUNCEMENT CAN BE FROM PUBLIC DOMAINS, AND THE NIH FUNDED RESEARCH STUDIES OR OTHER RESOURCES SUCH AS THE ELECTRONIC HEALTH RECORDS FROM CLINICIANS AND THE HOSPITALS. I HAVE A LIST OF AVAILABLE DATA SOURCES AND WE'D LIKE TO ENCOURAGE THE POTENTIAL APPLICANTS TO CHECK THESE DATASETS. WHY IS ALCOHOL -- -- THE THIRD ONE IS NIA AA DATA ARCHIVE. THIS IS NEW. IT HOUSES THE THE HUMAN SUBJECT DATA FROM NIAAA FUNDED RESEARCH, COLLECTED SINCE LAST YEAR. AND THEN WE HAVE NIDA DATA SHARE FOR CLINICAL TRIALS, NIH DATA REPOSITORY, DATABASE OF GENOTYPES AND PHENOTYPES AT NCBI. THANK YOU. IF YOU HAVE ANY QUESTIONS, DR. PARSIAN AND I ARE HAPPY TO ANSWER. [APPLAUSE] >> SO THANK YOU BOTH FOR THIS. I JUST WANT TO MENTION TO EVERYBODY, I THINK MOST OF YOU KNOW THAT THE ABC D-DAY TA ARE ALSO IN THE NIMH DATA ARCHIVE AND THAT'S ACCESSIBLE. I JUST WANT YOU TO KNOW, I'LL SPEAK FOR MYSELF BUT I AM VERY, VERY ENTHUSIASTIC ABOUT THE SECONDARY ANALYSES. I THINK WE HAVE LOTS OF LITTLE GOLD MINES THAT ARE SITTING OUT THERE THAT ARE JUST UNDERUTILIZED. SO IF YOU KNOW ANYBODY OUT IN THE REAL WORLD, OTHER THAN THE NIH WORLD WHO IS INTERESTED IN THIS KIND OF WORK, THERE ARE LITERALLY GOLD MINES FOR DEVELOPING HYPOTHESES. AND I REALLY APPRECIATE WENXING AND ABBAS FOR PUTTING THIS TOGETHER IN A COMPREHENSIVE WAY. >> WHEN I INITIALLY READ THIS, I WAS VERY EXCITED ABOUT IT, I CONTINUE TO BE, IT'S VERY WELL DONE. SO IMPORTANT, SO IMPORTANT TO TAKE ADVANTAGE OF WHAT'S ALREADY THERE. IT'S COST-EFFECTIVE. AND AS I WORK ON MY PRESENTATION OVER THE WEEKEND, I BEGAN TO THINK, GEE, SECONDARY DATA ANALYSIS IS REALLY RELEVANT IN OTHER AREAS AS WELL, PARTICULARLY HEALTH SERVICES RESEARCH, WHICH RELIES SO HEAVILY OR SO MANY DATA SOURCES OUT THERE. I'M WONDERING, HAS ANY CONSIDERATION BEEN GIVEN TO EXPANDING THIS BEYOND A FOCUS ON EPIDEMIOLOGY TO LOOK AT SOME OTHER AREAS THAT YOU CAN BENEFIT FROM SECONDARY DATA ANALYSIS? >> DEFINITELY. WE'RE NOT LIMITED TO JUST THE FULL EPIDEMIOLOGY OR EPIGENETIC STUDIES. ALL THE OTHER TOPICS ARE WELCOME. WE ARE NOT -- >> WE'LL TAKE ANY SECONDARY DATA ANALYSES THAT'S GOING TO GENERATE HYPOTHESES. LAURA? >> JUST TO REITERATE THAT FROM THE ORGAN INJURY SITE, THERE'S A LOT OF BIG DATASETS THAT ARE NOW PUBLICLY AVAILABLE AND I THINK IT'S A PERFECT TIME TO START TO INTEGRATE SOME OF THOSE. SO I THINK, AGAIN, JUST TO SAY OTHER AREAS BESIDES AUD. >> THEY CAN ADD THESE TO THE LIST IF YOU WILL SEND THEM AN EMAIL OR SEND ABE, BETTER YET, SEND TO ABE AN EMAIL WITH YOUR SUGGESTIONS. BOTH OF YOU AND ANYBODY ELSE BECAUSE THEY CAN ADD TO THE LIST. BUT WE'RE GOING TO TAKE ANYTHING, AT LEAST UNTIL SOMEBODY ELSE DECIDE OTHERWISE. >> WHAT DO YOU MEAN BY YOU'LL TAKE ANYTHING? >> ANY SECONDARY DATA ANALYSIS IS FAIR FOR FUNDING IF IT'S DESIGNED IN AN APPROPRIATE WAY TO GENERATE HYPOTHESES, IN MY OPINION. YOU KNOW, I THINK THERE WAS A TIME WHEN STUDY SECTION LOOKED DOWN ON AND FROWNED ON THESE SECONDARY ANALYSES. IT IS A PERFECT EXAMPLE OF THE USE OF AN R21 IN SOME CASES BECAUSE AN R21 WOULD GENERATE AN HYPOTHESIS IN THIS CASE AND THE DATA BACKING UP THAT HYPOTHESIS FOR AN R01. SO I MEAN, I CAN GIVE YOU AN EXAMPLE, I MEAN, THAT I GOT 20 EMAILS ABOUT, YOU KNOW, THERE'S A MINERAL CORTICOID ANTAGONIST THAT SEEMS TO HAVE A SIGNAL IN SOME ANIMAL STUDIES FOR DECREASING ALCOHOL CONSUMPTION, AND NOW THIS GROUP OF PEOPLE THAT SOMEHOW HAVE INCLUDED ME IN THE EMAIL BECAUSE I WAS IN ON THE ORIGINAL ANIMAL STUDY ARE DRILLING THROUGH THE MILLION VETERANS PROGRAM TO FIND OUT WHETHER PEOPLE ON THIS PARTICULAR DRUG DRINK LESS. I MEAN, YOU KNOW, THAT COULD GENERATE A CLINICAL TRIAL THAT MIGHT BE EVEN AN EFFECTIVE REPURPOSING OF A DRUG. SO THAT'S MY WORLD FOR YOU. ARE THERE OTHER COMMENTS? SCOTT? >> I JUST WAS -- I WANTED FURTHER CLARIFICATION ON ANY SOURCE. IT'S NOT JUST THE SOURCES THAT YOU GUYS LISTED UP THERE. EVERY HOSPITAL ACROSS THE COUNTRY HAS SOMETHING SET UP SO THAT YOU CAN DO SECONDARY ANALYSIS, WE EXPLOIT IT ALL THE TIME, SO THOSE WOULD ALSO BE APPROPRIATE? >> I THINK SO. I THINK CONNIE WISE NER WHO IS ON COUNCIL HAS BEEN TAPPING IN TO KAISER FOR EXACTLY THAT. I MEAN, YOU KNOW, IF EVERYBODY SENDS IN AN R21, THAT'S GOING TO GET COMPETITIVE, BUT RIGHT NOW, WE HAVE A DEARTH OF THEM. RIGHT, BOSS? >> YES, SIR. AT LEAST WE CAN ADD IT FOR SURE -- THAT DOESN'T GUARANTEE THAT -- CAN GET TO [OFF MIC] AS DR. KOOB SAID, CONTACTING US, TALK TO US -- AS BEST AS WE CAN -- WHICH IS VERY STRAIGHTFORWARD. >> THANKS, BOTH OF YOU. WE'RE GOING TO KEEP MOVING. WE'RE ONLY 2 MINUTES BEHIND SCHEDULE AT THIS POINT. >> OKAY. >> AND MARK EGLI IS GOING TO TELL US, WHO IS THE DEPUTY DIRECTOR OF THE DIVISION OF NEUROBIOLOGY, WHAT YOU GUYS CALL NEUROSCIENCE AND BEHAVIOR, IS GOING TO PRESENT THE INTEGRATIVE NEUROSCIENCE INITIATIVE ON ALCOHOLISM CONCEPT CLEARANCE. >> THANK YOU VERY MUCH. I THINK I'LL TALK A LITTLE HISTORY BECAUSE THAT WILL GIVE YOU A REALLY GOOD FRAMEWORK FOR THE BROADER EMPHASIS OF INIA THROUGHOUT THE LIFE OF THIS INITIATIVE. INIA WAS LAUNCHED IN FISCAL YEAR 2001 UNDER THE LEADERSHIP OF ANTONE YA NURONA, NOW DIRECTOR OF THE DIVISION OF NEUROSCIENCE AND BEHAVIOR, AND THE GENERAL GOALS ARE LISTED RIGHT HERE, I'M NOT GOING TO READ THEM VERBATIM. BUT I WANT YOU TO THINK ABOUT THREE THINGS. THINK ABOUT THIS CONCEPT EMERGED IN THE MILIEU OF THE DECADE OF THE BRAIN, SO THERE WAS A BIG EMPHASIS ON DEVELOPING RESEARCH ON THE BRAIN, WHICH IS SOMETHING THAT WAS NEEDED AT NIAAA. IT WAS ALSO AT A TIME WHEN NIH WAS HEAVILY ENCOURAGING THE DEVELOPMENT OF TEAM SCIENCE VERSUS SORT OF THE LONE R01 INVESTIGATOR WITH THEIR SET OF GRADUATE STUDENTS BUT WORKING COLLABORATIVELY IN MULTIDISCIPLINARY WAY ACROSS DIFFERENT DISCIPLINES. I'LL TALK MORE ABOUT THAT. AND ALSO IMPLIED IN THIS DISCUSSION IS -- WELL, IN THE TERM -- INIA IS INTEGRATIVE. AND I'LL TALK MORE ABOUT THAT. BUT I WANTED TO POINT OUT THE PRIMARY GOAL IS TO LOOK AT ACROSS LEVEL OF ANALYSES AT EXCESSIVE ALCOHOL CONSUMPTION, SO AT THE TIME A LOT OF THE WORK, PARTICULARLY IN THE ANIMAL LITERATURE AND STUFF WAS LOOKING AT ALCOHOL DRINKING LEVELS THAT WOULD REFLECT SOCIAL DRINKING, AND HERE THIS WAS AN EFFORT TO REALLY LOOK AT EXPLANATIONS AT THE NEUROBIOLOGICAL LEVELS IN TERMS OF NEUROADAPTATION OF THE PATHOLOGICAL LEVELS OF DRINKING. SO WE CAN TALK A LITTLE BIT ABOUT THAT. THERE'S TWO QUOTES HERE THAT I THINK SORT OF CHARACTERIZE INIA VERY WELL, THEN AND NOW. I THINK THEY'RE SELF-EXPLANATORY. DRIVING IN TODAY, THERE WAS AN ALZHEIMER'S DISEASE ON THE RADIO FOR A TV SHOW AND ONE OF THE CHARACTERS IS SAYING, THE TIMES ARE CHANGING, WE NEED TO CHANGE WITH THEM. I THINK INIA IS PART OF THE CHANGING TIMES. I THINK INIA IS -- IT HASN'T EVER BEEN A CASE WHERE WE'VE FELT WITH THIS KIND OF WORK, WE'VE GOT TO CATCH UP WITH OTHER PEOPLE. I THINK IN A LOT OF WAYS, INIA HAS, LIKE WAYNE GRETZKY SAID, ANTICIPATED WHERE THE PUCK IS GOING TO BE. ON THE OTHER SIDE OF THIS, AGAIN, DAVID MARR, WHO IF YOU DON'T KNOW WAS A PIONEERING COMPUTATIONAL NEUROSCIENTIST WHO WOAT WROTE A FAMOUS BOOK CALLED "VISION" IN 1982, IT WAS ACTUALLY POSTHUMOUS, BUT WE NEED TO STUDY MORE THAN JUST A SINGLE ASPECTS OF THINGS LIKE A FEATHER TO UNDERSTAND FLIGHT, YOU NEED TO UNDERSTAND AERODYNAMICS AND ALL THE THINGS THAT GO INTO THAT, SO CONCEPTUALLY THAT'S WHAT WENT INTO THIS APPROACH. SO LOOKING BACK, FORTUNATELY A LOT OF THE WORK THAT INIA HAS DONE OVER THE YEARS TURNED OUT TO BE VERY TIMELY AND PROACTIVE IN TERMS OF PRIORITIES AT THE NIH AND OTHER PLACES. AND THIS REALLY TIES INTO HOW WE VIEW THE VALUE OF INTEGRATION, SO ONE ASPECT OF INTEGRATION IS REPRODUCIBILITY. AND SOME OF YOU MAY KNOW THIS WAS A BIG CONCERN IN THE SCIENTIFIC COMMUNITY A WHILE BACK, AND WHEN THAT CONCERN EMERGED, WE WERE DELIGHTED THAT WE HAD ALREADY BEGUN ADDRESSING IT WITH OUR INIA INITIATIVE. THAT WAS DONE IN THE FORM OF DEVELOPING STANDARDIZED MODELS OF EXCESSIVE DRINKING, BOTH IN RODENTS AND IN NON-HUMAN PRIMATES, AS WELL AS PROTOCOLS FOR NEUROIMAGING IN NON-HUMAN LABORATORIES. SO WE HAD A HIGH DEGREE OF CONFIDENCE OF THE DATA THAT CAME OUT OF THIS WORKS WORK BECAUSE WE SAW THE RESULTS FROM MULTIPLE LABORATORIES. TRANSLATION AND BACK TRANSLATION HAS BEEN A BIG PART OF THE INIA INITIATIVE. I WAS LOOKING BACK AT A STATEMENT BY THE FAMOUS BEHAVIORAL -- ANIMALS AND HUMAN, WITHOUT GOING INTO IT IN DEPTH, THE APPROACH ADVOCATED THERE, AND THIS IS IN THE 1950s, IF YOU WANT TO GO FROM THE ANIMAL EXPERIMENTS TO HUMAN EXPERIMENTS, THE WAY TO DO THAT IS TO IMPROSE IMPOSE THE SAME VARIABLES IN BOTH -- CONDITIONS IN BOTH SPECIES AND SHE WHAT SEE WHAT RESULTS EMERGE. THAT IS ESSENTIALLY WHAT INIA HAS BEEN DOING WITH SOME OF THEIR NEUROIMAGING WORK IN ANIMALS. BECAUSE THE QUESTION WOULD BE WHY WOULD YOU WANT TO DO NEUROIMAGING IN ANIMALS IF YOU CAN DO MORE INVASIVE AND DIRECT ANALYSIS OF THE BRAIN? ONE REASON IS YOU GET A HIGHER DEGREE OF EXPERIMENTAL CONTROL, WHICH IS A JUSTIFICATION FOR ANIMAL RESEARCH IN GENERAL, BUT ONE OF THE THINGS THAT INIA HAS PUT A LOT OF WORK INTO WITH THE NEUROIMAGING IS TO LINK UP DATA FROM NON-HEUL MANS TO HUMANS, SO THAT IT CAN LINK THE MORE -- DATA COMING FROM THE MORE INVASIVE WORK WHERE IT'S DIRECT MEASURES OF NEUROCIRCUITRY AND GENE EXPRESSION AND SO FORTH IN THE BRAIN TO NEUROIMAGING STUDIES IN RELEVANT PATIENT POPULATIONS. INIA IS ALSO -- USES A LOT OF GENE EXPRESSION AND OTHER TYPES OF TECHNOLOGY RELATED TO THAT TO IDENTIFY TARGETS THAT COULD POSSIBLY BE USED FOR PHARMACOTHERAPY, AND WE'VE GENERATED LISTS LITERALLY OF HUNDREDS OF TARGETS AND MANY OF WHICH ARE DRUGS THAT KK CAN BE REPURPOSED. THE EXCITING THING ABOUT INIA, I DIDN'T PUT THE KEYWORD UP HERE BUT THIS IS ANOTHER PART OF INTEGRATION, IS EFFICIENCY. SO FOR EXAMPLE, ONE OF THE TARGETS THAT CAME UP WAS THE PHOSPHODAIS TRACE 4 INHIBITOR AND WE WERE ABLE TO TEST THE CONSORTIA WERE ABLE TO TEST THAT OUT RIGHT AWAY, IN MULTIPLE LABORATORIES, AND FIND THAT, IN FACT, SURPRISINGLY SOMETIMES IT PRODUCED A POSITIVE EFFECT, AND NOW THIS IS SOMETHING THAT WE CAN TEST IN HUMANS WITH A MEDICATION FOR VIE CYST. PSORIASIS AND WE'LL SEE HOW THAT WORKS. WE HEARD FROM JILL BECKER EARLIER ABOUT SEX AS A BIOLOGICAL VARIABLE, AND THIS HAS BEEN ANOTHER PLATFORM FOR LOOKING AT THAT VARIABLE. BUT I WON'T GO INTO THAT ANY FURTHER. A CHARACTERISTIC OF INIA PAST AND GOING FORWARD IS THAT IT'S BEEN A PLATFORM FOR BRINGING NON-ALCOHOL RESEARCHERS INTO THE ALCOHOL FIELD. AND I REALLY WANT YOU TO APPRECIATE THIS. IF YOU KIND OF LOOKED AT THE OLD MODEL THAT WAS JUST BASED ON& CENTERS AND PROGRAM PROJECTS, THOSE TYPES OF PROJECTS TENDED TO BE AT A SINGLE INSTITUTION, AND IF YOU WANTED A BADLY NEEDED EXPERT IN AN AREA, YOU WOULD START HAVING TO RECRUIT THEM ON TO YOUR FACULTY OR DEPARTMENT OR THINGS LIKE THAT. I MEAN, THAT WASN'T ENTIRELY TRUE BUT THE NICE THING AT INIA IS THESE ARE CONSORTIA OF PEOPLE AT MULTIPLE INSTITUTIONS. RIGHT NOW I THINK IT'S 11 INSTITUTIONS THAT ARE PART OF THE COLLECTIVE INIA CONSORTIUM. AND MANY OF THESE PEOPLE ARE EXPERTS IN AREAS BESIDES ALCOHOL THAT ARE ADDRESSING PROBLEMS THAT ARE EMERGING IN THIS WORK. YOU'LL RECOGNIZE SOME OF THE NAMES HERE. I APOLOGIZE IF I'VE FORGOTTEN ANYBODY. I THINK EIGHT OF THESE PEOPLE ARE CURRENTLY PIs AS PART OF THE INIA INITIATIVE. AND THE OTHER THING IS, ABOUT ONE-THIRD OF THEM GOT THEIR PH.D.s AFTER INIA WAS LAUNCHED, SO WE'RE BRINGING PEOPLE IN TO THIS PROCESS AS THE INITIATIVE GOES FORWARD. THE QUESTION NOW IS WHY IS INIA STILL RELEVANT? I THINK THERE ARE MANY EXAMPLES, I COULD TALK ABOUT HOW IT'S SKATED TO WHERE THE PUCK IS GOING TO BE, AND I THINK IT WILL CONTINUE TO DO SO. MUCH OF THE WORK REALLY ANTICIPATED SOME EMERGING IMPORTANT AREAS OF NEUROSCIENCE. WHEN YOU THINK ABOUT THE EMPHASIS IN THE YEAR 2000, WE'VE THOUGHT A LOT ABOUT NEURONS AND NEURAL CIRCUITS AND HOW THEY IMPACTED ON THINGS LIKE AUD. BUT ONE OF THE THINGS WE'RE LEARNING IS THAT IT'S THE STUFF AROUND THE NEURONS THAT HAS A LOT OF ACTION, AND IN FACT, ADRIENNE HARRIS POSED TO ME THIS WAY, THAT IN THE KNEW OWE DRAMA OF ADDICTION, THE GLIA ARE THE SCRIPT WRITERS AND DIRECTORS AND THE NEURONS ARE THE ACTORS. SO THERE'S A LOT OF INTERACTION BETWEEN THE CELLS AROUND THE NEURONS, AND THAT'S REALLY WHERE ALL THE EXCITEMENT HAS BEEN, AND THAT'S A BIG THEME FOR A LOT OF PATHOLOGIES RELEVANT TO THE BRAIN. INIA HAS BEEN ON THE CUTTING EDGE OF THAT. INIA HAS ALSO DONE A LOT OF WORK LOOKING AT STRESS, NEUROCIRCUITRY BEYOND THE HPA AXIS, WHICH IS SORT OF THE CLASSIC STRESS RESPONSE PHYSIOLOGICALLY, AND THAT'S GETTING INTO A WHOLE LOT OF INTERESTING EXCITE BEING AREAS THAT PREDICT VULNERABILITY TO HEAVY ALCOHOL USE AND ALSO INTERACTIONS WITH TRAUMA AND THINGS LIKE THAT WHICH ARE A PRIORITY THESE DAYS. I THINK ANOTHER THING I THINK THAT PEOPLE CAN APPRECIATE IS THAT A LOT OF THE WORK ON NEUROCIRCUITRY AND NEURAL NETWORKS AND SO FORTH HAS TAUGHT US TO APPRECIATE THAT THERE'S A LOT OF OVERLAP BETWEEN THE NEUROCIRCUITRY BEHIND EXCESSIVE DRINKING AND RELATED THINGS, AND OTHER CONDITIONS SUCH AS PAIN AND COGNITIVE CONTROL AND NEGATIVE AFFECT. AND I THINK THIS HAS IMPLICATIONS FOR WHAT WE HAVE TRADITIONALLY THOUGHT OF AS COMORBIDITIES. AND I THINK MAYBE A WAY TO LOOK AT THIS, BECAUSE OF THE COMMON MECHANISTIC UNDERPINNING AND THE FACT, FOR EXAMPLE, THAT, YOU KNOW, ROUGHLY HALF THE PEOPLE -- OR ANYONE WHO DOES CLINICAL WORK WITH PEOPLE WITH AUD KNOWS THAT THEY HAVE OTHER PROBLEMS BESIDES DRINKING TOO MUCH. BUT I THINK OUR THINKING GOING FORWARD AS INFORMED BY THIS KIND OF WORK IS GOING TO MAKE US RECONSIDER THIS, SO FOR EXAMPLE,& IF ROUGHLY HALF THE PEOPLE WITH AUD REPORT HAVING PAIN ISSUES, IS THAT REALLY A CO-MORBIDITY OR IS PAIN SENSITIZATION AND PAIN CONDITIONS ACTUALLY AN INTEGRAL PART OF THE AUD PHENOTYPE? SO THIS IS -- I THINK THIS KIND OF WORK ACTUALLY IS SHAPING HOW WE THINK ABOUT AUD IN GENERAL. SOME OF THIS WAS DISCUSSED EARLIER. THERE'S A TOOL DRIVEN REVOLUTION CURRENTLY UNDERWAY WITH THE BRAIN INITIATIVE AND OTHER SOURCES, AS WELL AS THE DEVELOPMENT OF DATA SCIENCE TOOLS, AND I'M REALLY IMPRESSED WITH HOW INIA IS POISED TO TAKE ADVANTAGE OF THOSE TYPES OF ADVANCES. NOW I HAVE TO GIVE A LITTLE CAVEAT TO REALLY GO INTO SOME OF THAT SPACE COMPLETELY AS BEYOND THE BUDGET THAT WE HAVE TO DO IT, BUT WHEN THESE THINGS ARE EMERGING IN THE FIELD AT LARGE, INITIATIVES SUCH AS INIA WILL INTERACT WITH THAT IN THAT WAY. AND SO WHAT WE'RE PROPOSING HERE, AND WHAT I HOPE YOU WILL APPRECIATE IS THAT INIA IS NOW MID-WAY THROUGH THEIR FOURTH ITERATION, AND I THINK THAT WHAT I WOULD LIKE TO PROPOSE IS THAT THE INITIATIVE GOES FORWARD WITH TWO RESEARCH CONSORTIA THAT ARE THEMATICALLY RELATED AND LED BY CONSORTIA -- EACH LED BY A CONSORTIUM COORDINATOR. THESE, BY THE WAY, AS I MENTIONED IN ONE OF MY EARLIER SLIDES, USES THE COOPERATIVE AGREEMENT, U MECHANISM. WE WERE A PIONEER IN DOING THAT AT NIH. AND THAT THE PROJECTS WORK COLLABORATIVELY TOWARD COMMON HYPOTHESES IN AN INTEGRATIVE WAY TOWARD COMMON HYPOTHESES. AND ANOTHER FEATURE I DIDN'T TALK ABOUT MUCH, BUT THE TWO CONSORTIA THAT WE'VE SUPPORTED WORK COLLABORATIVELY ON A REGULAR BASIS, EVEN THOUGH THEY KIND OF CARVE OUT DIFFERENT SPACE, THERE'S A LOT OF SHARING OF RESOURCES AND INTERACTIONS JUST IN TERMS OF HYPOTHESES THAT THEY'RE EXPLORING. AND IMPORTANTLY, INIA WOULD BE -- CONTINUE TO BE A PLATFORM FOR SUPPORTING EARLY STAGE INVESTIGATORS AND EXPERTS OUTSIDE THE ALCOHOL FIELD. IF YOU HAVE ANY QUESTIONS, I WILL TAKE THEM NOW. [APPLAUSE] >> IF WE USE ADRIENNE HARRIS' ANALOGY, THAT MAKES BRAD PITT, DOPAMINE AND YOAKAM PHOENIX CRF, IS THAT RIGHT? >> YES. [LAUGHTER] HE WAS THE ACTOR IN "THE JOKER." BRAD PITT WAS IN THE HOLLYWOOD MOVIE. >> I DIDN'T SEE THAT ONE. >> BEING FROM SOUTHERN CALIFORNIA, IT IS MY ABSOLUTE CALIFORNIA DUTY TO WATCH ALL THE OSCAR-NOMINATED MOVIES BEFORE THE OSCAR NIGHT, JUST FOR THE RECORD. >> WHAT'S YOUR PICK? ARE YOU GOING TO TELL US? >> USUALLY YOU HAVE TO WAIT UNTIL YOUR KIDS HAVE FLOWN THE COOP BEFORE YOU CAN ACTUALLY MEET THAT CRITERIA. OKAY. ANY QUESTIONS OR COMMENTS FOR MARK ON INIA? I REALLY SUPPORT ALL THE PIECES HE'S MADE. I WAS ONE OF THE PIs OF INIA WHEN IT FIRST STARTED, AND I THINK ONE OF THE THINGS THAT STILL I THINK IS A REALLY STONG PART OF IT IS THE ENGAGEMENT OF NEW INVESTIGATORS FROM THE NON-ALCOHOL AREAS INTO THIS CONSORTIUM. IT'S CROSS -- IT'S NOT IN ONE LOCALE, IT'S NOT ONLY IN THE NORTHEAST. WE BRING IN PEOPLE FROM DIVERSE AREAS AND DIVERSE DISCIPLINES. ANY OTHER THOUGHTS OR COMMENTS ON THAT? I SEE WE'VE OVERWHELMED YOU WITH CONCEPT CLEARANCES. I THINK YOU'RE GOOD, MARK. >> THANK YOU. >> IT'S COLONEL, RIGHT, MILLIKEN? >> ACTUALLY I'M A RETIRED COLONEL NOW. >> MY DAD WAS A COLONEL SO I HAVE GREAT RESPECT FOR COLONELS. SOME DAY I'LL TELL YOU ABOUT MY DAD. BUT YOU'RE ON. >> OKAY. ACTUALLY, THIS IS MY LAST WEEK AS A DEPARTMENT OF THE ARMY CIVILIAN. NEXT WEEK, I'M GOING TO BECOME A DOD CIVILIAN AS PART OF THE MOVE OF ARMY, NAVY AND AIR FORCE MEDICINE FROM UNDER THE SERVICES AND EACH OF THE SERVICES ACTUALLY HAVE A SURGEON GENERAL. UNDER A D.A. AGENCY. SO HAVING A BUREAUCRACY THAT'S NOT UNIFORMED RUN HEALTHCARE IS A LITTLE SCARY TO SOME OF US. YOU KNOW; BUT SINCE THIS IS MY LAST OPPORTUNITY TO TALK ABOUT ARMY ADDICTION, I JUST WANTED TO TAKE A FEW MOMENTS AND SUMMARIZE A FEW THINGS AND I THINK IT ACTUALLY HIGHLIGHTS A FEW THINGS THAT DR. HORGAN WAS TALKING ABOUT. FIRST OF ALL, WHAT'S RELEVANT ABOUT OUR SYSTEM IS -- AND GETS ME UP IN THE MORNING IS, WE HAVE THE FUTURE VETERANS IN OUR SYSTEM. IT'S AN OPPORTUNITY, AND ONE OF THE FRUSTRATING THINGS FOR THE FIRST SIX OR SEVEN YEARS OF THE WARS WAS EVERY TIME WE WOULD PUBLISH SOMETHING OR HIGHLIGHT SOMETHING, THEY'D GIVE THE V.A. MORE MONEY FOR BEHAVIORAL HEALTHCARE. OR ADDICTION CARE. AND IT REALLY WASN'T UNTIL 2007, 2008 THAT WE ACTUALLY GOT ADDITIONAL FUNDING AND WERE EVENTUALLY ABLE TO TRIPLE THE SIZE OF OUR BEHAVIORAL HEALTH AND ADDICTION ASSETS. AND AGAIN PART OF WHY THAT'S SO RELEVANT IS IF YOU THINK ABOUT OUR HEALTH SYSTEM, UNLIKE MOST HEALTH SYSTEMS THAT ARE DOLLAR-HEAVY AND THE OTHER END OF LIFE, WE'RE DOLLAR-HEAVY OR SHOULD E DOLLAR HEAVY IN THE EARLY END OF LIFE. THE MENTAL HEALTH AND ADDICTIONS ARE THE YOUNG PEOPLE DISEASE THAT WE SEE. SO SHAME ON US IF WE AREN'T THAT WAY, AND QUITE FRANKLY WE WEREN'T FOR MANY, MANY YEARS. THE OTHER THING I LIKE TO EMPHASIZE ABOUT JUST ALCOHOL IS THAT WHEN YOUNG MALESS ARE IN DISTRESS, THEY DON'T TEND TO COME INTO OUR MENTAL HEALTH CLINICS AND SAY, YOU KNOW, MY GRANDMA JUST DIED, MY PARENTS ARE GETTING A DIVORCE, I THINK I NEED TO TALK TO SOMEBODY. THEY GO OUT AND DRINK TOO MUCH. SO ALSO SHAME ON US IF WE TAKE TOO SIMPLISTIC APPROACH TO THESE PROBLEMS AND JUST PUT SOMEBODY IN A BUNCH OF ALCOHOL LECTURES OR GIVE THEM JUST A VERY STRAIGHTFORWARD ALCOHOL TREATMENT WITHOUT LOOKING AT THE WHOLE PERSON. SO ANYWAY, WE USED TO HAVE A SYSTEM THAT WAS VERY SILOED, THAT WAS PAPER CHARTS, AND ALSO THAT WAS BASICALLY THE EQUIVALENT OF -- THERE WAS MANDATORY CARE, YOUR COMPANY COMMANDER IS THE LEGAL AUTHORITY FOR YOU SO IT WAS PRACTICALLY THE EQUIVALENT OF COURT-ORDERED CARE. AND THAT'S ALL CHANGED AND I'LL GET TO THAT. PART OF THE EARLY CHANGE WAS WE HAD A CLUSTER OF MURDER-SUICIDES AT FT. HOOD IN 2002, AND ONE OF THE THINGS THAT CAME OUT OF THAT, I'M GOING TO SORT OF TALK ABOUT EVENTS AND SORT OF HOW WE ALMOST HAVE TO USE CRISES TO MAKE CHANGE IN A GOOD BURE BUREAUCRACY. THE GOOD ADDICTIONS IN OUR SYSTEM WERE RUN BY A BUNCH OF CIVILIANS, AN EXCELLENT BUREAUCRACY THAT VERY MUCH -- CHANGE. SO WE HAD SUICIDES OUT OF FT. HOOD, FOLKS RETURNING FROM DEPLOYMENT, SO MENTAL HEALTH QUESTIONS GOT ADDED TO THAT IN 2002. GREAT IDEA, RIGHT? IN 2004, THE RARE GROUP THAT I'VE BEEN -- HAVE BEEN A PART OF HISTORICALLY PUBLISHED IN THE NEW ENGLAND JOURNAL OF MEDICINE, WE GOT FANTASTIC ACCESS GIVEN BY THE LINE GENERALS TO FOLKS COMING BACK FROM THE FIRST WAVE OF THE IRAQ WAR, AND IT SHOWED UNSURPRISINGLY A REAL INCREASE IN PTSD, INCREASE IN DEPRESSION AND ANXIETY, BUT ALSO AN INCREASE IN ALCOHOL, DRINKING TOO MUCH. NOT JUST DRINKING, BUT DRINKING TOO MUCH, AND A CHANGE FROM PRE-DEPLOYMENT COHORTS. AS A RESULT OF THAT, THERE WAS ALCOHOL -- THERE WERE ALCOHOL QUESTIONS FINALLY ADDED TO THESE POST DEPLOYMENT SCREENINGS IN 2005, PROGRESS. IN 2007, WE WERE ABLE TO PUBLISH IN JAMA USING THESE QUESTIONS TO SHOW WHAT MOST OF US WHO ARE CLINICIANS HAD KNOWN FOR MANY YEARS, WHICH IS YOU CAN'T GET SOMEBODY TO GO OVER TO THE SUBSTANCE ABUSE CLINIC AND GET CARE BECAUSE THEY'RE WORRIED ABOUT THEIR CAREERS. I'M SITTING HERE TAKING CARE OF SOMEBODY THAT HAS PTSD, HE'S ALSO BEGUN TO DRINKING TOO MUCH, EVEN IF HE'D BEFORE DEPLOYMENT, BEFORE WAR EXPOSURE HAD HAD A VERY RESPONSIBLE RELATIONSHIP WITH ALCOHOL, HE'S HELPING HIMSELF CALM DOWN BEFORE HE FACES THE KIDS AT THE END OF THE DAY OR SHE'S HELPING HERSELF GET TO SLEEP AT NIGHT WITH A LITTLE EXTRA DOSE, TOLERANCE AND SO FORTH GOES UP, SOMEBODY SLIPS INTO -- YOU STILL CAN'T GET THEM TO GO OVER TO GET CARE FOR THE SUBSTANCE USE PROBLEM ALONG WITH THE PTSD YOU'RE TREATING THEM FOR. SO WE PUBLISHED IN THE NEW ENGLAND -- JAMA THIS TIME AND SHOWED THAT OF THE ALCOHOL SCREENING OF THE FOLKS COMING BACK THREE TO SIX MONTHS AFTER THEY WERE BACK, EVEN THOUGH 12% OF THAT POPULATION WERE SHOWING THEY HAD SIGNIFICANT PROBLEMS, ONLY 2% OF THAT 12% WERE REFERRED. I MEAN, BASICALLY THEY TALKED THE PRIMARY CARE GUY WHO WAS REVIEWING THIS OUT OF IT BECAUSE THEY WERE WORRIED ABOUT THEIR CAREERS AGAIN. THE NEXT MAJOR THING THAT HAPPENED YOU'LL RECALL THERE WAS AN ELECTION, THERE WAS ALSO SORT OF THE WALTER REED FIASCO, CONGRESS ASKED DOD TO STAND A TASK FORCE UP TO LOOK AT THINGS ACROSS OUR WHOLE SYSTEM, AND THE MONEY FELL FROM THE SKY IN 2007-2008. EACH OF THE SERVICES GOT $300 MILLION WHERE BEFORE WE WERE GETTING A MILLION HERE, A MILLION THERE TO ADD ADDITIONAL RESOURCES. SO IT WASN'T REALLY UNTIL 2008 THAT WE EVEN BEGAN TO HAVE THE OPPORTUNITY TO EXPAND OUR RESOURCE TO TAKE CARE OF THESE PROBLEMS. FORTUNATELY WE WERE ABLE TO MOVE PRETTY FAST AND WE HAD SOME REAL TALENTED LEADERSHIP IN THE ARMY, AND BY -- I FORGET WHAT YEAR IT WAS, 2016, THEY PUBLISHED IN THE HARVARD BUSINESS REVIEW NOT ONLY DID WE HAVE ALL THESE EXTRA PROVIDERS, BUT WE'D GONE FROM A FUTILE SYSTEM WHERE YOU LITERALLY -- IF SOMEBODY WOULD HAVE ASKED US IN 2006 HOW MANY PSYCHIATRISTS DO YOU HAVE IN THE ARMY, NOBODY WOULD EVEN BE ABLE TO ACCURATELY TELL YOU BECAUSE IT WAS SO DIFFERENT OF WHAT WAS HAPPENING FROM PLACE TO PLACE AND PEOPLE WERE HIRING YOU UNDERSTAND GWAT DOLLARS WHICH WERE JUST AN ANNUAL EXTRA SORT OF BUDGET KICKER FROM CONGRESS, SO ANYWAY, ALL THIS STUFF BECAME ORGANIZED, BUSINESS PRACTICES WERE PUT IN PLACE AND WE REALLY DEVELOPED A HECK OF A MENTAL HEALTH SITION SYSTEM. MEANWHILE ADDICTIONS IS OVER IN THE SILOED CLINIC, STILL USING PAPER CHARTS AND NOT REALLY COMMUNICATING WITH THE REST OF OUR SYSTEM. FORTUNATELY IN 2012, CONGRESS AGAIN PARTIALLY BECAUSE OF THE OPIATE CRISIS, ASKED THE INSTITUTE OF MEDICINE TO LOOK AT DOD SUBSTANCE ABUSE. CONNIE WEISNER WHO JUST LEFT THE COUNCIL WAS PART OF THAT, OR SORRY -- AND THEY MADE A BUNCH OF GREAT RECOMMENDATIONS, REALLY FANTASTIC. HOWEVER, NOT A WHOLE LOT HAPPENED UNTIL 2015 WHEN SOME INTERNAL DOCUMENTS THAT GOT TURNED OVER TO "U.S.A. TODAY," THERE WERE A SERIES OF ARTICLES PUBLISHED IN THE MEDIA. THEN THE SECRETARY OF THE ARMY STOOD UP A PANEL TO REVIEW WHAT WE WERE DOING WITH SUBSTANCE ABUSE, AND LOW AND BEE LOALD, A LOT OF THE RECOMMENDATIONS OF THE INSTITUTE OF MEDICINE FINALLY GOT TO HAPPEN. IN ADDITION TO THAT, PART OF WHAT THE INSTITUTE OF MEDICINE HAD ALSO RECOMMENDED WAS WE ALSO, IN ADDITION TO OUR MANDATORY KORTD COURT ORDERED PATH CREATED A VOLUNTARY PATH SO FOLKS COULD COME FORWARD WITH THEIR ALCOHOL PROBLEM, THEY COULD GET TREATMENT FOR IT, AND THERE WOULD BE NO HARM, NO FOUL AS LONG AS THEY TOOK RESPONSIBILITY FOR IT AND IT WASN'T SO PROFOUND THAT IT WAS GOING TO CAUSE THEM TO MISS DUTY OR CAUSE A REAL INCIDENT, SUICIDE, THE KIND OF THINGS YOU WOULD HOPE ARE IN PLACE. SO AS A RESULT OF THAT, WE GOT TO STAND UP A PILOT AND ACTUALLY SHOW THAT THIS COULD BE DONE AND DONE SAFELY. SO IN 2015 AS A RESULT OF THIS SECRETARY OF THE ARMY REVIEW, AGAIN I WAS ONLY THE ACTUAL MEDICAL PERSON ON THAT THING. AT THE TIME I ASKED DR. KOOB IF I NEED SOME BACKUP, YOU KNOW, WOULD NIAAA BE WILLING TO OFFER SOME EXPERTISE? ULTIMATELY I DIDN'T USE HIM OR THIS COUNCIL BUT TOM KOSTEN, WHO A LOT OF YOU KNOW, WHO HAD BEEN ON THE INSTITUTE OF MEDICINE WITH CONNIE WEISNER, WAS AN E AN EXTERNAL REVIEWER THAT LOOKED AT THE COMMITTEE'S WORK. HE WAS PROFOUND IN HELPING CHANGE THE DIRECTION OF THIS SHIP. FOLKS THAT ARE USING THEIR TIME TO SERVE ON BODIES LIKE THIS, ESPECIALLY WHEN IT COMES TO OUR GOVERNMENT SYSTEMS. IT REALLY CAN CARRY A LOT OF WEIGHT. SO NOW ALL KINDS OF GOOD THINGS HAVE HAPPENED SINCE 2016. OUR ALCOHOL ADDICTION PROVIDERS ARE ACTUALLY IN OUR BEHAVIORAL HEALTH CLINICS. THESE CLINICS ARE THE SAME ONES I WAS TALKING ABOUT, REALLY ARE ORGANIZED NOW. WE CAN TELL DOWN TO THE INDIVIDUAL PROVIDER WHETHER SOMEBODY -- WHETHER THEY'RE BUSY ENOUGH OR TOO BUSY, WHETHER THEY HAVE AVAILABLE APPOINTMENTS, WHETHER THEY'RE HANGING ON TO PATIENTS TOO LONG AND NOT LETTING NEW PEOPLE IN TO THEIR CASELOAD AND SO WE HAVE ALL KINDS OF TOOLS LIKE THAT. WE HAVE A LOT OF GOOD THINGS GOING ON. IN ADDITION, WE NOW HAVE THESE -- WE HAVE VOLUNTARY CARE, AND ON PAPER, WE'VE HAD ALCOHOL SCREENING AS PART OF OUR PRIMARY CARE, BUT WITHOUT FOLKS BEING ABLE TO ACKNOWLEDGE ACCURATELY WHAT WAS GOING ON AND ACCEPT A REFERRAL IF THAT WAS THE RIGHT THING TO DO, YOU KNOW, IT MADE ESPR KIND OF A JOKE FRANKLY, IT WAS A PAPERWORK EXERCISE. SO NOW WE HAVE THAT IN OUR PRIMARY CARE, AND WE HAVE ACTUALLY BEHAVIORAL HEALTH PERSON IN PRIMARY CARE IN ANY CLINIC OF ANY SIZE NOW THAT'S HELPING WITH THAT. SO AT THIS POINT, WE HAVE FOR LEVEL ONE CARE, OUTPATIENT CARE, WE HAVE ONE PROVIDER FOR EVERY 1400 SOLDIERS, WRI IS PRETTY WHICH IS PRET TY AMAZING, I THINK. WE HAVE AT OUR 12 LARGEST ARMY INSTALLATIONS, WE HAVE PARTIAL HOSPITAL PROGRAMS, 28-DAY PROGRAMS, AND WE HAVE FOUR RTFs ACROSS OUR SYSTEM NOW WITH ABOUT 60 BEDS. SO THE CARE HAS REALLY IMPROVED AND IT'S BEEN AN EXCITING JOURNEY, AND OUR HOPE -- WELL, THE OTHER THING IS, IN OUR SUBSTANCE USE PROVIDERS, ARE ALL LEVEL 2 PROVIDERS, THEY'RE ALL IND PENDLY CREDENTIALED BEHAVIORAL HEALTH PROVIDERS WHO CANNOT ONLY TREAT ALCOHOL BUT OTHER PROBLEMS, AND NEEDLESS TO SAY, A LOT OF OUR YOUNG FOLKS HAVE NOT ONLY THIS ADDICTION PROBLEM BUT A LIFE PROBLEM WHICH IS OFTEN AN ADJUSTMENT DISORDER AT LEAST IF NOT DEPRESSION AND ANXIETY PROBLEM OR PTSD. SO -- AND BECAUSE IT'S ALL HAPPENING WITHIN OUR BEHAVIORAL HEALTH CLINICS, THERE'S A LOT MORE COLLABORATION, A LOT MORE REFERRALS. THIS VOLUNTARY CARE TRACK IS NOW TAKING CARE OF 6,000 PEOPLE, AND THAT'S ABOUT 6,000 ADDITIONAL PEOPLE THAN WHAT WE WERE SEEING JUST THREE YEARS AGO. SO WE THINK THAT WE'RE GETTING TO A LOT OF PROBLEMS EARLIER BEFORE FOLKS HAVE THEIR DUI, BEFORE THEY HIT THEIR WIFE OR SEXUALLY ASSAULT A VULNERABLE PERSON OUT WHILE THEY'RE DRINKING TOO MUCH AND SO FORTH. IT'S REALLY A GOOD NEWS STORY, AND JUST PRIVILEGED TO BE ABLE TO SHARE IT WITH YOU ALL. >> THANK YOU, CHARLES. [APPLAUSE] EVERY TIME I HEAR FROM YOU AND THE V.A., I HAVE SOME HOPE. OBVIOUSLY IT'S A KEPT SYSTEM IN SOME SENSE. BUT YOU GUYS HAVE -- WHEN WE'VE HEARD FROM KAREN DRESSLER IN THE PAST ABOUT WHAT THE VA IS PROVIDING, THEY HAVE A PRETTY GOOD ARMAMENTARIUM THERE AS WELL. SO CONGRATULATIONS. IF WE CAN HELP WITH EVIDENCE-BASED INFORMATION, WE'RE HERE FOR YOU. >> THANK YOU. >> ANY QUESTIONS OR COMMENTS? OKAY. SO WE'RE ADJOURNED!