>> GOOD MORNING AND WELCOME TO DAY 2 OF THIS MEETING. I WANTED TO MAKE A COUPLE OF OBSERVATIONS. FIRST I WAS REALLY DELIGHTED BY THE TALKS YESTERDAY. I THOUGHT THE SPEAKERS DID A FANTASTIC JOB. WHEN WE PLAN ONE OF THESE MEETINGS AND WE INVITE PEOPLE, ON PAPER EVERYTHING LOOKS GOOD BUT I NEVER KNOW FOR SURE HOW IT WILL TURN OUT UNTIL WE HAVE THE MEETING. BUT I FOUND THE TALKS WERE WONDERFUL. AND WHAT I WAS REALLY STRUCK BY WAS THE EXCITEENT AND ENERGY, ESPECIALLY DURING THE BREAKS AND THE POSTER SESSION, WHICH I ONLY GOT TO DO FOR A LITTLE BIT BECAUSE OF MY MC ROLE I PLAY. BUT IT LOOKED LIKE THERE WAS A LOT OF DISCUSSION AND A LOT OF CONVERSATION ABOUT THE DATA AND HOW YOU MIGHT COLLABORATE, AND THAT'S THE POINT,ERWISE THERE IS NO REASON TO HAVE A MEETING AND HAVE PEOPLE COME ALL THE WAY HERE. BUT I THINK YOU REALLY CAN'T SUBSTITUTE GETTING PEOPLE TOGETHER WHO HAVE MAYBE NEVER MET AND HAVE THEM TALK ABOUT WHAT THEY ARE DOING AND SAYING, OH, YOU'RE DOING THIS? WELL, I'M DOING THAT. AND MAYBE THERE IS SAY WAYE I LOVED SEEING THE POSTERS. I THOUGHT EVERYTHING ABOUT YESTERDAY WAS GREAT. SO THAT WAS MY IMPRESSION. THAT SAID, I AM ALWAYS LOOKING FOR WAYS TO MAKE THIS MEETING BETTER. AND SO I INVITE YOU TO PROVIDE FEEDBACK. SOME PEOPLE ARE VERYANDID ABOUT THESE TYPES OF THINGS. SOME PEOPLE FEEL UNCOMFORTABLE. THERE IS NO PUNITIVE ACTION. I DON'T ALERT STUDY SECTION. I DO WANT TO KNOW IF THERE IS SOMETHING THAT YOU WISH -- SO I'LL GIVE YOU A CONCRETE EXAMPLE. LAST YEAR, A FEW PEOPLE SAID, THE BREAKOUT SESSIONS WE HAD IN THE PAST, THEY WERE GOOD AT THE VERY BEGINNING BUT MAYBE THEY RUN THEIR COURSE. YOU WILL NOTICE WE DIDN'T HAVE ANY BREAKOUT SESSIONS THIS TIME. WE USED THE TIME TO HAVE MORE TALKS BECAUSE NOW DATA IS STARTING TO COME OUT. WE TRIED TO HAVE A EXTENDED LUNCH PERIOD SO PEOPLE CAN MEET AND TALK. AND WE HAVE THIS POSTER SESSION. SO WE TAKE UP A FAIR AMOUNT OF TIME IN FREE SPACEOR YOU TO ALL INTERACT. AND IT'S THAT KIND OF FEEDBACK FROM ALL OF YOU, WHICH DRIVES WHAT WE DO NEXT TIME. AND ONE OF THE THINGS I'D LIKE TO KNOW, ACTUALLY, I DON'T WANT YOU TO GET UP AND TELL ME NOW. I WANT YOU TO THINK ABOUT IT. WHAT IS NEXT? BASED ON WHAT YOU HAVE SEEN AND ON WHAT YOU'RE THINKING ABOUT, WHAT SHOULD BE THE NEXT FOCUS? IF WE HAVE ANOTHER WORKSHOP NEXT YEAR, WHAT WOULD YOU WANT TO SEE TALKED ABOUT? WOULD YOU WANT TO SEE MORE DISCUSSION ABOUT DATA ANALYSIS? WOULD YOU WANT MORE OF THAT? DO YOU WANT TO SEE SOME TALKS -- I'M NOT TALKING ABOUT THE GRANTEE TALKS. NOW THAT GRANTEES ARE GENERATING DATA, WE WILL HAVE GRANTEE TALKS BECAUSE I WANT AN OPPORTUNITY FAR THEM TO AN OPPORTUNITY FOR THEM TO SHARE THE RESEARCH WITH YOU. BUT BEYOND THAT, WOULD YOU LIKE TO SEE TALKS WHICH DISCUSS HOW YOU GO ABOUT TAKING THESE PROJECTS DATA, OR YOUR DATA IF YOU'RE NOT A GRANTEE -- DOESN'T MATTER TO ME -- AND HOW DO YOU START TO DRIVE TRANSLATIONAL STUDIES WHICH WOULD ACTUALLY RESULT IN A CHANGE IN CLINICAL PRACTICE? BECAUSE THAT SEEMS TO BE AN IMPORTANT THING TO K ABOUT. BUT I WANT TO HEAR FROM YOU. IT'S REALLY THE SCIENTIFIC COMMUNITY. YOU WERE PART OF THAT PUZZLE THAT I MENTIONED ON THE VERY FIRST DAY THAT HELPS DRIVE AN INTELLIGENT, WELL THOUGHT OUT PROGRESS FOR THE HUMAN PLACENTA PROJECT, WHICH I WANT TO SAY IS NOT OVER. A FEW PEOPLE SAID, YOU HAVE GIVEN OUT SOME GRANTS. THERE IS PEOPLE DOING THEIR PROJECTS SO BASICALLY YOU'RE DONE. AND I DON'T THINK SO. LOT OF MOMENTUM AND GOT PEOPLE INTERESTED AND THINKING ABOUT THE PLACENTA. SO I PERSONALLY DON'T THINK WE ARE DONE. IF YOU DISAGREE, YOU SHOULD TELL ME. OKAY. I DON'T WANT WASTE TIME YAPPING WHEN THERE ARE REALLY GOOD TALKS SCHEDULED FOR THIS MORNING SO WITHOUT FURTHER ADIEU, I WILL ASK OUR FIRST SPEAKER, ALFRED ABUHAMAD TO COME UP AND GIVE US HIS TALK. >> DR. ABUHAMAD: GOOD MORNING, EVERYBODY. THANK YOU DAVID AND CATHY FOR THE HONOR TO SPEAK TODAY. SO I'M GOING TO TALK ABOUT ULTRASOUND IMAGING OF THE HUMAN PLACENTA. I'LL SHARE WITH YOU SOME NOVEL ULTRASOUND TECHNIQUES THAT ALLOWS US TO LOOK AT THE PLACENTA IN A MORE COMPREHENSIVE WAY THAN WE HAVE TRADITIONALLY DONE. SO I HAVE NO FINANCIAL DISCLOSURES OR CONFLICTS. WE ARE IN THE NICHD RESEARCH STUDY WE ARE DOING. SO AS WE KNOW, ABNORMAL PLACENTAL DEVELOPMENT IN EARLY GESTATION IS KNOWN TO BE ASSOCIATED WITH MA DISCERN FETAL ADVERSE OUTCOMES SUCH AS PREECLAMPSIA, AS YOU HEARD YESTERDAY, PRETERM DELIVERY AND FETAL GROWTH RESTRICTION. AND WE KNOW THAT PREGNANCY INSULT EARLY ON IN PREGNANCY, COULD RESULT IN ALTERATIONS IN PLACENTAL DEVELOPMENT, WHICH RESULTS IN PLACENTAL DYSFUNCTION. WE BELIEVE THAT MAY LEAD LATER ON IN PREGNANCY TO THE FETAL GROWTH RESTRICTION AND PREECLAMPSIA. AND THE GOAL OF OUR INVESTIGATION IS REALLY TRY TO STUDY THE PLACENTA IN EARLY GESTATION USING ULTRASOUND WITH THE GOAL OF IDENTIFYING SOME ALTERATION OF STRUCTURE AND FUNCTION THAT COULD PREDICT LONG TERM OUTCOME. SO WHAT ARE SOME OF THESE STRUCTURAL DEFECTS IN THE PLACENTA AND/OR FUNCTIONAL DEFECTS? YOU CAN SEE THE PLACENTA COULD BE SMALLER OR LARGER SUCH AS BIOMETRIC CHANGES. THE TISSUE DENSITY COULD CHANGE. THE CALCIUM CONTENT COULD ALSO CHANGE. OR THE VASCULAR SUPPLY OF THE PLACENTA, ON THE MA TERNITY OR FETAL SIDE COULD BE AFFECTED. -- MATERNAL. -- [ READING ] SO IF YOU BEEN ULTRASOUND, ULTRASOUND ADDRESSES A LONG LIST OF THOSE BOTH ON THE STRUCTURE AND FUNCTION OF THE PLACENTA. NOW, IS THERE ANY EVIDENCE THAT LINKS PLACENTAL STRUCTURE ABNORMALITIES TO PREGNANCY OUTCOMES? WE KNOW FROM THE LITERATURE TODAY THAT THERE IS SEVERAL STUDIES THAT LOOKED AT PLACENTAL BYOMITRY, BOTH SIDES AND 3D VOL EXHUME THICKNESS, AND MOST RESULTS HAVE BEEN -- 3D VOLUME AND THICKNESS AND THERE IS A LINK BETWEEN CHANGES IN PLACENTAL BIOMETRIC MEASUREMENTS AND PREGNANCY OUTCOMES. WE ALSO KNOW THAT PLACENTA TISSUE STRUCTURE IS IMPACTED. WE KNOW FROM LOOKING AT PLA SUBJECT SENT AS IN THE THIRD TRIMESTER AND LOOKING AT THEM AFTER DELIVERY, THERE IS INCREASE IN PLACENTAL INFARCTION, PREGNANCIES WITH STILLBIRTHS OR WITH GROWTH RESTRICTION. THERE IS INCREASE IN DENSITY ARRANGEMENTS AND INCREASE IN FIBROSIS IN THE PLACENTA. THESE ALL LEAD TO CHANGES IN PLACENTAL TISSUE DENSITY AND STRUCTURE. I'LL SHOW YOU THAT WE HAVE A TOOL AVAILABLE TODAY ON ULTRASOUND THAT WOULD ALLOW US TO STUDY THIS. SO IF YOU LOOK AT PLACENTAL TISSUE ELASTICITY, AT LEAST BASED ON THE EVIDENCE THAT EXISTS TODAY, STUDIES SUPPORT IN THE SECOND TRIMESTER AND THE THIRD TRIMESTER, THAT THE PLACENTA BECOMES MORE STIFF, IF YOU WILL, IN ASSOCIATION WITH PREECLAMPSIA. WE ALSO KNOW THAT THE PLACENTA BECOMES MORE STIFF IN ASSOCIATION WITH GESTATIONAL DIABETES. THERE ARE OTHER STUDIES ALSO ON FETAL ABNORMALITIES. WE ALSO KNOW THAT PLACENTAL MICROCALCIFICATION IS INCREASED IN THE PRESENCE OF ADVERSE PREGNANCY OUTCOMES. WHETHER IT IS RELATED TO STILL BIRTH, AS YOU SEE IN THE ACCUMULATIVE RISK OF STILL BIRTH HERE, OR RELATED TO POOR MATERNAL AND FETAL PREGNANCY OUTCOME. IN THIS TABLE, GROUP ONE REPORTS TO THE PRESENCE OF MICROCALCIFICATIONS AROUND 28-32 WEEKS AND GROUP TWO IS BEYOND THAT INTO THE THIRD TRIMESTER. AND IF YOU SEE IN THE HISTOLOGIC STUDIES, YOU SEE THE PRESENCE OF FIBROSIS IN ASSOCIATION WITH THE PRESENCE OF CALCIUM, MICROCALCIUM WITHIN THE VILLA. WE ALSO KNOW THAT PLACENTAL VASCULATURE IS IMPACTED SUBSTANTIALLY IN PREGNANCIES WITH POOR OUTCOMES WITH STUDIES SHOWING INCREASED URINE DOPPLER ABNORMALITIES WITH PRESENCE OF PEDENCE AND ALTERATIONS IN THE SPIRAL ARTERIES REMODELING IN THE PRESENCE OF THESE COMPLICATIONS. NOW WHY SHOULD ULTRASOUND BE CONSIDERED AS THE MAIN IMAGING MODALITY FOR PLACENTAL EVALUATION IN EARLY GESTATION? IT IS NOT INVASIVE. IT'S DONE IN REALTIME. IT'S WIDELY AVAILABLE AND PORTABLE. RELATIVELY LOW COST. REDDATIVELY SAFE WITH NO IONIZING RADIATION. CAN BE APPLIED IN EARLY GESTATION, AND IT ALLOWS FOR COMPREHENSIVE EVALUATION OF THE FETAL CARDIOVASCULAR FUNCTION, WHICH IS A VERY IMPORTANT PARAMETER IN TRYING TO ASSESS THE IMPACT OF PLACENTAL DISRUPTION ON THE FETUS. ALSO IT IS ALREADY INCORPORATED IN CLINICAL PRACTICE. SHOULD STUDIES RELATED TO THE HUMAN PLACENTA PROJECT AND ULTRASOUND FIND SIGNIFICANCE IN EARLY GESTATION, THAT CAN BE INCORPORATED IN CLINICAL PRACTICE FAIRLY RAPIDLY GIVEN HOW WIDELY ULTRASOUND IS AVAILABLE. AND I HEARD DAVID YESTERDAY IN HIS PRESENTATION ON THE HUMAN PLA SENTA PROJECT, MENTION THE THREE WORDS, SAFE, NON-INVASIVE AND REALTIME, AND I THOUGHT HE WAS TALKING ABOUT ULTRASOUND. ULTRASOUND IS ALSO WIDELY USED IN THE UNITED STATES. THIS IS A STUDY THAT WE DID ABOUT 4-5 YEARS AGO LOOKING AT ULTRASOUND IN THE UNITED STATES. DATA FROM INSURANCE COMPANIES, LARGE DATASETS, LOOKING AT LOW-RISK PATIENTS. THE AVERAGE NUMBER OF ULTRASOUNDS PERFORMED IN THE U.S. IS SOMEWHERE AROUND 4 PER PREGNANCY. THESE ARE IN LOW-RISK PATIENTS. WE HAVE DATA TO SUPPORT THAT MORE THAN 80% OF PREGNANCIES IN THE U.S. RECEIVE AN ULTRASOUND IN EARLY GESTATION. SO OUR NICHD STUDY WAS ENTITLED, THE NOVEL RESULT SOUND TOOLS FOR THE NON-INVASIVE EVALUATION OF THE HUMAN PLACENTA. THIS IS A COLLABORATION BETWEEN EASTERN VIRGINIA MEDICAL SCHOOL AND THE UNIVERSITY OF TEXAS MEDICAL BRANCH AND TOSHIBA MEDICAL. MYSELF AND DR. GEORGE SAADE ARE CO-PIs. OUR HYPOTHESIS IS NOVEL PLACENTAL INDEX IN EARLY PREGNANCY WILL DIFFERENTIATE BETWEEN NORMAL AND ABNORMAL PREGNANCIES AND OUR PRIMARY OUT COME WAS, ANY PREGNANCY THAT IS DELIVERED AT LESS THAN 37 WEEKS FOR ANY INDICATION. THE EXPLAIN TO RECRUIT 550 PREGNANCIES. 155 NORMAL AND 360 AT HIGH-RISK. AND THE PILOT OF 30IVF PREGNANCIES. THIS IS A LONGITUDINAL ULTRASOUND EVALUATION FROM 13 WEEKS ON ONWARD IN PREGNANCY WITH A TOTAL OF EIGHT ULTRASOUND EXAMINATIONS PER STUDY ASSEMBLE. WE ARE COLLECTING A LONG LIST OF RESULT SOUND PARAMETERS ALONG WITH BIOSAYS SPIN STORED AND MATERNAL AND CORD BLOOD AND PLACENTAL BY OPPOSITIES AND WE ARE ALSO STARTING SOON TO COLLECT MATERNAL BLOOD FOR NUCLEIC ACID ANALYSIS WE ARE LOOKING AT BYOMITRY, CALCIFICATIONS IN THE PLACENTAL AND VASCULATURE AND SOON ON GENETICS ASPECT. WHAT ARE WE EXACTLY CURRENTLY DOING? FOR THE FETAL BYOMITRY, WE ARE MEASURING THE STANDARD BIOMETRIC MEASUREMENTS IN EARLY GESTATION, THE HEAD CIRCUMFERENCE, THE FEMUR LENGTH IN THE FETUS STARTING AT 13 WEEKS, THE ABDOMINAL CIRCUMFERENCE, THE CROWN LENGTH FOR PREGNANCY DATING AND THE NUCLEO TRANSLOOSENSY. THEN MOVING INTO PLACENTAL BYOMITRY, WE ARE LOOKING AT THE PLACENTAL VOLUME, THE LENGTH AND WIDTH. AND THIS IS A 13-WEEK PLACENTA FROM ONE OF OUR PATIENTS AT HER INITIAL RESULT SOUND EXAMINATION FOR THIS STUDY. WE ARE ALSO LOOKING AT FETAL CARDIAC FUNCTION. WE BELIEVE EARLY GESTATION A REALLY INTEGRAL PART OF THE EVALUATION OF THE PREGNANCY LOOKING AT THE PLACENTA AND WHAT CHANGES IN THE HEART AND CARDIOVASCULAR SYSTEM THAT STARTS EARLY ON THAT IMPACTS FETAL DEVELOPMENT FROM THE FIRST TRIMESTER ONWARD. WE KNOW THAT FETAL CARDIAL FUNCTION HAS BEEN SHOWN TO BE AN EARLY MARKER FOR FETAL ADAPTATION TO DISEASE BEFORE ANY CHANGES IN THE FETAL PERIPHERAL CARDIOVASCULAR SYSTEM AND WE KNOW THESE CHANGES HAVE BEEN LINKED TO LONG TERM CARDIOVASCULAR EFFECTS IN CHILDREN. SO FROM THE FIRST ULTRASOUND, WE ARE LOOKING AT ALL CARDIAC PARAMETERS IN THE FETUS AND COLLECTING EVIDENCE ON THE INDEXES AND ON THE FLOW ACROSS CARDIAC VALVES AND LOOKING AT THOSE. WE ARE LOOKING AT PLACENTAL CALCIFICATION. THERE IS A NOVEL IMAGE PROCESSING FUNCTION THAT COMBINES NON LINEAR IMAGING AND SPECKEL SUPPRESSION AND PROVIDES IMAGES AS SUCH THAT WOULD HELP NORMAL PLACENTAS AND EVALUATE AND THEN COMPARE NORMAL PLACENTAS WITH THE PRESENCE OF CALCIFICATIONS. THEY ARE HIGHLIGHTED HERE, WHICH ALLOWS YOU TO MEASURE AND COUNT THE NUMBER OF CALCIFICATIONS THAT EXIST AND ALSO WHETHER THEY ARE CLUSTERED OR DIFFUSED. WE ARE ALSO USING SHEAR WEIGHT ELASING TO FEE TO ASSESS MR. SENTAL DENSITY. THE CONCEPT INVOLVES THE USE OF THE SHORT ACUTIC PUSH PULSE TO THE PLACENTAL CAUSING DISPLACEMENT. SO THE ULTRASOUND BEING A SIGNAL THAT PUSHES AN ACOUSTIC SIGNAL THAT GOES SIDEWAYS INTO THE PLACENTA AND THAT DISPLACEMENT MEASURES AND QUANTITATES. AND THAT PROPAGATION VELOCITY CAN BE CONVERTED TO A MEASURE OF TISSUE DENSITY. SO STARTING AT THE FIRST TRIMESTER, WE ARE ABLE TO MEASURE THE STIFFNESS OF THE PLACENTA USING THE SHEAR WEIGHT TECHNIQUE, BOTH IN ANTERIOR OR POSTERIOR PLACENTA AND BEING ABLE TO ASSESS THE CENTRAL PORTION, THE FRONTAL PORTION AND THE LOWER PORTION. WE ARE ALSO LOOKING AT PLACENTAL VASCULATURE USING A NOVEL ULTRASOUND TECHNIQUE THAT HIGHLIGHTS VASCULARITY WITHIN THE PLACENTA CALLED THE MICROVASCULAR IMAGING. THE WAY THIS WORKS, IT SEPARATES LOW VELOCITY WEAK FLOW SIGNALS FROM THE OVERLAYING TISSUE MOTION. THE DIFFICULTY IN REALLY SEEING CAPILLARY FLOW AND MAINLYTE FLOW IS THAT THE TISSUE VIBRATES AND THAT CREATES ARTIFACT. THAT SOFTWARE IS ABLE TO SEPARATE THE TWO THUS ENABLING US TO LOOK AT THE FLOW WITHIN THE PLACENTA IN A WAY WE HAVE NOT SEEN BEFORE. AND THE SMI SIGNAL THEN IS DISPLAYED ALLOWING US TO SEE MICROVASCULAR FLOW WITHOUT THE NEED OF CONTRAST AGENTS. NOT ONLY WE CAN SEE THE BLOOD FLOW BUT ALSO QUANTITATE THE BLOOD FLOW BY APPLYING DOPPLER SIGNALS. HERE IS SOME EXAMPLES OF WHAT WE CAN SEE TODAY. HERE IS THE SECOND TRIMESTER PLACENTA. YOU CAN SEE THE VASCULARITY WITHIN. HERE IS ANOTHER PLACENTA RIGHT HERE. THIS IS THE MATERNAL SIDE. THIS IS THE FETAL SIDE RIGHT HERE. AND THIS HERE AT 15-16 WEEKS YOU CAN ACTUALLY SEE THE FETAL CIRCULATION AND SEE THE MATERNAL CIRCULATION ON TOP. THAT ALLOWS US TO COUNT THE SPIRAL ARTERIES, TO COUNT THE FETAL ARTERIOLES AND QUANTITATE THEM USING DOPPLER TECHNIQUES. SO ON THE MATERNAL PLACENTAL VASCULAR SIDE, WE ARE LOOKING AT THE UTERINE ARTERIES. WE ARE LOOKING AT THE BASAL ARTERIES AND WE ARE LOOKING AT THE SPIRAL ARTERIES. NOT ONLY AT THE DOPPLER INDEXES, WHICH INCLUDE THE PEAK SYSTOLIC VELOCITIES, AND ALSO WE ARE LOOKING AT THE SIZE OF THE SPIRAL ARTERIES AS YOU SEE HERE. ON THE FETAL SIDE, WE ARE LOOKING AT THE UMBILICAL ARTERY AND UMBILICAL VAIN, AND LOOKING AT THE FETAL PLACENTAL VASCULATURE. HERE WE ARE LOOKING AT THE ARTERIOLES AND THEIR INDEXES AND ALSO LOOKING AT THE NUMBER AND WE ARE LOOKING AT THE PEAK SYSTOLIC VELOCITIES. ON THE PLACENTA WE ARE ALSO DOING A PLACENTAL VASCULAR INDEX. WE ARE TAKING A PORTION OF THE PLACENTA AND ASSESSING THE RATIO OF THE VASC LARD PICK CELLS WITHIN THAT IMAGE VERSUS THE NUMBER EVER GRAY SCALE CELLS WHICH GIVES US INDEX TO ASSESS HOW VASCULAR THAT BLOCK OF TISSUE IS AS WE LOOK AT IT AND WE CAN QUANTITATE THAT. AND ALSO WE ARE GETTING VOLUMES IN 3D OF THE VASCULAR PLACENTA. THIS IS A PLACENTA AT 13 WEEKS. THIS IS THE SAME PLACENTA I SHOWED YOU THE VOLUME OF AND OUR ABILITY TO ASSESS HOW DENSE THE BLOOD FLOW IS IN THE PLACENTA. MOVING INTO THE SECOND AND THIRD TRIMESTER, WE ARE ABLE TO OBTAIN IMAGES AS SUCH SHOWING THAT BASAL ARTERIES ARE HERE WITH THE SPIRAL ARTERIES COMING IN THE FETAL SIDE WITH THE FETAL ARTERIOLES COMING UP INTO THE PLACENTA. THE PLAN WAS TO TARGET 550 PATIENTS OVER FOUR YEARS. WE ARE ALMOST HALFWAY IN THE STUDY. W ENROLLED 254 PATIENTS THUS FAR AND 146 PATIENTS HAVE DELIVERED. I'M GOING TO SHOW YOU THE AGGREGATE DATA OF THE FIRST 100 PATIENTS. ONLY THE FIRST TRIMESTER ULTRASOUND, NOT A LONGITUDINAL DATA. JUST FOR THE SAKE OF SHOWING YOU A LITTLE BIT OF SOME OF THE RESULTS. SO ON THE DEMOGRAPHICS, YOU CAN SEE WHERE MATERNAL AGE, THE MEAN WAS ABOUT 30 YEARS OLD. SEE THE DISTRIBUTION FROM THE ETHNICITY AND RACE HERE. MATERNAL WEIGHT WITH BMI ABOUT 28. AND THE GRAPHITY AND PARITY OF THE FIRST 100 PATIENTS. HERE SHOWING SYSTOLIC AND DIASTOLIC BLOOD PRESSURE, NUMBER OF PRIOR PREGNANCIES AND THE NUMBER OF VAGINAL DELIVERIES AND MEDIANS AND RANGES AND NUMBER OF PRIOR C-SECTIONS. WHEN WE LOOK AT THE VASCULATURE, LOOKING HERE, WE WILL SHOW YOU WHAT THE MEDIAN IS HERE, THE MEAN IS OF THAT INDEX AND THE DISTRIBUTION OF THOSE PATIENTS. IN THE BOX PLOT DESIGN. THIS IS THE LEFT URINE ARTERY HERE. AGAIN WITH A MEAN KEY POSSIBILITY INDEX OF 1.4. AS WE MOVE INTO THE BASAL ARTERY, LET'S SEE WHAT WE GET. THE INDEX OF.6 AND AS WE MOVE INTO THE SPIRAL ARTERIES, YOU SEE THE NUMBER OF SPIRAL ARTERIES WE ARE ABLE TO IDENTIFY IN THE STUDY IS CLOSE TO 9.5, WHICH IS A SIGNIFICANT, I BELIEVE, COMPARED TO OTHER STUDIES THAT HAVE BEEN DONE BEFORE, PRIMARILY DUE TO THE TECHNOLOGY WE HAVE TODAY. WE ARE ALSO LOOKING AT THE POSITIVITY INDEX IN THE SPIRAL ARTERIES AND LOOKING AT THE PEAK SYSTOLIC VELOCITY, I WOULD LIKE YOU TO KNOW HOW HIGH IT IS. AND AS YOU CAN SEE, WE HAD SOME PATIENTS AT 13 WEEKS THAT HAD PEAK SYSTOLIC VELOCITIES APPROACHING 100 PER SECOND, INCREDIBLY HIGH VELOCITY FLOW IN THOSE PREGNANCIES. AND WE ARE LOOKING ON THE FETAL SIDE LOOKING AT THE NUMBER OF ARTERIOLES WE ARE ABLE TO STUDY. IT IS ABOUT ARTERIOLES ON THE FETAL SIDE. AGAIN, LOOKING AT THE POSSIBILITY INDEX OF THE INTRAPLACENTAL FETAL ARTERIOLES AND WE ARE LOOKING AT THE PEAK SYSTOLIC VELOCITY AT 6 CENTIMETERS PER SECOND. LOOKING AT THE SHEAR WEIGHT OF THE PLACENTA, WE TYPICALLY LOOK AT THREE SEGMENTS. HERE I'M SHOWING YOU CENTRAL SEGMENT RIGHT HERE WITH 6 .5 KILO PASCHALL. THAT'S WHERE WE ARE PLUS OR MINUS TWO FOR STANDARD DEVIATION AND THE CALCIFICATION WE SEE ON OUR EVALUATION, ABOUT 12% OF THE SAMPLE. NOW IF I PUT AT LEAST ALL OF THESE TOGETHER TO KIND OF CREATE A STORY OF HOW THE BLOOD FLOW COMING ON THE MATERNAL SIDE - YOU CAN SEAT UTERINE ARTERY PI IMPLIES FIRST IN THE TRIMESTER AND AS YOU GET CLOSE TO THE BASAL ARTERY AND FIND RESISTANCE DROPPING SUBSTANTIALLY ALL THE WAY THROUGH THE SPIRAL ARTERY AS YOU SEE HERE. AND THAT HAS BEEN KNOWN BEFORE AND NOW SUBSTANTIATED IN A LARGE DATASET. WE ALSO ARE ABLE TO SEE ABOUT EIGHT SPIRAL ARTERIES FOR ANALYSIS WHICH IS A SIGNIFICANT NUMBER, AND I MENTIONED HOW SIGNIFICANT THE PEAK SYSTOLIC VELOCITY, ABOUT 66 CENTIMETERS PER SECOND. NOW IF YOU ADD TO THAT, THE FETAL SIDE, OUR POSSIBILITY INDEX WAS AGAIN REFLECTIVE OF A LOW IMPEDENCE CIRCULATION ON THE FETAL SIDE WITH EIGHT FETAL ARTERIES WE ARE ABLE TO STUDY PER PLACENTA AND LOW PEAK SYSTOLIC. SO THERE IS ABOUT A 10-FOLD DROP IN THE VELOCITY OF FLOW OF BLOOD FROM THE MATERNAL TO THE FETAL SIDE, WHICH I THINK IS INTENDED BY DESIGN TO ALLOW BLOOD TO BE PUSHED FORCEFULLY INTO THEVILLE EYE FOR DIFFUSION AND FOR EXCHANGE. SO AS YOU CAN SEE THE EXISTING NOVEL ULTRASOUND TECHNOLOGY REALLY ALLOW US TO EVALUATE THE PLACENTA QUITE COMPREHENSIVELY AND IN REALTIME FROM EARLY GESTATION. THERE ARE SOME EVOLVING TOOLS COMING ABOUT AND WE ARE INCORPORATING THEM INTO THE STUDY, CONTINUE TO DO IRB MODIFICATION FOR THAT PURPOSE. THERE IS A NEW TOOL CALLED, INTENSITY ANALYSIS. INTENSITY ANALYSIS ON ULTRASOUND IS A PARAMETRIC IMAGING METHOD TO ALLOW US TO QUANTIFY TISSUE ECOGENESIS. SO THE SHEAR WEIGHT WE CAN DO TISSUE DENNIS. WE LOOK AT THE ECHO GENISITY, KIND OF LIKE THE HOMOGENAITY OF THE SUSPECT PATTERN WITHIN THE ULTRASOUND. THIS IS QUANTITATIVE METHOD. HERE YOU DISPLAY REALTIME COLOR MAP OF THE NORMALIZED LOCAL VARIANCE PARAMETER, AND THAT IS WHAT FOR INSTANCE THE NORMAL IS EQUAL TO ONE. AND WE ARE ABLE TO MEASURE THE MEAN AND DISPLAY ALONG A HISTOGRAM OF THE NORMAL. THIS IS WHAT THE INTENSITY ANALYSIS LOOKS LIKE. I CAN GET A PLACENTA AND CHOOSE AREAS WITHIN THE PLACENTA AND GET THESE MAPS THAT TELLS ME HOW DENSE -- HOW ECOGENIC THE TISSUE IS IN REFERENCE TO A STANDARD AND THAT COULD BE USED QUANTITATIVELY TO ASSESS THE TISSUE ECHO GENISITY, ANOTHER REFLECTION OF TISSUE DENSITY. THERE IS ANOTHER NEW NOVEL TECHNIQUE CALLED, ATTENUATION IMAGING. HERE YOU VISUALIZE AND MEASURE THE ATTENUATION COEFFICIENT CODE THROUGH TISSUES. SO IS IT IS BEING ATTENUATED BY THE QUALITY OF THE TISSUE IT IT IS GOING THROUGH AND NOW WE ARE ABLE TO MEASURE AND QUANTITATE THAT ATTENUATION COEFFICIENT. SO ULTRASOUND IS DISPLAYED VISUALLY WITH A REALTIME COLOR MAP AND ATTENUATION IMAGING IS A QUANTITATIVE METHOD, THOUGH, THAT ALLOWS US TO ASSESS TISSUE CHARACTERIZATION IN ANOTHER FORMAT OTHER THAN SHEAR WEIGHT. AND THAT MAY PROVIDE USEFUL CLINICAL INFORMATION. SO HERE IS A NORMAL ATTENUATION OF AN ANTERIOR PLACENTA HERE AND WE CAN QUANTITATE THAT AS YOU SEE HERE. AND THIS IS AN ABNORMAL ATTENUATION IN A PLACENTA THAT REFLECTS IN A DIFFERENT QUANTIFICATION. SO WE HAVE JUST STARTED TO ADAPT THESE TECHNIQUES INTO OUR STUDY AND ADDING THEM ON OUR ABILITY TO EVALUATE THE PLACENTA. SO AS I HAVE SHOWN YOU, THE CURRENT ULTRASOUND TECHNOLOGY DESPITE A LOT OF NOVEL TECHNIQUES THAT DID NOT REALLY EXIST 5 YEARS AGO ALLOWS US TO LOOK AT THE PLACENTA ON THE STRUCTURE AND FUNCTION OF THE PLACENTA AND CERTAINLY THE CARDIOVASCULAR, ADDING CARDIOVASCULAR ELEMENT ON THE FECAL SIDE WITH THE VASCULARITY AND THE PLACENTA SHOULD ALLOW US TO ANALYZE IT VERY COMPREHENSIVELY MOVING FORWARD. I TRULY BELIEVE THAT WHAT WE ARE LOOKING AT AN ULTRASOUND NOW IS JUST A TIP OF THE ICEBERG. AND I BELIEVE THAT AS YOU HAVE SEEN IN THE LAST SIX MONTHS, WE HAD NEW TECHNOLOGY. I REALLY FEEL THAT THE FUTURE OF ULTRASOUND TECHNOLOGY IS VERY, VERY BRIGHT AND OUR ABILITY TO STANDARDIZE THE APPROACH AND THE ABILITY TO EVALUATE THE PLACENTA QUITE COMPREHENSIVELY. SO, THE HUMAN PLACENTA PROJECT ALLOWED US TO STUDY THE FETUS AND THE PLACENTA IN REALTIME AND IN EARLY GESTATION, WHICH IS REALLY CRITICAL STARTING AT 13 WEEKS AND LONGITUDINALLY MOVING FORWARD. IT IS EASILY INTRODUCED TO CLINICAL PRACTICE. WE ARE HOPING THAT IF WE FIND A PLACENTAL INDEX, IF YOU WILL, OR A COMBINATION OF PARAMETERS THAT ARE PREDICTIVE OF PREGNANCY OUTCOMES, THEN THIS CAN BE ADAPTED FAIRLY QUICKLY TO CLINICAL PRACTICE. IT IS A QUANTITATIVE ASSESSMENT OF PLACENTAL STRUCTURE AND FUNCTION. IT'S NOT ONLY LOOKING AT THE IMAGE BUT ALSO BEING ABLING TO GET SOME QUANTITATIVE PARAMETERS WHICH ARE REALLY EASY TO ANALYZE, AND CONTINUES TO EVOLVE WITH NEW AMPLIFICATIONS. SO A LOT OF THANKS, FIRST TO THE NIH AND NICHD, FOR PUSHING US TO STUDY THE PLACENTA IN WAYS HAVE YOU NOT THOUGHT ABOUT BEFORE. THANKS TO CATHY FOR HER VISION INTO THIS AND FOR DAVID FOR REALLY HELPING US THROUGH THAT. I WANT TO THANK ITS EDMS AND UTMB TEAM, THE RESEARCHERS AND MY COINVESTIGATORS FOR REALLY A LOT OF DEDICATED WORK AND AS YOU CAN SEE, WE ARE NARROWLY ADVANCED IN PATIENT RECRUITMENT THANKS TO OUR NURSE COORDINATORS THAT HAVE DONE INCREDIBLE WORK, TWO OF THEM ARE IN THE AUDIENCE, LANA AND JOANNE, AND WE ARE REALLY EXCITED ABOUT THE FUTURE OF THIS AND VERY HOPEFUL. THANK YOU. [ APPLAUSE ] >> DR. WEINBERG: VERY NICE. WE HAVE TIME FOR A FEW QUESTIONS. >> AUDIENCE MEMBER: THANK YOU FOR AN INCREDIBLE LECTURE AND ALL OF THIS FANTASTIC PICTURES. ANY IDEA WHAT HAPPENS IN PATHOLOGY LIKE WITH THIS WONDERFUL SPIRAL ARTERIES. DO YOU SEE ANY DIFFERENCE IN PREECLAMPSIA? >> DR. ABUHAMAD: WE ARE OBTAINING PLACENTAL BIOPSIES TISSUE AND STORING THOSE. WE HAVE NOT ANALYZED THE PATHOLOGY IN RELATIONSHIP THO WHAT WE SEE. WE ARE HOPING WE WILL BE ABLE TO DO SO AS WE GET CLOSER TOWARDS THE END OF THE STUDY. >> AUDIENCE MEMBER: GOOD LUCK. >> DR. ABUHAMAD: THANK YOU. >> DR. WEINBERG: KEEP THE QUESTIONS BRIEF AND THE ANSWERS MAY HAVE TO BE BRIEF BECAUSE WE HAVE QUITE A LINE. >> AUDIENCE MEMBER: SURE. THE TWO MOST IMPORTANT QUESTIONS TO ME ARE, GENERALIZABILITY AND THEN I HAVE A SPECIFIC QUESTION ABOUT THE ANATOMY THAT YOU'RE SHOWING. I'M ASSUMING THAT THESE ARE ALL PROPRIETARY TOSHIBA-BASED GNOMOGRAMS, EQUATIONS, BLAH, BLAH, BLAH. AND I THINK AS I MADE CLEAR IN THIS METING EVERY YEAR I HAVE BEEN HERE THAT PROPRIETARY SOFTWARE LEADS TO A LACK OF GENERALIZABILITY IN LARGE CLINICAL SETTINGS. AND SO WHILE THE TOOLS AREERY NICE AND VERY PRETTY, IF YOU DON'T HAVE A TOSHIBA, YOU WON'T BE ABLE TO CONDUCT THESE KINDS OF TESTS. AND ARE YOU WORKING WITH ANY BIOENGINEERS THAT HAVE ACCESS TO THE SOFTWARE TO TEST WHETHER OR NOT THE CALCULATIONS AND EQUATIONS BEING USED BY THE PARENT COMPANY CARRY VALIDITY IN A LARGER AND BROADER SENSE? COULD THEY BE APPLIED TO ANY PATIENT ANYWHERE. >> DR. ABUHAMAD: LET ME ADDRESS THAT ISSUE. FIRST IN THE PROPRIETARY ASPECT, I HAVE BEEN IN THE WORLD OF ULTRASOUND FOR A LONG, LONG TIME. WHAT I HAVE NOTICED IS THE ULTRASOUND COMPANIES MEET EACH OTHER AT THE FOREFRONT ON MANY DIFFERENT ASPECTS. SO THAT TECHNOLOGY IS A TOSHIBA TECHNOLOGY BUT I ANTICIPATE IT WILL BE AVAILABLE IN MANY OTHER COMPANIES AS WE MOVE THROUGH TIME. THERE ARE NO ALGORITHMS THAT ARE SPECIFIED TO THIS OR FORMULAS. WE ARE DEVELOPING THE FORMULAS AS WE GO. IN OTHER WORDS, THAT HUMAN PLACENTA PROJECT IS GETTING THE GNOMOGRAMS FOR ALL PARAMETERS THAT WILL BE AVAILABLE TO EVERYBODY TO USE. THAT'S THEANTAGE OF A LONGITUDINAL STUDY THAT INCLUDES A LOT OF NORMAL PATIENTS. >> AUDIENCE MEMBER: AND THE SECOND QUESTION HAD TO DO WITH THE IDENTIFICATION OF BASAL ARTERIES IN THE SUB PNTAL VASCULAR BED. HOW WAS THAT DONE? WHO SAID THEY WERE BASAL ARTERIES? THEY LOOKED TO BE AN AFFIDAVIT MOTTIC PLEX US OF ARTERIOLE VENUS THAT FORM IN THE -- >> DR. ABUHAMAD: SO WE FOLLOW THE URINE ARTERIES UP ON THE PLACENTAL BED UNTIL IT BRANCHES INTO THE LARGE BASAL ARTERY COMING INTO THE PLACENTA. SO WHETHER THEY ARE TRULY THE BASAL ARTERIES OR A BRANCH BECOMES REALLY IRRELEVANT AS THE DATA IS ACCUMULATED. BECAUSE AS LONG AS THE TECHNIQ IS STANDARDIZED TO OBTAIN MEASUREMENTS FROM THAT VESSEL IT REALLY DOESN'T MATTER WHAT THAT VESSEL IS. IICIPATE I THE BASAL ARTERY B ON EXPERIENCE DOING THIS, BUT IF IT'S THE SUB BASAL ARTERIES, I DON'T THINK IT IMPACTS THE DATA OR THE RESULTS OF THE DATA. >> AUDIENCE MEMBER: I WOULD DISAGREE BECAUSE THE SUB PLACENTAL -- IS WHAT ALLOWS THE SPIRAL ARTERY JETS TO DECREASE INELOCITY SO THEY DON'T ACTUALLY DAMAGE THE UNDERLYING VILLAGE TISSUE. >> DR. ABUHAMAD: WE WILL LOOK INTO THAT. >> AUDIENCE MEMBER: VERY NICE PRESENTATION. I ENJOYED IT. THE THING IS YOUR GROUP IS FROM 13 WEEKS PREGNANCY. WILL YOU SEE A CHANGE BETWEEN -- 20. >> DR. ABUHAMAD: THE QUESTION IS DID I SEE A CHANGE? I HAVE NOT SEEN A CHANGE. >> AUDIENCE MEMBER: WHAT IS THE RATIONAL FOR STARTING 13 WEEKS? >> DR. ABUHAMAD: WE WANTED TO START EARLY GESTATION AND WANTED TO STARTED WHEN WE KNOW THE PREGNANCY IS WELL ESTABLISHED AND THE PATIENT WOULD TAKE INTO ACCOUNT RECRUITMENT AND 13 WEEKS SEEMED TO BE THE MOST -- >> AUDIENCE MEMBER: BUT THE VASCULATURE, CHANGES FROM 11 WEEKS FROM THE HIGH POTTIC STATE TO AN MOCKSIC STATE. SO IF THE VASCULATURE IS CHANGING DURING THAT TIME AND RE SEEING RELATED TO THAT TIME, WILL IT MAKE A DIFFERENCE? WE WON'T BE ABLE TO STUDY 11LY, WEEKS AND 12 WEEKS. WE ARE STARTING IN 13 WEEKS. MOSTATIENTS ARE ENROLLED THAT THE TIME AND FIRST ULTRASOUND IS 13 WEEKS. THERE IS SOME LIMITATIONS. I DIDN'T WANT TO START AT 10 OR 11 WEEKS. WE WANTED TO MAKE SURE WE CAN SAMPLE ALL THE INFORMATION WE NEED. SO THAT'S THE DECISION TO REALLY IS THAT RIGHT AT 13. WE WANTED TO START EARLY ENOUGH BUT AT THE SAME TIME WE WANTED TO MAKE SURE TECHNOLOGY IS APPLICABLE TO WHAT WE ARE MEASURING. THANK YOU. >> AUDIENCE MEMBER: REALLY NICE PRESENTATION. SO MY POINT WAS, CAN YOU USE THIS TECHNOLOGY TO STUDY THE FETAL BODY PARTS, ESPECIALLY VASCULATURE ORGAN SYSTEM, BRAIN, KIDNEY? EVENTUALLY THE EFFECT OF PLACENTAL WILL EFFECT THE FUNCTIONS OF THOSE AND A WHOLE NEW BRAVE NEW WORLD YOU CAN OPEN UP AND ALSO FOLLOW LONGITUDINALLY BECAUSE THAT IS THE ONE THAT DETERMINES WHETHER YOU WANT TO TERMINATE THE PREGNANCY OR CONTINUE. >> DR. ABUHAMAD: THANK YOU FOR THE COMMENT. YES, WE ARE. I DID NOT INCLUDE IT IN HERE BUT WE ARE DOING FLOOD FLOW IN THE FETAL BRAIN, THE FETAL STOMACH, THE FETAL LIVER AND SO FORTH. WE ARE COLLECTING THAT DATA USING THE TECHNOLOGY BUT WE HAVE NOT ANALYZED IT. THANK YOU. >> AUDIENCE MEMBER: THANK YOU. MARY RUTHERFORD FROM LONDON. IT WAS A GREAT TALK AND FABULOUS TO SEE ULTRASOUND MOVING FORWARD. IN MR, WE ARE PARANOID ABOUT SAFETY. COULD YOU JUST SAY A FEW WORDS ABOUT SAFETY IN THESE EMERGING TECHNIQUES. >> DR. ABUHAMAD: YES, THANK YOU. AND AS YOU KNOW, THERE IS SOME CONCERN ABOUT USING DOPPLER TECHNIQUES IN THE FIRST TRIMESTER AND THAT IS REALLY THE CONCERN IN ULTRASOUND, THE THEORETICAL RISK BECAUSE ESPECIALLY WHEN YOU FOCUS THE YOU'RE STUDYING.ETA THAT LOOKING AT THE PLACENTA AND LOOKING AT THE PLACENTAL VASCULATURE AND UTERINE WALL IS SAFE, BECAUSE YOU ARE NOT TARGETING THE FETUS. WELL WE DO DOPPLERS AND BLOOD FLOW ON THE FETUS, THROUGH OUR IRB AND WE ARE INCOME APPLIANCE WITH THE SOCIETIES WITH REGARDS REGARDING TO USE AS LOW AS REASONABLY ACHIEVABLE, YOU MUTT THE COLOR DOPPLER AND PULSE VERY QUICKLY AND MINIMIZE THE TIME YOU SPEND ON THE FETUS. WE ARE INCOME APPLIANCE WITH THE SOCIETIES REGULATIONS ON THAT -- IN COMPLIANCE. BUT THE TIME THAT IS SPENT STUDYING PLACENTA IS OUTSIDE OF THE FETUS SO IN THEORY, THE IT'S SAFE TO USE BECAUSE THE ULTRASOUND BEAM IS NOT DIRECTOD FETAL PARTS. >> AUDIENCE MEMBER: NICHD. ABOUT THE ULTRASOUND LIMITATION LACK OF RESOLUTION. THERE ARE WORK DONE BY FRENCH GROUP USING BUBBLES AS A CONTRAST AGENT AND FOLLOW THAT IS MAYBE AN ORD OF MAGNITUDE. RESOLUTION YOU NEED TO LOOK AT THE MICROCIRCULATION. WHAT IS YOUR TAKE ON THAT? AND AGAIN, THE WORK DONE FOR SUPER RESOLUTION, WHICH THERE SYSTEM OTHER THAN TOSHIBA LIKE THE SONY AND SO ON. WHAT DO YOU THINK ABOUT THIS? >> DR. ABUHAMAD: TWO WORDS. ONE ON CONTRAST 8. SO I THINK -- AGENTS -- WE SPENT WITH THE SOCIETY OF ULTRASOUND AND MEDICINE, AND SPENT A LOT OF TIME GETTING CONTRAST JUST APPROVED FOR LIVER APPLICATIONS IN ADULTS. IT TOOK ABOUT 10 YEARS OF WORK WITH THE FD TOO. GET THERE. I REALLY DOUBT VERY MUCH THAT WE WOULD HAVE THE ABILITY TO USE CONTRAST IN OB TECH IS CALL IMAGING ANY TIME IN THE NEAR FUTURE. HOWEVER -- OB TICKET CALL -- THE SOFTWARE WE HAVE TODAY IN ULTRASOUND IS CAN ALLOWING US TO LOOK AT THE MICROVASCULATURE WITHOUT THE NEED OF CONTRAST. THE ADVANCES WE ARE SEEING IN ULTRASOUND AND THOSE THAT WILL BE COMING IN THE NEXT 5-10 YEARS, IS GOING TO OPEN A LOT OF DOORS LOOK AT PLACENTAL TISSUE AND LOOK AT FETAL TISSUE WITHOUT THE NEED FOR CONTRAST. WITH REGARDS TO ULTRASOUND RESOLUTION, WE THOUGHT 15 YEARS AGO THAT WE GOT THE PEAK OF WHERE WE NEED TO BE IN ULTRASOUND AND YOU CAN SEE IT'S INCREDIBLE ADVANCEMENT EVEN IN THE PAST 5 YEARS AND THE QUALITY OF ULTRASOUND AND ALL MANUFACTURERS. THERE ARE TRANSDUCERS AT 10-12 MEGAHERTZ THAT ARE ABDOMINAL THA ALLOWS YOU TO SEE ANATOMY IN GREAT DETAIL. I'M VERY OPTIMISTIC ABOUT THE FUTURE OF ULTRASOUND WITH REGARDS TO OUR ABILITY TO STUDY THE EARLY PREGNANCY BECAUSE OF ALL THESE ADVANCEMENTS COMING ABOUT. >> AUDIENCE MEMBER: CHRISTIAN MEYERS FROM COLUMBIA UNIVERSITY. MECHANICAL ENGINEER. HAVE YOU LOOKED AT -- >> DR. ABUHAMAD: OHNO. >> AUDIENCE MEMBER: I THOUGHT A NICE VALIDATION COULD BE, HAVE YOU LOOKED AT THE CORRELATION BETWEEN THE FUNCTION PARAMETERS SUCH AS ELASTICITY AND MICROCALCIFICATION OR DENSITY? >> DR. ABUHAMAD: THE PLAN IS TO DO SO AT THE END. I JUST ANALYZED THE DATA LINEAR FOR THE FIRST TRIRESTER. THE PLAN IS TO CORRELATE ALL THE PARAMETERS AND TRY TO CORRELATE PARAMETERS WITH THE NICE LAKE ACID DATA WE WILL HAVE AND TRY TO CORRELATE OR COME UP WITH AN INDEX THAT MAYBE ULTRASOUND PLUS SOMETHING ELSE OR ULTRASOUND AND DIFFERENT THINGS THAT HAS A MUCH BETTER PREDICTIVE POWER. >> AUDIENCE MEMBER: I THOUGHT THAT WAS EXCELLENT. THIS IS A PLUG FOR YOU FOR CONTINUED FUNDING. I DON'T KNOW YOU AND YOU DON'T KNOW ME. I HAVE NO -- >> DR. ABUHAMAD: THANK YOU. >> AUDIENCE MEMBER: I'M WONDERING IF YOU HAVE THE POWER WITH YOUR N, TO SHOW ABNORMALITIES WHICH ARE NOT COMMON. LIKE UF. AND PREECLAMPSIA. I THINK WHAT YOU'RE DOING IS VERY EXCITING BUT I THINK YOU NEED A LOT MORE. >> DR. ABUHAMAD: THANK YOU. I AGREE AND I'M STA THE QUESTION AGAIN TO CATHY AND DAVID I NEED MORE FUNDING. [ LAUGHS ] >> AUDIENCE MEMBER: RICH MILLER, ROCHESTER. WONDERFUL TO SEE ALL OF YOUR WORK HERE, ESPECIALLY YOUR ELASOGRAPHY PROGRESS. YOU MADE OVER THE LAST YEAR IN THE ATTENUATION WORK. WITH ALL OF THE OTHER QUESTIONS ANSWERED, I'M JUST ADDING TO THE ACCOLADES FOR CONTINUED EFFORT AND CONGRATULATIONS. >> DR. ABUHAMAD: THANK YOU. THANK YOU. [ APPLAUSE ] >> DR. WEINBERG: SO THAT WAS GREAT NOW WE'LL FOLLOW WITH DR. LOONEY WHO I HAVE NOT HAD A CHANCE TO MEET. THERE HE IS. WHO ALSO WILL BE TALKING ABOUT ULTRASOUND. >> DR. LOONEY: THAN YOU FOR THE INTRODUCTION. TODAY I'M GOING TO BE INTRODUCING A SYSTEM WE HAVE BEEN DEVELOPING FOR AUTUMN SEGMENTATION OF THE PLACENTA IN TREATING ULTRASOUND. WHEN I SAY SEGMENTATION, I MEAN TAKING THE ULTRASOUND VOLUME AND DIVIDING IT UP INTO SUBREGIONS OF PLACENTAL TISSUE. I'M GOING TO FIRST INTRODUCE THE RATIONAL FOR THE PROJECT AND TELL YOU WHY THIS WORK WE ARE DOING IS IMPORTANT, TELL YOU ABOUT THE DATA WE HAVE THAT WE ARE USING AND GIVE YOU A BRIEF INTRODUCTION OF DEEP LEARNING AND THEN SHOW YOU SOME RESULTS USING TWO PIECES OF SOFTWARE. SO, FETAL GROWTH RESTRICTION HAS BEEN SHOWN -- IF YOU HAVE INSUFFICIENT PLACENTA YOU CANHAVE POOR GRO WTH OF THE FETUS AND ULTIMATELY. POOR PLACENTAL FUNCTION IS IMPLICATED IN 1/3 OF STILLBIRTHS WORLDWIDE. IF WE ARE ABLE TO IDENTIFY THOSE PREGNANCIES AT RISK, WE WILL BE ABLE TO ALLOCATE RESOURCES APPROPRIATELY SO, IN COUNTRIES WHERE RESOURCES ARE LIMITED AND IT'S NOT POSSIBLE TO REPEATEDLY SCAN WOMEN THROUGHOUT THE PREGNANCY, WE WILL BE ABLE TO APPROPRIATELY TARGET THOSE RESOURCE SYSTEM AND WE CAN AVOID INAPPROPRIATELY MEDICALIZING WOMEN. IF WE ARE ALSO ABLE TO IDENTIFY POPULATIONS OF WOMEN WHO ARE AT RISK THROUGHOUT THE PREGNANCY, WE WILL BE ABLE TO IDENTIFY THE POPULATIONS THAT CAN BE USED FOR STUDIES INTO TREATING GROWTH RESTRICTIONS AND THERE HAVE BEEN STUDIES LOOKING AT BOTH ANIMAL AND HUMAN MODELS. PLACENTAL VOLUME HAS LONG BEEN KNOWN TO BE ASSOCIATED TO BE A PREDICTER FOR GROWTH RESTRICTION AND PREECLAMPSIA. THE ISSUE WITH USING PLACENTAL VOLUME IS THAT IT IS VERY TIME CONSUMING. THE METHODS THAT ARE AVAILABLE TO DO SO ARE MANUAL SEGMENTATION, WHICH TAKES A LOT OF TIME, AND THERE ARE SEMI-AUTOMATED METHODS LIKE VO CALL, OR RANDOM WALKER METHOD. SO IF WE WERE ABLE TO AUTOMATE THIS PROCESS, IF WE WERE ABLE TO JUST PUSH A BUTTON AND HAVE A REALTIME ASSESSMENT OF THE PLACENTAL VOLUME, SHAPE AND OTHER MEASURES, WE WOULD BE ABLE TO DO THIS IN REALTIME BUT WE WOULD BE ABLE TO REMOVE OPERATOR DEPENDENCY, SO IT WOULD INCREASE ACCURACY AND REPRODUCIBILITY AND THIS WOULD ALLOW US TO PERFORM LARGE-SCALE TRIALS OF CLINICAL UTILITY AND PATIENT BENEFIT. WHAT OUR ULTIMATE GOAL IS TO PROVIDE A SIMPLE SCREENING TOOL THAT WILL ALLOW US TO IDENTIFY THOSE PREGNANCIES THAT ARE RISK FETAL GROWTH RESTRICTION AND PREECLAMPSIA. OUR SOFTWARE WILL BE OPEN-SOURCE AND THIS AUTOMATIC TOOL FOR SEGMENTING PLACENTA IN 3D ULTRASOUND WILL ALLOW US TO USE OTHER BIOMARKERS FROM 3D ULTRASOUND. SO WHAT DATA DO WE HAVE? WE HAVE 2,893, 3D ULTRASOUND VOLUMES. THESE HAVE BEEN ACQUIRED AT 11-13 PLUS 6 WEEKS. SO ALL THE VOLUMES HAVE HAD THE PLACENTA SEEDING. I MEAN THE GREEN IS THE CENTRAL TISSUE AND THE RED IS NON PLACENTAL TISSUE.& SO WE PERFORMED THE SEEDING ON ALL VOLUMES AND THE SEGMENTATION IS PASSING INTO THE RANDOM WALKER ALGORITHM AND THAT GIVES US SEGMENTATION IN 3D. SO THIS IS GIVEN US UNIQUE GROUND TRUTH IT'S TIME CONSUMING TO CREATE THIS SET AND IT'S BEEN HEAVILY QUALITY CONTROLLED. FIVE PEOPLE OVER THE SPACE OF THREE YEARS HAVE BEEN INVOLVED IN CREATING THIS DATASET. TO PERFORM THE RANDOM WALKER ALGORITHM, WE NEED TO TAKE OUR ULTRASOUND VOLUME AND TO PERFORM THIS SEEDING. SO HIGHLIGHT THE PLACENTAL TISSUE IN GREEN AND THE NON PLACENTAL TISSUE IN RED. AND DO THAT EVERY 10 SLICES THROUGHOUT THE ULTRASOUND VOLUME. SO THIS PROCESS TAKES ABOUT 3-8 MINUTES PER PLACENTA. SO CALCULATING THIS, WE ARE TALKING ABOUT 290 MAN HOURS AT LEAST TO CREATE THE DATASET AND THEN AN ADDITIONAL NUMBER OF DAYS TO PERFORM THE COMPUTATION COMPUTATIONS. I'M JUST GOING TOY SHOULD YOU A VIDEO OF THE SEEDING AND THE CORRESPONDING SEGMENTATION THAT WE GET FROM THE RANDOM WALKER ALGORITHM. SO THE YELLOW SHOWS THESE ARE THE PLACENTAL TISSUE AND THE GREEN IS THE NON PLACENTAL TISSUE. SO WHEN WE TAKE THIS SEEDING AND THE 3D ULTRASOUND VOLUME, WE PASS THAT INTO THE RANDOM WALKER ALGORITHM, THAT GIVES US OUR SEGMENTATION. AND THIS IS GOING TO FORM THE GROUND TRUTH DATA WE WILL USE TO PERFORM THE DEEP LEARNING WELL TO TRAIN OUR NEURONETWORK. WE ARE TRYING TO SIMULATE AND THEY TAKE THEIR 3D ULTRASOUND VOLUME AND LOOK AT INTENSITY VOLUMES AND DIVIDE IN COMPLEX WAYS AND THEY FORM A MAP OF THE SEGMENTATION SO THEYEATE A MODEL IN 3D OF THE PLACENTAL TISSUE AND NON PLACENTAL TISSUE. WE WANT TO BE ABLE TO AUTOMATE THAT PROCESS. FULLY CODED BY HUMAN. NO LEARNING INVOLVED AND THERE IS BEETLE INTRODUCED FROM THE HUMAN. THE ALTERNATIVE TO THIS IS DEEP LEARNING WHERE HAVE YOU VERY COMPLEX MODES. THERE IS MINIMAL INPUT FROM THE PROGRAMMER IN TERMS OF DEFINING HOW THIS MODEL BEHAVES AND THE MODEL WILL LEARN AND EVOLVE FROM NEW DATA AND WE AVOID BIAS IN THIS WAY. DEEP LEARNING IS UBIQUITOUS AND IT'S USED IN VOICE RECOGNITION SYSTEMS AND IMAGE RECOGNITION SYSTEM ON FACEBOOK, WEB SEARCH, GOOGLE, VIDEO GAMES. IT HAS TAKEN OFF. SO WHAT IS DEEP LEARNING? SO IT IS A METHOD FOR APPLYING SIMPLE MATHEMATICAL FUNCTIONS TO DATA. SO, YOU TAKE YOUR INPUT DATA AND APPLY A SERIES OF MATHEMATICAL OPERATIONS AND IT GIVES YOU YOUR OUTPUT. THE OUTPUT IS COMPARED TO YOUR GROUND TRUTH AND BASED UPON THAT COMPARISON, THE SIMPLE MATHEMATICAL OPERATIONS, PARAMETERS OF THESE SIMPLE MATHEMATICAL OPERATIONS ARE MODIFIED. AND THIS CYCLE CONTINUES TO LEARN SO YOU PASS YOUR DATA AND CONTINUE CITING THROUGH THIS PROCESS UNTIL YOU GET ADEQUATE PERFORMANCE. SO THE WAY IN WHICH THIS IS IMPLEMENTED IS USING THINGS CALLED ARTIFICIAL NEURONETWORKS. SO, WE HAVE SERIES OF LAYERS AND THESE ARE THE LAYERS OF MATHEMATICAL OPERATIONS AND IF YOU HAVE A LARGE NUMBER OF THESE LAYERS THAT GIVES YOU THE DEEP WITHIN THE DEEP LEARNING AND THE PROCESS OF LEARNING IS WHEN THE OUTPUT IS COMPARED TO THE GROUND TRUTH AND THESE MATHEMATICAL OPERATIONS ARE CHANGEDS AND THAT'S CALLED BACK PROPAGATION. THAT'S HOW THE PROCESS IS IMPLEMENTED. THE IDEA FOR DEEP LEARNING FOR NEURONETWORKS EXISTED SINCE THE 1980S. THE REASON WHY IT'S SO POPULAR NOW IS BECAUSE COMPUTATIONAL POWER IS NOW SO CHEAP. SO, OUR SYSTEM THAT WE ARE USING HAS PHENOMENAL AMOUNT OF COMPUTING SYSTEM BACK IN THE 70s. SO HOW DO I GO ABOUT DOING THIS TO IMPLEMENT A DEEP LEARNING SYSTEM? I NEED TO CHOOSE AN ARCHITECTURE, SO I CHOOSE TYPE AND NUMBER OF MATHEMATICAL OPERATIONS AND THEN TAKE MY DATASET AND DIVIDE IT INTO TRAINING AND VALIDATION AND TEST SET. I TAKE A PORTION, A BATCH OF MY TRAINING DATA, AND I LEARN ON THAT BATCH. I THEN EVALUATE THE PERFORMANCE AND REPEAT THAT THOUSANDS AND THOUSANDS OF TIMES SO THE MEAN SQUARED ERRORS APPLIED HERE. SO THIS IS THE ERROR OF THE OUTPUT COMPARED TO THE GROUND TRUTH. YOU HAVE A VERY HIGH MEANS ERROR INITIALLY AND THROUGHOUT THE LEARNING PROCESS DECREASES AND DECREASES UNTIL YOU REACH MINIMUM. YOU WILL NOTICE IT GRADUALLY STARTS TO INCREASE. THIS IS WHERE THERE IS NO MORE LEARNING GOING ON. THERE IS OVERFITTING GOING ON. SO ONCE YOU FINALLY ARE HAPPY WITH YOUR NEURONETWORK, TAKE IT AND EVALUATE IT ON THE SEPARATE TEST SET WHICH WILL GIVE YOU A MEASURE OF THE PERFORMANCE YOU WOULD EXPECT. NOW TO SHOW YOU SOME RESULTS WE HAVE USING DEEP LEARNING SYSTEM. BEFORE -- SO I'M GOING TO SHOW YOU USING TWO PIECES OF SOFTWARE : BEFORE I GET ON TO DISCUSS THOSE RESULTS, I WANT TO INTRODUCE A METRIC WHICH IS THE DISIMULATORY COEFFICIENT. SO THIS IS HOW WE ARE GOING TO COMPARE HOW WELL EVALUATED PERFORMANCE OF OUR SYSTEMS. THIS METRIC IS DEFINED TO BE TWICE THE INTERSECTION OF THE SEGMENTATIONS DIVIDED BY NUMBER OF ELEMENTS IN BOTH. SO EFFECTIVELY YOU GET ZERO IF THERE IS COMPLETE DISAGREEMENT AND NO OVERLAP AND YOU GET ONE IF THEY ARE EXACTLY THE SAME. AND THIS TOOL IS NOT AVAILABLE WITH SYSTEMS LIKE VO CALL BECAUSE YOU DON'T GET THE SEGMENTATION. SO, DEEP MEDIC IS SOFTWARE THAT WAS DEVELOPED IN LONDON TO APPLY DEEP LEARNING TO 3D MEDICAL IMAGING SEGMENTATION. THE SOFTWARE ALAOS SOME FLEXIBILITY IN TERMS OF ARK TECH TURP OF THESE MATHEMATICAL OPERATIONS SO WE CAN MODIFY THIS. AND IT WAS INITIALLY PUBLISHED BY TRAINING THE NEURONETWORK ON MRI IMAGES OF THE BRAIN TO DETECT LESIONS. SO WE HAVE TAKE THEN ARCHITECTURE, WHICH HAS TWO PATHWAYS OF DIFFERENT RESOLUTION, AND WE HAVE PATCHED IN OUR ULTRASOUND VOLUMES AND OUR GROUND TRUTHS AND WILL WE TRAINED IT. SO JUST SHOWING YOU SOME RESULTS. ON THE LEFT, WE HAVE OUR GROUND TRUTH AND ON THE RIGHT WE HAVE THE RESULT FROM DEEP MEDIC THAT IT PREDICTS ON THIS PARTICULAR CASE. SO THE DISIMILARITY COEFFICIENT FOR THIS PARTICULAR CASE IS IT -- TO OBTAIN THESE RESULTS, WE HAVE TRAINED IT ON 300 CASES. SO OUT OF OUR FULL DATASET. AND THE DISIMILARITY COEFFICIENTS THROUGHOUT THE LEARNING PROCESS WHICH IS WHAT WE ARE PLOTTING HERE. IT REACHES A PLATEAU AT THE END OF THE LEARNING PROCESS SO THAT CASE I SHOWED YOU IS REPRESENTATIVE OF THE MEDIAN THAT WE ATTAINED FROM DEEP MEDIC. SO WE ONLY USED 300 CASES FOR THIS WORK WE PUBLISHED THIS YEAR. CAN WE GET BETTER PERFORMANCE? TO DO THAT, WE HAVE TAKEN DEEP MEDIC AND INCREASED THE NUMBER OF CASES AND BECAUSE DEEP MEDIC ALLOWS YOU TO CONFIGURE IT, WE CAN INCREASE THE NUMBER OF MATHEMATICAL OPERATIONS WITH WHAT WE FIND. THE COEFFICIENT REMAINS THE SAME. WE DON'T GET INCREASE IN PERFORMANCE. THIS IS SOMEWHAT COUNTERINTUITIVE BECAUSE YOU WOULD CONVENTIONALLY THINK THAT BY INCREASING AMOUNT OF DATA AND COMPLEXITY OF MODEL, YOU WILL GET BETTER PERFORMANCE. SO THE QUESTION IS WHY? NOW TO TRY TO ANSWER THIS QUESTION, WE HAVE DEVELOPED OUR OWN IN-HOUSE SOFTWARE. SO THIS IS A NOVEL SYSTEM WE BUILT TO ALLOW US TO RAPIDLY DEVELOP AND ANALYZE THE PERFORMANCE OF DIFFERENT DEEP LEARNING ARCHITECTURES. WE HAVE NOW TESTED IT ON 24 DIFFERENTTINES OF ARCHITECTURES. AND WE HAVE BUILT THIS SOFTWARE ON TOP OF GOOGLE'S MACHINE LEARNING LIBRARY. SO THIS IS A PLOT SHOWING YOU THE DISIMILARITY COEFFICIENT AND BOX PLOT FOR EACH MODEL I MENTIONED. THERE ARE 24 DIFFERENT MODELS. THE DOTTED LINE SHOWS YOU THE MEDIAN VALUE THAT WE GOT FROM DEEP MEDIC. SO WE FIND THAT FOR SOME OF THESE MODELS, THE PERFORMANCE IS MUCH WORSE. FOR BETTER MODELS WE ARE GETTING A COEFFICIENT. SO WE GET SIGNIFICANT IMPROVEMENT AND PERFORMANCE FOR SOME OF THESE MODELS. SO THIS IS ALLOWING US TO RAPIDLY CHANGE ARCHITECTURES TO DIFFERENT TYPES OF ARCHITECTURES IN DEEP MEDIC THAT IS NOT POSSIBLE WITH DEEP MEDIC. SO LET ME SHOW YOU A COMPARISON OF THE GROWTH TRUTH TO THE SEGMENTATION FOR -- GROUND TRUTH -- FOR DE EP MEDIC AND USING A BETTER MODEL FROM OUR SOFTWARE. SO WHAT YOU SEE IS A DEEP MEDIC, AS IN EXTRA LOBES AND NOT PRESENT IN THE GROINED TRUTH NOR IN OX NET. SO YOU'LL SEE EXTRA TISSUE HERE THAT IS NOT PRESENT IN THE GROUND TRUTH NOR IN THIS REGION HERE AND AGAIN YOU'LL SEE IS THIS REGION HERE, NOT PRESENT IN GROUND TRUTH OR IN THE PREDICTION FROM OUR MODEL IN OX NET. DISIMILARITY COEFFICIENT FOR THE DEEP MEDIC IS.65 AND.8. SO THEY ARE REPRESENTED OF THE MEDIAN VALUES. WE CAN PLOT DISIMILARITY COEFFICIENT FOR BOTH OF THESE MODELS SO WE ARE PLOTTING THE DISIMILARITY COEFFICIENT FOR EACH INDIVIDUAL CASE FOR OX NET AND THE DISIMILARITY COEFFICIENT FOR EACH INDIVIDUAL CASE FOR DEEP MEDIC. THIS IS SAY LINE OF IDENTITY. SO WHAT WE SAID IS THE MEDIAN VALUE FOR OX NET IS INCREASED COMPARED TO DEEP MEDIC. BUT IT'S NOT CONSISTENTLY THE CASE THAT FOR ALL OF THESE CASES OX NET OUT% DEEP MEDIC. SOME OUTLIERS WHERE THE PERFORMANCE IS DRASTICALLY REDUCED AS COMPARED TO DEEP MEDIC. THERE ARE STILL QUESTIONS REMAINING. WITH THAT THEME WE NOTICED IN THE VIDEO, WHERE DEEP MEDIC ADDS IN A LOT OF EXTRA TISSUE, THIS IS SEEN THROUGHOUT THE DATASET. WHAT WE ARE PLOTTING HERE IS THE FALSE-POSITIVE ERROR FOR DEEP MEDIC VERSUS THE FALSE-POSITIVE ERROR FOR OX NET FOR EACH INDIVIDUAL CASE. SO WHAT YOU FIND IS THAT FOR ALMOST ALL CASES, DEEP MEDIC ADDS IN EXTRA TISSUE AT A GREATER RATE THAN OX NET. SO WE HAVE QUESTIONS REMAINING FOR OUR SOFTWARE. WHAT IS THE ARCHITECTURE? SIMILAR TO THE DEEP MEDIC, WE NEED TO INVESTIGATE. WE HAVE A LARGE TRAINING DATASET. ARE WE GETTING THE BEST PERFORMANCE OUT OF IT? HOW DOES IT VARY WITH CHANGES IN TRAINING DATA? AND WE HAVE IDENTIFIED THAT THERE ARE SOME OUTLIERS. IS THERE SOME KIND OF PATTERN TO THESE OUTLIERS? ISSUES WITH GAIN SETTINGS, PLACENTAL TYPE, LOCATION OF THE PLACENTA? THESE KINDS OF ISSUES. FINALLY THE COLONEL COLLUSION. SO SO CONCLUSION. SO WE HAVE FULLY AUTOMATED PLA SENTAL SEGMENTATION, THE FIRST AIM OF OUR UL1. THE PERFORMANCE WE OBTAINED USING OUR OX NET, WE HAVE SIGNIFICANTLY IMPROVED THE PERFORMANCE WE PREVIOUSLY PUBLISHED. AND THIS SOFTWARE OX FELT, WHICH ALLOWS YOU TO QUICKLY GENERATE DEEP LEARNING ARCHITECTURE, THIS COULD BE APPLIED TO OTHER IMAGING MODALITIES. SO WE WANT TO SEE HOW ADDING IN 3D POWER DOPPLER INTO THE TRAINING PROCESS MAY IMPROVE THE SEGMENTATION. WE CAN TAKE THE AUTOMATIC SEGMENTATION TOOL AND SEE HOW THE PREDICTIVE VALUE FOR ADVERSE PREGNANCY OUTCOMES IS. AND WE CAN TAKE ALREADY EXISTING TOOLS WITHIN OUR GROUP TO ANALYZE PLACENTAL AND APPLY TO AUTOMATIC SEGMENTATIONS. I'D LIKE TO THANK OUR MENTORS AND COLLABORATORS. I'D LIKE TO THANK THOSE FOR PROVIDING US WITH OUR GRAPHICS CARD TO PERFORM THESE COMPLICATIONS AND I'D LIKE TO ASK YOU FOR ANY QUESTIONS. [ APPLAUSE ] >> DR. WEINBERG: WE HAVE TIME FOR QUESTIONS. >> AUDIENCE MEMBER: HI, I HAVE A QUESTION. CAN WE TAKE US THROUGH A LITTLE BIT -- LIKE WHEN YOU USE THE DEEP MEDIC, IN LAYMAN'S TERMS COULD YOU SIMPLIFY FOR US LIKE WHAT THE COMPUTER WAS LOOKING -- WHAT THE COMPUTER WAS THRESHOLDING ON? LIKE WHAT THOSE DECONVOLUTION FUNCTIONS WERE IN YOUR MACHINE LEARNING, THOSE INNER SORT OF INNER PART OF THE NETWORK. WHAT WERE THE FUNCTIONS? SO WHAT WAS THE THRESHOLDING THAT IT WAS DOING AS PART OF THE DIGITAL PROCESSING TO RECOGNIZE THE PLACENTA? >> DR. LOONEY: IS THERE A TEXTURE ELEMENT? >> AUDIENCE MEMBER: LIKE IF YOU COULD EXPLAIN IN LAYMA TERMS WHAT WAS IT DOING? WHAT WAS THE DIGITAL PROCESSING GOING ON IN THERE? >> DR. LOONEY: IT'S SOMETHING THAT I'D LIKE TO LOOK INTO. THESE ARE COMPLEX MODELS SO IT'S DIFFICULT TO REALLY REASON ABOUT SPECIFICALLY THIS IS A 10-LAYER DEEP NETWORK. SO EXACTLY WHAT THESE FEATURES ARE AND WHAT THEY RELATE TO. MY HYPOTHESIS IS THAT IT WOULD BE TEXTURE ELEMENTS WITHIN THE 3D ULTRASOUND VOLUME. THAT WOULD BE -- >> AUDIENCE MEMBER: THAT'S REALLY COOL. SO BIT OF INSIGHT FOR ME. SO I GUESS DEEPRNING -- I DIDN'T KNOW THAT SO DEEP LEARNING IS SO, SO FIRST INDICATED THAT IT IS ACTUALLY PERFORMING FUNCTIONS THAT IS NOT -- WE DON 'T REALLY KNOW IN TERMS OF LIKE THE IMAGE PROCESSING, LIKE THE COMPUTER DOES IT IN THE DEPTH OF THE NETWORK. BUT WE REALLY CAN'T RECONSTRUCT THEH IT DID WAS. I NEVER KNOW THAT WAS A PROPERTY. >> DR. LOONEY: SO THROUGHOUT THE NETWORK, YOU CAN LOOK AT THE INDIVIDUAL LAYERS AND SEE WHAT IT IS OUTPUTTING AND IF YOU LOOK AT SOME PUBLICATIONS, THEY HAVE LOOKED AT THE INDIVIDUAL LAYERS WITHIN BRAIN MRI TO SEE WHAT THAT CORRELATES TO. AND IT CAN RELATE TO VARIOUS TISSUES WITHIN SPECIFICALLY FOR THE PUBLICATION OF DEEP MEDIC, WITHIN THE BRAIN AND SO ON. THAT IS SOMETHING THAT WOULD BE INTERESTING TO LOOK AT. >> AUDIENCE MEMBER: ONE LAST QUICK COMMENT. JUST BECAUSE PEOPLE MENTIONED CRAZY AND WILD THINGS. I THINK THIS IS IMPORTANT. I THINK IF WE HAD IMAGING BANKS, LIKE UNIVERSAL IMAGE BANKS, OR GLOBAL IMAGE BANKS LINKED WITH CLINICAL DATA AND THE OPPORTUNITY TO DO HIGH-LEVEL CLOUD PROCESSING, I THINK WE COULD LEARN A LOT. AND WILL THEN THE ISSUE OF DEEP -- WHATEVER, SO LIKE BROAD OUD-BASED NON-PROPRIETARY, GET OVER THE IRB PROBLEMS AND HAVE IMAGE BANKS TO HAVE NON-PROPRIETARY, CLOUD-BASED IMAGE PROCESSING BOTH HISTOLOGIY AND ALL OF THESE MEDICAL IMAGING AND LINK TO OUTCOMES AND BECAUSE GESTATIONAL AGE, IT MAKES A NECESSITY VERY LARGE NUMBERS SO THAT'S SOMETHING I THINK ABOUT. CHEERS. >> AUDIENCE MEMBER: JOHN FROM TORONTO. JUST TO REITERATE DAVID'S POINT. I THINK THAT THIS IDEA OF LEARNING WHAT IT IS YOUR PART OF VALING THAT IT DMPORTANT WHAT Y THINK IT DOES. AND ONE WAY TO START ON THAT IS THAT MANY OF THESE ALGORITHMS WERE BY AN UNSUPERVISED LEARNI OF A SPECIFYING TRANSFORMATION AND LOOKING AT WHAT THAT CONTAINS MIGHT BE CLUE TO WHAT IT IS THAT YOUR ALGORITHM IS FOCUSING ON. >> AUDIENCE MEMBER: HI [ INAUDIBLE ] SO MY QUESTION IS WHAT IS THE MAIN REQUIREMENT FOR HARDWARE? SO. >> DR. LOONEY: SORRY. I'M NOT QUITE FOLLOWING. >> AUDIENCE MEMBER: [ INAUDIBLE ] MINIMUM REQUIREMENT. HOW MANY NECESSARY TO RUN THE ACCELERATION -- >> DR. LOONEY: COMPUTATION RESULTS WE PUBLISHED WITH DEEP MEDIC, WE HAD A GPU WHICH HAD A TWO GIGABYTE MEMORY. SO WE COULD OBTAIN THOSE RESULTS I SHOWED YOU FROM DEEP MEDIC, WE OBTAINED ON THAT TO PRETREAT. MOVING INTO THE TYPE OF ARCHITECTURES WITH OX NET, WE HAVE BEEN USING THE TITAN XGPU, A HIGH SPECK GPU, BUT BECAUSE HAVE YOU ACCESS TO THAT MEMORY, YOU CAN -- IT DEPENDS ON THE ARCHITECTURE IS THE ANSWER TO YOUR QUESTION. AND BECAUSE E ARE SO MANY DIFFERENT TYPES OF ARCHITECTURE, SOME A VERY MEMORY INTENSIVE. OFHOSE ARE NOT. IT REALLY DEPENDS ON YOUR POTENTIAL. >> AUDIENCE MEMBER: AND ONE OF THOSE QUESTIONS IS LIKE -- I THINK IT WILL BE VERY HARD -- BETWEEN TISSUE -- IN THE BOUNDARY. SO I THINK DEEP LEARNING -- [ INAUDIBLE ] >> DR. LOONEY: I THINK THERE IS A FUZZY AREA THERE. I'M NOT SURE IT'S THAT EASY TOW CLINICALLY SEPARATE WITHIN THE ULTRASOUND VOLUME ITSELF THE PLACENTAL TISSUE AND NON-PLACENTAL TISSUE. I THINK THERE WILL BE SOME ERROR THERE IN TERMS OF THE SEGMENTATION. >> AUDIENCE MEMBER: OKAY. THANK YOU. >> AUDIENCE MEMBER: I THINK MY QUESTION FOLLOWS UP ON THAT. I'M WITH MIT. YOU LOOKED -- WHAT IS YOUR GUESS? HAVE YOU LOOKED AT HUMAN OPERATOR VARIABILITY? I DON'T HAVE EXPERIENCE WITH ULTRASOUND SO IT'S HARD TO GUESS SORT OF. IF YOU HAVE 5 PEOPLE SEGMENT THE PLACENTA, WHAT WOULD BE THE DICE? >> DR. LOONEY: THAT HAS BEEN PUBLISHED PREVIOUSLY BY SOME -- MY COLLEAGUES WHEN THEY WERE COMPARING MANUAL SEGMENTATION TO THE RANDOM WALKER METHOD. SO I WILL REFER YOU TO THAT. I CAN'T GIVE YOU VALUE OFF THE TOP OF MY HEAD. >> AUDIENCE MEMBER: I'M NOT LOOKING FOR RANDOM WALKER RELATIVE TO MANUAL SEGMENTATION, I'M ASKING FOR VARIABILITY AMONG THREE DIFFERENT CLINICIANS SAY WHO WOULD SEGMENT. BECAUSE THAT WOULD GIVE YOU THE NUMBER TO GO FOR WHEN EVALUATING USED IT'S IMPOSSIBLE TO TELL WHETHER 80% IS GREAT OR UNACCEPTABLE. >> DR. LOONEY: BUT WITHIN THAT WORK THEY LOOKED AT THAT AREA. AND I DON'T KNOW WHAT THE EXACT NUMBER IS. >> AUDIENCE MEMBER: AND THE OTHER QUESTION I HAD WAS, ABOUT THIS COMPARISONS OF THE NETWORK THAT YOU BUILT ON TENSER FLOW AND DEEP MEDIC. YOUR COMPARING TWO DIFFERENT SOFTWARE SYSTEMS AND IT SEEMS LIKE THE RIGHT THING TO COMPARE IS TWO DIFFERENT ARCHITECTURES OR K DIFFERENT ARCHITECTURES. WHAT ARE THE PROPERTIES OF THE SUGGESTS THAT MAKE YOU COMPARE THE SYSTEMS? TRAINING THE EXACTLY THE SAME ARCHITECTURE IN BOTH? >> DR. LOONEY: LIKE SO THE DEEP MEDIC IS SAY PIECE OF SOFTWARE NA HAS A ARCHITECTURE. I CANNISM THAT -- >> AUDIENCE MEMBER: YOU DON'T HAVE FLEXIBILITY OVER ARCHITECTURE? >> DR. LOONEY: THERE IS SOME FLEXIBILITY WITHIN DEEP MEDIC. >> AUDIENCE MEMBER: BUT THE COM BEAR SONS, WAS IT THE SAME ARCHITECTURE IN TWO SYSTEMS? >> DR. LOONEY: NO SO OX NET IS A SOFTWARE PLATFOR WE DEVELOPED ALLOW YOU TO DEVELOP DIFFERENT ARCHITECTURES. SO WE DEVELOPED LOTS OF DIFFERENT ARCHITECTURESES AND COMPARED THE BEST PERFORMING ONE TO DEEP MEDIC. >> AUDIENCE MEMBER: I DON'T SEE THE RELEVANCE OF WHAT SOFTWARE SYSTEM YOU IMPLEMENTED IT IN. IF YOU CAN COMPARE DIFFERET ARCHITECTURE INNE SYSTEM, I DON'T UNDERSTAND WHAT IF GIVES TO YOU IMPLEMENT IT -- >> DR. LOONEY: OUR INITIAL RESULTS WERE USING DEEP MEDIC. SO HAVING USED DEEP MEDIC, WE FIND A CERTAIN LEVEL OF PERFORMANCE. NOW OUR HYPOTHESIS WAS BY RADICALLY CHANGING THE ARCHITECTURE WE COULD ACHIEVE BETTER RESULTS. AND TO BE ABLE TO DO THAT, WE NEEDED TO BUILD A PIECE OF SOFTWARE, WHICH WE DID, OX NET, TO ALLOW US TO RADICALLY CHANGE THE ARCHITECTURE WHICH GIVES US BETTER PERFORMANCE. >> AUDIENCE MEMBER: BUT THE TENSE FLOW ITSELF GIVES YOU -- IT SOUNDS LIKE COFFEE BREAK DISCUSSION. I AGREE. THANK YOU. >> AUDIENCE MEMBER: CONRAD FROM WESTERN UNIVERSITY. I JUST WANTED TO ASK A COUPLE OF THINGS ABOUT THE MINIMUM AMOUNT THAT YOU WOULD NEED TO TRAIN FOR SEGMENTING THE ULTRASOUND. LIKE USED 300 HERE AND KIND OF HAD DIMINISHING RATE OF RETURN WHEN YOU PUT IN 2000. LIKE HOW DID YOU COME TO 300 AS SORT OF YOUR -- BECAUSE THAT WOULD BE 300 AUTOMATIC SEGMENTATIONS VERSUS 300 MANUAL SEGMENTATIONS THAT YOU HAD TO COMPARE IT TO, WOULD IT NOT? >> DR. LOONEY: WE TOOK 300 CASES AND WE USED 240 FOR TRAINING AND THEN 60 FOR -- 40 FOR VALIDATION AND 20 TO TEST. THE REASON WE CHOSE 300 WAS DUE TO HARDWARE LIMITATIONS. SO WE HAD A LOW SPECK GPU AND THAT WAS THE REASON WHY WE COULDN'T DO THE FULL DATASET. SO AS WE'VE ACQUIRED NEW HARDWARE, THAT ALLOWS US TO PERFORM LONGER TRAINING AND TO USE LARGER DATASETS. AND YOUR QUESTION IS ABOUT WHAT IS THE MINIMUM AMOUNT REQUIRED? >> AUDIENCE MEMBER: COULD I GET AWAY WITH 10? >> DR. LOONEY: THAT'S A GOOD QUESTION. I THINK DEEP MEDIC, THE INITIAL PUBLICATION I THINK HAS USED DIFFERENT DATASETS. IT WAS ON MRI. THEY USED OFF THE TOP OF MY HEAD, 50 TO 100. I THINK THE WORK THAT MARY MENTIONED YESTERDAY, FOR THE APPLICATION OF SIMILAR ARCHITECTURE TO DEEP MEDIC WAS TO PLACENTAL MRI. THEY USED 50 CASES. SO, I WOULD REFER YOU TO THE LITERATURE WHERE THEY HAVE DONE DEEP LEARNING ON PROSTATE AND THEY USED 50 CASES. AND I THINK AUTHOR IN THAT SPECIFIC PAPER SAYS THE IDEA THAT YOU NEED A LOT OF DATA TO DO DEEP LEARNING TELL RESULTS WITH SMALLER DATASETS. AND THAT'S SOMETHING THAT I HAVE SEEN. WITH 300 CASES, I DIDN'T EXEXIT TO GET SUCH GOOD RESULTS WITH DEEP MEDIC BUT WE DID. >> AUDIENCE MEMBER: THANK YOU. >> DR. WEINBERG: THANK YOU. THIS IS GREAT. I LOVE THIS CONVERSATION. I'M JUST TRYING TO KEEP US ON TIME HERE. SO THE NEXT SPEAKER IS RAEKA AIYAR TALKING ABOUT EMERGING CHIP TECHNOLOGY. >> GOOD MORNING. THANK YOU TO THE ORGANIZERS AND DAVID FOR HAVING ME. I'M GOING TO GIVE YOU AN OVERVIEW OF THE RESEARCH GOING ON AT THE TECHNOLOGY CENTER WHICH RANGES THE CENTERS PRIMARILY ON THE DEVELOPMENTFUL TECHNOLOGIES FOR GENOMICS AND INTEGRATING BIOCHEMISTRY AND ELECTRICAL ENGINEERING AND WE APPLIED THOSE TECHNOLOGIES TO A RANGE OF BIOLOGICAL QUESTIONS RANGING FROM BASIC AND FUNDAMENTAL BIOLOGY TO THE UNDERSTANDING OF DISEASE AND IS THE DEVELOPMENT OF TREATMENTS. UNLIKE JUST ABOUT EVERYTHING IN THIS ROOM WE DON'T WORK ON PLACENTAL HEALTH BUT WE ARE EAGER TO LOOK FOR WAYS TO COLLABORATE IN THIS FIELD. ESPECIALLY AFTER BEING HERE THE LAST COUPLE OF DAYS, IS THAT IS UNDERSCORED A FASCINATING AND IMPORTANT AREA OF RESEARCH THIS IS. AND I'M HOPEFUL THAT WHAT I PRESENT HERE WILL INSIGHT SOME IDEAS ON HOW TO APPLY SOME OF THESE TECHNOLOGIES. IN ADDITION TOO DEVELOPING GENOMIC TECHNOLOGIES AND TRYING TO TACKLE THOSE IN DIFFERENT WAYS THROUGH ELECTRICAL ENGINEERING FOR EXAMPLE, WE HAVE A FOCUS ON APPLYING TECHNOLOGIES TO DIFFERENT BIOLOGICAL COLUMNS AND DISSEMINATING AND COMMERCIALIZING AND SHARING THEM WITH THE COMMUNITY TOW MAXIMIZE UTILITY. AND MORE RECENTLY WE HAVE GOTTEN INTO DIAGNOSTIC TECHNOLOGIES, WHICH I WILL TALK ABOUT SHORTLY. THIS RESULTED IN A LOT OF PATENTABLE INVENTIONS, ABOUT 30 SPIN-UP COMPANIES IN THE LAST YEAR'S WE HAVE BEEN AROUND. SOME OF THE MAJOR INJURIES WE HAVE WORKED ON IN DETECTION HAVE BEEN NUCLEIC ACIDS AND DEVELOPING AUTOMATED TECHNOLOGY FOR THE HUMAN GENOME 52 PROJECT AND OL I GO NUCLEOTIDE AND THE MORE RECENTLY HLA GENOTYPING TECHNOLOGY THAT WAS SPUN OUT INTO A COMPANY JUST LAST YEAR. WE ALSO WORKED A LOT ON OL GO NUCLEOTIDE SYNTHESIS ESTABLISHING MOLEC DARR BAR THE YEAST DELETION COLLECTION AND BECAUSEst FOCUS ON ELECTRICAL ENGINEERING, WE ALSO HAVE DIRECT ELECTRICAL DETENTION AND BIOCHEMICAL REACTIONS. THIS LED TO THE ION TORRENT SEQUENCING TECHNOLOGIES AND OTHER PATENTS AND MORE RECENTLY BIOSENSORS WHICH I'LL TALK ABOUT SHORTLY. SOY THE MAIN AREAS WE ARE FOCUSING ON RIGHT NOW, A LOT OF PEOPLE HAVE BEEN TOUCHING ON THESE IN THE LAST COUPLE OF DAYS SO I DON'T NEED TO GET INTROVERY MANY DETAILS BUT APPLYING THIS SUITE OF GENOMICS AND OMICS TECHNOLOGIES TO LOOK INTO DISEASE MECHANISMS DISCOVER BIOMARKERS FOR DISEASE. AND USING NEW INNOVATIVE INTEGRATIVE STATISTICAL ANALYSIS METHODS AND MODELING TO BETTER UNDERSTAND THIS DITA AND ENGINEERING DIAGNOSTIC DEVICES AND DEVELOPING PLATFORMS FOR DRUG DISCOVERY AND SCREENING AND CHARACTERIZATION THROUGH CHEMICAL GENOMICS TYPE APPROACHES. AND THE APPLICATIONS ESPECIALLY ARE SOMETHING THAT IS CONSTANTLY EVOLVING AT OUR CENTER AND THAT REALLY DEPENDS A LOT ON THE NEEDS THAT WE SEE IN THE FIELD AND THE COLLABORATIONS THAT WE ESTABLISH. SO AGAIN, TOSSING THAT OUT THERE IN HOPES THAT WILL SPARK SOME THAT THE MEETING. WITH THE REMAINDER OF MY TIME, I'D LIKE TO TALK ABOUT THE DEVICES WE ARE DEVELOPING FOR MOLECULAR AND CELLULAR CHARACTERIZATION IN HOPES WE DO IDENTIFY BIOMARKERS ARE OR MOLECULES OF INTEREST OR CELLULAR PROPERTIES OF INTEREST, WE HAVE SOME REALLY EXCITING LOW-COST WAYS TO LOOK AT THOSE AND PROFILE THOSE. WE HAVE ALSO DEVELOPED MANY DIFFERENT METHODS FOR FUNCTIONAL GENOMICS AND LOOKING AT THE OUTPUT OF GENOMES THAT MIGHT ALSO BE OF JUDGE FOR THIS GROUP. AND I WILL END WITH A CASE STUDY IN WHICH WE APPLY LAY LOT OF THESE TECHNOLOGIES TO STUDY CHRONIC-FATIGUE SYNDROME, A DISEASE OF INTEREST TO US FOR REASONS I WILL GET INTO SHORTLY. SO THE FIRST DEVICE I WANTED TO PRESENT ARE NANONEEDLE BIOSENSORS AND THESIS ARE A SET OF ELECTRICAL SENSORS AT THE NANOSCALE. YOU CAN SEE THE SIDES OF THEM THERE. THAT'S AN ARRAY OF SEVERAL THOUSANDS OF SINCORS COMPARED TO A PENNY. WE USUAL I CARIESY THESE AROUND IN OUR POCKETS. BUT I FORGOT TO BRING THEM THIS TIME. AND WHAT THESE CAN BE USED FOR IS REALTIME ELECTRICAL IMPEDENCE. ONE OF THE REASONS WE LIKE ELECTRICITY IS BECAUSE IT'S CHEAP AND USUALLY GIVES YOU ROBUST SIGNALS AS OPPOSED TO FLUORESCENCE WHERE YOU NEED EXTENSIVE EQUIPMENT TO LOOK AT IT AND SOMETIMES THE DATA IS A LITTLE BIT NOISIER. SO WHY CAN GET THOUSANDS OF DATA POINTS PER SECOND WHEN WE USE DEVICES LIKE THESE. AND SO WHAT THESE NANOSENSORS CAN DO, YOU'RE ABLE TO CONJUGATE FOR EXAMPLE ANTIBODIES OR NUCLEIC ACID PROBES TO THEM AND IT WILL DETECT CHANGE IN BINDING EVENTS WHEN THE TARGET BINDS TO THOSE AND THAT WILL MANIFEST AS A REALTIME CHANGE IN ELECTRICAL IMPEDENCE. SO THIS IS JUST SHOWING THAT. IT WILL REGISTER AS A MEASURABLE CHANGE IN ELECTRICAL IMEXCEEDENCE HERE. SO, WHAT WE HAVE USED IS THAT FOR ARE DETECTING AND FOR EXAMPLE, TO DETECT DNA HYBRIDIZED. WE HAVE SHOWN THAT THIS CAN BE DONE IN SEQUENCE-SPECIFIC MANNER AND THIS IS SHOWING A VARIETY OF DIFFERENT PROBES WE TRIED, EVEN A SINGLE MISMATCH IS ENOUGH TO ABOLISH THE CHANGE IN ELECTRICAL IMPEDENCE WE OBSERVED. SO WE ARE WORKING ON ADAPTING THIS TECHNOLOGY TO A SELF DNA OR DETECT CERTAIN TRANSCRIPTS OF INTEREST WE MIGHT THINK ARE BIOMARKERS IN A DISEASE, FOR EXAMPLE. ALSO LIKE I SAID, WE CAN USE IT FOR ANTIGEN BODY BINDING AND I'LL SHOW YOU ANOTHER EXAMPLE HOW TO USE IT LATER ON WHEN I TALK ABOUT CHRONIC-FATIGUE SYNDROME. ANOTHER DEVICE WE ARE REALLY EXCITED ABOUT IS MAGNETIC LEVITATION PLATFORM WE HAVE DEVELOPED TO CHARACTERIZE DIFFERENT CELLULAR POPULATIONS AND THIS IS BASED ON MAGINENTS TO LEVITATE SALES. IF YOU IMMERSE CELLS IN A PARAMAGNETIC SOLUTION, THEY UPTAKE THAT IN A SOLUTION PROPORTIONATE TO THEIR DENSITY. THEN YOU CAN SEPARATE OUT CELLULAR POPULATIONS. THIS IS SAN EXAMPLE OF WHITE BLOOD CELLS AND RED BLOOD CELLS AND TUMOR CELLS THAT HAPPEN TO BE LESS DENSE AND SEPARATING OUT. AND YOU CAN SEE THAT IN REALTIME WHEN YOU PUT THEM BETWEEN A COUPLE OF MAGNETS. AND THIS GIVES YOU SOMETHING OF LIKE A MAGNETIC BLUEPRINT OF A CELLULAR POPULATION THAT CAN TELL YOU ABOUT DIFFERENCES IN CELLULAR POPULATION DUE TO TWO DIFFERENT PROPERTIES. AND I'LL GIVE YOU A COUPLE OF EXAMPLES. ONE COOL THING WE MANAGED TO USE THIS FOR IS DO SORT CELLS. I THINK THAT IS VISIBLE. YOU CAN SEE THIS IS A BLOOD SAMPLE AND YOU CAN SEE THE CELLS BEING SORTED INTO DIFFERENT FRACTIONS BEING SORTED INTO DIFFERENT CHANNELS BASED ON THEIR DENSITY. AND WE BE ABLE TO USE THIS TO CAPTURE CIRCULATING TUMOR CELLS, FOR EXAMPLE, AND THEN SUBSEQUENTLY PROFILE THEM AND STAIN THEM AND PROVE THEY ARE TUMOR CELLS. WE HAVE ALSO INTEGRATED THIS WITH CELL PHONE. THIS IS A PRETTY OLD iPHONE AND YOU CAN EVEN USE THAT FOR IMAGING. AND WHO THE WHOLE THING COSTS ABOUT 3 DOLLARS TO MAKE PER DEVICE. SO IT'S A REALLY LOW COST TECHNOLOGY. THE I SHOULD HAVE MENTIONED THAT AS WELL. NANONEEDLE IS 80 DOLLARS FOR FABRICATION BUT WE THINK WE CAN CUT THAT DOWN ONCE WE REALLY SCALE THAT UP. SO ONE EXAMPLE OF HOW WE HAVE LOOKED AT SINGLE CELLS USING MAGNETIC LEVITATION IS LOOKING AT BREAST CANCER CELLS AND EXPOSING THEM TO ENVIRONMENTAL TESSERS. AND YOU CAN SEE OVER TIME -- STRESSORS -- AS THEY DIE, THEY DROP OUT OF THE POPULATION. AND STOW THIS IS SOMETHING THAT WE HAVE ALSO EXPLOITED TO LOOK AT IN DIFFERENT DRUGS AND HOW THEY MIGHT EFFECT CANCER CELLS OR ANTIBIOTIC POPULATIONS AND HOW THEY EFFECT AND USING THIS TECHNOLOGY TO SCREEN FOR EXAMPLE A POPULATION OF BACTERIA TO SEE IF THEY ARE RESISTANT OR SUSCEPTIBLE TO PARTICULAR ANTIBIOTICS. WE ARE TRYING TO DEVELOP THAT NOW AS A TOOL TO DO PRESCREENING AND WE THINK WE CAN DO THIS IN ABOUT AN HOUR OR TWO HOURS RIGHT THERE TO SEE WHETHER A PARTICULAR POPULATION SHOULD BE PRESCRIBED THIS DRUG OR THAT DRUG. AND WHAT WE ARE ALSO WORKING ON, AND I THINK THIS IS PERHAPS WHAT PIQUED DAVID'S INTEREST IN BRINGING US ON THIS MEETING IS A LAB ON A CHIP PLATFORM WE PUBLISHED EARLIER THIS YEAR. THIS IS EXTREMELY LOW COST. IT'S PRINTED USING A REGULAR IN-CHECK -- INK JET PRINTER WITH NANOPARTICLES WHICH MEANS NO CLEAN ROOM IS REQUIRED. YOU DON'T NEED THE HARDCORE ENGINEERING EXPERTISE WE ARE LUCKY ENOUGH FOR A LOT OF OTHER DEVICES. IT COSTS ABOUT ONE CENT PER DEVICE TO PRINT EACH OF THESE OUT. THE ELECTRIC PORTION IS REUSABLE BECAUSE WE HAVE IT SET UP SO THERE IS NO CONTACT WITH THE SAMPLE. THE SAMPLE FLOWS THROUGH THESE CHANNELS IN THIS SEPARATE PLASTIC DEVICE HERE. AND WE HAVE SHOWN THAT IS IT MULTIFUNCTIONAL LIKE A LOT OF LAB ON A CHIP PLATFORMS. USE IT FOR MANIPULATIONS OF DIFFERENT CELLS IN SORTING, DIAGNOSTICS. I HAVE ANOTHER VIDEO HERE THAT SHOWS JUST ONE EXAMPLE THAT WE HAVE SORT OF USED IT IN AND IN USING ELECTRICAL FIELDS, YOU CAN ACTUALLY CONCENTRATE CELLS INTO THE CERTAIN LINES AND CHANNELS AND THEN YOU CAN COLLECT THEM TOGETHER. HERE WE GO. SO YOU CAN SORT OUT DIFFERENT POPULATIONS SO WE ARE WORKING ON A NANOFLOW CYTOMETER. WE ALSO USED IT TO DO ISOLATION OF RARE CELLS AND CONTIFICATION OF NEWER CELLS IN A POPULATION AND MORE. SOY WE ARE WORKING ON THE NANONEEDLE AND BIOSENSOR TECHNOLOGY INTO THIS MUCH MORE LOW COST ACCESSIBLE PLATFORM AND QUI ARE HOPEFUL THAT IT WOULD BE USEFUL IN THE DEVELOPING WORLD WHERE YOU DON'T HAVE ACCESS TO A CLEAN ROOM OR THESE KINDS OF THINGS. ALL YOU NEED IS A BLUEPRINT OF THESE DIFFERENT ELECTRODE ORGANIZATIONS AND CONFIGURATIONS AND YOU CAN PRINT THEM OUT AND USE THEM. ANOTHER AREA THAT WE WORKED ON IS WEARABLE SENSORS. SO WE RECENTLY DEVELOPED A WEARABLE SWEAT SENSOR THAT DETECTIVES DIFFERENT IONS AND MEFAB LIGHTS, IN PARTICULAR GLUCOSE, LACTATE AND SODIUM AND POTASSIUM USING A FLEXIBLE CIRCUIT BOARD THAT MEASURES OR USES BIOCHEMICAL REACTIONS ON THE CHIP TO ASSESS THE LEVELS OF THESE DIFFERENT METABOLITES. AND JUST ONE EXAMPLE OF HOW WE HAVE USED THAT IS IN ATHLETES. WE HAVE THEM WORK OUT AND COMPARING A GROUP THAT HAD WATER TO A GROUP THAT DIDN'T, WE COULD SEE A REALTIME SPIKE IN THE SODIUM LEVELS INDICATIVE DEHYDRATION. SO IMAGINE USING THIS WHEN YOU'RE WORKING OUT AND YOU MIGHT HAVE TO STOP AND HAVE SOME WATER. MORE RELEVANT TO DISEASE OUR LATEST MODEL ACTUALLY SCHEDULE INDUCTION OF SWEAT SO PEOPLE DON'T HAVE TO MOVE. WE ARE HOPING THIS WILL BE POPULAR IN AMERICA. WOULDN'T HELP IT. SORRY. I'M CANADIAN. -- USUALLY INDUCTION OF SWELT IS A LOT MORE INVASIVE AND THAT IS THROUGH A COLLABORATION WITH THE CYSTIC FIBROSIS CENTER AT STANFORD FINALLY A COUPLE OF OTHER TECHNOLOGIES. THESE ARE A BIT EARLY STAGE BUT WE ARE ALSO WORKING ON FLEXIBLE DEVICE IMPLANTS THAT CAN USE THE HEART'S ENERGY TO EMPOWER THEMSELVES. CHANGING THE POWER SOURCE CAN BE DIFFICULT. SO WE FIGURED OUT A WAY TO USE THE HEARTBEAT'S ENERGY THAT SORT OF BENDS THESE SENSORS AND GENERATES ENOUGH ENERGY TO KEEP THEM POWERED FOR A WHILE. WE HAVE THAT IN A SIMULATION AND WE ARE TRYING IT OUT IN MOUSE HEARTS RIGHT NOW. AND BIOMARKERS HAVE COME UP A LOT HERE SO I WANTED TO MENTION THAT WE HAVE SOME -- A BENCH TOP METHOD LOOKING TO ADAPT INTO A DEVICE THAT DOES SENSITIVE DETECTION OF PROTEINS FROM COMPLEX SAMPLES LIKE BLOOD OR URINE, AND THIS IS BASED ON A PROXIMITY ASSAY THAT USES, CONJUGATES DN TOO. ANTIBODIES AND SO THAT MEANS THAT YOU CAN READ UP THE DETECTION HAS USING ANY METHOD YOU CAN USE TO DETECT DNA SUCH AS SEQUENCING OR CIRCLE AMPLIFICATION OR KEY PCR OR WHAT HAVE YOU. THE COOL THING I THINK ABOUT THIS TECHNOLOGY IS THAT THIS EVEN WORKS REALLY WELL WITH LOW AFFINITY ANTIBODIES AND WE ALL HAD THOSE POORLY-PERFORMING ANTIBODIES FRUSTRATING TO WORK WITH. SO THAT IS WHY I WANTED TO POINT THAT OUT. AND FINALLY, WHEN WE HAVE TALKED ABOUT SINGLE CELLS QUITE A LOT IN THE LAST COUPLE OF DAYS. AND WE ALSO HAVE A NANOTECHNOLOGY TO TAKE SAMPLES FROM LIVE SINGLE CELLS AND WE HAVE USED IT SO FAR TO MEASURE INTRACELLULAR GLUCOSE AND PH. IT DID WIN THE NIH FOLLOW THAT CELL CHALLENGE. BECAUSE THE CELL STILL LIVED EVEN AFTER YOU TAKE THESE SAMPLES. AND WE ARE LOOKING INTO USING THAT TO LOOK AT OTHER INTRACELLULAR MOLECULES OR TRANSCRIPTS OR WHAT HAVE YOU. AND THAT IS IN DEVELOPMENT. SO NOW I'M GOING TO TALK ABOUT A COUPLE OF TECHNOLOGIES WE USE FOR FUNCTIONAL GENOMICS. A LOT OF PEOPLE ARE TALKING ABOUT OMICS TECHNOLOGIES. SO I DON'T NEED TO GET INTO DETAILS. WE HAVE DEVELOPED SOME VERY DETAILED PROTOCOLS TO LOOK AT DIFFERENT STEPS OF THE OUTPUT OF GENOMES AND THE COMPLEXITY OF EPIGENOMES. I APOLOGIZE FOR THE ACRONYMS. WE LOVE THESE IN GENOMICS. A BIT OF A DISEASE. THESE ARE JUST SOME OF THE WAYS THAT YOU CAN LOOK AT HOW GENES ARE BEING EXPRESSED AND RELATE THAT THE FROM GENOTYPE TO PHENOTYPE. WE HAVE A HIGH-THROUGHPUT METHOD FOR DOING CHIP SEEK TO LOOK AT PROM KIN CONFIGURATIONS AND DIFFERENT PROTEIN INVOLVED IN THAT. WE HAVE A LOT OF TECHNOLOGIES TO LOOK AT THE HETEROGENEITY OF THE TRANSCRIPTOME. RECENTLY WE PUBLISHED TRANSCRIPT ISOFORM SEE ISQUENCING WHICH SHOWS THAT EVEN JUST IN YEAST IN THE START AND END SITES OF TRANSCRIPTS THAT ARE PRODUCED IN A SINGLE ISOGENIC POPULATION, IS ENORMOUS. YOU HAVE MILLIONS OF DIFFERENT VARIANTS IN YEAST WHERE WE DON'T EVEN HAVE SPLICE VARIANTS TO WORRY ABOUT. THAT IS SOMETHING THAT WE ARE NOW APPLYING IN MAMMALIAN SYSTEMS ALSO LOOKING AT ALTERNATIVE 3 PRIME ISOFORMS AND 5 PRIME ISOFORMS. THERE IS SAY MASSIVE AMOUNT OF DIVERSITY THERE AND WE HAVE SHOWN THOSE CAN HAVE FUNCTIONAL IMPACTS ON POST TRANSCRIPTIONAL LIFE AND THE WAY THAT THOSE STABILITY OF THE TRANSCRIPTS FOR EXAMPLE AND HOW THEY ARE LATER USED BY THE CELL. AND IN TERMS OF SINGLE CELLTECHINOLOGYIES, I WANTED TO HIGHLIGHT IN PARTICULAR A TECHNOLOGY WE PUBLISHED EARLIER THIS YEAR CALLED INDEX OMICS. AND WE USED THIS TO LOOK AT THE HEMATOPOIETIC PROCESS AND THE DIFFERENTIATION OF HEMATOPOIETIC STEM AND PROGENITOR CELLS WHICH AS YOU KNOW, ARE THE ORIGIN OF ALL BLOOD AND IMMUNE CELLS. AND WHAT WE HAVE ESTABLISHED AS A METHOD THAT INTEGRATES FACS SORTING. SO WE LOOKED AT DIFFERENT MARKERS OF THE DIFFERENT CELLS ALONG THED DIFFERENTIATION TREE AND PERFORMED SINGLE CELL RNA-SEQ ON EACH OF THESE AND WE ARE ABLE TO INTEGRATE THE SINGLE CELL TRANSCRIPTOME DATA WITH THE FACTS IDENTITY OF THESE CELLS AND THEN SUBSEQUENTLY SEE WHERE OR HOW THOSE CELLS DIFFERENTIATED TO DISSECT THIS PROCESS OF DIFFERENTIATION. AND TO MAKE A LONG STORY SHORT, THIS KIND OF OVERTURNED THE MODEL OF HEMAPOIESIS. IT WAS TRADITIONALLY THOUGHT TO BE THE SORT OF HIERARCHAL TREE WHERE YOU HAVE THIS LIKE LATE-STAGE KIND OF BINARY BRANCHING AND COMMITMENT BUT WHAT WE FOUND BASED ON THE TRANSCRIPTOME DATA OF A LOT OF THESE CELLS IS THAT PRIMING ACTUALLY FOR THE DIFFERENT CELL TYPES OCCURS EARLIER THAN PREVIOUSLY BELIEVED. THERE IS NO BINARY BRANCHING AT THIS MULTIPOTENT PROGENITOR STEM CELL AS PREVIOUSLY THOUGHT AND THE TRANSITIONS BETWEEN THESE STATES ARE A LOT MORE CONTINUOUS AND THIS IS BECAUSE THESE MODELS ARE DEVELOPED BASED ON ALREADY SORTING THE CELLS BASED ON MARKERS. BUT WE DID THIS AND SORT OF MORE BIASED WAY AND WE ARE SORT OF ABLE TO DISCOVER THAT THE PROCESS OCCURS MUCH DIFFERENTLY THAN THOUGHT. SO I WANTED TO BRING THAT UP ESPECIALLY BECAUSE THERE IS SOME TALK HERE ABOUT HOW TO DEFINE THE DIFFERENT CELLS IN THE PLACENTA AND IT MIGHT BE USEFUL FOR LOOKING AT PLACENTAL DEVELOPMENT AND REALLY UNDERSTANDING HOW THE CELLS TRANSITION THROUGH THESE DIFFERENT PHASES. SO THAT IS SOMETHING THAT WOULD BE OF INTEREST THEN LET'S PLEASE TALK ABOUT THAT. SO THE FINAL SECTION OF MY TALK IS GOING TO BE ABOUT HOW WE ARE APPLYING A LOT OF TECHNOLOGIES TO STUDY VERY COMPLEX DISEASE. I'M HOPING THIS GIVES SOME INSPIRATION FOR HOW WE CAN APPLY TO HERE. SO CONNICK FATIGUE SYNDROME KNOWN AS MYOLOGIC IN SELF MILITIS, EFFECTS UP TO ONE MILLION AMERICANS. JUST BY A SHOW OF HANDS, HOW MANY PEOPLE HEARD OF CHRONIC-FATIGUE SYNDROME? HOW MANY PEOPLE KNOW SOMEONE WITH CHRONIC-FATIGUE SYNDROME? WOW. OKAY. SO YES, THAT IS SORT OF SPEAKS TO THE PREVALENCE OF THIS. AND SOME OF YOU MIGHT ALREADY KNOW THERE BUT IT'S A REALLY MISUNDERSTOOD DISEASE SO I JUST LIKE TO POINT OUT A COUPLE OF FEATURES OF IT. ONE OF THE LANES WE STARTED STUDYING THIS IS ONE OF THESE ONE MILLION AMERICANS IS THE SON OF RON DAVIDSON, THE CENTER DIRECTOR. SO RON HAS SORT OF PIVOTED OUR CENTER FROM USING ALL OF THESE TECHNOLOGIES AND APPLYING THEM TO CONNICK FATIGUE OR UNDERSTANDING WHAT IS WRONG WITH HIS SON. SO, CHRONIC-FATIGUE SYNDROME IS SOMETHING THAT IS ACTUALLY NOT JUST ABOUT TOO TEAING. IT'S EXERTION AND TOLERANCE. AND EXERTION CAN MEAN A LOT OF DIFFERENT THINGS. IN WHITNEY'S CASE IT ACTUALLY MEANS HE CAN'T TALK. HE CAN'T EAT. HE CAN'T TOLERATE SOUND. YOU'LL SEE THE NOISE CANCELING HEADPHONES ON HIS EARS BECAUSE HE CAN'T HANDLE ANY SOUND. SO THEY ARE JUST WAY TOO MUCH FOR HIM. HE CAN'T INTERACT. HE HE IS FED THROUGH A TUBE. SHE EXTREME CASE. SOME PATIENTS THAT THE MIGHT MEAN RUNNING AROUND THE BLOCK AND THEN THEY KIND OF HAVE TO CRASH FOR A COUPLE OF DAYS. AND THAT'S WHY IT'S CALLED INVISIBLE ILLNESS BECAUSE WHEN THEY ARE SICK, YOU DON'T SEE THEM AND WHEN THEY ARE NOT IN THAT CRASH STATE, THEY LOOK PRETTY NORMAL. SO A LOT OF PEOPLE THINK THAT THIS IS SOMETHING PSYCHOLOGICAL OR PSYCHOSO MATTIC AND THEY ARE JUST FAKING IT OR MAYBE THEY JUST DON'T WANT TO GO TO WORK. THIS IS REALLY NOT THE CASE. AND IT HAS BEEN NEGLECTED BY THE MEDICAL COMMUNITY AND BY A LOT OF FUNDING AGENCIES. BECAUSE OF THAT, I'M HAPPY TO SAY THAT IS STARTING TO CHANGE DUE TO A LOT OF HEAVY EFFICACY FROM PATIENT GROUPS AND BY RON HIMSELF AS WELL. NIH JUST RECENTLY RELEASED AN RFA FOR IT. BUT WE HAVE A LONG WAY TO GO. AT IS THIS POINT, THERE ARE NO FDA APPROVED TREATMENTS FOR THE DISEASE, NO BIOLOGICAL METHOD FOR DIAGNOSING IT WHAT SO EVER. THE DIAGNOSIS IS CURRENTLY BASED ON A LIST OF SYMPTOMS. BUT THANKS TO EFFORTS FROM NOT JUST OUR GROUP BUT MANY COLLABORATORS IN THE FIELD, THERE IS MOUNTING EVIDENCE NOW FOR MOLECULAR BASIS OF THIS DISEASE. AND THE FACT IT IS ACTUALLY -- THERE ARE CASES OF FAMILIES WHERE IT RUNS SO IT SEEMS THERE MIGHT BE SOME GENETIC COMPONENTS AS WELL. METABOLISM SEEMS TO BE ALTERED AS WELL. SO WE THINK THAT THERE IS SOMETHING REALLY MOLECULAR GOING ON WHICH IS A GREAT OPPORTUNITY FOR US. AND WE ARE LIKE I SAID, JUST SORT EVER THROWING EVERY TECHNOLOGY THAT WE EVER USED THAT THE DISEASE IS TO TRY TO UNDERSTAND IT BECAUSE WE ARE HOPING THERE IS A LOT OF LOW-HANGING FRUIT. AND SO THE GOAL THAT IS WE HAVE IN LOOKING AT THIS ARE REALLY SIMILAR GOALS TO WHEN WE ARE LOOKING AT ANY OTHER DISEASE IS TAKING A TECHNOLOGY AND DATE-DRIVEN APPROACH UNDERSTANDING, TRYING NOT TO GO IN IT WITH ANY PRECONCEPTIONSES BECAUSE IT'S SUCH A COMPLEX AND HETEROGENOUS DISEASE. WE ARE TRYING TO ESTABLISH A MECHANISTIC MODELS BECAUSE THERE IS PROBABLY MANY DIFFERENT WAY THAT IS THIS TECHNOLOGY CAN ARISE. WE ARE TRYING TO ESTABLISH A BLOOD-BASED DIAGNOSTIC TECHNOLOGY WHICH DIAGNOSIS TAKES YEARS BECAUSE IT'S REALLY NOT AN ACCESSIBLE THING AND A LOT OF DOLLARS DON'T KNOW WHAT IT IS EITHER. WHICH IS A SECOND PROBLEM -- DOCTORS. -- WE ARE TRYING TO APPLY SOME APPROACHES TO DEFINE SUBGROUPS OF THE DISEASE. IT'S CLEAR THERE IS PROBABLY SOME SUBGROUPS WE DON'T KNOW WHAT THAT MEANS AT A MOLECULAR LEVELS YET AND DEFINE BYOY MARKERS WE CAN LOOK AT AND FINALLY WE'D LOVE TO GET MORE DRUGS IN THE PIPELINE. RIGHT NOW IT'S PRETTY DRY AND WE WOULD LOVE TO BE ABLE TO ESTABLISH APPROACHES TO DO THAT. SO SOME OF THE MOLECULAR FACTORS, THIS IS OUR BEST GUESS AT WHAT IS GOING ON. A LOT OF PATIENTS REPORT ABOUT 70% OF PATIENTS REPORT HAVING INFECTION OF SOME KIND TO START WITH OR SOME OTHER SORT EVER TRAUMA OR EXPOSURE. AND WE, LIKE I MENTIONED, WE DO SEE SOME IMMUNOLOGICAL ALTERATIONS AND A LOT OF PRO-INFLAMMATORY CYTOKINES SEEM TO BE UP. WE DO SEE SOMETHING GOING ON WITH T-CELLS THAT WE ARE NOT QUITE SURE WHAT IT IS YET. AND WE SEE EVIDENCE OF HYPOMETABOLISM IN THE TCA CYCLE. AND WE KIND OF ARE GUESSING IT IS SOME SORT OF INTERACTION BETWEEN ALL OF THESE DIFFERENT FACTORS THAT IS CAUSING THE DISEASE. AND OF COURSE, THAT MEANS THAT INDIVIDUAL VARIATION IN ANY OF THESE SYSTEMS, COULD BE CONTRIBUTING TO THE DIFFERENCES, VAST DIFFERENCES WE SEE ACROSS PATIENTS. SO I WANTED TO SHOW YOU SOMETHING THAT IS PRELIMINARY BUT WE ARE REALLY EXCITED ABOUT IT. BECAUSE WE HAVE BEEN TRYING TO DEVELOP BLOOD DIAGNOSTIC AND WE WENT THROUGH PATIENT BLOOD INTO THESE NANOBIOSENSORS I SHOWED YOU IN THE BEGINNING OF THE TALK. AND WE EXPOSED THEM TO HYPERTONIC STRESS. AND WHAT WE FOUND IS A REALLY STRIKING DIFFERENCE BETWEEN THE PATIENT'S BLOOD -- THIS IS JUST PLASMA WITH PBMCs. AND VERSUS HEALTHY, AND WE SEE THAT LIKE THERE IS SORT OF A MAJOR DISRUPTION IN ELECTRICAL IMPEDENCE AS THE CELLS ARE EXPOSED TO SALT STRESS, WHEREAS THE HEALTHY SEEM TO BE A BIT MORE ROBUST TO THAT SAME LEVEL OF STRESS AND LIKE I SAID, WE ARE MEASURING THIS IN REALTIME AND IT'S CHEAP SO THAT MAKES IT -- KIND OF EXCITING. AND IT SEEMS THAT WE DON'T KNOW EXACTLY WHY, WHAT THIS BIG DIFFERENCE IMPEDENCE MEANS BUT IT DOES SEEM TO SUGGEST IS THERE A DIFFERENTIAL RESPONSE TO HYPERTONIC STRESS GOING ON IN THESE CELLS. SO WE ARE HOPEFUL THAT THIS MEANS THIS CAN BE USED AS A DIAGNOSTIC. THIS IS SHOWN UP THE SAME WAY IN ABOUT FIVE PATIENTS IN CONTROLS SO FAR. AND WE ARE OBVIOUSLY TRYING TO EXPAND THOSE NUMBERS RIGHT NOW. AND WE ARE HOPING THAT IT COULD BE USED AS REPORTER FOR DRUG SCREENS. WE ARE TRYING TO -- WE TRIED PUTTING A FEW SMALL MOLECULES IN THERE TO SEE IF ANY CAN CHANGE THE IMPEDENCE PATTERN AND SOME DO. WE ARE STARTING TO LOOK INTO WHY THAT IS. SO I WANTED TO SHOW THAT BECAUSE THAT IS JUST AN EXAMPLE OF A TECHNOLOGY THAT IS APPLIED WITHOUT HAVING A BIOMARKER OR WITHOUT REALLY UNDERSTANDING THE MECHANISMS OF THE DISEASE BUT WE CAN STILL USE SOME OF THESE METHODS TO SORT OF DISTINGUISH. AND THE IMPACT THAT THAT COULD HAVE ON DIAGNOSTICS AND HOPEFULLY DRUG SCREENING COULD BE HUGE. SO WE ARE VERY EXCITED ABOUT THAT. AND THAT SORT OF TIES INTO WHERE WE SEE ALL OF THIS GOING WHICH IS THAT WE HAVE OR WE ARE ABLE TO MONITOR WELLNESS RATHER THAN REACTING TO DISEASE. AND REALLY USE IT AND THIS WOULD BE DRIVEN BY LOW-COST TECHNOLOGIES THAT WE ARE TRYING TO DEVELOP TO ENABLE A MORE DATA-DRIVEN MEDICINE AND SOMETHING THAT WOULD ENABLE PERSONAL MOLECULAR MONITORS THAT CAN LOOK AT KEY BIOMARKERS, METABOLITES, IONS, FROM DIFFERENT BODILY FLUIDS. CAN INTEGRATE THAT WITH YOUR ACTIVITY DATA AND WE HAVE A BIG FOCUS ON MAKING THESE DEVICES PORTABLE SO THEY CAN BE USED IN THE CLINIC, OF COURSE. AND EVENTUALLY WOULD BE GREAT TO SEE THEM, MUCH MORE WEARABLE DATA AND MORE IMPLANTABLE DEVICES AS WE PROGRESS. BUT THIS REALLY UNDERSCORES A CHALLENGE THAT I THINK REQUIRES A GREAT COLLABORATION TO ADDRESS, WHICH IS ALSO BEEN HIGHLIGHTED IN THIS ROOM, IS REALLY WHAT SHOULD WE BE MONITORING AND HOW SHOULD WE BE MAKING USE OF THIS DATA? WE HAVE THESE -- A LOT OF THESE TECHNOLOGIES ARE ALREADY HERE BUT WHEN IT COMES SWEAT, WE DON'T EVEN UNDERSTAND VERY MUCH OF WHAT IS IN SWEAT AND HOW PHYSICAL LOGICALLY MEANINGFUL IT IS. SO, WHAT CAN WE DO WITH THAT DATA? SO, NA IS SOMETHING THAT I THINK WE NEED TO TAKE ON AS A SCIENTIFIC COMMUNITY AND I LOOK FORWARD TO DISCUSSING THAT FURTHER. AND WITH THAT, I WILL CLOSE AND ACKNOWLEDGE. THERE IS ABSOLUTELY TONSE OF PEOPLE WHO WENT INTO THE -- CONTRIBUTED TO THE WORK THAT I PRESENTED. I HIGHLIGHTED ONLY THE VERY MAIN ONES HERE. IT'S A REALLY EXCITING GROUP BRINGING TOGETHER ENGINEERS WITH BIOCHEMISTS AND GENETICISTS AND MEDICAL DOCTORS AND WE REALLY ENJOY EVERY MINUTE OF IT. THE ENGINEERS DON'T ALWAYS UNDERSTAND EXACTLY WHAT IS GOING ON AND WE DON'T UNDERSTAND WHAT THEY ARE DOING. BUT THEY SAY WE HAVE THE SOLUTIONS AND YOU GUYS HAVE THE PROX AND WE JUST HAVE TO WORK TOGETHER A BIT MORE. AND AND I WILL ALSO DO A LITTLE PLUG IF ANY OF YOU WERE INTRIGUED BY THE CHRONIC-FATIGUE SYNDROME STORY, WE ARE HOSTING A SYMPOSIUM ON THAT. IF YOU FEEL LIKE ESCAPING THE MUGGINESS OF THE DC AREA AND COMING UP TO STANFORD, YOU ARE VERY WELCOME TO DO SO OR PLEASE INFORM YOUR PATIENTS THAT YOU KNOW. I WAS STRUCK TO SEE HOW MANY OF YOU ARE FAMILIAR WITH PATIENTS. SO PLEASE LET THEM KNOW. THERE IS ALSO A LIVE STREAM AVAILABLE BECAUSE WE ARE VERY COGNIZANT OF THE FACT THAT A LOT OF PATIENTS CAN'T TRAVEL TO THESE MEETINGS AND WE ARE HOPING TO PRESENT AND HAVE A LOT OF DISCUSSIONS ABOUT WHERE THE FIELD IS GOING AND WHAT WE CAN DO. SO, WITH THAT, I WILL THANK YOU HAPPY TO TAKE ANY QUESTIONS. [ APPLAUSE ] >> DAVID DAVID WE DO HAVE TIME FOR ONE OR TWO QUESTIONS -- DR. WEINBERG: AND THEN WE'LL TAKE A BREAK AND YOU CAN ALSO TALK TO HER THEN. >> AUDIENCE MEMBER: I WAS QUITE INTRIGUED BY YOUR DATA ON ELECTRICAL IMPEDENCE FOR CFS. AND THE GRAPH SHOWS THE IS A TIME DELAY OF ABOUT 6000 SECONDS OR SO. COULD YOU COMMENT ON WHAT COULD BE THE REASON BEHIND IT? IT SEEMS LIKE THIS IS SOMETHING THAT HAPPENS WHEN YOU APPLY THE ELECTRIC CURRENT OVER TIME. >> DR. AIYAR: RIGHT, SO THE BEGINNING PHASE OF THAT, I DON'T KNOW IF WE CAN GET THAT BACK UP THERE. BUT THE BEGINNING PHASE OF THAT IS THE ONLY WAY TO ESTABLISH A BASELINE. SO IF WE DON'T APPLY A SALT STRESS LIKE ADDING UP TO 200 MICROMOLAR OF SALT, THEN WE DON'T SEE THAT CHANGE. LIKE THEY WOULD JUST STAY THE SAME. AND AS FOR WHY IT TAKES THIS AMOUNT OF TIME -- SORRY. I DO NEED TO CONVERT INTO MINUTES RATHER THAN SECONDS. THIS IS WHAT HAPPENS WHEN YOU WORK WITH ENGINEERS. BUT THE REASON THAT WE THINK THAT THAT -- THERE WE GO. THE REASON WE THINK THAT THAT MIGHT BE HAPPENING, AND AGAIN THIS IS ALL VERY HYPOTHETICAL AND EARLY DAYS, IS THAT THERE MIGHT BE SOME SORT OF EITHER -- SO FOR EXAMPLE, HYPERTONIC STRESS CAN CAUGHT ENDOPLASMIC RETICULUM STRESS AND MEMBRANE EXPANSION SO THERE MIGHT BE A DELAY BECAUSE THERE IS MEMBRANE PROLIFERATION. AND WE ARE LOOKING INTO THAT RIGHT NOW BY EXAMINING PHOSPHOLIPIDS. THERE MIGHT ALSO BE SOME SIGNALING PATHWAYS TO GET TRIGGERED, FOR EXAMPLE INFLAMMATORY CELL DEATH. WE THINK THESE CELLS MIGHT BE PARTICULARLY PRONE TO THAT. SO WE ARE ALSO PLANNING SOME EXPERIMENTS TO DO A SORT OF TIME COURSE WITH FACTS, DATA AND TRANSCRIPTOME DATA TO LOOK AT THAT A LITTLE BIT MORE IN DEPTH. BUT I DON'T HAVE A VERY GOODS ANSWER FOR YOU YET BEYOND THAT BECAUSE IT'S VERY HYPOTHETICAL. >> AUDIENCE MEMBER: HACKENSACK UNIVERSITY MEDICAL CENTER. I WAS INTRIGUED BY THE INDEX OMICS AND I WANTED TO ASK A COUPLE OF QUESTIONS ABOUT THAT. ONE OF WHICH WAS, ARE YOU LIMITED IN THAT? I MEAN IN THE FIRST STAGE, BY A PRIOR KNOWLEDGE OF THE SYSTEM YOU'RE LOOKING AT? IN OTHER WORDS YOU'RE LOOKING AT FACTS SORTING SO THAT IMPLIES YOU LABELED SOMEHOW, WHICH MEANS YOU HADWLEDGE OF WHAT YOU'RE LABELING. AND I'M SORT OF INTERETED IN THE POTAL FOR LINEAGE COMMITMENT WHERE YOU HAVE GOT UNKNOWNS WITHIN THAT SYSTEM. WHERE YOU CAN'T -- DON'T HAVE THAT PRIOR KNOWLEDGE BECAUSE OTHERWISE IT BECOMES VERY DIFFICULT TO DEVELOP THAT COMMITMENT IF YOU GOT NEW OR INTERMEDIATE CELLS IN THE SYSTEM, WHICH SHOULD FIT IN E, BUT YOU HAVEN'T GOT A MARKER TO IDENTIFY THEM AND FOLLOW THEM, NECESSARILY. >> DR. AIYAR: SO, THAT'S A VERY GUIDE POINT. I THINK IF YOU WANT TO SORT OF IDENTIFY WHERE THEY END UP AND HAVE YOU SOME MAR FOR THAT, I THINK YOU CAN STILL GET SOMETHING OUT OF THIS DATA JUST BECAUSE YOU ALSO HAVE THIS FUNCTIONAL DATA WHERE YOU SEE, YOU CULTURE THE CELLS AFTERWARDS AND SEE WHAT THEY BECOME AND YOU CAN TIE THAT TO THEIR ORIGINAL IDENTITY. THEY WOULD PROBABLY NEED TO -- I MEAN, IT'S SOMETHING I HAVE TO THINK ABOUT A BIT. BUT I THINK IT STILL WOULD BE POSSIBLE. WE'LL TALK ABOUT THAT OFF LINE. BUT I THINK YOU STILL COULD GET SOMETHING VALIDATING THAT BECAUSE YOU CAN LINKS THE PHENOTYPIC AND THE TRANSCRIIC DATA LIKE THAT. THANK YOU. >> I START TO GET DEPRESSED ABOUT THIS TIME IN THE MEETING BECAUSE, NOW IT'S THE HOMESTRETCH I HAVE SEEN THE MEETING HAS GONE JUST AS WONDERFULLY I WOULD HAVE HOPED AND I HEAR ALL THIS ENERGY AT THE BREAK AND I'M THRILLED AND THEN IT'S LIKE, OKAY, NOW SETTLE DOWN AND BEFORE WE KNOW IT THE MEETING WILL BE OVER AND YOU'LL BE ON YOUR WAY. SO WE HAVE A FEW MORE REALLY INTERESTING TALKS TO ROUND OUT THE MEETING. I HAVE BEEN ASKED TO MAKE A REQUEST. THERE ARE SOME BAGS IN THE AISLES. SO IF YOU COULD TRY TO GET THEM OUT OF THE AISLES, BECAUSE IT'S A FIRE CODE VIOLATION. SO IF YOU COULD DO THAT FOR ME, I APPRECIATE IT. ANYWAY, SO, WITHOUT TAKING ANYMORE TIME TO I'LL ASK CASSIDY BLUNDELL TO TALK TO US ABOUT VERY INTERESTING WORK. >> MS. BLUNDELL: GOOD MORNING. MY NAME IS SAY BLOND BLOND AND I'M A BIOENGINEERING STUDENT -- CASSIDY BLUNDELL I'LL BE TALKING WITH YOU ABOUT OUR WORK IN LEVERAGING ORGAN ON THE CHIP TECHNOLOGY TO STUDY THE HUMAN PLACENTA. OUR LAB FOCUSES ON CREATING MICROENGINEERED TECHNOLOGIES, KNOWN AS HUMORINGANCE ON A CHIP WHERE WE USE HUMAN CELLS TO MIMIC THE STRUCTURE AND DYNAMIC MICRO-ENVIRONMENT OF HUMAN TISSUES AND ORGANS. THIS WORK WAS STARTED BY MY ADVISOR, DAN HUH, WHEN HE DEVELOPED THE HUMAN BREATHING LUNG ON A CHIP WHERE THEY MIMICKED THE BLOOD, AIR INTERFACE IN THE HUMAN ALPH OLE' EYE AND WERE ABLE TO MIMIC THIS THREE-DIMENTIONAL MICROSTRUCTURE AND APPLY A VACUUM TO MIMIC THE MOTIONS OF BREATHING WITHIN THE ALVEOLI. WE EXPANDED IN OUR LAB TO CREATE A MODEL OF THE SMOKING LUNG ON A CHIP WHERE THERE IS SAY CHIP PLATFORM WHERE WE UTILIZE SMALL AIRWAY CELLS, STROMAL TISSUE AND LUNG ENDOTHELIUM AND CAN EXPOSE THE DEVICE TO SMOKING. AND MIMIC AND STUDY THE EFFECTS OF SMOKING ON THESE TISSUES. SO WE CAN SEE IN THE STROMAL COMPARTMENT THERE IS INCREASED DCM AS A RESULT OF SMOKING EXPOSURE AND THIS GIVES US A PLATFORM TO BETTER UNDERSTAND THE MECHANISMS AND STUDY DRUGS AS IN THE CONTEXT OF SMOKING RELATED DISEASES. IN ADDITION TO THE LUNG, OUR LAB WORKS ON AN EYE MODEL. SO WE ARE USING A NOVEL 3 D-CELL PATTERN AND TECHNIQUE TO RE-CREATE THE CORNUAL PATTERN OF TISSUE -- OF CELLS IN THE OCULAR SURFACE OF THE HUMAN EYE. AND THEN WE CAN ALSO INCORPORATE THE MECHANICAL ENVIRONMENT OF THE EYE BY USING A BIOMEM ETIC EYE LID EXPOSING OCULAR CELLS TO STRESS AND HYDRATE THE OCULAR SURFACE WITH A TEAR FILM. BUT A BIG AREA OF INTEREST WITHIN OUR LAB IS IN THE AREA OF REPRODUCTIVE BIOLOGY AND MEDICINE. AND SPECIFICALLY MY WORK IS FOCUSED ON THE DEVELOPMENT OF THE PLACENTA ON A CHIP. SO APPROACHING AND MODELING OF THE HUMAN PLACENTA WE FOCUSED ON THE BARRIER. THIS IS AN INTERFACE THAT MEDIATES THE TRANSFER OF ALL NUTRIENTS AND WASTE AND XENOBIOTIC AND LATER IN PREGNANCY, THIS STRUCTURE THINS TO BE COMPOSED OF TWO CELL TYPES WHICH ARE THE TROPHOBLAST CELLS AND FETAL ENDOTHELIUM WHICH ARE SEPARATED BY THIS THIN MEMBRANE. SO RECONSTITUTING THIS STRUCTURE, WE WANTED TO CREATE A COCULTURE PLATFORM TO ENABLE THE MAINTENANCE OF THESE TWO CELL TYPES AND AS THEY ARE THE KEY FLARES TRANSFER BETWEEN THE MATERNAL AND FETAL CIRCULATIONS. WE HAD A COCULTURE OF TROPHOBLASTS AND ENDOTHELIUM CELLS AND ACHIEVED THIS BY CREATING A DUAL COMPARTMENT PLACENTA ON A CHIP SYSTEM. FOR FABRICATION OF THE DEVICE, WE USED TWO LAYERS OF POLYMER CALLED PDMS, A INERT GAS PERMEABLE AND TRANSPARENT MATERIAL MAKING IT SUITABLE FOR CELL CULTURE TWO SLABS CONTAINING A MICROCHANNEL AND A MEMBRANE IS SANDWICHED BETWEEN THE TWO. THIS ENABLES THE FORMATION OF TWO COMPARTMENTS. SO THERE IS AN UPPER MATERNAL COMPARTMENT AND A LOWER FEEDAL COMPARTMENT, THAT ARE PHYSICAL SEPARATE BUT IN CONTACT THROUGH THIS POLYCARBONATE MEMBRANE. NEXT WE INCORPORATE THE CELLS TO CREATE THE MICROENGINEERED PLACENTAL BARRIER IN THE MATERNAL COMPARTMENT WE USE TROPHOBLAST CELLS, TRANSFORMED CELL LINE. YOU CAN SEE SHOWN IN GREEN HERE THESE CELLS ADHERE AND THEN PROLIFERATE TO FULLY COVER THE UPPER MICROCHANNEL WITHIN THE PLACENTA ON A CHIP SYSTEM. AND THEN SIMILARLY, IN THE LOWER BASAL SIDE OF THE SEMI-PERMEABLE MEMBRANE, WE INTRODUCE PRIMARY HUMAN ENDOTHELIAL CELLS WHICH ARE ISOLATED FROM PLACENTAS BY OUR COLLABORATOR, DR. EMILY SUE, AND SIMILARLY SHOWN IN BLUE, THEY PROLIFERATE AND FORM A LAYER IN THE LOWER MICROCHANNEL. AND ONCE WE HAVE ESTABLISHED THIS COCULTURE SYSTEM, WE CAN CONNECT THE PLACENTA ON A CHIP TO EXTERNAL SYRINGE PUMP TO ENABLE PROFUSION OF MEDIA FOR DYNAMIC FLOW TO MIMIC CHEMO DYNAMIC ENVIRONMENT OF THE HUMAN PLACENTAL BARRIER. IN CHARACTERIZING THIS SYSTEM, WE LOOKED AT JUNCTION, FORMATION IN BOTH CELL TIMES. THE TROPHOBLAST CELLS AND ENDOTHELIAL CELLS IS CONTINUOUS NETWORK COMPLEXES. IN READ THIS FORMS THROUGHOUT THE TROPHOBLAST POPULATION AND SIMILARLY IN ENDOTHIELIAL CELLS WE HAVE CONTINUOUS VE NETWORKS ESSENTIAL FOR THE BARRIER FUNCTION THAT WE ARE TRYING TO EMULATE IN THE SYSTEM YOU CAN GET A 3D RENDERING. THERE ARE TWO CONTINUOUS LAYERS OF CELLS SEPARATESSED BY A VERY SMALL DISTANCE WHERE THE MEMBRANE IS LOCATED IN THE DEVICE. AN INTERESTING FINDING THAT WE CAME ACROSS IS THAT THERE IS INCREASED MICROVILLE FORMATION UNDER DYNAMIC FLOW IN THE PLACENTA ON A CHIP SYSTEM. MICROVILLE I ARE PROTRUSIONS ON THE SURFACE OF THE TROPHOBLAST THAT ARE ESSENTIAL FOR PLACENTAL FUNCTION. WE FOUND THAT THE DENSITY AND THE SIZE OF THESE MICROVILLE I WERE INCREASED UNDER DYNAMIC CONDITIONSES AS COMPARED TO THE TRANSWELINSERT WHERE THERE IS STATIC CONDITIONSE AND THERE IS DECREASED MICROVILLE I FORMATION. WE CAN APPRECIATE THE DENSE PRONOUNCED MICROVILLE I CREATED ON THE CELL SUFFERS AS, IMPORTANT WHEN WE ARE USING THIS TO STUDY PLA SENT ALD TRANSPORT, THERE ARE A VARIETY OF KEY TRANSPORTERS AND THEY ALSO SERVE IN-VIVO TO INCREASE THE SUFFERS AREA FOR TRANSPORT DURING PREGNANCY WHICH WE ARE RECAPITULATING IN OUR SYSTEM. ANOTHER KEY STRUCTURE IN-VIVO IS FORMATION OF THE SI TISH YUM. THE CYTOTROPHOBLAST AGGREGATE AND FUSE TO FORM THIS IN PREGNANCY AND WE WERE LUCKY TO OBTAIN THE CLONE FROM DR. NICK'S LAB AND THIS WAS A SUB CLONE ESTABLISHED THAT WILL PROGRESSIVELY -- IN PRESENCE OF CYCLIC AMP. SO WE INCORPORATE THIS INTO THE MATERNAL MEDIA DURING DURATION AND EXPERIMENT. PRIOR TO TREATMENT, WE CAN SEE THAT THE IN-VIVO CELLS CYTOTROPHOBLAST WITH COCK PLEX NETWORK AND MOSTLY SMALL NUCLEI BUT AFTER 72 HOURS OF TREATMENT, WE SEE THAT THERE IS PROGRESSIVE AGGREGATION AND ALSO A LOSS IN EXPRESSION. TO QUANTIFY THESE CHANGES, WE USED CELL PROFILER WHICH IS AN ON LINE FREE SOFTWARE THAT ENABLES YOU TO MEASURE CELL AREA BESIDES ECAD HEARING IMAGES AND THERE IS A SIGNIFICANT INCREASE IN CELL AREA OVER 24-48 AND THEN 72 HOURS OF CULTURE. SIMILARLY, WE USED A MALT LAG SEGMENTATION AG GO RHYTHM TO QUANTIFY CHANGES IN NUCLEAR AREA. SO OVER THREE DAYS WITH TREATMENT, THERE IS INCREASE IN NUCLEAR SIZE. TO ENSURE THAT THIS DIFFERENTIATION IS NOT NEGATIVELY EFFECTING INTEGRITY, WE USED TO TEST THE PERMANENTABILITY OF THE SYSTEM. AND THEY FOUND OVER 72 HOURS FROM BARRIER PERMEABILITY DECREASED INDICATING FUSION WAS INCREASING THE BARRIER INTEGRITY OF OUR SYSTEM AND NO COMPROMISE. WE COULD ALSO USE TO QUANTIFY PRODUCTION OF HORMONES ON CHIP. PRODUCED BY THE DIFFERENTIATING IN VIVO CELLS. IN RED, YOU CAN SEE THERE WAS INCREASING BETA HTG PRODUCTION, BUT IN THE UNTREATED DEVICE, THE PRODUCTION THEFT HORMONE WAS NEGLIGIBLE. WE CAN RECAPITULATE THE PHYSIOLOGICALLY RELEVANT PHENOTYPE USING THE TRANSFORMED CELLS IN OUR PLACENTA ON A CHIP SYSTEM. MOVING FORWARD, WE WANTED TO LEVERAGE THIS PLATFORM FOR STUDYING MATERNAL FETAL TRANSPORT. WE STARTED BY LOOKING AT GLUCOSE. WE KNOW THAT GLUCOSE IS IMPORT DURING PREGNANCY AS IT SUPPORTS FETAL GROWTH AND DEVELOPMENT. GLUCOSE MOVES FROM THE MATERNAL CIRCULATION ACROSS THE PLACENTAL BARRIER INTO THE FETAL CIRCULATION AND THIS PROCESS IS MEDIATED BY GLUCOSE TRANSPORTERS EXPRESSED ON THE MEMBRANES OF THE TROPHOBLAST AS WELL AS THE FETAL ENDOTHELIAL CELLS. TO CONFIRM THAT OUR GLUCOSE TRANSPORTERS WERE EXPRESSED IN OUR SYSTEM, WE USED IMMUNOFLOURESENCE IMAGING AND FOUND THERE WAS WIDESPREAD EXPRESSION OF DLUF1. WE COULD ALSO USE CONFOCAL IMAGING TO FIND THAT THERE WAS A LOCALIZATION OF THIS TRANSPORTER SO A GREATER PROPORTION OF DLUT1 ON MICROVILLE I SURFACE OF THE TROPHOBLAST AND THIS IS SAY TREND THAT HAS BEEN REPORTED IN-VIVO AND BELIEVED TO BE VERY IMPORTANT IN KINETICS OF GLUCOSE TRANSPORTER IN THE PLACENTA. SO TO TEST THE FUNCTIONAL GLUCOSE TRANSPORT IN OUR SYSTEM, WE INCREASED THE GLUCOSE CONCENTRATION IN THE MATERNAL COM PARTMENT AND THEN TESTED THE MATERNAL AND FETAL CONCENTRATIONS CHANGES OVER THE COURSE OF THE EXPERIMENT. IN THE ACELLULAR CONDITION, WHEN IT WAS JUST A BEAR MEMBRANE SYSTEM, AND GLUCOSE WAS ABLE TO FREELY DIFFUSE ACROSS THE MEMBRANE, WE SAW GREATEST INCREASE IN FETAL GLUCOSE AS WE EXPECT AND THEN INCORPORATION OF TROPHOBLAST MONOCULTURE AND COCULTURE WAS DECREASED THE OVERALL TRANSFER OF FETAL GLUCOSE ACROSS THE PLACENTAL BARRIER. WE WANTED TO VALIDATE THESE RESULTS AGAINST EXISTING DATA TO TRY TO UNDERSTAND HOW WELL THE PLACENTA ON A CHIP WAS MIMICKING PHYSIOLOGY AND USING SOME PREVIOUSLY PUBLISHED EX-VIVO PROFUSION DATA, WHICH IS CONSIDERED THE GOLD STANDARD FOR PLACENTAL TRANSFER EXPERIMENTS, WE FOUND THAT OUR PERCENT RATE OF TRANSFER ON THE PLACENTA ON A CHIP SYSTEM, WOULD HAVE BEEN PREVIOUSLY REPORTED IN EX-VIVO STUDIES. MOVING FORWARD FROM THIS, WE WERE USING THE GLUCOSE TRANSPORT PROOF-OF-CONCEPT FOR USING PLATFORM FOR TRANSFER STUDIES AND RETURNED OUR ATTENTION TO DRUG TRANSPORT AMOUNT CRITICAL NEED FOR BETTER TOOLS TO TRY TO PREDICT THE SAFETY OF MEDICATIONS DURING PREGNANCY AND WE FEEL OUR PLATFORM HAS THE POTENTIAL TO AID IN THIS FIELD. SO USING TWO SUBSTRATES THAT HAVE BEEN STUDIED, SO HEPARIN AND GLYBURRIDE, WE STUDIED DRUG TRANSPORT IN OUR SYSTEM. FIRST, HEPARIN IS AN ANTICOAGULANT THAT IS RECOMMENDED FOR USE IN PREGNANCY. THERE ARE A FEW DECADES OF WORK ON STUDYING BOTH IN-VIVO AND EX-VIVO. IT'S KINETICS AT THE PLACENTAL BARRIER AND OVERWHELMING EVIDENCE POINTS TO THE FACT THAT IT DOES NOT CROSS THE PLACENTAL BARRIER DUE TO MOLECULAR SIZE. SO IN OUR SYSTEM, WE USED A FLUORESCENTLY LABELED HEPARIN AND PRO FUSED THE MATERNAL COMPARTMENT THIS SUBSTRATE AND THEN SURVEYED THE DEGREE OF TRANSPORT ACROSS THE MICROENGINEERED PLACENTAL BARRIER. IN THE ACELLULAR CONDITION, WHEN IT WAS BEAR MEMBRANE, THERE WAS 11% OF TRANSPORT ACROSS THE PLACENTAL BARRIER. THIS WAS SIGNIFICANTLY DECREASED TO JUST .2% NEARLY NEGLIGIBLE IN THE COCULTURE CONDITION SEWING WE CAN RECAPITULATE THIS PHENOMENON OF PREVENTING TRANSPORT OF HEP RAN. WE ALSO TURNED OUR ATTENTIONS TO ACTIVE TRANSPORT AT THE PLACENTAL BARRIER. BREAST CANCER RESISTANCE PROTEIN IS AN EFLUX TRANSPORTER EXPRESSED IN THE PLACENTA THAT HAS BEEN THE CENTERED OF GRAY GREAT DEALFUL RESEARCH IN PLACENTAL DRUG TRANSPORT T HAS BEEN FOUND TO PLAY A KEY FLOW SHUTTLINGS DRUGS EVEN AGAINST A CONCENTRATION GRADIENT BACK INTO THE MATERNAL CIRCULATION TO PROTECT THE DEVELOPING FEET FROES DRUG EXPOSURES. KIND OF LIMITS DRUG TOXICITIES IN PREGNANCY. WE LOOKED AT BCRP EXPRESSION IN THE CELLS AND FOUND AGAIN THERE IS WIDESPREAD EXPRESSION OF BCRP AND THE SIMILAR TO THE GLUTE 1, WE COULD SEE THIS WAS PREDOMINANTLY EXPRESSED IN THE MEMBRANE OF THE CELLS WHICH MIMICS THE PHYSIOLOGICAL PHENOTYPE. A DRUG HAS BEEN SHOWN TO BE TRANSPORTED BY ECR. AND THE LOW TRANSFER OF GLYZEWSKI BURRIDE IS ATRANSCRIPTED TO THE FUNCTION OF THE TRANSPORTER. IT IS A IS SECOND GENERATION USED IN THE TREATMENT OF DIABETES AND LEGACY. FAIRLY WIDELY USED SINCE DIABETES EFFECTS 10% OF EXPECTING MOTHERS. WE FOLLOWED A SIMILAR EXPERIMENTAL SETUP AS WITH HEPARIN, WHERE WE PRO FUSE THE MATERNAL COMPARTMENT WITH AFLUORESCENT GLYBURRIDE AND THEN WE ARE ABLE TO TRACK THE DEGREE OF TRANSPORT ACROSS THE MICROENGINEERED BARRIER. WE FOUND THAT OVER ALL, THE TRANSFER INTO THE FETAL COMPARTMENT WAS LOW THROUGHOUT THE DURATION OF THE 3 HOUR STUDY HOWEVER, IN THE MATERNAL COMPARTMENT, WE FOUND THAT GLYBURRIDE CONCENTRATION INCREASED OVER TIME BUT WAS STILL MUCH LOWER THAN THE MATERNAL CONCENTRATION IN THE MEMBRANE CONDITION. AND THIS IS DUE TO INITIAL ACCUMULATION OF GLYBURRIDE IN TROPHOBLAST CELLS BUT THEN THE SUBSTRATE IS PUMPED BACK INTO THE MATERNAL CIRCULATION BY FUNCTION OF THE BCRP TRANSPORTER. WE COULD ALSO IMAGE AT THE END OF THE 3 HOUR PROFUSION EXPERIMENT AND FOUND THAT THERE WAS ACCUMULATION WITHIN THE TROPHOBLAST CELLS IN THE MATERNAL CHANNEL SO LOOKING AT THE JUNCTION HERE ON THE DEVICE BUT THERE WAS NO FLUORESCENCE IN THE FETAL COMPARTMENT INDICATING LOW TRANCES FER INTO THE LOWER MICROCHANNEL OR THE FETAL CIRCULATION ON CHIP. TO BETTER UNDERSTAND HOW MUCH OF THESE RESULTS WERE DUE TO FUNCTION OF BCRP, WE USED K0143, A BCRP INHIBITOR AND FOLLOWED THE SAME PROTOCOL BUT ADDED THIS INHIBITOR INTO THE MATERNAL CIRCULATION. WE FOUND THAT THE MATERNAL GLYBURRIDE CONCENTRATION WOULD DECREASE IN THE PRESENCE OF KL143 OVER THE ENTIRE 180 MINUTE PROFUSION BUT IMAGING OF THE TROPHOBLAST CELLS SHOWED THAT THERE WAS INCREASED INTRACELLULAR ACCUMULATION OF DRUG SO THIS SHOWS THAT K0143 IS EFFECTIVELY BLOCKING BCRP MEDIATED GLYBURIDE INFLUX LEADING TO INCREASED CIRCULATION IN THE CELLS AND DECREASED TRANSPORTED BACK TO THE MATERNAL COMPARTMENT. THIS STUDY SERVES AS PROOF-OF-CONCEPT TO START TO CONTINUE TO EXPLORE GLYBURRIDE TRANSPORT AND OTHER DRUGS OF INTEREST. AND ANOTHER ONGOING LINE OF WORK IN OUR SLAB TO TRY TO CREATE A FULLY PRIMARY CELL PLACENTA ON A CHIP MODEL BECAUSE WHILE VIVO IS SAY GOOD MODEL, WE WOULD IDEALLY LIKE TO USE PRIMARY TROPHOBLAST ISOLATED FROM TERM PLACENTAS. WE WORKED TO OPT MICE THE CULTURE CONDITIONS FOR TROPHOBLAST CULTURE AND THEY DO NOT PROLIFERATE IF ANYONE HERE WORKS WITH PRIMARY TROPHOBLASTS, THEY CAN BE TRICKY AT TIMES. SO WE ARE WORKING O. TO OPTIMIZE CULTURE CONDITIONS BUT OBTAINED -- WORKING TOWARDS THAT GOAL AND SEE SOME OF THE HALLMARKS OF THE BARRIER IN THIS PRIMARY MODEL WHERE THERE IS NUCLEAR AGGREGATION INDICATING THAT IT IS SPONTANEOUSLY OCCURRING IN THE PRIMARY CELL MODEL. AND ALSO THERE ARE AREAS OF MICROVILLE I FORMATION WITHIN THE PRIMARY TROPHOBLAST. SO, THE ONGOING WORK WITH THIS SYSTEM IS TO CONTINUE TO OPTIMIZE THAT FULLY PRIMARY CULTURE MODEL. WE ARE ALSO WORKING TO CONTINUE TO CHARACTERIZE DRUG TRANSPORT AND IN COLLABORATION WITH,, WE ARE HOPING TO START TO STUDY PLACENTAL EXOSOME TRANSPORT THROUGH THE MATERNAL FETAL INTERFACE ALSO IN OUR WORK WITH THE MARCH OF DIMES, PRETERM BIRTH CENTER, WE'LL BE STUDYING THE EFFECTS OF METABOLIC ABNORMALITIES ON PLACENTAL BARRIER FUNCTION. SO I THANK YOU ALL FOR YOUR ATTENTION AND THANK YOU FOR THE OPPORTUNITY TO SPEAK TODAY. SO I WOULD WELCOME ANY QUESTIONS. [ APPLAUSE ] >> AUDIENCE MEMBER: HI, BROWN HOSPITAL. THE REASON -- YOU SAID YOU HAVE TROPHOBLAST CELLS -- [ INAUDIBLE ] >> MS. BLUNDELL: THAT'S WHAT WE ARE CURRENTLY WORKING. MOST OF THAT WORK WAS DONE WITH B30 CELLS BUT WE ARE WORKING TOWARDS THE USE OF PRIMARY AND THIRD TRIMESTER TROPHOBLAST. >> AUDIENCE MEMBER: THERE IS ALSO THE THIRD TRIMESTER TROPHOBLAST IS LOT MORE DIFFERENT THAN THE OTHER PARTS. AND ALSO WHAT IS THE PARTIAL PRESSURE OF OXYGEN IN WHICH THESE CELLS ARE -- THE EXPERIMENTS ARE CARRIED OUT? >> MS. BLUNDELL: THE CURRENT EXPERIMENTS ARE CARRIED OUT AT ROOM AIR, SO NORMAL OXYGEN BUT WE ARE INTERESTED IN PUTTING OUR SYSTEM IN A LOWER OXYGEN ENVIRONMENT. ESPECIALLY IF WE ARE TRYING TO MIMIC EARLIER NOINT GESTATION. >> AUDIENCE MEMBER: OKAY. >> AUDIENCE MEMBER: HI, CASSIDY, HACKENSACK. THAT WAS A REALLY NICE UPDATE FROM WHAT I SAW AT PENN A COUPLE OF YEARS AGO. THANK YOU VERY MUCH. THE QUESTIONS I HAD IS, I KNOW VERY WELL THE PRIMARY CELLS ARE TRICKY AND I WAS STRUCK WITH WHAT YOU SHOWED WITH THE DEVELOPMENT OF THE MICROVILLE I UNDER MORE PHYSICAL LOGIC CONDITIONS OF FLOW. SO WHAT ARE YOU USING TO MIMIC FLOW? >> MS. BLUNDELL: THE DEVICE IS CONNECTED TO AN EXTERNAL SYRINGE PUMP. SO ESSENTIALLY THIN TUBING THAT LEADS FROM THE MICROCHALLENGES TO EXTERNAL PUMP AND IT PULLS MEDIA THROUGH THE CHANNEL. >> AUDIENCE MEMBER: SO IT'S MEDIA -- WHAT PARTICULAR KIND? >> CASS KAS WE USE JUST THE STANDARD MEDIA YOU USE TO CULTURE THE CELLS IN-VITRO. AND THE SHEAR STRESS THAT THE CELLS EXPERIENCE IS BASED ON THE FLOW RATE THAT WE SET THE SYRINGE PUMP AT SO WE ARE ABLE TO CONTROL THAT. >> ODD SQUAD THAT LEADS ME TO THE REAL QUESTION I WANTED TO ASK -- >> AUDIENCE MEMBER: IT'S TRICKY TO GET PRIMARY CELLS -- DID YOU FIND IT WORKED BETTER UNDER NIS LOGIC FLOW CONDITIONS? I SUSPECT IT DOES? >> MS. BLUNDELL: AN INTERESTING POINT. WE HAVEN'T REALLY TESTED THAT YET BUT IT'S SOMETHING WE COULD LOOK AT. THE IMAGES I SHOWED WERE UNDER DYNAMIC CONDITIONS AND WE DID SEE SOME SIGNS OF MICROVILLE I SO IT WOULD BE VERY INTERESTING TO COMPARE THAT TO STATIC. >> AUDIENCE MEMBER: WOULD BE REALLY NICE ADVANCEMENT IN OUR KNOWLEDGE. THANK YOU VERY MUCH. MS. BLUND THA YOU. >> AUDIENCE MEMBER: RICH MILLER ROCHESTER. BEAUTIFUL WORK. THE QUESTION ABOUT PRIMARY CELLS THE OPPORTUNITY TO LOOK AT FIRST IMESTER TROPHOBLAST TISSUE? BECAUSE IT MIGHT BE ANTICIPATED THEY WOULD BE MORE SUCCESSFUL IN ESSENTIALIZING AND PROLIFERATING. >> MS. BLUNDELL: WE HAVE NOT HAD THE OPPORTUNITY TO WORK WITH FIRST TRIMESTER CELLS. I THINK SOME OF OUR COLLABORATORS, THE MED SCHOOL AT PENN, ARE CURRENTLY WORKING TO GET A PROTOCOL IN PLACE TO GET THOSE CELLS FROM PATIENTS. MAYBE NEXT YEAR WE WILL HAVE DATA ON THE USE OF FIRST TRIMESTER. >> AUDIENCE MEMBER: THANK YOU. >> MS. BLUNDELL: THANK YOU. [ APPLAUSE ] >> DAVID PERFECT. SO NOW FOR THE NEXT TALK, I'M GOING TO INVITE TWO SPEAKERS TOGETHER. Ms. JULIE HUNTER AND DR. MARILYN MILLER. I GUESS THAT WILL COME ONE AT A TIME? OKAY. >> MS. HUNTER: GOOD MORNING. I'M THE CLIENT ADVOCATE FOR HHS ACCOUNT FOR IBM SO IN THAT CITY, I HAV RESPONSIBILITY FOR A PORTFOL OF PRODUCTS AND SERVICES TO INCLUDE OUR TECHNOLOGIES. I'M DELIGHTED BE WITH YOU TODAY AND I HOPE TO SHARE SOME INSIGHTS ABOUT HOW COGNITIVE TECHNOLOGIES ARE TRANSFORMING THE HEALTH CARE AND LIFE SCIENCES INDUSTRIES. SO AS AN ESTABLISHED INNOVATOR, SERVICES PROVIDER AND TECHNOLOGY LEADER, IB. SOME COMMITTED TO HELPING SOLVE SOME OF THE WORLD'S GREATEST PROBLEMS. WE HAVE BEEN HELPING OUR CLIENTS FOR OVER 100 YEARS AND AS EVIDENCE OF OUR COMMITMENT TO INNOVATION, WE LEAD PATENT FILINGS YEAR AFTER YEAR AND SPEND 6 BILLION DOLLARS IN RESEARCH AND DEVELOPMENT ANNUALLY. 1/3 OF WHICH IS DEVOTE THE TOWARDS ARTIFICIAL INTELLIGENCE RESEARCH. OUR SOLUTION IS USED IN 45 COUNTRIES TODAY ACROSS 20 DIFFERENT INDUSTRIES AND HALF OF THE TOP 25 WEB SCIENCES COMPANIES. SO HEALTH CARE DISRUPTION IS UNDERWAY AND WHEN WE LOOK AT THE AMOUNT OF DATA THAT AN INDIVIDUAL WILL GENERATE, HEA CAREATA, IT COULD FILL 300 MILLION BOOKS OR 50,000 DVDs. WE HAVE LOOMING LEGISLATION WHICH CAUSES GREAT HEALTH CARE INDUSTRY CHALLENGES FOR OUR PAYORS AND PROVIDERS AND CONSUMERS TO KEEP UP WITH. AND OUR CHRONIC DISEASE CONTINUES TO OCCUPY EVER INCREASING PERCENTAGE OF GLOBAL HEALTH CARE SPEND. SO WE ESTIMATE THAT THE FREQUENCY OF WHICH HEALTH CARE DATA DOUBLES IS 24 MONTHS. WASHINGTON UNIVERSITY ESTIMATES MEDICAL DATA WILL DOUBLE EVERY 73 DAYS BY 2020. SO JUST A TREMENDOUS AMOUNT OF DATA OUT THERE THAT WE WANT TO HARVEST. WE NEED NEW TECHNOLOGIES TO REALLY HARVEST THAT DATA. SO 88% OF WHAT WE SPEND ON BEING HEALTHY IS TOWARDS MEDICAL SERVICES. 20% IS SPENT ON THE OTHER FACTORS THAT CAN REALLY LEAD TO MORE POSITIVE HEALTH OUTCOMES SUCH AS ADOPTING HEALTHY LIFESTYLES. SO GENETIC FACT ORALS A VERY STRONG DETERMINANT OF OUR HEALTH AS WE ALL KNOW. BUT WE ALSO NEED TO LOOK AT THE OTHER FACTORS SUCH AS SOCIAL, ENVIRONMENTAL, PHYSICAL, MENTAL WELL-BEING,ET CELTRA. AND THE CHALLENGES THAT MUCH OF THAT DATA EXISTS OUTSIDE OF MEDICAL SYSTEMS, AND MUCH OF IT IS UNSTRUCTURED. SO WE BELIEVE COGNITIVE TECHNOLOGIES CAN HELP US HARVEST THAT DATA. SO COGNITIVE COMPUTING IS MEANT TO TURN THE INFORMATION INTO KNOWLEDGE AND IT CAN HELP US IN A NUMBER OF WAYS. WHEN WE THINK ABOUT ENGAGEMENTS, WOULDN'T WE ALL HAVE A MORE POSITIVE EXPERIENCE WHEN WE CALL OUR BANKING INSTITUTION OR TELECOM PROVIDE IN TERMS OF DISCOVERY, SYNTHESIZING INFORMATION, TODAY YOU CAN LOOK AT YOUR AREA PROPERTIES AND FIGURE OUT UP COMING KNEE SURGERY WHICH HOSPITAL MIGHT GIVE YOU THE MOST POSITIVE OUTCOME AT LOWEST COST. I BELIEVE HHS PROVIDES THAT DATE A CLINICIANS NEED EVIDENCE-BASED INFORMATION TO MAKE TREATMENT DECISIONS. AND WOULDN'T BE IT BE NICE TO HAVE DATA DEPICTED IN A WAY THAT IS ATTRACTIVE AND THAT YOU CAN EASILY ACCESS TO DRILL DOWN INTO SUPPORTING INFORMATION? WE BELIEVE THAT COGNITIVE COMPUTING CAN CREATE A NEW PARTNERSHIP BETWEEN MAN AND COMPUTERS. SO WHAT IS WATSON? WE KNOW THE TRADITIONAL COMPUTING IS PROGRAMMED. IT'S LINEAR BASED ON LOGIC. IT DEALS WITH VARIOUS STRUCTURED DATA. WATSON TECHNOLOGIES OR COGNITIVE TECHNOLOGIES, ON THE OTHER HAND, ARE PROBABILISTIC. THEY LEARN SYSTEMATICALLY AND CAN DEAL WITH A VAST ARRAY OF DATA. STRUCTURED AND UNDESTRUCTURED. SO WATSON UNDERSTANDS THE REASONS AND CAN INTERACT WITH YOU AS A HUMAN BEING AND EXTRACTS AND UNCOVERS CONTENT VERY QUICKLY. SO WATSON CAN READ 800 MILLION PAGES PER SECOND AND IT CAN DO IT AT SCALE. IT PROVIDES ANALYSIS ACROSS VAST ARRAYS OF CRITERIA ACCORDING TO WHAT EVIDENCE YOU BELIEVE IS MORE IMPORTANT. AND IT WILL DIE FLAMICALLY UPDATE HYPOTHESES BASED ON -- DYNAMICALLY -- VARIABLE CHAINS OF EVIDENCE AND HOW YOU MIGHT FEED THAT INFORMATION INTO THE SYSTEM. BUT WATSON IS NOT MEANT TO BE A STAND ALONE SYSTEM. IT'S NO, I DON'T WORK ALONGSIDE HUMAN BEINGS BECAUSE NOTHING CAN REPLACE THE CREATE ACTIVITY AND IMAGINATION AND DISCOVERY THAT ONLY HUMAN BEINGS CAN DO. OUR WATSON HEALTH UNIT WAS DEVELOPED IN OR INITIATED, IN 2014. AND LAST SEVERAL YEARS WE HAVE DONE A NUMBER OF ACQUISITIONS TO AUGMENT OUR HOME-GROWN CAPABILITIES. SO IT STARTED WITH A ACQUISITION WHICH GAVE US A CARE MANAGEMENT SOLUTION. WE AWIDE OTHERS TO ADDRESS POPULATION HEALTH SPACE. THE MERGE HEALTH CARE ACQUISITION ALLOWED WATSON TECHNOLOGY TO SEE SEE MEDICAL IMAGES AND THE WEATHER COMPANY BROUGHT US ANOTHER DIVERSE SET OF DATA. WE KNOW HOW MUCH WEATHER CAN EFFECT BUSINESS OPERATIONS IN OUR DAY-TO-DAY LIFE. AND THEN THE ACQUISITION BROUGHT HUNDREDS OF HEALTH CARE PROFESSIONALS, CLINICIANS, STATISTICIANS AND EPIDEMIOLOGISTS TO THE IBM FAMILY. WITH THESE ACQUISITIONS, WE ACQUIRED NOT ONLY THE KNOWLEDGE IN THE FORM OF PEOPLE, BUT ALSO SIGNIFICANT AMOUNT OF DATA. SO THE WATSON HEALTH CLOUD HOLDS DATA ON 300 MILLION LIVES TODAY. BUT WE ALSO RELY ON PARTNERSHIPS AND ECOSYSTEM PARTNERS BECAUSE WE CAN'T REALLY ADDRESS ALL OF THESE CHALLENGES ON OUR OWN. SO WE DEVELOPED A NUMBER OF KEY STRATEGIC PARTNERSHIPS WITH COMPANIES LIKE APPLE, J AND J AND UNDER ARMOR AND I'M GOING TO, IN THE NEXT FEW SLIDES, HIGHLIGHT A FEW KEY PARTNERSHIPS AS WELL AS SOLUTIONS. SLEEP IS OBVIOUSLY VERY IMPORTANT TO OUR HEALTH AND OVER ALL QUALITY OF LIFE. AND WE DEVELOPED A PARTNERSHIP WITH THE AMERICAN SLEEP APNEA ASSOCIATION. SO WE KNOW THAT ONE-4 AMERICANS SUFFER FROM SLEEP PROBLEMS. 10% OF US HAVE CHRONIC INSOMNIA AND ACCORDING TO THE CENTERS FOR DISEASE CONTROL AND PREVENTION, 25 MILLION AMERICANS SUFFER FROM OBSTRUCTIVE APNEA. SO WE DEVELOPED A PARTNERSHIP WITH THE SLEEP APNEA ASSOCIATION AND THE UNIVERSITY OF CALIFORNIA. WE DEVELOPED A SLEEP HEALTH APP. SO YOU KNOW YOU CAN USE YOUR IWATCH TO TRACK SLEEP ACTIVITY SUCH AS WHEN YOU GO TO BED, WHEN YOU WAKE UP, BUT THE SLEEP HEALTH APP GATHERS ADDITIONAL DATA ABOUT YOUR SLEEP AND ALLOWS THE PARTICIPANT TO LOG SURVEYS RELATED TO THE SLEEP. IT'S THE APP ITSELF WAS DEVELOPED ON THE RESEARCH KIT WHICH IS AN OPEN-SOURCE FRAMEWORK FROM APPLE. IN 2011, WHEN WATSON COMPETED AND WON THE GAME OF JEOPARDY, IT RELIED ON FIVE KEY TECHNOLOGIES AND THEY ARE LISTED HERE. SO THE PROCESSING MACHINE LEARNING, QUESTION ANALYSIS, FEATURE ENGINEERING AND ONTOLOGY ANALYSIS. AND TODAY, BY THE END OF 2016, WE HAD OVER 50 WATSON APIs WHICH WE ADD TO EVERY YEAR. AND I'LL HIGHLIGHT JUST A FEW OF THESE APIs. WE HAVE A NATURAL LANGUAGE CLASSIFIER WHICH ALLOWS DEVELOPERS WHO ARE NOT TRAINED IN NATURAL LANGUAGE PROCESSING OR DON'T HAVE ADVANCED STATISTICAL AG GO RHYTHM BACKGROUND TO INCORPORATE THIS INTO THEIR BUSINESS APPLICATIONS WE HAVE A TONE ANALYZER WHICH CAN UNDERSTAND THE LINGUISTIC TONE PRESENT IN TEXT AND CAN SUGGEST BACK TO THE WRITER A WAY TO INCORPORATE MORE EFFECTIVE TONE IN HIS OR HER WRITING. THE SENTIMENT ANALYSIS CAN HELP BUSINESSES UNDERSTAND WHAT CONSUMERS REALLY THINK ABOUT THEIR PRODUCTS AND SERVICES. AND SPEECH TO TEXT AND TEXT TO SPEECH AND LANGUAGE TRANSLATION. WATSON CAN WORK WITH NINE LANGUAGES TODAY AND I'M SURE THAT WE'LL BE ADDING TO THAT REPERTOIRE. AND THEN THE IMAGE AREASON LA, WE HAVE IMAGE TAGGING AND FACE DETECTION SUCH THAT WATSON CAN READ AN IMAGE AND SEE WHAT OBJECTS ARE IN THAT IMAGE AND CAN ALSO WORK WITH MEDICAL IMAGING SYSTEMS. SO WE HAVE 500 PARTNERS WHO WORK WITH US IN THIS ECOSYSTEM. WE HAD OVER 80,000 DEVELOPERS WHO ACCESSED ONE OR MORE OF THESE APIs ON A PEAK MONTH, WE HAD 3 BILLION CALLS PER MONTH. AND IBM IS ALSO INVESTED 100 MILLION DOLLARS TO HELP VENTURE CAPITALISTS AND START UP FIRMS WHO MAY NEED ASSISTANCE AS THEY LEARN TO ACCESS APIs AND INCORPORATE THEM INTO THEIR BUSINESS APPLICATIONS. OUR WATSON FOR CLINICAL TRIAL MATCHING IS A COMMERCIALLY- AVAILABLE SOLUTION SOLUTION -- 30% OF CLINICAL TRIALS CLOSE BECAUSE THEY CAN'T ATTRACT THE APPROPRIATE NUMBER OF PARTICIPANTS. SO THE WATSON SOLUTION CAN READ THE ELECTRONIC MEDICAL RECORD LOCKING AT THE PATIENT ELIGIBILITY AND INCLUSION AIR AND IICS COLLUSIONIARY CRITERIA AND MATCH THAT UP TO RELEVANT CLINICAL TRIALS. AND IT CAN WORK THE OTHER WAY IN TERMS OF LOOKING AT A SINGLE CLINICAL TRIAL, READING A PATIENT DATABASE, AND COMING UP WITH A POTENTIAL LIST OF CANDIDATES OF PATIENTS THAT FIT THAT TRIAL. OUR WATSON FOR DRUG DISCOVERY IS OR HAS SEVERAL USE CASES THAT CUT ACROSS BIOLOGY AND CHEMISTRY AND GENOMICS. IT CAN ANSWER QUESTIONS SUCH AS WHAT BRO TEEN OR MOLECULES SHOULD I LOOK AT FOR A GIVEN WHAT PATHWAYS SHOULD I CONSIDER? WHAT IS IT THE SAFETY PROFILE FOR A GIVEN COMPOUND? THIS PARTICULAR SLIDE OUTLINES A RETROSPECTIVE STUDY THAT WAS DONE WITH BAYLOR COLLEGE OF MEDICINE IN WHICH WATSON WAS UTILIZED TO LOOK AT THE p53 PROTEINS THAT IDENTIFIED 7 OF THE 9 KNOWN p53 PROTEINS WHICH TOOK RESEARCHERS WORLDWIDE 10 YEARS TO DISCOVER AND WATSON IS DID THAT IN A MATTER OF WEEKS. SO IT'S A PRETTY POWERFUL TECHNOLOGY, IN ADDITION IT IDENTIFIED SIX ADDITIONAL CANDIDATES FOR CONSIDERATION. WE ARE ALSO WORKING WITH HOSPITALS AND HEALTH CARE ORGANIZATIONS FOR THE FIGHT AGAINST CANCER. AND WATSON TODAY SUPPORTS 8 DIFFERENT TYPES OF CANCERS. SO, WHEN RUNNING TESTS AGAINST CASES, WATSON WAS ABLE TO MATCH RECOMMENDATIONS UP TO 96% OF LUNG CANCER CASES, 81% OF COLON CASES, AND 93% OF RECTAL CANCER CASES. BY THE END OF THIS YEAR, WE ANTICIPATE A TRAINING ON FOUR ADDITIONAL CANCERS WHICH WOULD REPRESENT 80% OF THE GLOBAL INCIDENTS OF CANCER. AND WAS TRAINED THROUGH GREAT LACKS ASSISTANCE FROM DOCTORS FROM MEMORIAL SLOAN-KETTERING. SO GENOMIC TESTING, YOU ALL KNOW HAS GONE FROM RARE TO ROUTINE IN MANY CLINICAL SETTINGS. AND WE BELIEVE IT TAKES US VERY FAR ALONG THE PATHWAY TO LOOK AT PERSONALIZED MEDICINE. IN 2016, IBM OFFERED A SERVICE THROUGH QUEST LAB DIAGNOSTICS AND ALSO MEMORIAL SLOAN-KETTERING, WHERE YOU CAN ACCESS THE SOLUTION ON A NATIONWIDE BASIS. THERE WAS ALSO AN INTERESTING ARTICLE THAT WAS PUBLISHED TWO WEEKS AGO IN NEUROLOGY GENETICS WHICH HIGHLIGHTED A GLEOBLASTOMA CASE IN WHICH WATSON WAS ABLE TO COME UP WITH CLINICALLY-ACTIONABLE INSIGHTS WITHIN 10 MINUTES AND THAT WAS COMPARED TO 160 HOURS EVER MAN HOURS. SO, SOME PRETTY POWERFUL TECHNOLOGY. AND YOU CAN SEE THE CONTENT THAT WE USED TO TRAIN THE SYSTEM ON THE RIGHT-HAND SIDE OF THE SLIDE. AS PART OF THE NATIONAL CANCER MOONSHOT, IBM DEVELOPED A PRIVATE PARTNERSHIP WITH THE DEPARTMENT OF VETERAN'S AFFAIRS TO EXPAND AND SCALE ACCESS TO PRECISION MEDICINE WHERE 10,000 VETERANS SUFFERING FROM CANCER. SO WE KNOW THAT IS THE LARGEST IMMIGRATED -- INTEGRATED HEALTH SYSTEM SERVING 3.5% OF OUR NATION'S CANCER PATIENTS. SO IT'S A BIG GROUP OF CANCER PATIENTS. AND PATHOLOGISTS SEQUENCED THE DNA. IT WAS FED INTO THE WATSON SYSTEM AND WATSON PROVIDED BACK A REPORT TO THE DOCTORS OUTLINING LIKELY CANCER-CAUSING MUTATIONS AS WELL AS SOME POTENTIAL TREATMENT OPTIONS FOR CONSIDERATION BY THE DOCTOR. SO, WE TEND TO THINK OF WATSON HEALTH AT IBM AS OUR OWN MOONSHOT BUT WE CERTAINLY SHARE THE NATION'S GOALS AS IT RELATES TO THE WAR ON CANCER AND THE AIMS ASKER TICK LATED BY THE NATIONAL CANCER INSTITUTE AT THE TOP OF THE PAGE -- ARTICULATED -- TO MAKE MORE THERAPIES AVAILABLE TO MORE PATIENTS, IMPROVE OUR ABILITY TO PREVENT CANCER AND DETECT IT AT A EARLY STAGE. SO IN SUMMARY, WE SAY IS THAT IN 10 YEARS OR LESS THAN 10 YEARS, COGNITIVE SYSTEMS WILL LEAD TO COMPUTING WHAT TRANSACTION PROCESSING IS TODAY. AND SO WE ENVISION A WORLD OF MAN WORKING ALONGSIDE COMPUTERS WITH COMPUTERS REALLY BEING A TOOL THAT ENHANCES RELATIONSHIPS BETWEEN HUMANS AND THE WORLD. SO WITH THAT, I THANK YOU FOR YOUR ATTENTION. I HOPE YOU FOUND MY TALK INTERESTING AND I'D LIKE TO TURN THE PODIUM OVER TO DR. MILLER WHO WILL DISCUSS THE WORK AT THE NATIONAL INSTITUTED OF AGING AND HOW WATSON ALGORITHMS ARE BEING APPLIED TO STUDY ALZHEIMER'S DISEASE. [ APPLAUSE ] >> DR. MILLER: OKAY. SO WE ARE GOING TO SWITCH WAY FAR OVER, 180 DEGREES. TO THE OTHER END OF THE SPECTRUM THAT WE DON'T WANT TO THINK ABOUT. AND IF YOU LOOK AROUND THE AUDIENCE, JUST HAVE A PEEK AROUND, AMONG THE PEOPLE IN THIS AUDIENCE, BY THE AGE OF 65, 5% OF YOU ARE GOING DO HAVE ALZHEIMER'S DISEASE. BY THE TIME YOU'RE 75, 45% OF YOU WILL HAVE ALZHEIMER'S DISEASE. AND AS YOU MOVE INTO THE 80s, IT APPROACHES 90%. THIS REALLY IS A NATIONAL CRISIS. WE USED TO LIVE NOT AS LONG AS WE LIVE NOW. WE ARE OUT LIVING DISEASES THAT WE USED TO DIE OF. AND THAT MEANS THAT THOSE GENES THAT HAVE BEEN SITTING IN OUR POPULATION ARE NOW ABLE TO WORK AND NOW WE HAVE TO DISCOVER WHAT THOSE GENES ARE. IN ORDER TO DO THE TYPE OFK THAT WE DO, WE ARE LOOKING FOR RARE TO VERY RARE GENETIC VARIANTS. THEY ARE EXTREMELY DIFFICULT TO FIND. WE HAVE TAKEN MANY DIFFERENT APPROACHES OVER THE YEARS TO TRY TO FIND THEM. WE NEED VERY DEEPENED PHENOTYPING DATA BIOMARKERS, IMAGING, ALL KINDS OF BLOOD AND CSF DATA AND WE NEED AUTOPSY MATERIALS. SO IT'S AN EXTREMELY COMPLICATED SYSTEM. WE HAVE 31 ALZHEIMER'S DISEASE CENTERS COLLECTING ALL THIS INFORMATION. WE PUT MILLIONS OF DOLLARS INTO THERE AND WE STILL DO NOT HAVE A CURE. ALZHEIMER'S DISEASE IS A UNTREATABLE NEURODEGENERATIVE DISEASE. SO, WHAT WE NEED TO DO IS HAVE A LAW PUSHING US NOW. WE DO, IN FACT. WE IS HAVE THE NATIONAL ALZHEIMER'S PROJECT ACT WHICH SAYS, THAT BY 2025, WE, THE NIA, HAVE TO HAVE AID THERAPEUTIC TARGET FOR ALZHEIMER'S DISEASE. I DON'T KNOW WHAT HAPPENS TO ME IN 2025 IF WE DON'T HAVE THAT, BUT THAT'S THE LAW. AND SO WE ARE PUTTING EVERYTHING WE CAN POSSIBLY PUT INTO IT. AND WE LAUNCHED IN 2012 A SEQUENCING PROJECT WHOSE GOALS ARE TO IDENTIFY NEW GENES THAT ARE INVOLVED IN THE DISEASE, TO IDENTIFY GENE ALLELES THAT CONTRIBUTE TO INCREASED RISK AND PROTECTION BECAUSE WE THINK WITH PROTECTION, WE ARE GOING TO FIND OUR TARGETS, PEOPLE WHO LIVE LONGER WITH THE GENES HAVE SOMETHING THAT IS STOPPING THEM FROM GETTING THE DISEASE EARLIER. QUI WILL BE LOOKING FOR INSIGHT INTO WHY PEOPLE WITH KNOWN RISK FACTORS CAN ESCAPE THE DISEASE AND LOOKING FOR POTENTIAL AVENUES FOR THERAPEUTIC APPROACHES. SO, WE HAVE A SEQUENCINGJECT THAT IS PRETTY COMPLICATED. IT HAS BASICALLY THREE PHASES, A DISCOVERY, DISCOVERY EXTENSION AND FOLLOW-UP STUDY. THE DISCOVERY SEQUENCING TOOK THE FIRST THREE YEARS OF THE PROJECT. WE THEN RAN INTO AN ANALYSIS PHASE AS A COMPONENT OF THAT USING WHOLE EXOME SEQUENCING AND WHOLE GENOME SEQUENCING. WE FOUND VIRTUALLY NOTHING IN THE EXOMES, BEYOND WHAT WE ALREADY HAD IN GENOME-WIDE ASSOCIATION STUDIES. SO WE DROPPED EXOMES FOR ALZHEIMER'S DISEASE. THE MONEY IS IN BETWEEN THE PROTEIN CODING REGIONS IN THE REGIONS OF THE GENOME THAT HAVE TRANSCRIPTION FACTORS AND INITIATING FACTORS. IT'S NOT IN THE CODING REGIONS EXCEPT FOR A FEW SIMPLE EXAMPLES. IN THE EXTENSION PHASE, WE HAVE A CASE CONTROL SAMPLE SET AND FAMILY-BASED SET. AND THOSE DATA ARE NOW BEING ANALYZED. AND WE WILL BE LAUNCHING THIS FOLLOW-UP STUDY AGAIN WHOLE GENOME SEQUENCING. WE WILL SEQUENCE AT LEAST 10,000 WHOLE GENOMES FROM ETHNICALLY-UNIQUE COHORTS. AND WE WILL HAVE CONTROLS HOPEFULLY LEVERAGING WHERE WE CAN, EXISTING DATA FROM OTHER SEQUENCING PROJECTS. IF YOU LOOK AT THE LINEAR PROJECT, WE STARTED IN 2012 AT THE SAME TIME THE NATIONAL PLAN SAID WE HAD TO. AND THAT THE TIME, WE ALSO LAUNCHED A DATABASE, THE NIH GENETICS ALZHEIMER'S DISEASE STORAGE SITED, TURNED OUT TO BE THE LINCHPIN FOR THIS PROJECT. OVE THE NEXT THREE YEARS, THERE WAS BOTH SEQUENCING AND ANALYSIS. IN 2016, WE DECIDED BECAUSE WE HAD SEVERAL GENOME CENTERS PROVIDING US WITH DATA, AND THE DATE WERE ALL A LITTLE BIT DIFFERENT AND IT TOOK A LOT OF WORKING WITH THE DATA TO MAKE IT ALL LOOK THE SAME, WE DECIDED WE NEEDED TO HAVE A GENOME CENTER SO WE LAUNCHED A GENOME CENTER. AND WE ALSO FORTUNATELY, REEMYD OUR DATABASE. AND SIMULTANEOUS WITH THAT, WE AND THEN, I CAME BACK FROMCT. HOLIDAYS ON THE FIRST WEEK OF JANUARY, TO FIND THOUGHT DBGAP COULD NOT TAKE OUR DATA ANYMORE. AND SO, IT WASN'T JUST OUR SEQUENCING PROJECT T IS EVERY SEQUENCING PROJECT ACROSS NIH. NOBODY WAS ABLE TO PUT DATA, EXCEPT TINY DATASETS INTO DBGAP SO WE ALL SAT WITH OUR DATA IN CYBERSPACE FOR SEVERAL MONTHS UNTIL WE FIGURED OUT WHERE WE WERE GOING TO PUT THE DATA. WE DECIDED BECAUSE WE HAD JUST RENEWED THE DATABASE TO, REBUDGET AND TO MOVE EVERYTHING OVER TO OUR DATABASE. WE ARE NOW UP IN THE CLOUD. WE ARE SECURED WITH FEDERAL INFORMATION SAFETY MONITORING ACT PARAMETERS. PROTECTED AGAINST IN FRUITION AND EN SCRIPTING OUR DATA. AND ALL OF THE DATA ARE THEN GOING TO BE OVER THERE. THE OLD DATA STAY AT DBGAP AND THE NEW DATA ARE AT OUR DATABASE. WE WILL BE LAUNCHING, DESPITE THE PAUSE THAT WE HAD OUR SEQUENCING PROJECTS FOR THE FOLLOW-UP STUDY, AND THERE WILL BE WAVES OF SEQUENCING IN ANALYSIS. NOW AS CAN IMAGINE, THIS KIND OF DATA IS PRETTY BIG AND A PUBLICATION WAS OUT IN 2016 ABOUT A YEAR AGO WE WERE THE T LARGEST STUDY IN DBGAP BEHIND TCGA AND 1000 GENOMES. AND THEN WE HAD OUR LITTLE ISSUE WITH DBGAP. AND WE HAD TO MOVE ALL OF OUR DATA OVER TO OUR DATABASE, SO WE ARE SITTING HERE AT 68 TERABYTES BEFORE AND THEN ONE THOUSANDFOLD INCREASE IN THE AMOUNT OF DATA OVER 12 MONTHS AS OUR DATA NOW ARE A PETABYTE IN OUR DATA BIAS. AND WE ARE GOING TO, AS OUR NEW WAVES OF DATA ROLE IN, IASE THIS TO ABOUT 2023, WE EXPECT TO HAVE ABOUT 10 PETABYTES OF DATA. IF YOU LOOK AT THAT IN TERMS OF NUMBER OF WHOLE GENOMES, WE ARE APPROACHING 5000 RIGHT NOW. AND BY THE TIME WE GET TO 2023, WE WILL PROBABLY HAVE 35,000 WHOLE GENOMES IN THE DATABASE. SO AS YOU CAN IMAGINE, THIS IS A SERIOUS CHALLENGE. THESE ARE VERY, VERY BIG FILES AND THERE ISN'T JUST ONE FILE PER GENOME. THERE IS 4 FILES PER GENOME. IT'S VERY COMPLEX TO ANALYZE THE DATA AND UNFORTUNATELY FOR US, OUR INFORMATION ISN'T -- WE HAVE TO SEQUENCE THE WHOLE DARN THING AND WE HAVE TO DO IT IN LOTS OF PATIENTS. SO THIS IS A HUGE CHALLENGE TO US AND SO WE THOUGHT WE NEEDED SOMETHING THAT MIGHT HELP US MOVE A LOT FASTER THAN WE ARE GO WE HAVE T DEVELOP OUR OWN ANALYSIS PROTOCOLS FOR STRUCTURAL VARIANTS. THE BIG CHANGES IN THE GENOME BECAUSE THERE AREN'T ANY OUT THERE. WE ARE THE FIRST PEOPLE DOING IT. WE THOUGHT THE POSSIBLE SOLUTION TO THAT MIGHT BE TO ENGAGE MACHINE LEARNING AND WE ARE FORTUNATE TO HAVE A HAPPY RELATIONSHIP WITH IBM AND SO WHAT WE HAVE NOW IS IF YOU FOLLOW THE PROJECT THROUGH, WE œWE HAVE DNA AND THOUSANDS OF SUBJECTS WITH LOTS OF PHENOTYPIC DATA. MATERIAL TRANSFER AGREEMENTS, DATA TRANSFER AGREEMENTS, MEMORANDUM OF UNDERSTANDING. WE HAVE SEQUENCING CENTERS PROVIDING DATA EXOME OR WHOLE GENOME. THEY THEN SEND OUR DATA OVER TO THE GENOME CENTER WHICH HARMONIZES ALL OF THE DATA AND DOES ALL OF THE QUALITY CONTROL CHECKING FOR THE ENTIRE PROJECT. AND IN ADDITION, WE HAVE DATASETS THAT HAVE DATA SO WE ARE BRINGING THOSE DATA ALSO OVER TO THE GENOME CENTER FOR HARMONIZATION AND THEN THEY GO OVER TO THE NIAGADS FOR DATA SHARING AND HANDLING. AT THE HUB WE ENGAGED WATS SON BECAUSE THAT'S WHERE OUR INVESTIGATORS AND WATSON CAN BEST INTERFACE. A HYPOTHESIS OF THE PROJECT IS THAT ANALYSIS OF WHOLE GENOME SEQUENCE DATA FOR ALZHEIMER'S DISEASE CASES AND CONTROLS, USING MACHINE LEARNING APPROACHES WITH CONTRIBUTE TO OUR UNDERSTANDING OF AD GENETIC DATA. AND GIVEN THE FACT THAT THERE IS SPECIFIC REGIONS OF THE GENOME THAT ARE POLYMORPHIC, WE KNOW FOR SURE, WE HAVE HUNDREDS OF THOUSANDS OF SINGLE NUCLEOTIDE POLYMORPHISMS. WHAT IS IMPORTANT? I DON'T KNOW. MAYBE WHAT THE SON CAN TELL US. THEY CAN TELL US -- WATSON -- WE ARE GOING TO ASSUME THAT WATSON CAN PREDICT ASSOCIATION OF THESE FACTORS WITH ALZHEIMER'S DISEASE. SO THERE ARE SEVERAL COLLABORATIONS FOR THIS STUDY. JULIE MENTIONED THE CANCER MOONSHOT AND THAT GAVE US QUITE SOME CONFIDENCE BECAUSE WE KNOW THEY HAVE A LOT OF EXPERTISE NOW WITH THE HUMAN GENOME. WE HAVE A COLLABORATOR. THIS IS A SMALL BUSINESS WHICH IS FUNDED BY NIGM. AND THEIR JOB IS TO DEVELOP OPEN-SOURCE BIOIGE FORMATTICS SOFTWARE. AND IBM, WHICH AS YOU JUST HEARD, HAS A MAJOR EFFORT IN BEING PROACTIVE ON COMPLEX DISEASES. SO, NOW WE HAVE TO TAKE A LITTLE STEP BACK IN HISTORY TO TALK ABOUT WHAT CURE VERSE IS DOING. IF WE THINK ABOUT 8000 YEARS AND WE'RE IN AFRICA, WE REMEMBER THAT WAVES OF MIGRATION MOVE OUT FROM AFRICA AND THEY GO SOUTH TOWARDS INDONESIA AND SORT OF EAST TOWARDS BEIJING AND UP AROUND TOWARDS THE BEARING STRAIGHTS. AND SOME MOVE UP TOWARDS RUSSIA AND SOME MOVE UP TO THE EASTERN PART OF EUROPE AND SOME TO THE WESTERN PART OF EUROPE. AS THOSE GROUPS MOVED OUT IN VARIOUS WAVES, THEIR GENES STARTED TO TRANSIT SO THAT THE FURTHER PEOPLE ARE APART, THE FURTHER THEIR GENES ARE APART, AND PEOPLE WHO ARE IN THE SAME GROUPS SHARE COMMON STRAINS OF THE GENOME AND THOSE ARE CALLED HAPLOTYPES. SO, WHAT CURE VERSE DOES, IT CAN RECOGNIZE HAPLOTYPES. AND 2 -- LET'S SAY WE HAVE AFRICAN-AMERICANS, CAUCASIANS AND HISPANICS IN OUR GROUP. IT CAN RECOGNIZE WHO THOSE ETHNIC GROUPS ARE JUST BY THAT PIECE OF INFORMATION, KNOWING THE HAPLOTYPES AND LOOK AT THE GENOMES AND SAY, ALL OF THIS INFORMATION IS THE SAME IN ALL OF THESE GROUPS. SO LET'S COLLECTED THAT TOGETHER BECAUSE WE DON'T NEED TO LOOK AT IT AGAIN. AND THAT MEANS THAT EVERYTHING THAT IS DIFFERENT STICKERING OUT. YOU CAN COMPARE -- LINE UP ALL YOUR CONTROLS AND ALL YOUR CASES AND YOU CAN LOOK AT THE DIFFERENCES BETWEEN THE TWO GROUPS BY COLLAPSING THE THINGS THAT ARE THE SAME AND LOOKING AT THINGS THAT ARE DIFFERENT. THEN CURE VERSE SENDS THAT INFORMATION OVER TO IBM WATSON, AND WATSON WILL APPLY ALL OF LITTLE MACHINE LEARNING TECHNIQUES. AND MY WAY OF VISUALIZING THIS IS WATSON TAKES A 35,000 FOOT FLAMING CRUISE OVER THE GENOME AND SAYS TO OUR ALZHEIMER'S GENETICISTS, LOOK AT CHROMOSOME 17P23. THERE IS SOMETHING REALLY WIERD GOING ON THERE. THE STRUCTURE IS DIFFERENT. THEN WE'LL TAKE THAT BACK TO ARRAYER NET CYSTS AND OUR GUYS WILL GO INTO THE DEEP DIVE INTO THAT REGION AND WE'LL SEE WHAT IS DIFFERENT AND KEEPITERATING BACK AND FORTH. SO, THE RESEARCH TEAM THEN OPERATES ON HYPOTHESIS THEY CAN FIND GENES AND WE WILL TEST THAT FIRST OF ALL. WE KNOW FOR SURE THERE IS ONE GENE THAT THEY BETTER FIND. WE ARE TESTING THEM NOW. CAN YOU FIND A POEEE 4? AND IF YOU CAN FIND A POE E4, WE HAVE 20 MORE WE'D LIKE FOR YOU TO FIND. AND IF YOU CAN FIND THOSE IN OUR GROUP, THEN WE ARE GOOD TO GO. AND AFTER THAT ACID TEST IS PASSED, THEN THEY WILL BEGIN IDENTIFYING VARIANTS IN THE REST OF THE DATA AND TO LOOK FOR PROTECTIVE FACTORS AGAINST ANYTHING THAT MAY CAUSE ALZHEIMER'S DISEASE. SO, CURE VERSE CRUNCHES DATA AND DOES TILING. THEY COMPARE CASES AND CONTROLS AND PASS THE DATA OVER TO IBM. IBM IDENTIFIES PATTERNS AND REGIONS OF INTEREST AND THEY USE TWO METHODS AND I THINK JULIE WILL HAVE TO HELP ME OUT. BUT THEY ARE USING A METHOD THEY CALL MINT, WHICH I UNDERSTAND TO MEAN WHEN THERE IS SAY CHANGE IN THE STRUCTURE AND GENOME AND SPACIAL RELATIONSHIP BETWEEN THE BASE PAIRS CHANGES AND I THINK THAT THAT IS WHAT THIS TECHNOLOGY IS ASSESSING. THEY ALSO CAN DO METANALYSIS OF GWASS. WE HAVE ALL KINDS OF ALZHEIMER'S DATA BUT YOU CAN LOOK AT A BUNCH OF COMPLEX DISEASES AND PUT ALL OF THOSE DATA TOGETHER AND LOOK FOR COMMONALTIES. SO THEN, WE ARE GOING TO HAVE TOITERATE AMONG THE PARTNERS HERE, CURE VERSE TO IBM TO GENEST CYSTS AND THEN BACK OVER TO THE GENOME CENTER AND BACK AND FORTH. AND WE WILL TRY OTHER EXPERIMENTAL ALGORITHMS AS THE EXPERIMENT MATURES. SO WE HAVE OUR GENETICISTS WHO ARE GOING TO HAVE TO GO IN AND REPLICATE CHANGE THAT IS IBM AND CURE VERSE FIND AND IN THE END, ALL OF THE ITERATIONS WILL HAVE US LOOKING TOWARDS, CAN WE FIND THOSE THERAPEUTIC TARGETS? ARE THERE PATTERNS OF INTEREST IN ALZHEIMER'S GENOME THAT WE, BECAUSE WE ARE SO DOWN IN THE WEEDS AND LOOKING AT BASE PAIR ONE AT A TIME, CAN THEY TELL US IF THERE ARE PATTERNS IN THE GENOME OF THE ALZHEIMER'S ASSEMBLE THAT ARE DIFFERENT THAN OUR CONTROLS? WE ALSO HAVE METHYLATION AND OMICS DATESSA AND THERE IS ALL KINDS OF DATA FROM OTHER COMPLEX DISEASES THAT CAN BE LOOKED AT BY WATSON. WE CAN'T DO THAT. AND THEY CAN ALSO MINE LITERATURE. DOES SOMETHING HERE IN THIS PARTICULAR REGION OF THE GENOME AND ANOTHER DISEASE THAT MIGHT APPLY HERE? AND WE MIGHT BE HELPFUL FOR FINDING THERAPEUTIC TARGET. SO THE TRAJECTORY IS FROM THE GENOME CENTER TO CURE VERSE WITH THEIR TILES THEN TO MINT AND AUGMENTED GWAS OVER TO THE GENOME CENTER AGAIN FOR THE GENETICIST TO REPLICATE DATA AND THEN TO ANNOTATE. PLEASE WATSON, IF ONLY YOU CAN JUST HELP US ANNOTATE THE GENOME. EVERY WEEK WE HAVE A CALL ABOUT THE ANNOTATION AND THEY FIND ONE MORE THING THAT THEY HAVE TO ANNOTATE. AND I HAVE BEEN ON ABOUT 523 ANNOTATION CALLS. CAN WE JUST -- COULD WATSON JUST TELL US WHAT THE THINGS ARE THAT WE ARE SEEING THAT ARE UNUSUAL? MAYBE IT'S SEEN IN ANOTHER DISEASE AND WE DON'T NEED TO REINVENT THE WHEEL. SO, WE ARE UNDERWAY. THE DATE ARE MOVING THIS WEEK FROM OUR GENOME CENTER OVER TO CURE VERSE AND THEY ARE BEING CRUNCHED AND IN A COUPLE OF WEEKS THEY WILL SEND THE DATA TO IBM AND THEN IN ABOUT 20 MINUTES WATSON WILL SEND IT BACK. AND WE'LL TAKE IT OVER TO THE GENOME CENTER. AND, WATSON, IF YOU'RE LISTENING, I WOULD GO AND READ THE ALZHEIMER'S ASSOCIATION INTERNATIONAL CONGRESS ABSTRACTS FROM LAST WEEK IN LONDON WHERE THERE WERE 55 OR SO GENES MENTIONED. AND WE SURE WOULD LIKE IT IF YOU COULD TELL US IF ONE OF THOSE IS IMPORTANT AND WHILE YOU'RE READING THOSE WATSON, PLEASE NOTE THAT NEUROINFLAMMATION HAS BECOME, BECAUSE OF THE GENES THAT WERE REPORTED AT THAT MEETING, A KEY FACTOR IN ALZHEIMER'S DISEASE AND THE IMMUNE SYSTEM IS EQUALLY I INDICATED. THANK YOU. -- EQUALLY IMPLICATED. THANK YOU. [ APPLAUSE ] >> DR. WEINBERG: I HOPE THAT STIMULATED YOUR THINKING THE WAY IT STIMULATED MINE WHEN WE THINK ABOUT DATA AND THE PLACENTA AND THE POWER OF DEEP LEARNING. SO, WE HAVE TIME FOR A FEW QUESTIONS. ANYBODY WANT TO POSE THEM? >> [ OFF MICROPHONE ] >> DR. MILLER: JUST SHOUT. >> [ OFF MICROPHONE ] >> YOU ADDRESS ONE PIECE OF IT AND THEN INTEGRATE FURTHER. SO I'M SURE WE'LL BE ADDRESSING THAT. >> THE QUESTION IS WHAT IS SAY REAL CONTROL? SEE, OBVIOUSLY WE HAVE LOTS OF EPIDEMIOLOGISTS AND GENETIC EPIDEMIOLOGISTS ON THE PROJECT. AND ACTUALLY THE FIRST PART OF THE PROJECT WE REALLY CONTROLLED FOR THAT. BOY CHOOSING PEOPLE WHO WERE AT THE MOST RISK EARLY AND AT THE LEAST RISK LATE. SO WE SKEWED THE FIRST PART OF THE APPROACH SO WE COULD REALLY GENE LOAD ON ONE END OR THE OTHER. FOR THE REST OF THE PROJECT, WE ARE NOT DOING THAT BECAUSE WE DON'T HAVE ENOUGH SECRETARIES TO DO THAT AND THE LOADING -- SUBJECTS -- AND THE LOADING PART IS HAVING THAT APOE4 ALLELE BECAUSE THOSE ARE THE MOST AT RISK SUBJECTS. BUT THERE AREN'T THAT MANY PEOPLE WITH IT. SO, WE HAVE TO WORK WITH WHERE THE POPULATION IS. SO FOR WHAT THE CONTROLS ARE, WE HAVE REALLY DENSE ENDOTHELIAL TYPIC DATA. WE HAVE OUR ALZHEIMER'S CENTERS AND THEY ALL HAVE IMAGING. SO WE CAN LOOK AND SEE WHAT WE THINK NORMAL IS FOR NOW. I AM FULLY IN BELIEF OF THE FACT THAT EVERYBODY, PROBABLY CARRIES ANNALS HEIMISHES GENE AND IT MAY BE THAT YOU HAVE -- ALZHEIMER'S GENE AND MAYBE YOU HAVE TO HAVE THREE GENES TO GET PUSHED OVER A CLIFF. SO IT'S NOT JUST ONE THING. AND EVEN MORE COMPLICATED, IT'S NOT JUST ALZHEIMER'S. IT'S ALZHEIMER'S DISEASE AND REALITIESED DEMENTIAS. SO WE PUT OUT A POLICY STATEMENT LASTED YEAR SAYING, WE ARE LOOKING AT TOO NARROW HERE. GO OUT AND LOOK AT ALZHEIMER'S DISEASE RELATED DEMENTIA. ALL OF THOSE THINGS BECAUSE WE FOUND THOSE GENES IN OUR PROJECT SO WE KNEW IT'S NOT JUST ONE THING. SO IT'S COMPLICATED. WE ARE DOING THE BEST WE CAN. >> AUDIENCE MEMBER: HI, THAT WAS ABSOLUTELY FASCINATING. I'M CURIOUS TO KNOW, IT'S NOT MA AREA OF RESEARCH SEE FORGIVE MY LACK OF KNOWLEDGE. BUT, WHAT IS THE ATTRIBUTABLE GENETIC RISK FOR ALZHEIMER'S APART FROM THE FAMILIAL SHALLY ONSET SYNDROME WHICH HAS BEEN REASONABLY WELL CHARACTERIZED? >> DR. MILLER: THAT WAS JUST A CRUMMY THING WE DID IN 2000. WE SHOULD NEVER EVER HAVE DIVIDED INTO EARLY-ONSET AND LATE ONSET. BECAUSE IT IS REALLY -- FROM WHAT I HAVE SEEN, AND FROM THE GENES I'M SEEING AT THE VARIOUS STAGES, IT'S A CONTINUUM. YES, THERE ARE THREE KNOWN EARLY ON SET ALZHEIMER'S DISEASE BUT THEY ONLY POINT TOWARDS 5% OF THE EARLY-ONSET. 95% OF THE POPULATION IS CAUSED BY SOMETHINGELS AND WE HAVEN'T EVEN LOOKED AT THAT! SO WE ARE STARTING TO GET SEQUENCING PROJECTS ON THE EARLY-ONSET ONES. ALSO VERY INTERESTING IS THE S. THAT THERE ARE POPULATIONS LIKE THE -- COHORT WHICH HAS VERY LARGE ONES. SAME MUTATION IN THE SAME FAMILY WITH AN AGE OF ONSET 20 YEARS APART WITH THE SAME GENES. SO SOMEBODY HAS A PROTECTIVE FACTOR. WE WANT TO KNOW WHAT THAT IS. BECAUSE ONCE WE NAIL DOWN WHAT THE PROTECTIVE FACTOR IS, WE CAN START LOOKING FOR A THERAPEUTIC TARGET. >> AUDIENCE MEMBER: SO I UNDERSTAND WHAT YOU'RE SAYING BUT I STILL DON'T HEAR WHAT THE POPULATION BASED ATTRIBUTABLE GENETIC RISK IS IF IT'S -- WE HAVE TO DO THE GENETIC CHARACTERIZATION OF VERY, VERY CLEAR-CUT FAMILIAL TENDENCY. I UNDERSTAND THAT TO GET AT THE UNDERLYING PHYSIOLOGY. BUT, WHAT PROPORTION OF CASES GLOBALLY IS ACTUALLY TRACEABLE TO A GENETIC ORIGIN -- AND HOW MUCH IS SPORADIC? >> DR. MILLER: I'M NOT USING THAT WORD, SPORADIC. ALZHEIMER'S DISEASE SELL 80% HERITABLE. >> AUDIENCE MEMBER: THAT'S BIG. >> DR. MILLER: IT USED TO BE WE USED TO THINK, WHEN I FIRST STARTED THIS, IT WAS, I DON'T KNOW, 10%. NOW WITH THE -- WE HAVE SO MANY FAMILIES WITH MORE THAN ONE PERSON. ONCE YOU START LOOKING AROUND, IT'S IN FAMILIES. SO, OTHER PEOPLE IN THE FAMILY MIGHT HAVE DIED OF SOMETHING ELSE BUT I BELT YOU THEY HAD ANNALS HEIMERS GENE TOO. >> AUDIENCE MEMBER: JUST ONE LAST QUICK QUESTION. IN YOUR CONTROLS, DO YOU HAVE THESE CASES WITH ABSOLUTELY NO KNOWN FAMILIAL RISK TO GET AT THE SEEMINGLY -- >> DR. MILLER: I'M NOT SURE I COULD SAY THERE IS NO KNOWN FAMILIAL REFRESHING. I WOULD HAVE THOUGHT WE COULD SAY YES WE COULD PULL THOSE OUT BUT I'M NOT CONVINCED ANYMORE. I THINK WE ARE ALL -- LET'S SAY YOU CARRY FIVE ALZHEIMER'S GENES IN INFLAMMATORY PATHWAY, THAT'S GOING TO SET SOMETHING OFF. SO IT'S A NUMBERS GAME. DO YOU HAVE ENOUGH PROTECTIVE FACTORS THAT STOP THAT FROM GETTING KICKED OFF? WE NEED TO FIND THE PROTECTIVE FACTORS TO FIGURE THAT OUT. IT'S JUST NOT STANDARD GENETICS ANYMORE. >> AUDIENCE MEMBER: JUST FASCINATING. THANK YOU. >> AUDIENCE MEMBER: SO THANK YOU FOR A GREAT TALK. I'M WONDERING TIEING IT TOGETHER WITH THE THEME OF THIS MEETING WHICH IS THE PLACENTA. IF YOU COULD USE IT AS A MODEL OF HUMAN AGING, SO THERE IS SOME KIND OF PARALLEL PROCESS GOING ON. PLACENTA IS A HUMORING AN WHICH LIVES THE ENTIRE LIFE IN A 7-9 MONTH SPAN AND WHEN PLACENTA AGES PREMATURELY, WE CAN SEE DISEASES. WONDERING IF THERE IS ANY VALUE OR ANY STRUCTURE -- AM I ASKING A BAD QUESTION? >> DR. WEINBERG: YOU CAN KEEP GOING. >> AUDIENCE MEMBER: I THOUGHT THAT WAS A SIGN. DO YOU THINK THERE IS ANYTHING THAT YOU COULD GLEAN FROM PLACENTAL BIOLOGY THAT MIGHT -- LIKE PUT IN PLACENTAL GENES INTO WATSON AND THEN MAYBE COME UP WITH SOME IDEAS OF ALZHEIMER'S? >> DR. MILLER: I GUESS I'D FEEL BETTER ABOUT SAYING YES IF I KNEW THERE WAS SOMETHING NA COULD KEEP THE PLACENTA VIABLE FOR AN EXTENDED PERIOD OF TIME. WHAT WE ARE LOOKING AT IS THE BRAIN AND THAT IS KIND OF A PROTECTED AREA. ONLY CERTAIN PROTEINS CAN GET INTO THE BRAIN. >> AUDIENCE MEMBER: THAT IS TRUE OF THE PLACENTA AS WELL. >> DR. MILLER: THAT'S THE ANALOGY THAT I'M MAKING. SO MAYBE THERE IS -- MAYBE THAT IS A POSSIBILITY. >> AUDIENCE MEMBER: JUST SOMETHING TO THINK ABOUT. RANDOM THOUGHT. THANKS. >> DR. MILLER: HOW ABOUT A NICE R21? [ LAUGHS ] >> [ OFF MICROPHONE ] >> DR. WEINBERG: SO I'M GOING DO BRING THIS DISCUSSION TO A CLOSE. I'M SORRY. PLEASE FIND THEM AFTER THE MEETING ENDS AND SORT OF REFOCUS EVERYBODY. THANK YOU BOTH. [ APPLAUSE ] ALZHEIMER'S IS A GREAT TOPIC AND IT'S REALLY FASCINATING. AND WHAT REALLY STRIKES ME IS THAT WHEN I THINK ABOUT ALL THE DATA THAT WE ARE GENERATING ON THE PLACENTA AND THINKING ABOUT THE PLACENTA AND UNDERSTANDING IT, THAT IT'S NICE TO SEE A CONCRETE EXAMPLE OF DEEP LEARNING AND DATA ANALYSIS BECAUSE LET'S FACE IT, THE DATA THAT YOU'RE ALL GENERATING IS GOING UP-AND-UP AND UP. MAYBE NOT TO THE LEVEL HERE BUT WHO KNOWS WHERE WE ARE HEADED AND SO I THINK THAT WE COULD HAVE A LOT OF REALLY INTERESTING DISCUSSIONS ABOUT HOW TO LOOK AT DATA AND THINK ABOUT DATA AND STRUCTURE DATA. SO IS THIS THIS IS MY PLUG FOR MAYBE FUTURE THINGS TO THINK ABOUT. SO ANYWAY, THAT IS THE END OF THE FORMAL PRESENTATIONS. AND WE ARE ALMOST DONE. BUT I'D LIKE DO ASK DR. BIANCHI TO COME UP AND SHE'LL CLOSE OUT THE MEETING. >> DR. BIANCHI: THANK YOU, DAVID. I'M SO HAPPY TO SEE SO MANY OF YOU STILL HERE. FIRST OF ALL, I'D LIKE TO GIVE THANKS TO OUR WONDERFUL SPEAKERS. SO LET'S GIVE A ROUND OF APPLAUSE TO ALL OF OUR SPEAKERS. [ APPLAUSE ] AND THEN I'D LIKE TO THANK OUR CONTRACTING STAFF WHO HANDLE ALL THE LOGISTICS. SO THOSE WHO ARE SPEAKERS, WHO HAD TRAVEL ARRANGEMENTS OR THOSE OF YOU, JUST THE REGISTRATION PROCESS. EVERYTHING. SO I'D LIKE TO GIVE APPLAUSE TO THEM AND THANK THEM FOR VERY WELL-RUN MEETING. AND THEN I'D LIKE TO THANK THE NICHD STAFF, PARTICULARLY KRISTI ROGERS WHO COULDN'T BE HERE TODAY AND OF COURSE DAVID WEINBERG, WHO REALLY IS THE GURU OF THE HUMAN PLACENTA PROJECT. SO LET'S GIVE THEM A ROUND OF APPLAUSE. [ APPLAUSE ] AND AS I TOLD YOU YESTERDAY, I MISSED LAST YEAR. BUT DO ME, I SEE A TREMENDOUS DIFFERENCE BETWEEN YEAR TWO AND YEAR 4. I THINK THE ENERGY, THE COMMUNITY THAT HAS BEEN ESTABLISHED, THE COMMUNICATION, THE CONVERSATIONS THAT I HEARD IN THE HALLWAY. THERE IS SOMETHING VERY DIFFERENT ABOUT THIS MEETING. I ALSO FEEL THAT THERE HAS BEEN AN EMBRACING OF PEOPLE FROM OUTSIDE TRADITIONAL PLACENTAL BIOLOGY RESEARCH. AND SOME PEOPLE IN THE TALKS I HEARD WERE APOLOGETIC ABOUT THAT. BUT, THIS IS WHAT IS GREAT ABOUT THIS PARTICULAR CONFERENCE, THAT PEOPLE FROM OTHER -- THIS IS PART OF OUR MISSION IS TO WELCOME PEOPLE NOT WORKING IN TRADITIONAL PLACENTAL RESEARCH AND BRING THEM FROM. AND STOW YOU HEARD AN EXAMPLE OF THAT AND EVEN THE VERY LAST CONVERSATION ABOUT WHAT DOES AGING HAVE TO DO WITH THE PLACENTA? THE PLACENTA FUNCTIONS AS EVERY ORGAN. THE LUNGS, THE DIGESTIVE SYSTEM, IT IS THE BRAIN. AND YOU CAN GO ON AND ON AND - AND YET IT HAS A PLANNED SKIN ESSENCE DO IT. SO IT DOES ITS THING AND SOMETIMES IT AGES PREMATURELY BUT BASICALLY IT IS DESIGNED TO BE DISCARDED AT THE END OF THE PREGNANCY. SO THERE ARE LESSONS THAT CAN BE LEARNED THAT CAN MAKE PARALLELS BETWEEN AGING AND THE PLACENTA. I ALSO HEARD A LOT ABOUT DATA SHARING DURING THIS MEETING. AND I DO THINK THAT WE ARE GOING TO HAVE SOME CONVERSATION BUSY WHAT ARE THE BEST WAYS TO SHARE THE DATA THAT ARE BEING EMANATED FROM THIS PARTICULAR PROJECT. AND NOT ONLY DOES HE THAT ADVANCE THE SCIENCE, BUT IT ALSO ADVANCES RECOGNITION OF THE IMPORTANCE OF THE PLACENTA. AT THE VERY BEGINNING OF THE HUMAN PLACENTA PROJECT, I MADE THE COMMENT THAT PLACENTA IS THE RODNEY DANGER FIELD OF MEDICINE AND THAT WAS INCLUDED ON THE VIDEO. AND SOMEBODY TWEETED IT YESTERDAY. BUT, DID IS TRUE. MOST PEOPLE DON'T RECOGNIZE THE IMPORTANCE OF THE PLACENTA AND THEY ONLY THINK ABOUT WHAT THEY HEAR FROM KIM KARDASHIAN, FOR EXAMPLE, ON THE PLACENTA. SO, THE MORE WE CAN DATA SHARE, THE MORE WE CAN SHOW THAT THE DATA YOU ALL ARE GENERATING ARE IMPORTANT FOR MULTIPLE AREAS OF SCIENCE AND MEDICINE. IT WILL HELP US ALL. SO WE WILL BE THINKING ABOUT THAT AND WE WILL WELCOME YOUR INPUT IN TERMS OF HOW DO WE ADDRESS THE DATA SHARING ASPECT OF HPP. EVEN THOUGH WE ARE REALLY JUST HEARING ABOUT THESE INITIAL PROGRESS REPORTS, DAVE IS I ARE BEGINNING TO TALK ABOUT WHAT IS THE ENDGAME? WHAT IS THE NEXT STEP? WHAT PRODUCT WILL EMANATE FROM THIS? AND OF COURSE THE ULTIMATE PRODUCT IS TO ACCELERATE AND IMPROVE CLINICAL CARE. BUT THERE IS A TREMENDOUS AMOUNT THAT WE HEARD ABOUT OVER THE LAST FEW DAYS. AND I WOULD IMAGINE IN THE NEXT FEW YEARS, WE ARE GOING TO BE THINKING ABOUT SOME SORT OF EXECUTIVE SUMMARY OF WHAT DID THE 50 MILLION DOLLARS GENERATE? AND MAYBE THERE WILL BE A VERSION FOR SCIENTISTS, A VERSION FOR LAY PEOPLE. I THINK THAT TARA'S PRESENTATION YESTERDAY'S, I MEAN TARA IS GOING TO TAKE THE MESSAGE BACK TO HER CONSTITUENTS AND PEOPLE WHO READ HER BLOG, THAT THERE ARE SCIENTISTS WHO CARE ABOUT THE WORK THAT IS BEING DONE AND MAKE THAT CONNECTION WITH THE COMMUNITY OF PEOPLE WHO ARE EFFECTED BY STILL BIRTH, FOR EXAMPLE. BUT ALSO THIS MORNING, I WAS MEETING WITH 12 DIFFERENT REPRESENTATIVES FROM CONGRESS, A BIPARTISAN GROUP OF REPRESENTATIVES WHO WERE CONVENED IN A SPECIAL BREAKFAST MEETING BY PETE SESSIONS, WHICH CHAIRS THE HOUSE RULES COMMITTEE. AND JUST TO LEAVE THINGS ON A POSITIVE NOTE, I KNOW THAT EVERYBODY IS CONCERNED ABOUT FUNDING, BUT I HEARD A WONDERFUL TERM THIS MORNING FROM CHAIRMAN COAL WHO IS THE CHAIRMAN OF THE APPROPRIATIONS COMMITTEE THAT ULTIMATELY MAKES THE RECOMMENDATIONS ABOUT FUNDING FOR NIH; AND HE SAID HE REALLY WANTS TO PLUS UP FUNDING. I NEVER HEARD THAT TERM BEFORE. SO I THINK THAT SAY VERY HOPEFUL SIGN. THEY ARE EXTREMELY POSITIVE ABOUT NIH AND THE WORK THAT YOU ALE DOING, THAT WE ALL ARE DOING. AND WE NEED TO CONTINUOUSLY COMMUNICATE THE PRODUCTS OF THE HUMAN PLACENTA PROJECT BECAUSE IF WE EDUCATE OUR ELECTED REPRESENTATIVES, THAT THEY HAVE œTO A PLACENTA ONCE UPON A TIME AS WELL, AND THE FACT THAT THEIR PLACENTAS FUNCTION PRETTY WELL, IT'S WHY THEY CAN LIVE LONG ENOUGH TO BE A CONGRESSIONAL REPRESENTATIVE, THEN WE MAKE THAT HUMAN CONNECTION. [ LAUGHS ] SO, THE LAST THING I WANT TO MENTION IS, I REALLY AM EXCITED BY THE FACT THAT A NUMBER OF OUR PRESENTERS IN THE LAST FEW DAYS, WERE CONSIDERABLY YOUNGER THAN I AM. AND I WANT TO WELCOME THAT. I ALSO JUST WANT TO BE SURE TO MENTION THAT WE HAVE THIS NEXT GENERATION SCIENTIST INITIATIVE. SO YOU PROBABLY WERE AWARE OF THE BROUHAHA ABOUT THE GRANT SUPPORT INDEX AND CAPPING THE POINTS SYSTEM, WHICH SOUNDED A LITTLE BIT LIKE WEIGHT WATCHERS, BUT YOU COULD BASICALLY HAVE THREE RO1s BEFORE YOU WERE CUT OFF FROM FURTHER NIH FUNDING. THAT WAS A PROPOSAL THAT WAS FLOATED IN THE SPRING. AND BECAUSE OF THE TREMENDOUS PUSH BACK, IT HAS MORPHED INTO WHAT REALLY IS OUR GOAL, WHICH IS TO FUND THE NEXT GENERATION OF RESEARCHERS WHO ARE HAVING QUITE A BIT OF DIFFICULTY. SO I WANT YOU TO KNOW THAT NICHD TAKES THIS EXTREMELY SERIOUSLY. AND WE HAVE BEEN LOOKING AT A POOL OF 67 EARLY-STAGE INVESTIGATORS, NOT NEW INVESTIGATORS. THERE IS A DIFFERENCE. SO EARLY STAGE INVESTIGATOR IS SOMEBODY WHO IS WITHIN 10 YEARS OF THE COMPLETION OF THEIR TRAINING. WHEREAS A NEW INVESTIGATOR COULD BE 60 YEARS OLD, WORKING FOR IB. AND SUDDENLY DECIDING TO APPLY FOR A NIH GRANT. SHOW IS EARLY-STAGE INVESTIGATORS. SO WE ARE BEING ENCOURAGED TO PREFERENTIALLY FUND EARLY-STAGE INVESTIGATORS. SO, THAT IS SOMETHING TO WATCH IN THIS SPACE. AND AS I SAID, I'M VERY GRATIFIED WE ALREADY SEE THE FRUITS OF OUR LABORS BECAUSE A NUMBER OF OUR FUNDED YOUNG SCIENTISTS HAVE BEEN PRESENTING HERE OVER THE PAST FEW DAYS. SO I WANT TO WISH EVERYBODY A SAFE TRAVEL HOME. I HOPE YOU DON'T HAVE THE SAME TRAVEL ISSUES THAT A NUMBER OF US HAD COMING IN. AND WISH YOU WELL AND STAY TUNED AS TO WHETHER THERE WILL BE AN HPP5 OR NOT. WE HOPE THERE WILL BE. THANK YOU VERY MUCH. [ APPLAUSE ]