WELCOME TO NHLBI COUNCIL
I THINK THAT'S THE THING YOU HAD
TO SAY.
AS A REMINDER WE ARE BEINGNG
RECORDED AND SOMEONE WILL GET
RID OF THE NOTICE AND I'LL MAKE
A FEW ADMINISTRATIVE UNCEMENTS
STARTED.
I WANT TO WELCOME OUR PUBLIC
VISITORS AS WELL AS STAFF TO
OPEN SESSION.
THE NOTICE OF THE SCHEDULE MEET
WAS PUBLISHED IN THE FEDERAL
REGISTER AS REQUIRED.
AND I WISH SOMEBODY WOULD PLEASE
TURN OFF WHATEVER IS MAKING THE
NOISE THAT IS NOT SUPPOSED TO.
RECORDING, PLEASE REMEMBER THE
OPEN SESSION OF TODAY'S MEETING
IS BEING WEBCAST AND RECORDED.
THE VIDEO WILL BE ARCHIVED AND
AVAILABLE TO THE PUBLIC AND OUR
NIH COLLEAGUES FOR AN INDEFINITE
PERIOD MUCH TIME.
THEN I'M GOING TO GIVE YOU A
BRIEF OVERVIEW OF THIS
AFTERNOON'S AGENDA AND THE
MEETING WILL START WITH A REPORT
FROM THE DIRECTOR, DR. GIBBONS.
WE'LL HAVE A PRESENTATION FROM
DIR'S AND LASTLY REVIEW THE
CONCEPTS DISCUSSED AT THE APRIL
BOARD OF EXTERNAL EXPERTS
MEETING BEFORE WE END THE OPEN
SESSION.
I DON'T THINK WE WANT TO DELAY
ANY MORE.
WE'LL HAVE A REPORT FROM
DR. GIBBONS AND BREAK QUICKLY TO
PICK UP OUR LUNCHES AND HAVE A
WORKING LUNCH.
DR. GIBBONS.
YOU CAN SEE NIH HAS HAD A PRETTY
GOOD RUN OVER THE LAST FIVE TO
SIX YEARS WITH A NUMBER OF
INCREASES AND YOU SEE WHERE WE
LANDED IN FY23 WITH A
SIGNIFICANT INCREASE OF 4.2% ANA
PARTICULAR ELEMENTS PUT INTO
NHLBI'S BASE NOTABLY THE
COVID-19 DISPARITIES OR SEAL
PROGRAM AND THERE WERE A NUMBER
OF TOPICS RAISED.
IT'S A LITTLE DIFFERENT FROM THE
PREVIOUS ONES WHERE THE NIH
DIRECTOR SHARED IT WITH CDC AND
OTHER AGENCIES AND TOP OF THE
TOPICS INCLUDE THE NEXT
GENERATION, HEALTH DISPARITIES,
INCLUSIVE EXCELLENCE IN OUR
WORKFORCE AS WELL AS RURAL
HEALTH AND DIABETES AND DOWN
SYNDROME AND THEY'RE RELEVANT TO
NHLBI PORTFOLIO AND PRIORITIES
AS WELL.
EVERYONE READS THE NEWSPAPERS
AND SO IT WON'T SHOCK YOU SOME
US HAD TREPIDATION ABOUT SOME OF
THE CUTS THAT WERE BEING
CONTEMPLATED THAT WERE GOING TO
AFFECT A NUMBER OF AGENCIES
INCLUDING HHS THAT APPEAR TO
HAVE BEEN AVERTED IN THE
GREATEST SEVERITY BUT THERE'S
QUESTIONS WHERE WE LAND NOW THE
DEBT LIMIT HAS BEEN INCREASED.
WE ANTICIPATED FY24 WOULD BE A
TIGHT YEAR AND THE DEBT CRISIS
RELIEF STILL SUGGESTS IT WILL BE
TIGHT AND THE LAME DUCK YEAR OFF
A PRESIDENT OFTEN IS FAIRLY
TIGHT AS WELL AS WE GET WOUND UP
FOR NEW CONGRESS.
SO THIS WILL BE A LEANER PERIOD
IN THE NEXT YEAR OR TWO THAN THE
FOUR OR FIVE WE ENJOYED
PREVIOUSLY.
OBVIOUSLY THAT PUTS SOME TENSION
ON WHAT WE'RE ABLE TO DO AND
GOES TO THE
INVESTIGATOR-INITIATED PROGRAMS
AND PROJECTS IN SCIENCE AS OUR
BED ROCK INVESTMENT AND THERE'S
TRENDS TOWARDS INCREASED
APPLICATIONS.
SO A NUMBER OF APPLICATIONS HAVE
BEEN GOING UP AND THE COST OF
EACH GRANT IS PROBABLY GOING UP
OVER 30% OVER THE LAST FIVE
YEARS IT'S BECOMING MORE AND
MORE CHALLENGING TO MAINTAIN THE
SUCCESS RATES HOVERING AROUND
20% OR SO.
BUT AGAIN THOSE TWOVERS MORE
APPLICATIONS, MORE EXPENSIVE
GRANTS IT'S INCREASINGLY
DIFFICULT TO HIT THE AWARD
TARGETS THAT WE'D LIKE TO AND
MAINTAIN THE SUCCESS RATE AS
HIGH AS WE CAN.
WE STILL ENDEAVOR TO DO THAT FOR
THE NEXT GENERATION OF EARLY
STAGE INVESTIGATORS IN
PARTICULAR AND THIS YEAR WE HAD
TO HAVE A PAY LINE OF 14
PERCENTILE AND THE BONUS ESIs TO
24th PERCENTILE AND WE ARE USING
THE SELECTIVE PAY MECHANISM WE
ALWAYS HAD FOR MERITORIOUS ERGRE
PROGRAMMATIC BALANCE FOR THOSE
ABOVE THE PAY LINE.
ALSO AS PART OF OUR STEWARDSHIP
I WANT TO RELAY OUR WELCOME AND
TRANSITIONS PARTICULARLY IN
LEADERSHIP IN PARTICULAR A NEWER
DEPUTY, DR. CAROL LEWIS FROM THE
DEPUTY DIRECTOR IN TRANSITIONAL
RESEARCH AND INFORMATION SCIENCE
AND A BELATED WELCOME TO CINDY
COUGHMAN DEPUTY OF OSPEEC OFFICE
OF SCIENCE POLICY, EDUCATION AND
COMMUNICATION.
WE WELCOME THESE TWO NEW
LEADERS.
AND THIS IS A SHOUT OUT DLD WHO
WILL TAKE OVER THE ENTIRE
INSTITUTE NOW THAT THEY HAVE THE
FRONT LINE COUNCIL MEMBERS AND
HIS ARRIVAL AS WE APPRECIATE GUS
JOINING US AS WELL AS I WANTED
TO INTRODUCE TO COUNCIL AND THE
EXTRAMURAL COMMUNITY A MOVE
WE'RE MAKING THAT IS PART OF OUR
CLINICAL TRIAL AND CLINICAL
STUDIES STEWARDSHIP AND
PARTICULARLY ENSURING WE'RE
ALWAYS LEADING INVESTIGATORS TO
JOIN US IN THE INSTITUTE TO HELP
US WITH THAT STEWARDSHIP AND
MANAGEMENT AND TYPICALLY
INVESTIGATORS THAT HAD BEEN AT
THE FRONT LINES AND BRING THAT
PERSPECTIVE IN AND WE CREATED
THIS POSITION AND OF CHIEF
MEDICAL RESEARCH OFFICER AND
THAT'S NOW A COMMON ELEMENT
ACROSS MOST OF OUR CENTERS AND
DIVISIONS AND THE MOST RECENT
ADDITION ON THE DOD SIDE AND
ALSO A HINT OF AND DR. KILEY
WILL EXPAND ON SUBSEQUENTLY
WHERE WE'RE ALWAYS AS PART OF
THE STRATEGIC VISIONING REFRESH
AND EVERGREENING LOOKING TO
ADAPT WHERE THE SCIENCE IS GOING
AND WHERE WE NEED TO ADAPT
ORGANIZATIONALLY TO MAKE SURE
WE'RE STILL AT THE LEADING EDGE
OF IT.
IF NOT, AHEAD OF IT AND
APPRECIATE THE LONG DIVISION
TAKING THE STEP BACK.
IT HAD BEEN A STRUCTURE AT A
DECADE OR TWO AND FRANKLY THE
DIVISION ITSELF HAS PROBABLY
INCREASED MAYBE 40% AND
PARTICULAR NUMBERS BUT IT'S A
HARD WORKING GROUP AND THERE'S A
LOT OF NEW SCIENCE THAT'S COME
IN AND WANTED TO BE ALIGNED WIT
THE SCIENTIFIC OPPORTUNITIES
GOING FORWARD EGO WE HAVE
ATRUCTURE THAT WASNG TO
MEET THE SCIENTIFIC
OPPORTUNITIES WITH AFFECTIVE
LEADERSHIP A BETTER BALANCE OF
WORK LOAD AND BETTER BALANCE OF
SUCCESSION PLANNING, OPERATIONS
AND DEVELOPMENT OF NEW
LEADERSHIP.
THIS WILL RESULT IN THE
EXPANSION FROM THOSE TWO
BRANCHES TO FOUR AND EOB ALSO IS
THE HOME OF THE NATIONAL CENTER
FOR SLEEP DISORDER RESEARCH
PROGRAM AS WELL.
SO JUST WANTED TO GIVE THE
EXTRAMURAL COMMUNITY A HEADS UP
OF THE TRANSITIONS AND AGAIN
DR. KILEY WILL EXPLAIN THAT IN
GREATER DETAIL SUBSEQUENTLY.
AND WE TURN TO THE INTRAMURAL
PROGRAM AS PART OF TRANSPARENCY
TO ENSURE COUNCIL IS AWARE OF
PERFORMANCE REVIEWS OF THOSE
RESEARCH PROGRAMS PERFORMED BY
OUR BOARD OF SCIENTIFIC
COUNSELORS THAT GOES THROUGH AND
REVIEWS OF ALL OF OUR
INVESTIGAT
INVESTIGATORS AND THERE'S T
EXCEPTIONAL RESEARCH THAT
COMPLEMENTS AND EXTENDS OUR
RESEARCH PORTFOLIO.
THIS IS A SNAPSHOT OF THE NEXT
GENERATION OF NHLBI DIVISION OF
INTRAMURAL RESEARCH WITH A FOCUS
ON THE TENURE-TRAND I
WON'T BELABOR IT BUT YOU CAN SEE
FROM THE PHOTOS THE FACE OF THE
DIR IS CHANGING AND DIVERSE IN
MANY WAYS ACROSS THE INSTITUTE
AND DELIGHTED WE'LL BE ABLE TO
HIGHLIGHT ONE PARTICULAR PROGRAM
DR. AGBOR-ENOH WILL BE
PRESENTING LATER AND WANTED TO
GIVE HIM A PARTICULAR SHOUT OUT.
LET ME CLOSE WITH THE OTHER KEY
FEATURE OF OUR UPDATE TODAY AND
IT'S AN EXPRESSION OF APPRECIATE
TO ALL OF YOU TO BE PART OF THE
NHLBI 75th ANNIVERSARY AS AN
OPPORTUNITY TO DO A STRATEGIC
REFRESH OF OUR STRATEGIC VISION
DOCUMENT TO KEEP IT EVER GREEN I
BELIEVE BACK IN 2016 WHEN THAT
WAS RELEASED.
SO WE'RE DUE FOR THAT REFRESH
AND WE LOOK FORWARD TO A SESSION
WITH OUR ADVISORY COUNCIL AND
BOARD OF EXPERTS TO DO THAT
ACTIVITY THIS FALL BEFORE WE
HOPE TO REFLECT SOME OF THE
PROGRESS THAT HAS BEEN MADE AS
WE IMPLEMENTED THE STRATEGIC
VISION OF 2016 BUT ALSO TO PIVOT
AND LOOK FORWARD TO EMERGING
OPPORTUNITIES ORRT EXTENSIONS O
NEW DIRECTIONS WE MAY TAKE AS A
RESULT OF THAT AND INVOLVES
RECONVENING THE STAKEHOLDERS AND
ADVISORS SUCH AS ALL IN HELPINGT
PATH FORWARD IN WAYS THAT WILL
ENHANCE AND ADVANCE OUR SCIENCE
OF HLBS PORTFOLIO.
DON'T NEED TOEMIND OF YOU ALL
MUCH THE FOUR MAJOR GOALS OF
UNDERSTANDING HUMAN BIOLOGY,
REDUCING HUMAN DISEASE AND IT'S
ELEMENT OF TRANSLATION AS WELL
AS WORKFORCE WITH THE VARIOUS
OBJECTIVES THAT HAVE BEEN OUT I
WON'T BELABOR HERE BUT WE SEE
THE STRATEGIC REFRESH FOR THE
MOST PART PROBABLY CAN LEAF THE
BASIC GOALS THE OVER ARCHING
GOALS AND MANY STRATEGIC
OBJECTIVES I SUSPECT ARE ALREADY
SORTING OUT AND ESTABLISHING THE
REAL STRATEGIC INITIATIVES AND
CHALLENGES WE NEED TO TAKE ON IN
THE NEXT 5 TO 10 YEARS THAT WILL
OUR EVER
GREENING PROCESS THIS FAGR
TOWARD THAT END, I THINK ONE OF
THE ILLUSTRATIVE PRIORITIES WE
HAVE HAD UNTIL WE HAVE AN
EVIDENCE-BASED ELIMINATION OF
HEALTH DISPARITIES AND ADDRESS
HEALTH EQUITY THIS WILL BE AN
IMPORTANT PART OF OUR STRATEGIC
VISIONING AND IMPLEMENTATION THE
DIVISIONS AND CENTERS AND STAFF
HAVE ALREADY BEEN ENGAGED IN.
CLEARLY WE RECOGNIZE THE
PROBLEMS PERSIST AND RECOGNIZING
IN MANY WAYS THESE COMPLEX
PROBLEMS REPRESENT GOOD
OPPORTUNITIES PARTICULARLY TO
THE EXTENT THAT THEY'RE VEXING
AND PERSISTENT BECAUSE OF THE
COMPLEXITY AND ALSO PROBABLY
NECESSITATES SOME NOVEL
APPROACHES PERHAPS THE MAN IN
THE BOX APPROACHES AND CERTAINLY
MULTI-LEVEL, MULTI-DIMENSIONAL
ADDRESS THE DRIVERS OF THE
DISPARITY AND RELEVANT TO OUR
PORTFOLIO OF THE KEY ONES AND
THIS ILLUSTRATES THE GEOGRAPHIC
DISPARITIES UNDER PINNING THIS
WHETHER IT'S HYPERTENSION OR
COPD OR OBESITY AND A PUT IN
DIABETES AND I DON'T THIS
NOT LOST ON ANYONE THERE'S
CERTAIN GEOGRAPHICAL AREAS AND
COMMUNITIES AS YOU LIST VARIOUS
CONDITIONS IN WHICH THERE'S
HEALTH DISPARITIES THOSE
COMMUNITIES SEEM TO BE
DISPROPORTIONATELY OVER
REPRESENTED AND OVER BURDENED.
AND YET AS I THINK ALL OF YOU
KNOW IN COUNCIL, MANY OF THE --
MANY OF THE NIH INVESTMENTS GOES
TO THE COASTS AND NOT
PARTICULARLY OFTEN TO THE SAME
AREAS THAT HAD THE GREATEST
DISPARITIES AND MOST VULNERABLE
WITH THE MOST CHALLENGING HEALTH
STATUS.
I THINK THAT'S SOMETHING AS WE
DO A STRATEGIC REFRESH AND WE
THINK ABOUT OUR INVESTMENT
PORTFOLIO THAT WE THINK ABOUT
ADDRESSING SINCE THAT'S WHERE
OUR MISSION CHALLENGES ARE.
TOWARD THAT END THE STRATEGIC
REFRESH GIVES US AN OPPORTUNITY
TO REFLECT ON SOME OF THE
INVESTMENTS AND HOW WE CAN
INCORPORATE DIFFERENTRP MODELS D
PARADIGMS.
THIS ONE INDICATING THE SOCIAL
ECOLOGICAL FRAME OF PERSPECTIVE
ON THIS ANDG IN A I-DIMENSIONAL
MULTI-LEVEL WAY RECOGNIZING
GENETICS AND BEHTIF THE
INDIVIDUAL AND THE FAMILY AND
COMMUNITY ENVIRONMENT.
WE NOW HAVE THE TOOLS AND
CAPABILITIES TO DO THESE AT
DEPTH AS WELL AS SCALE.
THE PROGRA HELP US BRAIN
STORM WILL ENABLE TO DO THAT
MORE EFFECTIVELY.
AND PARTICULARLY RELATED TO THE
GEOGRAPHIC DISTRIBUTION OF SOME
OF THOSE HIGH-RISK COMMUNITIES,
WE THINK IT'S IMPORTANT TO
DEVELOP PROGRAMS THAT REFLECT
AND TARGET THOSE MOST AT-RISK
COMMUNITIES BECAUSE IF WE'RE
GOING TO UNDERSTAND THE DRIVERS
AND GOING TO INTERVENE TO MAKE A
DIFFERENCE, THIS IS WHERE I
BELIEVE WE DO NDO EMPHASIZE.
SO, WE'RE EXCITED THE EFFORT OF
THE SEAL PROGRAM THOSE DESIGN TO
ADDRESS COVID-19 DISPARITIES IS
MAKING A STRATEGIC PIVOT AS A
PLATFORM TO ENHANCE
COMMUNITY-ENGAGED RESEARCH
RELEVANT TO HEALTH EQUITY AND G
ACROSS MULTIPLE DISORDERS ANDDE
DISEASES AND BECOMING A
TRANS-NIH PLATFORM TO ADDRESS
HEALTH EQUITY FROM A
COMMUNITY-ENGAGED RESEARCH
PARADIGM.
SIMILARLY, THE SAME
COMMUNITY-ENGAGED RESEARCH
PLATFORM IS AMENABLE TO
TARGETING AND PARTNERING WITH
SPECIFIC POPULATIONS AND
CERTAINLY THOSE POPULATIONS
AFFECTED BY RACE, ETHNIC
DISPARITIES HAVE BEEN A KEY
TARGET.
IN PARTICULAR SEALS HAD A
SPECIFIC OUTREACH ARE RELATED TO
INDIGENOUS POPULATION, NATIVE
AMERICANS BOTH IN ALASKA,
HAWAI'I, PACIFIC ISLANDERS AS
S OTHER TRIBAL NATIONS.
SO, THE INSTITUTE'S BEING VERY
INTENTIONAL ABOUT THOSE
COLLABORATIVE PARTNERSHIPS WHERE
WE KNOW THAT IT'S CRITICAL TO
HAVE TRUSTWORTHY RELATIONSHIPS
THAT ARE SUSTAINABLE AND AGAIN
COLLABORATION WITH COMMUNITY.
HAVING PLATFORMS THAT HAVE THAT
SENSIBILITY AND PERSPECTIVE IS
KEY.
SO WE LOOK FORWARD TO CONTINUE
TO BUILD OUT THE SEAL PLATFORM.
SIMILARLY RELATED TO THOSE
GEOGRAPHIC DISPARITIES WE'RE
EXCITED ABOUT THE ONGOING ROLL
OUT OF RURAL AND LOOKING AT SOME
OF THE KEY REGIONS THAT ARE
EXPERIENCINGY DECLINES
IN CARDIOVASCULAR HEALTH
RELATIVELY SPEAKING.
CERTAINLY NOT THE EVER FALLING
RATES WE'RE SEEING IN OTHER
PARTS OF THE COUNTRY.
SO HERE'S A GREAT OPPORTUNITY
AGAIN TO DRILL DOWN AND MAKE A
DIFFERENCE IN RURAL AMERICA.
AND THEN FINALLY RELATED TO THE
COHORT STUDIES SOMETHING I
BELIEVE THAT'S ACTUALLY ON THE
TABLE FOR COUNCIL C THIS CYCLE
RELATE TO ENSURING OUR
COMMUNITY-BASED COHORTS ARE
REFLECTIVE AND BUILDING OUT OUR
CAPABILITY RELATED TO
ASIAN-AMERICAN POPULATIONS
INCLUDING NATIVE HAWAIIANS ANDI
PACIFIC ISLANDERS.
THIS IS IS A COMPLEMENTARY
COMPONENT THAT BRINGS IN THE
DIVERSITY OF THE ASIAN
POPULATION.
THESE ARE AIC A APPROACHES
WE'RE TAKING TO ADDRESS WHAT'S
BEEN A CHALLENGE IN CL AND
ETHNIC DISPARITIES AND DOING
THAT IN A VERY STRATEGIC WAY.
TOWARD THAT END ONE EXAMPLE THAT
RELATED TO INEQUITIES IN
MATERNAL HEALTH IN PARTICULAR
THE CHALLENGES OF MATERNAL CARE
DESERTS IN THE SAME HIGH-RISK
COMMUNITIES WE'RE ENCOURAGED BY
PROGRESS PROGRAMMATICALLY IN
PURSUIT OF THE VISION IN THIS
SPACE.
IT'S AN AREA THAT CLEARLY IS
RELEVANT TO OUR PORTFOLIO GIVEN
THE COMPLICATIONS OF HEART, LUNG
AND BLOOD DISORDERS THAT ARE
PART OF MATERNAL MORBIDITY AND
MORTALITY AND DEVELOPING THOSE
PROGRAMMATIC ATCAPA.
INCLUSIVE THE
E DCS EFFORT WITH
THE ENRICH PROGRAM OF EARLY RVE
CARDIOVASCULAR HEALTH INHERS
AND CHILDREN.
TREATING THAT AS A DIAD WITH
INTERVENTIONS.
YOU CAN SEE WHERE THE ENTITIES
ARE LOCATED AGAIN STRIVING TO GO
TO WHERE THE VEXING CHALLENGES
ARE AND THAT'S ALSO COMPLEMENTED
BY ANOTHER PD THAT TAKES
MORE OF A COMMUNITY-ENGAGED
IMPLEMENTATION SCIENCE LENS AND
THAT'S THE MATERNAL HEALTH
COMMUNITY IMPLEMENTATION PROGRAM
AND MOST RECENTLY NOT SHOWN HERE
BUT THAT'S BEEN EXTENDED TO BE
PART OF A TRANS-NIH PROGRAM IN
MATERNAL HEALTH CALLED IMPROVE
IN WHICH THE SAME PROGRAMMATIC
TEAMS ARE LEANING IN TO ADVANCE
THE NHLBI PERSPECTIVE BUT IN A
TRANS-NIH WAY IN THE IMPROVE
PROGRAM AND WE'RE DELIGHTED
AGAIN IT'S AITOMPLEMENTARY PIECE
HELPING TO DRIVE
COMMUNITY-ENGAGED RESEARCH AND
IMPLEMENTATION SCIENCE IN THIS
SPACE RELATIVE TO HEART, LUNG,
BLOOD AND SLEEP RESEARCH.
THESE ARE THE PLATFORMS WITH
MATERNAL HEALTH AS THE EXEMPLAR
CASES.
THIS GIVES AN OPPORTUNITY REALLY
TO ADDRESS THE SOCIAL
DETERMINATES THE MULTI-LEVEL
CHALLENGES IN WAYS WE HOPE WILL
MOVE THE NEEDLE AND MAKE A
DIFFERENCE.
CLEARLY, YOU ALL ARE WELL AWARE
OF THOSE DISPARITIES AS I
MENTIONED BEFORE IN MATERNAL
HEALTH AND IN MANY WAYS WE'VE
OFTEN TALKED ABOUTN PREGNANCY
BEING A STRESS TEST IN WHICH THE
MORBIDITIES OF GESTATIONAL
DIABETES, PREECLAMPSIA AND
CARDIO MYOPATHY MAY BECOME
MANIFEST TO THE DEGREE D WHICH
A BIRTH HAVING
LATER IN LIFE AND HAVE
COMORBIDITIES SUCH AS DIABETES
AND HYPERTENSION AND I THINK
THIS REFLECTS BOTH A CHALLENGE
IN HEALTH DISPARITIES AND ALSO
AN OPPORTUNITY BECAUSE IT REALLY
HAS THE MULTI-DIMENSIONAL
COMPONENTS TO IT WE CAN ADDRESS.
SO ONE OF THE QUESTIONS BECOMES
HOW ARE WE GOING TO BECOME MORE
EFFECTIVE AT PREDICTING,
PREEMPTING AND PREVENTING HEART,
LUNG, BLOOD AND SLEEP DISORDERS
AND ONE OF THOSE OPPORTUNITIES
THAT SHOULD BE PART OF THE
STRATEGIC VISION REFRESH OVER
THE NEXT FIVE TO 10 YEARS IS TO
LEVERAGE THE TOOLS AND ANALYTICS
AND CAPACITY TO UNDERSTAND
THINGS BOTH AT A BASIC LEVEL,
FUNDAMENTAL LEVEL AND
SINGLE-CELL RESOLUTION OF ALMOST
EVERY MOLECULE AND CELL AND
ORGAN WITH TIME IN AN
INTEGRATIVE WAY THAT I THINK
WE'LL BE ABLE TO BE MORE
MANIFEST IN THE NEXT FIVE YEARS
AND HAVE THAT BASIC
UNDERSTANDING ALSO TRANSLATE
INTO OUR BETTER UNDERSTANDING OF
PERTURBATIONS THAT OCCUR IN
DISEASE AND THEN ADD THESE OTHER
LAYERS OF THE ENVIRONMENTAL
EXPOSURES MO THAT AS
NGTHE GENETIC BACKGROUND.
ALL THOSE TOOLS INCREASINGLY IN
OUR GRASP AND CREATING THE
RESOURCES SUCH THAT HLBS
SCIENTISTS CAN LEVERAGE ALL THE
DIFFERENT TOOLS, TECHNOLOGIES
AND DATA SOURCES IN A ROBUST,
INTEGRATIVE WAY.
HOPEFULLY LEVERAGING THE TOOLS
IN SCIENCE, MACHINE LEARNING AND
ARTIFICIAL INTELLIGENCE TAKING
AND HOPE THE CATALYST WILL
HELP LEVERAGE ALL THE
TIES ACROSS THE
PORTFOLIO, MATERNAL HEALTH ONLY
BEING ONE EXAMPLE.
WHERE PERHAPS THIS IS BE AN
OPPORTUNITYRT US DO GREATER
TECHNO DEVELOPMENT
PARTICULARLY IN THINKING ABOUT
THE AREAS MOST AT RISK, THOSE
COMMUNITIES WHERE IN ESSENCE
THEY'RE IN MATERNAL CARE
DESERTS.
IS THERE AN OPPORTUNITY TO
LEVERAGE TECHNOLOGY IN THE
ANALYTIC TOOLS IN WAYS WE START
TO ERODE THE BARRIERS OF ACCESS
TO HIGH-QUALITY MATERNAL HEALTH
TO ALL COMMUNITIES AND SO THIS
BLEND OF HIGH-TECH AS WELL AS
HIGH-TOUCH THAT MAYT WITH
COMMUNITY HEALTH WORKERS A
DOULAS MAY BE A CONVERGENT
OPPORTUNITY OUR
COMMUNITY-ENGAGED RESEARCH AND
IMPLEMENTATION SCIENCE CAN MAKE
POSSIBLE FOR THE HIGH-RISK
COMMUNITIES AND WOMEN AT RISK.
INDEED WE'RE LEVERAGING IN THE
IMPROVE PROGRAM ONE OF THE
FAVORABLE OUTCOMES OF THE
PANDEMIC TO PLUG INTO THE
ENGINEERING COMMUNITY OF NIBIB
AND THE RAD X THAT LED TO RAPID
DIAGNOSTICS AND TESTING IN THE
PANDEMIC.
TO USE SOME OF THE SAME
INNOVATION FUNNELS AND PLATFORMS
TO TARGET NOW TO LUNG,
BLOOD, SLEEP SCIENCE AS WELL.
WE'RE LOOKINGE FORWARD TO LOOKG
TO GETTING OUTSIDE THE BOX A
BIT.
PERHAPS EVEN LEVERAGING WHAT YOU
HEARD -- WHAT YOU'LLOU HEAR ABO
IN TERMS OF THE CATALYZE PROGRAM
IN DEVELOPING INNOVATIVE
TECHNOLOGY TO ADDRESS SOME OF
THESE CHALLENGES.
I GUESS I HAVE A WHAT-IF IN
APPLYING THE TECHNOLOGIES.
THINKING ABOUT POSTPARTUM
DEPRESSION OR PREECLAMPSIA THAT
OCCURS AFTER DISCHARGE OR CARDIO
MYOPATHY THAT BECOMES MANIFEST
POST CHARGE IN THE MATERNAL CARE
DESERTS.
WHAT IF WE STARTED TO LEVERAGE
THE CAPABILITIES OF TECHNOLOGIES
AND MONITORING THE 24/7/365
COUPLES TO MACHINE LEARNING,
A.I. ALGORITHM CAN DO ALERTS AND
MAYBE DO DIAGNOSTIC ASSESSMENT
THIS IS THIS BE PART OF
STRATEGIC VISION REFRESH.
THIS IS FROM A PAPER FROM THE
V.A. IN WHICH IT WASN'TAS TO
SCALE BUT WAS INTERESTING IN
REGARD TO ENGAGING WITH A COHORT
OF V.A. PATIENTS THAT HAVE BEEND
WITH CERTAIN SENSOR CAPABILITIES
TO TEST WHAT THE DISCHARGE
BASELINE WAS IN HOPES OF
FIGURING OUT WHETHER THEY CAN
PREDICT WHO WOULD BE
RE-HOSPITALIZED BASED ON THE O
CONTINUOUS MONITORING OF HEARTO
RATE AND OTHER BLOOD SAMPLING
CAPABILITIES OF THE
WEARABLE SENSORS.
INDEED THERE WAS EVIDENCE
LOOKING AT THAT SOME OF THE DATA
IN WHICH THEY COULD TRAIN THEM
ON BASELINE AND FOLLOW THAT
PREDICTIVE MODEL TO SEE IF
THERE'S DEVIATIONS FROM THAT
OPTIMIZED POST-HOSPITAL BASELINE
AND WHETHER THEY WERE SLIPPING
INTO HEART FAILURE AGAIN AND THE
ALGORITHM IN THIS PARTICULAR
CASE BUT REALLY PROBABLY
INDICATIVE OF THE FORMATIVE
NATURE OF THE FIELD AND ONE WITH
A LOT OF PROMISE IN WHICH WE ARE
STARTING TO SEE THE CONVERGENCE
OF THE TECHNOLOGIES IN
COMPUTATIONAL MEDICINE IF YOU
WILL.
AND TOWARD THAT END TO GET WHAT
IF AND THIS I STARTING TO
FORESHADOW A LITTLE BIT OF HOW
WE MAY CHALLENGE YOU ALL WHEN
YOU COME IN THE FALL AND HELP US
BRING STORM THE OPPORTUNITIES
LOOKING AHEAD OF THE NOTION OF A
DIGITAL TRIN AND HANGING OUT
WITH OTHER DISCIPLINES AND THE
ENGINEERING.
THEY LOOK AT US DOCTORS AND SAY,
YOU KNOW,E WE ARE DE
BASICALLYSI EMPIRICAL MEDICINE D
MORE UNTIL THEY BECOMEY
PRE-RENAL AND STOP PEEING AND
THEN DRY AND THEN SENDING THEM
OUT AND MAKING THESE EMPIRICAL
KINDS OF GUESSES AND
UNFORTUNATELYING HALF OF
THEM DIE WITH HEART FAILURE AND
OVER FIVE YEARS.
WE SHOULD START TO GET BETTER AT
BEING ABLE TO PREDICT SOME OF
THOSE OUTCOMES AND HOPEFULLY
PREEMPT THEM AND PREVENT THEM.
THAT'S WHAT ENGINEERS DO THEY
DON'T SEND UP AIRPLANES AND SEE
IF THAT WORKS AND WAIT TO SEE
HOW MANY CRASH.
THEY'VE ALREADY SIMULATED WHAT'S
NECESSARY TO GET THE RIGHT
FLIGHT AND CAPABILITIES.
MOREOVER, TO THEN HAVE A SENSE
OF HOW IT'S FUNCTIONING, FLIGHT
AFTER FLIGHT AFTER FLIGHT AS TO
WHETHER THAT PANEL NEEDS TO BE
CHANGED OR THAT ENGINE NEEDS TO
BE ADJUSTED BY ALWAYS LOOKING
BACK AT THAT SIMULATED MODEL AND
SEEING DEVIATIONS AND MAKING THE
RIGHT ADJUSTMENTS IN THE ACTUAL
PHYSICAL WITH THE ENVIRONMENT.
AS YOU PLAY THAT OUT IN YOUR
AHEAD AS A THOUGHT EXPERIMENT,
AS WE GET BETTER AND BETTER WITH
EVERY O MOLECULE IN IT
UNDER NORMAL PHYSIOLOGY AND
PERTURBATION AND WHAT'S TO STOP
US FROM HAVING DIGITAL TWINS FOR
PREGNANCY?
WHAT'S TO STOP US FROM HAVING
DIGITAL TWINS FOR ASTHMA OR COPD
OR HEART FAILURE?
I WOULD HOPE THAT'S AVERAGING
THE DATA SCIENCE AND ANALYTICS
AT HAND NOW AS WE TALK LARGE
LANGUAGE MODELS AND ALL SORTS OF
THINGS WE SHOULD BE ABLE TO BE
TERMS OF OUR AGENDA.
TO CONCLUDE, ONE OF THE KEY
THINGS WE BELIEVE WOULD BE PART
OF THE STRATEGIC VISION REFRESH
AND VISIONSI FOR THE NEXT 5 TO
YEARS IS TO START TO LEVERAGE
THE TECHNOLOGIES AND CAPABLES
WITH THE TOP MED AND OTHER
REGISTRIES OR COMMUNITY-BASED
COHORTS OR COMMUNITY-ENGAGED
RESEARCH PLATFORMS IN
IMPLEMENTATION SCIENCE INTA
THAT APPRECIATES THE
MULTI-DIMENSIONAL NATURE OF
HEALTH AND DISEASE AND ALSO HOW
OUR RESEARCH AGENDA CAN BE
ADVANCED BY INTEGRATING THESE
VARIOUS INPUTS IN WAYS THAT
LEVERAGES THE COMPUTATIONAL
POWER AND ANALYTICAL TOOLS OF
MACHINE LEARNING AND A.I. IN
WAYS THAT WE PROBABLY COULDN'T
HAVE PREDICTED 5 TO 10 YEARS AGO
AND EXCITED WHAT WE HOPE YOU'LL
COME UP WITH THIS FALL AND WE'LL
START BRAIN STORMING HOW DO WE
LEVERAGE THESE CAPABILITIES TO
FULFILL OUR MISSION MORE
EFFECTIVELY PREEMPT HEART, LUNG
AND BLOOD SLEEP DISORDERS.
AND THAT'S WHAT WE'LL PUT BEFORE
YOU AND GET YOUR CREATIVE ENERGY
AND BRAIN POWER HELPING US THINK
ABOUT THE NEXT FIVE YEARS AND
HOW WE CANSH THE STRATEGIC
VISION IN A WAY THAT WILL BE
TRANSFORMATIVE TO OUR SCIENTIFIC
COMMUNITY AND OUR PATIENTS.
WE LOOK FORWARD TO THE FALL AND
THAT BRAIN STORMING SESSION AND
I'LL STOP THERE.
>>THANK YOU, DR. GIBBONS.
DOES ANYONE HAVE COMMENTS OR
QUESTIONS FOR DR. GIBBONS?
I GUESS NO ONE HAS QUESTIONS BE
ENLIGHTENING.
>>OR ASLEEP.
>>NEP ONE WOULD BE ASLEEP.
WE'LL TAKE ANOTHER QUICK BREAK
TO GET LUNCH.
IF YOU ORDERED LUNCH, IT'S JUST
AROUND THE CORNER.
IF YOU DIDN'T ORDER LUNCH THEN I
GUESS YOU'RE WAITING BECAUSE
THERE ISN'T ANY PLACE FOR YOU TO
GO AND GET IT IN THIS BUILDING
SO, UM, WE'LL BE BACK IN FIVE
MINUTES.
SO THE NEXT THING ON OUR AGENDA
THIS MORNING OR AFTERNOON NOW IS
WE'RE GOING TO BE HEARING FROM
THE NHLBI DIVISION OF LUNG
DISEASES ABOUT A PROPOSED
REORGANIZATION AND THAT WILL BE
PRESENTED BY THE DIVISION
DIRECTOR, DR. JIM KILEY.
>>THANK YOU, GOOD AFTERNOON
ALL.
GARY SET THIS UP A BIT AND I'LL
TRY TO BE BRIEF AND COVER THE
KEY POINTS OF WHAT I THINK ARE
IMPORTANT FOR US TO UNDERSTAND
AND SERVES AS THE FIRST OF A
COUPLE PUBLIC HEARINGS WE'RE
HAVING RELATED TO THIS
REORGANIZATION BECAUSE IT'S PART
OF THE WHOLE PROCESS WITHIN THE
GOVERNMENT TO DO CHANGES IN THE
STRUCTURE THERE'S A LOT OF
STEPS.
I'LL SPARE YOU ALL THE STEPS AND
TRY TO CUT TO THE CHASE OF WHAT
WE'RE TRYING TO DO HERE.
IT'S REALLY BUILT OFF TWO
THINGS, ENVISIONING THE FUTURE
INSTRUCTION FOR THE FUTURE OF
LUNG DISEASES AND CAPTURE
GROWTH.
IT'S AN AREA THAT'S SEEN
SUBSTANTIAL GROWTH AND WANT TO
ALIGN OURSELVES INTERNALLY WITH
THE EXTERNAL GROWTH THAT'S
OCCURRING IN THE COMMUNITY.
SO I'M GOING TO TELL YOU A BIT
ABOUT WHERE WE'VE BEEN, WHERE WE
ARE AND HOW TO GO FORWARD FROM
HERE AND HOPEFULLY WE'LL GET A
SENSE AND GET FEEDBACK FROM YOU.
SO THIS IS THE CURRENT STRUCTURE
THAT YOU SEE ON THE LEFT-HAND
SIDE OF THE SLIDE WHICH IS
REALLY THE WAY IN WHICH THE
DIVISION HAS BEEN STRUCTURED
OVER ABOUT THE PAST 20 YEARS.
IT'S REALLY QUITE SIMPLE WITH
THE OFFICE OF THE DIRECTOR PRO
BRANCHES A LUNG BRANCH AND
AIRWAY BRANCH THAT'S CAPTURED
THE TOTAL OF SLEEP, PULMONARY
AND CRITICAL CARE MEDICINE.
THAT REALLY COVERS THE ENTIRETY
OF THE FIELD FROM DNA MOLECULES
UP THROUGH IMPLEMENTATION.
NOW, ONE OF THE THINGS I PUT OUT
THE SIDE HERE RIGHT AWAY IS THAT
WE ARE NOT REALLY DOING ANYTHING
AT THE PRESENT TIME TO MAKE ANY
CHANGES TO THE NATIONAL CENTER
ON SLEEP DISORDERS RESEARCH.
YOU SEE THAT IN THE CURRENT
ORGANIZATIONAL STRUCTURE BECAUSE
AT THE PRESENT TIME IS WHERE THE
NCSDR LANDS.
WHY IS THAT THE CASE?
FIRST, WE DID RESTRUCTURING OVER
THE PAST TWO OR THREE YEARS.
WE HAVE POINTED A NEW DIRECTOR,
DR. BROWN HAS BEEN IN THE
POSITION A COME YEARS NOW.
WE ALSO DOUBLED THE SIZE OF THE
SUPPORT STAFF AND PROGRAM HAS
GROWN IN A WAY THAT HAS ALLOWED
IT TO EXPAND INTO THE AREAS THAT
ARE REQUIRED THROUGH ITS
LEGISLATIVE MANDATE.
SO WE DON'T BELIEVE AT THE
PRESENT TIME WE NEED TO MAKE
MUCH IN TERMS OF CHANGES TO THE
OVER ALL CENTER.
WE THINK IT IS OPTIMALLY
FULFILLING THE CONGRESSIONAL
MANDATE AND AS THE FULL SUPPORT
OF NHLBI LEADERSHIP TO DO SO AND
IS IN GOOD SHAPE.
YOU CAN SEE WHERE THE FOCUS
NEEDS TO BE NOW IS ON PULMONARY
AND CRITICAL CARE RESEARCH.
WE NEED TO MAKE THESE A LITTLE
BIT MORE GRANULAR IN TERMS OF
WHERE THESE AREAS ARE -- WHAT IS
ENCOMPASSED WITHIN THE AREAS.
AND THERE'S SIGNIFICANT GROWTH
IN THESE TWO BRANCHES AND THE
GROWTH HAS BEEN IN TERMS OF THE
NUMBER AND THE VALUE OF GRANT
AWARDS AND CONTRACTS AS WELL AS
THE SIZE OF THE DIVISION.
THE INSTITUTE'S BEEN VERY
GENEROUS IN TERMS OF STAFFING
THE DIVISION.
WE'VE HAD ALMOST A 50% BROTHER
OVER THE PAST FOUR OR FIVE YEARS
PARALLEL A SUBSTANTIAL INCREASE
AND THESE ARE AREAS WITHIN LUNG,
PULMONARY AND CRITICAL CARE
MEDICINE EMERGING AND THERE ARE
SOME CHALLENGES IN TERMS OF
BEING ABLE TO COVER THE BREADTH
OF THE FIELD RIGHT NOW.
SO THERE'S A LOT OF -- I SAID
THIS ALREADY INCREASING VOLUME
OF RESEARCH.
THERE'S LIMITED REPRESENTATION
IT FALLS INTO A BIG BUCKET.
AND FINALLY THERE'S LIMITED
POTENTIAL FOR PROMOTION,
RETENTION AND OPPORTUNITIES THAT
REALLY ALLOW STAFF TO GROW AND
DEVELOP WITHIN THE BRANCH AND
THE INSTITUTE.
AS YOU'VE SEEN WE'VE BEGIN IN
THE PAST YEAR BUILDING OUT THE
WHOLE NEW STRUCTURE.
WE HAVE A WHOLE NEW LEADERSHIP
TEAM AND EXCITED TO HAVE GUS AND
SAMIDA JOIN US AS PART OF THE
LEADERSHIP TEAM AND APPOINTED A
BRANCH CHIEF AND DR. CRAIG IN
THE LUNG BRANCH AND A MENTIONED
DR. BROWN RECENTLY APPOINTED
ADDS THE HEAD OF THE DIRECTOR OF
THE SLEEP CENTER.
YOU CAN SEE THE OVER ALL
LEADERSHIP OF THE DIVISION IS
ALSO CHANGING.
SO LET ME JUST SHOW YOU WHAT THE
PROPOSED DLD BRANCH EXPANSION
LOOKS LIKE AND MAYBE TO QUELL
ANYBODY'S FEARS WE'RE NOT TAKING
OVER THE INSTITUTE.
THIS IS A MODEST, I THINK,
EXPANSION BUT IT IS AN EXPANSION
AND WE'RE GOING FROM TWO
BRANCHES TO FOUR BRANCHES AND WE
BELIEVE THIS ALIGNMENT IS REALLY
DRIVEN BY THE SCIENCE.
IT'S REALLY DESIGN TO HAVE THE
MOST COHESIVE SCIENTIFIC
ALIGNMENT.
THE NEW STRUCTURE, AS YOU CAN
SEE HERE, WILL ALIGN WITH THESE
FIVE UNITS WITHIN THE DIVISION
AND THE BENEFITS OF THIS IT WILL
INCREASE SCIENTIFIC FOCUS ON THE
PROGRAM AREAS WITHIN THE BRANCH.
IT GIVES MORE REPRESENTATION OF
THE RESEARCH PROGRAMS INCLUDING
AT THE LEADERSHIP LEVEL.
IT INCREASES THE ADMINISTRATIVE
FOCUS SO THE BRANCH CHIEFS DO
NOT HAVE QUITE AS MANY DIRECT
REPORTS THEY HAVE TO
CONTINUOUSLY USE THEIR TIME TO
DEVELOP, PROMOTE PROFESSIONAL
DEVELOPMENT AND PROMOTION
OPPORTUNITIES FOR BOTH WITHIN
AND OUTSIDE THE DIVISION AND
INSTITUTE.
SO THE STRUCTURE IS REALLY BUILT
TO GROW TO GO WHERE THE SCIENCE
IS GOING AND TO RETAIN DIVISION
IDENTITY.
WHY THE FOUR BRANCHES IN THE
NCSDR?
I THOUGHT THIS WOULD BE A QUICK
WAY TO GIVE YOU A SENSE OF WHAT
WE ENVISION FALLING WITHIN THE
FIVE BRANCHES IN TERMS OF THE
OVER ALL SCIENCE.
THIS IS A HIGH-LEVEL BREAKDOWN
OF THE PROGRAMS THAT FALL UNDER
EACH BRANCH.
THEY'RE RELATED RESEARCH IS
PAIRED.
IT'S NOT PERFECT BUT IT ALLOWS
US TO ALIGN DISEASED AREAS WITH
DISEASE AGNOSTIC AREAS AS WELL
AS BEING ABLE TO MEET SOME OF
THE ADMINISTRATIVE REQUIREMENTS
THAT WE NEED TO ALSO ADHERE TO
IN ANY KIND OF RESTRUCTURING.
I WON'T GO THROUGH ALL THIS BUT
FOR MOST OF YOU CAN SEE IT HAS A
RELATIVELY LOGICAL FLOW TO IT.
THE TWO NEW THINGS YOU'LL SEE AS
A BRANCH THAT REVEALS RESTR
RESTRICTIVE AND VASCULAR LUNG
DISEASES GROWINGLY AND --
GROWING RAPIDLY AND LUNG
DISEASES AND RESTRICTIVE AND
VASCULAR LUNG DISEASES AND WE
THINK THEY'RE A NICE WAY TO MAKE
SENSE STRATEGICALLY AND
IMPLEMENTABLE TO MAKE THIS REAL
ALL SUBMITTING GRANT
APPLICATIONS AND WANTED TO KNOW
WHO TO TALK TO ABOUT YOUR
PARTICULAR AREA OF RESEARCH.
ALSO IMPORTANT IN ALL THIS IS
THE DIVISION MAINTAINS SOME
DIVISION-WIDE IDENTITY BUT
THERE'S A LOT OF CROSS-TALK THAT
WILL OCCUR WITHIN THE BRANCHES
AND WITHIN THE DIVISION AND A
LOT OF RELATIONSHIPS CAN BE
BUILT OF THE INTERACTIONS ACROSS
DLD AND ACROSS THE INSTITUTE.
WHERE ARE WE NOW?
WE WANT TO USE THE MEETING TODAY
AS A WAY TO INFORM THE COMMUNITY
ABOUT THE RESTRUCTURING OF THE
DIVISION.
WE WANT TO HEAR BACK FROM YOU AS
COUNCIL MEMBERS AND THE PUBLIC
ON WHAT YOU THINK ABOUT THIS.
WE'LL ALSO, TOMORROW, HAVE A
TWITTER ENGAGEMENT THAT WILL
WORK WITH OUR COLLEAGUES IN
OSPEEC TO HELP BROADCAST THIS
MORE BROADLY AND THE SECOND OVER
ALL HEARING AS OUR REQUIRED
STEPS IN THE PROCESS AND HAVE A
DLD REORG REEVENTS PAGE AND
WE'LL PUT THESE IN A FINAL
PACKAGE TO NIH FOR APPROVAL.
WE HOPE IT WILL MOF ALONG
RELATIVELY QUICKLY BUT MAY TAKE
UP TO 12 MORE MONTHS TO
COMPLETE.
I'LL BE HAPPY TO TAKE QUESTIONS
AND THANK YOU FOR YOUR ATTENTION
AND CONSIDERATION OF THE
REORGANIZATION PROPOSAL.
>>THIS IS THE RIGHT THING TO DO
AND FORWARD LEANING.
YOU COMMENTED HOW THE BUCKETS OF
DIFFERENT TOPICS WILL GO IN AND
FOUR DIFFERENT BRANCHES.
COULD YOU MAYBE EXPAND HOW A
CROSS-FUNCTIONAL HYPOTHESIS FOR
A GRANT SAY STEM CELLS AND COPD
TWO DIFFERENT SUBSECTIONS
BECAUSE IT'S SOMETHING IN MY OWN
PERSONAL EXPERIENCE AND OTHER
PEOPLE I KNOW HAD ISSUES WITH
THAT.
HOW DO YOU GET THE RIGHT PEOPLE
THAT WILL FOCUS ON THE TOPIC AND
HOW THAT WILL CROSS SECTION WILL
HAPPEN.
>>YOU SAW THE VERTICAL VIEW OF
THE DIVISION.
THERE'S ALSO A HORIZONTAL
COMPONENT AND IN TRANSLATIONAL,
FUNCTIONAL GENOMICS AND THREE OR
FOUR WE'VE IDENTIFIED WE THINK
WILL CUT -- THEY DON'T FIT
NICELY INTO ONE OF THE VERTICAL.
WE HOPE THE STAFF WILL PROMOTE
AND MAKE SURE THE SCIENCE YOU'RE
TALKING ABOUT RELATED TO STEM
CELLS, LUNG DEVELOPMENT AND
MAYBE PROGRESSION TO DISEASE
WILL ALL MAKE SURE THAT HAS A
NATURAL HOME AND GIVEN THE
ATTENTION WE THINK IT DESERVES.
THAT'S THE KEY PIECE I THINK YOU
RAISED IS MAKING SURE THAT THOSE
AREAS DON'T GET LOST OR ORPHANED
IN THE WHOLE PROCESS.
RIGHT NOW SOMEBODY WILL CALL UP
AND SAY I WANT TO DO THAT KIND
OF RESEARCH, WELL, WHERE DOES IT
FALL?
WHERE DOES IT FALL WITHIN THE
INSTITUTE.
WE WANT TO GIVE IT MORE CLARITY.
THANK YOU, GOOD QUESTION.
>>DR. SOL FIRST AND THEN
DR. ENBAR.
>>THANK YOU.
I JUST WANTED TO CONGRATULATE
YOU AND THE AREA IS WONDERFUL
AND IMPORTANT IN RESEARCH AND
WILL OFFER OPPORTUNITIES TO ALSO
PROGRAMMATICALLY WORK ACROSS
INSTITUTES WITH PEDIATRIC LUNG
DISEASE AND I DON'T KNOW IF
THERE'S PRELIMINARY THOUGHTS
ABOUT THAT BUT WOULD CERTAINLY
OPEN THE DOOR TO
ACROSS-INSTITUTE INITIATIVES
LIKE SOME IN THE BLOOD DISEASES
DIVISION.
>>GREAT, THANK YOU.
ANOTHER GREAT COMMENT.
WE ALREADY HAVE QUITE A FEW
INTERACTIONS WITH NICHD, FOR
INSTANCE, IN TERMS OF MATERNAL
HEALTH AND PREMATURITY AND HAVE
NETWORKS THEY INTERACTED WITH IN
TERMS OF PEDIATRIC LUNG DISEASES
AS WELL AS SLEEP.
THE NEW MOMS-TO-BE STUDY HAS A
BIG SLEEP COMPONENT IN IT AND
COMPLETED THE PREGNANCY PART OF
THIS.
SPOT ON.
THESE ARE AREAS WE CAN CONTINUE
TO BUILD OFF OF AND PUTTING THE
IDENTITY ON PEDIATRICS WILL
ALLOW US TO DO THAT IN A MORE
FORMAL WAY.
WE HAVE ABSOLUTELY FABULOUS
STAFF WE RECRUITED OVER THE PAST
FEW YEARS WHO HAVE EXPERTISE IN
PEDIATRICS AND LUNG DEVELOPMENT
AND PEDIATRIC CRITICAL CARE.
AND THESE ARE ALL GROWTH AREAS
AS WE SEE FOR THE FUTURE.
WE'RE EXCITED THIS.
THANK YOU FOR YOUR COMMENT.
>>I LIKE THE STRUCTURE.
I THINK IT'S GREAT FOR THE
REASONS YOU CITE.
I'M GOING TO ECHO BOTH THE LAST
TWO COMMENTS.
ONE QUESTION I HAVE AS YOU
REPRESENTED THIS, HOW DO YOU
BRING TOGETHER THE PREVENTION
POPULATION ISSUES IN
CAULAR ROUTE BUT IT
SOUNDS LIKE ACROSS CUT ON THAT
ONE.
>>THAT'S ANOTHER ONE THAT IS
CROSS-CUTTING.
>>THAT INTERFACES WITH THE
HEART PROGRAM.
WE'VE DONE QUITE A BIT IN THE
LAST FEW YEARS.
YOU HEARD ABOUT LUNG HEALTH AND
HAD INITIATIVES TOGETHER.
YOU POINTED OUT THE ASIAN
INITIATIVE THAT WILL LAUNCH,
HEART, LUNG, BLOOD, SLEEP.
I THINK WE DON'T WANT TO JUST
PUT A DIVISION IN PLACE THAT ARE
PART OF THEE D THAT IS A
SHARED KIND OF AREA AND THE
EXPERTISE REALLY THE STRONG
EXPERTISE IS IN THE HEART
PROGRAM.
TO LEVERAGE THAT
EXPERTISE.
>>THE OTHER GENERAL COMMENT IN
TERMS OF LINKAGES TO OTHER
INSTITUTES AND CENTERS IS I
THINK FROM A COMMUNITY
PERSPECTIVE, CRITICAL CARE A
WHERE DO CERTAIN ASPECTS COME
ALONG AND SOME OTHER PIECES
OVERLAP SEPSIS AND IS THE
CRITICAL CARE ISSUES WITH
LONG-TERM OUTCOMES HASN'T REALLY
HAD A DEFINED HOME WITHIN NIH.
SO I THINK THERE'S A LOT OF
POTENTIAL HERE FOR GROWING THAT
AND I THINK THOSE ISSUES ARE
IMPORTANT.
I THINK THIS IS A MAJOR STEP
FORWARD.
>>THANKS, DAVID.
I THINK THE ONE BRANCH, THE
ACUTE AND INFECTIOUS LUNG
DISEASE BRANCH WE HAVE DONE A
LOT TO GET THAT WORKED OUT IN
TERMS OF ASSIGNMENTS.
WE HAVE PROGRAMS IN TERMS OF
BASIC CLINICAL.
WE'RE MAKING PROGRESS.
IN TERMS OF THE SEPSIS COMMUNITY
THEY KNOW WHERE TO GO.
I THINK THEY KNOW NOW WHERE TO
GO.
IT'S TAKEN A WHILE TO GET THERE
BUT THEY KNOW WHERE TO MAKE THE
CALL.
I THINK WE CAN FIND THE RIGHT
HOME FOR THEM FAIRLY QUICKLY AND
LOGICALLY.
WE'RE EXCITE ABOUT THAT AS WELL.
I THINK WE CAN GET THIS TO PLAY
OUT IN A WAY THAT WORKS FOR ALL.
>>THANK YOU AND
CONGRATULATIONS.
>>THANKS.
>>THANK YOU, DR. KILEY.
I'M NOT SEEING ANY OTHER RAISED
BUT SURE YOU'LL GET COMMENTS
TOMORROW MAYBE AT YOUR TWITTER
SESSION AND OTHER ASPECTS OF
THIS YOU PLANNED.
NEXT, WHAT WE'VE GOT ON THE
AGENDA IS OUR SPEAKER FOR THE
DIVISION OF INTRAMURAL RESEARCH,
DR. SEAN AGBOR-ENOH.
HE RECEIVED HIS DEGREE FROM
UNIVERSITY OF CAMEROON AND
GEORGETOWN AND WAS A CHIEF
RESIDENT AT JOHNS HOPKINS AND
HAD A JOINT FELLOWSHIP IN
PULMONARY AND CRITICAL AREA
ATTAT
JOHNS HOPKINS AND IS A TENURE
TRACK INVESTIGATOR AT NHLBI AND
HIS RESEARCH AIMS TO IDENTIFY
NOVEL APPROACHES TO DETECT AND
TREAT TRANSPLANT REJECTION.
A MAJOR COMPLICATION THAT
CONTRIBUTES TO THE UNUSUALLY
HIGH MORTALITY IN LUNG
TRANSPLANT PATIENTS.
A VERY SAD THING INDEED.
HE LEADS A MULTI-CENTER
CONSORTIUM AND ALLIANCE FOR
TRANSPLANTATION, GRAFT, TO
PROVIDE A PATIENT COHORT AND
RESEARCH INFRASTRUCTURE FOR HIS
RESEARCH.
HIS WORK DEMONSTRATES THE NOVEL
BLOOD TESTS, CELL-FREE DNA
REJECTION EARLIER THAN THE
INVASIVE GOLD STANDARD THE
BIOPSY AND THE CELL TEST HAS
BEEN ADOPTED INTO ROUTINE
CENTERS TO PREDICT REJECTION AND
SHIFTS TO REDEFINE ACUTE
REJECTION TO IDENTIFY BETTER
TREATMENT OPPORTUNITIES.
HIS MECHANISTIC STUDIES IDENTIFY
BETTER DRUG TARGETS FOR ACUTE
REJECTION.
HE'S PLANNING CLINICAL TRIALS TO
TEST THE BENEFIT.
IT'S WORTH NOTING HE'S RECEIVED
RECOGNITION NATIONALLY AND
INTERNATIONALLY AND NAMED ONE OF
THE 1,000 INSPIRING BLACK
SCIENTISTS IN AMERICA IN 2020.
HE'S ALSO BEEN INDUCTED INTO THE
AMERICAN SOCIETY OF CLINICAL
INVESTIGATOR IN 2023 AND RECEIVE
THE 2021 JAMES T WILL ARSON
AWARD FOR THE BEST MANUSCRIPT
PUBLISHED IN CIRCULATION IN THE
PRECEDING 12 MONTHS.
THANK YOU FOR COMING.
WE LOOK FORWARD TO HEARING YOUR
TALK.
>>THANK YOU.
THANK YOU FOR THE KIND
INTRODUCTION.
I'VE SEEN LUNG TRANSPLANT
STATIS -- TRANSPLANTATION
PATIENTS.
PATIENTS WITH ADVANCED LUNG
DISEASE, DR. KILEY JUST TALKED
ABOUT PATIENTS WITH DIFFERENT
LUNG DISEASES AT VERY ADVANCED
STAGES OF THE LUNG DISEASES THE
PATIENTS HAVE NO ADDITIONAL
TREATMENT.
WE GIVE THEM A CHANCE AT A
SECOND LIFE.
JUST LISTEN TO THIS STORY.
>>IT'S SUCH A GOOD VIDEO JUST
THE IMAGES WILL TELL THE STORY.
THEN I CAN PLUG IN SOME WORDS AS
WELL.
HELP IS ON THE WAY.
>>HE WAS JUST 8 YEARS OLD IN A
CROSSWALK WHEN STRUCK BY A CAR.
HIS PARENTS HAD A TERRIBLE
DECISION TO MAKE.
JUST A FEW DOORS DOWN,
HOKESTEIN LAY
DYING.
>>I GOT TO THINKING THAT IF MY
SON DIDN'T MAKE IT MAYBE THAT
LITTLE BOY WOULD.
>>FOR THEM TO SAY YES HOW DO
YOU PUT THAT INTO WORDS.
>>FOR MORE THAN 20 YEARS THE
FAMILIES SEARCHED FOR EACH
EITHER.
>>IT'S SURREAL AND EXCITING HIS
S STILL BEATING INSIDE MY
CHEST.
>>ALWAYS APPRECIATING THE GIFT
THEY GAVE US.
>>GIVING A GIFT OF LIFE IS THE
GREATEST THING ANYONE CAN DO FOR
SOMEONE ELSE.
>>JOHN HOKESTEIN 20 YEARS AFTER
RECEIVING THE HEART THE MOTHER
CAN LISTEN TO HER SON'S
HEARTBEATING IN JOHN HOKESTEIN.
HE'SKE CURRENTLY ANT MEDICAL STT
IN HARVARD GRADUATING THIS YEAR
WITH THE AIM OF GOING INTO
THORACIC TRANSPLANTATION.
THIS THE STORIES ARE NOT ALWAYS
GLORIOUS AND THE IMMUNE SYSTEM
CAN THEN LEADTH DIFFERENT FORMS
OF REJECTION IT COULD BE ACUTE
CELLULAR REJECTION OR AN
ANTIBODY REJECTION, AMR.
IN ADDITION, THE LUNGS ARE
EXPOSED TO MULTIPLE, MULTIPLE
INFECTIONS AND THE ENVIRONMENT
AS WELL.
SO MULTIPLE INSULTS THAT WITHIN
FIVE TO SEVEN YEARS OF
TRANSPLANTATION, 50%, HALF OF
LUNG TRANSPLANT PATIENTS
OTHERWISE WILL NOT SURVIVE
BECAUSE THEY'LL LOSE.
THIS GRAPH WHILE I WAS IN
RESIDENCY AT JOHNS HOPKINS MADE
ME SWITCH MY SPECIALTY,
DR. GIBBONS, NO OFFENSE TO
PULMONARY MEDICINE.
JUST LOOK AT THIS.
HOW CAN THIS BE ACCEPTABLE?
RE LIED RESEARCH SSION.
THE REST IS REALLY JUST ONGOING.
AND THIS RESULTS FROM
COMPLICATIONS OF REJECTION AND
INFECTION.
AND IN THE LUNG DUE TO THE VERY
LARGE PULMONARY RESERVE, THESE
ARE OFTEN INITIALLY CLINICALLY
CITED.
THIS IS A LUNG TRANSPLANT
PROVIDER HERE.
SOMEONE LIKE ME, INSERTS A
BRONCHIAL SCOPE THROUGH THE NOSE
AND MOUTH INTO THEIR LUNGS TO
TAKE BITS AND PIECES OF THE LUNG
TO LOOK FOR REJECTION.
ON TOP IS A TIME LINE FROM
TRANSPLANTATION TO TWO YEARS
INDICATING WHEN THESE PATIENTS
GET BRONC JOE SHIAL SCOPY.
YOU CAN SEE WHETHER THE PATIENT
HAS SYMPTOMS WILL GET
SURVEILLANCE.
IF THEY DO HAVE SYMPTOMS THEY'LL
GET ADDITIONAL BRONCHOSCOPY.
AND THE PATIENTS GET UP TO 20,
25 HEART BIOPSIES IN THE FIRST
YEAR OF TRANSPLANTATION ALONE.
YOU CAN IMAGINE, GOING INTO
SOMEBODY'S LUNG OR HEART TO GET
PIECES IS CLEARLY AN INVASIVE
PROCESS AND ASSOCIATED WITH
MULTIPLE COMPLICATIONS AND THE
HISTOPATHOLOGY HAS ITS OWN
PROBLEMS.
THIS APPROACH OVER ALL CAN OFTEN
MISS REJECTION OR DIAGNOSIS AT
LATE STAGES AT WHICH POINT
TREATMENT IS INEFFECTIVE LEADING
TO FAILURE.
CLEARLY WE NEED AN ALTERNATIVE
APPROACH.
TRANSPLANTATION MAY OFFER THE
SOLUTION.
THE FACT THAT TRANSPLANTATION
OFFERS THE MIXING OF GENOMES, I
KEEP TELLING COLLEAGUES AT OTHER
PLACES, IF YOU TRULY WANT TO
STUDY HOW THE GENOME ADAPTS IN A
NEW ENVIRONMENT STUDY
TRANSPLANTATION.
YOU TAKE A LIVING GENOME FROM
ONE PERSON AND PLACE IT IN A
DIFFERENT ENVIRONMENT CREATES
TOO MANY OPPORTUNITIES OF
LOOKING AT HOW THE GENOME CAN
ADAPT TO DIFFERENT ENVIRONMENT.
COMING BACK TO US FOR REJECTION
THOUGH THIS MIXTURE OF TWO
GENOMES CREATES AN OPPORTUNITY
TO MONITOR FOR REJECTION BY
LOOKING AT BLOOD MOLECULES AND
HERE WE'RE TRYING TO FIND BETTER
WAYS OF DIAGNOSING REJECTION.
WE'RE READY TO MOVE OUR RESEARCH
INTO PHASE 2 WHICH IS
INTERVENTIONS.
NOW THAT WE KNOW, CAN WE DO
SOMETHING TO IMPROVE THAT
PATIENT'S OUTCOME?
THAT'S WHERE I'M HOPING TO GO
BUT WE'VE DONE PHASE 1 AND READY
TO GO INTO PHASE 2.
PHASE 1, WE STARTED WITH THREE
AIMS TO DEVELOP TOOLS AND
REDEFINE ACUTE REJECTION AND
IDENTIFY WHO AND WHEN TO TREAT
AND BUILD A CONSORTIUM OR
INFRASTRUCTURE TO DEVELOP THE
TESTS AND DO STUDIES TO TEST FOR
THE HIGH UTILITY.
WHAT IS THE CELL-FREE SOME
CONTENTS REMAINS IN THE BLOOD
AND BECAUSE IT'S OUT OF THE CELL
IT'S FREE FROM CELLS WE CALL IT
CELL-FREE DNA.
THEY'RE FRAGMENTS OF NUCLEIC
ACID CIRCULATING IN BLOOD.
THEY'RE QUITE ABUNDANT.
IF YOU CAN IMAGINE CELLS ALL
OVER RELIEVING -- RELEASING
BLOOD AND THIS IS BILLION WITH A
"B", FRAGMENTS OF SO QUITE
ABUNDANT AND DNA SO IT'S
PACKAGED WITH VERY RICH BIOLOGY
INFORMATION WHICH YOU CAN
HARVEST BY JUST STUDYING PLASMA
IN BLOOD.
LET'S COME TO TRANSPLANTATION
THE MIXTURE AND IT COMES FROM A
DIFFERENT PERSON THAT BE THE
RECIPIENT.
THEREFORE THE DNA IN THE LUNG IS
DIFFERENT FROM THE DNA IN THE
RECIPIENT.
IF YOU COLLECT BLOOD AND ISOLATE
PLASMA FROM THAT TRANSPLANT
PATIENT YOU'LL GET CELL-FREE DNA
FROM THE RECIPIENT OR IN GREEN,
CELL-FREE DNA FROM THAT AND USE
ANY METHOD OF INTEREST DIGITAL
DROP LET CPR, SEQUENCING, ANY
METHOD TO LOOK AT THE MATERIAL
AND ONE CAN LOOK AT THE FRACTION
OF DERMAL-DERIVED CELL-FREE DNA
AS A MARKER OF REJECTION.
DOES IT WORK?
LET ME START WITH THIS SLIDE.
THIS IS A STUDY WE INITIALLY DID
WITH INVESTIGATORS FROM STANFORD
WHEN HANNAH VALENTINE WAS HERE
BEFORE SHE MOVED TO STANFORD.
THEY DID REPLICATE ANALYSIS OF
THE SAMPLES IB OUR LAB AND AT
STANFORD.
YOU CAN SEE AND IN BLUE IS
ANALYSIS AT STANFORD.
AND THE GENOME IS PRETTY BIG.
THERE'S MANY REASONS WHY THIS IS
CORRECT.
HERE IS A PATIENT THIS IS A
HEART TRANSPLANT PATIENT WITH
REJECTION AND THE PATIENT
DEVELOPS REJECTION AND THE
LEVELS COME BACK DOWN.
AT THE NIH WE DO NOT HAVE A
LUNG, HEART, TRANSPLANT PROGRAM
AND WE GUIDE IT TOWARDS CREATING
AN INFRASTRUCTURE OR
INTERRUPTION A CONSORTIUM AND
CALL IT GENOMIC RESEARCH
ALLIANCE FOR TRANSPLANTATION OR
GRAFT.
IT'S A COMBINATION OF NHLBI
PROGRAMS.
IT'S EASY TO DRIVE UP, MEET UP
WITH CO-INVESTIGATORS AND THEY
HAVE BEEN THE INFRASTRUCTURE IN
MY MIND AND THE FOUNDATION FOR
THE FINDINGS I'LL SHOW YOU GOING
FORWARD.
IN THIS CONSORTIUM WE
STANDARDIZED SAMPLE COLLECTION
ACROSS ALL THE DIFFERENT CENTERS
AND BUILD COMMITTEES WHICH ARE
EXPERT PHYSICIANS FROM ACROSS
THE COUNTRY TO ADJUDICATE ALL
STUDY END POINTS.
IT'S BEEN HIGH FUNCTIONING.
WE HAVE ABOUT 690 SUBJECTS AND
MANY BIO SPECIMENS FOR RESEARCH.
COMING BACK TO THE ADJUDICATION
COMMITTEES IN TRANSPLANTATION,
THIS IS THE FIELD THINKS IT'S AN
IMPORTANT ASPECT BECAUSE IF YOU
TAKE A HUNDRED TRANSPLANT
DOCTORS IN THE SAME ROOM AND ASK
WHAT DIAGNOSIS THE PATIENT HAS
YOU MAY HAVE DIFFERENT ANSWERS.
NOT MAY, BUT YOU WILL HAVE
DIFFERENCE ANSWERS.
ACU
ADJUDICATED FOR THE STUDY END
POINTS IS RELEVANT TO BETTER
CHARACTERIZE TRANSPLANT
POSITIONS.
THIS IS THE CONSENSUS
HISTOPATHOLOGY TEAM AND ONE
EVERY SIX MONTHS THEY'LL FLY TO
THE NIH AND LOOK AT EVERY SLIDE
THAT IS COLLECTED AT THE CENTERS
OF EVERY PATIENT AND BETTER
CHARACTERIZE THEM FOR REJECTION.
WITH THIS INFRASTRUCTURE WE THEN
EMBARK ON TWO STUDIES.
ONE IN LUNG AND ONE IN HEART.
THE 169 PATIENTS IN LUNG AND WE
COLLECT SAMPLES AND MEASURE
CELL-FREE DNA ASKING HOW GOOD IS
CELL-FREE DNA IN DIAGNOSING
REJECTION?
THE FIRST THING WE REPORTED IS
THE LEVEL OF DDC DNA IN PLASMA
CORRELATES WITH THE SEVERITY OF
REJECTION IN BIOPSY.
IF YOU TAKE THE GRAPH HERE
GERMAL DERIVED CELL ON THE Y
AXIS AND GOING FROM ZERO TO 1 TO
2 YOU SEE INCREASES LEVELS OF
CELL-FREE DNA.
THIS IS IN MY MIND WHERE THE
POWER OF THE TECHNOLOGY IS.
IMAGINE THIS SLIDE HERE, TIMES
ZERO IS THE TIME THE BIOPSY
WHERE THE PATIENT SHOWS SYMPTOMS
AND IF YOU LOOK AT THE LEVELS AT
THAT TIME IT'S HIGH.
MORE IMPORTANTLY, TWO TO FOUR
MONTHS BEFORE THE BIOPSY SHOWS
SIGNS OF REJECTION OR BEFORE THE
PATIENT SHOWS ANY SIGNS OFFALO
GRAPH DISCUSSION YOU HAVE
ELEVATIONS OF CELL-FREE DNA IN
THE CASE OF ANTIBODY REJECTION
AND SHOW THE SAME IN HEART
TRANSPLANT AS WELL AND
IDENTIFIES AN EARLY TIME POINT
FOR WHICH WE CAN INTERVENE.
THE WORK HERE ALLOW ME TO THEN
ALLOW ME TO LOOK AT THE
LEADERSHIP AND I MET WITH OUR
LEADERSHIP TEAM AND THEY SAID IF
YOU WANT TO DO THE SCIENCE, YOU
WANT TO DO IT AND DO IT WELL.
SO WE SET UP THE GRAPH IN THAT
MANNER.
THE SAMPLE COLLECTION HAS TO BE
RIGOROUS AND THE END POINTS HAVE
TO BE RIGOROUS AND DOING IT THAT
WAY THE WORK BECAME MORE
ACCEPTED WITHIN THE TRANSPLANT
COMMUNITY.
TAKE THE NEXT SLIDE, FOR
EXAMPLE.
THIS IS ON HEART TRANSPLANTATION
ON JULY 1 WHEN I WAS ASKED TO
SEND THE SLIDES IT'S BEEN
DOWNLOADED 11,540 TIMES ACROSS
THE WORLD.
I WAS TRYING TO FIND COUNTRIES
FOR WHICH IT HAS NOT BEEN
DOWNLOADED I COULDN'T FIND THAT
AND THOUGH IT WAS PUBLISHED IN
2001 OR SO, IT'S STILL BEING
DOWNLOADED 250 TO 400 TIMES
EVERY MONTH.
THAT'S ONE THING.
SECONDLY, THIS IS WHERE I THINK
THIS DEEP DRIVER IN THE FIELD OF
TRANSPLANTATION AND THEN IF YOU
CONSIDER CELL-FREE DNA AS THE
GOLD STANDARD AND LEVELS GREATER
THAN 0 TO 2.5 SUGGEST SOMETHING
IS BAD OR LESS THAN THAT.
IF YOU DO THAT, YOU DO THAT AND
THIS IS WHAT WE SEE.
ONLY 20% OF THEM WHERE THE
BYPASS SHOWS SIGNS OF POSITIVE,
80% OF THE CELL-FREE DNA LEVELS
THAT ARE HIGH THE BIOPSY SHOWS
THEY'RE NEGATIVE.
IF YOU LOOK AT WHETHER IT'S
POSITIVE, NO, IF YOU LOOK AT
THAT 80%, 76% THE PATIENT WILL
GET A REJECTION IN THE FUTURE OR
THEY HAVE AN ALO GRAPH AND SEEMS
LIKE AN EARLY INDICATION OF
SOMETHING NOT RIGHT.
IT PICK UP BUT ONLY 1 IN 4
CLINICALLY ELEVATIONS OF
CELL-FREE DNA.
AND THIS WORK RECEIVE THE JAMES
T. WILLARSON AWARD.
AND WHAT HAS CELL-FREE DNA
ENABLED US TO DO?
WHO AND WHEN TO TREAT.
EARLY DETECTION AND LEVELS OF
CELL-FREE DNA IN THE EARLY
POST-TRANSPLANT PERIOD PREDICT
FAILURE AND PREDICT TIME FROM
TRANSPLANT PATIENT TO WHEN THE
PATIENT WILL AND BLO PATIENTS
AT TRANSPLANTATION DEVELOP HIGH
LEVELS OF CELL-FREE DNA.
THEY THEN GO ON TO SHOW
INCREASING LEVELS OF CELL-FREE
DNA AND SHOW POORER OUTCOMES
COMPARED TO PATIENTS WITH
EUROPEAN ASSENCESTRY PROVIDING
BIOLOGICAL DIFFERENCE IN WHY
THEY MAY HAVE POORER OUTCOMES.
CELL-FREE DNA HAS ALLOWED US TO
SEE WHO SHOULD BE TREATED AND
WHEN.
I'LL SKIP THIS SLIDE.
AND YOU CAN SET UP YOUR RESEARCH
INFRASTRUCTURE AND PUBLISHING
WORK IT BECOMES MORE EASILY
ACCEPTED.
AND IT'S GONE TO RECEIVE AWARDS
NATIONALLY AND INVITED
COLLABORATORS FROM DIFFERENT
PARTS OF THE WORLD AS WELL.
AND BEFORE I GO ON, THEN COVID
CAME.
WHEN COVID CAME, EVERYTHING WENT
ON THE PAUSE FOR A LITTLE BIT
AND THEN AN IDEA CAME UP.
WHEN COVID CAME UP TRANSPLANT
PATIENTS ARE IMMUNOCOMPROMISED.
YOU DON'T WANT THEM OUTSIDE.
YOU WANT THEM IN THEIR HOUSE.
HOW WILL THEY COME TO CLINIC TO
GET BIOPSIES?
HOSPITALS WERE STRUCK AND
TRANSPLANT CENTERS WERE STRUCK
AND NOBODY ENVISIONED COVID AND
WHO WILL YOU POINT THE FINGER
TO?
BOTH PHYSICIANS AND DOCTORS WERE
STUCK.
THEN WE FOUND A PARTNERSHIP WITH
AN INDUSTRY PARTNER WHICH I
THOUGHT GREAT BECAUSE THEY HAVE
THE INFRASTRUCTURE AND WE
LAUNCHED A STUDY THE ANALYSIS
FOR LONG MONITORING.
THE COMPANY OBTAINED FDA
COMPASSIONATE USE APPROVAL OF
CELL-FREE DAP.
WE ARRANGE D FOR PEOPLE TO GO T
THE PATIENT'S HOMES AND YOU CAN
MONITOR THEM MOSTLY FROM THEIR
HOMES AND THE DOCTORS AND WE
COULD THEN GUIDE PHYSICIANS TO
USE THAT TO MONITOR FOR
INFECTION AND REJECTION.
IF THESE LEVELS ARE LESS IT'S AN
ALL CLEAR.
A 99% PREDICTIVE VALUE.
IF THE LEVELS ARE BETWEEN 0.5
AND 1, WAIT, BE MORE CAREFUL.
CHECK THE PATIENT MORE OFTEN.
THEY'LL GO TO TWO-WEEK
MONITORING.
IF THE LEVELS ARE 1% OR HIGHER,
THAT'S A RED LIGHT.
BRING THE PATIENT IN AND FIGURE
OUT WHAT'S WRONG AND IF YOU
DON'T FIND ANYTHING, GO BACK TO
MONTHLY MONITORING BUT BE MORE
CAREFUL BECAUSE IT'S USUALLY AN
EARLY SIGN SOMETHING BAD IS
GOING TO HAPPEN.
IF YOU FIND SOME INFECTION OR
REJECTION YOU TREAT IT.
WE USE CELL-FREE DNA AS
SURVEILLANCE MONITORING INSTEAD
OF BRONCHO SCOPEE AND WE'RE ABE
IT AVOID 82% OF INVASIE IIVE
BRONCHOSCOPY AND NOW IN PLACE IN
U.S. AND CANADA.
THE CELL-FREE TEST IS BEING USED
AT JOHNS HOPKINS BASED ON THE
PROTOCOL PROPOSED IN THE STUDY
HERE.
HOWEVER, THE TEST HAS ONE FLAW
STILL.
ACUTE REJECTION AND INFECTION
ARE COMMON IN LUNG TRANSPLANT
PATIENT.
BOTH LEAD TO AN ELEVATION IN
CELL-FREE DAP AND IF PATIENT
HAVE A CELL-FREE DNA YOU DON'T
FLOW IF IT'S FROM INFECTION OR
REJECTION?
IT CAN TELL YOU SOMETHING IS
WRONG AND IT'S A RULE-OUT TEST.
IT'S NOT A SPECIFIC TEST.
CAN WE IDENTIFY A SPECIFIC TEST.
IF YOU THINK ABOUT IT, AND YOU
AND THERE'S NEUTROPHILS AROUND
THE CAPILLARIES OF ORGANS AND
TISSUES OPPOSED TO ACUTE
CELLULAR REJECTION WHICH THE
LYMPHOCYTIC PROCESS AND THE
REJECTION OR INFECTION FOR THAT
MATTER THAT INVOLVE DIFFERENT
CELLS AND DIFFERENT TISSUE
TYPES.
THESE ARE THE TISSUE TYPES THAT
WOULD BE PRODUCING CELL-FREE
DNA.
SO IF YOU THINK ABOUT IT, ONE IS
LOOKING AT EPIGENETIC
FINGERPRINTS ON CELL-FREE DNA.
WHILE THE DNA SEQUENCE IN YOUR
ENTIRE BODY IS IDENTICAL, THE
EPIGENETIC FINGERPRINTS ARE
DISTINCT.
INDEED THEY CONFER THE HEART TO
BE ABLE TO BEAT, THE LUNG TO DO
RESPIRATION AND BLOOD TO DO WHAT
IT DOES BEST AND IT'S THE
EPIGENETIC FINGERPRINT THAT
CONFER FUNCTION AND TISSUE
SPECIFICITY.
THESE ARE PRESERVED ON CELL-FREE
DNA.
IF I CAN SEQUENCE CELL-FREE DNA
I SCAN THE SIGNATURES ON THE
CELL-FREE DNA AND COULD THEN
PROVIDE A WHOLE BODY MOLECULAR
INJURY SCAN.
THE ANSWER IS YES BUT ALLOW ME
TO SHOW YOU A FEW SLIDES TO SHOW
THAT'S THE CASE.
WE HAVE CELL-FREE DNA AND WE
QUANTITATE THAT BY DIGITAL
DROPLETS AND LOOK AT DNA
METHYLATION.
AND THEN WE ALL KNOW THERE ARE
WELL-KNOWN SIGNATURES OF
TISSUE-SPECIFIC DNA METHYLATION
SIGNATURES AND THEY'RE WELL
KNOWN OF THE LUNGS.
EVERY TISSUE TYPE HAS DNA
METHYLATION SIGNATURES THAT ARE
TISSUE SPECIFIC.
THIS IS WELL KNOWN AND WELL
PUBLISHED.
IF WE KNOW THAT, WE SCAN THE
CELL-FREE DNA TO IDENTIFY THE
TISSUES WHICH IT'S COMING FROM.
AND I'LL SKIP THE SLIDE.
YOU CAN DO THIS LOOKING AT GENE
EXPRESSION THE MODIFICATION OF
CHROMATIN ALSO IS ALSO TISSUE
SPECIFIC.
YOU CAN GRAT THE MODIFICATION,
LOOK AT THE TISSUE-SPECIFIC MARK
TORE IDENTIFY WHERE THE
CELL-FREE -- MARKER TO IDENTIFY
WHERE THE CELL-FREE DNA IS
COMING FROM.
THESE ARE PATIENTS WITH
COVID-19.
ON THE Y AXIS IS THE AMOUNT AND
X AXIS IS DAYS FROM
HOSPITALIZATION OF THE PATIENTS.
THE KEY TO YOUR RIGHT ARE THE
DIFFERENT TISSUE TYPES PRODUCING
THE CELL-FREE DNA IN AN INSTANT.
IF YOU CLICK HERE THESE ARE TWO
PATIENTS WITH COVID-19 WHO DIED.
ON ADMISSION YOU CAN SEE
CELL-FREE DNA LEVELS RANGE FROM
1,000 TO 1,500.
BY REFERENCE IN HEALTHY CONTROL
THE RANGE IS 12% TO 20%.
THESE ARE HIGH LEVELS OF
CELL-FREE DNA.
FROM ADMISSION THE PATIENT GETS
ALL KIND OF TREATMENT AND
CELL-FREE DNA LEVELS COME DOWN
AND THESE PATIENTS GO INTO A
SECOND INFLAMMATORY PHASE OF
COVID, EXPONENTIAL RISE OF
CELL-FREE DNA AND BECAUSE THE
HALF LIFE IS SO SHORT, YOU CAN
SAMPLE QUESTIONS FREQUENTLY AND
ALMOST GIVE YOU A SNAPSHOT OF
WHAT INJURY PATENTS ARE GOING ON
IN THE BODY AT THAT INSTANT.
THE HALF LIFE IS 15 TO 30
MINUTES OF CELL-FREE DNA.
IT'S A GOOD SNAPSHOT IN TIME
COMPARED TO PATIENT WITH
COVID-19 WHO SURVIVE.
FIRST PATIENTS 150 TO 600 THEN
THE TRENDS OF THE CELL-FREE DNA
DIFFER.
THE TISSUES PRODUCING THE
CELL-FREE DNA DIFFER FROM
PATIENT WHO'S DIE.
FROM ADMISSION WE CAN ALMOST
PREDICT PATIENTS WHO NEED ICU
CARE WITH CARE SUBSEQUENTLY WITH
GOOD TEST CHARACTERISTIC.
IS IT ONLY IN COVID?
NO.
WE SHOW PATIENTS WITH PULMONARY
HYPERTENSION.
THE SECOND-GENERATION CELL-FREE
DNA APPROACHES ARE BROADLY
APPLICABLE IN CONDITIONS BEYOND
TRANSPLANTATION.
HAVING DEMONSTRATED THE PROOF OF
CONCEPT WITH TRANSPLANT DOCTORS
WE TURN OUR ATTENTION BACK TO
TRANSPLANTATION AND SAID WE
LOOKED AT CELL-FREE DNA AND CAN
WE LOOK AT THE TRANSPLANTED
ORGAN AND WHAT IT'S FACING IN
THE TRANSPLANT JOURNEY STARTING
FROM BEFORE TRANSPLANTATION.
A CREDIT TO GRAFT AND GRAFT
INVESTIGATORS BECAUSE THEY
STARTED SAMPLES BEFORE
TRANSPLANTATION AND COLLECTED
SERIAL SAMPLES AFTER AS WELL.
AND THE PATIENTS WILL GO ON TO
DIE EARLY AND THERE'S INJURY
FACED WHETHER LUNG, HEARD OR
KIDNEYS AND THERE'S PROFUSION
INJURY AND INFECTION OF OTHER
INJURIES AS WELL.
SO LET ME ORIENT YOU TO THE
COPIES OF ML PER CELL-FREE DNA
UP TO 250,000 AND HEALTHY
CONTROLS ALL THE WAY DOWN HERE.
IN TERMS OF COPIES, HEALTHY
PEOPLE HAVE ABOUT 2,000 COPIES
OF CELL-FREE DNA PLASMA.
THAT'S OUR ORIENTATION.
IF YOU LOOK AT PATIENTS AWAITING
TRANSPLANTATION YOU HAVE A
TWOFOLD HIGHER CELL-FREE DNA IN
THOSE THAN FROM HEALTHY CONTROLS
AND THE CELL-FREE DNA PREDICT
TIME TO ALLOGRAFT FAILURE.
THE INJURY STARTS BEFORE
TRANSPLANTATION.
AFTER, ONE TAKE-HOME POINT IS
THIS SLIDE, THE SECOND SLIDE.
THIS WAS DONE -- THIS IS SAMPLES
COLLECTED ON YEAR ONE OF
TRANSPLANTATION.
THE PATIENTS HAVE 154 HIGHER
CELL-FREE DNA THAN HEALTHY
CONTROLS.
IT'S A MARKER OF INJURY.
CAN MEASURE WHAT THE PATIENT IS
COMING OUT OF THE OPERATING ROOM
LOOKING AT.
YOU GO FROM ZERO TO 2.5 FOLD AND
YES IT COMES DOWN BUT THE LEVELS
DON'T JUST COME DOWN, IT'S FOUR
TIMES OF HEALTHY CONTROLS AND
THE LEVELS REMAIN HIGHER FOR
LEVELS WHO GO ON TO DEVELOP
ACUTE REJECTION.
WITH THESE TECHNOLOGIES AND THE
INFRASTRUCTURE IN GRAPH WE'RE
ABLE TO PROFILE INJURY STATES IN
THE TRANSPLANT PATIENT TO
IDENTIFY BETTER TIMES IN WHICH
WE CAN TREAT AND WHEN TO TREAT.
SO AS I MENTIONED, THESE
PATIENTS BEFORE TRANSPLANTATION
ARE ALREADY IN A HEIGHTENED
INJURY STATE.
THAT INCREASES AFTER
TRANSPLANTATION AND PERSISTS
UNFORTUNATELY, INCREASING THE
RISK OF ALLOGRAFT FAILURE.
ALLOW ME TO STOP AND SAY
CELL-FREE DNA ALLOWED US TO
DETERMINE EARLIER TIME POINTS TO
TREAT PATIENTS BEFORE
IRREVERSIBLE INJURY SETS IN AND
IDENTIFY RISK PROFILE AND WHO TO
PAY CLOSER ATTENTION TO AND WHO
TO TREAT AND WHEN TO TREAT
EARLY.
THE DATA I DID NOT SHOW YOU IS
IF YOU FOLLOW LEVELS OF
CELL-FREE DNA IT ALSO GIVES AN
EARLY INDICATION OF WHO IS
RESPONDING TO TREATMENT.
SO WE BELIEVE THAT AND THE LAST
EDITORIAL WE PUBLISHED AND
FORCED TO RAPIDLY EVOLVE BY THE
SARS COV2 PANDEMIC THE GROUP LED
BY SEAN ARBURG USED PRIOR
KNOWLEDGE WITH CELL-FREE DNA TO
PROTECT THEIR LONG TRANSPLANT
RECIPIENTS ON STAFF FROM THE
RISK OF TRANSMISSION OF SARS
COV2.
AS WE MOVE OUT OF THE POINT OF
CARE THIS REAL-WORLD DATA
SUGGESTS A NEW ERA OF LUNG
TRANSPLANT CARE, ONE OF GENOMIC
EVOLUTION IS DONE.
THIS IS AN EDITORIAL AND THE
ACCEPTANCE OF THE WORK, THE
ADAPTATION OF THE PROTOCOL THAT
REPROPOSED TO MONITOR PATIENTS
EVEN WITHOUT A RANDOMIZED
CONTROL TRIAL, THE CELL-FREE DNA
IS BEING ADAPTED BY AN
INCREASING NUMBER OF CENTERS.
THIS COULD BE POSSIBLE BECAUSE
OF THE MICROENVIRONMENT WE'VE
BEEN FORTUNATE TO BE PART OF AND
THE PROGRAM WHICH HOLDS THE
COMMUNITY TO IMPLEMENT AS MUCH
AS RIGOR IN THE WAY WE SET UP
OUR RESEARCH OBJECTIVES AND
RESEARCH INFRASTRUCTURE.
IN MY MIND THIS IS WHAT THE
EDITORIAL IS HIGHLIGHTING.
IT'S THAT MICROENVIRONMENT THAT
I'VE BEEN FOR THE TO BE A PART
OF.
WE BELIEVE WE FOUND A TOOL THAT
WE CAN EFFECTIVELY IDENTIFY
REJECTION, IDENTIFYING WHO, WHEN
AND I DIDN'T SHOW YOU SOME DATA
WITH WHAT.
WHAT TO USE AND WE'RE READY TO
MOVE TO THE NEXT PHASE, PHASE 2,
INTERVENTIONS.
I'VE BEEN FORTUNATE TO WORK IN
THE INTRAMURAL PROGRAM BUT TO BE
HAVE ACCESS OR HAVE FELLOWS THAT
CAN JOIN THE LAB FROM DIFFERENT
SPECIALTIES AND ATTRACT
DIFFERENT SPECIALTIES AND
THEY'VE COME TO THE LAB IN THE
LAST TWO YEARS.
ALLOW ME TO STOP HERE BY GIVING
A CONGRATULATORY SHOUT OUT AND
THE WASHINGTON HOSPITAL CENTER
AND VIRGINIA COMMONWEALTH CENTER
FORMING THE CONSORTIUM.
IT'S BEEN A PRIVILEGE WORKING
HERE AND THERE'S THE OFFICE AND
I'VE BEEN FORTUNATE TO WORK WITH
PEOPLEIT DIFFERENT
BACKGROUNDS AND WAYS OF THINKING
AND CULTURES AND ALL OF US WITH
AN EYE TOWARDS THE SAME GOAL.
THANK YOU SO MUCH.
ANY QUESTIONS?
>>THANK YOU FOR SOME FUN WORK
THOUGH I'M NERVOUS YOU'RE GOING
TO DRY UP MY SUPPLY OF BIOPSIES
BY REMOVING THE NEED.
I CAME FROM THE TRANSPLANT
MEETING AND A BIG DISCUSSION IN
THE LUNG TRANSPLANT COMMUNITY IS
TRYING TO FIGURE OUT WHICH
PATIENT TO TRANSPLANT FROM THOSE
WHO RECOVERED FROM COVID AND OUT
OF THE UNIT BUT STILL HAVE A
PULMONARY DISABILITY.
WILL THEY GET BETTER?
DO I NEED TRANSPLANT?
HAVE YOU THOUGHT OF LOOKING IN
THAT POPULATION TO DETERMINE
WHICH PATIENTS WHICH MAY BE
PROGRESSING OR THEIR LUNG
FUNCTION MAY BE IMPROVING INN
TERMS OF TRACKING YOUR CELL-FREE
DAP.
>>THANK YOU VERY MUCH.
>>YES.
A TRANSPLANT SURGEON AT U-PENN
WITH JOSH DIAMOND THE DIRECTOR,
IS ON THE P MEDICAL SIDETHEY AC
PATIENTS WHO HAVE TRANSPLANTED
BECAUSE OF COVID.
THEY HAVE COLLECTED SERIAL
SAMPLES ON THE PATIENTS.
SO WE'VE CREATED A COLLABORATION
AND WE GOT THE SAMPLES AND WE'RE
LOOKING INTO THAT.
I BELIEVE YOUR HYPOTHESIS IS
CORRECT.
IN OUR EXPERIENCE WITH OTHER
DISEASES, TRANSPLANTATION, FOR
EXAMPLE, WHEN THE PATIENT,
EVERYBODY'S CELL-FREE DNA IS
HIGH AND FOR PATIENT WHO'S
DEVELOP EARLY ALLOGRAFT DEVELOP
A SECOND RISE IN THE CELL-FREE
DNA LEVELS BEFORE THEY DEVELOP
CHRONIC REJECTION.
WE DON'T HAVE AN ANSWER YET BUT
HOPEFULLY NEXT YEAR WE WILL.
>>I WAS ASKING ABOUT THE
PATIENTS WHO HAVEN'T GOTTEN THE
TRANSPLANT YET AND DEBATING
WHETHER THEY NEED A TRANSPLANT.
THAT WOULD BE INTERESTING.
>>NICE PRESENTATION.
IF I'M UNDERSTANDING CORRECTLY,
THIS MAY BE, DARE I SAY,
NON-SPECIFIC MARKER OF INJURY
WITH HEART, LUNG, BLOOD.
COULD WE USE SOMETHING LIKE THIS
IN LOOKING IN BIOMARKERS AND
DISEASE ACTIVITY AND LUNG WERE
NOT TOO FAR TN T ROAD TO SAY
BUT T PATEING
WE THINK MAY
INTERVENE IN THE DISEASE.
HAVE YOU LOOKED SERIALLY AT SOME
OF THOSE PATIENTS, FOR EXAMPLE,
TO SEE IF OUR CURRENT DRUGS MAY
REDUCE THE AMOUNT OF CELL-FREE
DNA OR OTHER DISEASES BECAUSE
MAYBE IT'S TO SOME EXTENT A
NON-SPECIFIC DISEASE BIOMARKER.
>>WITH STEVE NATHAN AND OTHER
PEOPLE IN THE GRAFT CONSORTIUM
WE ARE LOOKING AT PATIENTS WITH
PULMONARY FIBROSIS BEING TREATED
WITH A NEW DRUG AND WE'RE SAYING
TO SEE IT SAYS BEFORE TREATMENT
AND REDUCES TREATMENT?
IN PLANS TRANSPLANTATION WHEN
YOU LOOK AT DONOR-DERIVED THE
CELL-FREE DNA COMING FROM THE
DONOR LUNG.
IF YOU LOOK AT THAT IN PATIENTS
WHO DEVELOP REJECTION, AS I
SHOWED YOU, THE CELL-FREE DNA
RISE.
WHEN YOU TREAT THE PATIENT THE
CELL-FREE DNA DROPS WITHIN DAYS.
THE LEVELS ARE DOWN.
FOR PATIENTS WHO WILL NOT
RESPOND TO TREATMENT, THE LEVELS
COME DOWN BUT DON'T GO BACK TO
BASELINE.
THEY REMAIN HIGH.
>>THIS COULD BE DONE IN CUL
DOOR.
-- IN CULTURE.
>>I'M SURE DR. KILEY IS LOOKING
FORWARD TO IT.
DOES ANYBODY ELSE HAVE A
QUESTION?
I'M NOT SEEING HANDS RAISED.
DR. GIBBONS -- SORRY, YOU'RE NOT
ALLOWED TO ASK QUESTIONS.
>>NICE WORK, SEAN.
CAN OUT PUT IN CONTEXT WHAT
YOU'RE DOING WITH THE PROFILES
ALMOST RELATED TO DAVID'S POINT.
IF YOU HAVE CELL-FREE DNA I HEAR
ABOUT PAMPS AND NETS.
ARE WE GETTING TO A POINT ARE WE
CAN PROFILE THESE OR WE LOOK AT
THROUGH A MICROSCOPE TO WHO IS
DOING WHAT AND WHAT STAGE OF THE
INJURY IS OVER?
YOU'RE SPOT ON.
THE CELL-FREE DNA IS ALSO
DAMAGE-ASSOCIATED MOLECULAR
PATHWAY.
IT'S NOT JUST A BIOMARKER, IT'S
DIRECTLY INVOLVED IN THE
PATHOGENESIS OF DISEASE.
I DID NOT SHOW THAT WORK.
THAT'S NUMBER ONE.
NUMBER TWO, THE PROFILE TELLS
YOU ONCOMING DISEASES.
IF YOU LOOK AT TRANSPLANTS, TWO
FOUR MONTHS BEFORE THE BIOPSY
WHICH SHOWS SIGN OF REJECTION IS
IT IN TRANSPLANT NOW?
IF YOU LOOK AT IT WITH PATIENTS
WITH COVID WE TAKE THE SAMPLES
AT THE TIME OF ADMISSION ASKING
THE QUESTION, WHICH PATIENTS
WILL GET P.E.
WHICH PATIENTS WILL DEVELOP
CARDIOVASCULAR MYOPATHY.
YOU START SEEING EARLY
INDICATIONS OF THE BIOMARKER
WHERE THE CHEMICAL MARKERS GO
OFF.
WE DON'T HAVE ENOUGH DATA TO
ANSWER YOUR QUESTION BUT THE
DATA FROM TRANSPLANT AND THOSE
FROM COVID AND HYPERTENSION
INDICATE THE PROFILES ARE
CLINICALLY RELEVANT AND EARLY
INDICATORS OF SOMETHING BAD THAT
IS GOING TO HAPPEN WITH THE
PATIENTS.
>>WE LOOKED AT A COHORT OF
PATIENTS WITH MULTI-SYSTEMIC
INFLAMMATORY DISEASE IN
CHILDREN.
THIS IS A SYNDROME THAT DEVELOPS
X NUMBER OF WEEKS AFTER COVID.
A TEAM HAS CHARACTERIZED THE
PATIENTS IN ADDITION TO CLINICAL
DATA AND IMMUNOLOGY PHENOTYPE
THEY COLLECTED PLASMA SAMPLES
SERIALLY WE MEASURED THE
CELL-FREE DNA POST MISC.
IN SOME PATIENT THE LEVEL COMES
UP.
NOT FOR ALL.
WHAT IT MEANS, I DON'T KNOW YET
BECAUSE WE'RE STILL LOOKING INTO
THE DATA AND X NUMBER OF MONTHS
AFTER COVID OR TREATING FOR
REJECTION OR AFTER PICK YOUR
DISEASE.
NOW WE ARE LOOKING TO SEE WHAT
ARE THE CLINICAL CORRELATES THE
CELL-FREE DNA IN THESE PATIENTS,
DO THEY HAVE LONG COVID.
AND IN THE INTRAMURAL WE HAVE A
COHORT OF PATIENTS WITH LONG
COVID.
WE LOOKED AT THE TOTAL CELL-FREE
DNA AND IT'S BACK TO BASELINE AS
HEALTHY CONTROLS.
WE'RE LOOKING AT THE TISSUE
TYPES THOUGH THE TOTAL CELL-FREE
DNA AS AN INDICATION OF GLOBAL
INJURY IS WITHIN RANGE WHERE THE
CELL-FREE RANGE FROM THE NEURONS
AND HEART OR FROM THE DIFFERENT
TISSUE TYPES ARE BACK TO
BASELINE.
WE WOULD BE ABLE TO ANSWER THAT
QUESTION.
>>OKAY.
IT LOOKS LIKE WE COVERED
EVERYTHING.
THERE WAS A WONDERFUL COMMENT IN
THE CHAT.
WE'RE ALREADY LATE SO GO AHEAD.
>>THE CELL-FREE DNA GRADUALLY
GOES UP.
DO WE KNOW WHEN TO INTERVENE AND
DOES IT MAKE A DIFFERENCE IN THE
PROGRESSION OF NATURAL DISEASE?
>>I DON'T HAVE THE ANSWER YET.
THAT'S WHERE I'M TRYING TO
CONVINCE DR. GIBBONS THAT WE'RE
READY TO GO THERE AND NEED
INFRASTRUCTURE AND RESOURCES TO
MOVE THERE.
THAT'S EXACTLY THE QUESTION AND
THE CELL-FREE DNA LEVEL IS
RISING.
SHOULD WE INTERVENE?
COULD WE INTERVENE OR WOULD THAT
MAKE A DIFFERENCE?
WE WOULD BE ABLE TO ANSWER THAT
QUESTION.
YOU TALK TO DR. GIBBONS AND
DR. CHARLES.
HE IS NOT HERE.
HE WAS HERE ALREADY.
>>SINCE WE'RE ALREADY LATE, IS
THERE UTILITY OF THE HOST AND
DONOR TRANSPLANT AND REFLECT THE
HOST IMMUNE RESPONSE AND THE
OTHER THE ORGAN.
AND THE HOST RESPONDS TO THE
ALLOGRAFT AND THE HOST RESPONDS
AND THE HOST RESPONSE PREDICTS
WHAT WILL HAPPEN IN THE
ALLOGRAFT AND EVEN BEFORE
TRANSPLANT THE HOST-DERIVED
CELL-FREE DNA LEVELS GOES UP
PREDOMINANTLY FROM INNATE IMMUNE
CELLS.
THE INNATE IMMUNE CELLS
CELL-FREE DNA PREDICT SURVIVAL
OF THE ALLOGRAFT.
THERE'S SOMETHING ABOUT WHAT THE
HOST DOES THAT INFLUENCES THE
LONGEVITY, WHICH WE EXPECT.
BUT THE COUNTERPART IS IF YOU
LOOK AT ORGANS WITHIN THE HOST,
THE KIDNEY, THE LIVER, THESE
ORGANS ALSO TAKE A HIT IN THE
LUNG TRANSPLANTATION AND GO TO
DYSFUNCTION.
IT COULD BE JUST DUE TO DRUGS.
THERE'S INHIBITORS THAT CAN DO
THIS BUT WE HAVE WORK SHOWING
INCREASING CELL-FREE DNA IN
BLOOD WILL TRIGGER MITOCHONDRIAL
PRODUCTION LEADING TO CELL
DEATH.
THE CELL-FREE DNA IS NOT JUST
THERE BUT CAUSING DAMAGE NOT
ONLY TO THE ALLOGRAFT BUT ALSO
TO THE RECIPIENT'S ORGAN AS
WELL.
THERE'S AN INTERRUPTION AT THE
MOLECULAR LEVEL BETWEEN THE
ALLOGRAFT AND HOST.
WE'RE TRYING TO FIGURE OUT WHAT
IT MEANS CLINICALLY.
>>THANK YOU TO TINA AND WE HAVE
TO MOVE ON.
THANK YOU FOR YOUR
THOUGHT-PROVOKING TALK.
WE FINALLY HAVE GOTTEN TO THE
POINT IN OUR SYSTEM OUR PLANS
FOR TODAY WHERE WE'RE GOING TO
MOVE TO OUR FINAL AGENDA ITEM.
THAT DOESN'T MEAN IT'S GOING
TOCK QUICK BUT THAT'S OKAY.
IT'S IMPORTANT.
WE'LL VOTE ON THE CONCEPTS.
SO BEFORE WE PROCEED, WE HAVE A
FEW REMINDERS.
IF YOU HAVE COMMENTS RELATED TO
THE CONCEPTS YOU SHOULD ADDRESS
ALL THE PANELISTS.
DON'T ADDRESS THE HOST OF THE
MEETING.
IF YOU'RE ENCOUNTERING ZOOM
TECHNICAL ISSUES CONTACT THE I
TECH STAFF.
THEY CAN'T HELP WITH DECISION
LENS ONLY YOUR LAPTOP AND I
THINK WE FIGURED THAT OUT BY NOW
AFTER ALL THE FUN TODAY.
FOR TECHNICAL ISSUES FORWARD
THOSE ISSUES TO THE DL
REPRESENTATIVES BRIAN GLEESON AT
REAL TIME TECH SUPPORT AND LAURA
SANG WILL PROVIDE BACK UP AND
YOU CAN PUT THAT IN THE CHAT AND
HOPEFULLY WE'LL GET GOING.
FIRST THING'S FIRST.
THE REFRESHER TRAINING.
BRIAN.
>>GOOD AFTERNOON.
I'M PAT QUIN.
WE HAD A CHANGE.
I'M REPLACING BRIAN.
THANK YOU FOR HAVING US SUPPORT
THE EVENT.
I'LL GIVE A BRIEF OVERVIEW OF
DECISION LENS.
THANKFULLY ALL OUR PANELISTS
HAVE USED IT BEFORE.
HERE AGAIN, TO GET STARTED
WITHIN THE LAST HOUR OR SO, YOU
SHOULD HAVE RECEIVED AN EMAIL,
TO RATE ALTERNATIVES AND SHOULD
COME FROM ADMINISTRATOR AT
DECISION LENS.com.
IF YOU OPEN THE E-MAIL AND CLICK
THE GET STARTED BUTTON IT THE
TAKE YOU TO DECISION LENS AND WE
CAN BEGIN THE VOTING THROUGH
THAT.
IF YOU LOGGED IN DIRECTLY YOU'LL
COME TO THE PAGE.
IF YOU LOG IN THROUGH THE LINK
SENT OUT YOU'LL COME IN HERE.
YOU CAN CLICK THAT ALTERNATIVES
TASK TO OPEN THIS UP.
IF YOU LOG IN YOU'LL SEE A FEW
THINGS.
THE BOTTOM HALF OF THE PAGE
YOU'LL SEE THE LIST OF THE
CONCEPTS BEING REVIEWED TODAY.
AND THEN UP HERE AT THE TOP
YOU'LL SEE THIS ORANGE ACTION
START READING ALTERNATIVES
BUTTON.
TO GET STARTED YOU CAN CLICK
THAT.
THIS IS GOING TO BRING YOU INTO
THE VOTING MODULE.
YOU HAVE THIS SELF-GUIDED TOUR.
YOU CAN READ IT OR CLOSE IT OUT.
IT'S UP TO YOU.
HERE YOU'LL SEE THE NAME OF THE
CONCEPT AND IF YOU CLICK ON THE
BLUE TEXT ON THE SIDE YOU'LL GET
MORE INFORMATION ON IT.
OBVIOUSLY THIS IS ALL GOING TO
BE BRIEF.
I DON'T THINK THIS IS ENTIRELY
NECESSARY FOR YOU BUT THERE IF
YOU NEED TO ACCESS IT.
AND BELOW THAT WE HAVE THE AREA
WHERE YOU MAKE THE RATING ON THE
CONCEPTS.
YOU'LL SEE IN THE PURPLE TEXT
THAT'S THE CRITERIA YOU'RE
EVALUATING THE CONTEXT AGAIN.
IN THIS CASE IT'S IMPORTANT FOR
THE ISSUE OR OPPORTUNITY AND
BELOW THAT IN THE BLACK REGULAR
TEXTUAL SEE A MORE DETAILED
DESCRIPTION SO IF YOU NEED MORE
CLARITY ON WHAT YOU ARE
EVALUATING THE CONCEPT AGAINST
YOU'LL SEE THAT AND SOMETIMES IF
IT'S A LONGER DESCRIPTION YOU'LL
CLICK MORE AND GET MORE
INFORMATION.
YOU CAN ALSO CLICK ON THE PURPLE
TEXT AND GET A MORE DETAILED
DESCRIPTION OF THE RATING SCALE.
WHAT IS MEANT BY IMPORTANT OR
MODERATELY IMPORTANT AS WELL AND
THAT'S ON THE PURPLE TEXT.
IN ORDER TO MAKE YOUR RATING,
SELECT THE ONE YOU BELIEVE BEST
FITS THE RESPONSE AND ONCE IT'S
HIGHLIGHTED IN GREEN YOU CAN
CLICK THAT AND NOW YOU'RE ON TO
THE NEXT CRITERIA.
YOU'RE STILL IN THE SAME
ALTERNATIVE UNTIL YOU'VE GOP
THROUGH ALL OF THEM.
YOU CAN USE MULE VIEW WHERE YOU
SEE THE ONE ALTERNATIVE AND ONE
CONCEPT AND ALL THE CRITERIA
YOU'RE EVALUATING IT AGAINST.
I'LL SWITCH THAT NOW AND YOU CAN
SEE WHAT THAT LOOKS LIKE AND I
RECOMMEND USING THAT FORMAT
INSTEAD.
YOU HAVE IN THE BLUE TEXT THE
CONTEXT YOU'RE EVALUATING AND
THEN NOW SINCE I'M DOING THIS IN
MULTIVIEW IT'S EASIER TO KEEP
TRAM OF WHAT YOU'RE DOING.
I'LL WALK THROUGH ALL THE
SELECTIONS.
AND FOR THE ORANGE NEXT BUTTON
IS NOW HIGHLIGHTED AND CLICK
NEXT AND NOW I'M ON THE SECOND
CONCEPT FOR THE DAY AND HAVE A
CLEAN SLATE ON ALL THOSE.
THAT'S AN OPTION TO GO AHEAD AND
USE THAT.
IF YOU WANT TO PROVIDE MORE
CONTEXT ON YOUR ANSWERS, I KNOW
WE LIKE TO MAKE USE OF THE
COMMENTS FEATURE, SO IF YOU WANT
TO MAKE A COMMENT IT'S ASSIGNED
FOR THE CONCEPT AND CRITERIA
LEVEL.
IF I WANTED TO LEAVE A COMMENT
ON 3891 I CAN MAKE A SELECTION
OR FOR MORE NUANCE I CAN GO TO
THE SPEECH BUBBLE TO GO TO VIEW
COMMENTS AND CLICK ON THAT AND
LEAVE MY COMMENT RIGHT THERE IN
A FREE-TEXT COMMENT AND ASSIGN
IT A CATEGORY OR INTENSITY
OPTION IF YOU HAVE ADDITIONAL
CATEGORIZATIONS YOU CAN DO THE
STRENGTH OR WEAKNESS OF IT OR
CHOOSE THE INTENSITY.
YOU'LL SEE IN THE UPPER RIGHT
HAND CORNER WE HAVE THE OVER ALL
PROGRESS.
IT WILL SHOW YOU EVERY CLICK YOU
HAVE TO MAKE.
THE SIXTH CRITERIA THE CONCEPTS
THROUGHOUT THE DAY.
EACH CLICK YOU MAKE YOU'LL SEE
IT INCREASES ALONG THE WAY.
THAT SHOULD LET YOU KNOW WHEN
YOU'RE 100% DONE AT THAT POINT.
ONCE YOU COMPLETED YOUR RATINGS
YOU'LL GET A POP UP THAT SAYS
YOU COMPLETED AND YOU CAN SEE
HOW YOU EVALUATE THE CONCEPTS.
THAT IS NOT THE FINAL RATING
JUST YOUR INDIVIDUAL ONES.
THE FINAL ONES ARE THE AGGREGATE
OF ALL THE VOTERS.
AND CLOSE OUT OF THE MODULE AT
THE TIME.
SO ANY PROGRESS YOU MAKE OR HAVE
AN INTERNET DISRUPTION THERE'S
IT'S ALL CAPTURED ALONG THE WAY.
WE'LL BE MONITORING PROGRESS AND
IF YOU EXCELLENTLY SKIP
SOMETHING WE'LL GO AHEAD AND TAP
YOU ON THE SHOULDER AND HELP YOU
WITH THAT AND FOR THOSE NOT IN
THE ROOM YOU CAN REACH US OVER
THE CHAT.
MY NAME IS PAT AND LAURA WILL
PUT OUR E-MAIL ADDRESSES IN
THERE IF SHE HAS NOT ALREADY.
BARRING ANY QUESTIONS, THAT'S
ALL I HAVE.
THANK YOU FOR HAVING US TODAY
AND IF YOU NEED ANYTHING WE'LL
BE IN THE BACK OF THE ROOM.
>>GOOD AFTERNOON, EVERYONE.
HAPPY IT SEE EVERYBODY.
-- HAPPY TO SEE EVERYBODY --
[ECHOING]
>>THERE'S SOME GREMLIN IN THE
ROOM TODAY FOR ECHOING.
>>THAT'S ALWAYS LIVELY.
WE'LL GO AHEAD AND GET STARTED.
IF YOU HAVE A PROBLEM REACH OUT
TO BRIAN OR LAURA IN THE ROOM
AND PAT IS AVAILABLE ONLINE.
THOSE ARE YOUR CONTACTS.
>>TO CONFIRM -- YOU DON'T NEED
TO JOIN.
>>YOU DON'T NEED TO.
>>GOOD AFTERNOON.
THERE'S THREE INITIATIVES FOR
YOUR CONSIDERATION.
THE FIRST ONE IS CONCEPT NUMBER
3890.
THIS IS A SHORT TERM EDUCATION
PROGRAM TO ENHANCE DIVERSITY IN
HEALTH-RELATED RESEARCH.
A REISSUE OF THE HFRH1002 AND
ENHANCING DIFFERS IF I IN THE
WORKFORCE IS CRITICAL TO THE
SUCCESS OF OUR NHLBI MISSION.
THE PURPOSE OF THIS SPECIFIC
MISSION IS TO SUPPORT
EDUCATIONAL ACTIVITIES THAT
ENHANCE THE DIVERSITY OF THE
WORKFORCE PROVIDING RESEARCH
EXPERIENCES AND RELATED
OPPORTUNITIES THAT CAN ENRICH
THE POOL OF INDIVIDUALS FROM
DIVERSE BACKGROUNDS INCLUDING
NATIONALLY UNDER REPRESENTED
GROUPS FOR RESEARCH TURNS AND TO
ENCOURAGE UNDERGRADUATE AND
COLLEGE STUDENTS AND HIGH SCHOOL
STUDENTS IN BIO MEDICAL AND
BEHAVIORAL SCIENCE AND EXPOSE
THEM TO RESEARCH TRAINING
OPPORTUNITIES IN OUR MISSION
AREA.
IN PARTICULAR, EMPHASIS ON
PROVIDING HANDS-ON EXPOSURE TO
RESEARCH ENFORCE TO GRADUATE
WITH A SCIENCE DEGREE AND
PREPARE THEM FOR CAREERS IN
RESEARCH.
THIS FUNDING ANNOUNCEMENT WILL
BE AN R25 FUNDING MECHANISM AND
CLINICAL TRIALS ARE NOT ALLOWED
AND SUPPORT NINE MERITORIOUS
AWARDS EACH YEAR EACH LASTING
FIVE YEARS.
I'LL STOP HERE TO SEE IF THERE'S
COMMENTS, SUGGESTIONS OR
QUESTIONS.
IF NOT PLEASE CAST YOUR VOTE.
>>WE'RE JUST WAITING ON A FEW
MORE.
OKAY.
WE CAN MOVE ON TO THE NEXT
INITIATIVE.
>>THANK YOU.
THE SECOND INITIATIVE IS NUMBER
3891.
A SECOND IN MULTI-SECTORIAL
PREVENTION INTERVENTIONS THAT
ADDRESS SOCIAL DETERMINATES OF
HEALTH IN POPULATIONS THAT
EXPERIENCE HEALTH DISPARITIES.
IT USES THE
UG3, UH3 MECHANISM.
THE NHLBI-WIDE INITIATIVE PART
OF OUR NIH EFFORT LED BY THE NIH
OFFICE OF DISEASE PREVENTION,
ODP AS KNOWN AS ADVANCED AND
STANDS BY ADVANCING PREVENTION
RESEARCH FOR HEALTH EQUITY.
THE ORIGIN OF THIS INITIATIVE IS
AN NIH-WIDE PORTFOLIO ANALYSIS
CONDUCTED BY ODP THAT SHOWED
THAT LESS THAN 10% OF ALL FUNDED
PROJECTS FOCUSSED ON THE LEADING
RISK FACTORS OR CAUSES OF DEATH
AND DISABILITY.
MANY OF WHICH FALL IN THE NHLBI
MISSION AREAS.
BETWEEN 2012 AND 2020, ONLY
ABOUT 4% OF PROJECTS FOCUSSED ON
COMMUNITIES FACING HEALTH
DISPARITIES AND MORTALITY AND
THE EMPHASIS IS MOVING BEYOND
JUST ADDRESSING KNOWLEDGE
ATTITUDES, AWARENESS, BEHAVIORS
AND LIFE STYLES OF INDIVIDUALS
TO GO INTO SUPPORTING
INTERVENTION RESEARCH USING
MULTI-SECTORIAL COLLABORATIONS
THAT ENGAGE COMMUNITY-BASED
ORGANIZATIONS THAT HAVE THE
POTENTIAL TO DEVELOP, IMPLEMENT
AND TO SUSTAIN PREVENTION
INTERVENTIONS IN THEIR
COMMUNITIES AND ADDRESS RELEVANT
SOCIAL DETERMINATES OF HEALTH
AND PROMOTE HEALTH EQUITY.
THESE RESEARCH PROJECTS WILL BE
PART OF THE NIH MULTISECTORIAL
INTERVENTION, RESEARCH NETWORK.
RESPONSIVE APPLICATIONS
INCLUDING MULTI-SECTORIAL
PARTNERSHIPS AND BETTER HELP
UNDERSTAND THE INNOVATION
MECHANISMS AND CONTRIBUTE TO
HEALTH OUTCOMES AND IMPORTANTLY
THERE MUST BE A FOCUS ON HEALTH
EQUITY IN THE COMMUNITIES FACING
HEALTH DISPARITIES.
THIS FUNDING OPPORTUNITY
ANNOUNCEMENT COOPERATIVE
AGREEMENT MECHANISM.
IMPORTANTLY, EACH PARTICIPATING
I.C. WILL BE EXPECTED TO FUND AT
LEAST ONE MERITORIOUS AWARDTOWN
THE MISSION AREA AND USING THE
PAY LINE APPROACH AND MANAGED BY
A COORDINATING CENTER FULLY
FUNDED BY THE OFFICE OF DISEASE
PREVENTION AND MANAGED BY OTHER
I.C.
AT THE MOMENT THERE'S ABOUT
SEVEN I.C.s THAT SIGNED ON TO
PARTICIPATE.
I'LL PAUSE TO SEE IF YOU HAVE
ANY COMMENTS OR QUESTIONS.
>>QUICK QUESTION.
IS PCORI INVOLVED?
>>THE REAL DISTINCTION IS TO GO
BEYOND THAT AND ENGAGED
COMMUNITY-BASED ORGANIZATIONS SO
THERE'S FOCUS IN THE
COMMUNITIES.
>>THANKS.
IF THERE'S NO COMMENTS OR
SUGGESTIONS, YOU CAN GO AHEAD
AND CAST YOUR VOTE, PLEASE.
>>WE'RE JUST WAITING ON ONE.
>>WE'RE READY TO MOVE ON.
>>THANK YOU.
THE LAST INITIATIVE IS CONCEPT
NUMBER 3916.
THIS IS A SECONDARY
PARTICIPATION IN THE FOGARTY
INTERNATIONAL TRAINING PROGRAM
FOR LOW AND MIDDLE INCOME
PAR22-151.
THIS IS AN NHLBI WIDE INITIATIVE
AND SUPPORTS A BROAD RANGE OF
THEMES FROM BASIC BIOMEDICAL
RESEARCH TO IMPLEMENTATION
SCIENCE.
IMPORTANTLY, IT IS DESIGN TO
LEVERAGE THE HIV/AIDS INVESTMENT
AND CAPACITY BUILT BY OTHER
FUNDERS BY, FOR EXAMPLE, NIAID,
THE U.S. AID, PEP FAR AND OTHER
PROGRAMS AND TO LEVERAGE THE
CAPACITY AND INFRASTRUCTURES FOR
TRAINING IN-COUNTRY EXPERTS ON
THE SCIENCE OF HEART, LUNG,
BLOOD AND SLEEP COMORBIDITIES IN
PEOPLE LIVING WITH HIV.
THE PROGRAM AIMS TO STRENGTHEN
THE CAPACITY OF LOW AND
MIDDLE-INCOME COUNTRY
INSTITUTIONS FOR HEART, LUNG,
BLOOD AND SLEEP COMORBIDITIES IN
HOME COUNTRIES.
IT'S ESTIMATE THE 30 TO 40
MILLION PEOPLE LIVING WITH HIV
AID LIVING LONGER AND LIVING AND
ELEVATED RISK FOR BLOOD AND
COMORBIDITIES.
THE RESEARCH NHLBI HAS FUNDED
SUCH AS THE REPRIEVE TRIAL HAS
SHOWN PARTICIPANTS ASSIGNED A
STATIN HAVE A 35% REDUCED RISK
FOR MAJOR ADVERSE CARDIOVASCULAR
EVENTS COMPARED TO THOSE ON
PLACEBO.
THE TIME IS REALLY RIGHT TO
TRAIN AND GROW THE NEXT
GENERATION OF LOW AND MIDDLE
INCOME COUNTRIES TO ADVANCE
HEART, LUNG, BLOOD AND SLEEP
RESEARCH.
THIS USE THE D43 FUNDING
MECHANISM AND UP TO FIVE-YEAR
INTERNATIONAL TRAINING GRANT
SIMILAR TO THE U.S.-BASED T32
STRUCTURE.
IMPORTANTLY, APPLICATIONS CAN BE
SUBMITTED BY AN ELIGIBLE, LOW OR
MIDDLE INCOME INSTITUTION OR
DOMESTIC U.S. INSTITUTION THAT
DEMONSTRATE COLLABORATION WITH A
LOW OR MIDDLE-INCOME COUNTRY.
I'LL STOP AND TAKE QUESTIONS OR
COMMENTS.
PLEASE CONTINUE THE VOTES,
PLEASE.
>>I'LL GIVE ANOTHER FEW
SECONDS.
>>WE'RE READY TO MOVE ON.
>>THANK YOU VERY MUCH.
WE'RE DONE WITH OUR
PRESENTATIONS AND I'LL TURN IT
OVER TO DR. GOTH FROM THE
DIVISION OF CARDIOVASCULAR
SCIENCE.
DAVID.
>>THANK YOU ALL.
OKAY.
SO WITH HAVE EYE NUMBER OF
CONCEPT TO BRING TO YOUR
ATTENTION, IDEAS NUMBERS 3872
AND 3873.
I'LL PRESENT THEM TOGETHER BUT
YOU WILL NEED TO RATE THEM
INDIVIDUALLY IN THE SYSTEM.
THESE ARE A DATA COORDINATING
CENTER AND CLINICAL TRIAL
CENTERS FOR CARDIOVASCULAR RISK
REDUCTION IN TYPE 1 DIABETES
CLINICAL TRIALS REQUIRED.
THE LEAD AUTHOR IS NICOLE REDMAN
I HOPE IS IN ZOOM LAND IN CASE
QUESTIONS COME UP.
NIDDK IS THE LEAD INSTITUTE FOR
THE SPECIAL STATUTORY FUNDING
PROGRAM FOR TYPE 1 DIABETES
RESEARCH PREFERRED TO AS SPECIAL
DIABETES PROGRAM A SPECIAL
APPROPRIATION FOR RESEARCH ON
THE PREVENTION AND CURE OF TYPE
1 DIABETES AND ITS
COMPLICATIONS.
AS YOU ALL KNOW, THERE'S RISK
FACTORS SUCH AS OBESITY OR
INFLAMMATION IN ADOLESCENTS AND
YOUNG ADULTHOOD.
THE EVENT RATES APPROXIMATE THE
EVENT RATES FOR CARDIOVASCULAR
DISEASE FOR ADULTS WITHOUT TYPE
1 DIABETES WHO ARE 10 TO 20
YEARS OLDER.
DESPITE THE HIGH RISK STATUS
THERE'S SIGNIFICANT EVIDENCE
GAPS THE OBSTACLES TO THE
DEVELOPMENT AND IMPLEMENTATION
OF GUIDELINE RECOMMENDATIONS FOR
INITIATION FOR PHARMACO THERAPY
AND RISK FACTORS IN PEDIATRIC
AND YOUNG ADULT TYPE 1 DIABETES
POPULATIONS.
SO IN AN EFFORT TO ADDRESS THIS
EVIDENCE GAP, THIS INITIATIVE
WOULD USE A PHASED AWARD
MECHANISM TO TEST APPROACHES TO
REDUCE CARDIOVASCULAR RISK IN
TYPE 1 DIABETES.
THE APPROACH OF USING THE PHASED
AWARD MECHANISM ALLOWS
FLEXIBILITIES TO MAKE DECISIONS
NOT TO TRANSITION TO THE SECOND
PHASE OF AWARD IF AN AWARD
DEMONSTRATES IT CANNOT
SUCCESSFULLY RECRUIT
PARTICIPANTS OR MEET OTHER
STUDIES THUS REDUCING THE OVER
ALL RISK TO THE INSTITUTE.
THIS INITIATIVE WOULD SIGNAL TO
THE EXTRAMURAL COMMUNITY THE
IMPORTANCE OF THE AREA OF
RESEARCH AND MAY STIMULATE
ADDITIONAL RESEARCH INCLUDING
RO1 STUDIES AND CAREER
DEVELOPMENT TRAINING AWARDS
INCLUDING SUPPLEMENT.
WE ANTICIPATE THE OPPORTUNITY
WILL CONTINUE OUR PARTNERSHIP
WITH NIDDK AND EXPAND THE
PORTFOLIO IN CARDIOVASCULAR
DISEASE.
I'LL BE HAPPY TO STOP AND
ENTERTAIN QUESTIONS ABOUT THE
TWO RELATED CONCEPTS OR
INITIATIVES.
WE CAN MOVE ON TO RATING.
>>JUST A REMINDER, YOU'RE GOING
TO BE VOTING ON 3872 AS WELL AS
3873, PLEASE.
>>WE CAN MOVE ON TO THE NEXT
CONCEPT.
>>THANK YOU.
THE NEXT CONCEPT IS NUMBER 3893.
THIS IS A RENEWAL BY CONTRACT OF
THE MULTIETHNIC STUDY OF
ATHEROSCLEROSIS AND THE AUTHOR
IS IN THE ROOM IN CASE THERE'S
QUESTIONS.
I PROPOSES RENEWAL OF THE FOLLOW
COMPONENT AND INFRASTRUCTURE OF
THE STUDY COHORT.
THE ORIGINAL COHORT CONSISTED OF
6,814 MEN AND WOMEN AGES 45 TO
84 AT BASELINE FROM FOUR ETHNIC
GROUPS, WHITES, BLACKS,
HISPANICS AND CHINESE AMERICANS
FREE OF CLINICAL CARDIOVASCULAR
DISEASE AT BASELINE.
SIX FIELD CENTERS ENROLLED
PARTICIPANTS AND NOW CONDUCTED A
SERIES OF LONGITUDINAL EXAMS
FOCUSSING ON HEALTH OUTCOMES
BEYOND CARDIOVASCULAR DISEASE.
THE RENEWAL OF CONTRACT SUPPORT
WOULD ALLOW THE STUDY TO
CONTINUE TO MAINTAIN REGULAR
CONTACT WITH STUDY PARTICIPANT
TO IDENTIFY AND ADJUDICATE
EVENTS AND MANAGE, STORE
BIOLOGIC DATA SPECIMENS TO SERVE
AS A PLATFORM FOR STUDIES AND
PROVIDE SUPPORT FOR A CORE
EXAMINATION COMPONENTS AND ALLOW
FOLLOW-UP AS THEY APPROACH A
PERIOD IN OLDER ADULTHOODS WHERE
CLINICAL EVENTS WILL ALMOST MORE
COMMON AND STUDY SUCCESSFUL
PULMONARY AGING AND STUDY HEART,
LUNG AND BLOOD AND SLEEPING
PROGRESSION AND DISCOVERY
SCIENCE AND ADDRESS QUESTIONS
AND BETTER UNDERSTAND THE
REASONS FOR RACIAL DISPARITIES
ACROSS THESE GROUPS.
HAPPY IT TAKE QUESTIONS AT THIS
POINT.
I DON'T SEE HANDS UP.
DO YOU SEE ANYTHING IN THE ZOOM
ROOM?
>>NOTHING'S CHANGED IN THE CHAT
SO WE LOOK GOOD.
>>THANK YOU.
I THINK WE CAN GO TO RATINGS.
THERE'S ONE OF KEY 13 NHLBI
STUDIES ADVANCING LUNG RESEARCH.
>>WE'RE READY TO MOVE ON.
>>ALL RIGHT.
THANK YOU.
THE NEXT CONCEPT IS IDS NUMBER
3902 UNDERSTANDING CHRONIC
CONDITIONS UNDER STUDIED AMONG
WOMEN R01 MECHANISM, CLINICAL
TRIAL OPTIONAL.
WE WOULD BE SECONDARY
PARTICIPANTS IN THE FUNDING
OPPORTUNITY LED BY THE OFFICE OF
RESEARCH ON WOMEN'S HEALTH AND
YES, THE LEAD AUTHOR IS IN THE
ZOOM ROOM.
THE OVERARCHING GOAL OF THIS
FUNDING OPPORTUNITY IS TO USE
RO1 MECHANISM TO STIMULATE
RESEARCH ADDRESSING RISING RATES
OF CHRONIC DEBILITATING
CONDITIONS IN WOMEN AND
OPPORTUNITIES IDENTIFIED AT THE
CONGRESSIONALLY REQUESTED
FUNDING ADVANCE ON WOMEN'S
HEALTH A 2021 CONFERENCE.
COMPARED TO MEN, WOMEN HAVE
HIGHER PREFERENCE OF CHRONIC
CONDITIONS OFTEN PRESENT WITH
DIFFERENT SYMPTOMS LIKE
DIZZINESS, CHEST PAIN WITH
CARDIOVASCULAR DISEASE ARE
AFFECTED BY DIFFERENT CHRONIC
CONDITIONS AND AUTOIMMUNITY
DISEASE AND MULTI-MORBIDITY AT
DIFFERENT LIFE COURSE TIME
POINTS.
PARTICIPA
PARTICIPATION IN THIS RFA WOULD
ADDRESS THE SIGNIFICANT IMPACT
OF HEART, LUNG, BLOOD AND SLEEP
RELATED DISEASES ON WOMEN'S
HEALTH ACROSS THE LIFE SPAN AND
FACILITATE DEVELOPMENT OF
RELEVANT PREVENTIVE DIAGNOSTIC
AND THERAPEUTIC APPROACHES AND
THERE'S HIGHER PREVALENCE OF
DISEASES OF WOMEN HISTORICALLY
UNDER STUDIED AND UNDER
REPRESENTED IN BIOMEDICAL
RESEARCH AND PARTICIPATION
ALIGNS WITH THE ONGOING
COMMITMENT TO ADDRESS THE
DISPARITIES AND IMPROVE OUTCOMES
FOR HEART, LUNG, BLOOD AND SLEEP
DISORDERS IN ALL WOMEN.
I'D BE HAPPY TO TAKE QUESTIONS
AT THIS POINT.
THIS IS INITIATIVE 3902.
YOU CAN GO TO RATING.
>>YOU CAN MOVE ON TO THE NEXT
CONCEPT.
>>ALL RIGHT.
BEFORE I GET INTO THE NEXT ONE I
WANT TO MENTION THE NEXT TWO
CONCEPTS ARE RELATED TO THE
RESOURCES WE PROVIDE TO SUPPORT
RESEARCH-RELATED TO GENE THERAPY
AND WHILE WE'RE GOING TO BE
ASKING TO YOU COMMENT ON EACH OF
THESE SEPARATELY, WE'D ALSO BE
INTERESTED IN ANYTHING YOU MIGHT
HAVE TO SHARE WITH US ABOUT THE
WAY WE SUPPORT GENETIC THERAPY
RESEARCH IN GENERAL BEYOND
WHAT'S IN THESE PROPOSALS AND
PERHAPS AFTER WE DISCUSS EACH OF
THESE WE MAY HAVE A LITTLE BIT
OF OPEN TIME TO DISCUSS GENE
THERAPY SUPPORT MORE BROADLY.
THE FIRST ONE IS IDS NUMBER 389
THE NATIONAL GENE VECTOR BIO
REPOSITORY CONTRACT RENEWAL.
THE AUTHOR IS RAY EBERT AND
SEEKS RENEWAL FOR THE REPOSITORY
KNOWN AS THE HCBB AND ORIGINS
CAN BE TRACED IN THE 1990s AND
THE FIRST FDA APPROVED GENE
THERAPY TRIAL BY INTRAMURAL
INVESTIGATORS FROM NHLBI AND NCI
TO TREAT ADA SKID AND THEY HAVE
CLINICAL INVESTIGATORS IN FIVE
AREAS.
FIRST, BY MAKING AVAILABLE OVER
70 RE-AGENTS, PLASMIDS,
RETROVIRAL PACKAGING FOR
CONSTRUCTING GENE-THERAPY
VECTORS AND PROVIDING STORING OF
SAMPLES.
THIRD, BY PERFORMING REPLICATION
COMPETENCY ASSAYS AND ANALYSIS
FOR PARTICIPANTS SICKLE CELL AND
OTHER STUDIES AND FIFTH BY
DEVELOPING NEW INTEGRATION
CYTOANALYSIS METHODS EXPECTED TO
BE NIGEEDED IN THE FUTURE.
A WELL ESTABLISHED FUTURE IS THE
PROGRAM'S TRACK RECORD OF
PROACTIVELY ANTICIPATING THE
NEEDS OF INVESTIGATORS OVER THE
PAST 15 YEARS.
A FEATURE THAT LEAD TO TIMELY
DELIVERY OF TOOLS AND
CAPABILITIES TO THE GENE THERAPY
INVESTIGATIVE COMMUNITY.
APPROVAL WOULD ENABLE MGBB TO
CONTINUE OPERATING AS A
COST-EFFECTIVE CENTER OF GENE
THERAPY EXCELLENCE FOR OUR
INSTITUTE.
HAPPY TO ENTERTAIN QUESTIONS AND
COMMENTS AT THIS TIME.
IS IT INSTITUTE SPECIFIC OR MORE
BROADLY?
>>IT'S USED MORE BROADLY.
RAY, IF YOU'RE OUT THERE AND
HAVE STATS IN YOUR BACK POCKET
THAT'D BE GREAT BUT MY
UNDERSTANDING IS IT'S USED MORE
BROADLY THAN NHLBI.
>>YES, THIS IS RAY.
THE VAST MAJORITY OF
BENEFICIARIES ARE NHLBI-FUNDED.
BUT IT IS AVAILABLE TO OTHER
INSTITUTES ON REQUEST.
WE CAN USUALLY WORK OUT
ARRANGEMENTS.
WE HAVE CLOSE COLLABORATION WITH
NCI AND THEY FUNDED THE WORK OB
THEIR OWN.
IT'S GENERALLY INSTITUTE WIDE.
THANK YOU FOR THE QUESTION.
>>OTHER QUESTIONS, COMMENTS?
NOT SEEING ANY I THINKS WE CAN
MOVE TO RATING.
>>JUST ANOTHER MOMENT OR TWO.
OKAY THE NEXT CONCEPT.
>>IT'S IDS NUMBER 3915.
THE GENE THERAPY RESOURCE
PROGRAM.
THIS IS A CONTRACT RENEWAL LEAD
AUTHOR IS CHERYL McDONALD IN THE
ROOM.
IT CALLED FOR NEWLY OF GTRP.
A CONTRACT PROGRAM FIRST
LAUNCHED IN 2007 AND WAS DESIGN
TO PROVIDE RESOURCES AT NO-COST
TO INVESTIGATORS TO FACILITATE
THE GENE THERAPY DISCOVERIES
INTO CLINICAL VANCE --
ADVANCEMENTS AND THERE'S THREE
CORES.
A CLINICAL COORDINATING CORE,
PRE-CLINICAL VECTOR CORE AND THE
PHARMACOLOGY TOXICOLOGY CORE AND
THE PLAN IS TO KEEP THE SAME
THREE CORES AND ADD RE-AGENT
CORE THAT HAS THE FLEXIBILITY TO
PROVIDE A BROADER RANGE OF
RESOURCES TO ADDRESS THE NEEDS
OF RESEARCHERS IN A MORE
INDIVIDUALIZED MANNER.
THROUGH JANUARY 2023, THE GTRP
HAS HAD 171 INVESTIGATORS
REPRESENTING 79 INSTITUTIONS IN
THE U.S. REGISTERED WITH THE
GTRP.
THE PROGRAM SERVICES ARE SECURED
BY REQUEST FOR SERVICE
APPLICATION OR RSA AND A TOTAL
OF 2005RSA'S HAVE BEEN FULFILLED
WITH 124 DIRECTLY SUPPORTING A
CURRENT GRANT.
OF THOSE GRANTS ABOUT
THREE-QUARTERS ARE R01s AND OF
THE REMAINING QUARTER PRIMARILY
PROGRAM PROJECTS.
THE GTRP HAS ENABLED 16 INDs FOR
CLINICAL TRIALS AND THE OTHER IS
CURRENTLY UNDERGOING ADDITIONAL
TESTING PRIOR TO LAUNCHING THE
CLINICAL TRIAL.
THEY ENABLED TWO AWARDING PATENT
AND ONE PATENT APPLICATION AND
THE PROGRAMS WERE PICKED UP BY
INDUSTRY ON ANEMIA AND ONE ON
SICKLE CELL DISEASE AND ANOTHER
ON CONGESTIVE HEART FAILURE SO
IT WOULD CONTINUE TO FOSTER
RESEARCH AND PLAY A ROLE IN THE
EVOLUTION OF GENE THERAPIES AND
THE IMPACT THAT WILL HAVE ON
MEDICINE.
SO HAPPY TO ANSWER QUESTIONS AT
THIS POINT.
ARE THERE ANY OUT THERE?
WE CAN MOVE ON TO RATING.
>>I SEE A COUPLE THINGS.
>>WE HAD SOMEONE ABOUT WHAT
CONCEPT WE WERE ON BUT DON'T
WORRY ABOUT IT.
>>THANK YOU.
>>SO WE'RE MAKE GOING PROGRESS.
JUST ANOTHER MOMENT OR TWO.
>>WE CAN GO TO THE NEXT
CONCEPT.
>>I KNOW WE'RE RUNNING A LITTLE
BIT BEHIND BUT THERE'S AN
OPPORTUNITY FOR COUNCIL MEMBER
TO GIVE US INPUT AS TO WHETHER
THERE ARE IMPORTANT GAPS IN WHAT
WE'RE DOING TO PROVIDE FOR THE
GENE RESEARCH COMMUNITY OR
THINGS WE'RE PROPOSING GOING
FORWARD WE SHOULD STOP OR DO
DIFFERENTLY.
IF YOU CAN GIVE US THAT FEEDBACK
NOW DURING THE DISCUSSION OR
LATER IF YOU'D LIKE TO GIVE MORE
THOUGHT TO THAT AND SEND ME AN
E-MAIL OR GIVE ME A CALL.
>>A LISTENER HAS HER HAND UP.
>>PLEASE COME OFF MUTE.
>>THANK YOU SO MUCH.
THERE SEEMS TO BE A LOT OF AREAS
OF OVERLAP BETWEEN THE LAST TWO
INITIATIVES.
THE GENE THERAPY RESEARCH
PROGRAM AND THE RENEWAL OF THE
GENE VICTORY BIO REPOSITORY
CONTRACT.
I'M WONDERING IF THERE'S A
POSSIBILITY TO ANALYZE AND THE
REAGENTS CORE HAVE POTENTIAL
AREAS OF OVERLAP.
>>WE APPRECIATE THAT AND WOULD
WORK TO MAKE SURE THERE'S NO
OVERLAP.
WE HAD SOME DISCUSSIONS
INTERNALLY WHETHER IT WOULD MAKE
SENSE TO BRING THESE TWO
PROGRAMS UNDER A LARGER
UMBRELLA.
PERHAPS WITH SUB AWARDS BUT
THERE AREN'T MANY PLACE QUALIFY
SERVE IN THE CAPACITY OF THE
NGBB BUT THE SUB AWARDS IS ONE
POSSIBILITY.
>>JUST TO CLARIFY.
>>TO BRING THEM UNDER THE
UMBRELLA.
>>AND REDUCE THE POSSIBILITY OF
REDUNDANCY.
OTHER COMMENTS?
>>SOME OF IT IS VERY ORGAN
SPECIFIC.
I WAS TRYING TO THINK ABOUT
ECONOMIES OF SCALE FOR THE MORE
UNIVERSAL COMPONENTS.
>>THANK YOU.
>>GARY?
>>MAYBE ALONG THE LINES OF THE
TWO COMMENTS AS WE LOOK AT THE
PROGRAMS THAT HAVE BEEN AROUND
15 YEARS OR SO, SOME OF THEM
ENGENDERED WITH FIRST IN HUMAN
STUDIES IN THAT ERA.
ONE THING IS FOR THE INSTITUTE
TO REMAIN ADAPTIVE AND NOT
FIGHTING THE NEXT WAR BUT
FINDING OUT WHAT THE COMMUNITY
NEEDS AND WHAT SUPPORTS THE
COMMUNITY NEEDS IN THE NEXT FIVE
TO 10 YEARS.
WE WANT TO BE SURE AND STAY
NIMBLE.
TOWARD THAT END, I'M GENERALLY
AWARE THERE'S A LOT OF CORES AND
VENDORS NOW AND BIO
MANUFACTURERS WE'VE HAD VACCINES
THAT ARE ABLE TO MAKE AB, ADENO
VIRAL VECTORS.
IT'S NOT AS CLEAR TO ME 15 YEARS
IN IT'S AS BIG OF A CHALLENGE TO
THE BASIC STUFF FOR MANY
LABORATORIES OR EVEN A MOUSE
COLONY TO GET ENOUGH VIRUS TO DO
AN EXPERIMENT RELATIVELY
CHEAPER.
I DON'T KNOW THE INSTITUTE HAS
TO DO QUITE AS MUCH AS IT DID 15
YEARS AGO OR NEED TO DO
SOMETHING DIFFERENT.
IT'S HEALTHY TO STEP BACK AND
SEE WHAT IS NECESSARY FOR THE
NEXT SPOT.
>>I WAS THINKING OF
CELL-SPECIFIC TARGETING.
ANY OTHER COMMENTS ON THIS
BEFORE I PASS THE BATON?
I APPRECIATE YOU ALLOWING A FEW
MORE MINUTES TO DISCUSS THIS
ISSUE.
IT'S REALLY IMPORTANT TO US AS
WE FIGURE OUT HOW TO MOVE
FORWARD TO SUPPORT THE IMPORTANT
AREA OF RESEARCH.
>>DR. KILEY.
>>OKAY.
PRESENT.
>>THANKS, DAVID.
WE'RE GOING TO MOVE ON AND TALK
ABOUT THE ONES LED BY THE
DIVISION OF LUNG DISEASES.
WE HAVE SIX INITIATIVES ALL
EXCEPT FOR MAYBE ONE ARE EITHER
HL WIDE OR NLH WIDE STARTING
WITH INITIATIVE 3897.
THE NATIONAL FERRET RESOURCE AND
RESEARCH CENTER LED BY THE LUNGS
DIVISION.
THIS PROGRAM STARTED BACK IN
2014 AS AN INVESTIGATOR
INITIATED R24 PROGRAM AND THEN
CONVERTED IN 2020 TO CONTRACT
PROGRAM.
SOMEWHAT SIMILAR TO THE RESOURCE
PROGRAM THAT DAVID JUST
MENTIONED FOR GENE THERAPY.
THE MAJOR GOALS FOR THIS
RESOURCE ARE TO CREATE AND
DISTRIBUTE GENETICALLY MODIFIED
FERRET MODELS RELEVANT TO HEART,
LUNG, BLOOD, SLEEP DISEASE AND
FACILITATING OUR USAGE AMONG THE
RESEARCH COMMUNITY AND SERVE AS
A CENTRALIZED RESOURCE FOR
HUSBANDRY AND TRAINING AND STUDY
DESIGN FOR FERRET RECEIVER.
THE RESOURCE ITSELF HAS BEEN
INSTRUMENTAL IN IMPROVING
PROCESS AND MOLECULAR BASIS OF
LUNG DISEASES WHILE ADVANCING
PRECLINICAL STUDIES TO MOVE
TREATMENT TO CLINIC.
ONE OF THE MAIN AREAS THAT WAS
SET UP FOR IN THE EARLY DAYS WAS
TO REALLY STUDY CYSTIC FIBROSIS.
THIS WAS THE FIRST ANIMAL MODEL
OF THE ET WHERE THEY -- FERRET
WHERE THEY WERE ABLE TO KNOCKOUT
THE GENE RESPONSIBLE AND THERE'S
BEEN STRIDES IN CF THERAPY DUE
TO USING THE ANIMAL MODEL.
ONE THING I THINK IS UNIQUE HERE
IS THAT THERE'S A LOT OF
SIMILARITIES WITH THE HUMAN
PULMONARY SYSTEM INCLUDING
COMMON ANATOMICAL STRUCTURE AND
THE AIRWAY IS SIMILAR TO
RESPIRATORY BRONCHIOLES.
THERE'S SHARED IMMUNOLOGICAL
RESPONSES AND THE ABILITY TO
COUGH.
FERRETS REALLY ARE A GOOD MODEL
FOR RESPIRATORY DISEASE AND
PARTICULARLY RESPIRATORY
INFECTION AND WHEN YOU COMPARE
IT TO THE MOUSE MODEL THEY CAN'T
RECAPITULATE AND WHEN YOU RAMP
UP TO PIGS, SHEEP AND NON HUMAN
PRIMATES IT GETS COSTLY.
THIS IS A CONTRACT RENEWAL FOR
THE FERRET RESOURCE AND THINK
IT'S BEEN A PRODUCTIVE RESOURCE
OVER THE YEARS.
AS MENTIONED, IT WAS FIRST USED
FOR THE CFTR GENE AND THEN AFTER
A BIT IT BECAME CLEAR IT COULD
BE ADAPTED TO STUDY OTHER LUNG
DISEASES SUCH AS DEFICIENCIES,
PULMONARY FIBROSIS AND COPD AND
THERE'S BEEN INNOVATIVE WORK
DONE NOT ONLY USING THE RESOURCE
ITSELF BUT PROVIDING THE ANIMALS
TO THE COMMUNITY AS A WHOLE.
IN FACT EVEN DURING THE COVID
ERA IT WAS UTILIZED FOR
RESPIRATORY TRACT INFECTIONS FOR
SARS COV2.
THEY WERE ADAPTIVE IN THE LAST
FEW YEARS.
HAVE BEEN HIGHLY PRODUCTIVE.
I WON'T TELL YOU ALL THE
DETAILS.
IT'S IN THE WRITE-UP BUT IT'S
BEEN A USEFUL RESOURCE FOR THE
PULMONARY COMMUNITY AND WE WOULD
LIKE TO CONSIDER RENEWING THIS.
LOTS OF STATISTICS BECAUSE
THEY'VE BEEN PRODUCTIVE ALL
AROUND.
ONE THING IN THE INSTITUTE WE'RE
EXCITE ABOUT IS THE POSSIBILITY
OF USING THE ANIMAL MODEL MORE
THAN JUST FOR LUNG DISEASE AND
CARDIOVASCULAR DISEASE AND OTHER
AREAS WITHIN NHLBI THE MODEL
COULD EXPAND TO.
AND IT'S BEEN VERY ADAPTIVE AND
MODIFIED.
IT'S OVER ALL PROCESSES AND
LEVERAGED AN AMAZING AMOUNT OF
RESOURCES LOCALLY AND ACROSS NIH
TO MAINTAIN THE COLONY AND THE
RESOURCE TO PROVIDE THESE
ANIMALS AND VARIOUS MATERIALS TO
THE INVESTIGATIVE COMMUNITY.
I'LL STOP THERE AND TAKE ANY
QUESTI
QUESTIONS AND GET YOUR FEEDBACK
ON THIS ONE.
>>NOT SEEING MUCH YOU CAN RATE
THIS ONE.
>>3897.
>>WE CAN MOVE ON TO THE NEXT
CONCEPT.
>>THANK YOU.
THE NEXT CONCEPT THIS IS A
PACKAGE LIKE YOU SAW FOR I THINK
MESA.
THIS ONE IS 3900 AND 3901 I'LL
PRESENT TOGETHER BECAUSE THEY'RE
THE SAME JUST USING TWO FUNDING
MECHANISMS THE UL1 AND U24.
YOU'LL NEED TO RATE THEM
INDIVIDUALLY BUT IT'S
ESSENTIALLY THE SAME INITIATIVE.
ENTITLE OF ENTITLED ADVANCING
METHODS FOR 24-HOUR BEHAVIORAL
PATTERNS AND DIET ACTIVITY AND
SLEEP AND UL 1, U24 RFA AND
WE'RE A SECONDARY SIGN-ON.
AND THE HEART DIVISION HAS BEEN
INVOLVED AND THERE'S A TEAM OF
NHLBI INSTRUMENTAL IN MOVING
THIS FORWARD.
THIS CONCEPT IS FOCUSSED ON
LEVERAGING EXISTING DATA TO
INTEGRATE AND EXAMINE BEHAVIORAL
PATTERNS OF DIET, PHYSICAL
ACTIVITY AND SLEEP LOOKING AT
HEART DISEASES AND DISORDERS.
AS A BACKGROUND IN SEPTEMBER OF
'22 THE WHITE HOUSE CONFERENCE
ON HUNGER, NUTRITION AND HEALTH
CALLED FOR HHS AND NIH TO
EXPLORE DEVELOPING VALIDATED
MEASUREMENTS TO ASSESS 24-HOUR
PATTERNS OF DIET, PHYSICAL
ACTIVITY AND SLEEP.
THIS ATTEMPTS TO ANSWER THE CALL
USING THE TWO FUNDING MECHANISMS
AND IT WOULD BE JOINTLY
SUPPORTED BY NHLBI, NCI AND THE
DIABETES DISEASE AND BEHAVIORAL
AND SOCIAL SCIENCES GROUP.
SO I THINK ALL OF YOU KNOW DIET,
PHYSICAL ACTIVITY SLEEP ALL
MODIFIABLE LIFE RISK FACTORS AND
STUDIES HAVE COLLECTED DATA ON
ALL THESE BEHAVIORS BUT FEW HAVE
EXAMINED HOW THEY COMBINED TO
EFFECT HEALTH AND DISEASE.
ACCORDINGLY, SIGNIFICANT GAPS
REMAIN ALONG THE RESEARCH
CONTINUUM.
SO WE'RE LOOKING TO FACILITATE
COLLABORATIVE EFFORTS TO ADVANCE
OUR UNDERSTANDING OF THESE
INTERRELATIONSHIPS IN TIME IN
TEMPORAL MANNER AND IN TERM OF
INTEGRATING THEM TOGETHER.
SO THE INITIATIVE WILL SOLICIT
PROPOSALS THAT LEVERAGE EXISTING
DATA AMONG DIVERSE POPULATIONS
TO INVESTIGATE HOW THE TIMING OF
DIET, PHYSICAL ACTIVITY AND
SLEEP SYNERGISTICALLY ADDRESS
CARDIO METABOLIC OUTCOMES
THROUGH THE DEVELOPMENT OF
ROBUST ANALYTICAL APPROACHES.
THIS CONCEPT HAS SIGNIFICANT
PUBLIC HEALTH AND IMPLICATIONS
AND WILL EXPAND OUR
UNDERSTANDING OF HOW THE TIMING
OF BEHAVIORAL PATTERNS MAY BE
LEVERAGED AND IMPLEMENTED INTO
TARGETED INTERVENTIONS AND
PRECISION MEDICINE.
THE KEY IN CASE I DIDN'T MAKE IT
CLEAR, THESE HAVE BEEN LOOKED AT
INDIVIDUALLY AND IN ISOLATION.
THIS IS AN ATTEMPT TO BRING IT
ALL TOGETHER AS BEST WE CAN AND
LOOK AT IT IN A HOLISTIC MANNER.
THAT'S THE THRUST OF THE TWO
INITIATIVES.
I'M HAPPY TO TRY TO TAKE
QUESTIONS ON THESE IF THERE ARE
ANY.
GO AHEAD AND RATE THESE AS WELL,
PLEASE, THE TWO OF THEM.
A QUICK REMINDER, THAT'S 3900
AND 3901.
WE CAN MOVE ON.
>>OKAY.
THE THIRD ONE IN THIS GROUPING
IS 3914.
THIS IS THE NHLBI PROGRAM
PROJECT APPLICATIONS.
THIS INITIATIVE HAS BEEN LED BY
DR. LISA POSTOE IN THE LUNG
DIVISION.
THIS IS A PROPOSAL TO RENEW THE
EXISTING PAR WITH REVIEW THAT
SUPPORTS PROGRAM PROJECT GRANTS
OR THE PL1s.
THIS WAS LAST PRESENTED ABOUT
THREE YEARS AGO SO IT'S TIME TO
RENEW THIS INITIATIVE.
IT WILL CONTINUE TO REQUEST
INVESTIGATOR-INITIATED PROGRAM
PROJECT APPLICATIONS THAT
INVESTIGATE FUNDAMENTAL
PROCESSES AND DISEASE IN HEART,
LUNG, BLOOD AND SLEEP.
MANY OF THE PO1 GRANTS WE HAVE
SUPPORTED AND WHAT COMES IN THE
DOOR FOCUS ON MECHANISTIC
RESEARCH.
ONE OF THE THINGS LIKE TO
ENCOURAGE AND HOPEFULLY SEE
DEVELOP IN THIS RENEWAL IS A
LITTLE BIT MORE IN THE WAY OF
TRANSLATIONAL AND IMPLEMENTATION
RESEARCH.
THOSE ARE TWO AREAS ENCOURAGED
AS WE PUT THIS BACK OUT ON THE
STREET.
AS MOST OF YOU KNOW, PPG NEEDS A
MINIMUM OF THREE INTERRELATED
PROJECTS.
THEY ALL HAVE TO BE AROUND A
COMMON THEME.
THEY INCLUDE SCIENTIFIC AND
ADMINISTRATIVE CORPS, FOSTERING
COLLABORATION WITH
INTERDISCIPLINARY RESEARCH FOR A
MAXIMUM SO YEARS AND MAXIMUM
BUDGET OF $5.51 MILLION AND NEW
INVESTIGATOR -- FIVE YEARS.
AND USED TO ENCOURAGE THE
CAREERS OF JUNIOR INVESTIGATORS
IN THE COLLABORATIVE ENVIRONMENT
IF THE PROJECT IS LED BY AN
EARLY STAGE INVESTIGATOR THE
REQUEST CAN BE UP TO $1.765
MILLION PER YEAR.
WE HOPE THE P.A.R. WILL CONTINUE
ALONG OVER A 10-YEAR PERIOD AND
PLAN TO AWARD 14 TO 15 A YEAR
AND HAVE A SET ASIDE FOR THE
P.P.G. MECHANISM.
IT'S AN IMPORTANT
INVESTIGATOR-INITIATED MECHANISM
AND HISTORICALLY PPG GRANTS
FUNDED IN THE GRANT PORTFOLIO
AND I POINT TO CYSTIC FIBE ROYCE
WHERE WE HAD LONG-STANDING PPGs
AND RELATIONSHIPS BETWEEN THEM.
GO AHEAD AND RATE THIS ONE.
>>WE CAN MOVE ON TO THE NEXT
CONCEPT.
>>THANK YOU.
WE'RE ON THE FOURTH IS NUMBER
3924, 3924.
THE NHLBI CLINICAL TRIAL PILOT
STUDIES.
THIS IS THE R34 CLINICAL TRIAL
OPTIONAL MECHANISM.
THIS ONE IS LED BY DR. MICHELLE
KRAMER IN THE LUNG DIVISION.
THIS HAS A NUMBER OF ADDITIONAL
STAFF
[LISTING NAMES]
ALL FROM HEART, LUNG, BLOOD AND
CONTRIBUTED.
THIS SHOULD BE FAIRLY FAMILIAR
BECAUSE YOU'VE SEEN THIS BEFORE.
THE PURPOSE OF THE R 34 IS TO
SUPPORT INVESTIGATORS IN
OBTAINING INFORMATION REQUIRED
TO COMPLETE THE DESIGN AND
PROTOCOL FOR A PHASE 2 CLINICAL
TRIAL AND OTHER CLINICAL TRIAL
OPPORTUNITIES BY ALLOWING
INVESTIGATORS TO ADDRESS
CRITICAL QUESTIONS PRIOR TO
SUBMISSION OF AN APPLICATION TO
SUPPORT THE PLANNED LARGER
TRIAL.
THE NHLBI IS USED THE R34 SINCE
2010.
WE PRESENTED THIS LAST IN
JANUARY OF 2018 TO ALL OF YOU.
AT THE TIME OF IT'S INCEPTION
STAFF RECOGNIZED THE MECHANISM
WHICH ALLOWS UP TO THREE YEARS
OF FUNDING WITH A TOTAL BUDGET
OF $450,000 IN DIRECT COST TO
IMPROVE THE CONDUCT OR OBTAIN
ADDITIONAL INFORMATION THAT MAY
BE REQUIRED TO DO THE MORE
INTENSE CLINICAL TRIAL AND
BELIEVE IT SERVES THE
INVESTIGATIVE COMMUNITY.
RIGHT NOW WE FUND APPROXIMATELY
20 TO 25 OF THESE PER YEAR.
THESE R34 APPLICATIONS.
AND THERE IS A RELATIVELY ROBUST
RESPONSE FROM THE INVESTIGATIVE
COMMUNITY THIS IS A VERY
IMPORTANT AND NEEDED MECHANISM.
RENEWAL OF THE PROGRAM WILL
CONTINUE TO SERVE THE
INVESTIGATOR COMMUNITY ACROSS
NHLBI AND WE WILL MAKE SURE THAT
LANGUAGE IS INCLUDED IN THE
ANNOUNCEMENT TO ENCOURAGE
DIVERSITY, EQUITY, INCLUSION AND
ACCESSIBILITY IN RESEARCH.
THIS IS ONE AREA YOU HEARD FROM
DR. GIBBONS WE'RE TRYING TO
STRATEGICALLY ADVANCE AND THIS
IS A MECHANISM THAT ALLOWS TO DO
THAT.
OTHERWISE, NOT VERY MANY CHANGES
TO THE FUNDING OPPORTUNITY
ANNOUNCEMENT ARE ANTICIPATED.
THIS IS PRETTY MUCH A RENEWAL OF
WHAT'S ON THE STREET.
I'LL STOP THERE AND TRY TO TAKE
QUESTIONS.
HOPEFULLY YOU CAN RATE THIS ONE
AS WELL.
>>THIS LAST ONE IS 3927.
IT'S SUB POPULATIONS AND
INTERMEDIATE OUTCOME STUDIES IN
COPD KNOWN AS SPIROMIC TO
IDENTIFY DIFFERENT INDIVIDUALS
WITH COPD AND DEFINE SPECIFIC
INTERVENTIONS.
THE GOAL IS BEING ACCOMPLISHED
BY INTENSIVE PHENOTYPING OF A
COHORT WITH A HISTORY OF SMOKING
WITH AND WITHOUT COPD AND
CONTROL PARTICIPANTS WITHOUT
COPD.
THIS IS A LIMITED COMPETITION
RENEWAL.
IN THE NEXT CYCLE OF SPIROMICS
THE INVESTIGATORS WILL BE
CHARGED OR CHALLENGED TO OBTAIN
ADDITIONAL LONGITUDINAL DATA
FROM THE COHORT AND THEY'LL
ADDRESS THREE CRITICAL TOPICS
THAT HAVE BEEN PROMPTED BY
RECENT FINDINGS WHETHER
NON-OBSTRUCTIVE AIRWAY DISEASE
IS SIMILAR TO COPD AND REPRESENT
AS A PRECURSOR CONDITION THAT
CAN PROGRESS TO COPD.
THE SECOND IS TO EXPLORE THE USE
OF NOVEL CT MEASURES TO IDENTIFY
EMP
EMPHYSEMA SUB TYPES AND TRACK
PROGRESSION OF THE ABNORMALITIES
AND CHARACTERIZE ENVIRONMENTAL
EXPOSURES AND SOCIAL
DETERMINATES OF HEALTH IN
POPULATIONS TO RELATE RISK
FACTORS TO PARTICULAR COPD SUB
TYPES AND RELATE THAT BACK TO
PATHOBIOLOGICAL MECHANISMS.
IT'S BEEN DRIVING UNDERSTANDING
ABNORMALITIES IN COPD.
IT'S HAD A PRODUCTIVE HISTORY.
IT COMPLEMENTS OUR OTHER
LONGITUDINAL STUDY.
IN LUNG WE HAVE TWO THAT RELATE
TO COPD GENE STUDY LOOKING AT
GENETICS AND NATURAL HISTORY AND
THIS LOOKS AT BIOMARKERS AND
DOES MORE INTENSE PHENOTYPING.
THE OTHER ELEMENT OF THIS
RENEWAL IS TO ROLL INTO
SPIROMICS YOUNGER SMOKERS CALLED
SOURCE BY BE AN INVESTIGATOR
INITIATED GRANT USING THE SAME
PLATFORM AND IT'S BEEN ACTIVE
ONLY A COUPLE YEARS AND IT'S
CURRENTLY ENROLLING IN
CHARACTERIZING THE YOUNGER
INDIVIDUALS USING THE SPIROMICS
PROTOCOL AND PROPOSE TO BRING
THEM IN DURING THE SECOND HALF
OF THE CONTRACT PERIOD.
ADDING SOURCE WILL INCREASE THE
SIZE OF THE COHORT AND IMPROVE
THE USEFULNESS IN STUDYING COPD.
THAT'S THAT PROGRAM AND HAPPY TO
TAKE QUESTIONS ON THAT OR TO
INPUT.
>>NOT SEEING ANY.
>>OKAY.
RATE THIS ONE AS WELL.
>>WE'RE READY TO MOVE ON.
>>THANK YOU VERY MUCH.
WE'LL MOVE ON TO THE BLOOD,
VISION.
>>THE DIVISION OF BLOOD DISEASE
OF DISEASES AND RESOURCES WILL
PRESENT ONE CONCEPT NUMBER 3922.
A REQUEST TO RENEW THE
MAINTENANCE OF MODELS OF HUMAN
BLEEDING DISORDERS RESOURCE LED
BY DR. GILLESPIE HERE.
THE RESOURCE HAS BEEN IN
EXISTENCE SINCE 1947 AND
CONTINUOUSLY NHLBI FUNDED BY A
FUNDING MECHANISM AND WE'RE
REQUESTING A RENEWAL OF FIVE
YEARS.
THE SCIENTIFIC PURPOSE IS TO
CONTINUE DOG MODELS OF BLEEDING
DISORDERS AND FACTOR 7
DEFICIENCY AND OTHERS.
SPECIFIC OBJECTIVES INCLUDE TO
MAINTAIN A BREEDING COLONY WITH
INHERITED BLEEDING DISORDER FOR
A COST-EFFECTIVE MANNER.
IN ADDITION TO PROVIDE
SPECIALIZED SUPPORT SERVICES FOR
THE VETERINARY CARE OF THE
ANIMALS THROUGHOUT THEIR LIFE
TIME BY INCLUDING CANINE BLOOD
BANKING AND COAGULATION MALL SIS
AND OTHER PROCEDURES FOR THEIR
CARE AND MAINTENANCE TO PRODUCE
PURPOSE-BRED RESEARCH ANIMALS TO
SERVE AS BLOOD DONORS FOR
HEMOPHILIA DOGS IN THE COLONY
AND SERVE AS CONTROL AND TO
ACQUIRE AND CHARACTERIZE NEW
MODELS OF INHERITED BLEEDING
DISORDER TO STUDY FOR HEME
ATOLOGICAL DISORDERS AND
FACILITATE NEW HUMAN THERAPIES.
RESEARCH USING THE CANINE COLONY
HAS MORE THAN DOUBLED DURING THE
PAST 20 YEARS AND WITH THE
CONTINUED FACILITATION OF THE
SCIENCES AND ACCELERATION OF THE
TRANSLATION OF DISCOVERIES INTO
THERAPEUTICS.
TO NOTE A FEW OF MANY NOTABLE
ACCOMPLISHMENTS FROM THE CANINE
RESOURCE INCLUDE FIRST
LABORATORY TEST TO IDENTIFY
HEMOPHILIA A IN HUMANS AND THE
DECLINING FACTOR OF A FACTOR 8
CONCENTRATE AND GENE THERAPY IN
HEMOPHILIA A AND B LEADING TO
RECENT FDA APPROVAL FOR
HEMOPHILIA B PRODUCTS.
IN SUMMARY THIS IS A UNIQUE
RESOURCE FOR INVESTIGATORS AND
NHLBI CONTRIBUTION IN THE
SUCCESS OF THE RESOURCE
INCLUDING SUPPORT OF
GROUND-BREAKING DISCOVERIES THAT
ADVANCE THE DIAGNOSIS AND
TREATMENT OF HEMOPHILIA AND
OTHER BLEEDING DISORDERS AND
IMPROVING AND SAVING LIVES.
I'M HAPPY TO DISCUSS AND TAKE
ANY QUESTIONS.
>>I DON'T SEE ANYTHING IN THE
CHAT.
>>ALL RIGHT.
THANK YOU.
>>CONGRATULATIONS I THINK WE'RE
DONE.
>>ARE THERE QUESTIONS?
YES, DAVID.
>>UNRELATED QUESTION.
>>JUST TO MAKE SURE NOBODY HAS
A RELATED QUESTION FIRST.
GO AHEAD AND ASKED YOUR
UNRELATED QUESTION.
>>I'M SEEING MORE AND MORE
DIVERSITY-RELATED RO1 OFFERINGS
FROM OTHER INSTITUTES.
I THINK THERE'S THE CANCER MOON
SHOT AND THE REWARDS PROGRAM AND
AT-RISK INVESTIGATORS PROGRAM.
AS WE'RE TALKING ABOUT NEW
CONCEPTS AND NEW PLACES TO PUT
MONEY I DIDN'T KNOW IF NHLBI WAS
THINKING ABOUT THAT.
>>WE PARTICIPATED IN A NUMBER
THINGS OFFERED BY OTHER
INSTITUTES AND THE UNITE PROGRAM
AND I THINK WE'RE CONTINUING TO
DEVELOP NEW POTENTIAL OFFERINGS
AND NOT SURE IF IT'S THE RIGHT
PLACE TO PUT OUR MONEY AND SOME
WE'D LIKE TO SEE IN AND OUT
BEFORE WE MAKE A DECISION ON
WHAT TO DO NEXT IN TERMS OF
INTERRELATEDNESS.
>>I DON'T KNOW THE
EFFECTIVENESS OF THOSE PROGRAMS
IS IT'S REALLY AN IGNORANCE
PROGRAM.
>>IT'S A GOOD QUESTION AND ONE
WE'RE ALL WONDERING ABOUT.
>>GARY.
>>WE'RE OPEN TO IDEAS AN
CONCEPTS IN THE SPACE.
FRANKLY, ACADEMIA, MANY
INSTITUTIONS HAVE BEEN AHEAD OF
THE CURVE IN THE SPACE.
IF THERE'S THINGS EVEN SHARING
BEST PRACTICES OR STRATEGIES,
THAT WOULD BE HELPFUL.
AND THE WAY THE PROGRAMS ARE
EXECUTED IS KEY.
THAT INVOLVES A LOT OF
CONSULTATION FRANKLY WITH OUR
OFFICE OF LEGAL COUNSEL TO MAKE
SURE WE'RE ALIGNED OF BEING
INCLUSIVE WITHOUT ANY
DISCRIMINATION AND THAT'S PART
OF THE PRINCIPLE.
SOME OF THAT IS ON THE SUPREME
COURT DOCKET AS WE SPEAK.
WE WANT TO DO THIS IN A SMART
WAY.
THAT'S WHERE YOU'RE SEEING A LOT
OF EXPERIMENTS AND WE'RE
TRACKING THEM AND AS LAURA'S
POINTING OUT TRYING TO BE
JUDICIOUS IN HOW WE GO.
TO BE FRANK, I THINK THE NHLBI
HAS A PRETTY ROBUST PORTFOLIO
WHEN IT COMES TO DIVERSITY PAYS
AND I THINK WE'VE BEEN AT THAT
VANGUARD AS LAURA WAS SAYING AND
SEEING WHERE THE EXPERIMENTS
HAVE BEEN DEVELOPED UP ADDITION
TO THE COSWIT WE'RE LINKED TO.
IT'S AN ACTIVE AREA AND STAY
TUNED ONE WHERE I THINK IT'S
GOOD FOR ACADEMIA AND DIALOGUE.
IT'S A COLLABORATION TO MAKE
THIS WORK SINCE AND TRYING TO
MAKE THEM CONDUCIVE.
>>WE'RE HAVING A CONVERSATION
IN THE CLOSED SESSION ABOUT
PROGRAMMATICALLY APPOINTED AND
WE LOST SOMEONE WHO WENT ON TO
BIGGER AND GREATER THINGS SO.
>>ONE THING WE REPORTED BEFORE
WAS THE DIVERSITY OF OUR Rs, Ts,
Ks, WHAT HAVE YOU AND ONE THING
WE'RE LOOKING AT IS OUR Ts.
IT'S AN AREA WHERE COUNCIL WILL
BE HELPFUL IN TERMS OF YOUR
EXPERIENCE.
IT'S FOR THE TRAINING
ENVIRONMENTS WE HAVE TO WORK
THROUGH HOW WE DO THAT AND HOW
WE THINK ABOUT BEING INCLUSIVE
AND INCLUSIVE AS YOU KNOW NOT
JUST IN TERMS OF SEX, GENDER,
RACE AND ETHNICITY BUT AS WE'VE
DISCUSSED ALL DAY DISCIPLINES
NOT ONLY IN HEART, LUNG, BLOOD
AND SLEEP BUT A VARIETY OF
PERSPECTIVE, DATA SCIENCE AND
OTHER ENGINEERING.
ALL THOSE WILL BE IMPORTANT FOR
OUR TRAINING PROGRAM.
I'LL STOP.
>>I THOUGHT I'D BRING SOMETHING
PARALLEL TO WHAT YOU DID.
WE'RE EXPERIENCE THE WORKFORCE
AND WHILE WE GROW INCLUSIVE
EXCELLENCE AND THE METRICS OF
HOW WE DO IN CLOSING DISPARITIES
IS HORRIBLE IN MULTIPLE
INSTANCES OVER THE PAST 20
YEARS.
WE HAVEN'T DEMONSTRATED UP
IMPROVEMENT IN THOSE SCIENCE
DISPARITIES WORK THAT CAN HELP
CLOSE THE GAP.
IT'S NOT ENTIRELY RELATED TO THE
WORKFORCE BUT ADDRESSING HEALTH
EQUITY.
SOME GUIDANCES TO WHAT WE CAN DO
DIFFERENTLY AS A NATION AND NOT
JUST OUR INSTITUTE.
NO MATTER WHAT YOU LOOK THE
MAJOR DRIVERS WE'RE NOT CLOSING
THE GAPS AND COULD USE YOUR
ADVICE.
>>MARTHA HAS HER HAND UP BEFORE
I LET YOU ANSWER, MARTHA, I WANT
TO POINT OUT GEORGE IS RIGHT ON
AND GIVEN ME AN OPPORTUNITY TO
PLUG THE SEPTEMBER MEETING WE'RE
ALL GOING TO HAVE AN OPPORTUNITY
TO GO TO THE BOARD OF EXTERNAL
EXPERTS TO WEIGH IN ON TOPICS
THAT HAVE BEEN VERY IMPORTANT TO
THE INSTITUTE.
SOME OF WHICH WE DISCUSSED
BEFORE AND SOME OF WHICH WE'LL
DISCUSS AGAIN IN TERMS OF OUR
EVER GREENING MISSION FOR THE
STRATEGIC VISION BUT THIS TIME
REALLY LOOKING AT A REFRESH
WHERE TO GO FOR THE NEXT FIVE
YEARS AND VERY MUCH INTERESTED
IN WHAT WE HEAR FROM ALL OF YOU.
WITH RESPECT TO WHAT GEORGE IS
TALKING ABOUT, THERE'S A
DISCONNECT BETWEEN WHAT WE'RE
DOING AND WHAT WE THINK SHOULD
HAPPEN.
IT'S NOT REALLY AS DISCONNECTED
AS YOU THINK IT IS.
WE TRY TO DIVIDE THINGS UP
DISCREETLY AND REALLY IF YOU
THINK ABOUT IT IF WE'RE NOT
MAKING ADVANCES IN A PARTICULAR
FIELD OR SUPPORTING RESEARCH IN
A PARTICULAR FIELD, THEN THE
PEOPLE THAT WE'RE RECRUITING WHO
HAVE AN INTEREST IN THE AREA WE
WANT TO ADDRESS AREN'T GOING TO
STAY.
IT'S ALL CONNECTED.
MARTHA, GO AHEAD, PLEASE.
>>WE NEED TO IMPROVE AND LOOK
BETTER AT ADDRESSING THE VERY
BIG GAP BUT AS A NATION THERE'S
SO MANY ISSUES BEYOND OUR
CONTROL THAT ARE KEY
DETERMINATES.
I DON'T KNOW WE CAN ADDRESS OR
HAVE POWER TO ADDRESS.
I THINK IT'S A CEILING TO HOW
MUCH WE CAN ACCOMPLISH AND I DO
THINK THE MAJOR DETERMIN DETERME
OUT OF SIGHT AND MAYBE I'M ALONE
BUT I'M THINKING THAT WAY.
>>I DON'T THINK YOU'RE ALONE.
ANYBODY ELSE WITH ANY COMMENTS?
ANYTHING ELSE ANYBODY WANT TO
BRING UP IN ADDITION TO WHAT
WE'VE BEEN CHATTING ABOUT.
IF NOT, DR. GIBBONS I BELIEVE
YOU CAN ADJOURN THE MEETING.
>>IN ORDER FOR YOU ALL TO MAKE
YOUR FLIGHTS, WE STAND
ADJOURNED.
>>THANK YOU FOR YOUR ATTENDANCE