>> GOOD MORNING. WELCOME, WE APPRECIATE YOU SHARING YOUR PRECIOUS TIME WITH US AS THE NHLBI ADVISORY COUNCIL AND WITH NO FURTHER ADO LET ME CALL TO ORDER THE 282ND MEETING OF THE NHLBI ADVISORY COUNCIL AND WE ARE LOOKING FORWARD TO A PACKED BUT EFFICIENT SCHEDULE LED BY DR. MOEN AND SO I'LL TURN IT OVER TO LAURA NOW. >> GOOD MORNING EVERYBODY, I WILL ECHO GARY'S THANKS FOR COMING WE APPRECIATE YOUR ATTENDANCE SO VERY MUCH AFTER ALL WE CAN'T DO THIS WITHOUT YOU. I'M GOING TO START WITH THE REQUIRED ADMINISTRATIVE ANNOUNCEMENTS AND IF YOU WILL JUST BEAR WITH ME FIRST OF ALL THIS MEETING WAS ADVERTISED IN THE FEDERAL REGISTER. AND I WILL REMIND YOU ABOUT CONFLICT OF INTEREST. COUNCIL MEMBERS REQUIRED TO ABSENT THEMSELVES DURING THE ROOM DURING REVIEW OF APPLICATION IF THEIR PRESENCE WOULD CONSTITUTE OR APPEAR TO CONSTITUTE A CONFLICT OF INTEREST. ACCORDING TO FEDERAL LAW COUNCIL MEMBERS MAY NOT ENGAGE IN ANY LOBBYING ACTIVITIES WHILE ATTENDING COUNCIL MEETINGS OR SPONSORED EVENTS FURTHER INFORMATION REGARDING CONFLICT OF INTEREST REGULATIONS ARE INCLUDED IN THE ELECTRONIC COUNCIL BOOK, I HOPE YOU HAVE ALL HAD A CHANCE TO READ THAT MATERIAL CAREFULLY. YOU SHOULD ALL HAVE A COI FORM. WE ASK THAT IMMEDIATELY FOLLOWING TODAY'S MEETING EACH OF YOU SIGN THE CONFLICT OF INTEREST FORMS THAT ARE AT YOUR SEAT AND GIVE THEM TO KAY OR ONE OF HER COLLEAGUES VALUED COLLEAGUES KAY AND HER TEAM ARE SITTING AT THE BACK TABLE THERE AND A NOTE ABOUT RECORDING I THINK MOST OF YOU REMEMBER BUT IN CASE YOU FORGOT THE OPEN SESSION OF TODAY'S METING IS BEING WEBCAST AND RECORDED THE VIDEO WILL BE ARRIVED AND REMAIN AVAILABLE TO PUBLIC AND NIH COLLEAGUES SO REMEMBER YOU ARE THERE FOR POSTERIORITY FOR COUNCIL MEMBERS ON THE PHONE I ASK THAT YOU PLEASE MUTE YOUR PHONES WHILE YOU'RE LISTENING REMEMBER TO UNMUTE WHEN YOU WOULD LIKE TO SPEAK AND MUTE WHEN YOU ARE FINISHED FOR THOSE OF YOU AT THE TABLE WHEN YOU SPEAK PLEASE TURN YOUR MICROPHONE ON AND SPEAK INTO IT AND TURN IT OFF WHEN YOU ARE FINISHED YOU CAN TELL THERE IS A LITTLE RED LIGHT UNDER THE MICROPHONE PART ITSELF THAT LET'S YOU KNOW IT'S TURNED ON. JUST A NOTE ABOUT COUNCIL ATTENDANCE, DR. ABLE WAS UNABLE TO JOIN US AT ALL TODAY WE MISS HIM HOWEVER AND DR. RICHARD SCOFIELD OUR EX OFFICIO MEMBER WAS ALSO UNABLE DIANE NUGENT AND WYRICK ARE ON THE PHONE AND HAVE A CHANCE TO CHIME IN JUST BEING ON THE PHONE DOES NOT EXEMPT THEM FROM CONTRIBUTING IN THE DISCUSSION WE WISH TO HAVE THEIR GUIDANCE, I WILL CALL YOUR ATTENTION TO THE FUTURE MEETING DATES FOR COUNCIL, FUTURE MEETING DATES THROUGH 2021 FOR THE ADVISORY COUNCIL HAVE BEEN PROVIDED TO YOU AND ARE LISTED ON EVERY AGENDA SO THAT YOUR ATTENDANCE WILL HOPEFULLY BE EASIER TO RECALL AND FACILITATE. I HOPE THAT YOU WILL MAKE A NOTE OF THESE DATES AND IF NECESSARY FOR THOSE OF YOU THAT ARE FORTUNATE ENOUGH TO HAVE AN ADMINISTRATIVE ASSISTANT ASK THEM TO GET THEM ON YOUR CALENDAR. YOUR PRESENCE IS GREATLY APPRECIATED AS WE SAID MANY TIMES. I HOPE THAT SAYING IT A LOT DOESN'T DECREASE THE DEGREE OF SINCERITY YOU DETECT IN OUR THANKS PARTICULARLY IN THE AFTERNOON WHEN WE REQUIRE A QUORUM TO CONDUCT THE GRANT REVIEW BUSINESS THAT IS REQUIRED BY LAW, THAT'S THE MOST IMPORTANT PART. WE THANK YOU FOR STAYING THROUGH THE END OF THE MEETING, I KNOW THAT WE ALL FEEL THAT WE ARE GETTING CALLED AWAY AS THE MEETING CONTINUES TO DRIVE ON BUT I THINK AS YOU KNOW WE DO TRY TO RUN A VERY EFFICIENT MEETING AND I ASSURE WE WILL DO OUR BEST TO GET YOU OUT ON TIME SO YOU CAN PROCEED WHAT WILL FOLLOW THE MEETING FOR YOU. AN AGENDA REVIEW JUST TO GO OVER THIS VERY QUICKLY, AFTER DR. GIBBONS'S DIRECTORS REPORT WE WILL RECEIVE A REPORT ON DATA STAGE JOHN KALTMAN IS GOING TO KICK THAT OFF WITH A PROGRAM FOLKS FROM THE DATA STAGE PROGRAM THEN THERE IS GOING TO BE A PRESENTATION FROM THE INTRAMURAL PROGRAM TITLED ALL ABODE VESICLES VIRUSES AND STRENGTHS IN NUMBERS BY DR. NIHAL ALTAN-BONNET WHO IS A SENIOR INVESTIGATOR AND HEAD OF THE LABORATORY OF HOST PATH AGAIN DYNAMICS AT NIB INTRAMURAL RESEARCH AND DO THE INITIAL REVIEW BECAUSE THIS IS THE TIME OF YEAR WE DO CONCEPT CLEARANCE AND LET YOU WEIGH IN ON THE THINGS WE ARE THINKING OF DOING AS AN INSTITUTE. THERE ARE INITIATIVES THAT WERE DISCUSSED WITH OUR BOARD OF EXTERNAL MEMBERS IN APRIL AND WITH THE EXTENDED CLOSED SESSION AND YOUR RETURN TRIPS IN MIND WE ARE PROBABLY JUST GOING TO TAKE A SHORT BREAK AND HAVE A WORKING LUNCH UNLESS OF COURSE YOU ALL TELL ME YOU DESPERATELY NEED A BREAK BECAUSE YOU GET TO RUN THAT PART OF THE SHOW WHEN WE RESUME IT WILL BE IN CLOSED SESSION FOR COUNCIL MEMBERS AND A FEW STAFF TO HEAR THE REPORT FROM THE BOARD OF SCIENTIFIC COUNSELORS AND WE WILL SEGUE IN THE CLOSED SESSION FOR GRANT REVIEW WITH THE REST OF THE STAFF PRESENT, WITH ALL OF THAT IN MIND I'M GOING TO GO AHEAD AND TURN THINGS BACK OVER TO DR. GIBBONS SO WE CAN GET STARTED WITH HIS DIRECTOR'S REMARKS. >> OKAY, WELL GOOD MORNING AND I'LL TRY TO SHARE THIS DIRECTOR'S REPORT TO GIVE YOU SOMETHING OF AN OVERVIEW OF SOME OF THE THINGS THAT HAVE TRANSPIRED SINCE THE LAST TIME WE GATHERED AND GIVE YOU AN UPDATE ON OUR ACCOUNTABLE STEWARDSHIP AS WELL AS SOME OF THE SCIENTIFIC ELEMENTS THAT WE SEE ON THE HORIZON. FIRST, TO OUR COUNCIL I WANT TO GIVE THIS SHOUT OUT IN RECOGNITION OF 50 YEARS OF NHLBI DIVISION OF LUNG DISEASE, DR. DR. KYLIE HAS BEEN ON A CONTINUOUS BIRTHDAY PARTY SWING THAT PROBABLY REACHED A ZEANETH AT THE RECENT ATS MEETING WHERE THE LUNG DIVISION HAD A BIG SPLASH SO WE ARE VERY PROUD OF THE LEGACY OF EXCELLENCE STARTED BACK AS YOU CAN SEE PRESIDENT NIXON'S TIME WITH THE VERY FIRST DIRECTOR OF THE LUNG DIVISION CLAUD BEFORE HE BECAME A NHLBI DIRECTOR AND SO WE HAVE BEEN ENJOYING THIS CELEBRATION OF 50 YEARS OF PULMONARY SCIENCE IN NHLBI AND I THINK THE INSTITUTE AND DIVISION WOULD BE QUITE PROUD OF THAT LEGACY OF EXCELLENCE. IT'S BEEN ADDRESSING SOMETHING THAT I STRUGGLE WITH AS A CARDIOLOGIST IN TRYING TO FULLY UNDERSTAND, I'M A SLOW LEARNER SO JIM HAS TO KEEP TEACHING ME ABOUT WHY THIS CURVE WORKS THE WAY IT DOES. THIS NOTION THAT I FIND DISTASTEFUL AND VEXING THAT THERE IS THIS DECLINE IN PULMONARY FUNCTION AFTER AN EXPOSER TO SOMETHING INJURIOUS AND WE TEND TO AS CLINICIANS WAIT UNTIL PATIENTS ARE SYMPTOMATIC TO THEN TRY TO EMELORIATE AND PALIATE WITH BRONCHODILATOR STEROIDS AND OXYGEN AND REALLY THE HOPE AND VISION OF BEGINNING TO UNDERSTAND THE PRECURSORS, THE EARLIER PRECLINICAL STATES OF LUNG DISEASE TOUR TOWARD PREVENTION AND PREEMPTION AND CREATING THE SORT OF SCIENTIFIC SANDBOX AND SET OF RESOURCES THAT CAN FURTHER ELUCIDATE THE MOLECULAR PATHWAYS THAT DRIVE THAT PROGRESSION OR INDEED PROMOTE RESILIENCE AND REPAIR AND IN THAT REGARD YOU AS COUNCIL HAVE PROVIDED YOUR ENDORSEMENT OF A NUMBER OF INITIATIVES THAT ALLOW FOR OBSERVATION OF THE DISCOVERY AND UNDERSTANDING THE NATURAL HISTORY AND PHENO TYPES OF LUNG DISEASES IS A KEY PART OF OUR RESEARCH PORTFOLIO, BUT AGAIN LINKING TO THOSE OBSERVATIONS AT A POPULATION AND CLINICAL LEVEL TO BASIC SCIENCE, WE ARE VERY EXCITED ABOUT THE ADVANCES IN USING TOOLS AND TECHNOLOGIES TO TAKE TO A SINGLE CELL RESOLUTION MOLECULAR PATHWAYS ASSOCIATED WITH BOTH LUNG HEALTH AND DISEASE, AGAIN ELUCIDATING PRECLINICAL STAGES OF PATHWAYS AND BEFORE YOU HAS COME THE LUNG MAP INITIATIVE AS ONE OF THE MOLECULAR ATLASS, SIMILARLY THAT TRANSLATION TO REFINEMENTS IN BIO MARKERS AND SUB PHENO TYPING INCLUDING IMAGING MODALITIES THAT ARE GOING TO TAKE THIS BIG WASTE BASKET OF TERMS OF CHRONIC LUNG DISEASE AND HOPEFULLY ELUCIDATE THEM MORE EFFECTIVELY AND CAN DRIVE THE DEVELOPMENT OF BETTER TARGETED THERAPIES AND THERAPEUTIC STRATEGIES WITH MORE PRECISION IN WAYS THAT REALLY CAN START TO BEND THE CURVE MORE EFFECTIVELY AND REALLY CHANGE THAT WHOLE NATURAL HISTORY AND SENSE OF ENEXURABLE DECLINE AND INDEED TALK ABOUT REVERSAL REPAIR AND REMISSION OF LUNG DISEASE, SO IN MANY WAYS AGAIN THE LUNG DIVISION IS PART OF THAT FORWARD LOOKING PARADIGM THAT WE HOPE TO CONTINUE TO RECAPITULATE AND BUILD ON THAT LEGACY OF EXCELLENCE. NOW TO MAYBE SWITCH GEARS FROM THAT UPDATE INTERNALLY TOWARDS OUR ACCOUNTABLE STEWARDSHIP AND WE WANT TO KEEP YOU APPRAISED OF THE FISCAL ENVIRONMENT AS YOU ALL KNOW THIS WAS AN EXCEPTIONAL FISCAL YEAR BECAUSE WE SEAMLESSLY TRANSITION FROM FISCAL YEAR 18 TO 19 AND ACTUALLY HAD A BUDGET AT THE BEGINNING OF OUR FISCAL YEAR, FIRST TIME THAT'S HAPPENED IN A LONG TIME AND IT WAS AN INCREASED BUDGET AT THAT SO THIS IS REALLY A BETTER YEAR 3.1 PERCENT INCREASE OVER FY18 AND WE'VE AS PART OF OUR ACCOUNTABLE STEWARDSHIP PRIORITIZE ACCORDING TO OUR ENDURING PRINCIPLES AND STRATEGIC PLAN TOWARDS THE ELEMENTS LISTED HERE AND INITIATED DISCOVERY SCIENCE NEXT GENERATION AND WORKFORCE DEVELOPMENT AND OUR STRATEGIC VISION ALIGNMENT AND OPPORTUNITIES. SIMILARLY WE HAD THE OPPORTUNITY TO COMPANY DR. COLLINS TO THE 2020 APPROPRIATIONS HEARINGS WHERE WE HAD AN OPPORTUNITY TO PUT FORWARD THE VALUE PROPOSITION TO OUR APPROPRIATORS AND A NUMBER OF TOPICS THAT THEY RAISED I THINK WERE OF INTEREST CERTAINLY RELEVANT TO OUR PORTFOLIO THAT INCLUDED THE EPIDEMIC OF E CIGARETTES PARTICULARLY AMONGST ADOLESCENTS THAT IS BOTH A CHALLENGE FROM THAT PUBLIC HEALTH STANDPOINT BUT ALSO POTENTIALLY A CLINICAL OPPORTUNITY AS A TOOL FOR PROMOTING SMOKING CESSATION AND REDUCTION OF RISK OF CARDIOPULMONARY DISEASE AND HOW WE CAN NAVIGATE THAT AS NIH SIMILARLY ANOTHER KEY ELEMENT THAT CAME UP PHEMATICALLY THE CHALLENGE OF MATERNAL MORTALITY AND THE NOTION THAT CERTAIN RACE ETHNIC GROUPS HAVE SEVERAL FOLD INCREASE IN MATERNAL MORTALITY. WE GOOD? AS WELL AS HEALTH DISPARITIES INDEED MATERNAL MORTALITY SHOWING A GEOGRAPHIC DISPARITIES AS WELL. SO THERE WAS A NUMBER OF INTEREST BY THE APPROPRIATORS IN THESE AREAS AND I THINK CLEARLY RELEVANT TO THE IN NHLBI PORTFOLIO AND ENCOURAGED AS A FOLLOW-UP TO THOSE HEARINGS IN THE MARKUP, SORT OF THE ROUGH DRAFT IF YOU WILL OF THE APPROPRIATIONS PROCESS ON THE HOUSE COMMITTEE SIDE THAT THEY DID APPROPRIATE A PLUS UP FOR NIH2400 MILLION FOR THE NHLBI THIS IS STILL A DRAFT KIND OF PRELIMINARY STAGES OF THESE THINGS THERE IS STILL A LOT OF NEGOTIATION THAT HAS TO GO FORWARD ABOUT WHAT THEY DO A MINI BUS AND DO A FEW OF THESE BILLS TOGETHER OR BIG THING OR FIGURING OUT THE TOP LINE, ALL KINDS OF POLITICAL GAMESMANSHIP GOING ON BUT WE ARE HOPEFUL THAT CONGRESS WILL CONTINUE THE COMMITMENT TO SUSTAINED INCREASES FOR NIH SO WE ARE PRAGMATICALLY OPTIMISTIC THAT WE WILL AVOID SEQUESTERED CUTS, HOPEFULLY GET THROUGH WITHOUT A SHUT DOWN AND INDEED MIGHT EVEN HAVE A PLUS UP ON OUR BUDGET. SO THAT'S THE LANDSCAPE BOTH POLITICAL AND ECONOMICALLY TO OUR APPROPRIATIONS. LET ME TURN TO SOME OF THE KEY HIGHLIGHT AREAS THAT RELATE TO OUR ENDURING PRINCIPLES PARTICULARLY INVESTIGATOR INITIATED DISCOVERY SCIENCE AND TRAINING IN PARTICULAR TODAY. FIRST, BECAUSE OF THOSE APPROPRIATIONS IT'S ENABLED US TO REALLY SOLIDIFIED OUR PRIORITIZATION ON MAKING SURE THAT THE RO1 POOL REMAINS ROBUST AND WE SUSTAINED A ROBUST SUCCESS RATE. NOW IN THE MID 20s THAT'S SOMETHING WE FEEL MORE COMFORTABLE THAT WE CAN SUSTAIN AND HOPEFULLY SEND A SIGNAL TO THE COMMUNITY AFTER SOME YEARS OF DECLINE SO WE ARE VERY MUCH ENCOURAGED BY THAT AND ANTICIPATE WE WILL BE ABLE TO DO THAT IN FY19 AND YOU WILL BE SEEING SOME OF THOSE COME BEFORE YOU TODAY. I DO WANT TO SHARE WITH YOU ONE OF THE CHALLENGES OF SUSTAINING THAT, HOWEVER. THE APPROPRIATIONS INCREASES HAVE BEEN GREAT, APPROXIMATELY 30% OVER THE LAST SEVERAL YEARS TO THE OVER ALL NIH BUDGET AND SOME MAY WONDER, YOU KNOW, SO WHY HAVEN'T THE NUMBER OF AWARDS INCREASED COMMENSURATELY AND ONE OF THE CHALLENGES WE HAVE IS THAT ALTHOUGH WE ARE COMMITTED TO INCREASING THOSE AWARDS AND SUSTAIN THOSE SUCCESS RATES ONE OF THE THINGS I SUSPECT YOU'RE AWARE OF FROM WHERE YOU SIT IS THAT THE USE OF MODULAR GRANTS HAS DECLINED PRETTY SUBSTANTIALLY AND IT SWITCHED OVER TO WHAT IS CALLED YOUR CATEGORICAL WHICH THERE IS A LOT MORE BUDGET FLEXIBILITY, THE PIS ARE USING UNDER THE 500 CASE CEILING SO AS A RESULT ACTUALLY THE AVERAGE COST PER RO1 IS GOING UP. AND SO NOT SURPRISINGLY, THEIR FEET ABOUT HOW TO FUND AS MUCH SCIENCE AS THEY POSSIBLY CAN WITH THEIR SPECIFIC AIMS AND THAT'S HAPPENING. AND SO AS WE MODEL WHAT WE CAN DO WITH A GIVEN BUDGET INCREASE, THIS IS INCREASINGLY AN ELEMENT WE HAD TO TAKE INTO CONSIDERATION THAT WE ARE GOING TO HAVE TO SPEND MORE MONEY PER AWARD AND JUST IN ORDER TO MAINTAIN THE KIND OF NUMBER OF AWARDS AND SUCCESS RATES THAT WE'VE ENJOYED. THE OTHER PART THAT I'D LIKE TO HIGHLIGHT OR THEE MATICILY TODAY RELATES TO THE PORTFOLIO OF OUR AWARDEES AND PARTICULARLY ITS DIVERSITY AND INCLUSION. AND THIS SLIDE SORT OF SUMMARIZES IN AGGREGATE NIH DATA RELATED TO WOMEN INVESTIGATORS WHO ARE FUNDED BY NIH ACCORDING TO THE BIG CATEGORIES OF MECHANISMS AND YOU CAN SEE THAT FOR THE MOST PART THERE IS A SENSE OF PARODY THAT 50/50 WHEN IT COMES TO CAREER DEVELOPMENT AWARDS OVER ALL BUT AS YOU SCAN DOWN TO THE RESEARCH PROGRAM GRANTS, THE RO1S, IF YOU WILL, THERE IS WHERE YOU SEE A REDUCTION IN THAT SENSE OF PARODY ONLY ABOUT A THIRD THERE AND SO THAT'S WHERE WE STILL HAVE SOME UNFINISHED BUSINESS IN TERMS OF ENSURING THAT WE HAVE THE MOST INCLUSIVE AND DID VERSE WORKFORCE THAT WE CAN, OBVIOUSLY WE WANT TO TAP INTO ALL THE TALENT IN THIS COUNTRY AND AGAIN THIS GAP IS ONE THAT WE HOPE TO CLOSE AND THE CAREER DEVELOPMENT AWARDS DATA SUGGESTED THERE ARE ENOUGH WOMEN GETTING PH.D.S WE KNOW I THINK WOMEN NOW SURPASS MEN IN MEDICAL SCHOOLS NOW AND SO IT'S PROBABLY NOT A PROBLEM OF GENERATING THE DEGREE PROGRAMS, WE ARE SEEING IT NOW IN HOW THOSE INDIVIDUALS WITH DOCTORATES GETTING AWARDS AND THE QUESTION IS HOW THEY MOVE THROUGH THE PIPELINE AND ALSO IMPORTANTLY ASCEND WITHIN ACADEMIA TO LEADERSHIP POSITIONS AND SUSTAIN RO1 FUNDED AWARDEES. IN TRYING TO PROBE THIS A LITTLE BIT FURTHER, THERE IS SOME EVIDENCE THAT FOR THE MOST PART WOMEN TRAIL MEN SLIGHTLY IN AWARD RATES, BUT IT IS KIND OF MODEST I WOULD SAY OVER ALL. SUGGESTING THAT YOU KNOW GRANT PER GRANT PRIORITY SCORE FOR PRIORITY SCORE THERE IS PROBABLY NOT A GREAT DEAL OF DISCRIMINATION IF YOU WILL EITHER CONSCIOUS OR OTHERWISE IN THE AWARD RATES ONCE WOMEN APPLY I THINK THE MORE STRIKING THING TO AT LEAST TO ME IN LOOK AT THIS CURVE IS THE PORTION OF MEN WHO ARE APPLYING RELATIVE TO WOMEN AND SO THAT'S WHERE I THINK THE DISPARITY SEEMS TO BE MOST STRIKING WHERE MEN HAS BEEN A RAPID UP SLOPE WOMEN IT SEEMS LIKE IT'S A SLIGHTLY SLOWER ONE, HOPEFULLY THAT IS NOT A PLATEAU THAT IS HAPPENING THERE BUT CERTAINLY IT'S CREATING A GAP, SO AND THERE IS ALSO SOME DATA THAT PERHAPS WOMEN MIGHT BE DISCOURAGED BY MORE OFTEN BY A HIGHER PRIORITY SCORE AND NOT RESUBMITTING AND AGAIN TAKING MORE SWINGS AT BAT AND/OR RENEWING THEIR GRANTS AT THE SAME RATE AS MEN SO SOME OF THESE ARE CREATING THIS DISPARITY. SIMILARLY VERY INTERESTING STUDY DONE BY NIGMS, AND LOOKED AT SORT OF THE LONG-TERM FUNDING RATES BY MEN AND WOMEN AND THIS CURVE IS SIMILAR TO I THINK ONE THAT MARK DID HERE AT NHLBI IN WHICH YOU GET YOUR FIRST RO1 AND THEN THERE TENDS TO BE SORT OF A SHARP DROP OFF AND COME BACK IN FOR RENEWAL AND THAT IS WHERE WE LOSE SOME FOLKS FROM THE PIPELINE AND THEN IT SORT OF SLIGHTLY ASYMPTOTES A BIT AND MANY PEOPLE TURN OUT TO BE LIFERS LIKE MANY OF THE PEOPLE AROUND THIS ROOM WITH CONTINUOUS FUNDING FOR 20, 25 YEARS. FOR THE MOST PART THIS CURVE KIND OF SUGGESTED WOMEN ONCE THEY GET THAT FOOT HOLD ARE ABLE TO SUSTAIN FAIRLY WELL, SO IT REALLY KIND OF SUGGESTS WE REALLY HAVE TO MANAGE THE MIDDLE AND REALLY GET FOLKS FROM CAREER DEVELOPMENT AWARDS THROUGH THAT FIRST RENEWAL AND MAKE SURE THEY ARE RESILIENT ENOUGH TO STAY IN THE SYSTEM AND IF WE GET THE RIGHT COHORT, COHORT OF TALENTED WOMEN WITH PH.D.S AND MDS WE SHOULD BE ABLE TO SHIFT THAT CURVE AND AGAIN HAVE A MORE INCLUSIVE AND D ISHGS VSHGS ESHGS RSHVEDIVERSE AND GETS THE RATE HIGHER THAN A THIRD. I BELIEVE THIS IS A COLLECTIVE CHALLENGE OF THE LEADERS AROUND THIS TABLE. IT'S NOT EASY TO AWARD RO1S IF YOU DON'T HAVE A FACULTY POSITION. AND SO THIS IS A SLIDE WE STOLE FROM HANNA VALENTINE'S OFFICE LOOKING AT DIVERSITY AND INCLUSION AND IT'S NOTABLE IN TERMS OF THE FACT THAT AGAIN THERE ARE A LOT OF FEMALE PH.D.S OUT THERE BUT WHAT WAS ALSO NOTED IS THE NUMBER OF NEW JOBS, THE NUMBER OF ASSISTANT PROFESSOR POSITION INHABITED BY WOMEN RELATIVE TO MALE. YOU AGAIN SEE A BIG GAP THERE AS WELL AND SO ALMOST PARADOXICALLY SO SO AGAIN PART OF THE CHALLENGES ENSURING THAT OUR INSTITUTIONS THAT WHERE WE DO OUR RESEARCH AND FUND OUR RESEARCH ARE ALSO INCLUSIVE AND DIVERSE PARTICULARLY FOR THIS NEXT GENERATION OF TENURED TRACKERS AND INDEED YOU CAN SEE ON THE RIGHT THAT IT'S GETTING THAT DIVERSITY AND INCLUSION EARLY ON IN THE CAREER TRAJECTORY THAT IS GOING TO BE CRITICAL BECAUSE CLEARLY THERE IS A SENSE OF A GLASS CEILING IF YOU WILL IN TERMS OF WOMEN STAYING IN THE SYSTEM AND AGAIN ASCENDING THE LADDERS OF LEADERSHIP AND THAT'S REALLY WHERE THE CULTURE STARTS TO CHANGE. SO I THINK WE HAVE A COLLECTIVE CHALLENGE AND RESPONSIBILITY AS PART OF OUR STEWARDSHIP OF THE WORKFORCE OF THE FUTURE. WE ALWAYS HAVE TO BE VERY CAREFUL HERE AT NIH NOT TO PREACH AND TALK IF WE CAN'T WALK THAT SAME TALK AND TO BE HONEST WE DO HAVE A GLASS HOUSE CHALLENGE THAT MIRRORS THE GLASS CEILING CHALLENGE IN WHICH AS WE LOOK AT THE NIH INTRAMURAL PROGRAM WE SEE THOSE SAME GAPS THAT EXIST IN ACADEMIA AND TODAY YOU WILL HEAR A LITTLE BIT ABOUT OUR INTRAMURAL PROGRAM AND ITS EVALUATION BY THE BOARD OF SCIENTIFIC COUNSELORS AND AS PART OF THAT WE WANT TO BE TRANSPARENT ABOUT HOW WE ARE DOING IN THIS SPACE AND I WOULD ACKNOWLEDGE THAT WE CAN AND NEED TO DO BETTER. WE ARE ABOUT CLOSE TO ACADEMIC AVERAGES, WE ARE ABOUT IN THE MIDDLE OF NIH, BUT I THINK WE SHOULD BE NOT SATISFIED WITH THAT FOR SURE AND AGAIN I KNOW OUR SCIENTIFIC DIRECTOR AND OUR TEAM IS COMMITTED TO TURNING THAT AROUND, BOTH IN TERMS OF NUMBERS BUT ALSO ENGAGEMENT IN LEADERSHIP OPPORTUNITIES AS WELL. ONE OF THE PROGRAMATIC THAT IS BY DR. VALENTINE OR CHIEF SCIENTIFIC OFFICER FOR WORKFORCE DIVERSITY ACTUALLY SHOWED IN THE MIDDLE A PICTURE ALONGSIDE THE TALL GUY WHO IS THE NIH DIRECTOR A MIST A PROGRAM THAT INVOLVES A DISTINGUISHED SCHOLAR PROGRAM IN ESSENCE A COHORT PROGRAM THAT IS MAKING A PARTICULAR EMPHASIS ON DIVERSITY AND INCLUSION WITH A SORT OF TARGETING, IF YOU WILL, OF A NUTUREANCE AND NETWORKING AMONG THE PARTICULAR DIVERSE SET OF TENURED TRACKERS THAT ARE PART OF THE INTRAMURAL PROGRAM, IT'S PART OF THE INVESTMENT IN THIS GROUP AND NURTUREANCE GROUP TO HOPE BEND THE CURVE IN TERMS OF THE INCLUSION AND DIVERSITY OF THE INTRAMURAL PROGRAM. ALSO IN THAT SAME SPIRIT TODAY WHERE WE SHARE WITH YOU THE ELEMENTS OF OUR INTRAMURAL PROGRAM WE ARE DELIGHTED THAT NEHN ESHE NIHAL WILL GIVE A PRESENTATION AND A CHIEF WHO TENURED THE PROCESS JUST A FEW YEARS AGO AND IS DOING AMAZING WORK THAT I'M SURE YOU WILL ENJOY AS SHE PRESENTS LATER ON TODAY AND AS WELL AS AN ACKNOWLEDGMENT OF CLAIRE WATERMAN WHO HAS RISEN TO THE PARTICULAR TITLE OF DISTINGUISHED SENIOR SCIENTIFIC INVESTIGATOR THAT IS A PARTICULARLY SELECT AND ELITE GROUP AMONGST ALL THE SENIOR TENURED INVESTIGATORS AT NIH AND RECENTLY INDUCTS TO THE NATIONAL ACADEMY OF SCIENCES AND AGAIN SHE IS DOING PIONEERING WORK, SHE IS ALSO ONE OF OUR SCIENTIFIC LEADERS, IS HEAD OF THE BRANCH ON CELL AND DEVELOPMENTAL BIOLOGY AND SHE HAS BEEN A WORLD LEADER IN ILUCIDATING SOME MOTILITY AND ADHESIONS AND MOLECULAR MACHINERY AND ACTUALLY MANY INNOVATIONS IN TERMS OF VISUALIZING THAT MOLECULAR MACHINERY WITH SUPER RESOLUTION, MICROSPOCY AND CELL BIOLOGY AND WE HAVE A NUMBER OF SHE-ROS TODAY AND HIGHLIGHTING DR. -- OKAY, TOLD ME TO STOP DANCING UP HERE. [ LAUGHTER ] APPARENTLY DISCONNECTING IT. WHAT CAN I SAY? I'M AN R AND B GUY, YOU KNOW, MOVING AROUND. SO I WAS MENTIONING DR. CAMPBELL WASH BURN WHO IS DOING SOME INCREDIBLE STUFF THAT WE ARE GOING TO HAVE TO HAVE HER COME AND PRESENT TO YOU. ACTUALLY AT THE RECENT ATS SHE WON ONE OF THEIR SORT OF YOUNG INVESTIGATOR AWARDS THIS BEAR CAGE THING COMPETITION AND SHE IS DOING JUST SOME INCREDIBLE STUFF ABOUT LOW FIELD MRI IN WHICH YOU ARE ABLE TO VISUALIZE SORT OF TAKE OR TURNING THE PARADIGM OF BIGGER AND BIGGER MAGNETS ON ITS HEAD AND YOU KNOW JUST BLOWING AWAY THINGS WITH NEW OPPORTUNITIES. I WON'T TRY TO SUMMARIZE WHAT SHE HAS BEEN ABLE TO DO, BUT VISUALIZING THINGS THAT, AGAIN, IF YOU WOULD HAVE THOUGHT WERE INVISIBLE AND SORT OF REDEFINING HOW AN MRI CAN STUDY REAL TIME PHYSIOLOGY AND IT'S GOING TO TRANSFORM I THINK INTER VENTRICLE RADIOLOGY AND CERTAINLY CARDIOLOGY SO WE ARE VERY EXCITED ABOUT THE FUTURE AND ITS INCLUSION AND WHAT SHE BRINGS TO THE TABLE. SO AS PART OF THAT CLEARLY THE INSTITUTE HAS TRIED TO STAY COMMITTED TO EXPANDING THIS POOL OF OPPORTUNITIES PARTICULARLY FOR THIS NEXT GENERATION THAT IS PROBABLY AMONGST THE MOST DIVERSE THAT THIS COUNTRY HAS HAD IN A LONG TIME AND, AGAIN, PART OF THAT IS COMMITMENT TO SUSTAINING THAT ROBUST SUCCESS RATE ON OUR ESI PROGRAM AND AGAIN I THINK THAT'S PART OF THE PAYING THE SEED CORN FOR THE FUTURE. I THINK AN ADDED BONUS TO THAT INVESTMENT IS NOT JUST GENERICALLY INVESTIGATED INITIATIVE DISCOVERY SCIENCE BUT WHEN YOU PROBE A LITTLE DEEPER AGAIN NOT SURPRISING THIS COHORT OF EARLY STAGE INVESTIGATORS IS PROBABLY MORE DIVERSE THAN OUR OVER ALL APPLICANT POOL AND OUR OVER ALL CERTAINLY ESTABLISHED INVESTIGATOR POOL AND THAT IS SHOWN ON THE LEFT THERE, YOU CAN SEE THE LARGER EXPANSE OF THAT PINK AREA AMONGST THE ESI WOMEN RELATIVE TO MEN EXPERIENCE RELATIVE TO EARLY STAGE INVESTIGATORS AND NOTABLY WHEN YOU LOOK AT RACE ETHNICITY AND UNDER REPRESENTED GROUPS, AGAIN, THE ESIS TEND TO BE A MORE DIVERSE POOL. NOW WE CERTAINLY WISH THAT THAT BAR WAS A LOT WIDER, BUT INDEED WE ARE ALMOST DOUBLE-DIPPING IF YOU WILL BY ENSURING THAT WE ARE GETTING ENOUGH ESIS IN OUR FUNDING OPPORTUNITIES BECAUSE THAT IN ITSELF IS PROMOTING INCLUSION AND DIVERSITY JUST BY THE NATURE OF THE POOL. IN THAT REGARD, THIS AS YOU'RE AWARE IS PART OF THE TARGETING FOR THE NEXT GENERATION INITIATIVE THAT IS NIH WIDE AND WE ARE PLEASED AND, YEAH, A LITTLE BIT PROUD THAT THE NHLBI IS AT THE VAN GUARD OF THAT PROCESS AMONGST ALL THE ICS IN TERMS OF HITTING THOSE TARGETS, NIH WIDE. THERE YOU CAN SEE THE NUMBER OF APPLICANT SIZE THAT COME INTO NIH AND WE ARE NOT NUMBER ONE THERE BUT INDEED WHEN IT COMES TO FINALLY CONVERTING THOSE INTO AWARDEES THAT'S WHERE WE ARE NEAR THE TOP OF THE CLASS ACROSS ALL OUR SISTER ICS, SO AGAIN YOU SEE WHY THIS IS AN IMPORTANT ELEMENT OF OUR PRIORITY AND OUR COMMITMENT OF NURTURING THAT NEXT GENERATION AND THAT'S CRITICAL PARTICULARLY AS WE STRIVE TO, AGAIN, PRIME THAT PUMP WITH THE K AWARDS AND THEN PROVIDE A MEANS FOR THEM TO GET A FOOT HOLD AS RO1 INVESTIGATORS AND AGAIN WE ARE COMMITTED TO DOING THAT ACROSS OUR PORTFOLIO. THIS EXTENTS AS WELL TO OUR R35 PROGRAM IN WHICH, AGAIN, A DIFFERENT FLAVOR OF COMMITMENT TO INVESTIGATOR INITIATED DISCOVERY SCIENCE WHERE INVESTIGATORS ARE GIVEN THE OPPORTUNITY TO FOLLOW THEIR NOSE BY HAVING PREDICTABLE SUSTAINED FUNDING OF 600,000 PER YEAR FOR 7 YEARS AND THEN WE CREATED TWO FLAVORS IF YOU WILL OF THIS, BOTH FOR THE OUTSTANDING INVESTIGATORS TENDING TO BE MORE OF A SENIOR AS WELL AS THAT GROUP OF EMERGING INVESTIGATORS WE CALL THEM SORT OF MID CAREER AT THAT DIP IN THAT CURVE THAT WE TALKED ABOUT WHERE WE HOPE THAT THIS AWARD CAN BUILD RESILIENCE AND THEY ARE LIFERS AS NIH AWARDEES SO WE TRIED TO GIVE YOU THAT UPDATE OF OUR INVESTMENT PORTFOLIO, WHERE WE ARE PRIORITIZING AND WHY AND AGAIN AS PART OF THIS FEEDBACK LOOP WITH OUR ADVISORY COUNCIL SO YOU CAN APPRECIATE THE THINGS THAT YOU APPROVE AND THE METRICS OF SUCCESS THAT WE ARE TRACKING CLOSELY TOWARDS FULFILLING THOSE PRINCIPLES AND OBJECTIVES, THIS ALL WORKS OUT IN AN OVER ALL CONTEXT OF INVESTMENTS IN WHICH YOU CAN SEE THAT THE RESEARCH PROGRAM GRANTS ARE THE MAJOR PART OF OUR EXPENDITURES. WE WANTED TO KIND OF WALK YOU THROUGH THE OTHER LINES OF OUR BUDGET THAT ARE MORE MODEST, VERY MODEST RESEARCH CENTER AND OTHER RESEARCH, THOSE ARE OFTEN SORT OF PLATFORM PROGRAMS, YOU SEE THE TRAINING BUDGET, R AND D CONTRACTS TEND TO BE A LOT OF HOW WE FINANCE OUR COHORT STUDIES LIKE FRAMINGHAM AND JACKS ET CETERA AND THEN I THOUGHT AGAIN FOR TRANSPARENCY WE SHOULD SINCE WE ARE HIGHLIGHTING THE INTRAMURAL PROGRAM AND EVALUATING AND REVIEWING IT THAT YOU KNOW HOW MUCH OF THAT IS IN OUR PORTFOLIO, I SHOULD ALSO NOTE THAT 6% IS RELATIVELY MODEST, RELATIVE TO THE REST OF NIH, PROBABLY AVERAGES MORE ABOUT 10% FOR MOST INSTITUTES, SEVERAL CERTAINLY SOME OF THE BIGGER ONES THAT ARE OUR PEERS GO UP TO 12-15% OF THEIR BUDGET NCI BEING A NOTABLE ONE IN THAT REGARD IN TERMS OF THE SIZE OF THEIR INTRAMURAL AS WELL AS EXTRAMURAL PROGRAM AND SO WE KEEP OUR SCIENTIFIC DIRECTOR BEING VERY RESOURCEFUL IN STRETCHING THAT 6% TO SUCH OUTSTANDING OUTCOMES AND SO WE ARE ALL BEING ACCOUNTABLE STEWARDS HERE WITH THE RESOURCES AND YOU WILL SEE HOW THE EVALUATION PROCESS ENABLES THAT ACCOUNTABLE STEWARDSHIP. LET ME CLOSE WITH SOME OF THE SCIENTIFIC OPPORTUNITIES AND SET UP A LITTLE BIT OF THIS MORNING'S DIALOG THAT COMES FROM JUST THE EXCITEMENT OF SCIENTISTS, WHY WE DO WHAT WE DO. I THOUGHT THIS WAS REALLY COOL, THIS PICTURE OF THE BLACK HOLE AND I FOUND THAT FASCINATING AND I WAS EVEN MORE FASCINATED WHEN I HEARD THE STORY OF KATIE BOWMAN WHO IS A POST-OP AS PART OF THIS OBVIOUSLY HUGE MULTI NATIONAL TEAM APPARENTLY PLAYED A KEY ROLE IN WRITING SOME OF THE ALGORITHMS THAT MADE IT POSSIBLE FOR US TO SEE THESE PICTURES AND IT KIND OF BLOWS YOU AWAY LOOKING AT THIS PHENOMENON THAT EINSTEIN PREDICTED OVER A HUNDRED YEARS AGO, THIS CONCENTRATION OF GRAVITATIONAL FORCES THAT LITERALLY SUCKS THE LIGHT OUT OF THE UNIVERSE AND SO THE NOTION THAT SOMEONE WOULD START A POST DOCTOR PROJECT SORT OF SAY OKAY LET ME TAKE A PICTURE OF SOMETHING IN WHICH THE PHOTONS ARE BEING SUCKED AWAY FROM ME THAT IS 50 MILLION LIGHT YEARS AWAY AND IS EQUIVALENT TO RESOLUTION OF TAKING A PICTURE OF AN ORANGE ON THE SURFACE OF THE MOON AND DO THAT WHILE YOU'RE POST DOCTOR AND MAKE THAT WORK AND BY THE WAY YOU WILL NEED A TELESCOPE THE SIZE OF EARTH IN ORDER TO DO THAT SO TO FIGURE THAT OUT AND MAKE THAT HAPPEN STRINGING TOGETHER ALL THESE MICROSCOPES AROUND THE COUNTRY, SNAPPING THE PICTURE AT DIFFERENT ANGLES A CLASSIC SMART DATA PROBLEM AND FIGURING OUT HOW TO MODEL THAT, A REAL TOUR DE FORCE SO I THOUGHT THAT WAS REALLY COOL. THE NOTION YOU COULD TAKE AN EINSTEIN THEORY, A BUNCH OF MATH AND PHYSICISTS AND DATA SCIENTISTS COMPUTER SCIENTISTS ALL OVER THE COUNTRY ALL OVER THE WORLD CREATE A DATA RESOURCE THAT THEY CAN MINE AND PROBE AND COLLABORATE ON TO MAKE THE INVISIBLE VISIBLE PRETTY COOL. IT THEN CAME TO ME AS TO WHY WE CAN'T DO THAT. WE JUST SHOWED YOU A NUMBER OF EXAMPLES OF SOME INCREDIBLE WOMEN WHO IN INNOVATIVE WAYS TO SEE HOW A CELL PROBES ITS SPACE AND HAS MOLECULES THAT ATTACH TO THE EXTRA CELLULAR SPACE AND SENSE IT AND MOVE AND CREATE SHAPE SHIFTING AT A MICRO SCALES BEYOND SUPER RESOLUTION AND ADRIAN'S WORK THAT TOOK WHAT LOOKS LIKE A NORMAL MRI FROM A PATIENT AND SEES ALL THIS INCREDIBLE EARLY STAGES OF PATHOLOGY. WE SHOULD BE ABLE TO DO THAT AND AS NIH WE SHOULD BE CREATING THOSE SCIENTIFIC PLATFORMS THAT ENABLE THAT SAME SORT OF THING TO HAPPEN AND INDEED I THINK THAT'S ONE OF THE OPPORTUNITIES THAT WE HAVE MOVING FORWARD, HOW CAN WE TAKE THESE APPROACHES OF TEAM SCIENCE TO SOLVE TOUGH PROBLEMS? I THINK THAT IS GOING TO BE ONE OF THOSE SPACES WHEN WE TAKE ON THINGS LIKE HEALTH DISPARITIES, VEXING PROBLEMS, COMPLEX PROBLEMS, MULTI LEVEL PROBLEMS, ONES THAT TAKE MULTI DISCIPLINE DISCIPLINARY MULTI STAKEHOLDER ENGAGEMENT TO TURN AROUND. WE LOOK AT THIS CURVE THAT WAS RAISED IN THE APPROPRIATIONS HEARING WHERE ALL AROUND THE WORLD IN DEVELOPED COUNTRIES THE MATERNAL MORTALITY IS GOING DOWN, IT'S IN SINGLE DIGITS ACTUALLY IT'S SHAMEFUL, EMBARRASSMENT IN THIS COUNTRY WE ARE STILL IN THE DOUBLE DIGITS AND, IN FACT, IT MIGHT EVEN BE GOING UP, CERTAINLY IN CERTAIN PARTS OF THE COUNTRY. THIS IS SOMETHING THAT WE SHOULD BE ABLE TO SOLVE AND IT COMES TO THIS COMMUNITY BECAUSE YOU LOOK AT THE PRIMARY DRIVERS OF MATERNAL MORBIDITY AND PROBLEMS WITH CARDIOVASCULAR DISEASE AND SLEEP DISORDER AND THROMBOSIS AND THESE ARE THINGS WE OUGHT TO BE ADDRESSING AS THIS DEVASTATES CERTAIN COMMUNITIES AFRICAN/AMERICAN WOMEN ARE TWOFOLD HIGH RISK OF MATERNAL MORTALITY, CERTAIN GEOGRAPHIC AREAS TWO TO FIVE FOLD MORE AND SO THIS IS SOMETHING THAT WE SHOULD HAVE AS A TOP OF MIND CERTAINLY HIGH PRIORITY IN ADDRESSING AND THAT IT WILL TAKE A MULTI PRONGED TEAM SCIENCE APPROACH TO ADDRESSING THIS FUNDAMENTAL PROBLEM IN WOMEN'S HEALTH AND I'D LIKE FOR THIS INSTITUTE TO BE AT THE FOREFRONT OF SOLUTION DISCOVERY. WE DO HAVE ELEMENTS IN OUR PORTFOLIO THAT I'D LIKE US TO BUILD ON INDEED ADDRESSING THE ISSUES OF HYPERTENSION IN PREGNANCY AND CERTAINLY THE CHAP STUDY IS AN ELEMENT OF THAT FURTHER DEFINING THE NATURAL HISTORY OF THE STRESSORS OF PREGNANCY AND HOW THAT PROMOTES CARDIOVASCULAR PROTOBATIONS FOR MOMS TO BE AND OTHER STUDIES BUT ALSO TO INTERVENE AND MAKE A DIFFERENCE AND AGAIN WE ARE INTRIGUED BY THE FINDING OF INCREASED SLEEP DISORDER BREATHING IN THE CONTEXT OF PREGNANCY AND THE OPPORTUNITY TO DO INTERVENTIONS TO ADDRESS THAT IN WAYS THAT IT MAY IMPROVE OUTCOMES FOR BOTH MOM AND THE BABY AND SO I THINK THIS IS A KEY PART OF THE AGENDA THAT WE HOPE TO BRING TO YOU AS PART OF OUR ADVISORY COUNCIL. SIMILARLY ANOTHER OPPORTUNITY FOR MULTI DISCIPLINARY, MULTI LEVEL RESEARCH COMES IN THE COMMUNAL SPACE THAT WE HOPE TO CREATE IN DISCOVERY SCIENCE AND THAT IS WHAT YOU WILL HEAR A LITTLE BIT LATER THIS MORNING OF THE DATA RESOURCE THAT IS BEING GENERATED AS WE TRANSFORM FROM A DOWNLOAD PARADIGM TO ONE WHERE SCIENTISTS GO TO THE DATA, ARE ABLE TO SHARE COMMUNAL SPACE AND ANALYZE WITH TOOLS AND TECHNOLOGIES TO SOLVE COMPLEX PROBLEMS MORE COLLECTIVELY, PERHAPS THIS IS OUR ABILITY TO AGAIN BE LIKE THAT BLACK HOLE DISCOVERY SORT OF PROJECT WHERE WE CAN BRING ALL OF OUR DATA TOGETHER INTO THESE COMMUNAL SPACES THAT CAN TAKE THINGS TO SCALE AND SCOPE THAT WE COULDN'T HAVE DONE IN THE DOWNLOAD ERA SO WE LOOK FORWARD TO THE DIALOG AND WE LOOK FORWARD TO YOUR ENGAGING AND OF THE SCIENTISTS THAT HAVE COME DOWN HERE AND INVOLVED IN DATA STAGE ALONG WITH JOHN KALTMAN THE REST OF THE PROGRAM STAFF TEAM THAT HAS DONE AN INCREDIBLE TEAM SHEPHERDING IT THROUGH AND TRANSFORM THE WAY WE ACCESS LARGE DATA SETS, MAKE THEM FAIR AND INTER OPERABLE REUSABLE AND PROVIDE THE USER COMMUNITY WITH A COMMUNAL SPACE FOR MINING, ANALYSIS AND INDEED INVITE IN OUR MACHINE FRIENDS WITH ARTIFICIAL INTELLIGENCE THAT WE HOPE WILL ENABLE US TO SEE PATTERNS THAT WE WERE NOT ABLE TO SEE BEFORE. INDEED PATTERNS OF PHOTONS MOVING 50 MILLION LIGHT YEARS CREATING IMAGES WE COULD NOT SEE BEFORE, INDEED THE EARLY FORMATIVE STAGES OF THAT ARE STARTING TO HAPPEN, INDEED SOME OF THAT IS STARTING TO HAPPEN EVEN WITHIN DATA STAGE CREATING A RESOURCE THAT SORT OF SAYS WHOA THE NHLBI FOR THE LAST 20 YEARS I DON'T THINK ANYBODY IN THIS ROOM, I HAVE TO ASK MY STAFF, HOW MANY CHEST CTS DO WE HAVE THAT WE FUNDED? ANYBODY? [ LAUGHTER ] THE PRECISE ANSWER I GOT WAS A LOT, OKAY? AND WHERE ARE THEY? WHERE IS THAT DATA? SO WE SPENT A LOT OF TAXPAYER MONEY DOING THOSE SCANS AND I DON'T KNOW THAT WE KNOW HOW MANY OF THEM WE ARE, WHERE THE DATA IS AND WHETHER ANYBODY COULD PROBE IT EFFICIENTLY AND EFFECTIVELY. THAT MIGHT BE PART OF THE BEGINNING OF UNDERSTANDING THAT CURVE WE STARTED OFF WITH OF THAT INEXURABLE DECLINE IN LUNG FUNCTION IN RESPONSE TO A TOXIC EXPOSURE AND I BELIEVE IF WE ARE GOING TO GET TO THAT, IF WE ARE GOING TO MAKE THE INVISIBLE VISIBLE WE ARE GOING TO HAVE TO START TO CREATE THESE SORT OF DATA RESOURCES AND ANALYTIC TOOLS TO MAKE THAT HAPPEN AND THAT'S MY CHALLENGE AND CHARGE TO THE DATA STAGE GROUP AS PART OF REALIZING THE PROMISE OF PRECISION MEDICINE, I BELIEVE IT WILL BE YEAH, I'M STILL DANCING, BE PART OF THE PROMISE OF TURNING MEDICINE INTO AN INFORMATION SCIENCE AND SO JUST TO CONCLUDE BEFORE I UNPLUG US AGAIN THIS IS WHERE WE HOPE TO CREATE THIS PARADIGM FOR TRANSLATING DISCOVERY SCIENCE INTO PUBLIC HEALTH IMPACT AS PART OF OUR MISSION AND IT BECOMES CREATING THIS DIGITAL COMMUNITY IN WHICH I HOPE THERE WILL BE THIS BRIGHT YOUNG FEMALE POST DOC AND MAYBE WE CAN INDI E DICE TWICE HER TO WORK ON SOME OF OUR PORTFOLIO, WOULDN'T THAT BE COOL? AND HOPEFULLY TRANSFORM HOW WE THINK ABOUT HEART, LUNG, BLOOD AND SLEEP DISORDERS AND WITH THAT BEFORE I UNPLUG MYSELF AGAIN THANKS A LOT. [ APPLAUSE ] WOULD ANYBODY LIKE TO ASK A QUESTION OR HAVE A COMMENT ABOUT THE REMARKS THAT YOU JUST HEARD FROM DR. GIBBONS? DONNA? GARY I REALLY APPLAUD WHAT YOU HAVE DONE FOR EARLY STAGE INVESTIGATORS AND THE APPLAUD OF WOMEN PROGRESSING THROUGH CONTINUED FUNDING. YOU KNOW HAVE YOU CONSIDERED OR WOULD IT BE ETHICAL TO HAVE A PAY LINE THAT IS DIFFERENT FOR WOMEN? LIKE YOU HAVE DONE FOR EARLY STAGE INVESTIGATORS? >> THOUGH IT'S A GREAT POINT, I THINK WHAT WE TRIED TO INDICATE WAS THE AWARD RATE FOR MEN VERSUS WOMEN IS NOT TRAUMATICALLY DIFFERENT SO, AGAIN, I'D LIKE OUR TEAM TO DIG A LITTLE BIT MORE ON THAT. I SUSPECT THAT IF YOU JUST LIKE YOU HAVE LOOKED AT YOUR COUNCIL BOOK FISH THROUGH THE SCORES AND THEN THE FINAL FUNDING DECISIONS THAT WILL BE MADE IN THIS COUNCIL AND COMPARE MEN AND WOMEN, I WOULD TEND TO BET YOU WOULD FIND IT PRETTY CLOSE. THAT SAID CERTAINLY WHEN WE LOOK AT WE WILL CALL SELECTIVE PAY AND LOOK AT PROGRAMATIC BALANCE ABOVE THE PAY LINE I THINK IT'S LEGITIMATE FOR THE INSTITUTE WITH THE ADVICE OF COUNCIL TO LOOK AT OUR OVER ALL BALANCE THAT INVOLVES INSTITUTE PRIORITIES, NOT TOTALLY DRIVEN BY A STUDY SECTION PRIORITY SCORE PAY LINE THAT BALANCE MIGHT RELATE FOR SOME PROGRAMS IN CARDIOVASCULAR RELATIVE TO LUNG RELATIVE TO BLOOD BUT CERTAINLY THE WORKFORCE CONSIDERATION IS ONE AND SO I THINK THAT IS NOT AN UNREASONABLE THING AS DIVERSITY AND INCLUSION AS ONE OF THOSE OTHER ELEMENTS OF CRITERIA THAT WE CAN PUT IN PLACE. I THINK ALL RIGHT I DON'T KNOW WHAT HAPPENED THERE. [ LAUGHTER ] SORRY. MY APOLOGIES. AND THAT ONE WAS -- THAT ONE WASN'T MY FAULT. I WASN'T OVER THERE FOR THAT ONE. >> SO GARY COULD I. >> ACTUALLY LET ME JUST ADD ONE OTHER THING TO YOUR IMPORTANT QUESTION. SO I DO THINK IT IS VERY LEGITIMATE FIRST TO THINK ABOUT WHAT MIGHT BE DRIVERS THAT COULD BE SEX SPECIFIC THAT MIGHT RELATE TO ATTRITION IN K TO OUR TRANSITION OR THAT EARLY FALL OUT AND SO CERTAINLY AS A FATHER O THREE CHILDREN, YOU KNOW, I RECOGNIZE THAT CHILD BIRTH FOR WOMEN DURING THAT CRITICAL PERIOD IS A MAJOR CHALLENGE AND I THINK THE INSTITUTE NIH CAN BE LOOKING AT OUR POLICIES AND PRACTICES RELATED TO OUR FLEXIBILITY AND OUR FUNDING RELATED TO THAT IMPORTANT PERIOD. WE OBVIOUSLY LIKE TO DO THAT IN CONCERT WITH INSTITUTIONS AS WELL TO BE SURE THAT DURING THAT PERIOD OF VULNERABILITY IF YOU WILL AND LIFE CHALLENGES THAT AGAIN WE ARE DOING THE THINGS THAT WILL SUSTAIN THE RESILIENCE OF THE WOMEN WHO ARE AT THAT CRITICAL STAGE OF CAREER DEVELOPMENT. >> AND IT MAYBE WORTHWHILE TO THINK HOW COULD YOU CREATE NEW PROGRAMS OR NEW TYPES OF GRANT APPLICATIONS THAT WOULD ALLOW WOMEN TO MAKE THAT TRANSITION SO THAT YOU HAVE A SPECIAL PROGRAM JUST FOR WOMEN THAT ALLOWS THEM TO STAY IN THAT PIPELINE AFTER THAT BIG DROP OFF PHASE AFTER THE K-99 OR RO. >> POINT WELL TAKEN AND I'LL SAY WE ARE IN SOME EARLY STAGES OF BRAINSTORMING IN THAT SPACE. STAY TUNED. >> ANYBODY ELSE? YES DR. WENZELL. >> I THOUGHT A LOT OF ENCOURAGING STATISTICS AND SOME NOT ENCOURAGING STATISTICS AND I THINK THE ONE THAT DISCOURAGED ME THE MOST WAS THE ONE FROM I THINK NIGMS WHERE THEY LOOKED AT THE NUMBER OF PH.D.S AWARDED TO WOMEN AND THEN THE NUMBER OF ASSISTANT PROFESSOR FACULTY POSITION WHERE THERE WAS A HUGE DROP OFF AND I GUESS MY QUESTION IS WHAT DO WE KNOW ABOUT THE REASONS FOR THAT? IS IT BECAUSE PEOPLE ARE DISCURRENTED? COURAGED AND SAY IT'S TOO TOUGH AND GOING IN INDUSTRY WHERE DO ALL THE WOMEN WITH THE PH.D.S GO? >> I DEFER TO MY COLLEAGUES HERE AND TO YOU AROUND THE TABLE, I SUSPECT YOU GUYS ARE GREATER INSIGHTS INTO THAT, YOU RAISE A COUPLE GOOD POSTULATES THERE HEADING OUT OF POST DOC MAYBE FIVE YEARS OF POST DOC IN A CRITICAL TIME OF YOUR LIFE LATE 20s, 30s AND YOU'RE TRYING TO FIGURE OUT WHAT DO YOU WANT TO DO FOR THE NEXT 40 YEARS THE NOTION OF CHASING RO1S MAY NOT BE THE MOST SECURE PATH TO TAKE, SO, YOU KNOW, AND CLEARLY THAT MAY BE PLAYING A ROLE. AGAIN, I WOULD BE OPEN TO OTHER THOUGHTS. I THINK IT STILL TRANSLATES BACK TO ME AS TO ACADEMIA WHO YOU'RE HIRING SO ARE THEY DISCOURAGED OR ARE WE DISCOURAGING THEM? AND THEN, TWO, ONCE THEY ARE IN ARE WE SUPPORTING THEM ENOUGH ONCE THEY DO HAVE THAT JOB? AND I THINK THAT'S A COLLECTIVE RESPONSIBLE FOR US TO FIGURE OUT OUT. >> WE CAN HAVE ONE MORE QUESTION, DR. GRAHAM AND THEN I'M GOING TO HAVE TO KEEP US MOVING FORWARD. >> SO I APPLAUD YOU FOR THE FACT THAT SUCH A LARGE AMOUNT OF YOUR TIME WAS ALLOTTED TO THE DISCUSSION AROUND DIVERSITY AND I THINK THAT IS REPRESENTATIVE OF YOUR LEADERSHIP IN GENERAL. MY QUESTION MAY BE FOR THE BROADER NIH AS OPPOSED TO NHLBI THE STATISTICS ARE SOMEWHAT MISLEADING BECAUSE WE FACE A CRISIS WITH AFRICAN/AMERICAN MEN AND MEDICINE IN GENERAL A GROUP OF US STARTED PUSHING IOM AND PUTTING A COMMITTEE THERE TO TRY TO PUSH HEALTHCARE IN GENERAL TO DEAL WITH THAT CRISIS. DO YOU GET A SENSE AND YOU KNOW AS WELL AS MANY IN THE ROOM KNOW SINCE THE 1970s NUMBERS ARE FLAT IF NOT WORSE COMPARED TO WHERE WE HAD PRECIVIL RIGHTS IT'S AMAZING TERRIBLE KIND OF IMPLICATIONS AND SOME OF THAT MAY BE THINGS THAT GET WAY BEFORE WE GET TO THE STAGE OF ACADEMIC MEDICINE, ARE YOU AWARE OF TRENDS IN NIH EFFORTS THAT ARE TARGETING WHAT I THINK IS YOU KNOW PERPETUATION OF CHALLENGES IN SOCIETY AND OTHERWISE AND IF NOT WHAT IS THE BEST WAY TO START THINKING ABOUT THAT? >> YOU KNOW YOU ARE RAISING A GREAT POINT GARTH AND AS YOU SAY THERE ARE DIFFER ELEMENTS OF DISPARITIES THAT PROBABLY WASN'T BROUGHT OUT AS WELL PARTICULARLY IN THIS PARTICULAR PRESENTATION AND THAT CURVE WAS NOT INDICATIVE OF AFRICAN/AMERICAN MEN AS YOU POINT OUT. I MUST ADMIT THAT THERE ARE INITIATIVES UNDERWAY FOR EXAMPLE BUILD AND THE NATIONAL MENTOR AND RESEARCH NETWORK, AGAIN, SOME OF THE ELEMENTS THAT DR. HANNA VALENTINE HAS PUT FORWARD THAT ARE IN THAT SPACE THOUGH YOU RAISE AN EVEN MORE DISTINCTIVE POINT RELATED TO AFRICAN/AMERICAN MALES IN PARTICULAR. I MUST CONFESS I'M NOT AWARE OF SYSTEMIC APPROACH TO ADDRESSING THAT SPECIFIC SUB GROUP THAT AS YOU POINT OUT PROBABLY IS LAGGING AMONGST THE MOST PERHAPS MAYBE NOT MUCH FURTHER AHEAD THAN NATIVE AMERICANS FOR EXAMPLE IN THIS COUNTRY, SO THAT IS A TOUGH ONE AND AS YOU POINT OUT WE SUSPECT THAT IT STARTS EARLIER THAN WHEN YOU GET YOUR DOCTOR DEGREE AND NIH TENDS NOT TO BE AS EFFECTIVE AS GOING AT THAT SORT OF ROOT CAUSE FROM K-12 WHERE WE HAVE A WHOLE DEPARTMENT OF EDUCATION SO THAT IS A TOUGH ONE. IF YOU HAVE IDEAS WE CERTAINLY WOULD BE OPEN TO CONTEMPLATE HOW TO ADDRESS THAT. >> THANK YOU ALL VERY MUCH FOR YOUR COMMENTS AND YOUR INTEREST IN DR. GIBBONS PRESENTATION, I THINK IT'S APPRECIATE TO NOTE THAT DR. MONICA CRAFT RECENTLY RECEIVED AWARD FOR MENTORING WOMEN AT THE ATS MEETING THE ELIZABETH AWARD SO KUDOS FOR THAT HONOR. [ APPLAUSE ] AND WITH THAT WE ARE GOING TO SEGUE INTO OUR NEXT PRESENTATION, JOHN KALTMAN IS THE CHIEF OF HEART DEVELOPMENT AND STRUCTURAL DISEASES BRANCH AND THE DIVISION OF CARDIOVASCULAR SCIENCE AT THE NATIONAL HEART LUNG AND BLOOD INSTITUTE IN ADDITION TO THAT HAT HE IS ALSO THE PROGRAM DIRECTOR OF THE DATA STAGE PROGRAM AND HE AND A TEAM ARE GOING TO TELL US A LOT MORE ABOUT THAT. I THINK YOU WILL HEAR SOME VERY EXCITEMENTING DEVELOPMENTS, JOHN. >> THANK YOU VERY MUCH. SO ACTUALLY INGRID IS GOING TO PRESENT THIS TALK BUT I'M JUST GOING TO GIVE SOME VERY BRIEF INTRODUCTORY REMARKS AND TRY TO PROVIDE A LITTLE BIT OF CONTEXT FOR WHY WE ARE DEVELOPING THE DATA STAGE. SO THIS SLIDESHOWS THE GROWTH RATE OF GENOME SEQUENCED BY THE TOP MED PROGRAM OVER THE LAST THREE YEARS AND THE MEMORY CAPACITY REQUIRED TO STORE THAT DATA. WE ARE CURRENTLY AT OVER 3PETIBYTES OF DATA OUR ABILITY TO GENERATE DATA IS CLEARLY OUT STRIPPING OUR ABILITY TO EFFICIENTLY AND EFFECTIVELY MANAGE AND STORE THAT DATA. IN ADDITION THIS DATA IS HIGHLY COMPLEX REQUIRING LARGE MULTI DISCIPLINARY MULTI GEOGRAPHIC TEAMS OF INVESTIGATORS TO OPERATE ON IT. FINALLY AS PART OF OUR PUBLIC MISSION NHLBI'S GOAL SO TO MAKE SURE THE DATA IS BROADLY SHARED ACROSS POPULATION EXPERTISE AND EXPERIENCE SO WE CAN HARVEST THE GREATEST AMOUNT OF KNOWLEDGE FROM THIS AND DATA STAGE WAS IN PART BORN FROM THE NEED TO MANAGE, STORE, SHARE AND DEMOCRATIZE NHLBI LARGE DATA RESOURCES. SO DR. INGRID IS THE CHAIR OF THE DATA STAGE STEERING COMMITTEE AND SHE WILL SHARE WITH YOU WHAT THE DATA STAGE IS AND HOW IT'S GOING DEVELOPED, THE DOCTOR IS A RENOWN GENETIC EPIDEMIOLOGIST HIGHLY INVOLVED IN VARIOUS NHLBI FUNDED EFFORTS INCLUDING THE CHARGE CONSORTIUM AND TOP MED AS WELL AS OTHERS. BEFORE INGRID TAKES THE PODIUM I WANT TO ACKNOWLEDGE THE MANY, MANY PEOPLE WHO HAVE BEEN INVOLVED IN THE DATA STAGE PROGRAM ONLY SOME OF WHOM ARE LISTED ON THIS SLIDE, MANY OF WHOM ARE ACTUALLY IN THE AUDIENCE TODAY AND WILL HELP WITH QUESTIONS FROM THE COUNCIL. THESE FOLKS HAVE ENTHUSIASTICALLY EMBRACED THE CHALLENGE OF BUILDING THE DATA STAGE AND I HOPE YOU ENJOY HEARING ABOUT THEIR EFFORTS, THANK YOU, INGRID. >> GOOD MORNING EVERYONE WE ARE SO DELIGHTED TO BE HERE TODAY TO BE ABLE TO SHARE WITH YOU SOME OF THE PROGRESS WE HAVE MADE IN THE DATA STAGE ACTIVITY OVER THE LAST YEAR OR YEAR AND A HALF OR SO. LIKE JOHN SAID I'M THE CHAIR OF THE STEERING COMMITTEE BUT THE WORK I'M PRESENTING HERE IS REALLY ATTRIBUTABLE TO A VERY TALENTED DEVELOPERS AND COLLABORATORS WHO PUT A LOT OF WORK INTO BRINGING IT TO THIS STAGE THAT I'M GOING TO SHOW YOU TODAY. SO THEY WILL BE HERE FOR AFTER THE TALK FOR ANY KIND OF DISCUSSION AND QUESTIONS THAT YOU MAY HAVE. SO WE ARE GOING TO START BY DESCRIBING WHAT IS DATA STAGE AND TO TRY TO GIVE YOU A SENSE OR A NOTION OF WHY WE BELIEVE THAT THIS PLATFORM IS GOING TO REALLY REVOLUTIONIZE POPULATION SCIENCE RESEARCH IN THE ERA OF BIG DATA SPECIFICALLY WE ARE GOING TO DO THIS BY ILLUSTRATING A USE CASE AND WE ARE GOING TO SHOW HOW IT SUPPORTS COLLABORATION OF THESE DIVERSE RESEARCH TEAMS AND ALSO THE COMPUTATIONAL SOLUTIONS WE ARE OFFERING IN ORDER TO EXPEDITE THE WORK A HAND. THE TOOLS FOR RESEARCH THAT WE ARE BUILDING CAN BE ACTUALLY CLASSIFIED INTO THESE FOUR MAJOR RUBRICS WHICH FALL UNDER DATA IDENTIFICATION AND ACCESS. THE CONDUCT OF DATA SCIENCE IN THE CLOUD, USE OF THESE NEW MACHINE LEARNING TOOLS AND SO FORTH. HAVING REPRODUCIBLE ANALYTICAL TOOLS AND WORK FLOWS SHARED WITH COLLABORATIONS AND COLLABORATION SUPPORT TO ALLOW EVERYONE IN THE SANDBOX SO THAT THEY CAN ALL INTERACT AND BE CREATIVE. THE INITIAL IS TO DEVELOP AND CREATE AN INTEGRATED ADVANCED INFRASTRUCTURE THAT WOULD HAVE LEADING EDGE TOOLS AND FAIR DATA TO SUPPORT THE NHLBI RESEARCH COMMUNITY. NOW FAIR IS AN ACRONYM YOU MAY NOT BE FAMILIAR WITH AND STANDS FOR FINDABLE ACCESSIBLE INTEROPERABLE AND REPRODUCIBLE AND THESE ARE FOUR KEY WORDS THAT ARE EXTREMELY IMPORTANT QUALITIES FOR THE ENVIRONMENT THAT WE ARE HAVING THAT WILL HELP US TO ACHIEVE THESE OBJECTIVES. I WANT TO MAKE CLEAR OUR GOAL IS TO CREATE THE CYBER INFRASTRUCTURE SUPPORT THIS WORK NOT TO DO THE ACTUAL WORK AND SO WE ARE PRODUCING THE ENVIRONMENT, THE PLATFORMS AND THE TOOLS AND SO FORTH SO AS TO EMPOWER THE PEOPLE THAT ARE ACTUALLY THE SUBJECT MATTER EXPERTS AND OUR VISION FOR THE FUTURE IS THAT THESE INDIVIDUALS WILL BECOME PART OF THE ECO SYSTEM IN THE FUTURE, CONTRIBUTING NEW DATA SETS, CONTRIBUTING NEW ANALYTICAL STRATEGIES AND FORMATIC PIPELINES AND SO FORTH SO THE DATA STAGE BECOMES REALLY A LIVING ECO SYSTEM THAT IS GOING TO LIVE THROUGH THE CONTRIBUTIONS OF THE PEOPLE THAT ARE ACTUALLY PUSHING THE SCIENCE FORWARD. THIS IS SORT OF A CARTOON OF THE BASIC STRUCTURE OF WHAT WE ARE DOING, WE ALWAYS START WITH THE RESEARCH COMMUNITY AND THEIR NEEDS. THEY ARE TRYING TO OPERATE ON THESE AS SETS THAT ARE AVAILABLE, THESE ARE THE HIGH VALUE DATA SETS THAT HAVE BEEN COLLECTED FOR YEARS THROUGH NHLBI FUNDING, THEY INVOLVE CLINICAL EPIDEMIOLOGICAL DATA, GENOMIC DATA AND OTHER ALMIC DATA AND ALSO THE ASSETS OF VARIOUS IMAGES AND OTHER KINDS OF ANCILLARY DATA THAT COULD BE LEVERAGED IN ORDER TO MOVE THE RESEARCH AGENDA FORWARD. AND OUR PROPOSITION IS TO HOUSE ALL OF THOSE ASSETS IN A CLOUD ENVIRONMENT SO THAT THEY ARE CENTRALLY LOCATED AND AVAILABLE TO THE RESEARCH COMMUNITY BUT ALSO TO PROVIDE PACKAGED WORK FLOWS FOR COMMONLY EXECUTED TASKS, A GOOD WELL EQUIPPED TOOL BOX, STRATEGIES AND THE ABILITY TO SUPPORT COLLABORATIVE INTEGRATE TEAMS AND WILL ACCELERATE THE PACE OF DISCOVERY AND WITH THE NOVEL BIOLOGICAL INSIGHTS THIS CAN GIVE US THE OPPORTUNITY TO THINK ABOUT NOVEL DIAGNOSTIC AND THERAPEUTIC OPTIONS AND SO THIS IS ALL IN THE BOTTOM LINE TOWARDS BETTER PATIENT OUTCOMES. THIS IS ALSO A CARTOON OF THE BASIC ARCHITECTURE OF THE DATA STAGE PLATFORM. AGAIN WE START WITH THE USER COMMUNITY AND WE ARE LOOKING TO REALLY COMPLETELY REVAMP THE DATA ACCESS PARADIGM AND WHAT WE ARE PROPOSING HERE IS SORT OF A PASSPORT SYSTEM WHERE AN INDIVIDUAL WILL BE ABLE TO COME IN, BE AUTHENTICATED AS TO THEIR CREDENTIALS AND ALSO IT WOULD HAVE SOME INFORMATION ABOUT WHAT DATA SETS THEY'RE AUTHORIZED TO SEE GIVEN THEIR RESEARCH USE STATEMENT. SO THE RESEARCH USE STATEMENT HAS TO BE COMPATIBLE WITH THE INFORMED CONSENTS OF THE PATIENTS SO ALL OF THIS, MUCH OF THIS CAN BE ACTUALLY AUTOMATED TO DECREASE THE LAG TIME IN OBTAINING THE PERMISSIONS OF ACCESSING THE DATA AND MOVING FORWARD WITH THE PROJECT. IN OUR INITIAL INCARNATION HERE THE SCIENTIFIC BIG DATA THAT WE ARE FOCUSING ON IS ACTUALLY THE TOP MED DATA SET WHICH IS NOT A SMALL DATA SET, IT'S OVER 150,000 INDIVIDUALS ALL OF WHOM I BELIEVE HAVE BEEN SEQUENCED AT THIS STAGE, MANY OF WHOM HAVE OTHER ALMIC DATA AND THERE IS VAST CLINICAL AND EPIDEMIOLOGICAL DATA ON MANY OF THE SUBJECTS. IN ADDITION WE ALSO HAVE AS PART OF THE MISSION IS TO PROVIDE FACILITY TO DEAL WITH THE IMAGES WHICH DR. GIBBONS MENTIONED THIS IS A TREASURER TROVE OF INFORMATION THAT HAS BEEN UNDER UTILIZED UP TO NOW PARTIALLY BECAUSE OF THE COMPUTATION CHALLENGES INVOLVED SO ONCE WE GET THE SCIENTIFIC BIG DATA TOGETHER WE WILL NOT STOP WITH THOSE. I JUST WANT TO MENTION THAT OUR PLANS INCLUDE IN THE FUTURE BRINGING IN AND BEING INTER OPERABLE WITH OTHER LARGE DATA SETS THAT ARE COMING ON BOARD INCLUDING ALL OF US, THE SICKLE CELL DISEASE CONSORTIUM, MILLION VETERANS AND A IN, VIL WHICH IS THE PLATFORM THAT IS BEING CRUMBLED BY NHGRI NOW AND EVENTUALLY ALL COMPONENTS WILL SPEAK TO ONE ANOTHER. WE WILL ALSO PROVIDE THE TOOLS AND APPLICATIONS THAT WILL BE NEEDED IN ORDER TO DEAL WITH THESE DATA SETS SO THE IDEA IS THAT THESE RESEARCHERS WOULD COME IN, THEY WOULD BE AUTHENTIC AND AUTHORIZE AND QUERY ALL THE DATA ASSETS THAT ARE NEEDED IN ORDER TO ANSWER THEIR SCIENTIFIC QUESTION, THOSE DATA ASSETS AND TOOLS WOULD BE DEPOSITED INTO A WORKSPACE AND THEY COULD ANALYZE AND PUBLISH THEIR DATA RIGHT THERE IN THE CLOUD. IT'S SORT OF FITTING THAT ON THE 50TH ANNIVERSARY OF THE LUNG DIVISION WE CHOSE TO KIND OF ILLUSTRATE WHAT WE ARE DOING THROUGH A USE CASE THAT COMES FROM COPD GENE THEY OF COURSE HAVE A LARGE NUMBER OF IMAGES, THERE IS OVER 10,000 INDIVIDUALS IN THE STUDY AND EACH INDIVIDUAL HAS MULTIPLE IMAGES AND SO THIS WAS THE USER NARRATIVE THAT THEY GAVE US, THEY CAME AND TOLD US WE WANT TO BE ABLE TO ANALYZE THOSE DATA, USE MACHINE LEARNING TOOLS AND COMBINE IT WITH OUR CLINICAL DATA IN ORDER TO GET AT THIS IDEA OF DISEASE HETEROGENAITY. SO CHRONIC OBSTRUCTIVE PULMONARY DISEASE AS I'M SURE MANY PEOPLE IN THE ROOM REALIZE IS EXTREMELY IMPORTANT, IT'S THE THIRD LEADING CAUSE OF DEATH IN THE UNITED STATES. IT'S CLINICAL FEATURES INCLUDE BRONCHITIS AND EMPHYSEMA AND VISUAL ON CT SCANS UP TO NOW WE LACKED A DEEP UNDERSTANDING OF THE BIOLOGICAL UNDER PINS OF DISEASE HETEROGENITY AND IMAGING THE CT WE CAN DEVELOP A SENSE FOR MEASURING NEW FEATURES THAT COULD HELP PARS SOME OF THE HETEROGENITY SO WHAT WE WANT TO DO IS EMPOWER THE INVESTIGATORS IN ORDER TO INTERACT WITH THESE IMAGES TO ANALYZE THEM USING SOME OF THE BIG DATA TOOLS THE MACHINE LEARNING KINDS OF ALGORITHMS TO SEE IF IT CAN HELP CLASSIFICATION OF INDIVIDUALS THAT HAVE MORE HOMEOGENOUS DISEASE PROGRESS AND GENE OLD GENOLOGY AND IT HAS THERE PUT C THERAPEUTICS IF WE UNDERSTAND THE HETEROGENITY AND AS WE LOOK AT THE COMPLEX BIOMED CALL TRAITS IT REALLY REQUIRES A VILLAGE OF EXPERTISE SO WE HAVE TO BRING INDIVIDUALS THAT HAVE ALL SORTS OF DIFFERENT TALENTS TO THE TABLE IN ORDER TO HAVE THE COMPREHENSIVE WHOLISTIC APPROACH IN ORDER TO MOVE THIS SCIENCE FORWARD SO I'M GOING TO INTRODUCE OUR THREE ADVITARS HERE BASED ON COPD GENE INVESTIGATORS BUT JUST AS AVITARS WE HAVE A CLINICIAN AND RADIOLOGIST WHOSE CONCERN IS THE CLINICAL MANAGEMENT OF THESE PATIENTS AND HAVE ANOTHER ONE WHO IS A COMPUTER SCIENTIST WHO IS LOOKING TO INNOVATE BY APPLYING THE MACHINE LEARNING KINDS OF STRATEGIES TO IMAGE DATA AND THEN WE HAVE A PULMONOLOGIST BIOLOGIST AND GENETIC EPIDEMIOLOGIST WHO IS INTERESTED IN LOOKING AT THE GENETIC ARCHITECTURE OF THE UNDER LYING TRAITS FOR THE INSIGHTS THAT MIGHT PROVIDE FOR THERAPEUTIC AND CLINICAL MANAGEMENT AND ALL OF THESE INDIVIDUALS HAVE TO ACCESS THE DATA, HAVE TO BE ABLE TO OPERATE ON THE DATA, SHARE THE RESULTS AND TALK IN ORDER TO HAVE THAT KIND OF VIBRANT SCIENTIFIC ENVIRONMENT IN WHICH REALLY THE NEW DISCOVERIES CAN OCCUR. THE FIVE MAJOR WAYS WHICH THE DATA STAGE PROPOSES TO MEET THE CHALLENGES OF THIS SORT OF COLLABORATION FIRST OF ALL JUST VERY FUNDAMENTALLY THEY NEED OB EMPOWERED TO DEAL WITH THEIR BIG DATA AND COMPUTATION THE FIRST CHALLENGE THE INVESTIGATORS ASKED US CAN YOU MOVE THE DATA INTO A CLOUD BECAUSE THEY DIDN'T EVEN HAVE THE TOOLS TO DO THAT SO EVEN JUST GIVING THEM A CLOUTED ENVIRONMENT IN WHICH THEY CAN OPERATE ON THE DATA IS A GOOD FIRST STEP. WE ALSO WANT TO FACILITATE SECURE ACCESS TO THE DATA, IF ANY OF YOU HAVE TRIED TO FIND DATA SETS AND DOWNLOAD THEM YOU WILL KNOW HOW MUCH TIME AND EFFORT IT TAKES TO DO SO AND SO WE ARE LOOKING TO FACILITATE THAT PROCESS AND STREAM LINE IT SO THAT WE CAN ALLOW RESEARCHERS TO MORE READILY ACCESS THE DATA AT HAND BUT IN A SECURE FASHION WHICH RESPECTS PATIENTS INFORMED CONSEN CONSENTS. THIS IS A NONTRIVIAL PROBLEM BUT I THINK WE ARE MAKING SOME GOOD PROGRESS IN THAT DOMAIN AS WELL. WE ALSO WANT TO ENABLE DATA MINING, THAT IS THIS NEW GENERATION OF INFO MATIC TOOLS AND MACHINE LEARNING AND SO FORTH THAT CAN HELP US FIND PATTERNS THAT MAY NOT BE VISIBLE TO THE NAKED EYE AND MAY GIVE US AN OPPORTUNITY TO MOVE FORWARD IN NOVEL DIRECTIONS. WE ALSO WANT TO PROVIDE THEM WITH A STATE OF THE SCIENCE TOOL SET, THERE ARE LOTS OF INNOVATORS OUT THERE THAT ARE CREATING STATISTICAL METHODOLOGY OR INFO MAT TICK PIPELINES AND SO FORTH THE ONES THAT ARE COMMONLY USED WE WANT TO BRING THEM IN THE ENVIRONMENT AND MAKE THEM AVAILABLE TO INDIVIDUALS COMING ON BOARD IN AN EASY FASHION AND FINALLY DOING THIS AND PROVIDING THE COMMON AREAS WHERE INVESTIGATORS CAN INTERACT WE HOPE TO FACILITATE COLLABORATION AND IDEA GENERATION WHICH CAN REALLY FUEL THE PROGRESS OF THE SCIENCE ITSELF. SO WE WILL START WITH THE TOOLS FOR RESEARCH. WHEN YOU BREAK DOWN THAT USER NARRATIVE FROM COPD GENE WE FIGURED THESE ARE THE THINGS THEY NEED TO KNOW HOW TO DO FIRST OF ALL THEY NEED SOMETHING TO EXPLORE THE DATA FOR FEASIBILITY SO THEY CAN GET THE HANDS ON THE IMAGES, THEY CAN SEE WHAT THE DATA ARE LIKE, THEY CAN DESIGN A STUDY. SECONDLY YOU HAVE TO UNDERSTAND THE COHORT CHARACTERISTICS ANYBODY THAT HAS HAD EPIDEMIOLOGY TRAINING KNOWS HOW IMPORTANT THAT IS TO ASSEMBLE THE RIGHT GROUP OF INDIVIDUALS WITH THE RIGHT CHARACTERISTICS FOR THE HYPOTHESIS AT HAND AND IDENTIFY THE SUBJECTS WITH THE APPROPRIATE CT IMAGES OR FUTURES THAT ARE OF INTEREST IN ORDER TO ACCUMULATE THEM FOR A PARTICULAR ANALYSIS WE WANT TO ANALYZE IMAGES WITH DEEP LEARNING TOOLS SO WE WANT TO PROVIDE THE TOOLS AS WELL AS GIVE AN ENVIRONMENT IN WHICH TO CONDUCT THAT AND THEN PERHAPS IN THE NEW FEATURES WE WOULD LIKE TO DO GENOTYPE PHENO TYPE ANALYSIS TO LOOK AT QUESTIONS OF THE UNDER LYING GENETIC ARCHITECTURE AND OF COURSE PUBLISH AND SHARE RESULTS NOT ONLY TO ALL COLLABORATORS BUT ALSO TO THE GREATER SCIENTIFIC COMMUNITY. IN THESE SLIDES THIS WHITE AND GRAY WHAT WE ARE TRYING TO COMMUNICATE HERE IS SORT OF THE TRADITIONAL BARRIERS THAT INVESTIGATORS HAVE ENCOUNTERED IN ACCOMPLISHING THIS WORK AND WHY IT'S BEEN CHALLENGING AND IN THE GRAY SIDE WHAT WE ARE DOING IS TRYING TO GIVE YOU THE ATTRIBUTES OF THE DATA STAGE SOLUTION. AND THE UP SHOT OF THIS PARTICULAR SLIDE IS THAT BY CENTRALLY LOCATING ALL OF THOSE HIGH VALUE DATA SETS AND STREAMLINING THE ACCESS IT'S GOING TO MAKE IT MUCH EASIER FOR THESE INDIVIDUALS TO GET ON WITH THE SCIENCE RATHER THAN TO BE BOGGED DOWN IN THE DETAILS OF ASSEMBLING ALL THOSE DATA SETS. SO HERE WE HAVE A VIDEO AND WE ARE GOING TO LOOK AT THE WAY THAT PEOPLE CAN INTERACT WITH THE DATA SET THIS IS FROM COPD GENE, I'M GOING TO SHOW YOU A SERIES OF VIDEOS OF PEOPLE ACTUALLY OPERATING ON DATA STAGE AS WE HAVE IT RIGHT NOW. WE HAVE BEEN WORKING REALLY HARD TO MAKE SURE THAT PEOPLE HAVE THE END TO END FUNCTIONALITY THEY NEED TO DO MEANINGFUL ANALYSIS AND SO THAT'S WHAT I'M GOING TO SHOW YOU HERE AND IN THE COMING MONTHS WE ARE GOING TO BE WORKING ON SORT OF THE BRANDING AND THE LOOK OF THE PAGE TO PROVIDE A SEAMLESS EXPERIENCE FOR THE USER SO THAT IS COMING BUT FOR THE MOMENT I WOULD ASK YOU TO KIND OF FOCUS YOUR ATTENTION ON THE FUNCTIONALITY THAT WE ARE DEMONSTRATING. SO HERE IS AN EXAMPLE OF A BROWSER THAT ALLOWS US TO ACTUALLY COME UP WITH QUERIES, COPD GENE IS LOCATED HERE AND HERE WE ARE ASKING TO BRING UP THE NUMBER OF INDIVIDUALS THAT ARE AFFECTED IN THE DATA SET AND IT BRINGS YOU THE TOTAL NUMBER OF SUBJECTS THERE IS A DROP DOWN MENU AND YOU CAN ACTUALLY FIND THE ITEMS THAT DESIGNATES WHO OF THOSE ARE SMOKERS AND AS WE FINE THE SAME NUMBER OF INDIVIDUALS BECAUSE THAT'S THE DESIGN OF THE STUDY, THESE ARE SMOKERS WITH C O PD, BUT NOW WE MAY WISH TO RESTRICT THE AGE RANGE TO CORRESPOND TO SOMETHING THAT WAS PREVIOUSLY PUBLISHED SO HERE WE ARE SELECTING FOR INDIVIDUALS THAT ARE BETWEEN 60-80 YEARS OF AGE AND THAT BRINGS DOWN THE SAMPLE SIZE A LITTLE BIT AND NOW WE ARE INTERESTED IN THE PREVALENCE OF A CERTAIN VARIANT THAT HAS BEEN SUGGESTED TO BE IMPORTANT SO THERE IS A CERTAIN NO MEN -- NOMENCLATURE AND THREE CASES POSSES THE RARE VARIANT AND SIMPLY CHANGING THE DESIGNATION TO CONTROLS WE FIND THERE IS ZERO PATIENTS AMONG CONTROLS THAT HAVE THAT SO THIS WAS THE RESULT THAT WAS ACTUALLY PUBLISHED BY THE COPD GENE INVESTIGATORS FINDING THIS RARE VARIANT ASSOCIATED WITH CASE STATUS AND WE WERE ABLE TO REPLICATE THAT RESULT BY BUIANT OPERATION IN UNDER A MINUTE SO THIS IS A POWERFUL WAY TO INTERACT WITH THE DATA AND DO EXPLORATORY DATA ANALYSIS GATHER SAMPLE SIZES DESIGN YOUR SAMPLE STUDY AND POWER INVESTMENT IN ABLE TO LAUNCH YOUR STUDY. MOVING ON IN THIS BROWSER WE CAN ALSO GO ON AND THERE IS ADDITIONAL FUNCTIONALITY THAT IS AVAILABLE AND SO BRINGING UP AGAIN THE COPD DATA SET HERE WE HAVE ALL OF THE TERMS THAT ARE AVAILABLE WITH THE DATA THAT HAVE BEEN LOADED AND HERE WE ARE GOING TO DO SOME CASE CONTROL COMPARISONS, DRAG AND DROP, THOSE CATEGORIES. COULD BE ANYTHING COULD BE MALES FEE MEALS COULD BE EUROPEANS VERSUS AFRICAN/AMERICANS HERE WE LOOK AT CASE CONTROL BY HITTING SUMMARY STATISTICS WE GET THE BASIC DEMOGRAPHIC DISTRIBUTION OF CASES VERSUS CONTROLS SHOWS YOU THE AGE DIFFERENCES AND THE SEX DIFFERENCES. NOW PERHAPS YOU'RE INTERESTED IN SOME EXPLORATORY DATA ANALYSIS AND WOULD LIKE TO KNOW WHAT ARE THE CASES BETWEEN CASES AND CONTROLS FOR SOME CLINICALLY RELEVANT VARIABLE THEY ARE LOADED HERE WE CAN SEE WHAT ARE THE CLINICAL VARIABLES THAT ARE AVAILABLE AND PERHAPS INTERESTED IN OXYGEN SATURATION AND COMES UP AND GIVES YOU THE DIFFERENCES IN THE DISTRIBUTION OF OXYGEN SATURATION CASES AND CONTROLS AND ALSO PROVIDING AN ELEMENT SIGNIFICANCE TEST YOU GET AN IDEA OF WHETHER THIS IS SOMETHING TO WRITE HOME ABOUT OR NOT SO THIS IS VERY INTUITIVE PROCESS OF BEING ABLE TO INTERACT WITH AND EXPLORE THE DATA IN ORDER TO DESIGN THE STUDY THAT WOULD BE SUITABLE FOR ANSWERING YOUR HYPOTHESIS. SO THE INVESTIGATORS ESSENTIALLY WANT TO CONDUCT ADVANCED ANALYSIS ON THESE IMAGES IN ORDER TO IDENTIFY NOVEL FEATURES THEY IDENTIFY THE DISEASE SUBTYPES, SOME OF THE TRADITIONAL BARRIERS HERE INCLUDE WHAT WE CALL INFRASTRUCTURE DISTRACTION, IF ANYONE HAS EVER TRIED TO RUN THEIR OWN CLUSTER OR YOU KNOW TRY TO FIGURE OUT WHAT THEY NEED IF THEY ARE TAKING TIME OUT ON A SUPER COMPUTER, THE DATA STAGE SOLUTION WILL SOLVE A LOT OF THAT BY PROVIDING A DEVELOPED AND SUPPORTED COMPUTING ENVIRONMENT SO THAT THE INVESTIGATORS CAN REALLY MAINTAIN THEIR SCIENTIFIC FOCUS AND NOT WORRY ABOUT IT ISSUES. IT'S SMART AND IT'S ELASTIC SO YOU ONLY PAY FOR WHAT YOU USE AND YOU DON'T HAVE ALL THESE OTHER WORRIES. IN OUR EXAMPLE HERE AGAIN WE ARE TALKING ABOUT THESE CT IMAGES OF THE LUNG. THE RED BOXES HERE SHOW AREAS OF THE LUNG TO A RADIOLOGIST PERHAPS THAT SHOWS AREAS WHERE THERE IS EMPHYSEMA SO AGAIN DEMONSTRATING THAT SOME OF THESE FEATURES ARE ACTUALLY VISIBLE ON CT SCANS AND PERHAPS MEASUREMENT OF THESE FEATURES OR AREAS AND VOLUMES COULD GIVE SOME KIND OF QUANTITATIVE INDICATOR OF DEGREE OF BEING EFFECTIVE SO THE FIRST THING WE NEED TO DO IS PUT THE SCANS IN THE HANDS OF THE INVESTIGATORS SO THEY COULD INTERACT WITH THEM SO ONE OF THE FIRST THINGS WE HAVE DONE HERE IS TO BUILD A VIEWER FOR THE SCANS AND IN THIS PARTICULAR EXAMPLE WE HAVE LOADED UP TEN PATIENTS WORTH JUST FOR DEMONSTRATION PURPOSES. SO HERE WE LOG INTO, WE CHOOSE THE DICOM VIEWER AND WE LOG IN THROUGH A WEBSITE WHICH IS AN ADDITIONAL STEP MEANT TO PROTECT AND SECURE THE DATA. AND WHEN IT COMES UP WE COME TO OUR AREA WITH THE PATIENT DATA LOADED UP. SO ONE CAN ACTUALLY CHOOSE THE PARTICULAR PATIENT THAT ONE MIGHT WANT TO LOOK AT. THERE ARE SEVERAL DIFFERENT VIEWS OF THE LUNG THIS IS AN AXIAL AND SEVERAL DIFFERENT IMAGES UPON EXPIRATION AND INSPIRATION AND SO FORTH SO YOU CAN CHOOSE THE VIEW YOU LIKE. AND THEN THERE IS OPPORTUNITY TO IMPROVE THE QUALITY OF THE IMAGE BY ALTARING THE CONTRAST AND SO FORTH AND THERE IS ALSO AN SAGITTAL STAFF GOING DOWN THROUGH THE LUNG SO YOU CAN ACTUALLY SCROLL THROUGH THAT GOING DOWN UNTIL YOU GET DOWN TO THE LEVEL THAT YOU MAY WISH TO BE LOOKING AT. ONCE YOU ARRIVE THERE YOU CAN ENLARGE THE IMAGE AND YOU CAN START LOOKING AND SO WE ARE NOT RADIOLOGISTS BUT WE ARE GOING TO SAY SAY YOU FIND THAT FEATURE THAT LOOKS INTERESTING, YOU CAN ACTUALLY PUT A PIN IN IT AND GIVE IT SOME NAME, YOU CAN EVEN MAKE SORT OF FIRST ORDER MEASUREMENT OF ITS SIZE, CONTINUE LOOKING ALONG YOU MAY FIND ANOTHER FEATURE THAT APPEARS INTERESTING, NAME IT SOMETHING ELSE AND ALSO MEASURE IT USING THESE ELECTRONIC TOOLS AND THEN THESE ANNOTATIONS ARE SAVED AS A METADATA SET SO THAT IF YOU WANTED TO GO BACK LATER AND ACCUMULATE ALL THE SCANS THAT HAS A PARTICULAR FEATURE THAT THEY HAVE ANNOTATED ONE CAN DO THAT OPERATING ON THOSE ANNOTATIONS. SO THIS IS JUST I THINK A FANTASTIC WAY TO PUT THOSE SCANS JUST READILY IN THE HANDS OF THE INVESTIGATOR SO THEY CAN INTERACT WITH THEM AND UNDERSTAND WHAT THEY HAVE AVAILABLE. NOT ONLY DO WE WANT TO DO THAT BUT WE ALSO WANT TO GIVE THEM THE OPPORTUNITY TO USE THESE MACHINE LEARNING TOOLS ON THESE DATA SETS SO ONE OF THE CHALLENGES OF DOING THIS FROM WHAT I UNDERSTAND IS THIS CONCEPT OF SEGMENTATION ERROR WHICH IS DISTINGUISHING THE RELEVANT LUNG TISSUE FROM THE SURROUNDING TISSUE SO THAT YOU CAN GET PRECISE MEASUREMENTS OF THESE AREAS AND VOLUMES OF DISEASED TISSUE AND UPON USING THESE MACHINE LEARNING TOOLS ON A SERIES OF IMAGES IT HAS BEEN FOUND BY THE INVESTIGATORS THAT THE CLASSIFICATION ERROR IS REDUCED BY MORE THAN 50% OVER TRADITIONAL METHODS AND SO OF COURSE HAVING LESS NOISY PHENO TYPES IS REALLY GOING TO HELP THE POWER OF THE ANALYSIS WHEN ONE IS TRYING TO MEASURE THESE KINDS OF FEATURES. IN A FIGURE HERE THESE ARE SIMPLY THREE DIFFERENT SUBJECTS, RIGHT AND LEFT LUNG, WHICH NOW SHOWS GRAPHICALLY HOW THE SEGMENTATION WAS DETERMINED USING THE MACHINE LEARNING ALGORITHM. GOING TO THE NEXT STEP ONCE WE HAVE PUT THOSE IMAGES IN THEIR HANDS AND WE HAVE GOT THE DEEP LEARNING TOOLS IN PLACE THEY WOULD LIKE TO USE SOME OF THE GENOMIC ANALYSIS PIPELINES IN ORDER TO CALL VARIANTS AND GENO AND PHENO TYPE ANALYSIS AND DO IT RATHER QUICKLY TRADITIONAL BARRIERS IT'S DIFFICULT TO GET AND PUT TOGETHER AN END TO END TOOL BOX AND HAVE IT BE REPRODUCIBL REPRODUCIBLE. THE DATA STAGE SOLUTIONS IS THAT WHAT WE WOULD DO IS TO TAKE MANY OF THESE COMMONLY USED TOOLS AND PUT THEM IN DOCORIZED CONTAINERS AND END TO END WORK FLOWS THAT CAN BE APPLIED TO THE DATA SET AND THEY COULD BE SPECIFICALLY REFERENCED SO ANOTHER PERSON COULD USE THE EXACT SAME WORK FLOW AND THERE IS VERSION CONTROL THERE SO YOU KNOW WHAT VERSION OF THE TOOL THAT YOU ARE USING AND ALSO THE PROVIDENCE WHERE IT CAME FROM AND SO FORTH. SO IN DOING THIS THERE ARE TWO BASIC, THREE BASIC STEPS FIRST OF ALL YOU ARE GOING TO SELECT THE DATA SET THAT YOU WANT, IT MAY BE COMBINING DATA SETS TO MAXIMIZE POWER IT MAY BE SUBSETTING DATA SETS TO PARS HETEROGENITY SO SELECT THE DATA YOU WILL PUT IN THE ANALYSIS AND SELECT THE WORK FLOW THAT IS THE WORK THAT YOU'RE TRYING TO ACCOMPLISH, YOU PUT THEM TOGETHER IN A WORKSPACE AND YOU LAUNCH THE JOB SO THOSE ARE THE BASIC STEPS. NOW YOU MIGHT THINK THAT THE WORK FLOW COULD BE A LITTLE BIT DAUNTING TO UNDERSTAND AND ACTUALLY IF YOU ARE LOOKING AT MACHINE CODE I THINK YOU WOULD BE RIGHT. IT'S HARD TO KNOW EXACTLY WHAT'S HAPPENING AS YOU ARE MOVING INPUTS AND OUTPUTS THROUGH THESE VARIOUS COMPUTATIONAL TOOLS SO WHAT WE HAVE DEVELOPED IS THIS GRAPHICAL REPRESENTATION OF THE WORK FLOW. OVER HERE WHAT YOU SEE IS THE BLUE NODES ARE THE ACTUAL COMPUTATIONAL PARTS, THOSE ARE THE ONES THAT ARE MANIPULATING THE DATA IN SOME WAY AND THE WHITE NODES ARE THE INPUTS AND THE OUTPUTS. AND SO THIS IS CERTAINLY A MUCH EASIER WAY OF APPRECIATING WHAT THE WORK FLOW IS DOING BY JUST LOOKING AT THIS GRAPHICAL REPRESENTATION. BUT SAY THERE IS A NEW TEAM THAT YOU NEED TO INCLUDE IN THE WORK FLOW AND SO HOW ARE YOU GOING TO DO THAT, DO YOU NEED TO GET A PROGRAMMER TO DO IT? NO. WHAT WE HAVE DEVELOPED IS A WAY OF MODIFYING THIS PARTICULAR WORK FLOW FROM THE LIBRARY YOU JUST CHOOSE WHAT IS THE NEW ROUTINE THAT YOU WOULD LIKE TO DO, YOU DRAG AND DROP IT ON TO THE SCREEN AND THEN YOU ATTACH IT APPROPRIATELY TO ITS INPUTS AND OUTPUTS AND THAT MODIFIES THE DOCKER CONTAINER WORK FLOW OF WHAT YOU ARE GOING TO DO. NOW IS IT COMPLETELY MINDLESS? NO, IT IS NOT. SO THERE IS A -- [ LAUGHTER ] SO THERE IS A MENU THAT COMES UP HERE WHICH GIVES YOU A DESCRIPTION OF THE TOOL, TALKS A LITTLE BIT ABOUT ITS LIMITATIONS AND STRENGTHS AND IF THERE IS ANY CONFIGURATION THAT'S NEEDED IT ALLOWS YOU TO DO IT THERE. BUT IT'S A WONDERFUL WAY OF SERVING UP THAT OPPORTUNITY AND TOOL WITHOUT HAVING TO HAVE A GREAT DEAL OF COMPUTATIONAL KNOWLEDGE. OKAY THE NEXT THING THAT WE WANT TO DO IS TO SELECT THE WORK FLOW SO THAT WAS AN EXAMPLE OF A WORK FLOW SO HOW DO WE GET IT? SO AS I'VE MENTIONED THESE WORK FLOWS ARE PUT TOGETHER IN DOCKER CONTAINERS SO IT HAS ALL OF THE INPUTS OUTPUTS AND ALL THE COMPUTATIONAL PIECES ALL STITCHED TOGETHER AND WRAPPED UP IN A DOCKER CONTAINER AND THAT IS WHY WE PUT UP ALL OF OUR WORK FLOWS INTO THE DOCK STORE SO WE HAVE A DOCK STORE ONLINE AND INDIVIDUALS CAN LOG IN AND THEY CAN LOOK FOR THE KINDS OF WORK FLOWS THAT ARE RELEVANT TO THEM, HERE WE CAN GO TO THE TOP MED AREA WHICH CONTAINS ALL TOP MED PERTINENT WORK FLOWS AND IN THIS CASE WE ARE SHOWING AND CHOOSING A LINER THAT WAS DEVELOPED BY THE UNIVERSITY OF MICHIGAN, THE INFRAMATIC RESEARCH CENTER AND BRING IT UP AND SEE THE CODES THERE YOU DON'T NEED TO MESS WITH THE CODE BUT YOU CAN ACTUALLY SELECT THAT WORK FLOW AND YOU CAN PUT IT IN A DESTINATION WORKSPACE. SAY I'M GOING TO TAKE THE WORK FLOW AND ASSOCIATE IT WITH THIS WORKSPACE AND YOU CAN PROVIDE ANCILLARY INFORMATION ON BILLING AND AUTHORIZATION AND SO FORTH AND THERE IT IS. YOU CAN THEN ACTUALLY NAVIGATE TO THE WORK FLOW AND PRESUMABLY WE HAVE ALREADY ASSOCIATED DATA WITH THAT WORKSPACE AS WELL SO THEN YOU CHOOSE THOSE ARE ALL THE FILES THAT ARE ASSOCIATED WITH THE WORK FLOW AND YOU CLICK RUN ANALYSIS LAUNCH AND OFF IT GOES. OKAY, SO IT'S ALL POINT AND CLICK OPERATIONS. WHILE THERE IS PROVISION FOR COMMAND LINE USE TOO FOR PEOPLE THAT ARE YOU KNOW VERY SAVVY VBT THINGS A LOT OF POINT AND CLICK TECHNOLOGY DOES NOT ABSOLVE YOU OF WHAT YOU ARE DOING BUT MAKES IT EASIER TO PUT IT TOGETHER AND CONDUCT AN ANALYSIS SO A POST DOC CAN COME IN AND BEGIN TO NAVIGATE THIS TERRITORY. SO NOW WE HAVE TO BRING THEM TOGETHER IN A WORKSPACE AND WHAT WE ARE REFERRING TO SPECIFICALLY IS BRINGING THE DATA PIECE AND SO HERE WE HAVE ANOTHER VIDEO SHOWING LOGGING IN TO A DATA STAGE PLATFORM AND OVER HERE WE ARE GOING TO CHOOSE THESE ARE THE PUBLICALLY AVAILABLE DATA THERE IS VERY FEW OF THEM BUT WE DIDN'T WANT TO HAVE ANY SENSITIVITIES ABOUT WHAT WE ARE SHOWING HERE, WE CAN SUBSET AND CHOOSE THE HISPANIC LATINO ORIGIN AND FEMALES AND SO YOU CAN CRAFT YOUR DATA SET HOWEVER YOU LIKE IT AND THEN, PAUSE, IT IS EXPORTED HERE WHERE YOU HAVE SEVERAL OPTIONS OF WHERE YOU CAN TAKE THAT DATA SET THAT YOU'VE JUST SELECTED AND ONE OF THE MORE IMPORTANT ONES TO POINT OUT IS R STUDIO WHICH IS A COMMON PROGRAMMING LANGUAGE TO DO BASIC STATISTICAL ANALYSIS EVERYBODY WILL HAVE TO RUN A REGRESSION OR A JUST PHE IN, O TYPE AND EVERYTHING CAN BE DONE UNDER R STUDIO BUT WHEN YOU ARE READY FOR THE BIGGER KIND OF ANALYSIS WHETHER IT'S DOING A G-WAS OR DOING ACTUALLY VARIANT CALLING AND ALIGNING AND SO FORTH YOU WOULD WANT TO CHOOSE A MORE ROBUST, BIGGER WORKSPACE AND SO HERE WE ARE DEMONSTRATING JUST BY POINTING AND CLICKING GOING TO THE TERRA PLATFORM AND CREATING A WORKSPACE THERE AND NOW THE DATA THAT WE HAVE IDENTIFIED ARE ASSOCIATED WITH THAT WORKSPACE AND IN CONJUNCTION WITH HAVING CHOSEN THE WORK FLOW AGAIN THIS IS A VERY EASY WAY OF BRINGING TOGETHER WORK FLOWS AND DATA AND THEN THERE IS A LAUNCH BUTTON AND YOU CAN JUST LET IT GO. WE'VE ALSO DEVELOPED SOME SMART TOOLS THAT HELP THE USER TO -- USER DOESN'T HAVE TO DETERMINE THAT WILL HELP DEVELOP THE KINDS OF CLOUD INSTANCES THAT ARE NEEDED IN ORDER TO SUPPORT THE WORK THAT'S BEING PROPOSED. SO THIS WILL ALSO HELP CONTAIN COSTS. EVENTUALLY YOU WILL GET TO THE GWAS AND FEWAS AND THIS IS JUST A BRIGHT SIDE KIND OF CARTOON OF WHAT MAY HAPPEN, YOU MAY GET YOUR TO PRESUMPTIVE DISEASE SUBTYPES AND YOU MIGHT RUN A GWAS SCAN ON THE TWO DIFFERENT SUBTYPES CONTRASTING THE GENETIC ARCHITECTURE TO START GETTING AN IDEA OF WHAT MIGHT BE THE BIOLOGICAL UNDER PINNINGS TO THE HETERIGENITY AND GIVE SOME CLUES TO CLINICAL MANAGEMENT AND THERAPEUT THERAPEUTICS WE ALSO WANT TO MAKE SURE THE TOOLS AND EVEN THE DATA RESULTS ARE REPRODUCIBLE AND REUSABLE. TRADITIONALLY IT'S BEEN VERY DIFFICULT, THERE IS DIFFERENT VERSIONS OF DATA, DIFFERENT VERSIONS OF TOOLS, PEOPLE ARE CONSTANTLY INNOVATING AND YOU HAVE TO STRING TOGETHER A BUNCH OF TOOLS AND EVERYONE HAS DONE THAT IN AD HOC MANNER OVER HERE WE WILL HAVE ALL THE COMPONENTS BE INTER OPERABLE. THESE WORK FLOWS ARE GOING TO BE ALL SEAMLESSLY PUT TOGETHER AND ALL OF THESE DATA ELEMENTS WHETHER THEY BE DATA OR TOOLS OR WORK FLOWS OR WHAT NOT WILL HAVE UNIQUE IDENTIFIERS SO THAT ANYBODY LOGGING INTO THE ENVIRONMENT CAN SAY I WANT TO USE THE WORK FLOW THAT WAS PUBLISHED IN THIS PAPER AND APPLY IT TO MY DATA OR I WANT TO USE THE EXACT SAME DATA THAT WAS PUBLISHED IN THAT PAPER AND DO A FOLLOW-UP ANALYSIS ON IT. THESE THINGS WILL BUT NEARLY IDENTIFIED SO THAT I CAN BE REPRODUCIBLY GRABBED AND ANOTHER ADVANTAGE ONCE ANALYSIS IS ARE UNA GREAT EXAMPLE IS A GWAS ANALYSIS IT DOESN'T HAVE TO BE RUN AND RERUN THEY CAN BE CAPTURED AND PUBLISHED WITHIN DATA STAGE SO THAT OTHER PEOPLE CAN COME IN AND SIMPLY DO LOOK UPS AND INSTEAD OF HAVING TO CONTACT INVESTIGATORS OR RERUN THE ANALYSIS OR WHAT NOT. SO WE HAVE HAD ALFA USERS ON THESE PLATFORMS. LARGELY FROM THE COPD GENE GROUP BUT ALSO FROM SOME FOR SOME OF THE OTHER PLATFORMS AND WE ASKED THEM TO PROVIDE SOME VERBAL FEEDBACK SO THAT YOU CAN SEE HOW OUR USER GROUP IS RESPONDING TO WHAT WE HAVE BEEN DEVELOPING THUS FAR. WE ARE ALSO COLLECTING SYSTEMATIC FEEDBACK TO HELP IN THE CYCLE OF REFINEMENT AND EXPANSION OF WHAT WE HAVE ALREADY DONE SO WE ARE ALSO COLLECTING MORE TECHNICAL FEEDBACK FROM THEM BUT AS YOU CAN SEE FROM THE COMMENTS HERE IT SEEMS THAT AT LEAST FOR THE MOMENT EX SYMPTOMS FOR THE PERSON WHO SAYS IT HAS NOT YET THAT WE ARE SORT OF HITTING OUR GOALS, THAT THESE PEOPLE ARE EXPERIENCING WHAT WE SET OUT AS GOALS FOR HOW WE CAN IMPROVE THE WAY THAT THEY ARE CONDUCTING THIS KIND OF POPULATION SCIENCE RESEARCH. THERE IS FEW OTHER ACTIVITIES I WANTED TO APPRAISE YOU OF LIKE I SAY WE ARE ROLLING ON BOARD SOME ADDITIONAL ALFA USERS IN THE COMING MONTH OR TWO BECAUSE ACTUALLY THERE ARE MANY MORE PLATFORMS AND TOOLS THAN WHAT I WAS ABLE TO SHOW YOU TODAY AND WE WANT ALL OF THEM TO BE VETTED BY THESE SORT OF REALLY COMPUTATION SAVVY KNOWLEDGEABLE USERS TO BE SURE WE IRON OUT ALL THE BUGS IN PREPARATION FOR FALL OF 2019 WHERE WE ANTICIPATE OPENING UP OUR DOORS TO SORT OF THE GENERAL TOP MED USER SO THESE WILL STILL BE BETA TESTERS AND COMING IN AND GIVING US FEEDBACK AND HELPING US MOVE FORWARD WITH THESE PLATFORMS BUT IT'S ANTICIPATED THAT THROUGH WILL BE CAPABLE OF DOING PRODUCTION LEVEL ANALYSIS TOWARDS PUBLICATION SO IT WILL START COUNTING, WON'T JUST BE TESTING, THEY WILL BE PRODUCING USABLE RESULTS. ALSO IN PREPARATION FOR THAT MILESTONE WE HAVE ACTUALLY KICKED INTO GEAR OUR USER ENGAGEMENT AND HELP COMMITTEE WHERE WE ARE BEGINNING TO THINK ABOUT HOW WE WANT TO BRING PEOPLE ON BOARD, PROVIDING IT AN ON BOARDING EXPERIENCE FOR THEM AND THEN SOME TRAINING MATERIALS TO ORIENT THEM TO THE TOOLS AND THE POSSIBILITIES AND HOW TO NAVIGATE ALL OF THESE PLATFORMS. ALSO AS WE ARE COMPLETING THE FIRST CYCLE OF NARRATIVES WHICH WE ARE REALLY QUITE EXTREME BECAUSE WE STARTED FROM NOTHING TO TRYING TO GET THEM FROM BEING ABLE TO ACCESS THEIR DATA, MANIPULATE IT AND CONDUCT ANALYSIS AND PUBLISH RESULTS IT'S KIND OF A FULL MENU OF OPTIONS, WE ARE FINISHING UP THOSE THINGS NOW BUT WE ARE IN ACTIVE CONVERSATIONS WITH OUR RESEARCH GROUP, OUR USER GROUP ABOUT WHAT ELSE DO THEY NEED AND WHAT ARE THE THINGS COMING DOWN THE PIKE THAT ARE GOING TO REALLY HELP THEM MOVE THINGS FORWARD OR WHAT HAVE THEY NOT BEEN ABLE TO DO UP TO NOW THAT REALLY WOULD BE GREAT SO WE ARE ALL IN A CYCLE OF GENERATING OUR NEXT GENERATION OF NARRATIVES THAT WE WILL BE WORKING INTO OUR DEVELOPMENT CYCLE FOR THE NEXT YEAR OR TWO. DURING THAT TIME WE ARE ALSO PUSHING FORWARD SOME OF THESE INNOVATIONS AND DATA ACCESS PROCEDURES THIS IS QUITE A COMPLICATED PROBLEM, NOT ONLY INVOLVES CYBER INFRASTRUCTURE BUT ALSO SOME POLICY CHANGES BUT WE ARE WELL ON OUR WAY TO DOING SOME PILOT STUDIES TO DETERMINE THE FEASIBILITY OF THIS KIND OF APPROACH AND I THINK THIS IS VERY EXCITING AND WE HOPE WE WILL HAVE SOME DEFINITE NEWS TO TELL YOU ABOUT IN A YEAR OR SO. IN TERMS OF COLLECTING IDEAS FOR WHERE WE SHOULD GO FROM HERE, TOP MED IS A PRETTY ROBUST USER COMMUNITY OVER A THOUSAND INVESTIGATORS ARE SORT OF SIGNED UP SO IT'S A LARGE CADRE OF HEART LUNG INVESTIGATORS BUT IT'S NOT EVERYBODY SO WHAT WE HAVE DONE NOW CURTESY OF NHLBI IS SET UP A PAGE ON THE IDEA SCALE UTILITY AND THE LINK IS SHOWN AT THE VERY TOP AND THAT LINK CAN BE DISTRIBUTED TO ANYONE AND EVERYONE THAT IS INTERESTED IN DATA STAGE AND THE UP SHOT IS THAT IT GIVES PEOPLE AN OPPORTUNITY TO SUBMIT A NEW IDEA SO TO PUT IN A NARRATIVE OR A TOOL OR A REQUEST OR A COMMENT WHATEVER AND WE WILL MONITOR THIS INPUT AND THEN DETERMINE WHAT ARE THE PRIORITIES OF THESE SUGGESTIONS AND TRY TO CONTINUALLY WORK THEM INTO OUR DEVELOPMENT CYCLE. I WANTED TO CLOSE WITH A QUOTE FROM ONE OF OUR COPD GENE COLLABORATORS, DR. ESTAPOD THE COMPUTER SCIENCE GUY WHO IS IMPLEMENTING TECHNIQUES TO THIS AND SAYS THE STAGE HAS THE FIRST IN KIND COMMON COMPUTING AND DATA SHARING ENVIRONMENT TO TRANSLATE ARTIFICIAL INTELLIGENCE AND COMPUTING BASED TOOLS INTO REPRODUCIBLE SCIENCE THAT IS A PROFOUND MOUTHFUL AND WE ARE ON OUR WAY TO PROVIDING THIS AND I THINK IT'S GOING TO BE TRANSFORMATIVE FOR POPULATION SCIENCE. I WANTED TO SAY THERE ARE MANY OF THE -- SEVERAL OF THE KEY INVESTIGATORS ARE HERE IN THE ROOM WITH US, AND THIS IS THE END OF MY PRESENTATION BUT WE WILL HAVE THE OPPORTUNITY TO HAVE SOME DISCUSSION AND HAVE THEM ANSWER YOUR QUESTIONS AND CONCERNS AS WELL. THANK YOU. [ APPLAUSE ] WELL THANK YOU VERY MUCH FOR THAT IT WAS FASCINATING I'M SURE OUR COUNCIL MEMBERS HAVE SOME QUESTIONS FOR YOU I'M GOING TO LET YOU GO AHEAD AND RECOGNIZE PEOPLE WHEN THEY HAVE A QUESTION TO FACILITATE THINGS AND WOULD LIKE TO POINT OUT IF YOU HAVE MEMBERS OF YOUR TEAM IN THE AUDIENCE WHO HAVE THE ABILITY TO CONTRIBUTE TO THE DISCUSSION I WOULD APPRECIATE IT IF THEY WOULD COME TO THE MICROPHONE BECAUSE THIS IS BEING RECORDED AND WEBCAST AND I WANT OUR AUDIENCE TO BE ABLE TO HEAR WHATEVER IS BEING SAID SO WITH THAT I'M JUST GOING TO OPEN THE LOOR FOR QUESTIONS AND THE DOCTOR WILL RECOGNIZE YOU PLEASE IDENTIFY YOURSELF WHEN YOU BEGIN TO SPEAK. >> THANK YOU. YES. >> THIS IS INCREDIBLY POWERFUL. I JUST WANT TO THANK YOU FOR THIS. >> WELL THANK YOU VERY MUCH, IT'S REALLY BEEN A PLEASURE. WE REALLY LIKE GETTING THE WORD OUT, TELL YOUR FRIENDS BECAUSE ALL RIGHT HERE I AM, WE ARE THINKING ABOUT PUB PUBLICATIONS FOR THE AVAILABILITY OF THESE RESOURCES AND HOPING NOT TO GET THOUSANDS OF PEOPLE COMING ALL AT ONCE BUT WE DO WANT TO SLOWLY GROW THIS AND OPEN UP OUR DOORS TO INDIVIDUALS THAT WOULD MAKE USE OF THIS ENVIRONMENT. >> WELL IN SAYING THAT ARE THERE GOING TO BE SORT OF WEBINARS OR HOW DO YOU PLAN TO OPERATIONALIZE THE TRAINING TO REALLY HAVE ACCESS TO THIS RESOURCE? I KNOW YOU TOUCHED ON IT BUT WONDERED IF YOU HAD A LITTLE MORE DETAIL. >> YEAH, SO SOME INITIAL THOUGHTS ARE TO HAVE SOME LIKE WE ARE PILOTING OUR VIDEOS HERE AND THINKING WE WOULD HAVE SOME WEBINARS AND INITIALLY WE WOULD LIKE TO DO THEM WITH THE EXPERTS IN OUR AREA TO ACTUALLY INVITE PEOPLE ON BOARD SO THERE CAN BE DIALOG BUT WE WOULD RECORD THEM AND HAVE THEM AVAILABLE OFF OUR WEBSITE TOO SO THAT OTHER INDIVIDUALS COULD LOOK AT THEM AT THEIR CONVENIENCE. WE ALSO THOUGHT OF SUCH THINGS AS FACTS, YOU KNOW HAVING A SERIES OF QUESTIONS WHERE PEOPLE CAN LOOK THINGS UP AND YOU KNOW EVENTUALLY THE LONGER TERM PLANNING IS IN THE EARLY STAGES OF DISCUSSION BUT WE ARE GOING TO NEED SOME KIND OF A HELP DESK DATA CONCIERGE AND STARTING TO THINK IN THAT DIRECTION BUT OUR IMMEDIATE FIRST ORDER GOAL IS TO FACILITATE THE ON BOARDING OF THE TOP INVESTIGATORS AND GET THEM PRODUCTIVE SO WE NEED TO DEVELOP SOME TRAINING TOOLS, THESE ARE GENERALLY COMPUTATIONALLY SAVVY PEOPLE AND SO YOU KNOW EVEN IF WE CAN DO SOME EXAMPLE WORK FLOWS AND SO FORTH SO THAT THEY CAN GET GOING AND PLAY AROUND WITH IT AND THEN START DOING PRODUCTIVE WORK THOSE ARE OUR IMMEDIATE GOALS FOR TRAINING. ANYBODY ELSE WANT TO SAY ANYTHING ABOUT THAT FROM THE STAGE GROUP? >> IF YOU DO PLEASE COME UP TO THERE IS A MICROPHONE DOWN AT THE HEAD OF THE TABLE NEXT TO DR. ARNETT. >> ANYBODY ELSE? YES, SIR. >> DEAN SHEPPARD SO ARE YOU PLANNING TO EXTEND THIS TO OTHER BIG DATA SETS LIKE THE LUNG TISSUE RESOURCE CONSORTIUM HAD CT SCANS, GENE EXPRESSION ANALYSIS, THOSE SORTS OF SYSTEMS ARE NOT REALLY CURRENTLY INTEGRATED IN A WAY THAT WOULD BE ACCESSIBLE TO INVESTIGATORS. >> YES, I MEAN I'M GOING TO JUST SAY YES BECAUSE CONCEPTUALLY THAT IS EXACTLY WHAT WE WANT TO DO IS CENTRALIZE ALL THESE RESOURCES. WHAT YOU'RE SUGGESTING IS LESS OF A DEVELOPMENT CHALLENGE AS IT IS A DATA ACCESS CHALLENGE AND SO, YOU KNOW, SLOWLY WE ARE GOING AFTER THE BIG HIGH VALUE DATA SETS FIRST THAT ARE GOING TO HAVE THE BIGGEST IMPACT BUT EVENTUALLY I THINK WE ARE GOING TO WANT TO NEGOTIATE ACCESS TO ALL THESE OTHER ASSETS AND INVITE THEM TO UPLOAD THEIR DATA. AND IF I DIDN'T MENTION IT, YOU KNOW, WE ANTICIPATE ALSO THAT INVESTIGATORS WILL HAVE THE OPPORTUNITY TO UPLOAD THEIR SEQUESTERED LITTLE DATA SETS AND THEIR TOOLS AND SO FORTH AND TO REALLY MAKE THIS ENVIRONMENT YOU KNOW RUN. I KNOW LOTS OF INDIVIDUALS WHO ARE LIKE PHYSICIANS WHO HAVE CASE SETS AND THEY WANT TO FIND CONTROLS TO MATCH WITH THEM OR TO ANALYZE THEIR DATA WITH OTHER ESTABLISHED DATA SETS, YOU KNOW, SO I THINK THAT NOT ONLY WILL WE TRY TO CURATE SUCH KNOWN RESOURCES BUT WE WILL ALSO GIVE INVESTIGATORS THE OPPORTUNITY TO UPLOAD AND SHARE THEIR SEQUESTERED RESOURCES. YES, MA'AM. >> LUISA I'M INCREDIBLY IMPRESSIVE AND ENABLE TO COMMUNITY TO LEVERAGE EACH OTHER'S WORK AND YOU KNOW THE POTENTIAL OF THIS REALLY MAKING AN IMPACT IN A SHORT AMOUNT OF TIME IS UNBELIEVABLE. NOW, TWO QUESTIONS, ONE IS IN RELATION TO UP LOADING DATA THERE HAS GOT TO BE SOME KIND OF CURATION, RIGHT, I MEAN, HOW IS THAT DATA GOING TO BE MONITORED AND ENSURE THAT IT'S APPROPRIATE AND SO FORTH AND SO ON FIRST QUESTION? SECOND QUESTION IS SO I JUST WENT ON LINE TO SEE CAN I GET IN ALREADY AND I'M READY. >> OKAY. >> IT'S NOT ACCESSIBLE THOUGH SO YOU ARE SAYING SUMMER SO WHEN IS THIS GOING TO BE REALLY OPEN TO INVESTIGATORS? >> IT'S GOING TO BE -- IT'S ALREADY OPEN TO INVESTIGATORS NOW BUT PRECEDING THESE -- THIS NEW INNOVATION AND DATA ACCESS PROCEDURES WHAT WE HAVE DONE IS CREATED A WHITE LIST FOR INVESTIGATORS SO THAT THEY CAN GET ON BOARD AND START -- SO IT'S NOT A GENERAL KIND OF A DATA ACCESS, IT'S REALLY CURATE CURATED, WE GET THE NAMES OF THE PEOP PEOPLE AUTHORIZED TO COME ON BOARD AND TOP AND HAVE THE PROVISIONS IN PLACE TO BE ACCESSING AND LA LOOKING AT THE DATA AND SO FORTH AND THERE WE DOT THE IS AND CROSS THE TS AND NOT ALLOWING ACCESS TO ANYTHING THAT PEOPLE SHOULD NOT HAVE ACCESS TO BUT AS WE OPEN THIS UP WHAT WE WILL HAVE IS A MORE GENERAL ON BOARDING APPROACH WHERE WE WILL HAVE SOME KIND OF AN ID FOR PEOPLE, THERE WILL BE SOME CREDENTIALING INVOLVED AND THEN THEY CAN COME ON BOARD AND START LOOKING AT THESE AS SETS. I'M GLAD YOU BROUGHT UP THE ISSUE OF SECURITY, THIS IS SOMETHING THAT IS A VERY ACTIVE DISCUSSION FOR US RIGHT NOW. WE WANT TO MAKE SURE THAT NOT ONLY ARE PEOPLE NOT DOING MALICIOUS THINGS AND THAT IS SOMEONE LOOKING AT THE DATA SETS AND MAKING SURE THERE IS NOT ANYTHING FUNKY GOING ON AND MAKING SURE THAT THE DATA ARE SECURE AGAINST ANYBODY ACCESSING THEM IN AN UNAUTHORIZED MANNER. DOES -- PLEASE, PAUL AVALOCK RIGHT HERE OR YOU CAN COME UP HERE IF YOU LIKE. >> I WILL COME UP HERE. THANKS AND TO YOUR FIRST QUESTION ABOUT HOW DO WE HANDLE THE DATA CREATION AND THE BEST WAY TO DO IT IS TO GO BACK TO THE ORIGINAL INVESTIGATOR WHO PRODUCED THE DATA SO WHEN WE SHOWED AND BRINGING FOR EXAMPLE AND THIS IS JUST AN EXAMPLE THE COPD GENE PIS WHEN THEY SAW THE DATA BEING IN THE DATA STAGE ENVIRONMENT THEY SAID THAT IS NOT MY DATA YES IT IS THAT IS WHAT YOU GAVE IN GAP AND MAYBE YOU SHOULD CORRECT IT. WHEN THEY WERE ABLE TO SEE THEIR OWN DATA AND BEING ABLE TO TOUCH IT AND REALIZE OKAY NOW THE BEST WAY TO DO IT IS NOT TO REINVENT TE WHEEL AND TO REDO ALL THE ANALYSIS IT'S REALLY TO GO BACK TO THE INITIAL INVESTIGATOR TO MAKE SURE THAT THIS IS THEY CAN EASILY TOUCH AND EASILY SHARE AND THAT'S WHY IT'S THE BEST WAY TO IMPROVE THE QUALITY CONTROL BETWEEN THE VARIOUS DATA SETS. >> SECURITY IS YET ANOTHER ISSUE THAT IS THE QUALITY OF THE DATA BUT WE ALSO WANT TO MAKE SURE BOB ARE YOU GETTING UP? HE IS OUR GUY IN CHARGE OF DATA SECURITY SO. >> I'M PART OF THE TEAM. >> HE IS PART OF THE TEAM. >> BOB GROSSMAN. >> CHECK. I WASN'T AT THE MEETING YESTERDAY WHICH IS WHY I'M BEING ASKED TO TALK ABOUT SECURITY TODAY. >> THAT IS WHAT HAPPENS. >> SO SECURITY IS ALWAYS -- WE HAVE A LOT OF EXPERTS OUT THERE SO I'M GOING TO SAY VERY LITTLE SECURITY IS ALWAYS A TRADEOFF BETWEEN PROTECTING THE DATA BECAUSE OF WHERE IT COMES FROM THE PATIENTS AND BENEFITTING THE PATIENTS BY HAVING IMPACT BY ALLOWING RESEARCHERS TO ACCESS IT, SO IT'S RISK MITIGATION IN THAT CONTEXT. THERE HAS BEEN A HUGE AMOUNT OF EFFORT WITHIN THE STAGE PLATFORM TO PUT BEST PRACTICES IN PLACE. AND TO MAKE SURE THAT WHEN ANYONE WHO ACCESSES THE DATA HAS THE PROPER AUTHORIZATIONS AND THAT IS GOING TO CHANGE OVER TIME TO ACCESS THE DATA AND THAT THEY ACCESS THE DATA USING PLATFORMS THAT HAVE SECURITY BOUNDARIES AND THEY CAN DO THE WORK WITHIN THE SECURITY BOUNDARIES. SO THAT IS THE 50,000 FEET IS THE PHILOSOPHY IF YOU HAVE A SPECIFIC QUESTION ABOUT SECURITY WE CAN TALK ABOUT IT. DID YOU HAVE A SPECIFIC CONCERN? >> NOT PARTICULARLY. I MEAN, YOU KNOW, THIS IS JUST SO SUCH A NEW COMPONENT TO NHLBI AND THE INTERFACE OBVIOUSLY WITH EVERYTHING THAT HAS BEEN HAPPENING IN TERMS OF HACKING AND HOSPITALS HAVING ISSUES, I MEAN THESE ARE CONCERNS THAT WE ALL SHARE SO YOU KNOW PROTECTION IS ONE THING BUT THEN THE OTHER THING IS JUST MALICIOUS REMOVAL AND/OR MANIPULATION OF DATA, THAT IS GOING TO HAVE LONG-TERM CONSEQUENCES. >> THE ISSUES FOR MOST IN OUR MIND. >> COULD I PLEASE SAY IF YOU'RE USING THE HAND HELD MICROPHONE MAYBE STEP OFF TO THE SIDE AND THEN INGRID CAN USE THE ONE AT THE PODIUM AND WE WON'T GET FEEDBACK THAT IS MY PLAN. >> YOU MIGHT ALSO ALLUDE TO SORT OF GOVERNMENT STANDARDS FOR SECURITY. >> YEAH, SO THANK YOU, SO THE PARTICULAR WAY IN WHICH THE PLATFORMS SO STAGE IS A SYSTEM AND TO BE PART OF THAT SYSTEM EACH COMPONENT OF THAT SYSTEM OPERATES AT WHAT IS CALLED FHISOMODERATE SO THIS IS A SET OF SECURITY BASICALLY A SET OF POLICIES OF WHAT CAN BE DONE, PROCEDURES THAT ALLOW CERTAIN THINGS TO BE DONE AND CONTROLS TO CHECK THAT THOSE THINGS ARE BEING DONE, THIS IS USED GOVERNMENT WIDE. THERE ARE THREE LEVELS. THIS IS A FAIRLY STRINGENT LEVEL, THE POLICIES PROCEDURES AND CONTROL TAKE UP HUNDREDS OF PAGES AND THERE IS PROCESSES INCLUDING WHAT IS CALLED CONTINUOUS MONITORING TO MAKE SURE THAT THOSE POLICIES, PROCEDURES AND CONTROLS ARE BEING DONE WITHIN THE BOUNDARY. ON THE OTHER HAND ALL SYSTEMS HAVE ISSUES AND I THINK THE WAY THE PHILOSOPHY OF THE STAGE TEAM IS WE ARE TRYING TO, YOU KNOW, WHETHER THE DATA IS ANALYZED AT A UNIVERSITY OR ANALYZED WITHIN NHLBI OR ANALYZED IN A PLATFORM LIKE THIS THERE IS ALWAYS AT RISK SO WE ARE JUST TRYING TO REDUCE THAT RISK AND WE ARE CONSTANTLY ASKING HOW WITHIN THESE FHISO MODERATE SYSTEMS RESEARCHERS CAN DO WORK AND BE EFFECTIVE BUT WE CAN MANAGE THAT RISK USING WHATEVER BEST PRACTICES ARE AVAILABLE AND THESE CHANGE OVER TIME AND A LOT OF THE EFFORT HERE IS TO PUT THE BEST PRACTICES AT A PARTICULAR TIME INTO THE SYSTEM AND THAT'S A CONTINUOUS PROCESS. BUT, YOU KNOW, THERE ARE RISKS AND OUR GOAL IS TO MANAGE THOSE RISKS AND AGAIN I'M NOT SURE WHY I'M TALKING BUT I'M SPEAKING FOR THE TEAM. >> THANK YOU, BOB. THANK YOU. YES, MA'AM. >> SO AGAIN I THINK THIS IS FABULOUS AND CERTAINLY I'D LIKE TO BELIEVE THAT THIS IS A WONDERFUL AVENUE EVENTUALLY FOR JUNIOR FOLKS TO HAVE ACCESS TO DATA ET CETERA SO IT GETS ME BACK TO THE CREDENTIALING AND HOW WILL IT BE DECIDED OR IS THERE A GLOBAL PLAN FOR CREDENTIALING AS OPPOSED TO EACH COMMUNITY DEVELOPS ITS OWN CREDENTIALING I WORK FOR SHARP OR WHATEVER SO I HAVE THIS DATA ACCESS COMPARED TO SOMEBODY IN ANOTHER COMMUNITY. >> DO WE HAVE A DATA ACCESS EXPERT IN THE ROOM THAT WOULD LIKE TO SPEAK TO THIS? WHAT WE ARE LOOKING FORWARD TO, OH, GOOD, HERE COMES ALISTER, PERFE PERFECT. >> HI ALISTER THE NATIONAL ALBCIO SO I CARE ABOUT SECURITY A LOT THE BASIC RULE HERE IS IF YOU HAVE A COMMON SCAN YOU WILL BE ABLE TO BE GRANTED ACCESS, EVERYTHING WE DO AT THE MOMENT IS TIED TO DB GAP AND IF YOU HAVE APPLICATION THAT IS BEING APPROVED YOU HAVE ACCESS TO THE DATA AND WORKING ON WAYS TO GET BETTER ACCESS TO THE GENERAL RESEARCH USE DATA SO IF YOU HAVE PERMISSIONS TO DO GENERAL RESEARCH USE DATA YOU SHOULD HAVE ACCESS IN DATA STAGE VERY VERY QUICKLY THE IDEA IS TO GET THE BARRIER OF ENTRY IN TERMS OF CREDENTIALING AS LOW AS POSSIBLE AND RELYING ON THE THINGS THAT WE ALREADY KNOW WORK THE ERA PROCESSES, INSTITUTIONAL SUPPORT OF A INDIVIDUN INDIVIDUAL HEADER. >> THANKS ALISTER. THIS WILL BE AN EVOLVING AREA NO DOUBT YOU KNOW WE ARE STARTING WITH OUR KNOWN TRUSTED INSIDERS AND AS WE GET BIGGER AND BIGGER THE IDEA WOULD BE SO THAT SOMEBODY POST DOC COULD COME IN AND START BUILDING AN ANALYSIS TESTING THEIR OWN HYPOTHESIS USING ALL OF THESE AS SETS THAT ARE AVAILABLE TO THEM, GARY KNOWS WE WERE PART OF THE PRIDE PROGRAM TOO AND IN MENTORING SOME OF THESE INDIVIDUALS THEY JUST NEEDED ACCESS TO YOU COULD EVEN SEE THE YOUNG INVESTIGATORS COMING ON BOARD AND DESIGNING STUDIES WITH THE ASSETS AT HAND AND BEING ABLE TO USE THEM WITH FACILITY. ANYBODY ELSE? DO WE HAVE ANY MORE QUESTIONS? IF NOT I WANT TO THANK YOU AGAIN DOCTOR AND THE MEMBERS OF YOUR TEAM. THANK YOU SO MUCH. [ APPLAUSE ] WE ARE NOW GOING TO HEAR THE REPORT FROM OUR DIVISION OF INTRAMURAL RESEARCH I THINK YOU WILL FIND THIS TO BE QUITE INTERESTING WE WILL START WITH DR. BALABAN AND GIVE A BRIEF INTRODUCTION TO OUR SPEAKER DR. ALTAN-BONNET. >> HI, ARE WE OKAY? OKAY, AND STAY AWAY FROM THERE, I GOT THAT, I SAW THAT. FIRST OFF THANK YOU VERY MUCH FOR COMING. I APPRECIATE THE INTRODUCTION THAT GARY GAVE TO OUR PROGRAM EVERY JUNE WE HAVE OUR FINAL BS KRCHL REPORT THAT DR. BONNET WILL MAKE A REPORT IN THE CLOSED SESSION AND WHAT WE LIKE TO DO IS GIVE YOU A LITTLE FLAVOR FOR THE SCIENCE IN THE INTRAMURAL PROGRAM WE HAVE A KIND OF AN ACKNOWLEDGMENT PROGRAM CALLED THE ORLOF SCIENCE AWARDS EVERY YEAR WE TRY TO FIND A PARTICULAR OUTCOME FROM THAT YEAR THAT WE CELEBRATE AND ALSO TRY TO MAKE A LAY GEARED VIDEO A SHORT VIDEO ON THAT PARTICULAR SCIENCE BECAUSE IN OUR STRATEGIC SESSION WE FOUND MOST PEOPLE DIDN'T KNOW THAT THERE EVEN WAS A DIR FOR A NHLBI OR NIH IN GENERAL SO WE THOUGHT THIS WAS A GOOD WAY OF STARTING IF YOU WILL SPREAD THE WORD OF THE TYPE OF WORK BEING DONE. SO A ONE OF THE PEOPLE WHO WON THIS YEAR WAS DR. HIGH YOU WILL HEAR ABOUT HIM IN THE CLOSED SESSION AND HE WAS REVIEWED THIS YEAR AND LET'S START IT AND SEE IF WE GET SOUND. I SAW 36-YEAR-OLD WITH PSORIASIS AND NOT THE SEVERE FORM IT WAS ELBOWS AND KNEES AND HAD A CORONARY SCAN DONE ON HIM AND HE HAD ART ARTERY PLAQUE THAT LOOKED LIKE HE WAS 60 YEARS OF AGE AND I SAID I GOT TO FIGURE THIS OUT I'M THE HEAD OF THE INFLAMMATION AND CARDIAC DISEASE AT THE HEART LUNG AND BLOOD INSTITUTE. OUR OBSERVATION IS THE FIRST IN HUMAN DISCOVERY THAT TREATMENT OF REMOTE INFLAMMATION IN THE BODY CAN REDUCE THE PLAQUE THAT IS PRONE TO RUPTURE TO CAUSE HEART ATTACK CLASSICALLY A HEART ATTACK IS CAUSED BY ONE OF FIVE DIABETES HYPERTENSION HIGH CHOLESTEROL FAMILY HISTORY OR SMOKING BUT NOW WE HAVE EVIDENCE THAT THERE IS A SIXTH FACTOR AND THAT FACTOR IS INFLAMMATION AND IT'S CRITICAL TO NOT ONLY THE DEVELOPMENT BUT THE PROGRESSION OF ARTHROSCLEROSIS AND WE LOOKED AT OVERACTIVE SKIN SELLS IN THE SKIN AND WHEN WE LOOKED IN THE BODY THEY WERE THE SAME CELLS WE WERE FINDING IN THE HEART ARTERIES AND STARTED MAKING A CONNECTION BETWEEN THE FIRST PART OF INFLAMMATION LEADING TO HEART ARTERY DISEASE GOING IN WE ASKED IS THE IMMUNE SYSTEM ASSOCIATED WITH HEART ARTERY PLAQUE BUILD UP THAT WAS THE FIRST QUESTION AND THE SECOND QUESTION IS IF YOU TREAT THE SKIN DISEASE WHICH IS DRIVING THE IMMUNE SYSTEM OVERACTIVE CAN YOU REDUCE THE HEART ARTERY DISEASE? OUR LAB HAS DISCOVERED THAT THERE IS A DISEASE STATE THAT LEADS TO HEART DISEASE AND THAT IS PSORIASIS OUR DISCOVERY HAS BEEN DEMONSTRATING THAT THERE IS AN ACCELERATED LIPID RICH PLAQUE OR SOFT IN THE HEART THAT CAUSES MIOCARDIAL INFARCTION AND WHEN WE TREATED THE SKIN DISEASE THEIR HEART ARTERIES ACTUALLY LOST THAT AGE. SO TREATING THE SKIN DISEASE ACTUALLY REVERSED THE IMMUNE RESPONSE WHICH INTERN REVERSED THE HEART ARTERY DISEASE IT'S ASTONISHING IN THE STUDY WE HAVE COMPLETED WE SAW NO AFFECT ON LIPIDS GLUE CLOSE OR CARDIOVASCULAR AND THIS IS PURELY ANTIINFLAMMATORY AND WE STILL GOT THE HEART ARTERIES BETTER THE ONLY THING THAT CHANGED WAS THEIR INFLAMMATION SO I THINK THAT THE INCREMENTAL VALUE HERE IS WE ARE CHANGING THE NATURAL HISTORY OF THAT CORONARY PLAQUE THAT IS SO COOL AND NEVER HAVE BEEN ABLE TO CHANGE THE HISTORY OF THE PLAQUE AND TREATING REMOTE INFLAMMATION IN THE BODY CAN REDUCE HEART ARTERY DISEASE, INFLAMMATION THOUGHT OF A RISK FACTOR CAN BE SOMETHING WE TREAT AND TARGET TO POTENTIALLY SAVE THE LIVES OF MILLIONS OF PEOPLE FROM DEVELOPING HEART ATTACK AND HEART DISEASE. SO THIS IS -- [ APPLAUSE ] THIS IS ONE OF ABOUT 20 ON YOUTUBE AND THE TEAM LED BY LANORE AND A PHENOMENAL JOB PUTTING THESE TOGETHER TO TELL THE STORY AND NIHAL IS THE LAST CLINICAL INVESTIGATORS AT NHLBI TO MOVE FORWARD, WE HOPE IF YOU APPROVE THE DECISION OF THE BOARD THIS MORNING THAT HE WILL MOVE ON TO TENURE BEING THE FIRST TENURED INVESTIGATOR. THE LASKAR PROGRAM IS VERY IMPORTANT AND LET'S US BRING IN JUNIOR CLINICAL INVESTIGATORS AND GIVE THEM EIGHT YEARS OF UNINTERRUPTED SUPPORT AND A POINT OF FACT HALFWAY THROUGH THERE THEY DECIDE SOMEWHERE ELSE MIGHT BE A BETTER PLACE FOR THEM TO GO THEY CAN CARRY THE MONEY TO THE OUTSIDE BACK TO AN OUTSIDE INSTITUTION FOR THE REMAINING EIGHT YEARS IT'S KIND OF LIKE HAVING AN McARTHUR GENIUS AWARD TO FOLLOW YOU IN YOUR CAREER SO IT'S A REALLY IMPORTANT TOOL IN TERMS OF GETTING MORE PEOPLE LIKE NIHAL HERE SO TODAY IS GOING TO BE A NIHAL SQUARED PRESENTATION. THE NEXT SPEAKER IS NIHAL ALTAN-BONNET SHE IS A NEURO STAFF INVESTIGATOR ANALOGOUS TO ALASKAR BROAD SEARCHERS ON THE INWHETHER CLINICAL SIDE AND SHE IS THE CHIEF LABORATORY OF HOST PATHOGEN AND DID UNDER GRAD AT HUNTER PH.D. AT ROCKEFELLER AND POST DOCKET AT CHILD HEALTH AND DEVELOPMENT AND STAFF INVESTIGATORS 13-17 AND WAS JUST RECENTLY TENURED IN 2017. I THINK THIS STORY THAT SHE IS GOING TO TELL IS SOMETHING THAT YOU KNOW IS KIND OF THEME IN THE INTRAMURAL PROGRAM IS WE ARE NOT NECESSARILY SPECIFIC TO MISSION BUT WE ARE SPECIFIC TO IDEAS AND FINDING OUT HOW THINGS WORK IN OUR BODIES AND IN BIOLOGY AND I THINK THIS IS A WONDERFUL EXAMPLE OF GOING FROM A LABORATORY AND ACTUALLY HAVING WHAT MAY POTENTIALLY BE HUGE CLINICAL IMPACT IN THE FUTURE NIHAL. >> GOOD MORNING EVERYBODY, THANK YOU FOR BEING HERE. I'M NIHAL ALTAN-BONNET I'M THE HEAD OF THE LABORATORY OF HOST PATHOGEN DYNAMICS AND TODAY I'D LIKE TO TELL YOU ABOUT A DISCOVERY WE MADE IN OUR LAB HERE AT NHLBI ABOUT A NEW FORM OF VIRAL TRANSMISSION, A VERY VIRALANT TRANSMISSION WHERE VIRUSES MOVE AND TRANSMIT TO OTHER HOSTS INCLUDING HUMANS IN THE FORM OF POPULATIONS IN THE FORM OF CLUSTERS, HIDDEN INSIDE MEMBRANE BOUND VESICLES. SO LET ME TELL YOU WHEN WE GOT INTO THIS WORK WHAT THE OLD PARADIGM OF VIEWING VIRAL TRANSMISSION WAS LIKE AND THIS IS A MOVIE I TOOK FROM NPR BASICALLY WHAT GENERALLY WAS WRITTEN IN THE TEXTBOOKS AND WHAT EVERYBODY IN THE VIROLOGY FIELD THOUGHT OF VIRAL TRANSMISSION WAS HAPPENING THROUGH IS SINGLE VIRAL PARTICLES WHERE A VIRUS WOULD INFECT THE CELL REPLICATE INSIDE THE CELL AND LEAVE THAT CELL THROUGH A BUDDING OR ANALYTIC PROCESS AND THEN SPREAD TO OTHER HOSTS AND THE KEY TAKE HOME POINT MESSAGE FROM HERE IS THE VIRUS ARE MOVING TO OTHER HOST OF INDEPENDENT PARTICLES AND INFECTIOUS UNITS AND, IN FACT, THIS FORM OF INDEPENDENT MOVEMENT OF VIRAL PARTICLES HAD ALWAYS BEEN THOUGHT TO BE TO MAKE VIRAL TRANSMISSION VERY EFFICIENT BECAUSE IT COULD THE VIRUSES THIS WAY BY MOVING INDEPENDENTLY FROM ONE ANOTHER COULD SPREAD TO AS MANY HOSTS AS POSSIBLE. SO WHEN WE STARTED THIS WORK WE WANTED WE REEXAMINED THIS PARADIGM WHETHER IT WAS REALLY CORRECT OR NOT THAT VIRUSES MOVE AROUND INDEPENDENTLY FROM ONE ANOTHER AND IN THE LAB WE STARTED WORKING WITH A NUMBER OF VIRUSES AND I'M JUST GIVING YOU SOME OF THESE VIRUSES HERE THAT WE WORK WITH, THESE ARE ALL R AND A VIRUSES AND THEY CAUSE MANY IMPORTANT HUMAN DISEASES FOR INSTANCE POLIO VIRUS CAUSES POLIO MIE MYLITIS AND ROTO VIRUS CAN SOMETIMES LEAD TO DEATH IN THE VERY YOUNG AND VERY ELDERLY AND COCSACKI IS A VIRUS ONE OF THE CAUSE OF AGENTS OF MIOCARDITIS AND THIS ONE THAT RECENTLY HAS BEEN IN THE NEWS AND VIRUS D68 ASSOCIATED WITH THE POLIO LIKE ILLNESS IN CHILDREN CALLED ACUTE FLACIDMYLITIS AND WE LOOKED AT THE TRANSMISSION ISSUE AND THE VIRUSES I SHOWED YOU IN THE PREVIOUS SLIDE I HAVE ONE THING IN COMMON OR AT LEAST ONE THING IN COMMON THAT WAS THOUGHT ABOUT THEM IN ADDITION TO BEING R AND A VIRUSES IS THEY ALL AFTER REPLICATION IN THE CELL WERE THOUGHT TO LEAVE THE CELL THROUGH LYTIC RELEASE BECAUSE THESE VIRUSES DO NOT HAVE AN ENVELOPE ON THEM, IT'S JUST A PROTEIN SHELL, SO IT WAS ASSUMED AND CERTAINLY SOME LABORATORY DATA BACKED UP THIS ASSUMPTION THAT CELLS THAT WERE INFECTED WITH THESE VIRUSES WOULD LICE IN ORDER FOR THESE VIRUSES TO COME OUT AND OF COURSE THE LYSIS METHOD OF RELEASE INEVITABLY LED TO SINGLE PARTICLE DISSEMINATION AND THE THOUGHT VIEW VIRUSES BEING RELEASED THROUGH INDEPENDENT SINGLE PARTICLES ANOTHER FEATURE I WANT TO BRING OUT HERE THAT WILL BE OF IMPORTANCE LATER ON IS THAT R AND A AND SOME DNA VIRUSES AFTER REPLICATION HAVE A TREMENDOUS AMOUNT OF GENETIC DIVERSITY BECAUSE DURING THE REPLICATION PROCESS ANY ERRORS THAT ARE BECOMING CODED INTO THE NEW VIRAL GENOMES DON'T GET CORRECTED BY THE PRELIMINARY THAT DO THE REPLICATION BECAUSE THE VIRAL ENZYMES LACK THE PROOFREADING MECHANISMS SO I JUST WANT TO REMIND YOU OF THAT LATER ON TOO THAT THERE IS A TREMENDOUS AMOUNT OF GENETIC DIVERSITY IN THE PROGENY OF THESE VIRUSES. SO WITH THESE VIRUSES AT HAND WE STARTED USING OUR MICROSPOCY AND THE STRENGTH OF MY LAB IS A VARIETY OF LIGHT AND ELECTRON MICROSCOPIC TOP END PERIMETER NEARS TO LOOK AT HOST INTERACTIONS TO LOOK WHAT HAPPENS TO A CELL INFECTED WITH POLIO VIRUS DURING THE TIME WINDOW WHEN IT'S BEING RELEASED FROM THE CELL. NOW REMEMBER WHAT WAS ASSUMED WAS THAT THIS WAS AN LYTIC PROCESS THE CELL WOULD LYCE FOR THE VIRUS TO RELEASE AND LOOKED BY SCANNING EM ON SURFACE OF THE SELLS INFECTED WITH POLIO VIRUS WE SAW THERE WERE VESICLES THIS IS A PORTION OF THE CELL, CELLULAR PROJECTIONS AND SEE THE LARGE VESICLES ABOUT 400NANO METERS EMERGING FROM THE CELLS AND THESE VESICLES WE SHOWED ACTUALLY CONTAIN POLIO VIRUS SO POLIO VIRUS WE ARE LABELING WITH AN ANTIBODY IT'S A FLOWUORESCENT ANTIBODY AND HAVE POLIO VIRUS IN THEM AND THE FIRST HINT TO US MAYBE THIS VIRUS HAS ANOTHER METHOD-RELEASE FROM THE CELLS NOT NECESSARILY LYSIS AND WHAT WAS MORE EXCITED IS WHEN WE ACTUALLY COLLECTED THE VESICLES FROM THE OUTSIDE OF THE CELLS FROM THE MEDIA OF THE CELLS AND DID ANOTHER TYPE OF EM METHOD TRANSMISSION AND SECTIONED THE VESICLES AND BLOWN AWAY WE FOUND THE VESICLES HERE IS ONE OF THE VESICLES CONTAINED MANY POLIO VIRUS PARTIBLES INSIDE THEM WHAT I MEAN BY MANY IS FROM 30-100 PARTICLES WERE PACKAGED WITHIN ONE OF THESE VESICLES AND THIS IS SORT OF A CARTOON DEPICTION OF ONE OF THE EM SLIDES. SO THIS WAS REALLY EXCITING. AND SINCE THIS DISCOVERY THERE HAVE BEEN MANY OTHER LABS WHO HAVE FOUND THAT THEIR FAVOR VIRUSES ARE ALSO TRAVELING IN CLUSTERS INSIDE EXTRA CELLULAR VESICLES AND THIS IS A CARTOON THAT I DREW SO UP HERE ARE THE ONES POLIO VIRUS AND COC AND RYNO USE EXTRA CELLULAR VESICLES TO COME OUT OF CELLS AND OTHER HAVE SHOWN HEPATITIS A, E, HEPATITIS C, WEST NILE AND DANGNE HAVE A FORM WHICH VIRAL PARTIBLES OR NAKED INFECTIOUS GNOMES ARE PACKAGED AND RELEASED FROM CELLS AND RECENTLY WE SHOWED ROTO USES THE CELLS TO TRANSMIT CLUSTERS OF ITSELF FROM THE CELL AND THE OTHER THING I WANT TO POINT OUT FROM THIS SLIDE IS THAT THERE IS ESSENTIALLY THREE CELLULAR PATHWAYS THAT THESE VIRUSES EXPLOIT IN ORDER TO COME OUT OF CELLS IN THE VESICLES ONE IS THE OTOPHOGY PATHWAY AND THEY GO AWAY FROM LYSOSOMES TO PLASMA AND RELEASE OF A VESICLE THE SECOND IS THE MULTI VESCICULAR AND MAKING THE SMALLER VESICLES THAT FUSE WITH THE PLASMA AND RELEASES THEM AND THIRDLY IS THE PLASMA MEMORY DEVICE VESICLES THAT DIRECTLY BUD FROM THE PLASMA MEMBRANE AND TAKE ALONG WITH THEM VIRAL PARTICLES OR NAKED INFECTIOUS GENOMES AND THE LIST IS GROWING SO RIGHT NOW THERE IS ABOUT 50 DIFFERENT VIRUSES RNA AND SOME DNA AS WELL THAT ARE PACKAGING THEMSELVES AND RELEASING AN EXTRA CELLULAR VESICLES TO BE TRANSMITTED TO OTHER HOSTS. SO ONE OF THE THINGS MY LAB WANTED TO KNOW WHEN WE DISCOVERED THIS WAS ARE THESE PACKETS INFECTIOUS AND AGAIN WE DID THESE EARLY STUDIES WITH POLIO VIRUS BUT MUCH OF WHAT I'M GOING TO TELL YOU ACTUALLY HAS BORN TO BE TRUE WITH OTHER VIRUSES INCLUDING COCSECK AND NOROVIRUS, D68 AND DID SIMPLE EXPERIMENTS AT THE BEGINNING AND TOOK VESICLES AND INOCCULATED IN A DISH OF CELLS AND PARALLEL WE TOOK THE CONTENTS OF VESICLES IN OTHER WORDS THE FREE VIRUSES AND INOCULATED THEM INTO ANOTHER DISH OF CELLS AND ASKED VERY SIMPLE QUESTIONS FIRST QUESTION WAS DID WE GET INFECTION IN THESE CELLS WHERE VIRAL GENOMES ABLE TO BE TRANSFERRED IN THE CY CYTO PLASM AND WHAT YOU SEE HERE IS A SINGLE MOLECULE CMA AND A SINGLE CELL HERE TAKEN FROM THIS DISH AND YOU SEE A CLUSTER OF GENOMES THAT HAVE GONE IN THE CYTO PLASM AND LIFE CONTAINING VESICLES ARE ABLE TO TRANSFER THE VIRAL GENETIC CONTENT IN THE CYTO PLASM OF THE CELLS AND WITH THE FREE VIRUSES OF COURSE WE EXPECTED TO FIND VIRAL GENOMES AND WE DID AND HERE IS A CELL, HERE IS THE NUCLEUS AND LONELY ONE SITTING IN THE CYTO PLASM BEFORE REPLICATING ITSELF AND CAN BE TRANSFERRED INTO CYTOSOL AND ASKED WHICH DISH IF WE WAIT NUMBER OF HOURS AND LET THESE VIRUSES REPLICATE WHICH DISH WILL GIVE US MORE VIRAL YIELD. AND IF WE LOOK AT THIS CARTOON THINKING WITH THE OLD PARADIGM WE WOULD THINK THAT THIS DISH WOULD HAVE A BETTER CHANCE OF PROVIDING MORE VIRUS, WHY? BECAUSE THE VIRAL PARTICLES ARE MOVING AROUND INDEPENDENTLY, THEY ARE GOING TO BE ABLE TO SPREAD OUT AND INFECT MANY MORE CELLS WHEREAS IN THIS DISH LET'S SAY WE ONLY HAVE THREE VESICLES YOU ONLY ARE GOING TO GET AT MOST THREE CELLS INFECTED. EACH VESICLE IS GOING TO GO INTO ONE SO THE OTHER CELLS WILL REMAIN EMPTY AND NOT BE ABLE TO PRODUCE VIRUS BUT WHAT WE FOUND SURPRISED US. THIS DISH ENDED UP PRODUCING MORE VIRUS THAN THIS DISH. AND WHAT THAT TOLD US AND I'M SKIPPING OVER A LOT OF DATA IN INTEREST OF TIME THAT SUPPORTS THIS IDEA WHAT WE THINK NOW IS THAT THERE ARE SIGNIFICANT BARRIERS TO REPLICATION WHEN TWO FEW OF VIRUSES INFECT A CELL. AND THESE BARRIERS CAN COME FROM DIVERSE SOURCES, ONE IS THAT WHEN A VIRUS GOES INTO A CELL IT NEEDS TO TRANSLATE ITSELF, IT NEEDS TO REPLICATE ITSELF AND THESE PROCESSES TAKE TIME AND DURING THIS TIME THE HOST IN AN IMMUNE RESPONSE IS REACTING TOWARDS THE VIRUS AND THAT CAN LEAD TO DEGRADATION OF THE VIRUS AND DISMISSAL OF THE VIRUS. IN ADDITION, AS I MENTIONED EARLIER THESE VIRUSES ARE CARRY A LOT OF MUTATIONS IN THEM, SOME OF THESE MUTATIONS CAN BE ADVANTAGEOUS BUT SOME CAN BE DELL DELETERIOUS AND IF IT SLOWS DOWN THE TRANSLATION OR SLOWS DOWN THE REPLICATION IT'S GOING TO BE EVEN MORE VULNERABLE TO THE HOST'S DEFENSE. HOWEVER, WHEN MULTIPLE VIRUSES GO IN, INSIDE ONE OF THE EXTRA CELLULAR VESICLES THEY LITERALLY GO IN AS AN ARMY AND YOU WILL RAMP UP PROTEIN TRANSLATION AND REPLICATION VERY, VERY QUICKLY AND IF THERE ARE MUTATIONS AMONG THESE VIRUSES WHAT WE ARE FINDING RIGHT NOW IS THAT THERE CAN BE COMPLIMENTARY COOPERATIVE EVENTS TAKING PLACE AMONG VIRAL GENOMES AND ONE IS NOT ABLE TO MAKE IT WE ARE FINDING IT CAN USE THE POLIMORACE THE BROTHER IT WENT IN THE CELL WITH AND SHARE MACHINERY AND GET ITSELF TO REPLICATE. SO WE WANTED TO HAVE THE DATA WAS IN VETRO AND REALLY WANTED TO KNOW ARE THESE EXTRA CELLULAR VESICLES CONTAINING VIRAL CLUSTERS RELEASED FROM ANIMALS AND HUMANS AND ARE THEY A SIGNIFICANT FORM OF VIRAL TRANSFORMATION IN THE POPULATION AND IN ORDER TO BE ABLE TO DO THESE STUDIES WE RESORTED TO LOOKING ATRO TO VIRUS AND NORO VIRUS THESE TWO VIRUSES ARE THE MAJOR CAUSES OF MORBIDITY WITH DIARRHEA AND ANIMAL MODELS AVAILABLE AND HUMAN SAMPLES READILY AVAILABLE THROUGH THE CLINICAL CENTER AT NIH AND BOTH VIRUSES REPLICATE IN THE INTESTINE. AND SO WITH THESE CLINICAL SAMPLES THAT WE WERE ABLE TO RECEIVE FROM THE BUILDING TEN ONE OF THE FIRST THINGS WE DID TO LOOK FOR THESE VESICLES IS FIRST TO SEE IF THEY WERE TRULY POSITIVE FOR ROTO AND NORO VIRUS WE HAVE THIS MACHINE IN OUR LAB NOW MADE BY QUIGIN UNDER AN HOUR CAN GIVE US QPCR-CT VALUES FOR 65 PATHOGENS AND WE DIRECTLY PUT IN THE SAMPLE AND IT CAN BE STOOL OR SPUTUM OR INTRA NASAL AND SERUM IN THE MICRO FLUID CASSETTES WITH NO PROCESSING AT ALL STICK IT IN THE MACHINE AND UNDER AN HOUR WE GET CT VALUES SO FIRST WE DO THIS IN ORDER TO LET US KNOW WHETHER THE SAMPLE WE HAVE TRULY IS POSITIVE FOR ROTO OR NORO VIRUS THEN WE USE A TECHNIQUE WE DEVELOPED IN THE LAB TO ISOLATE THE POTENTIAL VESICLES FROM SAY THE STOOL SAMPLE IN AN ROTO VIRUS INSPECTED OR NOTO VIRUS INFECTED PATIENT THIS METHOD IS BRIEFLY TAKING ADVANTAGE OF A DISCOVERY WE MADE THAT THESE VIRUS CONTAINING VESICLES IN VETRO HAD LIPIDS ON THE OUTER MEMBRANE LEAFLETS AND USE BEADS FOR LIPID BINDING PROTEINS TO ESSENTIALLY PULL THESE VESICLES DOWN IF THEY ARE THERE FROM A STOOL SYSTEM OR A BLOOD SAMPLE OR INTRA NASAL LAVAGE SAMPLE AND DOING THIS WHAT WE DISCOVERED IS THAT HUMAN ROTO VIRUS INFECTED AND NOTO VIRUS INFECTED STOOLS 50% OF THE VIRUS IN THOSE STOOLS IS INSIDE VESICLES AND YOU CAN SEE HERE THESE ARE TWO VESICLES CONTAINING ROTO VIRUS A HALF A MICRON IN SIZE EACH AND CONTAIN MULTIPLE PARTICLES AND HUMAN NORO VIRUS WHICH ARE SMALLER IN SIZE A COUPLE HUNDRED NANO METERS AND CONTAIN FEWER PARTICLES IN THEM AND WANTED TO KNOW ARE THESE VIRAL CLUSTERS IN THE VESICLES ARE THEY ABLE TO TRANSMIT AMONG ORGANISMS SO USING ANIMAL MODELS MOUSE MODELS WE LOOKED AT THIS QUESTION AND I'M SHOWING YOU THE DATA HERE WITH ROTO VIRUS AND FIRST WE WANTED TO KNOW ARE THESE VESICLES THAT ARE IN THE STOOL ARE THEY STABLE IF THEY ARE INGESTED THROUGH ANOTHER HOST SO ROTO VIRUS IS TRANSMITTED THROUGH THE ORAL FECAL PATHWAY SO WE WANTED TO KNOW ARE THE VESICLES ABLE TO RETAIN THEIR VIRAL CLUSTERS AS THESE VESICLES MOVE DOWN THE GI TRACT OF THE NEXT SUSCEPTIBLE HOST AND WE TOOK THE VESICLES FROM THEM, LABELED THE VESICLES WITH A FLUORESCENT DIE ON THEIR MEMBRANE AND FED THESE VESICLES TO ANOTHER ANIMAL, A MOUSE IN THIS CASE AND DIFFERENT TIME POINTS AFTER INJECTION WE HARVESTED THE SMALL INTESTINE CONTENTS AND LOOKED FOR THESE VESICLES BY MICROSPOPY AND WE FOUND IN THE UPPER PARTS OF INTESTINE AFTER HAVING PASSED THROUGH THE STOMACH WE COULD STILL FIND THESE VESICLES AND THESE VESICLES RETAIN THEIR ROTO VIRUS CONTENT SO REMARKABLY THESE VESICLES ARE STABLE AS THEY ARE GOING DOWN VERY LOW PH, PROTO ENVIRONMENT AND TRYING TO UNDERSTAND WHY THAT IS SO AFTER HAVING DONE THIS EXPERIMENT WE HAD CONFIDENCE IN ORDER TO DO THE FOLLOWING EXPERIMENT WHICH IS COMPARE THE VIRALANCE AND INFECTION CONSISTENCY OF ANIMAL FED VIRUS TO FEED AND THIS IS LIKE THE POLIO IN CELL CULTURE BUT DOING IT WITH ANIMALS AND WE FED ONE SET OF MICE VESICLES WITH ROTO PARTICLES AND ANOTHER MOUSE THE VIRUS PARTICLES BUT IN THE FREE FORM AND INDEPENDENT FORM AND POUND FOR POUND EACH VIRUS ANONYMOUS GOT THE SAME AMOUNT OF VIRAL PARTICLES AND WE MONITORED THE MOUSE FOR CLINICAL SIGNS OF ROTO VIRUS INFECTION AND INTESTINAL VIRAL LOAD WHICH I'M PRESENTING HERE AND WHAT WE FOUND WAS THAT THE MICE THAT WERE FED THE VESICLES WITHIN 24 HOURS THEY STARTED REPLICATING THE VIRUS INSIDE THEIR INTESTINE AND BY THREE DAYS IT WAS THE VIRAL BURDEN WAS QUITE HIGH WHEREAS IT TOOK NEARLY THREE DAYS IN ORDER FOR US TO BE ABLE TO DETECT VIRAL REPLICATION IN THE MICE THAT WERE GIVEN THE FREE FORM OF THE ROTO VIRUS AND REMEMBER EACH SET OF ANIMALS GOT EXACTLY THE SAME NUMBER OF VIRAL PARTICLES EXCEPT THE RED ANIMALS HERE GOT THE VIRUS IN THE VESICLE FORM AND WHEN WE LOOKED INTO THE INTESTINE SO THIS IS A DEJUNIUM FROM THE MICE YOU SEE LOTS INFECTED WITH ROTO THIS IS THREE DAYS POST INFECTION AND LOOK AT THE FREE VIRUS FED MICE THERE ARE FEW SITES THAT ARE INFECTED AND BLACK AND WHITE DIFFERENCES IN THE INFECTION EFFICIENCY OF THE VESICLES. AND ONLY BY FEEDING THE MICE MUCH HIGHER DOSES OF FREE VIRUS COULD WE MIMIC SOME OF THE EFFECTS OF THE VESICLE FED ANIMALS SO ONLY BY DUMPING TONS OF FREE VIRUS INTO THE GUTS OF THESE ANIMALS FEEDING THEM COULD WE ACTUALLY GET SIMILAR NUMBERS OF ANTERO VIRUS INFECTED SO THE MODEL RIGHT NOW WHAT THE VESICLES DO IS ESSENTIALLY INCREASE THE MULTIPLICITY OF INFECTION AS THEY ARE GOING DOWN TO THE INTESTINE SO VESICLE ENDS UP DELIVERING A BOLUS OF VIRUSES AND FREE VIRUSES END UP BEING DILUTED AS THEY COME DOWN AND VERY LOW NUMBER OF VIRUSES HIT THE INTESTINE AND BECAUSE OF THOSE REPLICATION BARRIERS WE THINK THAT ARE TAKING PLACE THEY DON'T END UP REPLICATING MUCH AT ALL. SO I JUST WANT TO END AND JUST GIVE YOU A BRIEF OVERVIEW OF SOME OF THE CURRENT STUDIES WE ARE DOING NOW WITH THIS WE CALL IT THE NEW TYPE OF PATHOGEN CLOAKED VIRUSES AND FOCUSED ON THREE AREAS AND ADAPTIVE CELLULAR MECHANISMS WITH VESICLES AND WONDERING HOW THE VESICLES ARE ABLE TO TRANSFER GENOMES AND BIO HOW DOES THAT WORK AND THIRDLY THE ENVIRONMENTAL PUBLIC HEALTH IMPACT OF THE VESICLES SO JUST GIVE YOU A BRIEF OVERVIEW WHAT WE FOUND AND THIS IS A WORK THAT WE ARE PUTTING TOGETHER IS THAT WHEN MULTIPLE VIRUSES ENTER A CELL THE WHOLE INNATE RESPONSE OF THE CELL IS COMPLETELY MESSED UP THERE IS NO INTERRON OR KITOKINE AND WHEN THEY ENTER CELLS WE KNOW CELLS START REACTING AND START PRODUCING INTERFERON BETA IN COPIOUS AMOUNTS TO INVITE EVERYBODY IT'S AND IT'S SNEAKTY TO HIJACK IT AND SHUT IT DOWN SO THE CELL DOES NOT THINK IT'S INFECTED WITH VIRUSES. SECONDLY WE FOUND IN A SIMILAR VAIN THE ADAPTIVE IMMUNE RESPONSE IN ANIMALS IS COMPLETELY BLUNTED WHEN VIRUS GO IN VESICLES HERE I'M JUST GIVING YOU AN EXAMPLE OF WHAT HAPPENS TO THE MILK ANTIBODIES THE MILK OF MOMS WHOSE PUPS HAVE BEEN INOCULATED WITH ROTO VIRUS A CHILDHOOD INFECTION WHEN THE PICKUPS HAVE BEEN INOCULATED WITH FREE ROTO VIRUS THE MOMS START HAVING IGA IN THE MILK AND GETS PASSIVELY TO THEIR PICKUPS AND HELPS IN THE PROTECTION OF THE PUPS BUT THE PUPS FED WITH THE VESICLES THE MOMS MAKE NO RESPONSE AT ALL AND THE MOMS ARE COMPLETELY OBLIVIOUS TO PUPS GETTING INFECTED WITH THESE VIRUSES SO WE ARE STUDYING WHY, WHAT IS THE BASIS OF THIS, WHAT IS THE MECHANISM. FINALLY IN TERMS OF PUBLIC HEALTH WE HAVE A COLLABORATION WITH GW THE ENVIRONMENTAL ENGINEERING DEPARTMENT WHERE THEY ARE STUDYING THE STABILITY OF VESICLES CONTAINING NOTO AND ROTO VIRUS IN WASTEWATER AND WASTEWATER TREATMENT CONDITIONS AND WHAT THEY ARE FINDING AND THIS IS JUST A VERY A LITTLE BIT OF DATA HERE IS THAT THESE VESICLES ARE HIGHLY STABLE IN WASTEWATER AND THEY RETAIN THE VIRUSES INSIDE THEM AND WE CAN COLLECT THEM FROM THE WASTEWATER AND RE IN -INOCCUR LATE THEM AND HOW DO THEY FAIR UNDER TYPICAL WATER TREATMENT CONDITIONS SUCH AS HEAT, FREE CHLORINE, OZONE, UV, IS THERE ANY SPECIAL PROPERTIES OF THESE VESICLES THAT MIGHT MAKE THEM MORE RESISTANT TO THESE TREATMENTS AND CAN WE LEARN FROM THAT AND MAKE POTENTIALLY MAKE THESE WATER TREATMENT PROCEDURES MORE EFFECTIVE AGAINST VESICLE CONTAINED VIRUSES. SO I JUST WANT TO END INTRODUCE MY GROUP MY GROUP HERE DID ALL THE WORK I SHOWED YOU. SOME PEOPLE ARE MISSING, THEY MOVED ON AND ALSO I WANT TO THANK THE CLINICAL CENTER WHO HAS BEEN VERY GENEROUS IN PROVIDING HUMAN SAMPLES FROM INFECTED PATIENTS, I GAVE YOU SOME OF THE DATA WITH ROTO AND NORO VIRUS AND OTHER PATIENTS INFECTED WITH OTHER VIRUSES THAT ARE SEEN AT THE CLINICAL CENTER AND THE CLINICAL CENTER FOLKS HAVE REALLY GENEROUSLY PROVIDED THE SPECIMENS TO US AND VERY EASILY PROVIDED THE SPECIMENS TO US. I ALSO WANT TO THANK THE ANIMAL CORE, THE EM CORE, THE FLOW CORE AND THE PROTIONOMICS AT NHLBI THEY ARE REALLY INCREDIBLE FACILITIES AND WORK WITH US TO MAKE ALL OF THESE EXPERIMENTS POSSIBLE AND THE RESULTS YOU SEE POSSIBLE. THANK YOU FOR YOUR TIME. [ APPLAUSE ] SO I SEE A QUESTION ALREADY FROM DR. KRAFT. >> FANTASTIC WORK AND PUT VIRAL RESEARCH ON ITS HEAD WITH NEW CONCEPTS THIS IS TERRIFIC, I HAVE ABOUT 7 QUESTIONS BUT I WILL ONLY ASK YOU TWO YOU MAY HAVE MENTIONED HOW YOU THOUGHT THE VESICLES ENTERED THE CELLS BECAUSE WE THINK OF INDIVIDUAL PARTICLES I'M A LUNG PERSON AND INTERESTED IN RINO VIRUS AND THE VESICLES WORK VERY DIFFERENTLY AND SOUNDS LIKE THEY OFFER SOME IMMUNE PROTECTION CLEARLY WITH A DELAYED RESPONSE IN INTERFERONS IS THERE AN EVENTUAL INTERFERON RESPONSE IS IT DELAYED HAVE YOU DONE TIME COURSES? BECAUSE EVENTUALLY THE HOST WOULD NEED TO BE ABLE TO DETECT THESE VIRUSES OTHERWISE THAT WOULD BE NOT SO GREAT FOR THE HOST. >> CAN YOU USE THE MICROPHONE, PLEASE? THANK YOU. >> FIRST QUESTION WE LOOKED AT THAT, WE ARE LOOKING AT IT STILL, WE THINK THERE ARE ESSENTIALLY TWO PATHWAYS WHICH THE VIRUS VESICLES ARE ABLE TO TRANSMIT THE GENOMES TO ANOTHER CELL AND THE FIRST IS THROUGH THE VESICLES BEING ENDOCYTOSED BY THE CELL AND LYPASE DEGRADE THE MEMBRANE AND RELEASES THE VIRUS TO BIND RECEPTORS WHICH ARE PRESENTED IN THE ENDOSOME AND RINO WE THINK USES THIS PATH TO GET OUT. THE PS LIPIDS ON THE VESICLES WE THINK ALSO PLAY AN IMPORTANT ROLE IN TETHERING THESE VESICLES TO CELLS THROUGH PS RECEPTORS EXPRESSED ON CELLS. THE SECOND METHOD IS ONE THAT HAS BEEN OBSERVEDED FOR INSTANCE FOR HEPATITIS AND DENGAY AND BUDDED VIRUS AND A SECOND FORM WHERE SMALL VESICLES CONTAINING INFECTIOUS GENOME OF HEPATITIS C ARE RELEASED FROM CELLS IN THE CASES THE VESICLES SEEM TO DIRECTLY FUSE WITH CELLS AND RELEASE THEIR GENOMES IN THE CYTO PLASM AND RAISES AN IMPORTANT QUESTION WHAT IS TROPOSIM IS THERE SOMETHING ON THE VESICLES THAT TETHERS THOSE VESICLES TO CERTAIN CELL TYPES SAY FOR HEPATITIS C AND LIVER SELL OR DANGE AND IMMUNE CELL IN ADDITION ARE THERE INTRA CELLULAR RESTRICTION ELEMENTS RESTRICTING ELEMENTS THAT ULTIMATELY DETERMINE WHETHER THAT VIRAL GENOME REPLICATES OR NOT AND MAYBE THE VESICLES END UP FUSING WITH MANY DIFFERENT CELL TYPES BUT ONLY IN CERTAIN CELL TYPES THERE IS A PERMISSIVE ENVIRONMENT FOR THE GENOME TO REPLICATE. REGARDING YOUR SECOND QUESTION WITH THE VESICLES CONTAINING VIRUSES, WE ARE SEEING THAT THE INTERFERE RON PATHWAYS COMPLETELY SHUT DOWN UNTIL THERE ARE CELLS THAT YOU KNOW THAT DEGRADE THE VESICLES OR THE VESICLES LYSE AT THAT POINT THE FREE PARTICLES EMERGE AND THE INTERFERON IS TRIGGERED AND THE VESICLES ARE IMPORTANT IN ESTABLISHING INFECTION IN THE EARLY STAGES. LATER ON THE HOST STARTS MAKING IMMUNE RESPONSE BECAUSE OF THE LYSIS OF SOME OF THE VESICLES AND SO FORTH BUT IN THE EARLY STAGES IT REALLY WE FEEL GIVES A LEG UP TO THE VIRUS AND GOING UNDER THE RADAR, YEAH. >> SO THE FACT THAT SYRON IS A SIGNAL FOR UP TAKE DO THESE VESICLES TRIGGER THE SAME ANTIINFLAMMATORY RESPONSES THAT THE CELLS TRIGGER? >> YES, WE BELIEVE SO. SO PS LIPIDS ARE KNOWN TO TRIGGER FOR INSTANCE RELEASE OF TGF BETA AND TEN FOR MACROFAGE AND IT'S A BONUS OF VESICLES AND MIMICKING THE CELLS IN A WAY THEY QUIET DOWN THE INNATE IMMUNE SYSTEM, YES. >> WHERE HAVE THEY BEEN SPEAKING BIOLOGY AND HOW ARE THEY DIFFERENT WITH THE VESICLES IN SOME PARTS OF THE CELL. >> WHEN WE FIRST DISCOVERED THIS WITH THE POLIO AND RINO VIRUS WE THOUGHT THIS WAS A DENOVO PATHWAY FUSING WITH THE PLASMA BEM MEMBRANE AND IT'S NOT TRUE AND CELLS SOME END UP FUSING WITH THE PLASMA MEMBRANE AND RELEASING CONTENT SO WE THINK THE VIRUSES ARE JUST THROUGH EPITOPES THEY CARRY ON PROTEINS DIVERTS THE PATHWAY TO THEMSELVES AND CLOAKING THEMSELVES IN THE PATHWAY AND UP REGULATING SO IN CELLS FOR INSTANCE INFECTED WITH POLIO VIRUS MUCH OF THE PATHWAY IS DIVERTED TO THE SECRETORY PATH OPPOSED TO A DEDRADAT AND THE NOTO VIRUS EXISTS IN ALL CELLS TO RELEASE RNA AND GROWTH FACTORS WHEN THE VIRUS GOES IN IT SNEAKS IN THE PATH WHICH USING CAPSID PROTEINS AND TARGET SOME MACHINERY THE PROTEINS OF THE PATHWAY AND CLOAKS ITSELF IN THE EXOSOMES TO BE RELEASED. >> SO JUST A FOLLOW-UP ON THAT. >> SURE. >> SO IF ONE WERE TO LOOK AT THE PATHWAYS THAT ARE ACTIVATED WOULD YOU LOOK FOR THE PROPERTIES OR LC3 PROTEINS? I MEAN WHAT PART OF THE PACKAGING IS ACTIVATED AND DOES THAT CHANGE ACCORDING TO THE VIRUS? >> SO LET'S TAKE THE ATOPHOGY PATHWAY FOR INSTANCE WHAT WE ARE FINDING IS THERE ARE CERTAIN SUBSET OF CARGO RECEPTORS USED FOR AUTOPHAGOSOMES BEING HIJACKED BY POLIO VIRUS AND BROUGHT TO THE ER MEMBRANE WHERE THE CAP IS ASSEMBLED AND THE AUTOPHAGOSOME IS BEING MADE THERE AND CARGO RECEPTORS IN THE CASE OF POLIO RECEPTORS THAT ARE BEING HIJACKED AND NORMALLY WOULD BE USED FOR SOMETHING ELSE SO WE ARE LOOKING RIGHT NOW AT THOSE INTERACTIONS BETWEEN WHAT IS ON THE CAPSID AND HOW IS IT ABLE TO GET THE SUBSET, YES. >> ANYONE ELSE BEFORE WE CLOSE THE DISCUSSION? >> I WAS GOING TO DEFER TO ALL MY PULMONOLOGIST'S IN THE GROUP SO BOB APPROPRIATELY SAID THAT THE DIR YOU FOLLOW YOUR NOSE, IT'S NOT PARTICULARLY RELATED TO WHICH IC YOU'RE IN AND YOU DID THE GI TRACT, I WAS WONDERING WHAT HAPPENS IN THE LUNG? >> SORRY. >> HOW DOES THIS PROCESS PLAY OUT IN THE LUNG? WHEREAS YOU SHOWED IN THE OLD CARTOON THAT IS WHERE WE WERE GETTING HIT WITH THESE. >> SO WE HAVE SOME DATA WITH RINO VIRUS AND WE ARE FINDING VESICLES IN SPUTUM AND INTRA BRONCHIAL LAVAGE FROM RHINO VIRUS INFECTED PATIENTS AND THINK THE VESICLES ARE WHEN YOU COUGH ARE ESSENTIALLY BEING AEROSOLIZED AND IN DROPLETS THAT ARE IN THE AIR AND THAT WILL GET INHALED BY OTHER HOSTS, SO WE THINK THEY ARE ACTUALLY INSIDE THE SPUTUM WAS THAT YOUR QUESTION THAT THE VESICLES ARE? >> YES, SO I'M A LITTLE SELFISH AND PROCHIAL AND MIGHT TO MAKE SURE IT APPLIES AND AN ORGAN DIFFERENT FROM THE GUT SHOULD HAVE A LOT OF DEFENSE MECHANISMS AND A LOT OF THINGS THAT WOULD SHEPPARD AN INVASION AND SORT OF TRIAGING IT OUT. >> ABSOLUTELY SO ONE OF THE THINGS WE ARE DOING IS WE HAVE THESE PRIMARY BRONCHIAL CULTURES WITH MUCOUS ON THEM AND BASICALLY TAKING SOME VESICLES DUMPING THEM ON THEM FLUORESCENT SEE HOW THEY PASS THROUGH THE MUCOUS AND SILIA AND SIMPLE CELL BIOLOGY EXPERIMENTS BUT WANT TO GO AFTER THEM NOW THEY EXIST IN THE AEROSOLIZED DROPLETS, YEAH. >> BEFORE WE CLOSE THE DISCUSSION I WOULD JUST LIKE TO SAY ANOTHER ASPECT OF THAT THAT I THINK WOULD BE INTERESTING IS UNDERSTANDING THE INTERACTION WITH THE MICRO BIOM IN THE LUNG AIRWAYS AND HOW IT MAY PROTECT OR PERHAPS BE CIRCUMVENTED BY THIS RATHER TROJAN HORSE APPROACH THE VIRUSES ARE TAKING. >> ABSOLUTELY AND I AGREE WITH YOU AND WE HAVE A MICRO BIOM FACILITY AT NIH WE ARE WORKING WITH RIGHT NOW FOR INSTANCE NORO VIRUS THAT IS ONE VIRUS THAT HAS BEEN SHOWN IT'S INFECTION HAS BEEN SEWN SHOWN BY THE MICROBE CONTENTS OF THE INTESTINE BUT ASSUME TO BE PASSING AS FREE VIRAL PARTICLES NOW WITH THE KNOWLEDGE IN HAND WE WANT TO SEE HOW THE VESICLES INTERACT WITH THE BACTERIA ABSOLUTELY, YEP. >> SO I WANT TO SAY THANK YOU VERY MUCH FOR YOUR PRESENTATION DR. ALTAN-BONNET. I LOOK FORWARD TO HEARING MORE FROM YOU. AND WITH THAT WE WILL LET YOU GO SO THAT WE CAN PROCEED TO OUR NEXT FEATURED EVENT WHICH IS GOING TO BE CONCEPT CLEARANCE PRIOR TO STARTING THE CONCEPT CLEARANCE WE ARE GOING TO HAVE OUR REPRESENTATIVES FROM DECISION LENS COME UP AND GIVE THE COUNCIL MEMBERS A REFRESHER ON HOW TO USE IT SINCE IT'S BEEN A WHILE. AS WE GET STARTED MY COLLEAGUE MARIA IF YOU CAN RAISE YOUR HAND IS WALKING AROUND THE ROOM, SHE CAN HELP YOU WITH ANYONE THAT IS HAVING LOG IN ISSUES IN DECISION LENS BUT I WILL DEMONSTRATE WHAT WE ARE DOING TODAY SO WHEN YOU LOG IN DECISION LENS WE ARE USING THIS TO VOTE ON AND PRIORITIZE THE VARIOUS PROPOSALS THAT YOU ALL WILL BE HEARING OR TASKS WE WILL BE HEARING ABOUT TODAY SO WHEN YOU LOG IN YOU WILL SEE A SECTION CALLED MY TASKS AND IT'S GING TO ASK YOU TO RATE ALTERNATIVES FOR THE PORTFOLIO TITLED IDP JUNE 2019 COUNCIL. YOU WILL CLICK HERE AND IT WILL BRING YOU TO A PAGE WHERE THIS IS WHERE YOUR RATING BEGINS SO ESSENTIALLY YOU ARE RATING ON 13 DIFFERENT TOPICS TODAY AND YOU'RE GOING TO BE DOING TOPIC BY TOPIC SO ONCE THE TOPIC IS PRESENTED YOU WILL CLICK ON THE START RATING ALTERNATIVES OR YOU CAN FIND THAT SPECIFIC ALTERNATIVE DOWN HERE BY ITS TITLE. WE WILL GO START RATING ALTERNATIVES. AND WHAT YOU WILL SEE ON THIS PAGE IS THAT IT'S ASKING YOU TO RATE THE PARTICULAR ALTERNATIVE OR TITLE, THAT'S THE BLUE TEXT ON THE SCREEN, IN RESPECT TO CRITERIA THAT HAS BEEN PREVIOUSLY SAT BY YOUR ALL THE GROUP IS UNDER THE PURPLE TEXT SO IF YOU ARE CURIOUS WHAT THE IMPORTANT OF PUBLIC HEALTH OR ISSUE RELATED OPPORTUNITY YOU CAN SEE HOW THAT IS OPERATIONALLY DEFINED HERE AND UNDERNEATH WE HAVE A SCALE RANGING FROM NOT IMPORTANT TO EXTREMELY IMPORTANT. YOU WILL SELECT YOUR VOTE, SO YOU THINK IT'S MODERATELY IMPORTANT SO STEP ONE IS LOG YOUR VOTE, IT WILL TURN GREEN WHEN IT'S LOGGED. ADDITIONALLY AND I WANT TO CALL SPECIFIC ATTENTION TO THIS POINT WHAT WE WOULD LIKE YOU TO DO IS PROVIDE ANY COMMENTS OR SUBSTANTIATION AS TO WHY YOU VOTED THAT WAY. SO HERE YOU CAN SEE YOU CAN ENTER ANY TEXT AND THEN IT'S VERY IMPORTANT THAT YOU PRESS ADD COMMENTS THAT THAT COMMENT IS LOGGED. AND WE WILL DO THIS FOR EACH SPECIFIC ALTERNATIVE THAT YOU'RE VOTING ON. IF YOU WOULD PREFER THIS TO BE A BIT QUICKER AND FOR YOU TO BE ABLE TO SEE MULTIPLE CRITERIA AT ONCE, YOU CAN CLICK ON THIS LITTLE BUTTON HERE WITH THE ELLIPSE AND YOU CAN CLICK WRITE THIS IN MULTI VIEW AND MARIE AND I WILL BE WALKING AROUND SO IF YOU FORGET RAISE YOUR HAND AND THIS IS WHAT WE WILL HAVE DISPLAYED ON THE SCREEN AS YOU ALL VOTE AS A REMAINDER SO AGAIN YOU RATE THE ALTERNATIVE OR THE TITLE HERE WITH RESPECT TO THESE VARIOUS CRITERIA AND WHEN YOU CLICK YOUR VOTE AND IT'S GREEN IT MEANS IT'S BEEN LOGGED, PLEASE ADD COMMENTS AS NECESSARY AND THEN YOU WILL SEE THAT THERE ARE MULTIPLE CRITERION PER TITLE AND THEN WHEN YOU ARE DONE RATING, WHEN ALL YOUR VOTES ARE IN FOR THAT PARTICULAR TITLE OR ALTERNATIVE, THIS NEXT BUTTON WILL TURN ORANGE AND YOU WILL MOVE TO THE NEXT IN WHICH IT WILL BE PRESENTED. SO THAT IS THE GIST OF VOTING. AGAIN WE WILL BE AROUND TO ANSWER ANY QUESTIONS, ARE THERE ANY QUESTIONS AT THIS POINT THAT FOLKS HAVE? THAT CONCLUDES OUR DEMO PORTION >> OKAY, GOOD MORNING, THE FIRST INITIATIVE I WANT TO INTRODUCE IS ENTITLEED PRECISION MEDICINE INTER GENERATIONAL RESOURCE FOR THE STUDY OF FACTOR 8 IN SEVERE HEMOPHILIA AND PRIMARY AIMS GENERATE UNIQUE PRECISION RESOURCE OF APPROXIMATELY 65,000 ROBUSTLY ANNOTATED BIO SPECIMENS FROM COHORT AND SECOND MAKE THE RESOURCE IMMEDIATELY AVAILABLE TO THE BROADER RESEARCH COMMUNITY WITH INTENT TO FOSTER FUTURE INVESTIGATOR INITIATED RESEARCH ON MECHANISMS OF FACTOR 8IMMUNOGENICITY AND HEMOPHELIA AND A SEVERE PHENO TYPE AND 30% HAVE FACTOR 8 ANTIBODIES AND THOSE ANTIBODIES AND HALF OF THOSE ARE DIFFICULT TO ERADICATE AND ALTERATIONS IN TREATMENT AND STUDIES DONE TWO DECADES AGO THE AVERAGE COST PERCEIVE PEMOPHILIA-A WAS A MILLION A YEAR FOR REPLACEMENT THERAPY AND IT WAS FAR LESS ADVOCATE THAN FOR NON-INHIBITOR PATIENTS AND THE PATHOGEN WHY THIS OCCURS IS AS COMPLICATED AS HURRICANE IMMUNOLOGY AND WORKED WITH INVESTIGATORS IN THE PORTFOLIO ADVISED IT'S GOING TO REQUIRE HUMAN RELATED IMMUNOGENICITY STUDIES AND ANIMALS WILL NOT RECAPITULATE NECESSARILY THE BIOLOGY TO UNDERSTAND THIS AND THEREFORE TO INTERVENE ON IT. ALSO HOW DO WE PROPOSE TO ACCOMPLISH THIS? AS INDICATED IN THE NARRATIVE WHICH WE READ IT CREATES AN OPPORTUNITY FOR INVESTIGATORS TO DESIGN THIS RESOURCE USING MULTIPLE HYPOTHESIS PROTOCOLS FOR PERRY AND POST NATAL CHARACTERIZATION OF THE INFLAMMATORY AND BIOLOGICAL STATE AND TO GUIDE THE COLLECTION OF INTERPRETATIVE SOCIAL AND PHENOTYPIC AS SHOWN ON THE NARRATIVE AND IT'S THROUGH COLLABORATION BETWEEN A CLINICAL COORDINATING CENTER AND BIO SPECIMEN RESOURCE CENTER TO BUILD AN UNIQUE RESOURCE AND IT WILL CODEVELOPED WITH THE HEMOPHELIC FUNDED BY C.D.C. AS A SOURCE FOR HUMAN SPECIMENS AND HUMAN PHENOTYPIC DATA ACROSS DISCIPLINARY AND USE ALL THE EXPERTISE THAT I'VE APPLIED UP TO AND INCLUDING THE PLACENTAL BIOLOGY OF THE MOM AND INCELOCO MODELING BASED ON THE IMMUNOLOGIC DEVELOPMENTAL WORK, IT WILL REQUIRE STATE OF THE ART EXPERTISE BECAUSE A LOT OF IMMUNOLOGIC IN THE PERRY NATAL PERIOD NECESSITATE REAL TIME CELL PROCESSING BECAUSE JUST STORY QUICK OBTAINING SPECIMENS AND PROCESSING IN TRADITIONAL WAYS WILL DESTROY THE BIOLOGICAL MECHANISMS FOR UNDERSTANDING WHAT IS HAPPENING IN REAL TIME. THE B COMMENTS GAVE THE PROJECT TEAM GAVE DUE DILIGENCE TO THE ASCERTAINMENT OF FEASIBILITY OF THIS AMBITIOUS PROJECT IN A RARE DISEASE AND FEASIBLE WAS FURTHER CONFIRMED IN A DETAILED RESPONSE TO QUESTIONS RAISED BY B. WE'VE SOUGHT BROAD SUPPORT ACROSS NIH FOR THIS INCLUDING INTEREST BY NIAD AND NICHD AND HAVE SUPPORT OF C.D.C. AND FDA PARTNERS WHO VIEW THIS RESOURCE AS IMPORTANT TO THE FEDERAL MISSIONS AND HEMOPHELIA ACTIVITIES THEY ARE RESPONSIBLE FOR. POSSIBLE QUESTIONS COULD INCLUDE THE BUDGET WHICH IS SUBSTANTIAL BUT THE TOTAL NUMBER OF SPECIMENS IS 65,000 THE TYPE OF BIOLOGY THAT IS GOING TO BE IMPLICATED HERE WILL LEVERAGE OTHER ON GOING BIOLOGICAL DETERMINATION MECHANISMS LIKE TOP MED AND WHICH WILL INCLUDE THE TRANS NOMIC AND INFLAMMATORY BIO MARKERS AND THE COST FOR SPECIMEN IS 500. WE HAVE PUT TOGETHER CONCERTEDLY WITH THE STATE OF THE SCIENCE AND WORKED TOGETHER WITH OUR COLLEAGUES AT NIH AND OTHER INSTITUTES INCLUDING THE HUMAN PLACENTAL PROJECT AND TOP MED PROGRAM AND IF WE DON'T DO THIS IT WILL NOT BE DONE BECAUSE THE SCOPE IS REALLY MATERNAL ANTINATAL, PRENATAL, POST NATAL AND INFINTILE CHARACTERIZATION OF HUMAN RESPONSE TO A SPECIFIC ANTOGEN WITH FAR REALLY VANED BEYOND 8HUMOGENICITY ALONE SO WITH THAT I'LL STOP IT QUESTIONS OR COMMENTS AND FOR COMPLICATED ONES I WILL ALSO BRING IN MY PARTNER IN CRIME, THE DEPUTY DR. KELLY BETWEEN US WE SPENT A FAIR AMOUNT OF EFFORT WITH OUR TEAMS AND THE STATE OF THE SCIENCE PEOPLE ON THIS. >> MADAM CHAIRMAN CAN WE COMMENT FROM THE INTERNET OUT HERE? >> YES, THOSE OF YOU LOST IN THE INTERNET PLEASE MAKE YOUR COMMENT, DR. NUGENT. >> ALL RIGHT, I JUST REALLY WANT TO SPEAK STRONGLY FOR THIS PARTICULAR ITEM BECAUSE OF THE UNLIKE SO MANY OTHER BROAD PROJECTS THAT WE PROPOSE WE REALLY HAVE ALL THE SPECIMENS COLLECTED, THE NETWORK OF 135HDCS ARE ALL POISED TO FOLLOW THROUGH WITH SPECIMENS FOR SUPPLEMENTING THE PRENATAL AND NATAL WORK. THIS IS NOT LIKE OTHER STUDIES WHERE YOU BEGIN TO FORM A NETWORK, THE NETWORK IS FORMED. THE SAMPLES HAVE ALREADY BEEN COLLECTED THROUGH FUTURE AND ARE ALREADY IN TOP NET AND HAVE BEEN CONVERTED OVER. IT WOULD BE AN INCREDIBLE LOSS OF MOMENTUM IF THIS WERE NOT PLACED IN THE HIGHEST CATEGORY. THERE WAS RECENTLY THE STATE OF THE SCIENCE TWO-DAY CONVOCATION WITH ALL OF THE BASIC SCIENTISTS WHO WERE THERE. I AND I THINK MANY OTHER PEOPLE IN THE ROOM PARTICIPATED IN THAT AND WE HAD THE REALIZATION THAT THIS IS A MOMENT THAT WOULD NOT ONLY IMPACT HEMOPHILIA IN A MAJOR WAY BUT THE MODELS AND THE UNDERSTANDING THAT THE IMMUNE SYSTEM WOULD REALLY TRANSLATE INTO MANY OTHER DISORDERS AND I THINK THAT'S WHY NIAD AND OTHER INSTITUTES ARE HEAVILY COMMITTED TO THIS PROJECT SO THERE IS A HUGE SYNERGISM NOT JUST FROM FUNDING FROM NHLBI BUT WILL COME FROM OTHER INSTITUTES TOO TO SUPPLEMENT THIS MAN POWER AND ALSO JUST DATA, IT WAS GREAT TO HEAR THE DATA STAGE PRESENTATION BECAUSE THIS PROJECT I SHOULD THINK WOULD BE ONE OF THE FIRST THAT WOULD REALLY SHOW THE BENEFIT OF THAT AS WELL, SO JUST A BRIEF COMMENT BUT CANNOT ADVOCATE ANY MORE STRONGLY FOR HAVING THIS TO HAVE A REALLY HIGH SCORE, SO THANK YOU TO EVERYONE AROUND THE TABLE. >> ANYONE ELSE? DR. ARNETT? >> WELL THANK YOU FOR DIANE THOSE COMMENTS FROM THAT PERSPECTIVE. I LOOKED THROUGH THE BEE ADVISORS COMMENTS AND YOU KNOW ONE OF THE CONCERNS I HAVE AND I DON'T THINK IT'S QUITE BEEN ADEQUATELY ADDRESSED IS HOW WE CAN DO THE OMIX ON A SAMPLE SIZE OF 50 MOTHERS AND THEIR CHILDREN. I THINK YOU COULD DO SOME THINGS LIKE RNA EXPRESSION BUT I'M NOT SURE HOW YOU COULD DO MORE BEYOND THAT AND I DON'T KNOW HOW YOU GET THE 6500 SAMPLES OUT OF THE 50 MOTHER-CHILD PAIRS MAYBE IF YOU CAN TELL US HOW THINGS ARE BEING MEASURED IT COULD OVERCOME SOME OF THAT CONCERN. >> OKAY, SO AND I MAY RELY ALSO ON DONNA WHO CAN ADD MORE SPECIFICITY THAN WHAT I WILL COMMENT TO BUT THERE IS THE IMMUNOPHENO TYPING ALONE WILL BE DONE ON THE MOM AT THE TIME OF DELIVERY ON THE BABY AND THEN LONGITUDINALLY UNTIL 50 EXPOSURE DAYS UP TO FACTOR 8 WHICH IS OBVIOUSLY THE HIGH RISK PERIOD FOR DEVELOPING ANTIBODY. THAT WILL BE CORRELATED WITH THE GENOMICS AND THE TRANSCRIPT OMICS AND OTHER NOMICS IN THE PROCESS AND THE TREATMENT CENTERS WILL PROVIDE THE PHENOMICS PIECES BECAUSE THEY ARE FOLLOWED LONGITUDINALLY ANYWAY THE PART THAT IS ABSOLUTELY UNIQUE THE BEST WE HAVE BEEN ABLE TO ASCERTAIN IS THE MATERNAL FETAL TO PERI NATAL PIECE SO LONGITUDINAL COMPARISONS WITH EVERY SUBJECT BOTH MOM AND BOY, MOSTLY 99% BOYS, AS HIS OWN CONTROL GOING FORWARD. SO THAT IS A COMPARISON. IN ADDITION WE ARE IN THE PROCESS OF TRYING TO ADDRESS THE BROADER CROSS SECTIONAL COMPARISON WHAT YOU ARE RAISING AND WORKING WITH THE PRIVATE COMMUNITY TO SEE IF WE CAN ACTUALLY GET PARALLEL COHORTS FROM INDIVIDUALS WHO BEGAN THE STUDY WITHOUT THE MOM THAT IS BECAUSE SPONTANEOUSLY THE MUTATIONS OCCUR TO ACCOUNT FOR ANYWHERE FROM 40-50% OF NEW HEMOPHELIA AND OBVIOUSLY YOU DON'T KNOW WHO THE MOMS ARE AND NOT ABLE TO CAPTURE THEM BUT A PARALLEL COHORT AND PAID FOR PRIVATELY WHICH WE ARE CONSIDERING AND GETTING POSITIVE FEEDBACK FROM THE COMMUNITY THEN THAT WILL ALSO BROADEN AND EXTEND THE CROSS SECTIONAL POWER THAT WE HAD DISCUSSED IN B THAT WOULD THEN ACTUALLY INCREASE THAT TO WHERE AND WE HAVE DONE SOME COMPLEX WITH THE HELP OF OUR BS OUR BIO STATISTICAL BRANCH IN DCVS DONE SOME PRETTY COMPLEX GENOMIC ANALYSIS TO SAY THE CROSS SECTIONAL IN THE PHENOMIC ARE POSSIBLE NOT AS POWERFUL ON THE GENOMIC SIDE BUT THEY ARE POSSIBLE. >> SO DONNA THAT IS A GOOD QUESTION AND OBVIOUSLY THE MAJOR QUESTION WHICH IS WHY YOU HAD TO READ SO MUCH IN TERMS OF THE RESPONSE TO IT AND I JUST WANTED TO SAY NOT ONLY -- AND WE THOUGHT A LOT ABOUT THIS EVEN BEFORE WE PUT THE INITIATIVE TOGETHER BECAUSE THE FEASIBILITY OF ACTUALLY ACQUIRING MORE THAN 50 MOTHER-BABY PAIRS IS ACTUALLY QUITE LOW ALTHOUGH WE THINK WE CAN DO THE 50 I'M NOT SURE WE CAN DO MUCH MORE THAN THAT OTHER THAN COHORT ENRICHMENT IN THE POST NATAL PHASE AS KEITH DESCRIBED SO BUT WE DID GO BACK AND REALLY SERIOUSLY ADDRESS THIS AND WE ADDRESSED THIS BOTH FROM THE STANDPOINT OF YOU KNOW THE IMMUNOLOGY AS WELL AS THE OMIX AND I THINK THE STRENGTH IS IN THE OMIX BECAUSE OF THE LARGE NUMBERS OF SAMPLES THAT IS HOW WE GET TO 65,000 SPECIMENS IS THAT WE WILL BE DOING FAIRLY INTENSIVE LONGITUDINAL SAMPLING NOT ONLY ACROSS YOU KNOW THROUGH THE PREGNANCY AND AT DELIVERY AND THEN SAMPLE THE PLACENTA BUT ACTUALLY DO A FAIR AMOUNT OF LONGITUDINAL SAMPLING IN THE BABY LOOKING NOT ONLY AT THE BASE LINE IMMUNOLOGY BUT THE PERTUBATIONS FROM CHILDHOOD INFECTIONS IMMOBILIZATION AND LOOK AT THE IMMUNOLOGY-WITH FACTOR 8 EXPOSURE SO AT THE STRENGTH OF IT EVEN THOUGH WITH THE SMALL NUMBERS IS ACTUALLY IN THE NUMBER OF SAMPLINGS, THE LONGITUDINAL DATABASE ON EACH INDIVIDUAL THAT, YOU KNOW, I'M NOT A STATISTICAL EXPERT ESPECIALLY NOT IN THIS FIELD BUT NOT ONLY HAVE WE GONE TO OUR OWN INSTITUTE BUT WE WENT TO NCI WHERE WE HAVE GENETIC EPIDEMIOLOGISTS WHO ALSO WORKED IN THE FIELD OF HEMOPHELIA AND THROUGH SOME OF THEIR MODELING WE WERE ABLE TO ASCERTAIN WE HAVE THE STATISTICAL POWER TO UNDERSTAND THIS DISEASE FROM A TRANS OMIX PERSPECTIVE. >> ANY OTHER COMMENTS? MAYBE FROM THE PHONE, DR. W DR. WEYRICH DO YOU HAVE ANY COMMENTS? . >> YES, I HAD MY MUTE BUTTON ON. I THINK THIS IS JUST SOMETHING THAT WE AND IN THIS AREA WE HAVE BEEN ON FOR A LONG TIME AND I'M A CHAMPION OF THIS AND DR. NUGENT'S COMMENTS WERE REALLY IMPORTANT INITIATIVES TO SUPPORT. >> OKAY, THIS IS DIANE NUGENT AGAIN CAN I JUST GIVE ONE OTHER POINT FROM THE STATE OF THE SCIENCE CONFERENCE. >> YES, IF YOU COULD MAKE IT BRIEF, PLEASE. >> YES. IN BETWEEN B AND THERE WE CAN OBTAIN FETAL TISSUE OF COURSE OR FETAL GENOME FROM MOTHERS SO THAT ARE PREGNANT AND THAT IS AN AREA THAT WILL BE EXPANDED AND IN ADDITION I JUST WANTED TO REENFORCE THAT THERE ARE A NUMBER OF BABIES THAT WE KNOW ARE GOING TO BE BORN WITH SEVERE HEMOPHELIA AND NOT AS OPTIMISTIC OF GETTING ALL THE PLACENTS SO I WILL STOP THERE. >> SO IF YOU CAN ALL VOTE THAT WOULD BE GREAT. I SEE MOST OF YOU HAVE ALREADY PLACED YOUR VOTES SO I WILL JUST WAIT A MINUTE FOR THE REMAINING VOTES TO COME IN. WE CAN MOVE ON TO THE NEXT INITIATIVE. >> THE LAST INITIATIVE FROM DBDR IS ENTITLED SICKLE CELL DISEASE AND SUB SAHARA AND AFRICAN AWARDS AND IT'S A U24 COMBINED WITH U01 AND IT'S A RENEWAL AND AN EXTENSION SO THE SICKLE CELL CONSORTIUM WAS CREATED IN 2017 FOR FOUR YEARS AS A PILOT FOR PROOF OF PRINCIPLE FOR CREATING INFRASTRUCTURE FOR CLINICAL AND TRANSLATION RESEARCH IN SUB SAHARA AND AFRICA IT WAS REQUIRED ALSO TO HAVE A CORE DATABASE DEVELOPMENT WHICH WAS CALLED SAD ACC OR THE SICKLE CELL AFRICA DATA COORDINATING CENTER. THE PRIMARY COORDINATION FOR THE CLINICAL CORE WAS FROM DORIS AND TANZANIA AND CAPETOWN SOUTH AFRICA AND CHARGED WITH A REGISTRY DATABASE SYSTEM TO ESTABLISH WITHIN AFRICAN COHORTS-PHENO TYPE AND REGIONAL AND DEVELOP REGIONALLY APPROPRIATE MANAGEMENT GUIDELINES, SKILLS DEVELOPMENT FOR SICKLE CELL MANAGEMENT AND PLANNING FOR COHORT STUDIES AND EXTENSION INTO AREAS SUCH AS NEW BORN SCREENING FOR SICKLE CELL DISEASE INFECTIOUS PREVENTION WITH BOTH VACCINATION AND PENICILLIN ADMINISTRATION AND DATABASE EXPANSION THIS WAS OUR FIRST STEP INTO SUB SAHARA AND SICKLE CELL AND NOT THE ONLY STEP AND YESTERDAY I WAS IN CHICAGO WHERE INVESTIGATORS FROM SUB SAHARA AND AFRICA WERE MEETING WITH U.S. COLLEAGUES AND I HAVE TO SAY THEY MADE A NUMBER OF AREAS MOST IMPRESSIVE ADVANCE OVER THE LAST FIVE YEARS BECAUSE THERE WERE A COUPLE CLINICAL TRIALS THAT WE FOUND THAT BEGAN BEFORE THIS. BUT JUST SOME ASTOUNDING NUMBERS LIKE NO HARM STUDY FOR THAT WAS DONE IN UGANDA KENYA AND DEMOCRATIC REPUBLIC OF CONGO THEY HAVE 100% RETENTION RATE FOR ANYBODY WHO HAS DONE SICKLE CELL STUDIES IN THE UNITED STATES THAT IS INCREDIBLE. AND THEY HAVE JUST MANAGED TO AND WITH THIS PROGRAM BUILD THE INFRASTRUCTURE TO ALLOW THOSE KIND OF STUDIES TO GO FORWARD. THEY PROPOSED WITH THREE COUNTRIES TO ENROLL 13,000 OVER THE FOUR YEARS, THE FOURTH YEAR ENDED ON APRIL I MEAN THE SECOND YEAR ENDED ON APRIL 2019 AT WHICH TIME THEY HAVE 6500 SO THEY ARE HALFWAY THERE WITH HALF THE TIME LEFT TO GO. THE NEXT PHASE WILL BE TO BUILD IT BEYOND THREE COUNTRIES. AND AS YOU CAN SEE FROM THE NARRATIVE AND THEY HAVE ALSO IN THAT TIMELINE USING RED CAP TECHNOLOGY DEVELOPED HERE AT VANDERBILT IN COOPERATION WITH THE DATA STAGE PEOPLE THEY MANAGED TO CREATE A WHOLE DENOVO WITH COMMON AFRICA DEFINITIONS TAT ARE COMPLIMENTARY AND UNIQUE TO THEIR OWN NEEDS AND THEY HAVE BEGUN LOOKING AT DENOVO STEPS FORWARD WHICH WE WOULD BE PROPOSING IF THIS FUNDING OPPORTUNITY GOES FORWARD INCLUDING NEWBORN SCREENING FROM NOT JUST THE THREE COUNTRIES BUT MORE EXTENSIVELY INTO THROUGH OTHER COUNTRIES PLUS SATELLITES IN EXISTING COUNTRIES TO GO VERY BROADLY AND NOT JUST WITH THE EXISTING LONGITUDINAL FOLLOW-UP OF THE 13,000 THAT WILL BE IN THEIR REGISTRY BY THAT TIME THEY ARE FOLLOWING PHENO TYPES VERY CAREFULLY INCLUDING PAIN CRISIS AND ACUTE CHEST SYNDROME AND THEY ARE WORKING WITH THEIR MINISTRIES OF HEALTH AND WITH OTHER PROGRAMS THAT WE AND OTHERS FUND TO TRY TO BUILD BRIDGES, NOT TO DUPLICATE ANYTHING IF IT'S NOT IMPOSSIBLE NOT TO DO SO AND THEY ARE BEGINNING TO LOOK AT HOW TO ENGAGE ON SOCIAL ECONOMIC FACTORS AND I WON'T NOR SHOULD I PROLONG THIS DISCUSSION BUT A LOT OF DISCUSSION WENT INTO THAT YESTERDAY BECAUSE PARTICULARLY WHEN YOU GET TO THE CLINICAL TRIAL STAGE WHEN YOU CAN AFFORD YOU CANNOT AFFORD 15 CENTS PER DAY FOR HYDROXYEURIA IS A CHALLENGE BUT THEY ARE MAKING PROGRESS. >> THANK YOU DOCTOR HOOTS AND I WILL START LOOKING AROUND THE ROOM AND DR. NARLA HAS A QUESTION OR COMMENT. >> A COMMENT ON THE STUDY, IT LOOKS LIKE A FACE. YEAH. ACTUALLY, THE STUDY THAT WAS MENTIONED WAS AT THE ACHE PLENARY SESSION AND I-BEEN FOLLOWING THE STUDIES FROM THE BEGINNING WITH THE ADVISORY BOARD AND WHEN I STARTED ON IT I FELT THEY WOULD NOT BE ABLE TO DO IT EITHER BUT IT WAS A REMARKABLE ACCOMPLISHMENT AND IT WAS PUBLISHED IN THE NEW ENGLAND JOURNAL SO I THINK IT'S AN IMPORTANT ISSUE GLOBALLY IN SICKLE CELL DISEASE AND TO DO THESE KIND OF STUDIES IN AFRICA IS VERY VERY IMPORTANT AND THE SITE IN TANZANIA IS REALLY REMARKABLE AND FEEL REALLY STRONGLY WHATEVER WE CAN DO TO DO SOMETHING IN AFRICA WILL BE IMPORTANT FOR THE FUTURE NOT ONLY UNDERSTANDING THE DC BUT ALSO HOW WE CAN DO BETTER IN NORTH AMERICA SO I STRONGLY SUPPORT THIS INITIATIVE. >> THANK YOU. DR. SMITH WHITLEY. >> I WOULD LIKE TO REITERATE WHEN YOU THINK OF SICKLE CELL DOZEN 300,000 BEING BORN GLOBALLY AND UNDERSTANDING THAT THE BEFORE AGE FIVE MORTALITY IN WEST AFRICA IS MOST LIKELY OVER 50% IT IS STAGGERING WHAT WE CAN DO WITH THIS PROJECT. AND AS DR. NARLA MENTIONED WITH ACHE WE CAN ALSO LEARN BY DEVELOPING INFRASTRUCTURE FOR CLINICAL RESEARCH AND CLINICAL CARE AND THEY HAVE BEEN ABLE TO SHOW A MOVE AND THE MARK ON MATERNAL MORTALITY IN LABOR AND DELIVERY PERIODS, THAT'S BEEN VERY, VERY IMPRESSIVE SO I LOOK FORWARD TO SEEING THIS MOVING FORWARD. >> THANK YOU VERY MUCH. DR. SHEPPARD. >> YEAH, I ALSO WANT TO STRONGLY SUPPORT THIS PROPOSAL. IT'S REMARKABLE THE IMPACT FOR THE SMALL RELATIVELY SMALL INVESTMENT THAT THE NHLBI IS MAKING TO HAVE SUCH AN IMPACT ON A BIG PORTION OF THE WORLD. IT'S JUST INCREDIBLY EXCITING SO YOU KNOW IF YOU COMPARE THIS TO SOME OF THE AMOUNTS OF MONEY WE ARE SPENDING ON SOME OTHER THINGS WE ARE DOING SEEMS LIKE THIS OUGHT TO BE EXTREMELY HIGH PRIORITY. >> GREAT SO I'LL JUST ASK IF EITHER OF OUR COLLEAGUES ON THE PHONE HAVE A COMMENT THAT THEY WOULD LIKE TO MAKE? >> THIS IS DR. WEYRICH I AGREE TO ALL THE COMMENTS HERE, THIS IS A GREAT INITIATIVE FOR A SMALL AMOUNT OF MONEY AND GETTING BIG BANG FOR OUR BUCK. >> THANKS DR. NUGENT ANY COMMENTS? >> NO, JUST AGREE WITH EVERYONE AND I THINK THIS IS PARTICULARLY IMPORTANT THIS YEAR THAT WE RECOGNIZE THE EVER INCREASING NUMBER OF IMMIGRANTS FROM AFRICA THAT HAVE SICKLE CELL THAT WE ARE ALL TAKING CARE OF. IT'S THE SECOND ONLY TO ENGLAND AND INDIA SO WE REALLY WILL BENEFIT EVEN HERE IN THE UNITED STATES WITH BETTER UNDERSTANDING OF THE DISORDER IN AFRICA. >> THANK YOU FOR THAT PERSPECTIVE. UNLESS THERE IS ANY MORE COMMENTS I WOULD ENCOURAGE ALL OF YOU TO VOTE SO THAT WE CAN MOVE TO THE NEXT INITIATIVE. I'M WAITING ON THE REMAINING THREE PEOPLE. I'LL GIVE THEM A MOMENT OR TWO TO COMPLETE THEIR DECISION. WE CAN MOVE ON TO THE NEXT INITIATIVE AND PRESENT. >> THANK YOU VERY MUCH DR. MOEN THE CENTER FOR TRANSLATION AND RESEARCH IMPLEMENTATION SCIENCE HAS THREE INITIATIVES ALL ADDRESS OUR FOUR STRATEGIC VISION GOALS AND SEVERAL STRATEGIC OBJECTIVES WITH SPECIAL EMPHASIS ON ADVANCE AND TRANSLATION RESEARCH AND IMPLEMENTATION SIGNS AND DEVELOPING THE WORKFORCE AND RESOURCES NEEDED TO ACCOMPLISH OUR MISSION. AT THE VERY FIRST INITIATIVE I PRESENT IS 1394 THAT IS INCREASING NATIONAL AWARENESS OF THE SICKLE CELL DISEASE CHALLENGE JUST FOLLOWING UP ON DR. HOOTS PRESENTATION. THIS IS A COLLABORATIVE EFFORT BETWEEN CYTRUS AND BLOOD DIVISION AND SCIENCE POLICY ENGAGEMENT AND COMMUNICATION AND A CHALLENGE WITH THREE PRIZES FOR ONE TIME SINGLE YEAR AWARD TOTALING 50,000 AND SPECIFICALLY DESIGNED TO INCENTIVIZE TEAMS OF THREE TO FIVE STUDENTS AT THE GRADUATE AND UNDER GRADUATE LEVEL FROM MULTI DISCIPLINE BACKGROUND TO COMPETE FOR THE PRIZE. AND WE ARE USING THE CHALLENGE AS A VERY INNOVATIVE WAY TO ENCOURAGE TEAM SCIENCE AS ONE BUT ALSO TO EXPOSE THESE STUDENTS EARLY TO THE CONCEPTS OF DISSEMINATION AND IMPLEMENTATION RESEARCH WHILE AT THE SAME TIME INCREASING PUBLIC AWARENESS OF A VERY MISSION CRITICAL CONDITION SICKLE CELL DISEASE. PRIMARY OBJECTIVE FOR THE TEAMS TO DEVELOP INNOVATIVE APPROACHES FOR INFORMATION DISSEMINATION AND TOOLS, PLATFORMS, VIDEOS, AND DEVICES THAT MAY BE USED TO INCREASE THE PUBLIC'S AWARENESS OF SICKLE CELL DISEASE. THE CHALLENGE ALSO SERVES TO INTRODUCE THE STUDENTS TO NHLBI SCIENTISTS AND GRANT TEES AND SERVE AS MENTORS IN SICKLE CELL DISEASE AND DISSEMINATION AND IMPLEMENTATION SCIENCE THROUGH TRAINING, THROUGH MENTORING AND CONTINUED CONNECTION WHILE HIGHLIGHTING THE POTENTIAL CONTRIBUTIONS FOR THIS NEXT GENERATION OF RESEARCHERS THE BAU IS ENTHUSIASTIC AND BEYOND THE THREE PRIZES SO WE CAN CONTINUE TO MAINTAIN THE INTEREST OF ALL THOSE WHO APPLY SO I WILL STOP HERE AND SEE IF YOU HAVE ANY COMMENTS, SUGGESTIONS AND QUESTIONS FOR U US. >> ANY COMMENTS AROUND THE ROOM? ANY COMMENTS FROM THE PHONE? HEARING NONE I WOULD ENCOURAGE EVERYBODY TO VOTE. I GUESS THAT WAS CRYSTAL CLEAR DR. MENTA. >> I WAS GOING TO ADD BUT I DID NOT WANT TO INTERRUPT YOU I THOUGHT FOR NOT COSTING A LOT OF MONEY IT WAS AN UNIQUE WAY TO USE THE FUNDS AND ALWAYS WANTED TO ACKNOWLEDGE WHEN NIH DO UNIQUE THINGS TO GET TO DIFFERENT POPULATIONS INSTEAD OF THE SAME OLD SAME OLD. >> DR. SMITH WHITLEY. >> I THINK IT'S IN ALIGNMENT WITH OTHER NHLBI INITIATIVES IN THE SICKLE CELL SPACE AS WE MOVE TOWARDS IMPROVING QUALITY OF LIFE AND CURATIVE THERAPIES TO UNDERSTAND KNOWING YOUR SICKLE CELL STATUS AND IMPROVING AWARENESS OF YOUR STATUS AS WE MOVE INTO THESE NEXT INITIATIVES IT WILL BE VERY IMPORTANT. >> THANK YOU VERY MUCH FOR THE COMMENT COMMENTS. >> WE ARE ALMOST READY FOR MOVE ON, I WILL WAIT ANOTHER MOMENT. WE CAN PROCEED TO THE NEXT INITIATIVE. >> IS 1396 THAT IS CASCADE FH FOR FAMILIAL HYPER CHOLESTEROLEMIA AND IMPLEMENTATION RESEARCH EFFORT TO TRY TO IDENTIFY INNOVATIVE WAYS FOR DEVELOPING AND TESTING OPTIMAL AND SUSTAINABLE STRATEGIES THAT WOULD IMPROVE CASE FINDING, CASCADE SCREENING AND EFFECTIVE TREATMENT OF PATIENTS WITH HYPER CHOLESTEROLEMIA THIS IS AN INITIATIVE WE DEVELOPED IN PARTNERSHIP WITH CARDIOVASCULAR AND PUBLIC HELD GEMOMICS AT THE DISEASE CONTROL AND PREVENTION C.D.C. AND SHOULD EMPHASIZE WE ARE USING FH ONLY AS A PROTOTYPE OF A COMMON INHERITED GENETIC CONDITION IN WHICH THE BASIC SIGNS THE CLINICAL SIGNS AND POPULATION SIGNS HAS BEEN VERY WELL UNDERSTOOD AND FOR WHICH THERE ARE PROFESSIONAL SOCIETY GUIDELINES TELLING US WHAT TO DO ABOUT CASCADE SCREENING, CONDITIONS FOR WHICH EFFECTIVE TREATMENT INCLUDING GENERICS ARE AVAILABLE YET IT'S NOT BEING DONE. SO IF YOU TAKE THE CASE OF FH FEWER THAN 10% OF THE 1.3-1.5 MILLION AMERICANS WHO HAVE THIS DIAGNOSIS HAVE BEEN CONDITION HAVE BEEN DIAGNOSED AND, IN FACT, CASCADE SCREENING DOESN'T EXIST. ALTHOUGH EFFECTIVE IDENTIFICATION AND SCREENING OF FAMILY MEMBERS WOULD OFFER APPROPRIATE TREATMENT CAN LEAD TO AS MUCH AS 80% REDUCTION IN DOWNSTREAM CORNER EVENTS SO IT'S A REALLY HUGE CHALLENGE WE THINK WE HAVE AN OPPORTUNITY TO CRACK. THE WE ARE PROPOSING TO SUPPORT AFTER FIVE MERITORIOUS APPLICATIONS USING THE R61, R33 SINGLE SITE MECHANISM, THE IDEA IS THAT WE WILL GET INNOVATIVE TEAMS THAT WILL BE TRULY MULTI DISCIPLINARY, WE HEARD THIS MORNING ABOUT AVITARS AND HAVE GENETICS AND GENOMICS AND PEDIATRICS AND INTERNAL MEDICINE AND FAMILY PRACTICE AND GENETICS COUNSELORS AS WELL AS SOCIAL SCIENTISTS THESE GROUPS TOGETHER WITH BIO CAN HELP US CRACK THIS. WHAT IS REALLY EXCITING SEVERAL PUBLICATIONS JUST THE LAST MONTH ALONE AND COULD NOT GET IN YOUR WRITE UP IN THE GEMA CARDIOLOGY THERE IS A GROUP FROM TEXAS IN DALLAS THAT LOOKED AT A DECADE OF SIMPLE BLOOD DONATIONS AND THEN USED THE OLD FASHION MET PAD CRITERIA OUT OF 1.2 MILLION INDIVIDUALS WHO DONATED BLOOD WERE ABLE TO IDENTIFY 3500 AVERAGE PATIENTS WHO WERE UNDIAGNOSED THAT WAS ONE. AGAIN LAST MONTH IN NATURE THE GROUP AT STAMFORD PUBLISHED A MACHINE LEARNING ALGORITHM THAT IS JUST TOOK ALL THE STAMFORD HEALTH ELECTRONIC MEDICAL RECORDS AND WAS ABLE TO IDENTIFY WITH A PREDICTIVE OF 85% OF THESE INDIVIDUALS BUT THE GENETIC TESTING AND THE IDENTIFICATION I THINK WE HAVE A HANDLE ON IT, THE REAL CHALLENGE IS HOW DO YOU DO THE CASCADE SCREENING, GETTING INTO THE FAMILY AND IDENTIFYING ASYMPTOMATIC INDIVIDUALS THAT IS WHERE WE REALLY NEED THE HELP SO HOPEFULLY WE WILL BE ABLE TO FIND INNOVATIVE APPROACHES THAT WOULD COMBINE ELECTRONIC BIG DINNER APPROACHES, MACHINE LEARNING ALGORITHMS AND WORK WITH OUR SOCIAL SCIENTISTS AND GENETIC COUNSELORS TO PUT TOGETHER GENERALIZABLE APPROACHES EVEN THOUGH WE ADDRESS IN FCHL H IT WOULD WORK FOR HYPERTROPHIC MYOPOTHY AND WORK FOR ESPECIALLY CARDIAC ARREST OF UNIDENTIFIED SOURCES SO WE ARE VERY EXCITED ABOUT THIS AND HOPE WE HAVE YOUR SUPPORT. >> THE FLOOR IS OPEN DR. ARNETT. >> AM I GOING TO RUN OUT OF QUESTIONS SOON DO YOU THINK? GEORGE THIS IS INCREDIBLY IMPORTANT, I'M SO DELIGHTED TO SEE IT IN THE PROPOSAL TODAY AND I THINK IT WILL EXTEND TO ALL OF THOSE CONDITIONS THAT YOU JUST OUTLINED. HAVE YOU -- I KNOW YOU ARE WORKING WITH C.D.C. HAVE YOU THOUGHT ABOUT WORKING WITH THE FH FOUNDATION BECAUSE THEY ARE ACTIVE IN THIS AREA AND A GOOD PARTNER. >> ABSOLUTELY FANTASTIC PARTNER ACTUALLY THIS YEAR HAPPENS TO BE THE 20TH ANNIVERSARY OF THE ORIGINAL WORLD HEALTH ORGANIZATION GUIDELINES AS YOU KNOW SO TOGETHER WITH THE WORLD HEALTH ORGANIZATION AND THE WORLD HEALTH FEDERATION AND THE FH FOUNDATION AND BY THE WAY THE STAMFORD STUDY FROM JOSH KNOLES WAS IN PARTNERSHIP WITH THE FH FOUNDATION THE STARS ARE ALL REALLY LINED UP VERY NICELY WITH THE 20TH ANNIVERSARY THE FH FOUNDATION IS PROBABLY ONE OF THE BEST PATIENT ADVOCACY GROUP AND THINK NHLBI LEADERSHIP CAN REALLY PULL ALL OF THIS TOGETHER. WE ARE VERY EXCITED ABOUT THIS. WE THINK ONE THE NEXT 5-7 YEARS WE CAN DO BETTER THAN THE NETHERLANDS AND OTHER EUROPEAN COUNTRIES HAVE DONE. >> ANYONE ELSE? DR. THOMAS. >> SO IT'S REALLY INTERESTING, I GUESS I HAD A COUPLE QUESTIONS FH IS OBVIOUSLY WE NOW HAVE GOTTEN SOME TREATMENTS TO BE ABLE TO DEAL WITH THAT BUT MANY OF THE OTHER CONDITIONS PARTICULARLY ASYMPTOMATIC INDIVIDUALS WE ARE NOT SURE EXACTLY WHAT TO DO WITH THOSE FOLKS SO EVEN IF YOU FIND THEM HOW DOES THIS RESEARCH BEGIN TO HELP US UNDERSTAND HOW TO MANAGE FOLK WHOSE ARE ASYMPTOMATIC PARTICULARLY WITH SOME OF THE GENETIC ARYTHEMAS THAT YOU TALKED ABOUT. >> WE KNOW WHAT TO DO IN THE NEXT 5-7 YEARS THERE IS A LOT WE CAN LEARN AND EVEN IN THE HYPERTROPHIC CARDIOMYOPATHY AND ARYTHEMAS AND THE SUDDEN CARDIAC ARREST THERE ARE PACE MAKERS AND SOME SETTINGS MEDICATION THAT CAN BE USED SO IT'S A WORK IN PROGRESS BUT THE MOST IMPORTANT THING IS EVEN IDENTIFYING THESE INDIVIDUALS AND PROVIDING THE APPROPRIATE GENETIC COUNSELING CAN LEAD TO SOME APPROPRIATE LIFESTYLE CHANGES THAT CAN BE VERY VERY SUPPORTIVE BUT THE BEST IS STATINS FOR LOWERING CLOTHESEL AND IT'S ABSOLUTELY A SHAME WHERE ALL GUIDELINES SUGGEST THAT AGGRESSIVE INTENSIVE STANTIN THERAPY SHOULD BE USED 15% WITH FH HAVE BEEN DONE AND I THINK WE CAN DO BETTER. >> ANY COMMENTS FROM OUR FOLKS ON THE PHONE? OKAY, PLEASE DO FINISH VOTING. WE HAVE A FILIBUSTER RULE FOR THIS, JUST JOKING. LOOKS LIKE ALL THE VOTES ARE IN FOR THIS ONE SO WE CAN CONTINUE. >> GREAT, THANK YOU. THE LAST INITIATIVE DR. MOEN WILL BE PLEASED TO HEAR, THIS IS NUMBER 1402 AND STIMULATE AND YOU MIGHT RECALL IN THE LAST FISCAL YEAR WE CAME TO YOU WITH A PROPOSAL TO DEVELOP AN OPTIMAL STRATEGY FOR INTEGRATING PROVEN EFFECTIVE INTERVENTIONS ACROSS THE HEART LUNG BLOOD AND SLEEP CONDITIONS THAT RFA WAS PUT OUT LAST YEAR BUT INDEPENDENTLY IT DID NOT ALLOW CLINICAL TRIALS. IT HAD THREE RECEIVE DATES AND AS WE PREPARED FOR THE FIRST RECEIVE DATES THERE WAS VERY ROBUST INTEREST BY MOST IDEAS THAT INVESTIGATORS HAD RELATED TO CLINICAL TRIALS THAT COULD NOT BE PUT IN. SO THE RESPONSE WE GOT FOR THE FIRST RECEIPT DATE WAS VERY DISAPPOINTING. IN DISCUSSING THE AVAILABLE OPTIONS IN THE NHLBI LEADERSHIP WE BELIEVE THAT RATHER THAN GOING THROUGH AND DOING ALL THREE RECEIPT DATES WE WANT TO REPLACE THE THIRD RECEIPT DATE WITH A SIMULATE TWO THAT ALLOWS CLINICAL TRIALS AND WE THINK WITH THE BEST USE OF RESOURCES IT WOULD ALLOW US TO GET THE BEST SCIENCE AND SHOULD MENTION PART OF THE REASON WE THOUGHT OF NOT ALLOWING CLINICAL TRIALS TO COME IN IS FOCUS ON SYSTEM LEVEL CHANGES AND ORGANIZATIONAL CHANGES BUT GIVEN THE DEFINITION FOR CLINICAL TRIALS IT'S ALMOST IMPOSSIBLE TO GET THE BEST SCIENCE WITHOUT ALLOWING CLINICAL TRIALS AND THIS IS SIMPLY A BUDGET NEUTRAL REPLACEMENT OF THE THIRD RECEIPT DATE OF THE ORIGINAL STIMULATION WITH THE NEW AND IMPROVED STIMULATION TWO THAT WOULD USE MILESTONE DRIVEN BY BASIC APPROACH OF THE R33 MECHANISM AND I'LL STOP HERE FOR YOUR COMMENTS AND YOUR SUGGESTIONS. >> COMMENTS FROM ANYBODY, PLEASE? I SEE A LOT OF SMILES AROUND THE ROOM BUT NOBODY IS GOING TO VENTURE FORTH, THAT IS OKAY. DO WE HAVE ANY COMMENTS FROM THE PHONE? OKAY SO YOU HAVE BEEN ASKED TO VOTE ON THE RECREATION OF STIMULA STIMULATE VERSION TWO WHICH IS ALWAYS BETTER THAN VERSION ONE, VERY STIMULATING, PLEASE VOTE IF YOU HAVEN'T ALREADY. MOVING ALONG PRETTY QUICKLY WITH THE VOTES I WILL GIVE EVERYONE ANOTHER OPPORTUNITY TO JUST CHECK OVER WHAT THEY HAVE DONE. JUST WAITING ON ABOUT THREE MORE PEOPLE HERE. I'LL WAIT JUST A LITTLE LONGER FOR THOSE REMAINING VOTERS. OKAY WE CAN CONTINUE ON WARD. WE ARE UP NEXT, DR. DEKYLEE. >> THE LUNG DIVISION HAS TWO DIVISION SPECIFIC INITIATIVES THAT WE WANT TO PRESENT TO YOU TODAY. THE FIRST ONE IS NUMBER 1403 THIS IS ENTITLED SARCADIAN EXPRESSION ASSOCIATED WITH DISEASE AND CALL THIS DIVISION SPECIFIC DISEASE THIS IS TRANS NHLBI AND LED BY THE CENTERS OF SLEEP RESEARCH WHICH HAS A TRANS IH COORDINATING FUNCTION THIS IS ACTUALLY A TRANS NIH INITIATIVE AS IT'S CURRENTLY DESIGNED. SO THIS INITIATIVE AIMS TO ACCELERATE THE IDENTIFICATION OF ABNORMALITIES IN SARCADIAN CLOCK EXPRESSION GEMOMIC MECHANISMS TO IMPROVE DISEASE MECHANISMS DISEASE RISK AND G ESHENOMIC THAT MODIFY TREATMENTS AND INITIATIVE CALLS FOR EXPERTS IN GEMOMICS OF DISEASE AND DISEASE SPECIFIC EXPERTISE TO LEVERAGE THE NEW FOUND CAPACITY TO IDENTIFY ABNORMALITIES AND CLOCK ORDER GENE TRANSCRIPTION AND TO MODIFY RESILIENCE TO DISEASE. THE INITIATIVE IS DESIGNED TO SUPPORT MECHENISTIC USING MODELS ANIMALS IN VETRO TISSUE PREPARATIONS AND LOOKS AT BASIC CLINICAL RESEARCH AND INVOLVES UTILIZATION OF EXISTING GEMOMIC DATA RESOURCES OR A COMBINATION OF THOSE APPROACHES AS NEEDED TO ADDRESS SPECIFIC SCIENTIFIC OPPORTUNITIES TO COUPLE THE SARCADIAN ORDERED GENE EXPRESSION PROFILES WITH UNDERSTANDING BASIC BIOLOGY AND DISEASE MECHANISMS THE INITIATIVE PROVIDES AN OPPORTUNITY TO BUILD A LOT OF INTER DISCIPLINARY TEAMS WHICH IS INCREDIBLY IMPORTANT TO DO THIS KIND OF SCIENCE AND IT WILL ALLOW IDENTIFICATION OF SPECIFIC ABNORMALITIES IN CLOCK COUPLED G GENOMIC LINKED TO DISEASE AND PROVIDE OPPORTUNITIES AND POSSIBILITIES TO IDENTIFY BIO MARKERS AND OBJECTIVELY HOW SLEEP IS TIED TO HEALTH AND THIS BIOLOGY IS BEST CAPTURED BY FUTURE TRENDS OMIX RESEARCH ACTIVITIES. THE BEE WAS VERY EXCITED ABOUT THIS INITIATIVE, IT RANKED QUITE HIGHLY, THEY FELT IT WAS EXTREMELY TIMELY AND AN EXCITING AREA OF RESEARCH AND IT WAS REALLY AT A POINT WHERE A PUSH FORWARD COULD POTENTIALLY REALLY ACCELERATE THE SCIENCE IN A BIG WAY AND I WILL STOP AND ANSWER ANY QUESTIONS ABOUT THIS INITIATIVE, YES, MONICA. >> JUST A COMMENT IT REMINDS ME OF MY ROOTS WHEN I FIRST GOT INTO THIS WORLD INTO THIS BUSINESS AND LOOKING AT NOCTURNAL AND LUNG FUNCTION AND FEEL WE HIT A WALL WITH THIS BECAUSE I'M REALLY HAPPY TO SEE THIS MOVE FORWARD. THERE IS THIS WHOLE FIELD OF CRONO BIOLOGY AND THERAPY WE HAVE NOT TAPPED INTO AND REALLY MAXIMIZED AND I THINK THIS IS ONE PIECE OF THAT PUZZLE THAT WILL HELP MOVE THIS FORWARD AT A MUCH MORE MECHANISTIC WAY BECAUSE THAT IS WHERE WE ARE AT THIS POINT AND THAT IS EXCITING. >> THANK YOU VERY MUCH. OTHER COMMENTS ON THIS ONE? ON THE PHONE ANYONE? >> I JUST WILL SPEAK FOR DR. Z WHO IS NOT HERE ANY MORE BUT THIS IS A GREAT ADDITION TO WORK AND SLEEP AND I'M REALLY GLAD TO SEE THAT IT'S FAIR AND HIGHLY SIGNIFICANT, HOPE WE CAN SUPPORT IT, THANK YOU DR. KYLIE. >> THANK YOU DIANE. >> I WOULD LIKE TO ADD I THINK. >> YOU HAVE TO PUSH THE LITTLE FACE. >> EXCUSE ME. >> THE FACE, YEAH. >> IT'S SUBTLE. I AGREE, I MEAN THIS IS A VERY MODEST PROPOSAL FOR THE BENEFIT THAT IS LIKELY TO COME OUT OF THIS. IT'S AN AREA THAT'S UNDER STUDIED. WE REALLY DON'T KNOW WHAT IS HAPPENING AT DIFFERENT TIMES OF DAY AS DR. KRAFT POINTED OUT AND HOW WE CAN TREAT THEM IT ALSO IS RELATED TO OTHER INSTITUTES WHO SUPPORT THIS NIDA IS A SUPPORTER AND I THINK IF THIS MOVES FORWARD OTHER INSTITUTES WILL JOIN IT. >> AND EVEN HOW OUR CURRENT MEDICATIONS SCREW IT UP BECAUSE OF USE OF STEROIDS WE ARE COMPLETELY YOU KNOW DESTROY YOUR SARCADIAN RHYTHM. >> I DID NOT MENTION IT IN MY BRIEF COMMENTS BUT WE ALREADY HAVE THE NATIONAL INSTITUTE OF DRUG ABUSE THAT HAS SIGNED ON TO THIS, WE THINK CHILD HEALTH MIGHT SIGN ON TO THIS SO THERE IS LIKELY TO BE MULTIPLE ICS THAT ARE GOING TO ENGAGE IN THIS TOPIC AND SO I THINK IT IS OF HIGH INTEREST TO A LOT OF NIH STUDENTS. >> OKAY VERY GOOD THANK YOU ALL FOR THOSE VERY POSITIVE COMMENTS. HOW ARE WE DOING MOVE ON OR VOTING? >> WE ARE STILL WAITING ON FOUR PEOPL PEOPLE. >> OKAY. >> I'LL GIVE THOSE FEW EXTRA PEOPLE A MOMENT MORE TO COMPLETE THEIR VOTES. ALMOST DONE. WE CAN MOVE ON. >> OKAY VERY GOOD SO THE SECOND ONE FOR SOMETHING A LITTLE DIFFERENT HERE THIS IS INITIATIVE NUMBER 1405 IT'S ENTITLED LUNG TRANSPLANT CLINICAL RESEARCH CONSORTIUM A COOPERATIVE AGREEMENT PROGRAM, THIS IS A PROGRAM THAT HAS BEEN DEVELOPED WITHIN THE DIVISION I WANT TO GIVE MATT CRAIG AND NEIL AND STAFF OF THE LUNG DIVISION A SHOUT OUT HERE BECAUSE OF THE ENORMOUS AMOUNT OF WORK DEVELOPING THE PROGRAM AND THE PURPOSE IS TO CREATE A LUNG TRANSPLANT CONSORTIUM THAT WILL FACILITATE CLINICAL RESEARCH AND LUNG TRANSPLANTATION BY BUILDING THROUGH A CONSENSUS PROCESS HARMONIZED AND STANDARDIZED OBSERVATIONAL DATA COLLECTION ACROSS LUNG TRANSPLANT CENTERS IN THIS COUNTRY. DATA FROM THIS CONSORTIUM WILL SERVE AS THE BASIS FOR FORMULATING AND ADDRESSING SCIENTIFIC QUESTIONS RELATED TO PRIMARY AND ACUTE LUNG ALOGRAPH DYSFUNCTION WITH THE END GOAL OF IMPROVING THE OTHERWISE STAGNANT OUTCOMES WITH LUNG TRANSPLANTATION I DON'T HAVE TO TELL THIS GROUP MUCH THAT THE FIVE YEAR ABOUT LUNG TRANSPLANTS STATISTICS BUT THE FIVE YEAR MORTALITY FOR ADULT LUNG TRANSPLANT RECIPIENTS HAS HOVERED AROUND 45% SINCE ABOUT 2002 A RATE THAT IS DOUBLE THE MORTALITY OR GRAPH FAILURE RATES OBSERVED FOR OTHER ORGANS SO THE LUNG IS CLEARLY WAY BEHIND PRIMARY GRAPH DYSFUNCTION AND ACUTE LUNG ALOGRAPH DYSFUNCTION ARE CAUSES OF EARLY MORBIDITY FOLLOWING LUNG TRANSPLANTATION AND ALSO THE PRIMARY RISK FACTORS FOR THE DEVELOPMENT OF CHRONIC LUNG ALOGRAPH DYSFUNCTION RESPONSIBLE FOR FOR THE LONG-TERM FAILURE AND DEATH IN RECIPIENTS. THEY VERY GREATLY BUT BETWEEN 5-50% ACROSS THE LUNG TRANSPLANT CENTERS. NHLBI HAS BEEN IN THE SPACE FOR A WHILE AND JUST RECENTLY WE HELD A WORKSHOP AND ALSO WE RELEASED A REQUEST FOR INFORMATION TO TRY TO GET A HANDLE ON THE VARIABILITY AND PRACTICES ACROSS THE COUNTRY IN LUNG TRANSPLANT CENTERS. AND WHAT OUR RFI TOLD US IS THAT THEY ARE HIGHLY INCONSISTENT CRITERIA FOR LUNG DONOR AND RECIPIENT IN CLINICAL MANAGEMENT PRACTICES AS WELL AS DIAGNOSTIC ASSESSMENT METRIC ACROSS CENTERS SO THERE IS REALLY A LONG WAY TO GO TO KIND OF STANDARDIZE IN THE DIFFERENT APPROACHES THAT ARE BEING USED. PRACTICE VARIABILITY SERVES AS A MAJOR IMPEDIMENT TO PERFORMING MULTI SITE CLINICAL RESEARCH SO WE CAN'T GET IN THE RESEARCH SPACE UNTIL STUDIES ARE DESIGNED TO BETTER UNDERSTAND WHY THE OUTCOME DISPARITIES EXIST ACROSS THE TRANSPLANT AREA. SO THE CONSORTIUM WILL PROVIDE THE FIRST CRITICAL STEPS TOWARDS IDENTIFYING BEST EARLY CLINICAL MANAGEMENT AND ASSESSMENT PRACTICES IN LUNG TRANSPLANTATION. ULTIMATELY THIS CONSORTIUM WILL BE POSITIONED TO FACILITATE FUTURE INNER TEAR VENT SHUN TO IMPROVE THE SHORT AND LONG-TERM OUTCOMES FOR ALL LUNG TRANSPLANT RECIPIENTS AS YOU CAN SEE THIS IS A LONG-TERM PROGRAM IT'S IN PHASES AND THE FIRST PHASE WE FEEL WITH THIS CONSORTIUM IS TO RALLY GET OUR HANDLE GET OUR HANDS AROUND THE HARMONIZATION AND THE STANDARDIZATION OF THE DATA AND THEN LEADING TOWARDS POTENTIALLY EARLY CLINICAL MANAGEMENT TRIALS. SO PARDON ME THE B WAS VERY ENTHUSIASTIC ABOUT THIS INITIATIVE ALSO, THEY HAD A NUMBER OF QUESTIONS ABOUT COORDINATING ACROSS ICS, ALSO LEARNING FROM EXPERIENCES WITHIN THE INSTITUTE THROUGH VARIOUS NETWORKS WE HAVE HAD AND WE HAVE BUILT ALL THAT INTO THE WRITE UP SO WITH THAT I'LL STOP AND I'LL BE HAPPY TO ANSWER IN ANY QUESTIONS. >> DEAN. >> SO I THINK YOU SHOULD BE CONGRATULATED ON THIS IT'S REALLY INCREDIBLY IMPORTANT INITIATIVE, LUNG TRANSPLANT HAS BEEN GOING NOW FOR 18, 19 OR 17 YEARS I GUESS AND YOU KNOW IT'S BEEN MOSTLY STARTED BY BUSY CLINICIANS, IT'S BEEN SORT OF RELATIVELY MADE UP AREA IN TERMS OF SCIENCE SO PEOPLE JUST DECIDED WHAT THEY WERE GOING TO DO THAT IS WHY THERE IS SO MUCH CHAOS NOW WE HAVE A CRITICAL MASS I THINK OF YOU KNOW SCIENTISTS WHO ARE ENGAGED IN LUNG TRANSPLANTATION AS THESE PROGRAMS HAVE GROWN SO IT'S A GREAT TIME TO TRY TO BUILD A STRONG CONSORTIUM LIKE THIS. I THINK IT WILL HAVE A HUGE IMPACT ON ADDING SCIENTIFIC RIGOR TO APPROACHES THAT ARE TAKING. >> THE GOAL AND THE WAY THE PROGRAM IS DESIGNED WILL CAPTURE PROBABLY ABOUT HALF OF THE TRANSPLANT CENTERS ACROSS THE COUNTRY SO IT WON'T BE POCKETS OF BIG SITES THAT DO LOTS OF VOLUME. >> THAT IS GREAT. NOT A WHOLE LOT TO HAD TO DEAN'S COMMENTS OTHER THAN THAT IS A LONG TIME COMING I'M THRILLED TO SEE IT, IT'S SO NEEDED FOR THE SCIENCE BECAUSE A LOT OF WHAT'S BEING DONE IS SO CENTER SPECIFIC AND REALLY ANECDOTAL SO VERY HAPPY TO SEE IT. >> THANK YOU. YES. >> MAYBE IT'S THE ONLY PERSON IN THE ROOM WHO HAS EVER DONE A LUNG TRANSPLANT I WOULD AGREE THAT A LOT OF ARTISTS AT WORK HERE SO THIS BRINGS SOME ORDER TO THE CHAOS SO I STRONGLY SUPPORT IT. >> THANK YOU, DOCTOR. OKAY ON THE PHONE, JUST NOT TO LEAVE ANYONE OUT HERE. OKAY, NOT SEEING ANY MORE COMMENTS COMING ALONG OR AROUND THE ROOM SO GO AHEAD AND VOTE ON THIS ONE AND WE WILL MOVE ON ONCE WE GET THE NOD. >> WE ARE MOVING PRETTY WELL ON THIS ONE SO WE CAN CONTINUE. >> ONCE AGAIN WE ARE READY TO MOVE ON TO THE NEXT INITIATIVE. >> OKAY THANKS SO THE NEXT CATEGORY OF INITIATIVES ARE CALLED TRANS NHLBI AND JUST SO HAPPENS THE FIRST OF THE FIVE OF THESE THAT WE ARE GOING TO PRESENT TO YOU IS LED BY THE LUNG DIVISION SO I'LL PRESENT THAT ONE AND THEN TURN IT OVER TO DR. GOTH WHO WILL DO THE REMAINING FOUR INITIATIVES THAT ARE TRANS NHLBI THE FIRST ONE IN THIS BOX OR THIS CATEGORY IS INITIATIVE 1395 IT'S A RENEWAL ACTUALLY IT'S A LIMITED COMPETITION OF SMALL GRANT PROGRAM FOR NHLBI KO1 AND 8 AND 23 RECIPIENTS AND THE RO3 AS YOU KNOW IS A SMALL GRANTS PROGRAM SO THIS IS A RENEWAL AS I MENTIONED OF AN RO3 THAT WAS INITIATED AS A PILOT IN 2015 TO SUPPORT NHLBI KO1, 8 AND 23 AWARDEES TO ADD THEM IN THE TRANSITION TO INDEPENDENCE SO THE RO3 PROGRAM AIMS TO PROVIDE SOME CONTINUITY OF SUPPORT FOR THE BIOMED CALL RESEARCH WORKFORCE WITH PARTICULAR EMPHASIS ON THE PHYSICIAN SCIENTISTS AND IT WAS DESIGNED TO MAXIMUM THE VALUE OF THE NHLBI K AWARDEES SO IF YOU THINK ABOUT THIS IT'S A BIT OF A BRIDGE FROM THE END OF YOUR K TO WHEN YOU MIGHT OBTAIN YOUR FIRST RO1 AND ONE OF THE ISSUES THAT HAS COME UP CONTINUOUSLY IS THAT OFTEN TIMES PHYSICIAN SCIENTISTS AS PART OF THEIR K TRAINING DO NOT HAVE ENOUGH TIME IN THAT K TO REALLY GET THE DATA THEY NEED TO GET THAT RO1 FUNDED SO THE IDEA WAS TO PROVIDE THIS RO3 TWO YEAR AWARD MAXIMUM BUDGET OF 50K AND DIRECT COSTS, THE ELIGIBILITY FOR THE RO1 INCLUDES THOSE THAT WERE SUPPORTED BY THE K AWARD WHO ARE IN THE LAST COUPLE OF YEARS OF THEIR SUPPORT AND THAT THE K WAS ABOUT OR THE K WAS ABOUT TO END. IT'S A SHORT DURATION PROGRAM AND WHAT WE DID WITH THIS PROGRAM IS WE DID A PRELIMINARY ANALYSIS OF THE ASSESSMENT FROM 2015 WHEN WE FIRST STARTED IT AND ALTHOUGH THE RESULTS ARE REALLY EARLY IT WAS QUITE POSITIVE 40% OF THE RO3 APPLICANTS WENT ON TO RECEIVE RO1S WHILE ONLY 25% OF THE NON-RO3 APPLICANTS GOT RO1S SO WE SAW THIS UPTICK IN THE ABILITY OF THOSE WHO RECEIVED THE RO3 TO GO ON AND GET THE RO1. WE NEED TO DO SOME LONGITUDINAL FOLLOW-UP OF THAT INITIAL COHORT AS WE HOPE TO DO AS PART OF THE NEXT PHASE BUT I THINK WE ARE ENCOURAGED ENOUGH TO THINK THIS IS A HAVING A POSITIVE IMPACT ON OUR TRAINEES AND PROPOSING TO RENEW THIS FOR FOUR YEARS, WE HOPE THAT OVER THIS PERIOD OF TIME WE WOULD MAYBE FUND IT A LITTLE OVER 50 AWARDS WHICH WILL BE A LITTLE BIT ABOUT JUST ABOUT THE SAME OR A LITTLE BIT MORE THAN WHAT WE HAVE AWARDED IN THE PAST FEW YEARS OF THE PROGRAM AND I WILL STOP AND THE B WAS ENTHUSIASTIC ABOUT THIS PROGRAM AND PROBABLY DON'T HAVE TO MENTION THAT ONE THEY THINK IT'S AN IMPORTANT ELEMENT TO WHAT WE ARE DOING TO HELP THE PHYSICIAN SCIENTISTS WORKFORCE SO WITH THAT I'LL STOP AND BE HAPPY TO ANSWER QUESTIONS. >> ANYBODY ON THE PHONE? GIVEN THIS MORNING I THINK THIS IS THE KIND OF THING WE NEED TO KEEP TRYING AND IN FOUR YEARS YOU WOULD KNOW HOW IT DID BUT EVEN 40% OR 20% SAYS IT'S WORKING WELL. >> OKAY, ANY OTHER COMMENTS? I SEE THUMBS UP OVER THERE BUT DR. ARNETT WHICH I'M HAPPY TO SEE. WE ARE ALL PRETTY EXCITED ABOUT THIS PROGRAM. WE THINK IT'S PROVIDING A LOT OF VALUE AND WHEN WE TALKED TO OUR K AWARDEES THEY OFTEN TIMES WILL REALLY BRING IT UP AS HOW DO I GET ONE OF THESE. OKAY, JEN. >> YOUR ENTHUSIASM IS VERY EVIDENT BECAUSE ALL THE VOTES ARE IN AND MOVE TO THE NEXT ONE. >> OVER TO DR. GOTH SO THE DIVISION OF CARDIOVASCULAR SCIENCES WILL PRESENT FOUR TRANS HLBS INITIATIVES AND EXCITED ABOUT ALL OF THEM AND HOPE YOU WILL BE TOO. THE FIRST ONE IS NUMBER 1392 SECONDARY ANALYSIS OF EXISTING DATA SETS IN HEART LUNG AND BLOOD DISEASES AND SLEEP DISORDERS IT'S AN R21 RECOGNITION. THIS WOULD BE THE THIRD ISSUE OF THIS PAR. SO THIS OPPORTUNITY AIMS TO STIMULATE EXISTING DATA SETS FOR SECONDARY ANALYSIS TO TEST PREVENTION OR TREATMENT AND IMPLEMENTATION OF EVIDENCE BASED INTERVENTIONS FOR HLBS DISEASES AND CONDITIONS THAT ARE RELEVANT TO OUR MISSION. ANALYZING THE EXISTING DATA SETS PROVIDES A COST EFFECTIVE METHOD TO ADDRESS RESEARCH QUESTIONS AND GENERATE PRELIMINARY DATA FOR SUBSEQUENT RESEARCH PROPOSALS. SO THIS TRANS HLBS PROGRAM WAS INITIATED WITH THE GOAL OF LEVERAGING THE NHLBI INVESTMENT THAT IS MADE IN CLINICAL AND OBSERVATION STUDIES AND STIMULATE THE USE OF THOSE EXISTING DATA. AND ALTHOUGH NHLBI DOES NOT PARTICIPATE IN THE PARENT R21 MECHANISM WE BELIEVE THAT THE R21 MECHANISM IS AN IMPORTANT AND EFFECTIVE WAY TO SUPPORT THIS SPECIFIC TYPE OF RESEARCH. IN TERMS OF THE RETURN ON INVESTMENT, THIS WOULD BE THE THIRD ISSUANCE AND WE HAVE PRETTY GOOD DATA ON THE FIRST ROUND, THE PAR ISSUED IN FISCAL YEAR 13 RESULTED IN 367 APPLICATIONS, 49 AWARDS INCLUDING EIGHT TO EARLY STAGE INVESTIGATORS AND RESULTED IN 149 PUBLICATIONS AS OF JANUARY OF THIS YEAR INCLUDING IN SUCH LOW JOURNALS AS NATURE CIRCULATION AND NEW ENGLAND JOURNAL OF MEDICINE SO SOME OF THESE ARE IN REALLY HIGH I'LL IMPACT PLACES IT'S LESS EASY TO EVALUATE AND HALF OF THE EARLY AWARDEES HAVE PUBLISHED, THERE IS 16 PUBLICATIONS ALREADY AS OF JANUARY INCLUDING NATURE CARDIOLOGY AND CIRCULATION SO WITH THAT I'LL BE HAPPY TO ANSWER ANY QUESTIONS ABOUT THIS INITIATI INITIATIVE. >> DON'T SEE ANYBODY IN THE ROOM, ANYBODY ON THE PHONE? OKAY, WELL PLEASE VOTE. MORE THAN HALFWAY THERE WITH THE VOTES SO I'LL GIVE EVERYONE ANOTHER MINUTE TO MAKE THEIR DECISION. ALL THE VOTES ARE IN WE ARE READY TO MOVE ON TO THE NEXT INITIATIVE. >> ALL RIGHT THE SECOND IS NUMBER 1404, SMALL RESEARCH GRANTS FOR ANALYSIS OF GABRELLA PEDIATRIC RESEARCH DATA RO3 MECHANISM THIS IS SECONDARY PARTICIPATION IN AN INITIATIVE LED BY NICHD. THE OBJECTIVE OF THIS INITIATIVE IS TO CAKALIZE WITH STRUCTURAL BIRTH DEFECTS OR CHILDHOOD CANCER WITH SEQUENCE DATA SETS BEING GENERATED AS PART OF THE GABREILLA KIDS FIRST PEDIATRIC RESEARCH PROGRAM SO THIS LEVERAGES INSTITUTE RESOURCES TO ENABLE INVESTIGATORS FOR PRIMARY RY AND SECONDARY DATA SETS AND NHLBI CONTINUED PARTICIPATION ON THIS PAR WILL ENABLE SUBMISSION OF ADDITIONAL APPLICATIONS TO ANALYZE DATA FROM PROJECTS WITH HEART LUNG AND BLOOD PHENO TYPES. AS YOU KNOW THE GEMOMICS HOLDS PROMISE FOR EFFECTIVE AND TARGETED THERAPIES BASED ON THE UNDER LYING CLASSIFICATIONS WHICH IS THE FOCUS OF PRECISION MEDICINE DEVELOPMENTAL DEVELOPMENTS THE COMMON ORGAN DEVELOPMENT COMBINED EFFORTS OF BASIC SCIENCE STUDYING THE GENETIC NETWORKS AND SCIENTISTS WITH PATIENT COHORTS TOGETHER PLACE THE FIELD OF STRUCTURAL BIRTH DEFECTS ON THE VERGE OF MAJOR ADVANCES NOW IN TERMS OF RETURN ON INVESTMENT THIS IS A RENEWAL AND IN THE INITIAL PHASE OF THIS FOIA, 38 APPLICATIONS RECEIVED AND TWO ASSIGNED TO NHLBI AND ONE IS FUNDED AND TOO EARLY TO TELL WHAT THE OUTCOMES WILL BE SO WE WOULD ANTICIPATE WITH THE GABRIELLA KIDS FIRST PROGRAM FUNDED THROUGH FISCAL YEAR 24 THAT THIS MAY BE THE FINAL ISSUANCE OF THIS FOIA IF APPROVED, IT'S POSSIBLE ONE MORE CYCLE WOULD GET FUNDED OR WOULD GET ISSUED IN THE FUTURE. WE WOULD COME BACK TO YOU FOR THAT IF THAT WERE THE CASE AND WE DON'T KNOW AS OF TODAY WHETHER GABRIELLA MILLER KIDS FIRST WILL BE RENEWED FOR FURTHER FUNDING AFTER THIS FIRST TEN YEAR CYCLE WITH THAT I'LL BE HAPPY TO ANSWER ANY QUESTIONS. >> IS THERE A PARTICULAR PROCESS DRIVING THE DECISION MAKING THAT WOULD AFFECT OUR DECISIO MAKING HERE? >> YOU MEAN WHETHER THERE WILL BE A RENEWAL OF THE UNDER LYING PROGRAM AFTER THE FIRST TEN YEARS? >> RIGHT. >> I DON'T KNOW IF MARTIN LYRIX OR JOHN KALTMAN IS IN THE ROOM JOHN DO YOU HAVE INSIDE INFORMATION ON THE DECISION MAKING FOR WHETHER THE TEN YEAR INITIATIVE WOULD BE RENEWED? YOU CAN COME FORWARD AND YOU ARE WELCOME TO COME FORWARD AND USE THE MIC. THANKS, JOHN. >> SO THIS IS A CONGRESSLY AUTHORIZED PROGRAM AND THE LEGISLATION WAS FOR TEN YEARS SO WE ARE NOT SURE BEYOND THAT. >> ENOUGH SAID. >> BUT THIS PARTICULAR PART OF IT WHICH IS A SEPARATE INITIATIVE IS REALLY TO STIMULATE USE OF THE DATA SO THE UNDER LYING PROGRAM IS GENERATING THE DATA AND THIS MECHANISM IS TO STIMULATE SCIENTISTS TO ACTUALLY USE THE DATA SO THEY CAN GET FUNDING FOR SECONDARY ANALYSIS WHICH IS REALLY DIFFICULT TO DO THROUGH THE TRADITION RO1 MECHANISM IT DOESN'T REVIEW WELL OFTEN IN THE TYPICAL STUDY SECTION SO RO3 MECHANISM IS VIEWED AS AN EFFECTIVE WAY OF STIMULATING INVESTIGATOR ACCESS AND USE OF DATA THAT IS ALREADY BEING GENERATED. >> ANY OTHER QUESTIONS OR COMMENTS IN THE ROOM OR ON THE PHONE? IF NOT PLEASE VOTE. >> I WAS GOING TO MENTION I'M SURPRISED DR. KALTMAN DIDN'T THAT A KEY ELEMENT THAT WE DESCRIBED WAS TO LINK THE GABRIELLA MILLER DATA SETS AND DATA SETS TO DATA STAGE SO AS YOU ARE POINTING OUT A RICH DATA RESOURCE HAS BEEN CREATED OVER THE LAST DECADE AND ENHANCING ABILITY TO MINE THAT AND FACILITATING PEOPLE'S ACCESS TO THAT WILL BE KEY. >> YEAH AND I THINK AN IMPORTANT ASPECT OF THAT IS WHENEVER THE UNDER LYING FUNDING FOR THAT PARTICULAR INITIATIVE ENDS THERE WILL BE MECHANISMS IN PLACE TO ALLOW SCIENTISTS TO CONTINUE TO ACCESS THE DATA THROUGH OUR DATA STAGE SUPPORT AS WELL AS THROUGH THE INFRASTRUCTURE THAT GABREILLA MILLER KIDS FIRST IS CREATING, WE ARE WORKING ON HAVING INTER OPERABILITY AS YOU HEARD THIS MORNING BETWEEN DATA STAGE AND GABRIELLA MILLER KIDS FIRST. >> ARE WE READY TO MOVE ON? >> YES, EVERYBODY HAS ALREADY VOTED. >> OKAY, LET'S SEE I THINK I'M GETTING OUT OF ORDER HERE. NEXT ONE IS NUMBER 1393 LEVERAGING THE ADOLESCENT BRAIN AND COGNITIVE DEVELOPMENT COHORT, THIS IS ALSO A SECONDARY PARTICIPATION INITIATIVE AND AS WELL AS A TRANS HLBS INITIATIVE. SO THE INTENT OF THIS PROPOSAL IS TO SUPPORT NOVEL EPIDEMIOLOGICAL HEART BLOOD LUNG AND SLEEP TO CONTINUE TO COFUND THE NATIONAL DRUG ABUSE ADOLESCENTS BRAIN COGNITIVE DEVELOPMENT STUDY OR ABCD DURING THE FOURTH ABCD COHORT EXAMINATION WHICH WILL BE CONDUCTED BETWEEN 2020-2022 AT WHICH TIME THE PARTICIPANTS WILL BE 13-14 YEARS OLD AND SPECIFICALLY THIS INITIATIVE WILL PROVIDE FURTHER SUPPORT FOR MEASURES RELEVANT TO HLBS DEVELOPMENTAL PROCESSES UNDER LYING MECHANISMS OF HLBS DISORDERS AND RELATIONSHIPS WITH COGNITIVE AND BRAIN FUNCTIONING. SO ABCD IS CURRENTLY FUNDED BY NIDA WITH ADDITIONAL SUPPORT FROM TEN OTHER INSTITUTE CENTERS AND OFFICES INCLUDING NHLBI AS WELL AS OTHER FEDERAL AGENCIES INCLUDING C.D.C. SO NHLBI BEGAN COFUNDING THIS PROJECT DURING THE SECOND EXAMINATION WHICH WAS FROM 2018-2020, AT THAT TIME WE PROVIDED SUPPORT FOR ADDITIONAL MEASURES CONSISTENT WITH OR AT LEAST APPROXIMATING THE AMERICAN HEART ASSOCIATION LIFE SIMPLE 7 MEASURES OF CARDIOVASCULAR HEALTH THINGS LIKE BLOOD PRESSURE CHOLESTEROL DIET BLOOD GLUCOSE PHYSICAL ACTIVITY AND SO FORTH THAT WERE NOT ALREADY FUNDED BY NIDA OR OTHER PARTNERS. THEY WERE ALREADY COLLECTING BODY MASS INDEXES PHYSICAL ACTIVITY AND SMOKING DATA BUT WE FILLED OUT THE REST OF IT. WE ADDED MEASURES OF HEMOTOLOGIC AND C.D.C. AS WELL AS SALARY SUPPORT FOR PEDIATRIC WITH FOCUS ON HEART LUNG BLOOD AND SLEEP DOMAIN. IN THIS NEXT ROUND WE WILL CONTINUE TO SUPPORT COLLECTION OF LONGITUDINAL MEASURES IN THOSE DOMAINS AS WELL AS STRENGTHENING DATA COLLECTION FROM A SURVEY PERSPECTIVE ON RESPIRATORY HEALTH. SO WITH THAT I'D BE DELIGHTED TO ENTERTAIN ANY QUESTIONS OR COMMENTS ABOUT THIS INITIATIVE. >> NO QUESTIONS OR COMMENTS IN THE ROOM, ANYBODY ON THE PHONE? >> HALF THE VOTES ARE IN. >> PEOPLE ARE GETTING HUNGRY. SHOULD HAVE BROUGHT PIZZA IN. >> THAT'S IT, THAT'S IT IT'S HIGHLY EFFECTIVE SURE I'LL GO WITH THAT, IT MAKES ME FEEL GOOD, MAKES MY FOOT FEEL BETTER. WE READY? >> WE ARE ALMOST READY FOR MOVE ON, I'M WAITING FOR TWO MORE VOTES. WE CAN MOVE ON. >> WELL THIS LAST ONE AND YOU KNOW EXCITED ABOUT THIS ONE TOO NUMBER 1389 SECONDARY PARTICIPATION IN THE HUMAN HEALTH EXPOSURE ANALYSIS RESOURCE AND THIS IS SECONDARY PARTICIPATION IN A RESOURCE THAT SUPPORTED PRIMARILY BY NIHS WITH PARTNERSHIP FROM OTHER ICS. SO THE GOAL OF THE HUMAN HEALTH EXPOSURE ANALYSIS RESOURCE WHICH WE WILL CALL HERE FROM NOW ON IS TO PROVIDE INFRASTRUCTURE FOR ADDING OR EXPANDING EXPOSURE ANALYSIS TO ADVANCE UNDERSTANDING OF THE IMPACT OF ENVIRONMENTAL EXPOSURES ON HUMAN HEALTH THROUGHOUT THE LIFE COURSE. THE FUNDAMENTAL OBJECTIVE OF HERE IS TO SUPPORT AN INFRASTRUCTURE THAT PROVIDES CENTRALIZED HIGH QUALITY EXPOSURE ASSESSMENT ACROSS THE BREATH OF THE EXPOSE TO THE GRANTEE COMMUNITY SO THE CON CONSORTIUM WILL BE A FULL SERVICE INFRASTRUCTURE OF LABORATORIES DATA AND COORDINATING CENTERS THAT WILL PROVIDE VALUE BOTH TO THE INDIVIDUAL CLIENT UTILIZING THE RESOURCE INDIVIDUAL STUDY AND THE BROADER COMMUNITY THROUGH ENHANCED DATA SHARING AND RESOURCING AND EXPOSURE ANALYSIS AND THE DEVELOPMENT AND VALIDATION OF NEW METHODS. THE HERE PROGRAM IS IMPLEMENTING A PLAY TO PAY WITH OTHER NIH PARTICIPATING INSTITUTES CONTRIBUTING TO THE COST OF THE RESOURCE PROGRAMS. SEVERAL OTHER INSTITUTES ARE CONSIDERING PARTICIPATION INCLUDING NCI, NIA, NIDA, NIDDQ AND ECHO PROGRAM IN THE INITIAL FORM IT WAS CALLED CHEER THE CHILD HEALTH EXPOSURE ANALYSIS RESOURCE AND IT WAS REALLY FOCUSED PRIMARILY ON THE ECHO PROGRAM AND OTHER PEDIATRIC STUDIES SO NHLBI AS YOU KNOW INVESTED HEAVILY PHENO AND GENOTYPE LARGE SCALE COHORTS GENERATING ENORMOUS DATA YOU HEARD ABOUT THAT THIS MORNING AND TOP MED AND DATA STAGE PARTICIPATING IN THIS RFA WILL LEVERAGE OUR INVESTMENT IN THOSE SORTS OF STUDIES TO GAIN A GREATER UNDERSTANDING OF THE GENETIC AND ENVIRONMENTAL UNDER PINNINGS OF HEART LUNG BLOOD AND SLEEP HEALTH AND CONDITIONS. THE WRITE UP INCLUDED EXAMPLES OF RESEARCH QUESTIONS OF IMPORTANCE FOR HEART LUNG AND BLOOD CONDITIONS. AND I THINK SUPPORTED TO NOTE CHEER HAS PROVIDED SUPPORT FOR TWO PROJECTS THAT WERE RELEVANT TO HEART AND LUNG DISEASE ONE RELATED TO CHILDHOOD OBESITY THAT WAS RO1 AND ANOTHER TO A K AWARDEE WHO WAS STUDYING CHILDHOOD PULMONARY HEALTH AND SOME OF THE ENVIRONMENTAL EXPOSURES ASSOCIATED WITH THAT. SO OUR COFOUNDING OF ABOUT A MILLION A YEAR FOR FOUR YEARS WOULD BE USED TO COFUND THE LABORATORIES ONLY THE LABORATORIES NOT THE REST OF THE INFRASTRUCTURE THAT IS SUPPORTED BY NIHS AND ALLOW US TO PROVIDE SOMEWHERE AROUND 5,000 ESSAYS A YEAR OR TOTAL OF 20,000 ESSAYS OVER A PERIOD OF SUPPORT TO THE HEART LUNG BLOOD AND SLEEP COMMUNITY. AND WITH THAT I'D BE HAPPY TO TAKE ANY QUESTIONS OR COMMENTS ON THIS INITIATIVE, YES. >> SO I'M UNCLEAR HOW THIS MECHANISM IS GIVEN OFFERED TO INVESTIGATORS IS THIS PART OF AN INVESTIGATOR RO1 IN ADDITION I WOULD LIKE TO APPLY TO THIS AS TO TASK MY ANIMALS IN THIS ENVIRONMENT. >> MY UNDERSTANDING THIS IS FOR HUMANS SO IT WOULDN'T BE FOR ANIMAL STUDIES BUT THE UNDER LYING QUESTION OF HOW PEOPLE GET ACCESS TO IT THE HERE PROGRAM HAS A PROCESS OF REACHING OUT TO THE INVESTIGATOR COMMUNITY TO LET THEM KNOW ABOUT THE AVAILABILITY OF THIS RESOURCE, OUR SCIENTIFIC STAFF TEAM WOULD WORK WITH THEM AND WOULD COMMUNICATE WITH OUR GRANTEE COMMUNITY AS WELL TO PROMOTE KNOWLEDGE ABOUT THE AVAILABILITY OF THIS RESOURCE AND HOW TO APPLY TO GET THE USE, THERE IS INFORMATION ON THEIR WEBSITE CURRENTLY THAT IS FOCUSED MORE ON CHILD CHEER THAN HERE AND MICHELLE WAS HERE THE LAST I HEARD HERE IS STILL UNDER AND BEING COMPETED, I DON'T KNOW WHETHER THE DECISIONS ABOUT THE LABS AND AWARDS TO THE COORDINATION CENTER HAVE BEEN MADE BUT THEY ARE IN THE PROCESS OF DOING THAT THEN THE WEBSITES WILL BE UPDATED TO FOCUS ON HERE RATHER THAN JUST CHEER. WE WILL WILL A SEAT AT THE TABLE IN TERMS OF SCIENTIFIC STAFF FROM A NHLBI IN THE PROCESS OF SELECTING THE, YOU KNOW, THE IN TERMS OF DETERMINING WHO GETS ACCESS TO THE RESOURCE, IT'S ACCESS TO A RESOURCE, NOT FUNDING PER SE THAT THE INVESTIGATORS GET BUT WE WILL BE WORKING CLOSELY WITH NIHS TO MAKE SURE THE INFORMATION GETS OUT TO OUR GRANTEE COMMUNITY. >> VERY SMALL INVESTMENT FOR A LOT OF POTENTIAL OUTCOME. >> YEAH, I MEAN I THINK, YOU KNOW, DR. GIBBONS AND I HAVE THIS DISCUSSION ABOUT THIS ISSUE AND I'M A PUBLIC HEALTH GUY SO I'M ABSOLUTELY CONVINCED THAT THE ENVIRONMENTAL EXPOSURES ARE REALLY GOING TO BE WHERE WE LEARN A LOT ABOUT WHAT'S DRIVING VARIATION AND GENE EXPRESSION SO I THINK THIS IS A REALLY EXCITING OPPORTUNITY FOR US TO GET A TREMENDOUS RETURN ON A FAIRLY SMALL INVESTMENT. IN FACT, I WOULD LOVE FOR PEOPLE TO SAY YOU SHOULD SPEND MORE ON THIS BECAUSE I THINK 20,000 WE GOT 150,000 WHOLE GENOME SEQUENCE IN TOP MED A LOT OF OMIX IN TOP MED THE EPI OR THE TRANS SCRIPTOME AND THESE ENVIRONMENTAL WILL DRIVE PATTERNS AND GENE EXPRESSION PATTERNS AND I WILL STOP BEFORE TERRY GETS THE HOOK OUT. >> JUST TO UNDERSTAND RESILIENCE RESILIENCE I THINK THIS WILL BE VERY IMPORTANT THUMBS UP. >> AGREE COMPLETELY. >> I ALSO AGREE THAT IT'S REALLY IMPORTANT RESOURCE TO HAVE AVAILABLE TO PEOPLE, I WOULD SUGGEST MAYBE INVESTING A LITTLE BIT MORE IN ADVERTISING THE ACCESSIBILITY OF THIS RESOURCE SO THAT PEOPLE REALLY KNOW IT'S THERE AND CAN TAKE ADVANTAGE OF IT. >> YEAH WE INTENT TO WORK VERY CLOSELY WITH NIHS TO MAKE SURE THE WORD IS OUT ABSOLUTELY. ANY OTHER COMMENTS ON THE PHONE? FINAL COMMENTS IN THE ROOM? EVERYBODY VOTE? THANKS DR. MILLER. >> I'LL GIVE OUR REMAINING TWO PEOPLE A MOMENT OR TWO TO COMPLETE THEIR VOTES. ALL RIGHT WE CAN MOVE ON TO OUR LAST INITIATIVE SO OUR LAST NICHE INITIATIVE AND MAKE SURE EVERYBODY HAS THE SECONDARY SIGN ONS THIS INITIATIVE IS ACTUALLY A SECONDARY SIGN ON BUT BECAUSE IT INVOLVES OR COMMITMENT OF FUNDS WE BRING IT TO YOU. NHLBI PARTICIPATION IN METHODS TO APPROVE REPRODUCIBILITY OF IPSC GROWTH AND DIFFERENTIATION USING SMALL BUSINESS INITIATIVE FUNDS THE SBIR FUNDS. AS YOU PROBABLY NOTICED FROM THE WRITE UP THAT WAS PROVIDED IN YOUR MATERIALS IT'S REALLY ABOUT A VARIETY OF ISSUES THAT CAN EFFECT THE DERIVATION OF IPSC AND GROWTH STABILITY AND DIFFERENTIATION INCLUDING THE SPECIFIC CHARACTERISTICS OF THE STARTING CELL OR TISSUE SAMPLE ALONG WITH A VARIETY OF OTHER VARIABLES THAT CAN EITHER DETERMINE WHETHER YOU'RE GOING TO BE SUCCESSFUL OR NOT. SIMILARLY THESE VARIABLES CAN EFFECT REPRODUCIBILITY AND THE ABILITY OF ONE GROUP OF PEOPLE TO DEVELOP SOMETHING THAT OTHER PEOPLE CAN USE IN A RELIABLE REPRODUCIBLE MANNER. THIS INITIATIVE ACTUALLY ADDRESSES AN IMPORTANT NIH RESPONSE TO LEGISLATIVE INTEREST AND EXPLORING WAYS TO DECREASE THE USE OF FETAL TISSUES WHICH IS SOMETHING ELSE THAT I THINK WE NEED TO KEEP IN MIND, IT'S SPONSORED BY NIGMS AND SEEMS LIKE A GOOD OPPORTUNITY FOR US TO BE GOOD CORPORATE CITIZENS AND PARTICIPATE IN THIS IMPORTANT INITIATIVE ACROSS THE NIH AND USES THE STRENGTH OF THE SMALL BUSINESS COMMUNITY, THERE IS A LOT OF CREATIVE PEOPLE OUT THERE IN SMALL BUSINESSES THAT ARE LOOKING INTO WAYS TO LEVERAGE EXISTING BASIC SCIENCE RESEARCH AND OTHER RESEARCH THAT HAS ALREADY BEEN DEVELOPED AND OTHER SECTORS AT THE NIH PORTFOLIO INCLUDING OURS AND IT MIGHT PROVIDE A WAY TO ENHANCE THE POTENTIAL FOR COMMERCIALIZATION WHICH REALLY REQUIRES THE ABILITY TO SUSTAINABLY SCALE PRODUCTION IN A REPRODUCIBLE WAY SO WE THOUGHT THAT THIS WAS A WINNING OPPORTUNITY FOR US TO DO THAT USING SMALL BUSINESS FUNDS AND I WOULD BE HAPPY TO TAKE YOUR QUESTIONS. >> I SEE THIS ON THE LIST IN THE RANGE AND I KNOW I'M AWARE OF A VARIABLE IN THE LITERATURE AND VERY HARD BUT IT'S TREMENDOUS WE ARE MOVING IN THIS DIRECTION. THIS IS DEFINITELY THE FUTURE ANYWHERE BUT I THINK IT'S WISE. >> YEAH WE NEED TO HAVE SOME PEOPLE WHO CAN GO AT IT AND HAVE AN OPPORTUNITY TO EITHER DEMONSTRATE THAT IT'S GOING TO WORK QUICKLY OR PERHAPS REALIZE CERTAIN APPROACHES ARE GOING TO BE DEAD END SO WE CAN FOCUS OR ENERGIES LATER ON THINGS THAT ARE PROBABLY MORE VALUABLE. ANY COMMENTS FROM FOLKS ON THE PHONE? ANYBODY ELSE? PLEASE VOTE. MOST OF THE VOTES ARE IN. I'M WAITING ON TWO PEOPLE. ONE PERSON. AND WE ARE DONE. NO WE ARE NOT. AS I SAID WE HAVE TO GO OVER THE SECONDARY THINGS YOU ARE DONE VOTING BUT NOT LISTENING FOR A FEW MORE SECONDS I KNOW IT'S BETWEEN US AND LUNCH SO YOU DID HAVE A LONG LIST OF SECONDARY SIGN ON INITIATIVES, THESE ARE BEING PROVIDED FOR INFORMATION SINCE WE ARE NOT REQUIRED TO BRING THEM TO YOU FOR APPROVAL HOWEVER I DO HOPE THAT IF YOU HAD ANY QUESTIONS ABOUT ANY OF THESE YOU WOULD WANT TO BRING THEM UP AT THIS TIME. DID ANYBODY HAVE ANY QUESTIONS OR CONCERNS OR COMMENTS ABOUT ANY OF THOSE ADDITIONAL INITIATIVES? I PARTICULARLY WANTED TO CALL YOUR ATTENTION TO THE TRANS NIH INTERNATIONAL EPIDEMIOLOGY DATABASE TO EVALUATE THE AIDS PROGRAM INITIATIVE THAT IS AT THE VERY END OF THE LONG LIST, THIS IS AN IMPORTANT RFA IN WHICH WE WILL BE PARTICIPATING USING OUR AIDS ALLOCATION AND I THINK IT'S GOOD FOR YOU TO KNOW ABOUT IT. ANY OTHER QUESTIONS? FOR THOSE OF YOU ON THE PHONE, IT'S OBVIOUS THAT EVERYBODY WANTS TO GET OUT FOR LUNCH AND I WILL SAY I'M GOING TO BE HAPPY TO JOIN THEM BECAUSE IT SEEMS TO BE COOLER IN HERE THAN IT WAS BEFORE, MAYBE SOMEBODY TURNED DOWN THE AIR CONDITIONING TO SPEED US UP, WE HAVE 20 MINUTES TO JUST GO ACROSS THE CORRIDOR GET SOME LUNCH AND BRING IT BACK HERE AND WOULD LIKE TO RECONVENE FOR SUPER CLOSED SESSION, STAFF YOU DON'T HAVE TO BE BACK FOR LET'S SEE 20 MINUTES FOR LUNCH AND 30, YOU SHOULD PLAN TO BE BACK HERE IN 5-0 MINUTES 50, NOT 15, 50 BECAUSE I DON'T THINK IT WILL TAKE US MORE THAN 30 MINUTES TO HANDLE OUR BOARD OF SCIENTIFIC COUNSELORS REVIEW,