1 00:00:05,760 --> 00:00:10,120 >>WELCOME TO THE SUBCOMMITTEE 2 00:00:10,120 --> 00:00:13,440 MEETING OF THE DIVISION OF 3 00:00:13,440 --> 00:00:16,480 ALLERGY IMMUNOLOGY AND 4 00:00:16,480 --> 00:00:17,840 TRANSPLANTATION ADVISORY 5 00:00:17,840 --> 00:00:18,040 COUNCIL. 6 00:00:18,040 --> 00:00:22,600 WE HAVE A TERRIFIC GROUP OF 7 00:00:22,600 --> 00:00:30,240 SPEAKERS THIS AFTERNOON WHO WILL 8 00:00:30,240 --> 00:00:32,600 BE BRINGING US UP-TO-DATE IN THE 9 00:00:32,600 --> 00:00:34,160 ASTHMA AND ALLERGY PORTFOLIO. 10 00:00:34,160 --> 00:00:40,080 BEFORE WE BEGIN, I HAVE A COUPLE 11 00:00:40,080 --> 00:00:41,760 ANNOUNCEMENTS TO MAKE WHICH ARE 12 00:00:41,760 --> 00:00:45,160 LOGISTICAL FOR THIS AFTERNOON 13 00:00:45,160 --> 00:00:48,080 AND THE FIRST IS ANY INTERESTED 14 00:00:48,080 --> 00:00:50,840 MEMBERS OF THE PUBLIC CAN FILE 15 00:00:50,840 --> 00:00:52,640 WRITTEN COMMENTS WITH THE 16 00:00:52,640 --> 00:00:54,120 EXECUTIVE SECRETARY OF THE 17 00:00:54,120 --> 00:00:56,080 COMMITTEE WITHIN 15 DAYS OF 18 00:00:56,080 --> 00:00:57,800 TODAY'S MEETING. 19 00:00:57,800 --> 00:00:59,080 THOSE COMMENTS WILL BE INCLUDED 20 00:00:59,080 --> 00:01:04,080 IN THE MINUTES TO THE EXTENT 21 00:01:04,080 --> 00:01:05,520 THAT IS PRACTICABLE. 22 00:01:05,520 --> 00:01:06,520 THE MAILING INFORMATION TO DO 23 00:01:06,520 --> 00:01:09,960 THAT WAS PUBLISHED IN THE 24 00:01:09,960 --> 00:01:10,840 FEDERAL REGISTER NOTICE 25 00:01:10,840 --> 00:01:11,680 ANNOUNCING TODAY'S MEETING SO IF 26 00:01:11,680 --> 00:01:13,960 YOU ARE INTERESTED IN SUBMITTING 27 00:01:13,960 --> 00:01:15,400 COMMENTS, PLEASE DO SO. 28 00:01:15,400 --> 00:01:18,360 AND THEN A REMINDER TO OUR STAFF 29 00:01:18,360 --> 00:01:25,360 AND TO COUNCIL MEMBERS, PLEASE, 30 00:01:25,360 --> 00:01:30,120 ANYBODY WHO IS SHOULD BE ON 31 00:01:30,120 --> 00:01:35,600 CAMERA AND AND ANYBODY WHO WOULD 32 00:01:35,600 --> 00:01:39,520 LIKE TO USE THE CHAT ROOM, 33 00:01:39,520 --> 00:01:41,120 PLEASE DO NOT THAT WON'T BE 34 00:01:41,120 --> 00:01:44,640 INCLUDED IN THE OFFICIAL MEETING 35 00:01:44,640 --> 00:01:45,200 NOTES. 36 00:01:45,200 --> 00:01:52,200 SO IF YOU HAVE QUESTIONS OR 37 00:01:52,200 --> 00:01:55,560 COMMENTS, WAVE YOUR HAND OR 38 00:01:55,560 --> 00:01:56,640 RAISE YOUR HAND USE THAT 39 00:01:56,640 --> 00:02:06,240 FUNCTION AND WE'LL BE SURE TO 40 00:02:06,240 --> 00:02:12,480 FIND YOU. 41 00:02:12,480 --> 00:02:13,800 PATRICE BECKER WILL GIFT HISTORY 42 00:02:13,800 --> 00:02:19,400 ON ONE OF THE INSTITUTES' VERY 43 00:02:19,400 --> 00:02:21,160 LONGSTANDING IN CHILDHOOD 44 00:02:21,160 --> 00:02:22,200 PATRICE, THE FLOOR IS YOURS. 45 00:02:22,200 --> 00:02:24,200 >>THANK YOU FOR THE 46 00:02:24,200 --> 00:02:26,800 OPPORTUNITY TO INTRODUCE THIS 47 00:02:26,800 --> 00:02:27,200 TOPIC. 48 00:02:27,200 --> 00:02:28,760 THOSE OF YOU I HAVEN'T MET I'M 49 00:02:28,760 --> 00:02:31,240 THE SECTION CHIEF FOR ASTHMA AND 50 00:02:31,240 --> 00:02:34,240 AIRWAY BIOLOGY IN THE DIVISION 51 00:02:34,240 --> 00:02:36,840 OF ASTHMA AND IT'S MY GREAT 52 00:02:36,840 --> 00:02:37,440 PLEASURE TO ZOO OUR SPEAKERS 53 00:02:37,440 --> 00:02:39,360 TODAY WHO WILL TELL YOU A LITTLE 54 00:02:39,360 --> 00:02:45,480 BIT ABOUT SOME OF THE OVERVIEW 55 00:02:45,480 --> 00:02:48,080 AND EXCITING DATA FROM THE URBAN 56 00:02:48,080 --> 00:02:51,520 CHILDHOOD ASTHMA STUDY ALSO 57 00:02:51,520 --> 00:02:56,080 KNOWN EUREKA. 58 00:02:56,080 --> 00:02:57,480 URECA GREW OUT OF PROGRAMS 59 00:02:57,480 --> 00:03:07,160 WITHIN NIAID AND AND CHILDREN 60 00:03:07,160 --> 00:03:08,800 FROM DISADVANTAGED POPULATIONS 61 00:03:08,800 --> 00:03:11,280 OF COLOR IN LOW INCOME URBAN 62 00:03:11,280 --> 00:03:13,040 ENVIRONMENTS WHO YOU ARE BURDEN 63 00:03:13,040 --> 00:03:14,600 BIAS MA TO BETTER UNDERSTAND THE 64 00:03:14,600 --> 00:03:17,600 FACTORS THAT WERE INVOLVED IN 65 00:03:17,600 --> 00:03:20,000 BOTH ASTHMA PATHOGEN A SIS AS 66 00:03:20,000 --> 00:03:21,000 WELL AS ASTHMA MANAGEMENT IN 67 00:03:21,000 --> 00:03:31,480 THIS POPULATION AND WITH RISK 68 00:03:35,480 --> 00:03:36,600 FACTORS IN THESE URBAN CHILDREN 69 00:03:36,600 --> 00:03:41,200 AND CONTINUING ON WITH A 70 00:03:41,200 --> 00:03:42,640 ENVIRONMENTAL SELECTION STUDY 71 00:03:42,640 --> 00:03:44,520 WITH A MAJOR FACTOR IN THIS 72 00:03:44,520 --> 00:03:50,280 POPULATION AS AN ASTHMA RISK AND 73 00:03:50,280 --> 00:03:52,400 THE ICAS STUDY AND LED INTO 74 00:03:52,400 --> 00:03:54,280 FUNDING CYCLES OF WHAT WAS 75 00:03:54,280 --> 00:03:57,480 CALLED THE INNER-CITY ASTHMA 76 00:03:57,480 --> 00:03:59,640 CONSORTIUM STARTING IN 2002 AND 77 00:03:59,640 --> 00:04:06,680 IT WAS IN 2005 THAT THIS WAS 78 00:04:06,680 --> 00:04:07,040 INITIATED. 79 00:04:07,040 --> 00:04:08,200 WE'VE HAD SEVERAL MORE 80 00:04:08,200 --> 00:04:10,720 ITERATIONS OF FUNDING THAT HAVE 81 00:04:10,720 --> 00:04:12,120 INVOLVED INTERVENTIONAL TRIALS 82 00:04:12,120 --> 00:04:14,200 WITH DIAGNOSTICS IN THIS 83 00:04:14,200 --> 00:04:17,560 POPULATION AND THERAPEUTICS AND 84 00:04:17,560 --> 00:04:19,560 LOOKING AT PHENOTYPING AND 85 00:04:19,560 --> 00:04:23,280 PILOTING BOTH BUY LOGICS AND 86 00:04:23,280 --> 00:04:25,880 IMMUNO THERAPEUTICS AND BUY 87 00:04:25,880 --> 00:04:30,040 LOGICS FOR ASTHMA AND MANAGEMENT 88 00:04:30,040 --> 00:04:31,920 AND THERAPY AND OUR ITERATION 89 00:04:31,920 --> 00:04:33,920 WHICH WAS FUNDED LAST YEAR THAT 90 00:04:33,920 --> 00:04:35,520 WAS RENAMED TO THE CHILDHOOD 91 00:04:35,520 --> 00:04:38,320 ASTHMA AND URBANS SETTINGS 92 00:04:38,320 --> 00:04:38,840 NETWORK. 93 00:04:38,840 --> 00:04:49,880 LOOKING AT THOSE OBSERVATIONALAY 94 00:04:50,160 --> 00:04:55,200 2000s THERE'S BEEN THIS URECA 95 00:04:55,200 --> 00:04:56,800 BIRTH COHORT THAT'S BEEN 96 00:04:56,800 --> 00:04:57,120 INVOLVED. 97 00:04:57,120 --> 00:05:01,440 I TELL YOU ABOUT URECA IT WAS TO 98 00:05:01,440 --> 00:05:03,080 ESTABLISH IMMUNE LOGIC CAUSES 99 00:05:03,080 --> 00:05:05,640 FOR THE DEVELOPMENT OF ATM 100 00:05:05,640 --> 00:05:07,520 REOCCURRING ASTHMA IN THESE 101 00:05:07,520 --> 00:05:09,560 CHILDREN OF COLOR FROM URBAN LOW 102 00:05:09,560 --> 00:05:11,360 INCOME POPULATIONS AND AS I 103 00:05:11,360 --> 00:05:13,600 MENTIONED, IT WAS INITIATED IN 104 00:05:13,600 --> 00:05:16,120 2005 AT FOUR OF THE SITES THAT 105 00:05:16,120 --> 00:05:18,000 PARTICIPATING IN THE FIRST 106 00:05:18,000 --> 00:05:19,840 ITERATION OF THE INNER-CITY 107 00:05:19,840 --> 00:05:20,880 ASTHMA CONSORTIUM. 108 00:05:20,880 --> 00:05:24,720 IT'S A LONGITUDINAL PROSPECTIVE 109 00:05:24,720 --> 00:05:26,240 EVALUATION WHERE CHILDREN WERE 110 00:05:26,240 --> 00:05:31,800 RECRUITED AT BIRTH AND THIS YEAR 111 00:05:31,800 --> 00:05:33,200 BEGINNING THEIR AGE 17 FINAL 112 00:05:33,200 --> 00:05:33,920 STUDY VISITS. 113 00:05:33,920 --> 00:05:36,840 THIS STUDY INITIALLY RECRUITED 114 00:05:36,840 --> 00:05:38,000 560 PREGNANT MOTHERS WITH BABIES 115 00:05:38,000 --> 00:05:39,560 WHO WERE AT HIGH-RISK FORAY 116 00:05:39,560 --> 00:05:46,080 LEDGE FORALLERGIC DISEASE AND 4N 117 00:05:46,080 --> 00:05:48,120 RECRUITED WITHOUT PARENTAL 118 00:05:48,120 --> 00:05:49,560 HISTORY DISSERVICE AND CONTROLS. 119 00:05:49,560 --> 00:05:51,680 IT'S BEEN A PRODUCTIVE STUDY. 120 00:05:51,680 --> 00:05:52,720 IF WE COUNT WHAT WE CONSIDERED 121 00:05:52,720 --> 00:05:55,240 TO BE THE PRIMARY MANUSCRIPTS, 122 00:05:55,240 --> 00:05:56,960 PRE DEFINED BY ITERATIONS OF THE 123 00:05:56,960 --> 00:05:58,760 PROTOCOLS THERE ARE CLOSE TO 40 124 00:05:58,760 --> 00:06:00,320 AND AS YOU WILL HEAR FROM OUR 125 00:06:00,320 --> 00:06:01,800 SPEAKERS, THERE ARE MANY, MANY 126 00:06:01,800 --> 00:06:03,560 MORE ADDITIONAL MANUSCRIPTS THAT 127 00:06:03,560 --> 00:06:05,440 HAVE BEEN GENERATED AND ARE 128 00:06:05,440 --> 00:06:07,280 CONTINUING TO BE GENERATED FROM 129 00:06:07,280 --> 00:06:09,440 THIS COHORT AND THE DATA AS YOU 130 00:06:09,440 --> 00:06:11,440 WILL HEAR FROM AGAIN OUR 131 00:06:11,440 --> 00:06:15,720 SPEAKERS, IS NOW BEING LOOKED AT 132 00:06:15,720 --> 00:06:20,120 IN THE CONTEXT OF OTHER STUDIES 133 00:06:20,120 --> 00:06:23,120 AND COHORTS OF CHILDHOOD ASTHMA 134 00:06:23,120 --> 00:06:24,560 IN DIFFERENT DEMOGRAPHICS 135 00:06:24,560 --> 00:06:25,280 POPULATION S WITH SOME 136 00:06:25,280 --> 00:06:26,640 INTERESTING FINDINGS. 137 00:06:26,640 --> 00:06:29,160 SO OUR THREE SPEAKERS TODAY, YOU 138 00:06:29,160 --> 00:06:31,360 HEARD BRIEFLY INTRODUCED BY TONY 139 00:06:31,360 --> 00:06:35,720 AT THE OPEN SESSION AT 10:30 AND 140 00:06:35,720 --> 00:06:38,120 JIM GERN PROFESSOR IN THE 141 00:06:38,120 --> 00:06:41,000 DIVISION CHIEF OF ALLERGY AND 142 00:06:41,000 --> 00:06:45,360 RHEUMATOLOGY AND RESEARCH IN 143 00:06:45,360 --> 00:06:46,920 SPEED ADD TRICKS AND JIM HAS 144 00:06:46,920 --> 00:06:48,680 BEEN THE PRINCIPAL INVESTIGATOR 145 00:06:48,680 --> 00:06:53,480 OF THE STUDY SINCE 2005 AND 146 00:06:53,480 --> 00:06:57,120 ACTIVE PARTICIPANT IN ALL OF THE 147 00:06:57,120 --> 00:07:00,800 STUDIES AND CAROLE OBER WHO IS 148 00:07:00,800 --> 00:07:02,000 INVOLVED IN THIS NETWORK FOR 149 00:07:02,000 --> 00:07:05,120 MANY YEARS. 150 00:07:05,120 --> 00:07:07,600 THE BLUM-RIESE DIS TINGE FISHED 151 00:07:07,600 --> 00:07:08,880 SERVICE PROFESSOR AND CHAIR OF 152 00:07:08,880 --> 00:07:13,240 HUMAN GENETICS AT UNIVERSITY OF 153 00:07:13,240 --> 00:07:15,640 CHICAGO AND MATT ALTMAN AND ALSO 154 00:07:15,640 --> 00:07:19,200 AN ASSOCIATE SCIENTIST AT THE 155 00:07:19,200 --> 00:07:20,240 BENAROYA RESEARCH INSTITUTE. 156 00:07:20,240 --> 00:07:24,000 I'M GOING TO TURN THINGS OVER TO 157 00:07:24,000 --> 00:07:34,440 JIM SO HE CAN KICK US OFF. 158 00:07:45,800 --> 00:07:50,680 >> THANK YOU, VERY MUCH FOR THE 159 00:07:50,680 --> 00:07:52,320 KIND INTRODUCTION AND FOR IN 160 00:07:52,320 --> 00:07:53,520 INVITE US US TO SPEAK WITH US 161 00:07:53,520 --> 00:07:54,880 HERE TODAY AND I'LL TALK ABOUT 162 00:07:54,880 --> 00:07:59,200 PHENOTYPES OF ASTHMA AND 163 00:07:59,200 --> 00:08:03,120 RHINITIS IN CHILDREN IN URECA 164 00:08:03,120 --> 00:08:06,120 COHORT. 165 00:08:06,120 --> 00:08:16,720 EUREKA THERE WAS 560 CHILDREN AL 166 00:08:20,880 --> 00:08:22,120 HIGH-RISK NOT ONLY WHERE THEY'RE 167 00:08:22,120 --> 00:08:24,040 GROWING UP FAMILY MEMBERS EITHER 168 00:08:24,040 --> 00:08:25,680 MOM OR DAD HAD ALLERGIES AND AS 169 00:08:25,680 --> 00:08:27,720 MA AND AS WE NOTED DURING 170 00:08:27,720 --> 00:08:29,800 RECRUITMENT IT APPLIES TO 85% OF 171 00:08:29,800 --> 00:08:32,240 FAMILIES IN THE INNER-CITY AND 172 00:08:32,240 --> 00:08:36,320 OUR FINAL COHORT HAD 72% BLACK 173 00:08:36,320 --> 00:08:41,960 CHILDREN AND 20% HISPANIC AND 8% 174 00:08:41,960 --> 00:08:52,440 OTHER AND WHAT ARE THE EARLY 175 00:08:53,360 --> 00:08:58,960 ENVIRONMENTAL AND WE FOCUSED ON 176 00:08:58,960 --> 00:09:04,200 FOUR MAIN CATEGORIES, HOUSE 177 00:09:04,200 --> 00:09:07,840 DUST ALLERGEN AND SMOKING, VIRAL 178 00:09:07,840 --> 00:09:09,760 RESPIRATORY ILLNESSES AMONG A 179 00:09:09,760 --> 00:09:13,960 HOST OF OTHER EVALUATIONS. 180 00:09:13,960 --> 00:09:15,320 SO THIS SLOWS THE MAJOR 181 00:09:15,320 --> 00:09:16,800 PREDICTORS AND OUTCOMES 182 00:09:16,800 --> 00:09:18,760 EVALUATED IN URECA AND THEY'RE 183 00:09:18,760 --> 00:09:21,360 FOUR MAIN TIME PERIODS SO THAT 184 00:09:21,360 --> 00:09:28,000 PERRY NATHAT -- PERINATAL AND PL 185 00:09:28,000 --> 00:09:29,880 FACTORS VIRAL RESPIRATORY 186 00:09:29,880 --> 00:09:32,880 ILLNESSES, ALLERGANS, MICROBES, 187 00:09:32,880 --> 00:09:34,480 STRESS, POLLUTION AND DIET. 188 00:09:34,480 --> 00:09:36,960 DURING THE PRESCHOOL PERIOD, THE 189 00:09:36,960 --> 00:09:41,200 MAIN OUTCOMES WERE ALLEGEIC AND 190 00:09:41,200 --> 00:09:43,280 RECURRENT LEADS AND THESE MAIN 191 00:09:43,280 --> 00:09:44,360 EVALUATIONS WERE ABOUT THROW 192 00:09:44,360 --> 00:09:47,920 YEARS OF AGE AND THEN DURING THE 193 00:09:47,920 --> 00:09:49,840 SCHOOL AGE TIME PERIOD, WE 194 00:09:49,840 --> 00:09:52,080 EVALUATED RESPIRATORY AND ASTHMA 195 00:09:52,080 --> 00:09:54,280 PHENOTYPES FROM LONGITUDINAL 196 00:09:54,280 --> 00:09:56,120 MEASUREMENTS OF WHEEZE, ALLERGIC 197 00:09:56,120 --> 00:09:58,080 SENSATION AND LUNG FUNCTION AND 198 00:09:58,080 --> 00:09:59,200 CURRENTLY WE'RE IN THE PROCESS 199 00:09:59,200 --> 00:10:00,880 OF LOOKING AT THAT TRANSITION 200 00:10:00,880 --> 00:10:02,200 BETWEEN SCHOOL-AGE AND 201 00:10:02,200 --> 00:10:03,880 ADOLESCENTS AND LOOKING AT 202 00:10:03,880 --> 00:10:04,960 HORMONAL INFLUENCES, THE 203 00:10:04,960 --> 00:10:07,600 INFLUENCE OF OBESITY AND ASTHMA 204 00:10:07,600 --> 00:10:09,640 INCIDENTS AND REMISSION AND 205 00:10:09,640 --> 00:10:13,080 AGAIN, AS MA PHENOTYPES, LUNG 206 00:10:13,080 --> 00:10:14,920 FUNCTION AND AIRWAY HYPER 207 00:10:14,920 --> 00:10:15,400 RESPONSIVENESS. 208 00:10:15,400 --> 00:10:19,720 AND IN ADDITION, WE OBTAINED TWO 209 00:10:19,720 --> 00:10:23,080 MAIN SETS OF SAMPLES FOR 210 00:10:23,080 --> 00:10:24,800 MECHANISTIC STUDIES INCLUDING 211 00:10:24,800 --> 00:10:26,200 AIRWAYS CELLS FOR GENE 212 00:10:26,200 --> 00:10:28,400 EXPRESSION AND DNA METHYLATION 213 00:10:28,400 --> 00:10:30,920 AND ALSO BLOOD CELLS FOR GENETIC 214 00:10:30,920 --> 00:10:36,600 STUDIES AND THESE INCLUDE 17 215 00:10:36,600 --> 00:10:37,560 17Q1221 SNIPS AS WELL AS WHOLE 216 00:10:37,560 --> 00:10:39,360 GENOME SEQUENCES AND CAROLE AND 217 00:10:39,360 --> 00:10:43,520 MATT WILL DISCUSS THESE FACTORS. 218 00:10:43,520 --> 00:10:45,040 SO WE'LL START FIRST WITH THE 219 00:10:45,040 --> 00:10:47,880 FINDINGS DURING THE PRESCHOOL 220 00:10:47,880 --> 00:10:49,880 PERIODND ONE OF THE SURPRISING 221 00:10:49,880 --> 00:10:52,600 FINDINGS WERE INDOOR ALLERGEN 222 00:10:52,600 --> 00:10:54,560 EXPOSURE WAS INVERSELY 223 00:10:54,560 --> 00:10:58,200 ASSOCIATED WITH RECURRENT WHEEZE 224 00:10:58,200 --> 00:11:01,240 AT AGE THREE THE UNIQUE PATTERN 225 00:11:01,240 --> 00:11:04,480 OF ALLERGAN EXPOSURE IN THOSE 226 00:11:04,480 --> 00:11:05,800 CHILDREN WOULD LEAD TO MORE 227 00:11:05,800 --> 00:11:07,400 MORBIDITY BUT WHAT YOU SEE IN 228 00:11:07,400 --> 00:11:09,000 THESE GRAPHS STARTING WITH 229 00:11:09,000 --> 00:11:10,720 COCKROACH, WE HAVE EXPOSURE AND 230 00:11:10,720 --> 00:11:12,040 THIS IS IN NEAR ONE AND IT WAS 231 00:11:12,040 --> 00:11:14,360 THE SIMILAR FOR YEARS ONE TWO 232 00:11:14,360 --> 00:11:19,120 AND THREE AND THE MORE COCKROACH 233 00:11:19,120 --> 00:11:20,440 ALLERGAN IN THE HOUSE DUST OF 234 00:11:20,440 --> 00:11:22,720 THE HOMES, THE LOWER OF RISK OF 235 00:11:22,720 --> 00:11:27,320 RECURRENT WHOSE IT WAS A 236 00:11:27,320 --> 00:11:31,720 SUBSTANTIAL EFFECT ACROSS THOSE 237 00:11:31,720 --> 00:11:37,160 THREE EXPOSURE TUR TILES AND CAT 238 00:11:37,160 --> 00:11:38,640 AND MOUSE. 239 00:11:38,640 --> 00:11:39,520 DUST MIGHT DIDN'T FOLLOW THE 240 00:11:39,520 --> 00:11:42,480 SAME PATTERN BUT AGAIN, THESE 241 00:11:42,480 --> 00:11:44,320 THREE MAJOR INDOORALLER AGAINST 242 00:11:44,320 --> 00:11:50,080 WERE INVERSELY ASSOCIATED WITH 243 00:11:50,080 --> 00:11:51,240 RECURRENT WHEEZE. 244 00:11:51,240 --> 00:11:52,680 WE LOCKED AT THE COMBINED EARLY 245 00:11:52,680 --> 00:11:57,400 LIFE ALLERGAN AND MICRO BIOTA 246 00:11:57,400 --> 00:11:58,880 AND COMPARED THIS TO CHILDREN 247 00:11:58,880 --> 00:12:01,800 WHO WERE CATEGORIZED PAID ON 248 00:12:01,800 --> 00:12:02,760 RECURRENT WHEEZE AT THREE YEARS 249 00:12:02,760 --> 00:12:03,360 OF AGE. 250 00:12:03,360 --> 00:12:05,440 SO FIRST OF ALL, THE KIDS AND 251 00:12:05,440 --> 00:12:10,240 THE FOUR COLUMNS HERE, KIDS WHO 252 00:12:10,240 --> 00:12:13,000 HAD NEITHER RECURRENT WHEEZE AND 253 00:12:13,000 --> 00:12:17,520 KITS WHO HAD ONLY WHEEZING AND 254 00:12:17,520 --> 00:12:18,800 NO SENSATION KIDS ONLY SENSE A 255 00:12:18,800 --> 00:12:20,160 TIESED WITHOUT WHEEZE AND KIDS 256 00:12:20,160 --> 00:12:24,600 WHO HAVE BOTH AND AND WE CUT 257 00:12:24,600 --> 00:12:25,800 RICHNESS AND EARLY AGAIN 258 00:12:25,800 --> 00:12:29,560 EXPOSURE IN THE FIRST THREE 259 00:12:29,560 --> 00:12:31,320 YEARS INTO DIFFERENT CATEGORIES 260 00:12:31,320 --> 00:12:32,760 BASED ON ABOVE OR BELOW THE 261 00:12:32,760 --> 00:12:33,080 MEDIAN. 262 00:12:33,080 --> 00:12:38,160 THE RED IS HIGH, HIGH ROBES ARE 263 00:12:38,160 --> 00:12:43,520 IN AND LOW ALLERGANS AND GROWN 264 00:12:43,520 --> 00:12:47,520 AND LOW MICROBES AND YOU CAN SEE 265 00:12:47,520 --> 00:12:48,720 MARKET DIFFERENCES IN THE 266 00:12:48,720 --> 00:12:52,280 ENVIRONMENT IF THE FIRST THREE 267 00:12:52,280 --> 00:12:53,480 YEARS FOR CHILDREN IN THE 268 00:12:53,480 --> 00:12:55,080 DIFFERENT OUTCOME CATEGORIES SO 269 00:12:55,080 --> 00:12:57,680 KIDS WHO HAD NEITHER WHEEZE NOR 270 00:12:57,680 --> 00:12:59,000 OTHER SENSATIONS WERE MOST 271 00:12:59,000 --> 00:13:00,360 LIKELY TO GROW UP IN 272 00:13:00,360 --> 00:13:02,240 ENVIRONMENTS THAT HAD HIGH 273 00:13:02,240 --> 00:13:04,520 EXPOSURE TO BOTH MICROBES 274 00:13:04,520 --> 00:13:08,920 ANDALL ALLERGAN AND LEAST LIKELO 275 00:13:08,920 --> 00:13:11,320 GROW UP IN ENVIRONMENTS IN HOMES 276 00:13:11,320 --> 00:13:14,200 WITH LOW MICROBIAL EXPOSURE AND 277 00:13:14,200 --> 00:13:15,480 LOW ALLERGAN EXPOSURE. 278 00:13:15,480 --> 00:13:17,200 IF YOU MOVE TO THE RIGHT, THE 279 00:13:17,200 --> 00:13:21,280 KIDS WITH BOTH WHEEZING AND 280 00:13:21,280 --> 00:13:22,560 ATOPY WERE LESS LIKELY TO GROW 281 00:13:22,560 --> 00:13:24,480 UP IN HIGH EXPOSURE HOMES AND 282 00:13:24,480 --> 00:13:27,120 MOST LIKELY TO GROW UP IN LOW 283 00:13:27,120 --> 00:13:27,880 EXPOSURE HOMES. 284 00:13:27,880 --> 00:13:30,240 SO AS WE MOVE FORWARD TO SCHOOL 285 00:13:30,240 --> 00:13:33,680 AGE WE FIRST STARTED TO TAKE A 286 00:13:33,680 --> 00:13:36,080 LOOK AT EARLY LIFE ENVIRONMENTAL 287 00:13:36,080 --> 00:13:39,800 EXPOSURES AND ASTHMA AT AND WE 288 00:13:39,800 --> 00:13:41,360 FOUND POSITIVE RELATIONSHIPS 289 00:13:41,360 --> 00:13:43,080 WITH MATERNAL DEPRESSION SCORES 290 00:13:43,080 --> 00:13:46,320 AND AS MA AND MATERNAL PERCEIVED 291 00:13:46,320 --> 00:13:49,120 STRESS AND HAS MA AND THIS IS 292 00:13:49,120 --> 00:13:50,160 PRE-NATAL OVER THE FIRST THREE 293 00:13:50,160 --> 00:13:51,680 YEARS AND THE MORE ILLNESSES 294 00:13:51,680 --> 00:13:58,960 REPORTED BY THE CHILD, THE 295 00:13:58,960 --> 00:13:59,920 GREATER ASTHMA. 296 00:13:59,920 --> 00:14:01,120 THE AND THE AIR AND HOME 297 00:14:01,120 --> 00:14:03,160 EXPOSURE SIMILAR TO WHAT WE 298 00:14:03,160 --> 00:14:04,680 REPORTED AT THREE YEARS OF AGE 299 00:14:04,680 --> 00:14:07,720 AND THIS INVERSE RELATIONSHIP 300 00:14:07,720 --> 00:14:09,080 WAS TRUE FOR KIDS WHO WERE SENSE 301 00:14:09,080 --> 00:14:10,920 A TIESED AND KIDS WHO WERE NOT 302 00:14:10,920 --> 00:14:12,120 SENSE A TIESED AND YOU CAN SEE 303 00:14:12,120 --> 00:14:13,760 OVER ALL IN THE SENSE TIESED 304 00:14:13,760 --> 00:14:20,800 KIDS HAVE A HIGHER RISK OF 305 00:14:20,800 --> 00:14:30,960 ASTHMA AND 306 00:14:41,920 --> 00:14:43,480 LUNG FUNCTION IN THE FIRST 10 307 00:14:43,480 --> 00:14:45,320 YEARS THAT WE USED TO PUT 308 00:14:45,320 --> 00:14:47,560 TOGETHER LONGITUDINAL 309 00:14:47,560 --> 00:14:52,000 TRAJECTORIES AND FOR EACH OF 310 00:14:52,000 --> 00:14:58,240 THESE AND A MATRIX WAS AND THESE 311 00:14:58,240 --> 00:15:00,360 PHENOTYPES WERE RELATED TO EARLY 312 00:15:00,360 --> 00:15:01,760 LIFE ENVIRONMENTAL EXPOSURES AND 313 00:15:01,760 --> 00:15:03,240 I'LL SHOW YOU THOSE DATA IN THE 314 00:15:03,240 --> 00:15:05,800 NEXT COUPLE OF SLIDES AND MATT 315 00:15:05,800 --> 00:15:06,960 IS GOING TO SHOW YOU 316 00:15:06,960 --> 00:15:10,880 RELATIONSHIPS TIGER WOODS 317 00:15:10,880 --> 00:15:12,400 RELATIONSHIP -- GREEN EXPRESSION 318 00:15:12,400 --> 00:15:15,320 AND NASAL BRUSHINGS AT 11 YEARS 319 00:15:15,320 --> 00:15:16,200 OF AGE. 320 00:15:16,200 --> 00:15:18,960 SO HERE WERE THE SIX PHENOTYPES 321 00:15:18,960 --> 00:15:22,640 JUST NAMED FOR THEIR DIFFERENT 322 00:15:22,640 --> 00:15:24,880 PATTERN OF WHEEZE, ATOPY AND 323 00:15:24,880 --> 00:15:25,280 LUNG FUNCTION. 324 00:15:25,280 --> 00:15:27,920 THESE WERE THE HEALTHIEST SO LOW 325 00:15:27,920 --> 00:15:34,600 WHEEZE, LOW A TOP' AND WE HAVE 326 00:15:34,600 --> 00:15:37,600 THIS AND THEN A GROUP OF KIDS 327 00:15:37,600 --> 00:15:39,600 WITH MODERN AMOUNTS OF WHEEZING 328 00:15:39,600 --> 00:15:44,000 IN LOW ATOPY AND THIS GROUP OF 329 00:15:44,000 --> 00:15:45,880 CHILDREN WHO DIDN'T WHEEZE BUT 330 00:15:45,880 --> 00:15:49,640 HAD HIGH ATOPY THIS GROUP WITH 331 00:15:49,640 --> 00:15:51,400 MODERATE WHEEZING AND HIGH ATOPY 332 00:15:51,400 --> 00:15:53,800 AND A GROUP THAT HAD THE HIGHEST 333 00:15:53,800 --> 00:15:56,640 RATE OF WHEEZING, HIGH ATOPY AND 334 00:15:56,640 --> 00:15:58,440 UNIQUELY EVIDENCE OF AIRWAY 335 00:15:58,440 --> 00:15:58,760 OBSTRUCTION. 336 00:15:58,760 --> 00:16:01,400 AND ALL OF THESE GROUPS HAD 337 00:16:01,400 --> 00:16:02,840 DECENT SAMPLE SIZES SO WE CAN 338 00:16:02,840 --> 00:16:05,000 REALLY START TO LOOK AT EARLY 339 00:16:05,000 --> 00:16:07,440 LIFE ENVIRONMENTAL FACTORS. 340 00:16:07,440 --> 00:16:08,600 AND FIRST OF ALL, WE'LL JUST 341 00:16:08,600 --> 00:16:10,600 TAKE A LOOK AT PATTERNS OF 342 00:16:10,600 --> 00:16:13,440 WHEEZE, ALLERGIC SNESITIZATION 343 00:16:13,440 --> 00:16:22,000 AND LUNG FUNCTION AMONG THESE 344 00:16:22,000 --> 00:16:30,600 SIX WE HAD TWO MODERATE WHEEZE 345 00:16:30,600 --> 00:16:32,800 GROUP AND KIDS WHO HAD LITTLE OR 346 00:16:32,800 --> 00:16:35,080 NO WHEEZING WITH OR WITHOUT 347 00:16:35,080 --> 00:16:40,600 ALLERGICALLEGE SENSITIZATION. 348 00:16:40,600 --> 00:16:43,040 THERE WERE TWO GENERAL PATTERNS 349 00:16:43,040 --> 00:16:44,840 SO WE HAD THREE GROUPS HERE THAT 350 00:16:44,840 --> 00:16:47,720 HAD INCREASING AMOUNTS OF ARROW 351 00:16:47,720 --> 00:16:49,680 ALLERGAN SENSITIVITY SO NOT 352 00:16:49,680 --> 00:16:51,200 SURPRISINGLY, THIS HIGH WHEEZE, 353 00:16:51,200 --> 00:16:53,320 HIGH ATOPY AND LOW LUNG FUNCTION 354 00:16:53,320 --> 00:16:56,360 AND ALSO THE MODERATE WHEEZE 355 00:16:56,360 --> 00:16:57,920 GROUP AND A GROUP THAT DIDN'T 356 00:16:57,920 --> 00:17:00,760 HAVE WHEEZING AND YET HAD 357 00:17:00,760 --> 00:17:03,440 SIMILAR PATTERNS OF ALLERGIC 358 00:17:03,440 --> 00:17:04,400 SENSITIZATION OVER TIME AND 359 00:17:04,400 --> 00:17:06,920 THREE GROUPS WITH LITTLE OR NO 360 00:17:06,920 --> 00:17:08,800 ALLERGIC SENSITIZATION. 361 00:17:08,800 --> 00:17:10,200 WITH LUNG FUNCTION WE HAD TWO 362 00:17:10,200 --> 00:17:12,360 DIFFERENT MEASUREMENTS SO FEV1 363 00:17:12,360 --> 00:17:17,720 AND FEC, VERY TRADITIONAL 364 00:17:17,720 --> 00:17:18,960 MEASURE OF AIRWAY OBSTRUCTION 365 00:17:18,960 --> 00:17:23,800 AND REACT WHICH MEASURES THE 366 00:17:23,800 --> 00:17:26,280 HETEROGENEITY OF SMALL AIRWAVES 367 00:17:26,280 --> 00:17:27,920 CALENDER AND FUNCTION AND FOR 368 00:17:27,920 --> 00:17:34,960 THE RATIO YOU CAN SEE THAT THE 369 00:17:34,960 --> 00:17:42,000 KIDS EXCEPT FOR THIS GROUP WHICH 370 00:17:42,000 --> 00:17:49,400 IS PART FOR THE NA THAT YOUNG 371 00:17:49,400 --> 00:17:51,040 KIDS HAVE TROUBLE WITH SUSTAINED 372 00:17:51,040 --> 00:17:53,720 EX PA TORI MANEUVER SO THEY 373 00:17:53,720 --> 00:17:55,440 MIGHT BE UNDERESTIMATING AND 374 00:17:55,440 --> 00:17:57,200 CLEARLY ONE GROUP STANDING APART 375 00:17:57,200 --> 00:18:01,040 AND THIS HIGH WHEEZE HIGH ATOPY 376 00:18:01,040 --> 00:18:01,720 LOW FUNCTION GROUP. 377 00:18:01,720 --> 00:18:03,600 IF YOU LOOK AT THE REACT ANTS 378 00:18:03,600 --> 00:18:11,760 AREA THEY'RE MUCH MORE PARALLEL 379 00:18:11,760 --> 00:18:20,040 AND AND NEXT WE'LL LOOK AT 380 00:18:20,040 --> 00:18:21,440 CLINICAL ASSOCIATIONS WITH THE 381 00:18:21,440 --> 00:18:22,720 PHENOTYPES SO THEY'RE ALL IN THE 382 00:18:22,720 --> 00:18:24,760 COLUMNS HERE AND THEN THE 383 00:18:24,760 --> 00:18:26,040 MEASUREMENTS ARE GROUPED IN 384 00:18:26,040 --> 00:18:29,400 TERMS OF CO-MORBIDITY SO ASTHMA, 385 00:18:29,400 --> 00:18:31,600 ECZEMA, CHRONIC NASAL SYMPTOMS 386 00:18:31,600 --> 00:18:32,680 AND LUNG FUNCTION MEASUREMENTS 387 00:18:32,680 --> 00:18:34,960 SUCH AS PC20 AND THIS WAS AT AGE 388 00:18:34,960 --> 00:18:38,520 10 AND FEV1 AT AGE 10 AND 389 00:18:38,520 --> 00:18:44,080 MEDICATION USE IN THE 10 YEAR OF 390 00:18:44,080 --> 00:18:45,320 LIFE AND WHAT CAN YOU SEE BY 391 00:18:45,320 --> 00:18:46,600 LOOKING AT THE DIFFERENT COLUMNS 392 00:18:46,600 --> 00:18:48,680 IS IT'S REALLY THIS HIGH WHEEZE, 393 00:18:48,680 --> 00:18:50,680 HIGH ATOPY LOW LUNG FUNCTION 394 00:18:50,680 --> 00:18:52,800 THAT HAS THE CLOSEST ASSOCIATION 395 00:18:52,800 --> 00:18:55,280 WITH CO-MORBIDITY AND A LITTLE 396 00:18:55,280 --> 00:18:59,160 MORE ECZEMA WITH THIS MODERATE 397 00:18:59,160 --> 00:19:02,040 WHEEZE HIGH ATOPY GROUP AND THE 398 00:19:02,040 --> 00:19:04,040 FUNCTION FUNCTIONS WERE MOST 399 00:19:04,040 --> 00:19:05,280 ABNORMAL IN THIS GROUP AND MOST 400 00:19:05,280 --> 00:19:08,640 LIKELY TO BE USING EITHER INHALE 401 00:19:08,640 --> 00:19:14,400 STEROIDS OR OR ALTER VOIDS SO 402 00:19:14,400 --> 00:19:16,160 WE'LL LOOK AT ENVIRONMENTAL 403 00:19:16,160 --> 00:19:16,960 EXPOSURES AND THE PHONE OWE 404 00:19:16,960 --> 00:19:19,760 TYPES AND WE'RE LOOKING AT 405 00:19:19,760 --> 00:19:21,400 MATERNAL DEPRESSION SCORES AND 406 00:19:21,400 --> 00:19:22,840 MA THESE ARE CUMULATIVE FOR THE 407 00:19:22,840 --> 00:19:24,440 FIRST THREE YEARS AND THE 408 00:19:24,440 --> 00:19:26,120 ALLERGAN EXPOSURE INDEX SO THIS 409 00:19:26,120 --> 00:19:31,120 IS IF YOU ADD UP EXPOSURE TO IN 410 00:19:31,120 --> 00:19:32,480 YOU HOUSE DUST TO CAT, DOG, 411 00:19:32,480 --> 00:19:36,400 MOUSE AND COCKROACH, THAT'S WHAT 412 00:19:36,400 --> 00:19:39,480 THIS INDEX IS AND HOUSE DUST IS 413 00:19:39,480 --> 00:19:45,200 A MEASUREMENT OF FUNGEL EXPOS 414 00:19:45,200 --> 00:19:45,840 EXPOSURE. 415 00:19:45,840 --> 00:19:47,160 SO, MATERNAL STRESS AND 416 00:19:47,160 --> 00:19:49,680 DEPRESSION WAS ASSOCIATED WITH 417 00:19:49,680 --> 00:19:52,360 OTHER WHEEZING PHENOTYPES BUT 418 00:19:52,360 --> 00:19:56,600 MOST CLOSELY ASSOCIATED WITH 419 00:19:56,600 --> 00:19:59,360 THIS MODERATE WHEEZE AND IN 420 00:19:59,360 --> 00:20:01,440 CONTRAST THE HIGH WHEEZE, LOW 421 00:20:01,440 --> 00:20:04,840 LUNG FUNCTION PHENOTYPE HAD THE 422 00:20:04,840 --> 00:20:06,160 LOWEST ALLERGAN EXPOSURE IN 423 00:20:06,160 --> 00:20:07,440 EARLY LIFE, CONTINUING THAT 424 00:20:07,440 --> 00:20:09,320 THEME WE SAW AT AGE THREE AND 425 00:20:09,320 --> 00:20:10,360 AGE SEVEN. 426 00:20:10,360 --> 00:20:13,520 ALSO, HAD INCREASED EXPOSURE IN 427 00:20:13,520 --> 00:20:16,320 EARLY LIFE TO ERGOSTEROL AND 428 00:20:16,320 --> 00:20:20,320 THIS IS A MEASUREMENT OF FUNG 429 00:20:20,320 --> 00:20:28,600 ALEX POSE YOU'RE. 430 00:20:28,600 --> 00:20:32,000 THIS ANALYSIS GOES THROUGH UNTIL 431 00:20:32,000 --> 00:20:38,520 AGE 12 AND WE'RE DEVELOPING THIS 432 00:20:38,520 --> 00:20:39,800 DATA THERE WERE FOUR WITH 433 00:20:39,800 --> 00:20:42,400 PATTERNS WE USED A SIMILAR 434 00:20:42,400 --> 00:20:45,640 VALUED APPROACH HERE AND KIDS 435 00:20:45,640 --> 00:20:47,520 HAVE LOW TO MINIMUM RHINITIS 436 00:20:47,520 --> 00:20:54,520 EVERYONRYAN OVERTIME AND THOSE E 437 00:20:54,520 --> 00:20:55,160 PERSISTENT RHINITIS IN THE GREEN 438 00:20:55,160 --> 00:20:58,160 AND THOSE WHO HAVE PERSISTENT 439 00:20:58,160 --> 00:20:59,760 RHINITIS THAT DECREASES A LITTLE 440 00:20:59,760 --> 00:21:05,000 BIT IN EARLY LIFE AND THIS 441 00:21:05,000 --> 00:21:06,000 PERSISTENT RHINITIS PHENOTYPES 442 00:21:06,000 --> 00:21:09,920 SEEMS TO BE THE ONE THAT IS MOST 443 00:21:09,920 --> 00:21:10,800 PROBLEMATIC WITH A FAMILY 444 00:21:10,800 --> 00:21:14,960 HISTORY OF ALLERGIC DISEASE AND 445 00:21:14,960 --> 00:21:16,880 PRO NAL AT POST EXPOSURE AND 446 00:21:16,880 --> 00:21:18,440 ANTIBIOTIC USE AND RAPID WEIGHT 447 00:21:18,440 --> 00:21:23,440 GAIN IN EARLY LIFE AND CLOSELY 448 00:21:23,440 --> 00:21:25,360 WITH BIOMARKERS AND ASTHMA RISK 449 00:21:25,360 --> 00:21:26,720 AND I'LL JUST MENTION AS WELL 450 00:21:26,720 --> 00:21:29,320 THAT THESE PATTERNS ARE RHINITIS 451 00:21:29,320 --> 00:21:31,000 REALLY PARALLEL TO THE LARGE 452 00:21:31,000 --> 00:21:32,560 EXTENT OF WHAT WE FOUND IN TERMS 453 00:21:32,560 --> 00:21:38,000 OF PATTERNS OF WHEEZE SO, THIS 454 00:21:38,000 --> 00:21:40,200 IS A SUMMARY OF SOME OF THE PURE 455 00:21:40,200 --> 00:21:46,200 EQUAL A DATA AS A INDIVIDUAL 456 00:21:46,200 --> 00:21:52,680 COHORT AND AND MODERATE TO 457 00:21:52,680 --> 00:21:55,360 SEVERE AS MA AND MOST OF THE 458 00:21:55,360 --> 00:21:58,120 ASTHMA IN URECA IS MILD AND ALSO 459 00:21:58,120 --> 00:22:00,520 THE DATA ARE POPULATION SPECIFIC 460 00:22:00,520 --> 00:22:02,720 AND IT'S DIFFICULT TO COMPARE 461 00:22:02,720 --> 00:22:07,080 ACROSS DIFFERENT POPULATIONS AND 462 00:22:07,080 --> 00:22:09,040 ACROSS DIFFERENT ENVIRONMENTS 463 00:22:09,040 --> 00:22:10,280 AND THEY HAVE DIFFERENT 464 00:22:10,280 --> 00:22:11,880 POPULATIONS OF CHILDREN AND THIS 465 00:22:11,880 --> 00:22:14,440 IS WHERE COLLABORATIONS WITHIN 466 00:22:14,440 --> 00:22:16,760 THE ECHO, THE ENVIRONMENTAL 467 00:22:16,760 --> 00:22:19,520 INFLUENCES ON CHILD HEALTH 468 00:22:19,520 --> 00:22:20,640 OUTCOMES AND CROW CHILDREN'S 469 00:22:20,640 --> 00:22:22,480 RESPIRATORY AND ENVIRONMENTAL 470 00:22:22,480 --> 00:22:24,280 WORKGROUP PROGRAMS HAS REALLY 471 00:22:24,280 --> 00:22:27,760 BEEN WONDERFUL AND THESE ARE TWO 472 00:22:27,760 --> 00:22:30,880 PROGRAMS SUPPORTED BY THE 473 00:22:30,880 --> 00:22:34,280 NATIONAL INSTITUTE OF HEALTH AND 474 00:22:34,280 --> 00:22:40,160 SIX OWE IS COHORTS AND THESE 475 00:22:40,160 --> 00:22:50,720 WERE ECHO WAS FUNDED IN CREW IS 476 00:23:17,320 --> 00:23:20,080 ONE OF THE 31 ECHO AWARDS AND 477 00:23:20,080 --> 00:23:22,200 CONSISTS OF 13 BIRTH GOERS THAT 478 00:23:22,200 --> 00:23:25,080 INCLUDE URECA AND 9,000 NEWBORNS 479 00:23:25,080 --> 00:23:27,000 AND THE OUTCOMES ARE RELATED TO 480 00:23:27,000 --> 00:23:31,120 CHILDHOOD ALLERGY AND ASTHMA AND 481 00:23:31,120 --> 00:23:34,160 TOGETHER, EITHER ECHO OR CREW 482 00:23:34,160 --> 00:23:35,440 REALLY PROVIDE POPULATION 483 00:23:35,440 --> 00:23:36,640 DIVERSITY WITHIN EACH OF THESE 484 00:23:36,640 --> 00:23:38,560 STUDIES AND THIS IS IN TERMS OF 485 00:23:38,560 --> 00:23:42,800 GEOGRAPHIC DIVERSITY ALSO THE 486 00:23:42,800 --> 00:23:46,400 YEAR OF BIRTH. 487 00:23:46,400 --> 00:23:48,000 13469 COHORTS ARE STILLEN 488 00:23:48,000 --> 00:23:50,600 ROLLING AND INCLUDING URBAN, 489 00:23:50,600 --> 00:23:53,400 SUBURBAN AND RURAL CHILDREN AND 490 00:23:53,400 --> 00:23:59,920 A VERY REPRESENTATIVE VARIETY OF 491 00:23:59,920 --> 00:24:02,080 THESE ARE THE FOUR URECA COHORTS 492 00:24:02,080 --> 00:24:03,720 IN BLUE AND MAD SIN IS THE 493 00:24:03,720 --> 00:24:04,800 LEADERSHIP CENTER AND ROW HAS 494 00:24:04,800 --> 00:24:09,480 BEEN THE COORDINATING CENTER FOR 495 00:24:09,480 --> 00:24:12,440 CAUSE AND YOU CAN SEE IF WE ADD 496 00:24:12,440 --> 00:24:14,360 IN THE CREW COHORT WE HAVE 13 497 00:24:14,360 --> 00:24:15,800 NOW WITH BETTER REPRESENTATION 498 00:24:15,800 --> 00:24:17,720 RA CROSS THE COUNTRY WE HAVE A 499 00:24:17,720 --> 00:24:19,440 COUPLE OUST WEST AND A COUPLE IN 500 00:24:19,440 --> 00:24:21,720 THE SOUTH AND SO FOURTH AND YOU 501 00:24:21,720 --> 00:24:23,440 REALLY SEE TREMENDOUS DIVERSITY 502 00:24:23,440 --> 00:24:26,320 IF YOU ADD IN THE 69 COHORTS 503 00:24:26,320 --> 00:24:33,640 THAT ARE PARTICIPATING IN ECHO 504 00:24:33,640 --> 00:24:44,280 AND WE HAVE U.S. CHILDHOOD 505 00:24:44,280 --> 00:24:45,600 ASTHMA AND PATTERNS FROM THE 506 00:24:45,600 --> 00:24:48,480 ECHO CONSORTIUM TO HIGH FIE 507 00:24:48,480 --> 00:24:50,800 HIGH-RISK GROUPS INFORM PRIMARY 508 00:24:50,800 --> 00:24:51,800 PREVENTION. 509 00:24:51,800 --> 00:24:54,440 THESE ARE THE PAR PARTICIPATING 510 00:24:54,440 --> 00:24:56,280 SITES AND AND THE STUDY DESIGN 511 00:24:56,280 --> 00:25:01,040 WAS A DISTRIBUTE META ANALYSIS 512 00:25:01,040 --> 00:25:03,240 INCLUDING URECA OVER 12,000 513 00:25:03,240 --> 00:25:04,640 CHILDREN AND THE OUTCOMES WAS 514 00:25:04,640 --> 00:25:09,360 THE INCIDENTS OF Dr. DIAGNOSED 515 00:25:09,360 --> 00:25:12,920 ASTHMA WHICH ACROSS THE UNITED 516 00:25:12,920 --> 00:25:13,160 STATES. 517 00:25:13,160 --> 00:25:15,240 OF THIS STUDY WAS LED BY 518 00:25:15,240 --> 00:25:20,400 CHRISTINE JOHNSON. 519 00:25:20,400 --> 00:25:21,840 IT'S EXPECTED THIS YOU LOOK AT 520 00:25:21,840 --> 00:25:22,720 ASTHMA INCIDENTS RATES ONE OF 521 00:25:22,720 --> 00:25:24,600 THE IMPORTANT FACTOR IS FAMILY 522 00:25:24,600 --> 00:25:26,120 HISTORY IF YOU LOOK AT THE TWO 523 00:25:26,120 --> 00:25:27,960 COLUMNS HERE WE HAVE DATA FOR 524 00:25:27,960 --> 00:25:29,280 CHILDREN WITH NO FAMILY HISTORY 525 00:25:29,280 --> 00:25:36,200 OF ASTHMA AND IF 526 00:25:36,200 --> 00:25:39,320 YOU LOOK ACROSS KIDS WITH FAMILY 527 00:25:39,320 --> 00:25:40,440 HISTORY HAVE GREATER INCIDENTS 528 00:25:40,440 --> 00:25:43,280 RATES OVER ALL AND THE 529 00:25:43,280 --> 00:25:44,720 INFLUENCES OF SEXES AS EXPECTED 530 00:25:44,720 --> 00:25:46,920 WE'VE KNOWN THIS FOR PREVALENCE 531 00:25:46,920 --> 00:25:49,440 DATA FOR YEARS AND GREATER 532 00:25:49,440 --> 00:25:51,400 INCIDENTS IN BOYS UP UNTIL ABOUT 533 00:25:51,400 --> 00:25:56,960 TUBER PEE AND THOSE LINES CROSS 534 00:25:56,960 --> 00:25:57,880 AND THEY STILL LOOK THERE IN THE 535 00:25:57,880 --> 00:25:59,480 KIDS WITH THE POSITIVE FAMILY 536 00:25:59,480 --> 00:26:01,040 HISTORY BUT WHAT IS REALLY 537 00:26:01,040 --> 00:26:03,680 REMARKABLE IF YOU LOOK AT THE 538 00:26:03,680 --> 00:26:07,600 INFLUENCE OF RACE ON ASTHMA 539 00:26:07,600 --> 00:26:11,840 INCIDENTS, INCIDENTS HIGHER IN 540 00:26:11,840 --> 00:26:16,880 BLACKS OR IF YOU LOOK IN THE 541 00:26:16,880 --> 00:26:20,960 FIRST FEW YEARS LIFE YOU HAVE 542 00:26:20,960 --> 00:26:22,760 THREE TIMES THE ASTHMA INCIDENTS 543 00:26:22,760 --> 00:26:24,560 RATES IN NON HISPANIC BLACK 544 00:26:24,560 --> 00:26:26,120 CHILDREN COMPARED TO NON 545 00:26:26,120 --> 00:26:26,880 HISPANIC WHITE CHILDREN. 546 00:26:26,880 --> 00:26:28,720 IF YOU GO OUT INTO THE 547 00:26:28,720 --> 00:26:29,760 ADOLESCENTS AND TEEN YEARS, THE 548 00:26:29,760 --> 00:26:32,960 INCIDENTS THERE IS HIGHER IN 549 00:26:32,960 --> 00:26:34,800 WHITE CHILDREN AND IF YOU ARE 550 00:26:34,800 --> 00:26:37,880 PREDISPOSED TO ASTHMA IN YOUR A 551 00:26:37,880 --> 00:26:39,200 BLACK CHILD, YOU ARE GOING TO 552 00:26:39,200 --> 00:26:40,840 GET THAT DISEASE IN EARLY LIFE 553 00:26:40,840 --> 00:26:43,640 WHICH IS A PROBLEM AND WE KNOW 554 00:26:43,640 --> 00:26:45,920 THAT EARLY ONSET ASTHMA IS MORE 555 00:26:45,920 --> 00:26:48,280 SEVERE AND HAVE MORE AND MORE 556 00:26:48,280 --> 00:26:50,080 MORBIDITY AND JUST LOOK AT THE 557 00:26:50,080 --> 00:26:51,360 DISPARITY IF CHILDREN HAD A 558 00:26:51,360 --> 00:26:52,760 POSITIVE FAMILY HISTORY OF 559 00:26:52,760 --> 00:27:03,280 ASTHMA AND JUST SKY HIGH RATES 560 00:27:13,520 --> 00:27:15,240 WE HAVE A SECOND PAPER THAT IS 561 00:27:15,240 --> 00:27:17,560 JUST BEEN PUBLISHED IN THE LAST 562 00:27:17,560 --> 00:27:19,880 WEEK LED BY ANTON ELLA AND 563 00:27:19,880 --> 00:27:22,240 DIANNE GOLD AND THIS IS AN ECHO 564 00:27:22,240 --> 00:27:28,320 CREW PAPER AND SO DO 565 00:27:28,320 --> 00:27:29,240 NEIGHBORHOOD LEVEL SOCIAL 566 00:27:29,240 --> 00:27:31,000 ECONOMIC INDICATORS EXPLAIN 567 00:27:31,000 --> 00:27:32,760 THESE BIG RACIAL AND ETHNIC 568 00:27:32,760 --> 00:27:33,920 DISPARITIES IN CHILDHOOD 569 00:27:33,920 --> 00:27:35,960 WHEEZING AND ASTHMA? 570 00:27:35,960 --> 00:27:39,480 WE USED THE CREW POPULATION OVER 571 00:27:39,480 --> 00:27:44,800 5800 CHILDREN AND 43,000 PLUS 572 00:27:44,800 --> 00:27:46,560 THEY WERE A HAZARD MODEL TO 573 00:27:46,560 --> 00:27:48,360 DEVELOP HAZARD RATIOS OF ASTHMA 574 00:27:48,360 --> 00:27:50,640 INCIDENTS AND LOGISTIC 575 00:27:50,640 --> 00:27:52,120 REGRESSION TO CAT CUE LATE THE 576 00:27:52,120 --> 00:27:54,120 ODDS RATIO FOR EARLY AND 577 00:27:54,120 --> 00:27:54,640 PERSISTENT WHEEZE. 578 00:27:54,640 --> 00:27:57,400 THE THE MAIN EXPOSURE WAS 579 00:27:57,400 --> 00:27:58,760 NEIGHBORHOOD LEVEL AND DEFINED 580 00:27:58,760 --> 00:28:02,040 BY U.S. CENSUS TRACKS LINKED TO 581 00:28:02,040 --> 00:28:03,640 PARTICIPANT'S BIRTH ADDRESS AND 582 00:28:03,640 --> 00:28:05,720 DECADE OF BIRTH IN THE MAIN 583 00:28:05,720 --> 00:28:07,960 OUTCOME IS THE PREVALENCE OF 584 00:28:07,960 --> 00:28:09,320 EARLY PERSISTENT WHEEZE AND THE 585 00:28:09,320 --> 00:28:12,800 DATA ARE THE ASTHMA INCIDENTS 586 00:28:12,800 --> 00:28:14,720 DATA HERE ARE THE MAIN FINDINGS 587 00:28:14,720 --> 00:28:17,600 AND NOT PRICINGLY RACE, 588 00:28:17,600 --> 00:28:19,240 ETHNICITY, POVERTY AND LOWER 589 00:28:19,240 --> 00:28:20,800 HOUSEHOLD INCOME INCREASED RISK 590 00:28:20,800 --> 00:28:26,920 FOR CHILDHOOD ASTHMA AND 591 00:28:26,920 --> 00:28:28,280 HOWEVER, THEY WERE A RISK FACTOR 592 00:28:28,280 --> 00:28:33,680 AFTER ADJUSTING FOR NEIGHBORHOOD 593 00:28:33,680 --> 00:28:35,920 INCOME SO THE INTERACTIONS 594 00:28:35,920 --> 00:28:41,520 BETWEEN RACE ETHNICITY AND 595 00:28:41,520 --> 00:28:44,160 SOCIAL ECONOMIC SKATERS WERE NOT 596 00:28:44,160 --> 00:28:45,800 SIGNIFICANT THAN BLACK AND 597 00:28:45,800 --> 00:28:48,080 SIGNIFICANT CHILDREN IN HIGHER 598 00:28:48,080 --> 00:28:49,040 INCOME NEIGHBORHOODS STILL HAD 599 00:28:49,040 --> 00:28:53,680 INCREASED ASTHMA INCIDENTS 600 00:28:53,680 --> 00:28:53,920 RATES. 601 00:28:53,920 --> 00:28:58,040 SO IN CONCLUSION REGARDING URECA 602 00:28:58,040 --> 00:29:04,920 ASTHMA PHENOTYPES WE IDENTIFIED 603 00:29:04,920 --> 00:29:06,040 SIX. 604 00:29:06,040 --> 00:29:07,160 THE HIGH WHEEZE IS AN 605 00:29:07,160 --> 00:29:09,920 INTERESTING ONE SO IT'S A T-2 606 00:29:09,920 --> 00:29:12,760 LOW PHENOTYPE IN RICH FOR ASTHMA 607 00:29:12,760 --> 00:29:14,560 AND ASSOCIATED WITH MA TERNE AT 608 00:29:14,560 --> 00:29:15,360 STRESS AND DEPRESSION AND THERE 609 00:29:15,360 --> 00:29:18,680 COULD BE A NUMBER OF SEW 610 00:29:18,680 --> 00:29:24,120 VARIANTS ASSOCIATED WITH THOSE 611 00:29:24,120 --> 00:29:25,600 AND THE PHENOTYPE WITH THE 612 00:29:25,600 --> 00:29:28,440 GREATEST MORBIDITY WITH LOW 613 00:29:28,440 --> 00:29:29,960 ALLERGAN EXPOSURE IN EARLY LIFE 614 00:29:29,960 --> 00:29:34,000 AND HIGH FUNCTIONAL EXPOSURE AND 615 00:29:34,000 --> 00:29:36,680 YOU WILL SEE IN THE NEXT COUPLE 616 00:29:36,680 --> 00:29:37,360 PRESENTATIONS AND BASED ON THE 617 00:29:37,360 --> 00:29:42,360 OUTCOMES AND BIOSPECIMENS THAT 618 00:29:42,360 --> 00:29:43,320 WERE GATHERED THROUGHOUT THE 619 00:29:43,320 --> 00:29:45,120 YEARS AND IMPORTANTLY, WE CAN 620 00:29:45,120 --> 00:29:46,680 LEARN A LOT FROM URECA BUT THESE 621 00:29:46,680 --> 00:29:48,160 CHILDREN HAVE SOME OF THE SAME 622 00:29:48,160 --> 00:29:51,840 CHALLENGES IN ALL FOUR OF OUR 623 00:29:51,840 --> 00:29:54,040 URECA SITES AND IT'S I WILL LUS 624 00:29:54,040 --> 00:29:55,680 TRA TIVE TO COMPARE THEM TO 625 00:29:55,680 --> 00:29:57,800 STUDIES AND CHILDREN ACROSS THE 626 00:29:57,800 --> 00:29:58,200 COUNTRY. 627 00:29:58,200 --> 00:29:59,640 THE ASTHMA RATES ARE AMONG THE 628 00:29:59,640 --> 00:30:06,560 HIGHEST IN THE U.S. AND IN ECHO 629 00:30:06,560 --> 00:30:08,000 THEY ARE THE HIGHEST. 630 00:30:08,000 --> 00:30:09,520 THERE'S ONSET OF DISEASE AND WE 631 00:30:09,520 --> 00:30:12,240 NEED TO UNDERSTAND WHAT THOSE 632 00:30:12,240 --> 00:30:14,440 FACTORS ARE CLEARLY LOW 633 00:30:14,440 --> 00:30:16,200 SOCIOECONOMIC STATUS IS A STRONG 634 00:30:16,200 --> 00:30:17,320 CONTRIBUTING FACTOR BUT IT 635 00:30:17,320 --> 00:30:20,400 DOESN'T ACCOUNT FOR ALL OF THE 636 00:30:20,400 --> 00:30:21,560 INCREASED RISK IN AFRICAN 637 00:30:21,560 --> 00:30:22,320 AMERICAN CHILDREN RAISING 638 00:30:22,320 --> 00:30:23,800 QUESTIONS AS TO WHAT DOES AND 639 00:30:23,800 --> 00:30:26,640 WHAT MIGHT THOSE OTHER FACTORS 640 00:30:26,640 --> 00:30:28,160 BE AND LISTED THROW 641 00:30:28,160 --> 00:30:30,600 POSSIBILITIES HERE AND WE HAVE 642 00:30:30,600 --> 00:30:32,200 THIS PERSISTENT SIGNAL FOR 643 00:30:32,200 --> 00:30:36,000 MATERNAL STRESS AND DEPRESSION 644 00:30:36,000 --> 00:30:38,320 AND THIS IS BEFORE THE MASS HAS 645 00:30:38,320 --> 00:30:39,640 APPEARED AND THERE CAN BE 646 00:30:39,640 --> 00:30:43,080 ADDITIONAL STRUCTURAL EQUITIES 647 00:30:43,080 --> 00:30:45,480 THAT HAVEN'T BEEN EVALUATED YET 648 00:30:45,480 --> 00:30:49,680 AND THEN GENE BY ENVIRONMENT 649 00:30:49,680 --> 00:30:52,040 INTERACTIONS SO WITH THAT I'D 650 00:30:52,040 --> 00:30:53,480 LIKE TO ACKNOWLEDGE GREAT 651 00:30:53,480 --> 00:30:56,760 COLLEAGUES AND INSTITUTIONS AND 652 00:30:56,760 --> 00:31:03,920 IT WAS STARTED IN ICA AND THE 653 00:31:03,920 --> 00:31:04,960 INVESTIGATORS HERE ARE LIST 654 00:31:04,960 --> 00:31:08,280 INSIDE BOLD TYPE AND AT BOSTON 655 00:31:08,280 --> 00:31:12,680 UNIVERSITY COLOMBIA AND JOHN 656 00:31:12,680 --> 00:31:19,520 HOPKINS WITH THERE'S BEEN A TALK 657 00:31:19,520 --> 00:31:25,160 SOON AND CERTAINLY WE ARE 658 00:31:25,160 --> 00:31:26,840 THANKFUL FOR SUPPORT OF THE NIH 659 00:31:26,840 --> 00:31:29,320 AND IT'S BUILT A TERRIFIC AND 660 00:31:29,320 --> 00:31:30,920 COMPREHENSIVE PICTURE OF ASTHMA 661 00:31:30,920 --> 00:31:36,760 IN URBAN CENTERS THANK YOU VERY 662 00:31:36,760 --> 00:31:47,160 MUCH FOR YOUR ATTENTION. 663 00:31:50,520 --> 00:31:51,880 PATRICE DO YOU WANT QUESTIONS 664 00:31:51,880 --> 00:31:54,480 NOW OR HOLD THEM? 665 00:31:54,480 --> 00:31:56,200 WE CAN DO IT EITHER WAY. 666 00:31:56,200 --> 00:31:57,520 THEY'RE REALLY DISTINCT IN TERMS 667 00:31:57,520 --> 00:32:02,960 OF THE FOCUS ON CLINICAL VERSUS 668 00:32:02,960 --> 00:32:05,880 TRANCE TRIP OMICS AND IF ANYONE 669 00:32:05,880 --> 00:32:07,120 HAS QUESTIONS WE WOULD BE HAPPY 670 00:32:07,120 --> 00:32:09,880 TO TAKE THEM AND WE CAN ALWAYS 671 00:32:09,880 --> 00:32:11,040 HAVE ADDITIONAL QUESTIONS AFTER 672 00:32:11,040 --> 00:32:19,840 ALL THREE TALKS IF WE HAVE TIME. 673 00:32:19,840 --> 00:32:23,880 THAT WAS A WONDERFUL 674 00:32:23,880 --> 00:32:27,040 PRESENTATION AND VERY 675 00:32:27,040 --> 00:32:28,120 PROVOCATIVE YOU SEE SURPRISING 676 00:32:28,120 --> 00:32:31,120 IN WORSE ASSOCIATION BETWEEN 677 00:32:31,120 --> 00:32:32,800 EXPOSURE AND WHEEZE AND ATOPY SO 678 00:32:32,800 --> 00:32:36,320 I JUST WANTED TO HOPE THAT WE 679 00:32:36,320 --> 00:32:38,760 LEARN MORE IN THE NEXT TWO WEEKS 680 00:32:38,760 --> 00:32:42,800 BUT OVER ALL WHAT IS YOUR SENSE 681 00:32:42,800 --> 00:32:43,840 OF WE ARE VERY INTERESTING IN 682 00:32:43,840 --> 00:32:48,360 THIS ASPECT OF HOW IT MIME 683 00:32:48,360 --> 00:32:50,440 IMPACT NOT ONLY OF COURSE ALL 684 00:32:50,440 --> 00:32:53,760 KINDS OF BUT IMMUNE CELLS FOR 685 00:32:53,760 --> 00:32:58,280 SURE AND WE HAVE VERY NEW MODEL 686 00:32:58,280 --> 00:33:02,080 THAT'S WE HAVE ESTABLISHED WE'VE 687 00:33:02,080 --> 00:33:04,200 SEEN IMPACTING ON CELL DEATHS SO 688 00:33:04,200 --> 00:33:10,040 ANY THOUGHTS THAT YOU HAVE 689 00:33:10,040 --> 00:33:12,520 THERE? 690 00:33:12,520 --> 00:33:14,800 WE THOUGHT IT WAS A SNELL DUE 691 00:33:14,800 --> 00:33:16,400 THE MICROBIOME THE MOUSE BRINGS 692 00:33:16,400 --> 00:33:18,400 INTO THE HOME OR THE COCKROACH 693 00:33:18,400 --> 00:33:25,280 AND IT TURNED OUT NOT TO BE THE 694 00:33:25,280 --> 00:33:26,480 CASE. 695 00:33:26,480 --> 00:33:28,840 SO, YOU KNOW, HOW COULD INCREASE 696 00:33:28,840 --> 00:33:30,400 ALLERGAN EXPOSURE HAVE 697 00:33:30,400 --> 00:33:32,320 BENEFICIAL EFFECTS, WELL, YOU 698 00:33:32,320 --> 00:33:34,440 KNOW, I STARTED MY WORK WITH 699 00:33:34,440 --> 00:33:37,360 BIRTH COHORTS IN THE COST BIRTH 700 00:33:37,360 --> 00:33:40,720 COHORT AN THERE THE STRONGEST 701 00:33:40,720 --> 00:33:42,800 FACTOR IN TERMS OF EXPOSURE WAS 702 00:33:42,800 --> 00:33:44,040 EXPOSURE TO DOGS. 703 00:33:44,040 --> 00:33:46,240 SO SOME COMMONALITY THERE AND 704 00:33:46,240 --> 00:33:49,680 THEN, STUDIES ON FARMING 705 00:33:49,680 --> 00:33:53,120 ENVIRONMENTS HAVE SHOWN THAT 706 00:33:53,120 --> 00:33:54,960 EXPOSURE TO THE CENTRAL WES CON 707 00:33:54,960 --> 00:33:56,880 SIN COHORT THE MORE ANIMALS THAT 708 00:33:56,880 --> 00:33:58,680 MOTHERS EXPOS TO DURING THE 709 00:33:58,680 --> 00:34:02,040 PRE-NATAL PERIOD AND EARLY POST 710 00:34:02,040 --> 00:34:03,160 NATAL PERIOD THE BETTER THE KIDS 711 00:34:03,160 --> 00:34:03,520 DO. 712 00:34:03,520 --> 00:34:04,680 SOME OF THIS IS NO DOUBT GOING 713 00:34:04,680 --> 00:34:07,000 TO BE DUE TO THE MICROBIOME BUT 714 00:34:07,000 --> 00:34:08,920 THERE MAY BE EFFECTS OF JUST 715 00:34:08,920 --> 00:34:11,160 BROAD ANTIGEN EXPOSURE EARLY 716 00:34:11,160 --> 00:34:12,880 LIFE AND WE'VE LEARNED FROM THE 717 00:34:12,880 --> 00:34:14,240 LEAP STUDY JUST HOW POWERFUL 718 00:34:14,240 --> 00:34:16,280 THAT IT CAN BE ORALLY AND 719 00:34:16,280 --> 00:34:17,600 PERHAPS WE'RE SEEING THE SAME 720 00:34:17,600 --> 00:34:20,600 SORT OF THING IN THE RESPIRATORY 721 00:34:20,600 --> 00:34:22,840 TRACT AND THAT ANTIGEN EXPOSURE 722 00:34:22,840 --> 00:34:26,600 MAY BE SOMETHING THAT HELPS WITH 723 00:34:26,600 --> 00:34:28,280 MATURATION OF DENDRITIC CELLS OR 724 00:34:28,280 --> 00:34:29,560 TRACKING THEM INTO THE AIRWAY. 725 00:34:29,560 --> 00:34:31,920 >> YES, SO, I WILL MENTION TO 726 00:34:31,920 --> 00:34:33,920 YOU, WE HAVE PUBLISHED ONE PAPER 727 00:34:33,920 --> 00:34:35,880 BUT WE HAVE NOT YET PUBLISHED 728 00:34:35,880 --> 00:34:39,320 THE NEXT ONE WHICH IS THE MORE 729 00:34:39,320 --> 00:34:40,680 EXCITING STUDY WE ARE DOING. 730 00:34:40,680 --> 00:34:42,240 MAYBE BETWEEN THE MICE THIS IS 731 00:34:42,240 --> 00:34:43,880 AN OPPORTUNITY BECAUSE IT'S A 732 00:34:43,880 --> 00:34:45,760 STRIKING GENE ASSOCIATED WITH 733 00:34:45,760 --> 00:34:48,000 CELL MIGRATION AND BOTH, AND 734 00:34:48,000 --> 00:34:51,040 THIS WAS AN OLD PAPER OF A 735 00:34:51,040 --> 00:34:53,320 PUBLISHED BY ALAN AND NEVER 736 00:34:53,320 --> 00:34:58,800 PICKED UP OF THE IT WAS MA 737 00:34:58,800 --> 00:34:59,840 MACROPHAGES AND I WAS HOPING 738 00:34:59,840 --> 00:35:03,000 SOMEONE WOULD BE DOING THIS TYPE 739 00:35:03,000 --> 00:35:04,440 OF AND IT WOULD BE NICE TO 740 00:35:04,440 --> 00:35:05,960 DISCUSS IS THIS FURTHER AND GET 741 00:35:05,960 --> 00:35:10,680 SAMPLES FROM YOU AND YOUR 742 00:35:10,680 --> 00:35:11,880 COLLEAGUES TO SEE WEATHER WE 743 00:35:11,880 --> 00:35:12,640 COULD DO SOMETHING TOGETHER. 744 00:35:12,640 --> 00:35:17,600 >> THANK YOU SO MUCH. 745 00:35:17,600 --> 00:35:19,080 >> MATT, DO YOU WANT TO ASK M. 746 00:35:19,080 --> 00:35:22,760 YOU HAVE YOUR HAND UP? 747 00:35:22,760 --> 00:35:26,080 THIS IS A GREAT PRESENTATION 748 00:35:26,080 --> 00:35:28,320 SKID A QUESTION MAYBE A LITTLE 749 00:35:28,320 --> 00:35:30,040 SERVE SELFING BUT I LOOKED AT 750 00:35:30,040 --> 00:35:36,200 THE PIC PICTURES AND NO FAMILY 751 00:35:36,200 --> 00:35:37,680 HISTORY VERSUS FAMILY HISTORY OF 752 00:35:37,680 --> 00:35:39,400 ASTHMA AND IN THE FAMILY HISTORY 753 00:35:39,400 --> 00:35:42,040 OF COURSE MUCH HIGHER BUT 754 00:35:42,040 --> 00:35:44,000 DECREASING WHERE THE LACK OF 755 00:35:44,000 --> 00:35:44,920 FAMILY HISTORY IT'S PARTICULAR 756 00:35:44,920 --> 00:35:46,920 THE GIRLS CONTINUALLY INCREASING 757 00:35:46,920 --> 00:35:50,200 AND JUST SORT OF SPECULATING 758 00:35:50,200 --> 00:35:51,640 ABOUT WHAT IS GOING ON THERE AND 759 00:35:51,640 --> 00:35:53,840 WHAT YOU THINK THE DIFFERENCE IS 760 00:35:53,840 --> 00:35:56,040 IN TERMS OF PHENOTYPES AND 761 00:35:56,040 --> 00:35:56,960 MECHANISMS AND I DON'T KNOW IF 762 00:35:56,960 --> 00:36:01,240 IT WAS DISCUSSED IN THE PAPER OR 763 00:36:01,240 --> 00:36:06,040 YOU'VE DONE IT THROUGH ECHO. 764 00:36:06,040 --> 00:36:08,000 IT'S HARD BECAUSE WITH 765 00:36:08,000 --> 00:36:09,040 PHENOTYPES THEY'RE BASED ON WHEN 766 00:36:09,040 --> 00:36:10,440 THEY START AND SO FOURTH SO THAT 767 00:36:10,440 --> 00:36:19,080 MAKES IT A LITTLE THEY ARE 768 00:36:19,080 --> 00:36:19,920 STARTING PEARL LATE AND THERE'S 769 00:36:19,920 --> 00:36:23,480 SPECIFICS POLLS OF THAT IN THE 770 00:36:23,480 --> 00:36:27,440 LITERATURE AND ONE OF THE NEXT 771 00:36:27,440 --> 00:36:28,760 STUDIES WE'LL DO IN ECHO AND 772 00:36:28,760 --> 00:36:30,160 CREW IS TO LOOK AT INFLUENCE OF 773 00:36:30,160 --> 00:36:39,400 AIR POLLUTION AND THEY'RE BORN 774 00:36:39,400 --> 00:36:45,920 IN THEY HAVE SENSITIVE LUNGS 775 00:36:45,920 --> 00:36:49,480 WITH AND FERNANDO MARTINEZ 776 00:36:49,480 --> 00:36:51,280 DESCRIBED THE PHENOTYPE OF 777 00:36:51,280 --> 00:36:52,520 ASTHMA THAT BEGINS IN TEENAGE 778 00:36:52,520 --> 00:36:54,240 GIRLS IN THEY'RE OVERWEIGHT, 779 00:36:54,240 --> 00:36:57,080 GOING INTO PUBERTY YOU GET ONSET 780 00:36:57,080 --> 00:36:59,480 AND THERE'S A FORM OF ASTHMA 781 00:36:59,480 --> 00:37:02,840 THAT IS HORMONALLY DEVIATED THAT 782 00:37:02,840 --> 00:37:05,240 STARTS AT 10, 11, 12 YEARS OF 783 00:37:05,240 --> 00:37:05,400 AGE. 784 00:37:05,400 --> 00:37:06,200 WE'RE JUST FINDING DIFFERENT 785 00:37:06,200 --> 00:37:16,560 FORMS OF ASTHMA AND 786 00:39:35,200 --> 00:39:36,080 >> THANK YOU, CAN YOU SEE MY 787 00:39:36,080 --> 00:39:36,320 SLIDES? 788 00:39:36,320 --> 00:39:36,680 >> YES. 789 00:39:36,680 --> 00:39:40,880 >> AND YOU SEE THE RIGHT VIEW? 790 00:39:40,880 --> 00:39:42,520 >> OK. 791 00:39:42,520 --> 00:39:46,800 LET ME JUST GIVE MY LASER 792 00:39:46,800 --> 00:39:49,520 POINTER AND I'M GOING TO THANK 793 00:39:49,520 --> 00:39:51,360 THE PA TREES AND OTHERS FOR IN 794 00:39:51,360 --> 00:39:56,720 INVITING US TO GIVE THIS 795 00:39:56,720 --> 00:39:57,040 PRESENTATION. 796 00:39:57,040 --> 00:39:58,280 AND TO PREVIOUS SPEAKERS TO 797 00:39:58,280 --> 00:39:59,440 GIVING AN EXCELLENT BACKGROUND 798 00:39:59,440 --> 00:40:00,880 TO WHAT I'M ABOUT TO TALK TO YOU 799 00:40:00,880 --> 00:40:04,520 OVER THE NEXT 20 MINUTES OR SO. 800 00:40:04,520 --> 00:40:06,640 SO, MY LAB HAS BEEN REALLY 801 00:40:06,640 --> 00:40:08,280 FOCUSED OVER THE PAST MANY YEARS 802 00:40:08,280 --> 00:40:10,600 AND I'M TRYING TO PARSE OUT THE 803 00:40:10,600 --> 00:40:13,280 EFFECTS OF GENES AND ENVIRONMENT 804 00:40:13,280 --> 00:40:16,480 AND AS MA AND ALLERGY AS A 805 00:40:16,480 --> 00:40:24,560 DISEASE AND ALSO AS INDIVIDUALES 806 00:40:24,560 --> 00:40:26,240 AND THESE EFFECTS ARE FROM BOTH 807 00:40:26,240 --> 00:40:32,440 ENDS OR REAL REAL MEDIATE BY THE 808 00:40:32,440 --> 00:40:33,600 TRANSPORTATION DESCRIPTIONAL 809 00:40:33,600 --> 00:40:34,000 LANDSCAPES. 810 00:40:34,000 --> 00:40:35,920 I'M GOING TO TALK TO YOU ABOUT 811 00:40:35,920 --> 00:40:39,000 AGAIN HE HAD TICKS AND EPI 812 00:40:39,000 --> 00:40:40,400 GENETICS AND THE TRANSCRIPTIONAL 813 00:40:40,400 --> 00:40:42,440 SINGLES IN THE SAME GROUPS OF 814 00:40:42,440 --> 00:40:49,080 CHILDREN AND TELL TWO DIFFERENT 815 00:40:49,080 --> 00:40:59,240 STORIES I 816 00:41:02,040 --> 00:41:08,960 NEED TO STOP SHARING FOR A 817 00:41:08,960 --> 00:41:14,760 MINUTE. 818 00:41:14,760 --> 00:41:19,680 CAN YOU SEE THAT? 819 00:41:19,680 --> 00:41:22,040 SO I'M GOING TO START OFF WITH A 820 00:41:22,040 --> 00:41:23,120 SERIES OF STUDIES THAT WE'VE 821 00:41:23,120 --> 00:41:27,240 DONE THAT STARTED WITH A GWAS WE 822 00:41:27,240 --> 00:41:28,960 PERFORMED A FEW YEARS AGO IN 823 00:41:28,960 --> 00:41:33,560 OVER 9,000 CASES AND 318,000 824 00:41:33,560 --> 00:41:34,640 CONTROLS WHO WERE PARTICIPANTS 825 00:41:34,640 --> 00:41:37,000 SO THOSE ARE WHITE, BRITISH 826 00:41:37,000 --> 00:41:40,240 INDIVIDUALS AND WE CONDUCTED 827 00:41:40,240 --> 00:41:42,400 SEPARATE GWAS AND CHILDHOOD 828 00:41:42,400 --> 00:41:45,640 ASTHMA AND I'M SHOWING HERE THE 829 00:41:45,640 --> 00:41:47,720 PLOT FOR CHILD ONSET ASTHMA 830 00:41:47,720 --> 00:41:49,440 WHERE THE VALUES ON THE BUY 831 00:41:49,440 --> 00:41:51,080 ACTION I GUESS AND THE LOCATION 832 00:41:51,080 --> 00:41:52,320 OF EACH INDIVIDUAL VARIANT WHICH 833 00:41:52,320 --> 00:41:56,200 IS A DOT IS SHOWN ON THE X AXIS 834 00:41:56,200 --> 00:42:02,760 AND THERE'S LOTS OF LOW SIDE 835 00:42:02,760 --> 00:42:06,440 ASSOCIATED WITH CHILDHOOD ASTHMA 836 00:42:06,440 --> 00:42:11,800 AND THIS IS 17 Q1 2LOCUS 837 00:42:11,800 --> 00:42:13,480 REPLICATED CHILDHOOD ONSET 838 00:42:13,480 --> 00:42:14,560 ASTHMA LOCUS. 839 00:42:14,560 --> 00:42:20,040 AND THIS PEAK OF SIGNAL OF 840 00:42:20,040 --> 00:42:22,320 SIGNIFICANT SNIPS IS REFLECTING 841 00:42:22,320 --> 00:42:25,200 THE STRUCTURE OF THIS REGION 842 00:42:25,200 --> 00:42:27,640 SHOWN HERE ON TWO LOCUS PLOTS SO 843 00:42:27,640 --> 00:42:32,080 NOW WE'RE LOOKING AT AT THAT 844 00:42:32,080 --> 00:42:33,840 LOCUS SPECIFICALLY AND WE'VE 845 00:42:33,840 --> 00:42:39,560 LOOK AT CHILDHOOD ONSET RESULTS 846 00:42:39,560 --> 00:42:41,360 AND AND P VALUES ON THE Y AXIS 847 00:42:41,360 --> 00:42:43,040 AND THE GENES IN THIS REGION ON 848 00:42:43,040 --> 00:42:46,000 THE X AXIS AND THE FIRST REALLY 849 00:42:46,000 --> 00:42:47,200 STRIKING FINDING IS IS THAT 850 00:42:47,200 --> 00:42:52,240 THERE IS ABSOLUTELY NO SIGNAL AT 851 00:42:52,240 --> 00:42:54,280 THIS LOCUS AND WE USED A STRICT 852 00:42:54,280 --> 00:42:55,920 CRITERIA FOR ADULT ONSET ASTHMA 853 00:42:55,920 --> 00:42:57,080 BECAUSE WE WERE TRYING TO AVOID 854 00:42:57,080 --> 00:43:02,040 ANYTHING IN THAT PERIOD OF 855 00:43:02,040 --> 00:43:03,760 PUBERTY SO WE HAD 26 AND 75 856 00:43:03,760 --> 00:43:05,480 YEARS OF AGE AND YOU CAN SEE 857 00:43:05,480 --> 00:43:07,040 THAT THERE'S JUST NOTHING HERE 858 00:43:07,040 --> 00:43:11,120 AND IN THE CHILDHOOD ONSET LOCUS 859 00:43:11,120 --> 00:43:12,920 WE SEE HIGHLY SIGNIFICANCE 860 00:43:12,920 --> 00:43:14,920 ASSOCIATIONS BUT A VERY BROAD 861 00:43:14,920 --> 00:43:18,400 REGION OF ASSOCIATION WHICH 862 00:43:18,400 --> 00:43:21,880 SPANS 150 KILL' BASIS WHICH IS 863 00:43:21,880 --> 00:43:24,240 LARGE EVEN IN EUROPEAN 864 00:43:24,240 --> 00:43:25,520 POPULATION AND THE COLORS OF 865 00:43:25,520 --> 00:43:27,200 THESE VARIOUS SNIPS THAT ARE 866 00:43:27,200 --> 00:43:31,120 SHOWN IN CIRCLES, THE CLOSER TO 867 00:43:31,120 --> 00:43:33,120 RED YOU ARE THE MORE HIGHLY 868 00:43:33,120 --> 00:43:33,840 CORRELATED WITH THE SNIPS ARE 869 00:43:33,840 --> 00:43:37,960 WITH EACH OTHER SO YOU CAN PRO 870 00:43:37,960 --> 00:43:39,080 DICTIONARY THE NINO TYPE OF 871 00:43:39,080 --> 00:43:41,040 ANOTHER SNIP AND WE REFERRED TO 872 00:43:41,040 --> 00:43:48,160 THIS AS LINKAGE IN EUROPEANS 873 00:43:48,160 --> 00:43:49,800 IT'S DIFFICULT TO SAY WHICH OF 874 00:43:49,800 --> 00:43:54,440 THESE MANY VARIANTS IS ACTUALLYL 875 00:43:54,440 --> 00:43:56,040 CAUSAL AND WHICH ARE TAGGING 876 00:43:56,040 --> 00:43:58,040 ALONG BECAUSE THAT WITH THE 877 00:43:58,040 --> 00:43:59,040 CAUSAL VARIANTS. 878 00:43:59,040 --> 00:44:01,360 ALL OF THE SNIPS BECAUSE OF THIS 879 00:44:01,360 --> 00:44:03,400 HIGH LT ARE ASSOCIATE WITHED 880 00:44:03,400 --> 00:44:05,280 EXPRESSION OF TWO GENES, GSD AND 881 00:44:05,280 --> 00:44:08,080 B AND ORMD F-3 AND THESE ARE THE 882 00:44:08,080 --> 00:44:10,840 TWO PRIMARY CANDIDATE GENES OF 883 00:44:10,840 --> 00:44:12,560 THIS LOCUS BUT IT'S VERY 884 00:44:12,560 --> 00:44:14,000 DIFFICULT TO FIGURE OUT WHICH 885 00:44:14,000 --> 00:44:15,600 GENE IS CAUSAL AND WHICH 886 00:44:15,600 --> 00:44:21,200 VARIANTS ARE EFFECTIVE IN WHICH 887 00:44:21,200 --> 00:44:21,400 GENE. 888 00:44:21,400 --> 00:44:24,280 SO THIS IS SHOWING A LINKAGE 889 00:44:24,280 --> 00:44:26,720 PLOT IN EUROPEAN ACCESS TREE 890 00:44:26,720 --> 00:44:28,400 INDIVIDUALS IN THE STUDY THAT WE 891 00:44:28,400 --> 00:44:30,640 DID WHERE WE SELECTED NINE SNIPS 892 00:44:30,640 --> 00:44:33,720 ACROSS THIS BROAD REGION THAT 893 00:44:33,720 --> 00:44:39,640 MORE OR LESS CAPTURED THE LD 894 00:44:39,640 --> 00:44:47,880 PATTERNS AND CONSORTIUM THAT FOR 895 00:44:47,880 --> 00:44:56,000 THE THIS HIGH CORRELATION 896 00:44:56,000 --> 00:44:57,800 BETWEEN THE VARIANTS AND 897 00:44:57,800 --> 00:44:59,640 CORRESPONDING TO THE FIVE SNIPS 898 00:44:59,640 --> 00:45:01,840 THAT ARE WHAT WE CALL THE CORE 899 00:45:01,840 --> 00:45:07,160 REGION OF THE LOCUS IN THIS 900 00:45:07,160 --> 00:45:08,360 ORANGISH RED ON THE FLANKING 901 00:45:08,360 --> 00:45:09,520 REGION BLUE AND GREN ON THE 902 00:45:09,520 --> 00:45:13,360 OTHER SIDE AND NOW CONTRAST THAT 903 00:45:13,360 --> 00:45:15,920 TO WHAT WE SEE WITH AFRICAN 904 00:45:15,920 --> 00:45:16,960 AMERICANS AND IT'S OBVIOUS IN 905 00:45:16,960 --> 00:45:19,800 AFRICAN AMERICANS, OR AFRICAN 906 00:45:19,800 --> 00:45:21,240 ANCESTRY INDIVIDUALS, THERE'S 907 00:45:21,240 --> 00:45:22,960 BEEN A SIGNIFICANT BREAKDOWN OF 908 00:45:22,960 --> 00:45:27,760 THE THE LD DUE TO THE OLDER AGE 909 00:45:27,760 --> 00:45:30,120 OF THESE POPULATIONS OF THE 910 00:45:30,120 --> 00:45:30,880 COMBINATIONS BETWEEN VARIANTS SO 911 00:45:30,880 --> 00:45:35,600 IN THE AFRICAN AMERICANS, 912 00:45:35,600 --> 00:45:37,080 SEPARATE OUT THE EFFECTS OF 913 00:45:37,080 --> 00:45:39,440 VARIANTS IN THIS BLOCK OF THEIR 914 00:45:39,440 --> 00:45:41,120 SNIPS THAT ARE TOTALLY 915 00:45:41,120 --> 00:45:43,480 CORRELATED IN EUROPEAN AMERICANS 916 00:45:43,480 --> 00:45:47,720 AND SO WE GENOTYPE THESE 917 00:45:47,720 --> 00:45:50,600 VARIANTS AND THE CREW COHORTS 918 00:45:50,600 --> 00:45:54,840 AND WE META ANALYZE THOSE DATA 919 00:45:54,840 --> 00:46:03,000 WITH A LARGER SAMPLE OF AND WHEN 920 00:46:03,000 --> 00:46:04,760 WE DID THAT AND TOOK INTO 921 00:46:04,760 --> 00:46:08,480 ACCOUNT THE TWO GROUPS 922 00:46:08,480 --> 00:46:14,640 SEPARATELY, SIMILAR EFFECT SIZES 923 00:46:14,640 --> 00:46:17,720 BUT IN THE AFRICAN AMERICANS 924 00:46:17,720 --> 00:46:19,640 THERE WERE TWO ASSOCIATED WITH 925 00:46:19,640 --> 00:46:21,480 ASTHMA AND THOSE TWO ARE IN HIGH 926 00:46:21,480 --> 00:46:25,520 LD AND EVEN IN THE ASTHMA 927 00:46:25,520 --> 00:46:26,880 POPULATION AND WE CAN EXCLUDE 928 00:46:26,880 --> 00:46:28,880 ALL THE OTHER SNIPS ACROSS THIS 929 00:46:28,880 --> 00:46:30,760 REGION AND SOME HAD OPPOSITE 930 00:46:30,760 --> 00:46:33,520 ASSOCIATIONS IN THAT THE REAL 931 00:46:33,520 --> 00:46:35,280 BITS ASSOCIATED WITH ASTHMA AND 932 00:46:35,280 --> 00:46:39,680 EUROPEANS IS ALLELE WITH NON 933 00:46:39,680 --> 00:46:42,000 RISK IN THE AFRICAN AMERICANS. 934 00:46:42,000 --> 00:46:47,320 IN ADDITION, WE WANTED TO SEE IF 935 00:46:47,320 --> 00:46:49,520 WE CAN PURSE OUT AND THE TWO 936 00:46:49,520 --> 00:46:53,080 GENES AND SO WE USED SEEN 937 00:46:53,080 --> 00:46:55,080 EXPRESSION DATA PROVIDED TO US 938 00:46:55,080 --> 00:46:57,040 FROM CELLS AND BLOOD CELLS IN 939 00:46:57,040 --> 00:46:58,400 EUREKA CHILDREN TO SEE IF WE CAN 940 00:46:58,400 --> 00:47:00,640 START TO GET AT NOT ONLY THE 941 00:47:00,640 --> 00:47:10,200 CAUSAL SAMPLE THE CAUSAL GENE. 942 00:47:10,200 --> 00:47:15,360 AND AFTER WE ACCOUNTED FOR LD 943 00:47:15,360 --> 00:47:16,640 WITH ANOTHER SNIP THAT IS A 944 00:47:16,640 --> 00:47:22,520 STRONG ENHANCER FOR BOTH GENES 945 00:47:22,520 --> 00:47:24,320 AND HOWEVER WE SAW A VERY 946 00:47:24,320 --> 00:47:27,880 UNEXPECTED RESULTS WHEN WE 947 00:47:27,880 --> 00:47:30,960 LOOKED AT UPPER AIRWAY 948 00:47:30,960 --> 00:47:32,120 EPITHELIAL CELLS BECAUSE WE SAW 949 00:47:32,120 --> 00:47:35,680 A VERY SIGNIFICANT ASSOCIATION 950 00:47:35,680 --> 00:47:39,360 BETWEEN GSDMB AND THE LEAD SNIPS 951 00:47:39,360 --> 00:47:42,600 AND NOT SO MUCH WITH THE SECOND 952 00:47:42,600 --> 00:47:46,800 ONE AND NEITHER ASSOCIATED WITH 953 00:47:46,800 --> 00:47:49,880 THE CELLS SO THIS DATA REALLY 954 00:47:49,880 --> 00:47:54,720 SUPPORTED GSDMB AS THE CAUSAL 955 00:47:54,720 --> 00:47:57,480 GENE WITH ONSET ASTHMA AND THIS 956 00:47:57,480 --> 00:47:59,600 SNIP OR ONE THAT IS LD WITH IT 957 00:47:59,600 --> 00:48:01,920 BECAUSE WE DIDN'T TYPE EVERY 958 00:48:01,920 --> 00:48:12,440 SNIP OF THE REGION WAS IN ONE 959 00:48:22,720 --> 00:48:23,840 STUDY SHOWED THAT ALL THE 960 00:48:23,840 --> 00:48:25,880 FUNCTIONAL PROPERTY OF THE 961 00:48:25,880 --> 00:48:29,480 PROTEIN AND THE GASTRO AND GREAT 962 00:48:29,480 --> 00:48:32,080 CANDIDATE GENES FOR ASTHMA AND 963 00:48:32,080 --> 00:48:38,480 THEY IMMEDIATE OPTOSIS SO WE 964 00:48:38,480 --> 00:48:40,760 HAVE ON GOING STUDIES NOW AND 965 00:48:40,760 --> 00:48:42,480 OTHERS IN CREW CONSORTIUM TO 966 00:48:42,480 --> 00:48:47,400 REALLY TRY TO UNDERSTAND HOW 967 00:48:47,400 --> 00:48:52,600 THESE GAS TOE AND I WILL ALSO 968 00:48:52,600 --> 00:48:54,200 MENTION AFTER WE PUBLISHED THIS, 969 00:48:54,200 --> 00:48:59,320 TWO OTHER STUDIES ALSO CONCLUDED 970 00:48:59,320 --> 00:49:07,680 FROM THE WORK THAT IT'S NOW WE 971 00:49:07,680 --> 00:49:10,480 WERE VERY INTRIGUED BY THE 972 00:49:10,480 --> 00:49:12,160 UNUSUAL LD PATTERNS OR THE BIG 973 00:49:12,160 --> 00:49:14,120 DIFFERENCE IN LD PATTERNS WHICH 974 00:49:14,120 --> 00:49:16,040 IN THE AFRICAN AMERICANS AND THE 975 00:49:16,040 --> 00:49:17,560 EUROPEAN AMERICANS AND WE 976 00:49:17,560 --> 00:49:21,920 WONDERED WHETHER THERE WERE AN 977 00:49:21,920 --> 00:49:29,040 ACTUAL AND CHARLES WASHINGTON 978 00:49:29,040 --> 00:49:31,400 TOOK ON THIS STUDY ON THE FIVE 979 00:49:31,400 --> 00:49:32,880 SNIPS THAT WERE IN THE CORE 980 00:49:32,880 --> 00:49:34,560 REGION AND EXAMINE THE EFFECTS 981 00:49:34,560 --> 00:49:37,400 OBJECT ASTHMA LIST IN THE 982 00:49:37,400 --> 00:49:38,440 CONSORTIUM AND WHAT I'M SHOWING 983 00:49:38,440 --> 00:49:40,280 YOU HERE, THESE ARE THE FIVE 984 00:49:40,280 --> 00:49:43,240 SNIPS IN THE CORE REGION THAT 985 00:49:43,240 --> 00:49:45,440 INDICATES THE SNIPPET THAT WE'VE 986 00:49:45,440 --> 00:49:52,800 REPORTED IS THE LIKELY CAUSAL 987 00:49:52,800 --> 00:49:56,480 SNIPPING THESE ARE THE FREQUENCY 988 00:49:56,480 --> 00:49:57,600 IN EUROPEAN AMERICANS AND 989 00:49:57,600 --> 00:50:02,400 AFRICAN AMERICANS AND THESE TWO 990 00:50:02,400 --> 00:50:08,360 TYPES ACCOUNT FOR 90% OF ALL 991 00:50:08,360 --> 00:50:10,440 ACROSS THIS REGION WERE IN 992 00:50:10,440 --> 00:50:11,800 AFRICAN AMERICANS IT ONLY 993 00:50:11,800 --> 00:50:17,000 ACCOUNTS FOR 57% AND SO THIS WAS 994 00:50:17,000 --> 00:50:20,480 IMMEDIATELY QUITE INTERESTING TO 995 00:50:20,480 --> 00:50:25,320 US AND WE DID A TEST OF 996 00:50:25,320 --> 00:50:26,960 ASSOCIATION OF THE PAP LOW TYPE 997 00:50:26,960 --> 00:50:34,320 USING THE NON RISK IN YELLOW. 998 00:50:34,320 --> 00:50:36,000 HAPPEN LOW TYPE AND WE'RE 999 00:50:36,000 --> 00:50:46,640 CALLING THIS THE RISK AND OUR PS 1000 00:50:47,000 --> 00:50:48,200 STUDY IN CREW. 1001 00:50:48,200 --> 00:50:49,560 FOR THE AFRICAN AMERICANS THERE 1002 00:50:49,560 --> 00:50:51,280 WAS REALLY NOT MUCH EVIDENCE IN 1003 00:50:51,280 --> 00:50:53,600 THE ASSOCIATION WITH ASTHMA WITH 1004 00:50:53,600 --> 00:50:56,720 THIS PARTICULAR HAPLOTYPE. 1005 00:50:56,720 --> 00:50:57,760 THE ODDS RATIO WAS GREATER THAN 1006 00:50:57,760 --> 00:50:59,920 ONE BUT NOTHING ELSE WAS 1007 00:50:59,920 --> 00:51:01,360 CONVINCING WITH ALL THE DATA YOU 1008 00:51:01,360 --> 00:51:02,640 HAVE. 1009 00:51:02,640 --> 00:51:03,800 WE LOOKED AT THE OTHER 1010 00:51:03,800 --> 00:51:04,600 HAPLOTYPES AND WHAT WE 1011 00:51:04,600 --> 00:51:06,040 DISCOVERED IN THE SAMPLE WAS 1012 00:51:06,040 --> 00:51:08,760 THERE WERE TWO FAIRLY COMMON 1013 00:51:08,760 --> 00:51:09,400 HAPLOTYPES IN AFRICAN AMERICANS 1014 00:51:09,400 --> 00:51:11,800 THAT ARE ABSENT IN EUROPEAN 1015 00:51:11,800 --> 00:51:15,760 AMERICANS AND BOTH CARRY THE 1016 00:51:15,760 --> 00:51:18,000 RISK ALLELE AT THIS CAUSAL SNIP. 1017 00:51:18,000 --> 00:51:21,080 AND IN FACT, ONE OF THEM HAS 1018 00:51:21,080 --> 00:51:23,080 VERY SIGNIFICANT AND HIGH ODDS 1019 00:51:23,080 --> 00:51:25,680 RATIO FOR ASTHMA AND THE SECOND 1020 00:51:25,680 --> 00:51:30,360 ONE IS MIDWAY BETWEEN THOSE TWO 1021 00:51:30,360 --> 00:51:31,680 SUGGESTING THERE'S SOMETHING 1022 00:51:31,680 --> 00:51:33,560 ABOUT THIS HAPLOTYPE 4 THAT IS 1023 00:51:33,560 --> 00:51:35,000 CARRYING ADDITIONAL RISK FOR 1024 00:51:35,000 --> 00:51:38,360 ASTHMA IN THE AFRICAN AMERICANS. 1025 00:51:38,360 --> 00:51:40,840 SO WE THEN USED WHOLE GENOME 1026 00:51:40,840 --> 00:51:45,160 SEQUENCES THAT WE HAVE IN BOTH 1027 00:51:45,160 --> 00:51:50,000 EUREKA AND APIK AND TWO PUBLIC 1028 00:51:50,000 --> 00:51:53,080 DATASETS ON EIGHTH AND C.A.A. PA 1029 00:51:53,080 --> 00:51:54,480 TO IDENTIFY VARIANTS THAT ARE 1030 00:51:54,480 --> 00:51:55,800 RICH IN AFRICAN AMERICANS IN 1031 00:51:55,800 --> 00:51:57,520 ABSENT IN EUROPEANS. 1032 00:51:57,520 --> 00:51:59,160 AND I'M GOING TO SUMMARIZE ON 1033 00:51:59,160 --> 00:52:03,520 THE NEXT SLIDE, A VERY 1034 00:52:03,520 --> 00:52:05,360 COMPLICATED LONG STUDY BUT WE 1035 00:52:05,360 --> 00:52:10,400 IDENTIFIED A 24KB CRITICAL 1036 00:52:10,400 --> 00:52:14,600 REGION THAT WAS SHARED BY ALL 1037 00:52:14,600 --> 00:52:15,400 HAPLOTYPE 4 CHROMOSOMES BUT NOT 1038 00:52:15,400 --> 00:52:18,240 ON THE OTHER CHROMOSOMES AND 1039 00:52:18,240 --> 00:52:20,800 CLEARLY NOT ANY EUROPEAN 1040 00:52:20,800 --> 00:52:24,520 CHROMOSOMES AND THIS 24KB REGION 1041 00:52:24,520 --> 00:52:27,000 INCLUDED NINE SNIPS SHOWN IN RED 1042 00:52:27,000 --> 00:52:30,440 AND THEY ARE AFRICAN SPECIFIC 1043 00:52:30,440 --> 00:52:33,600 AND ONLY RECENTLY EVEN IN THE 1044 00:52:33,600 --> 00:52:35,120 DATABASEs BECAUSE NOW 1045 00:52:35,120 --> 00:52:38,440 EVERYBODY IS DOING GENOME 1046 00:52:38,440 --> 00:52:41,680 SEQUENCING BUT UP AT THE POINT 1047 00:52:41,680 --> 00:52:42,360 WE DISCOVERED THEY WERE THEY 1048 00:52:42,360 --> 00:52:43,320 WERE NOT PREVIOUSLY ACKNOWLEDGED 1049 00:52:43,320 --> 00:52:47,800 OR INCLUDED IN ANY. 1050 00:52:47,800 --> 00:52:51,640 THESE SNIPS WERE CANDIDATE SNIPS 1051 00:52:51,640 --> 00:52:53,280 FOR THE DRIVING OF THE 1052 00:52:53,280 --> 00:52:55,000 ASSOCIATION OF ASTHMA IN AFRICAN 1053 00:52:55,000 --> 00:52:58,760 AMERICANS AND THIS SNIP IS ONE 1054 00:52:58,760 --> 00:53:02,480 OF THE FIVE WE INCLUDED AND THIS 1055 00:53:02,480 --> 00:53:06,480 REGION EXTENDS FROM THE GSDMB 1056 00:53:06,480 --> 00:53:09,960 AND ALL THE WAY THROUGH TO 1057 00:53:09,960 --> 00:53:10,720 REGION OF. 1058 00:53:10,720 --> 00:53:12,960 THE FIRST THING WE ASKED WAS, 1059 00:53:12,960 --> 00:53:13,960 ARE THESE SNIPS AND THESE SNIPS 1060 00:53:13,960 --> 00:53:15,360 ARE ALL VERY HIGH LD BECAUSE 1061 00:53:15,360 --> 00:53:17,600 THEY OCCUR IN THE SAME 1062 00:53:17,600 --> 00:53:19,800 HAPLOTYPES BUT ARE THESE SNIPS 1063 00:53:19,800 --> 00:53:21,080 ASSOCIATED WITH THE EXPRESSION 1064 00:53:21,080 --> 00:53:25,760 OF ANY GENE IN AIRWAY EPITHELIAL 1065 00:53:25,760 --> 00:53:27,880 CELLS WITHIN OMEGA BASE FLANKING 1066 00:53:27,880 --> 00:53:30,360 REGION OF EACH GENE OF EACH 1067 00:53:30,360 --> 00:53:30,560 SNIP. 1068 00:53:30,560 --> 00:53:34,480 WE WERE PLUS OR MINUS 500KB 1069 00:53:34,480 --> 00:53:36,120 AROUND EACH SNIP AND TEST FOUR 1070 00:53:36,120 --> 00:53:36,960 ASSOCIATIONS AND THERE'S ONE 1071 00:53:36,960 --> 00:53:41,680 GENE IN THIS REGION THAT THESE 1072 00:53:41,680 --> 00:53:43,440 FIRST EXPRESS WAS ASSOCIATED 1073 00:53:43,440 --> 00:53:48,960 WITH GENOTYPE SNIPS AND THAT WAS 1074 00:53:48,960 --> 00:53:53,080 GSDA AND IT'S 50 KILL A BASIS 1075 00:53:53,080 --> 00:53:55,160 DISTAL TO THIS LAST SNIP AND YOU 1076 00:53:55,160 --> 00:53:58,240 CAN SEE IN THIS FIGURE THAT 1077 00:53:58,240 --> 00:54:01,640 CARROTTING OF THE T ALLELE, THE 1078 00:54:01,640 --> 00:54:02,720 AFRICAN-SPECIFIC ALLELE IS 1079 00:54:02,720 --> 00:54:03,800 ASSOCIATED WITH HIGHER 1080 00:54:03,800 --> 00:54:08,080 EXPRESSION OF GSDMA AT THE 1081 00:54:08,080 --> 00:54:10,240 ALLELE CELLS AND THIS OCCURS 1082 00:54:10,240 --> 00:54:13,560 ABOUT 12% FREQUENTLY IN AFRICAN 1083 00:54:13,560 --> 00:54:14,080 AMERICANS. 1084 00:54:14,080 --> 00:54:16,760 IT'S LESS THAN .01 FREQUENCY IN 1085 00:54:16,760 --> 00:54:20,520 EUROPEANS AND IN THE LARGE 1086 00:54:20,520 --> 00:54:22,040 DATABASE AND IT WASN'T PRESENT 1087 00:54:22,040 --> 00:54:26,960 ALONE SO IF THESE SNIPS ARE 1088 00:54:26,960 --> 00:54:28,720 REGULATING THE EXPRESSION, WE 1089 00:54:28,720 --> 00:54:31,440 SUGGESTED THAT THIS MUST BE MORE 1090 00:54:31,440 --> 00:54:33,440 SNIPS MUST BE RESIDING IN AN 1091 00:54:33,440 --> 00:54:35,440 ENHANCER REGION THAT IS 1092 00:54:35,440 --> 00:54:37,440 REGULATING EXPRESSION OF GSDMA 1093 00:54:37,440 --> 00:54:40,480 SO WE USE PUBLICLY AVAILABLE 1094 00:54:40,480 --> 00:54:42,360 DATA TO LOOK AT THAT AND WHEN 1095 00:54:42,360 --> 00:54:48,920 I'M SHOWING HERE NOW, ACTIVE 1096 00:54:48,920 --> 00:54:51,640 ENHANCER MARKS AND TRACKS THOSE 1097 00:54:51,640 --> 00:54:55,240 AND UNDER THIS ARE TRACKS OF 1098 00:54:55,240 --> 00:54:57,000 OPEN CALL TANT REFLECTING ACTIVE 1099 00:54:57,000 --> 00:54:59,000 GENE ACTIVITY AND YOU CAN SEE 1100 00:54:59,000 --> 00:55:04,000 THAT AT THIS END OF THE REGION, 1101 00:55:04,000 --> 00:55:05,760 THERE'S HUGE PEAKS FOR ENHANCER 1102 00:55:05,760 --> 00:55:07,440 EXPRESSION AND ENHANCER ACTIVITY 1103 00:55:07,440 --> 00:55:09,880 AND LOTS OF OPEN CHROME TIN 1104 00:55:09,880 --> 00:55:12,040 SHOWN BY THE DARKER BLACK BOXS 1105 00:55:12,040 --> 00:55:14,520 SO THIS NARROWED OUR SEARCH TO 1106 00:55:14,520 --> 00:55:16,560 THREE OF THESE NOVEL 1107 00:55:16,560 --> 00:55:17,840 AFRICAN-SPECIFIC VARIANTS THAT 1108 00:55:17,840 --> 00:55:21,360 MIGHT BE CAUSAL FOR THE 1109 00:55:21,360 --> 00:55:29,800 ASSOCIATION OF GSDMA. 1110 00:55:29,800 --> 00:55:32,760 WE USED PROMO TIVE CAPTURE HIGH 1111 00:55:32,760 --> 00:55:36,040 C DAN AND BETWEEN PROMOTERS AND 1112 00:55:36,040 --> 00:55:38,160 ENHANCERS THAT ARE FAR APART, 1113 00:55:38,160 --> 00:55:47,360 NOT IN THE SAME GENE. 1114 00:55:47,360 --> 00:55:52,840 THIS IS THE FIVE PRIME ENDS OF O 1115 00:55:52,840 --> 00:55:56,240 R&D L3 AND THE ENHANCER MARKS AT 1116 00:55:56,240 --> 00:55:59,080 THEN OF THE REGION AND WHAT WE 1117 00:55:59,080 --> 00:56:03,000 SHOW ARE THE PRO MOTOR REGION OF 1118 00:56:03,000 --> 00:56:04,600 GSDMA IS INTERACTING WITH TWO 1119 00:56:04,600 --> 00:56:06,760 DIFFERENT PIECES OF THIS REGION 1120 00:56:06,760 --> 00:56:09,640 AND BOTH OF WHICH KIND OF 1121 00:56:09,640 --> 00:56:11,960 OVERLAP THESE TWO RIGHT HERE. 1122 00:56:11,960 --> 00:56:12,640 AND THIS SNIP THAT I'M SHOWING 1123 00:56:12,640 --> 00:56:18,120 YOU HERE IS ONE OF THESE TWO 1124 00:56:18,120 --> 00:56:18,480 SNIPS. 1125 00:56:18,480 --> 00:56:20,400 WE THINK THIS STORY IS 1126 00:56:20,400 --> 00:56:21,800 COMPELLING THAT THESE NOVEL 1127 00:56:21,800 --> 00:56:24,200 AFRICAN AMERICAN VARIANTS ON 1128 00:56:24,200 --> 00:56:25,040 HAPLOTYPE 4 AND SOME OF THE 1129 00:56:25,040 --> 00:56:28,720 OTHERS BUT NOT AS COMMONLY AS 1130 00:56:28,720 --> 00:56:30,480 HAPLOTYPE 4 IS IN AN DISRUPTING 1131 00:56:30,480 --> 00:56:34,360 AN ENHANCER OR ACT RATE ISING AN 1132 00:56:34,360 --> 00:56:36,080 ENHANCER THAT INTERACTS WITH THE 1133 00:56:36,080 --> 00:56:38,600 PROMOTER OF GSDMA SO WE ASK 1134 00:56:38,600 --> 00:56:40,040 WHETHER THIS WAS ASSOCIATED WITH 1135 00:56:40,040 --> 00:56:44,440 ANY PARTICULAR PHENOTYPES IN 1136 00:56:44,440 --> 00:56:46,040 EUREKA AND TOGETHER WHAT WE SAW 1137 00:56:46,040 --> 00:56:47,920 WAS THAT THE GENE WHEEL WAS 1138 00:56:47,920 --> 00:56:50,160 ASSOCIATED WITH LOWER LUNG 1139 00:56:50,160 --> 00:56:51,440 FUNCTION, LOWER BLOOD COUNTS AND 1140 00:56:51,440 --> 00:56:57,680 LOWER IGE LEVELS IN THIS EUREKA 1141 00:56:57,680 --> 00:56:58,920 PLUS SPECIFIC OF AFRICAN 1142 00:56:58,920 --> 00:57:00,240 AMERICAN CHILDREN. 1143 00:57:00,240 --> 00:57:03,520 FINALLY, WE HAVE DATA IN AFRICAN 1144 00:57:03,520 --> 00:57:06,840 AMERICAN ADULTS BUT WE DIDN'T 1145 00:57:06,840 --> 00:57:10,400 HAVE FULL GENOME SEQUENCING SO 1146 00:57:10,400 --> 00:57:15,320 WE USED HAPLOTYPE 4 AS A SORROW 1147 00:57:15,320 --> 00:57:17,000 GET AND WE SAW A STRIKING 1148 00:57:17,000 --> 00:57:19,600 ASSOCIATION OF ASTHMA SEVERITY 1149 00:57:19,600 --> 00:57:23,080 IN ADULTS SO THESE ARE MILD, 1150 00:57:23,080 --> 00:57:24,080 MODERATE AND SEVERE AND CAN YOU 1151 00:57:24,080 --> 00:57:29,120 SEE THE FREQUENCY OF HAPLOTYPE 4 1152 00:57:29,120 --> 00:57:32,280 IS HIGHER THAN THE SEVERITY. 1153 00:57:32,280 --> 00:57:34,640 SO, THIS STUDY ADDS TO THE ON 1154 00:57:34,640 --> 00:57:37,480 GOING COMPLEXITY OF THE REGION 1155 00:57:37,480 --> 00:57:41,760 AND SHOWN THAT AFRICAN-SPECIFIC 1156 00:57:41,760 --> 00:57:45,680 CAN MONDAY FIE THE GWSA AND 1157 00:57:45,680 --> 00:57:49,600 ASTHMA SEVERITY AND BOTH GSDM 1158 00:57:49,600 --> 00:57:52,520 AND GSDMA OF THE AFRICAN 1159 00:57:52,520 --> 00:57:56,200 SPECIFIC HAPLOTYPE ARE SEVERE 1160 00:57:56,200 --> 00:57:57,240 ASTHMA AND WE HAVE A NUMBER OF 1161 00:57:57,240 --> 00:57:59,720 ON GOING STUDIES NOW TO FURTHER 1162 00:57:59,720 --> 00:58:02,800 CHARACTERIZE THE LONGITUDINAL 1163 00:58:02,800 --> 00:58:05,840 THEME EVENTS OF THESE VARIANTS. 1164 00:58:05,840 --> 00:58:07,960 SO NOW WE'LL SWITCH GEARS AND 1165 00:58:07,960 --> 00:58:09,360 TELL YOU A LITTLE BIT ABOUT A 1166 00:58:09,360 --> 00:58:11,160 STUDY THAT WE'VE JUST COMPLETED 1167 00:58:11,160 --> 00:58:15,760 ON LOOKING AT THE METH A LOAM 1168 00:58:15,760 --> 00:58:17,520 WHICH IS THE MARK THAT WE HAVE 1169 00:58:17,520 --> 00:58:20,200 STUDIED ALONG IN OUR LAB. 1170 00:58:20,200 --> 00:58:22,840 SO I THINK EVERYONE IS FAMILIAR 1171 00:58:22,840 --> 00:58:25,160 WITH THE CONCEPT THAT EPI 1172 00:58:25,160 --> 00:58:26,880 GENETICS IS THE LINK BETWEEN 1173 00:58:26,880 --> 00:58:28,600 ENVIRONMENT AND DOWNSTREAM 1174 00:58:28,600 --> 00:58:30,360 MOLECULAR RESPONSES AND THE 1175 00:58:30,360 --> 00:58:37,560 SHOWN ON THE CARTOON ON THE LEFT 1176 00:58:37,560 --> 00:58:42,120 AND IT CAN 1177 00:58:42,120 --> 00:58:43,400 RESULT IN HEALTH AND DISEASE 1178 00:58:43,400 --> 00:58:47,880 STATES DEPENDING ON WHETHER IT'S 1179 00:58:47,880 --> 00:58:53,040 POSITIVE OR NEGATIVE AND DNA IS 1180 00:58:53,040 --> 00:58:55,560 THE MOST COMMON EP GENETIC MARK 1181 00:58:55,560 --> 00:58:59,920 IN THE GENOME AND THE CPG IS 1182 00:58:59,920 --> 00:59:03,320 COMMON WITH MORE THAN 38 MILLION 1183 00:59:03,320 --> 00:59:05,040 CPGs THAT ARE POTENTIALLY 1184 00:59:05,040 --> 00:59:07,160 SUSCEPTIBLE TO THE MODIFICATION 1185 00:59:07,160 --> 00:59:10,320 AND DNA CAN CONTRIBUTE TO 1186 00:59:10,320 --> 00:59:13,760 DIRECTLY TO THE DISEASE RISK OR 1187 00:59:13,760 --> 00:59:24,280 BE INTERACTIONS AND RELATIVELY 1188 00:59:25,200 --> 00:59:28,200 LITTLE AS KNOWN ABOUT INTER 1189 00:59:28,200 --> 00:59:29,960 INDIVIDUAL AND VARIATION AND 1190 00:59:29,960 --> 00:59:32,840 IT'S REALLY PRIMARILY RELATED TO 1191 00:59:32,840 --> 00:59:43,320 THE CONTENT ON THE AND WE WERE 1192 01:00:07,040 --> 01:00:09,440 LUCKY IN THAT WE THOUGHT IT WAS 1193 01:00:09,440 --> 01:00:11,120 A IMPORTANT QUESTION TO PROVIDE 1194 01:00:11,120 --> 01:00:12,680 US WITH FUNDS TO DO THIS AND 1195 01:00:12,680 --> 01:00:16,000 WHAT WE DID WAS PERFORM A WHOLE 1196 01:00:16,000 --> 01:00:19,280 GENOME SEQUENCING STUDY AND 1197 01:00:19,280 --> 01:00:21,920 AIRWAY CELLS TO IDENTIFY 1198 01:00:21,920 --> 01:00:23,960 DIFFERENT REGIONS THROUGH OUT 1199 01:00:23,960 --> 01:00:25,480 GENOME WITHOUT ANY BIAS 1200 01:00:25,480 --> 01:00:27,840 SELECTION CRITERIA SO THERE WAS 1201 01:00:27,840 --> 01:00:30,200 AND WE PERFORMED THIS STUDY IN 1202 01:00:30,200 --> 01:00:32,000 20 EUROPEAN AMERICAN CHILDREN 1203 01:00:32,000 --> 01:00:34,360 FROM THE COAST COHORT AND 1204 01:00:34,360 --> 01:00:37,120 AFRICAN AMERICAN CHILDREN EUREKA 1205 01:00:37,120 --> 01:00:39,240 AND HALF OF THOSE CHILDREN IN 1206 01:00:39,240 --> 01:00:42,000 EACH HAD ASTHMA PLUS ALLERGIES 1207 01:00:42,000 --> 01:00:44,240 AND HALF HAD NO ASTHMA AND NO 1208 01:00:44,240 --> 01:00:47,280 ALLERGY AND WE LOST ONE SAMPLE 1209 01:00:47,280 --> 01:00:50,920 ALONG THE WAY. 1210 01:00:50,920 --> 01:00:58,160 WE IDENTIFIED CPGs AND WE 1211 01:00:58,160 --> 01:00:59,880 SELECTED THE CPGs THAT WOULD 1212 01:00:59,880 --> 01:01:01,560 BE THE MOST FUNCTIONAL AND 1213 01:01:01,560 --> 01:01:04,280 THEY'RE HIGH VALUE CPGs AND 1214 01:01:04,280 --> 01:01:07,120 WITH THESE WE TOOK ALL THE 1215 01:01:07,120 --> 01:01:10,240 CPGs AT REGIONS AND IT WAS 1216 01:01:10,240 --> 01:01:11,880 ABOUT 100,000 OF THOSE AND WE 1217 01:01:11,880 --> 01:01:15,440 TOOK ALL CPGs AT ASTHMA OR 1218 01:01:15,440 --> 01:01:18,080 EARLY GEE OR WITH DIFFERENTIAL 1219 01:01:18,080 --> 01:01:19,920 IN THE PREVIOUS ASTHMA ALLERGY 1220 01:01:19,920 --> 01:01:22,800 STUDY AND WE THEN FILTERED THOSE 1221 01:01:22,800 --> 01:01:24,720 CPGs FOR OVERLAP WITH AT LEAST 1222 01:01:24,720 --> 01:01:26,440 THREE DIFFERENT FUNCTIONAL 1223 01:01:26,440 --> 01:01:30,040 ANNOTATIONS SUCH AS PREDICTIVE 1224 01:01:30,040 --> 01:01:31,200 ENHANCERS, TRANSCRIPTION FACT 1225 01:01:31,200 --> 01:01:35,360 OWE BINDING SITES AND ET CETERA, 1226 01:01:35,360 --> 01:01:41,120 AND THEN WE EXCLUDED ANY CPG ON 1227 01:01:41,120 --> 01:01:43,720 THE RAY AND OVERLAPPED WITH 1228 01:01:43,720 --> 01:01:45,040 REGIONS THAT MADE INTERPRETATION 1229 01:01:45,040 --> 01:01:48,200 DIFFICULT AND THEN WE WORKED 1230 01:01:48,200 --> 01:01:51,960 WITH ALUM INA TO DESIGN A CUSTOM 1231 01:01:51,960 --> 01:01:53,920 ASTHMA ALLERGY AND THE IDEA IT 1232 01:01:53,920 --> 01:01:57,040 WOULD BE A 50,000CPG ARRAY THAT 1233 01:01:57,040 --> 01:02:00,520 WAS A BOOSTER TO THE EPIC ARRAY 1234 01:02:00,520 --> 01:02:03,440 AND THE CPGs AND AFTER 1235 01:02:03,440 --> 01:02:04,320 MANUFACTURE AND ALL THE OTHER 1236 01:02:04,320 --> 01:02:06,200 THINGS WE HAVE TO GO THROUGH AND 1237 01:02:06,200 --> 01:02:13,120 WE ENDED UP WITH ABOUT 1238 01:02:13,120 --> 01:02:15,640 38,000CPGs AND WE SHOULD BE 1239 01:02:15,640 --> 01:02:26,160 CLOSER TO 50K THEY THEN STUDY 1240 01:02:29,400 --> 01:02:30,640 AND THE PAPER DESCRIBING WHAT 1241 01:02:30,640 --> 01:02:32,160 I'M GOING TO TALK ABOUT HAS JUST 1242 01:02:32,160 --> 01:02:34,640 BEEN POSTED ON ARCHIVES AND 1243 01:02:34,640 --> 01:02:38,280 SUBMITTED FOR PUBLICATION AND SO 1244 01:02:38,280 --> 01:02:40,640 AS EXPECTED. 1245 01:02:40,640 --> 01:02:44,360 MOST OF THE CPGs OVERLAP WITH 1246 01:02:44,360 --> 01:02:46,600 ENHANCER MARK OR TRANSCRIPTION 1247 01:02:46,600 --> 01:02:48,240 FACTOR BIND SEWING 94% WITH THE 1248 01:02:48,240 --> 01:02:55,320 FIRST AND 90% WITH THE AT THE 1249 01:02:55,320 --> 01:03:05,840 AND SO THIS IS TELLING US VERY 1250 01:03:22,400 --> 01:03:24,120 DIFFERENT THAN WHAT GWAS TELLS 1251 01:03:24,120 --> 01:03:28,200 US IN ADDITION, THE CPGs ON 1252 01:03:28,200 --> 01:03:30,000 THE CUSTOMER ARRAY ARE ENRICH 1253 01:03:30,000 --> 01:03:33,440 FOR INTERMEDIATE CPGs AND 1254 01:03:33,440 --> 01:03:39,520 DEPLETED FOR HYPO METH OWE LATED 1255 01:03:39,520 --> 01:03:44,880 PCGs THAT'S S AND THAT'S BETA VH 1256 01:03:44,880 --> 01:03:47,960 IS THE PERCENT METHODDATION AT 1257 01:03:47,960 --> 01:03:51,880 EACH CPG SITE AND EACH NINE THIS 1258 01:03:51,880 --> 01:03:52,480 DENSITY PLOT IS AN INDIVIDUAL 1259 01:03:52,480 --> 01:04:00,320 AND THESE ARE THE SAME URECA AND 1260 01:04:00,320 --> 01:04:03,440 THERE ARE THESE HUGE PEAKS OF 1261 01:04:03,440 --> 01:04:08,600 CPGs THAT ARE HYPER METH OWE 1262 01:04:08,600 --> 01:04:10,600 LATED AND HYPO METH OWE LATED 1263 01:04:10,600 --> 01:04:21,160 REGION AND IN FACT, WHEN WHICH W 1264 01:04:26,680 --> 01:04:34,040 THIS WE WERE FIRST WORRIED THAT 1265 01:04:34,040 --> 01:04:36,120 SOMETHING WAS WRONG BUT WE 1266 01:04:36,120 --> 01:04:37,920 DEFLEET FOR THESE HIGH PER 1267 01:04:37,920 --> 01:04:48,440 METHYLATED REGIONS AND WE TOOK 1268 01:04:52,560 --> 01:04:54,720 THE CPGs ON THE EPIC AND PUT 1269 01:04:54,720 --> 01:04:56,280 THEM THROUGH THE SAME PIPELINE 1270 01:04:56,280 --> 01:04:58,280 THAT WE USED, AND IN DEED, WHEN 1271 01:04:58,280 --> 01:05:01,000 WE DO THAT, WE GET RID OF THE 1272 01:05:01,000 --> 01:05:03,400 EXTREMES AND WE ENRICH FOR INTER 1273 01:05:03,400 --> 01:05:06,240 MEDIATED METH A LATED CPGs AND 1274 01:05:06,240 --> 01:05:07,840 THEY'RE FILTERED EPIC CPGs ON 1275 01:05:07,840 --> 01:05:09,760 THE EPIC BUT THEY WERE THE ONES 1276 01:05:09,760 --> 01:05:11,080 THAT WERE THE PASS THROUGH THE 1277 01:05:11,080 --> 01:05:13,560 FILTER IF WE DIDN'T EXCLUDE THE 1278 01:05:13,560 --> 01:05:16,840 EPIC CPGs FROM OUR ARRAY. 1279 01:05:16,840 --> 01:05:27,360 OK, SO THEN, WE NEXT DID A WE 1280 01:05:38,360 --> 01:05:40,440 HAD THE PERCENT POSITIVE 1281 01:05:40,440 --> 01:05:42,640 SKIN-PRICK TEST OUT OF 14 1282 01:05:42,640 --> 01:05:44,880 AIRBORN OR ALL ALLERGENS AT AGE 1283 01:05:44,880 --> 01:05:48,120 10 AND THE EPITHELIAL CELLS WERE 1284 01:05:48,120 --> 01:05:50,240 COLLECTED AT AGE 11. 1285 01:05:50,240 --> 01:05:53,040 AND SO THIS IS THE RESULTS OF 1286 01:05:53,040 --> 01:05:58,360 THE EWAS AND LOOKING AT VOLCANO 1287 01:05:58,360 --> 01:06:01,360 PLOTS, THIS IS THE LONG 2 FOLD 1288 01:06:01,360 --> 01:06:04,560 CHANGE ON THE X AXIS AND THE 1289 01:06:04,560 --> 01:06:08,560 MINUS LONG 10P VALUE ON THE Y 1290 01:06:08,560 --> 01:06:10,160 AXIS AND CUSTOM IS ON THE BOTTOM 1291 01:06:10,160 --> 01:06:12,840 AND THESE ARE THE NUMBER OF 1292 01:06:12,840 --> 01:06:14,440 CPGs THAT WERE METH LATED OR 1293 01:06:14,440 --> 01:06:24,920 LESS METH LATED EVEN THOUGH 1294 01:06:40,440 --> 01:06:41,680 THERE ARE MORE BECAUSE THE ARRAY 1295 01:06:41,680 --> 01:06:45,360 IS SO MUCH LARGER, THERE'S AN 1296 01:06:45,360 --> 01:06:47,480 ENRICHMENT FOR DNC ON THE 1297 01:06:47,480 --> 01:06:50,160 CUSTOMER WHERE IT'S 5% WERE 1298 01:06:50,160 --> 01:06:52,360 DIFFERENTIAL COMPARED TO .2% ON 1299 01:06:52,360 --> 01:06:54,800 THE EPIC AND IN ADDITION, WE'RE 1300 01:06:54,800 --> 01:06:58,120 SHOWING IN PURPLE HERE, THE 1301 01:06:58,120 --> 01:07:00,120 CPGs ON THE FILTER EPIC AND 1302 01:07:00,120 --> 01:07:07,440 BLUE IS THE NON WHAT WE NOTED 1303 01:07:07,440 --> 01:07:12,320 WAS 16% OF THE EPIC DMCs ARE 1304 01:07:12,320 --> 01:07:14,480 FILTERED COMPARED TO 3.5% OF ALL 1305 01:07:14,480 --> 01:07:16,840 AND THE PIPELINE WE USE ENRICHED 1306 01:07:16,840 --> 01:07:19,480 FOR CPGs THAT ARE ASSOCIATED 1307 01:07:19,480 --> 01:07:21,080 WITH SENSITIZATION AND I WON'T 1308 01:07:21,080 --> 01:07:23,240 HAVE TIME TO SHOW YOU BUT WE 1309 01:07:23,240 --> 01:07:24,480 REPLICATED THESE RESULTS ON 1310 01:07:24,480 --> 01:07:26,720 CUSTOMER ARRAY AND THE INSPIRE 1311 01:07:26,720 --> 01:07:30,720 COHORT WHICH IS NUMBER CHILDREN 1312 01:07:30,720 --> 01:07:33,760 MUCH MORE WHITE AND MOVING IN 1313 01:07:33,760 --> 01:07:36,360 CENTRAL TENNESSEE AND SO THAT WE 1314 01:07:36,360 --> 01:07:41,360 KNOW NOW THAT THE ARRAY IS 1315 01:07:41,360 --> 01:07:44,800 ROBUST TO AGE RACE AND GEOGRAPHY 1316 01:07:44,800 --> 01:07:46,040 AND EVEN THOUGH THE DENSITY 1317 01:07:46,040 --> 01:07:47,600 PLOTS THAT I SHOWED IN THE 1318 01:07:47,600 --> 01:07:49,800 PREVIOUS SLIDE SHOWED BIG 1319 01:07:49,800 --> 01:07:54,440 DIFFERENCES BETWEEN THE EPIC IN 1320 01:07:54,440 --> 01:07:56,800 CUSTOM AWAY IF WE DO THE DENSITY 1321 01:07:56,800 --> 01:07:58,680 PLOTS FOR THE CPGs THEY WERE 1322 01:07:58,680 --> 01:08:02,080 NEARLY IDENTICAL SO AGAIN, THIS 1323 01:08:02,080 --> 01:08:06,120 IS REINFORCING THE IDEA THAT 1324 01:08:06,120 --> 01:08:07,120 INTERMEDIATE LEVEL METHYLATION 1325 01:08:07,120 --> 01:08:08,920 ARE THE CPGs THAT ARE REALLY 1326 01:08:08,920 --> 01:08:11,880 THE ONES THAT ARE ASSOCIATED 1327 01:08:11,880 --> 01:08:12,720 WITH PHENOTYPES. 1328 01:08:12,720 --> 01:08:14,120 WE ALSO ASKED, ARE THEY ALSO 1329 01:08:14,120 --> 01:08:15,640 MORE LIKELY TO BE ASSOCIATED 1330 01:08:15,640 --> 01:08:18,400 WITH THE EXPRESSION OF NEARBY 1331 01:08:18,400 --> 01:08:21,120 GENES AND THE ANSWER TO THAT IS 1332 01:08:21,120 --> 01:08:21,560 YES. 1333 01:08:21,560 --> 01:08:31,280 AND SO FOR BOTH ARRAYS, THE IF 1334 01:08:31,280 --> 01:08:33,800 YOU JUST LOOK AT THOSE 1335 01:08:33,800 --> 01:08:36,880 CORRELATED AND BETWEEN THE CPG 1336 01:08:36,880 --> 01:08:39,920 METHYLATION LEVELS AND THE 1337 01:08:39,920 --> 01:08:43,760 EXPRESSION OF THE GENE. 1338 01:08:43,760 --> 01:08:45,640 AND THE OTHER LAST THING THAT 1339 01:08:45,640 --> 01:08:47,560 I'LL MENTION IS THAT VERY 1340 01:08:47,560 --> 01:08:50,120 STRIKING PATTERN OF ASSOCIATION 1341 01:08:50,120 --> 01:08:53,200 DIFFER IT'S A THE CPGs ON SO 1342 01:08:53,200 --> 01:08:54,720 VERSUS A TYPICAL RESULT THAT YOU 1343 01:08:54,720 --> 01:08:57,560 SEE ON THE EPIC AND IT'S A LOW 1344 01:08:57,560 --> 01:08:59,440 SYSTEM PLOT BUT I'M PLOTTING THE 1345 01:08:59,440 --> 01:09:02,120 CPGs AND THE P VALUES FOR THE 1346 01:09:02,120 --> 01:09:04,200 DIFFERENTIAL METHYLATION LOT 1347 01:09:04,200 --> 01:09:04,760 ASSOCIATION. 1348 01:09:04,760 --> 01:09:07,280 AND HERE, THERE'S A SINGLE CPG 1349 01:09:07,280 --> 01:09:14,080 ON THE EPIC ARRAY THAT IS 1350 01:09:14,080 --> 01:09:17,560 METHYLATED IN THE CENTERING IT'S 1351 01:09:17,560 --> 01:09:20,040 A NICE CANDIDATE WITH VERY 1352 01:09:20,040 --> 01:09:21,920 LITTLE SUPPORTING EVIDENCE FROM 1353 01:09:21,920 --> 01:09:31,440 OTHER CPGs SHOWN IN BLUE AND 1354 01:09:31,440 --> 01:09:32,440 AND THEY'RE NOT SIGNIFICANT AT 1355 01:09:32,440 --> 01:09:35,240 ALL AND THE TWO DIFFERENCE MINDS 1356 01:09:35,240 --> 01:09:39,960 ARE SHOWING 5% FDR AND EPIC AND 1357 01:09:39,960 --> 01:09:46,960 THE CUSTOM AND WE DIDN'T CHERRY 1358 01:09:46,960 --> 01:09:49,400 PICK THIS RESULT OF TOP 10 MOST 1359 01:09:49,400 --> 01:09:55,360 SIGNIFICANT CPGs AND AND EIGHT 1360 01:09:55,360 --> 01:09:58,000 OF THE 10 WAS NOT FROM THE NON 1361 01:09:58,000 --> 01:10:02,480 FILTER AND THIS IS A TYPICAL 1362 01:10:02,480 --> 01:10:09,560 RESULT THAT WE THE SPIKES OF 1363 01:10:09,560 --> 01:10:15,720 ASSOCIATION AND ON THE EPIC AND 1364 01:10:15,720 --> 01:10:20,560 THE INSPIRE AND ON THE CUSTOM 1365 01:10:20,560 --> 01:10:28,920 AND EUREKA AND WE HAVE SUPPORT 1366 01:10:28,920 --> 01:10:30,320 WHERE THERE'S BOTH FILTER EPIC 1367 01:10:30,320 --> 01:10:32,400 AND NON FILTER EPIC IN THIS SAME 1368 01:10:32,400 --> 01:10:42,960 AND THIS WEEK IS IN THE EX ON WE 1369 01:10:51,160 --> 01:11:01,640 SAW SHOWN ON THE X AXIS AND AND 1370 01:11:03,440 --> 01:11:08,280 WHEN WE LOOK AT THE RELATIONSHIP 1371 01:11:08,280 --> 01:11:09,560 BETWEEN INCREASING METHYLATION 1372 01:11:09,560 --> 01:11:12,360 YOU CAN SEE THAT THE MORE 1373 01:11:12,360 --> 01:11:22,880 METHYLATED THIS LOCUS THE FEWER 1374 01:11:24,640 --> 01:11:34,720 HIGHEST EXPRESSERS OF THIS GENE. 1375 01:11:34,720 --> 01:11:37,600 THIS IS A NEGATIVE REGULATORS OF 1376 01:11:37,600 --> 01:11:39,000 SIGNALING IN PREVIOUS STUDIES 1377 01:11:39,000 --> 01:11:47,720 AND INCREASE EXPRESSION OF MRNA 1378 01:11:47,720 --> 01:11:52,200 AND CELLS AND IN THIS ONE PAPER 1379 01:11:52,200 --> 01:11:54,680 IT WAS SUGGESTED AS PROTECTION 1380 01:11:54,680 --> 01:11:56,640 ASTHMA AND THESE ARE BOTH 1381 01:11:56,640 --> 01:11:58,160 CONSISTENT WITH OUR RESULTS AND 1382 01:11:58,160 --> 01:12:05,320 WHICH FURTHER SUGGEST THAT THE 1383 01:12:05,320 --> 01:12:07,080 ASSOCIATED WITH ALLERGIC 1384 01:12:07,080 --> 01:12:08,360 SENSITIZATION AND IT'S NOTABLE 1385 01:12:08,360 --> 01:12:11,200 TO ME, THAT THIS GENE IS NOT AT 1386 01:12:11,200 --> 01:12:14,200 AN ASTHMA OR ALLERGY GWAS LOCUS 1387 01:12:14,200 --> 01:12:17,320 IS SUGGESTING THAT EPI GENETIC 1388 01:12:17,320 --> 01:12:18,480 MODIFICATION REFLECTS RESPONSE 1389 01:12:18,480 --> 01:12:21,200 TO EXPOSURES OR GENE ENVIRONMENT 1390 01:12:21,200 --> 01:12:23,320 INTERACTIONS AND IT CLEARLY 1391 01:12:23,320 --> 01:12:25,280 DOESN'T HAVE A MAIN GENETIC 1392 01:12:25,280 --> 01:12:33,800 SIGNAL THAT IS DRIVING THIS 1393 01:12:33,800 --> 01:12:41,560 PHENOTYPE SO TO WRAP 2 HAS A 1394 01:12:41,560 --> 01:12:42,920 RESOURCE FOR INTEGRATED STUDIES 1395 01:12:42,920 --> 01:12:45,160 ON THE DEVELOPMENT OF ASTHMA AND 1396 01:12:45,160 --> 01:12:47,600 LEADING TO THE DISCOVERY OF 1397 01:12:47,600 --> 01:12:48,400 CAUSAL VARIANTS AND GENES OF THE 1398 01:12:48,400 --> 01:12:53,200 MOST IMPORTANT CHILDHOOD SOME 1399 01:12:53,200 --> 01:12:55,840 SPECIFIC TO CHILDREN OF AFRICAN 1400 01:12:55,840 --> 01:12:57,920 ANCESTRY AND SIGNATURE OF HIGH 1401 01:12:57,920 --> 01:12:59,560 FALL FUNCTION CPGs AND THEIR 1402 01:12:59,560 --> 01:13:01,640 ROLE IN MEDIATING THE EFFECTS OF 1403 01:13:01,640 --> 01:13:04,760 ENVIRONMENTAL EXPOSURES ON ALERT 1404 01:13:04,760 --> 01:13:07,280 DESENSITIZATION AND OTHER HEALTH 1405 01:13:07,280 --> 01:13:07,720 OUTCOMES. 1406 01:13:07,720 --> 01:13:09,400 OUR ULTIMATE GOALS IS TO 1407 01:13:09,400 --> 01:13:11,280 IDENTIFY NEW DRUG TARGETS OR 1408 01:13:11,280 --> 01:13:15,360 PREVENTATIVE STRATEGIES TO 1409 01:13:15,360 --> 01:13:22,920 REDUCE THE INI GRAVE A HUGE 1410 01:13:22,920 --> 01:13:24,680 THANKS TO THE URECA 1411 01:13:24,680 --> 01:13:26,080 INVESTIGATORS AND IT'S AN HONOR 1412 01:13:26,080 --> 01:13:36,480 BEING INVITED AND THEY 1413 01:13:42,520 --> 01:13:44,000 DELIBERATELY DID EVERYTHING AND 1414 01:13:44,000 --> 01:13:46,040 I'LL GET TO CHARLES IS THE 1415 01:13:46,040 --> 01:13:47,760 GRADUATE STUDENT WHO WORKED ON 1416 01:13:47,760 --> 01:13:58,280 THE MAPPING STUDIES AND AND SO 1417 01:14:06,400 --> 01:14:08,040 HE IS REALLY OVERSEEING ALL OF 1418 01:14:08,040 --> 01:14:12,080 THESE STUDIES THAT I'VE 1419 01:14:12,080 --> 01:14:14,120 DESCRIBED TODAY. 1420 01:14:14,120 --> 01:14:16,520 AT THIS FOR YOUR ATTENTION. 1421 01:14:16,520 --> 01:14:18,720 THANK YOU, CAROLE, THAT WAS 1422 01:14:18,720 --> 01:14:18,960 FANTASTIC. 1423 01:14:18,960 --> 01:14:21,120 WE CAN PROBABLY TAKE ONE OR TWO 1424 01:14:21,120 --> 01:14:23,160 QUICK QUESTIONS AND THEN AGAIN 1425 01:14:23,160 --> 01:14:26,160 WE CAN TRY TO TAKE ANYMORE AT 1426 01:14:26,160 --> 01:14:27,800 THE END IF THERE ARE UNANSWERED 1427 01:14:27,800 --> 01:14:30,360 OR UNADDRESSED. 1428 01:14:30,360 --> 01:14:31,920 SO PLEASE FEEL FREE TO JUMP OUT 1429 01:14:31,920 --> 01:14:33,240 OR STICK YOUR HAND UP, WHATEVER 1430 01:14:33,240 --> 01:14:43,520 IS EASIEST. 1431 01:14:47,080 --> 01:14:48,440 I FOUND IT WAS TOWARDS THE END 1432 01:14:48,440 --> 01:14:50,640 THERE, WHEN YOU WERE SHOWING THE 1433 01:14:50,640 --> 01:14:51,960 DIFFERENCE IN IDENTIFICATION OF 1434 01:14:51,960 --> 01:14:53,640 SITE BY THE EPIC ARRAY VERSUS 1435 01:14:53,640 --> 01:14:58,480 THE CUSTOM ARRAY AND WHEN IT'S 1436 01:14:58,480 --> 01:15:08,400 ON THE IT'S A FEATURE OF HOW YOU 1437 01:15:08,400 --> 01:15:10,880 DESIGNED YOUR ARRAY VERSUS EPIC 1438 01:15:10,880 --> 01:15:13,000 ARRAY WOULD IT MAKE SENSE TO 1439 01:15:13,000 --> 01:15:15,000 HAVE EVERYTHING YOU IDENTIFIED 1440 01:15:15,000 --> 01:15:16,640 BY THE WHOLE GENOME BY WHOLE 1441 01:15:16,640 --> 01:15:19,000 FACE SEQUENCING ON THE EPIC 1442 01:15:19,000 --> 01:15:19,560 ARRAY GOUGH THROUGH THE SAME 1443 01:15:19,560 --> 01:15:20,920 PROCESS SO YOU HAVE THE REGION 1444 01:15:20,920 --> 01:15:24,560 AROUND THAT CPG OR IS THAT 1445 01:15:24,560 --> 01:15:25,000 UNNECESSARY? 1446 01:15:25,000 --> 01:15:31,400 >> SO, THAT IS, I AGREE WITH 1447 01:15:31,400 --> 01:15:33,520 THAT AND IN FACT MOST OF THE 1448 01:15:33,520 --> 01:15:34,720 SIGNALS THAT WERE PICKED UP BY 1449 01:15:34,720 --> 01:15:39,280 THE EPIC DON'T HAVE ANY CUSTOM 1450 01:15:39,280 --> 01:15:49,800 ARRAY AND WITHOUT REALIZING IT 1451 01:15:58,040 --> 01:15:58,960 AROUND CLUSTERED AROUND GENES SO 1452 01:15:58,960 --> 01:16:01,560 WE DON'T COVER AS MUCH SCOPE AS 1453 01:16:01,560 --> 01:16:08,440 THE EPIC RESULTS THEY'RE REALLY 1454 01:16:08,440 --> 01:16:08,960 SPREAD OUT. 1455 01:16:08,960 --> 01:16:10,120 >> HAVE YOU BEEN ABLE TO START 1456 01:16:10,120 --> 01:16:13,160 TO LOOK AT WHETHER THERE'S ANY 1457 01:16:13,160 --> 01:16:15,000 CLINICAL ASSOCIATIONS EITHER 1458 01:16:15,000 --> 01:16:20,000 BASED ON THE INDIVIDUALS 1459 01:16:20,000 --> 01:16:23,280 PHENOTYPE OR THE ENVIRONMENT 1460 01:16:23,280 --> 01:16:26,320 THAT ARE ASSOCIATED WITH THE 1461 01:16:26,320 --> 01:16:27,000 EPIGENETIC MODERATIONS THAT YOU 1462 01:16:27,000 --> 01:16:28,720 ARE SEEING? 1463 01:16:28,720 --> 01:16:30,360 >> WELL, DO YOU KNOW WHAT I 1464 01:16:30,360 --> 01:16:30,760 MEAN? 1465 01:16:30,760 --> 01:16:34,640 ARE THERE FEATURES SO PETS OR 1466 01:16:34,640 --> 01:16:38,000 ANYTHING LIKE THAT? 1467 01:16:38,000 --> 01:16:40,600 >> THAT'S A PROJECT TO LOOK AT 1468 01:16:40,600 --> 01:16:42,400 ALL THE ENVIRONMENTAL EXPOSURES 1469 01:16:42,400 --> 01:16:44,240 AND EUREKA BUT WE HAVE SOME 1470 01:16:44,240 --> 01:16:45,440 RESULTS ON POLLUTION WHICH I 1471 01:16:45,440 --> 01:16:46,680 DIDN'T HAVE TIME TO GO INTO BUT 1472 01:16:46,680 --> 01:16:50,440 I FORGOT TO TAKE IT OUT OF THE 1473 01:16:50,440 --> 01:16:51,880 SLIDE AND THERE ARE PREVIOUSLY 1474 01:16:51,880 --> 01:16:54,600 STUDIES THAT SUGGESTED THAT 1475 01:16:54,600 --> 01:16:56,000 INTERMEDIATE CPGs ARE THE ONES 1476 01:16:56,000 --> 01:16:57,640 THAT ARE REALLY RESPONSIVE TO 1477 01:16:57,640 --> 01:16:59,320 ENVIRONMENTAL STIMULUS. 1478 01:16:59,320 --> 01:17:01,520 AND IN OUR POLLUTION STUDIES 1479 01:17:01,520 --> 01:17:02,840 WE'RE SUPPORTING THAT AND IT'S 1480 01:17:02,840 --> 01:17:03,920 VERY PRELIMINARY SO I DIDN'T 1481 01:17:03,920 --> 01:17:10,640 WANT TO PRESENT THEM YET AND 1482 01:17:10,640 --> 01:17:21,160 THERE'S AND EXPOSURE IN WE'RE 1483 01:17:21,960 --> 01:17:23,800 EXCITE TODAY DO IN URECA BECAUSE 1484 01:17:23,800 --> 01:17:26,440 THEY HAVE A LOT OF ENVIRONMENTAL 1485 01:17:26,440 --> 01:17:27,720 EXPOSURES AND EVEN LIKE STRESS 1486 01:17:27,720 --> 01:17:29,240 AND ALL THE THINGS THAT SEEM TO 1487 01:17:29,240 --> 01:17:31,120 BE ASSOCIATED WITH DIFFERENT 1488 01:17:31,120 --> 01:17:32,520 ASTHMA PHENOTYPES WE'LL LOOK AT 1489 01:17:32,520 --> 01:17:35,320 WITH RESPECT TO THESE USING THE 1490 01:17:35,320 --> 01:17:37,760 ARRAY AND TO SEE IF WE CAN 1491 01:17:37,760 --> 01:17:38,720 ACTUALLY PARSE OUT THE EFFECTS 1492 01:17:38,720 --> 01:17:40,160 OF GENES VERSUS ENVIRONMENT ON 1493 01:17:40,160 --> 01:17:43,440 THE DNA METHYLATION LANDSCAPE. 1494 01:17:43,440 --> 01:17:43,920 >> EXCELLENT. 1495 01:17:43,920 --> 01:17:45,400 >> IT'S A GREAT QUESTION. 1496 01:17:45,400 --> 01:17:48,040 WE HAVEN'T DONE IT YET. 1497 01:17:48,040 --> 01:17:50,840 >> I HAVE A COUPLE OF QUESTIONS 1498 01:17:50,840 --> 01:17:52,240 BUT IF THERE'S TIME. 1499 01:17:52,240 --> 01:17:52,960 >> OK. 1500 01:17:52,960 --> 01:17:54,880 >> IF YOU ARE OK WITH THAT, 1501 01:17:54,880 --> 01:17:58,160 WE'LL TURN THINGS OVER TO MATT. 1502 01:17:58,160 --> 01:18:00,200 >> HE WILL SHOW SOME OF HIS DATA 1503 01:18:00,200 --> 01:18:01,480 ON THE TRANSCRIPTIONAL 1504 01:18:01,480 --> 01:18:08,520 SIGNATURES IN THIS POPULATION. 1505 01:18:08,520 --> 01:18:10,280 >> I HAVE MY SCREEN HERE. 1506 01:18:10,280 --> 01:18:12,320 YEAH, I JUST SAID ALSO VERY 1507 01:18:12,320 --> 01:18:15,280 HONORED TO BE INVITED. 1508 01:18:15,280 --> 01:18:16,960 I'VE NOT JOINED ONE OF THESE 1509 01:18:16,960 --> 01:18:18,880 SESSIONS BEFORE AND IT'S BEEN A 1510 01:18:18,880 --> 01:18:22,000 VERY INTERESTING DAY AND ALWAYS 1511 01:18:22,000 --> 01:18:25,560 HAPPY TO TALK ABOUT THE URECA 1512 01:18:25,560 --> 01:18:27,360 DATA AND ALWAYS INTERESTING TO 1513 01:18:27,360 --> 01:18:29,920 FOLLOW AFTER JIM AND CAROLE, WHO 1514 01:18:29,920 --> 01:18:34,200 HAVE SUCH AN OUTSTANDING DATA 1515 01:18:34,200 --> 01:18:35,960 AND HOPEFULLY WHAT I'LL SHOW 1516 01:18:35,960 --> 01:18:42,720 HERE IS A LITTLE MORE ONE OR TWO 1517 01:18:42,720 --> 01:18:44,000 STORIES BUT A NICE ADDITION 1518 01:18:44,000 --> 01:18:47,160 ABOUT WHAT WE HEARD ABOUT THE 1519 01:18:47,160 --> 01:18:47,960 UCECA COHORT. 1520 01:18:47,960 --> 01:18:57,480 I'M GOING TO TALK ABOUT AIRWAY 1521 01:18:57,480 --> 01:18:58,440 EPITHELIUM GENE EXPRESSION END 1522 01:18:58,440 --> 01:19:00,760 OWE TYPING OF MASS AND RHINITIS 1523 01:19:00,760 --> 01:19:01,280 IN URBAN CHILDREN. 1524 01:19:01,280 --> 01:19:06,200 THIS IS A QUICK REMINDER, THE 1525 01:19:06,200 --> 01:19:07,680 URECA BIRTH COHORT THE IDEA THAT 1526 01:19:07,680 --> 01:19:14,920 YOU KNOW, THERE'S JUST GREAT 1527 01:19:14,920 --> 01:19:17,000 DETAIL ABOUT FACTOR FROM 1528 01:19:17,000 --> 01:19:21,760 PRE-NATAL AND THROUGH NOW 1529 01:19:21,760 --> 01:19:23,040 TEENAGE YEARS OF RISK FACTORS 1530 01:19:23,040 --> 01:19:25,400 FORT DEVELOPMENT OF DISEASE AND 1531 01:19:25,400 --> 01:19:27,120 ALL OF THAT IS FACT ORDER INTO 1532 01:19:27,120 --> 01:19:29,000 THESE ANALYSIS AND WHAT I'M 1533 01:19:29,000 --> 01:19:30,120 SPECIFICALLY GOING TO TALK ABOUT 1534 01:19:30,120 --> 01:19:32,920 THIS IS LOOK AT THE AGE 10 AND 1535 01:19:32,920 --> 01:19:35,240 11 TIME POINT WHEN THIS VERY 1536 01:19:35,240 --> 01:19:36,920 DETAILED FINE OWE TYPING WAS 1537 01:19:36,920 --> 01:19:39,720 DONE AROUND RESPIRATORY 1538 01:19:39,720 --> 01:19:42,320 PHENOTYPES AND RHINITIS FI 1539 01:19:42,320 --> 01:19:44,720 PHENOTYPES AND LOOKING AT 1540 01:19:44,720 --> 01:19:46,120 SAMPLES FROM THE UPPER AIRWAY 1541 01:19:46,120 --> 01:19:49,520 AND USED FOR RNA SEQUENCING 1542 01:19:49,520 --> 01:19:50,040 ANALYSIS. 1543 01:19:50,040 --> 01:19:53,200 SO, AGAIN, REMINDER THAT USING 1544 01:19:53,200 --> 01:20:01,640 THIS CLUSTERING METHOD, THERE 1545 01:20:01,640 --> 01:20:03,960 WERE SIX FINE OWE TYPES THAT 1546 01:20:03,960 --> 01:20:05,160 DELL OVER THE FIRST 10 YEARS OF 1547 01:20:05,160 --> 01:20:15,640 LIFE AND BASED ONTHIS IS THE 1548 01:20:41,440 --> 01:20:43,240 MOST SEVERE GROUP BEING 1549 01:20:43,240 --> 01:20:44,800 RELATIVELY SEVERE ALLERGIC 1550 01:20:44,800 --> 01:20:45,960 ASTHMA AND WHERE WE SEE THIS 1551 01:20:45,960 --> 01:20:48,600 LOSS OF FUNCTION AND THIS MEDIUM 1552 01:20:48,600 --> 01:20:50,280 FLOW GROUP AS SOMETHING MORE OF 1553 01:20:50,280 --> 01:20:54,840 A NON OR AT LEAST A LOW ALLERGY 1554 01:20:54,840 --> 01:20:57,800 AMA GROUP. 1555 01:20:57,800 --> 01:20:59,720 THIS SLIDE IS KIND OF A STAND-IN 1556 01:20:59,720 --> 01:21:03,360 NOR THE METHODOLOGY THAT I'LL 1557 01:21:03,360 --> 01:21:11,360 DESCRIBE HERE BASICALLY AND USED 1558 01:21:11,360 --> 01:21:13,880 FOR HOST MRNA SEQUENCING AND 1559 01:21:13,880 --> 01:21:17,200 THIS TABLE IS THE SHOW THAT WE 1560 01:21:17,200 --> 01:21:20,000 HAD GOOD SAMPLE SIZE AND FAIRLY 1561 01:21:20,000 --> 01:21:22,920 SEEK DISTRIBUTION ACROSS THE SIX 1562 01:21:22,920 --> 01:21:26,760 PHENOTYPES OF INTEREST AND THE 1563 01:21:26,760 --> 01:21:30,760 METHOD WE USED FOR THOSE WHO ARE 1564 01:21:30,760 --> 01:21:32,520 FAMILIAR WITH AND SOMETHING LIKE 1565 01:21:32,520 --> 01:21:37,240 A TRANSRIPTOME DATA SET IT'S 1566 01:21:37,240 --> 01:21:39,240 NICE TO USE A NETWORK ANALYSIS 1567 01:21:39,240 --> 01:21:41,000 TYPE APPROACH TO REDUCE THE 1568 01:21:41,000 --> 01:21:44,200 DIMENSIONALITY OF THE DATA AND 1569 01:21:44,200 --> 01:21:47,520 INFUR COHERENT BIOLOGY AND WE 1570 01:21:47,520 --> 01:21:50,800 USED THIS WGCNA NETWORK ANALYSIS 1571 01:21:50,800 --> 01:21:53,680 AND TO PURELY DATA DRIVEN 1572 01:21:53,680 --> 01:21:55,800 FASHION AND COLLAPSE CORRELATED 1573 01:21:55,800 --> 01:21:58,920 GENES INTO NETWORKS AND WHILE WE 1574 01:21:58,920 --> 01:22:01,840 CALL MODULES SO 26 DISTINCT 1575 01:22:01,840 --> 01:22:02,920 MODULES WHICH REPRESENT 1576 01:22:02,920 --> 01:22:04,960 DIFFERENT BOYOLOGY AND DIFFERENT 1577 01:22:04,960 --> 01:22:06,480 PATTERNS OF THE DATA AND WE CAN 1578 01:22:06,480 --> 01:22:07,840 THEN USED TO MODEL FOR OUR 1579 01:22:07,840 --> 01:22:11,160 QUESTIONS OF INTEREST AND SO, 1580 01:22:11,160 --> 01:22:12,800 LINEAR MODELING, ASKING 1581 01:22:12,800 --> 01:22:14,600 DIFFERENCES BY GROUP OR RELATING 1582 01:22:14,600 --> 01:22:17,120 A MODULE TO LUNG FUNCTION OR 1583 01:22:17,120 --> 01:22:18,560 OTHER CONTINUOUS VARIABLES AND 1584 01:22:18,560 --> 01:22:21,840 WE CAN ADJUST THESE FOR THINGS 1585 01:22:21,840 --> 01:22:23,480 LIKE CELL FREQUENCY OR CLINICAL 1586 01:22:23,480 --> 01:22:29,320 SITES AND TO ULTIMATELY COME AT 1587 01:22:29,320 --> 01:22:30,720 SPECIFICALLY IMPORTANT 1588 01:22:30,720 --> 01:22:33,720 DIFFERENCES THAT EXIST. 1589 01:22:33,720 --> 01:22:35,360 I'LL START WITH THIS COMPLICATED 1590 01:22:35,360 --> 01:22:36,920 HEAT MAP WHICH IS MEANT AS A 1591 01:22:36,920 --> 01:22:40,320 GLOBAL OVERVIEW OF THE MANY 1592 01:22:40,320 --> 01:22:41,240 SIGNALS THAT EXIST DESCRIBING 1593 01:22:41,240 --> 01:22:42,320 THESE DIFFERENT PHENOTYPES AND 1594 01:22:42,320 --> 01:22:44,320 I'LL FOCUS ON A FEW OF INTEREST 1595 01:22:44,320 --> 01:22:46,360 AND SO HERE WHAT I'M IN EFFECT 1596 01:22:46,360 --> 01:22:48,960 SHOWING IS A GROUP LEVEL 1597 01:22:48,960 --> 01:22:52,440 EXPRESSION OF EACH OF THESE 26 1598 01:22:52,440 --> 01:22:55,760 MODULES EACH ROW IS THESE SCORES 1599 01:22:55,760 --> 01:22:58,280 SO NORMALIZED SHOWING THE 1600 01:22:58,280 --> 01:22:59,000 RELATIVE DIFFERENCE AND 1601 01:22:59,000 --> 01:23:02,640 EXPRESSION A CROSS THE GROUPS 1602 01:23:02,640 --> 01:23:04,920 AND ONE OF THE FIRST HEAT MAPS 1603 01:23:04,920 --> 01:23:06,840 ARE TRICKY TO READ BUT ONE OF 1604 01:23:06,840 --> 01:23:09,680 THE OBVIOUS FINDINGS AND AS I 1605 01:23:09,680 --> 01:23:18,280 LABEL THE BOTTOM, THEY ARE IS A 1606 01:23:18,280 --> 01:23:23,680 CLEAR DICHOTOMIATION AND I HAVE 1607 01:23:23,680 --> 01:23:25,120 INCREASING WHEEZE FREQUENCY AND 1608 01:23:25,120 --> 01:23:27,240 WITH LOW ATP ON THE LEFT AND 1609 01:23:27,240 --> 01:23:31,600 HIGH ATP ON THE RIGHT AND LOW 1610 01:23:31,600 --> 01:23:34,520 ATP AND IT'S CLEAR THERE ARE 1611 01:23:34,520 --> 01:23:37,160 BLOCKS AND FOR EXAMPLE IN THAT 1612 01:23:37,160 --> 01:23:39,160 HIGH WHEEZE HIGH ATP LOW 1613 01:23:39,160 --> 01:23:42,600 FUNCTION GROUP AND AND THE 1614 01:23:42,600 --> 01:23:44,960 MEDIUM WHEEZE LOW ATP AND I'LL 1615 01:23:44,960 --> 01:23:48,440 SHOW YOU KEY BIOLOGIC RESULTS 1616 01:23:48,440 --> 01:23:52,200 IRRELEVANT TO EACH OF THOSE. 1617 01:23:52,200 --> 01:23:54,120 SO ACTUALLY FIRST LET ME DISCUSS 1618 01:23:54,120 --> 01:23:58,240 ONE EXAMPLE AND SHOULD BE A GOOD 1619 01:23:58,240 --> 01:24:00,160 GROUNDING BY BIOLOGIC GROUNDING 1620 01:24:00,160 --> 01:24:02,400 IN DISTINGUISHES AND GROUPS FROM 1621 01:24:02,400 --> 01:24:05,960 LOW ATP GROUPS AND THIS IS TH2 1622 01:24:05,960 --> 01:24:10,080 AND ILC2 AND THE REASON FOR THIS 1623 01:24:10,080 --> 01:24:14,680 IS THAT CONTAINS GENES OF COURSE 1624 01:24:14,680 --> 01:24:17,400 VERY MUCH AND FUNCTIONS OF THEM 1625 01:24:17,400 --> 01:24:19,360 SO IT INCLUDES FOR EXAMPLE, THIS 1626 01:24:19,360 --> 01:24:23,840 IS A GENE-GENE NETWORK PLOT 1627 01:24:23,840 --> 01:24:27,280 SHOWING THE CORE GENES SO IL13 1628 01:24:27,280 --> 01:24:30,560 AND IL1 WHICH IS ST2 THE 1629 01:24:30,560 --> 01:24:33,040 RECEPTORS FOR IL33 AND OTHERS 1630 01:24:33,040 --> 01:24:35,440 ARE FAIRLY SPECIFIC TO THOSE TWO 1631 01:24:35,440 --> 01:24:37,240 CELL TYPES AND WHAT WE CAN SEE 1632 01:24:37,240 --> 01:24:40,080 HERE IS THAT THE NOW RATHER THAN 1633 01:24:40,080 --> 01:24:41,600 SHOWING THIS HEAT MAP SCORE YOU 1634 01:24:41,600 --> 01:24:43,480 CAN SEE THE DISTRIBUTION OF THE 1635 01:24:43,480 --> 01:24:45,320 DATA BY BOX PLOT AND THE REASON 1636 01:24:45,320 --> 01:24:46,440 THAT THIS IS SIGNIFICANT, IS 1637 01:24:46,440 --> 01:24:53,280 BECAUSE OF THE THE DIFFERENCE OF 1638 01:24:53,280 --> 01:24:55,200 OBSERVED HIGH AND LOW ATM WITHIN 1639 01:24:55,200 --> 01:24:58,720 EACH OF THOSE AND SO, THAT WILL 1640 01:24:58,720 --> 01:25:02,000 BE SOMEWHAT IN CONTRAST TO THIS 1641 01:25:02,000 --> 01:25:03,800 NEXT EXAMPLE WHERE WE PICK UP A 1642 01:25:03,800 --> 01:25:05,440 NUMBER OF PATHWAYS RELATIVELY 1643 01:25:05,440 --> 01:25:06,760 SPECIFIC IN ONE MANNER OR 1644 01:25:06,760 --> 01:25:09,040 ANOTHER AND SO THE HIGH WHEEZE 1645 01:25:09,040 --> 01:25:18,000 HIGH ATP LOSS OF LUNG FUNCTION 1646 01:25:18,000 --> 01:25:28,120 GROUP. 1647 01:26:33,520 --> 01:26:38,520 >> ONE ADDITIONAL ONE SHOWED THE 1648 01:26:38,520 --> 01:26:42,400 GRAPHICAL ABSTRACT AND BUT NOW 1649 01:26:42,400 --> 01:26:43,800 SHOWING A MODULE THAT IS 1650 01:26:43,800 --> 01:26:46,800 SPECIFICALLY ELEVATED WITHIN A 1651 01:26:46,800 --> 01:26:49,360 HIGH WHEEZE HIGH ATOPY LOSS OF 1652 01:26:49,360 --> 01:26:52,880 FUNCTION GROUP AND THIS IS A 1653 01:26:52,880 --> 01:26:56,640 MUCUS HYPER SECRETION PATHWAY 1654 01:26:56,640 --> 01:26:58,560 AND YOU CAN SEE THE CORE BIOLOGY 1655 01:26:58,560 --> 01:27:01,520 HERE IN THIS NETWORK BUT NOT 1656 01:27:01,520 --> 01:27:04,800 ONLY THE EFFECTER GENE ITSELF 1657 01:27:04,800 --> 01:27:08,720 BUT THE LIFE OWE SIM AND OTHER 1658 01:27:08,720 --> 01:27:10,320 PROTEINS FOX A3 CRITICAL TRANS 1659 01:27:10,320 --> 01:27:12,800 DESCRIPTION FACTOR AND TF F-1, 2 1660 01:27:12,800 --> 01:27:19,240 AND 3 OF THE MUCUS LAYER AND 1661 01:27:19,240 --> 01:27:20,560 HERE AGAIN WE SEE THIS 1662 01:27:20,560 --> 01:27:22,800 RELATIONSHIP TO LUNG FUNCTION 1663 01:27:22,800 --> 01:27:24,400 AND PULLED THIS OUT OF THE 1664 01:27:24,400 --> 01:27:26,880 RELATIVELY UNIQUE ASPECT TO 1665 01:27:26,880 --> 01:27:28,400 THOSE INDIVIDUALS WITH IMPAIRED 1666 01:27:28,400 --> 01:27:33,840 DEVELOPMENT OF LUNG FUNCTION. 1667 01:27:33,840 --> 01:27:35,480 THIS WAS ALL PUBLISHED IN ONE 1668 01:27:35,480 --> 01:27:38,200 PAPER IN JACI A YEAR AGO AND WE 1669 01:27:38,200 --> 01:27:48,240 ACTUALLY EXTENDED THIS WORK WE 1670 01:27:48,240 --> 01:27:50,280 WANTED TO LOOK AT GENE BY TEEN 1671 01:27:50,280 --> 01:27:57,040 EXPRESSION RELATIONSHIP SO USING 1672 01:27:57,040 --> 01:27:58,680 GENOTYPES FROM THAT RNA 1673 01:27:58,680 --> 01:28:00,440 SEQUENCING DATA WE HAVE THE GNA 1674 01:28:00,440 --> 01:28:03,920 SEAT DATA FROM CAROLE AND WE'VE 1675 01:28:03,920 --> 01:28:08,920 BEEN ABLE TO SEE A NUMBER OF 1676 01:28:08,920 --> 01:28:12,720 SNIPS WITHIN THE MUC5AC AS BEING 1677 01:28:12,720 --> 01:28:14,160 RELATED TO THE LEVEL OF 1678 01:28:14,160 --> 01:28:17,560 EXPRESSION SO THIS IS AN EQTL 1679 01:28:17,560 --> 01:28:20,560 ANALYSIS AND IN FACT, IT'S HARD 1680 01:28:20,560 --> 01:28:22,160 TO APPRECIATE FROM THIS LD PLOT 1681 01:28:22,160 --> 01:28:24,520 ON THE BOTTOM, BUT FUNDAMENTALLY 1682 01:28:24,520 --> 01:28:28,520 THERE ARE TWO DISTINCT LD 1683 01:28:28,520 --> 01:28:31,880 LIBERALS WITHIN MUC5AC AND EACH 1684 01:28:31,880 --> 01:28:33,960 OF WHICH HAVE A SIGNIFICANT 1685 01:28:33,960 --> 01:28:37,080 RELATIONSHIP TO THE LEVEL OF 1686 01:28:37,080 --> 01:28:41,440 MUC5A EXPRESSION IN THE URECA 1687 01:28:41,440 --> 01:28:42,880 CHILDREN AND THIS ONE ON THE 1688 01:28:42,880 --> 01:28:46,280 LEFT BEING QUOTE-UNQUOTE DELL 1689 01:28:46,280 --> 01:28:48,160 TIER YUS AND ASSOCIATED WITH 1690 01:28:48,160 --> 01:28:52,760 HIGHER EXPRESSION MUC5LA AND 1691 01:28:52,760 --> 01:28:55,160 PROTECTED YOU WOULD SAY WERE THE 1692 01:28:55,160 --> 01:28:57,120 REVERSE HERE AND RELATES TO 1693 01:28:57,120 --> 01:28:58,600 LOWER AND I DON'T SHOW IT BUT 1694 01:28:58,600 --> 01:29:00,000 WHEN YOU LOCK AT THEM TOGETHER 1695 01:29:00,000 --> 01:29:05,440 THE COMBINATION OF THE TWO AND 1696 01:29:05,440 --> 01:29:06,960 HAVE A ADDITIVE EFFECT ON THE 1697 01:29:06,960 --> 01:29:09,520 DEGREE OF EXPRESSION AND ONE 1698 01:29:09,520 --> 01:29:11,280 NICE THING BECAUSE WE HAVE THE 1699 01:29:11,280 --> 01:29:13,760 RNA SEQUENCING WE CAN RUN ANNA 1700 01:29:13,760 --> 01:29:14,400 LEGAL SPECIFIC EXPRESSION AS 1701 01:29:14,400 --> 01:29:19,240 WELL AND SEE IN DEED IN THOSE 1702 01:29:19,240 --> 01:29:22,400 WHO ARE -- WHO HAVE BOTH ALLELE 1703 01:29:22,400 --> 01:29:25,200 WE SEE HIGHER EXPRESSIONS OF THE 1704 01:29:25,200 --> 01:29:27,680 ALLELE ASSOCIATED GREATER 1705 01:29:27,680 --> 01:29:31,760 EXPRESSION IN THE ANALYSIS AND 1706 01:29:31,760 --> 01:29:34,840 JUST TO DIVERGE AND ONE NICE 1707 01:29:34,840 --> 01:29:36,520 THING THAT WE WERE ABLE TO DO 1708 01:29:36,520 --> 01:29:41,120 AND THIS IS LEVERAGING ICAC TO 1709 01:29:41,120 --> 01:29:42,880 CAUSE THIS AND ANOTHER 1710 01:29:42,880 --> 01:29:47,120 POPULATION AND THIS WAS THE 1711 01:29:47,120 --> 01:29:49,000 COHORT AND WITH ESTABLISHED 1712 01:29:49,000 --> 01:29:51,320 RELATIVELY SEVERE EXACERBATION 1713 01:29:51,320 --> 01:29:53,400 PRONE AR MASS AND WE WERE ABLE 1714 01:29:53,400 --> 01:29:55,320 TO LOOK AT THOSE GENOTYPES IN 1715 01:29:55,320 --> 01:29:59,200 RELATION TO MUC5A EXPRESSION AND 1716 01:29:59,200 --> 01:30:01,120 PARTICULARLY DURING RESPIRATORY 1717 01:30:01,120 --> 01:30:02,800 ILLNESS AND WHAT THIS SHOWED US 1718 01:30:02,800 --> 01:30:07,000 WAS THAT IN FACT THESE SNIPS 1719 01:30:07,000 --> 01:30:13,920 HAVE AN INDEASE ABLE E DUCE ABLG 1720 01:30:13,920 --> 01:30:14,880 EXACERBATION IN PARTICULAR, WE 1721 01:30:14,880 --> 01:30:16,760 SEE A GREATER DEGREE OF UP 1722 01:30:16,760 --> 01:30:18,920 REGULATION OF THIS IN THE 1723 01:30:18,920 --> 01:30:20,800 EFFECTED GENOTYPE AND THE FINAL 1724 01:30:20,800 --> 01:30:22,320 FINDINGS JUST CIRCLEELING BACK 1725 01:30:22,320 --> 01:30:30,480 TO MY EARLIER DEMONSTRATION OF 1726 01:30:30,480 --> 01:30:35,880 THE 1727 01:30:35,880 --> 01:30:38,960 AND THIS IS A VARIABLE AGES FOR 1728 01:30:38,960 --> 01:30:43,040 THE COHORT BUT THIS ALLELE 1729 01:30:43,040 --> 01:30:47,640 HAVING A DIRECT RELATION TO LUNG 1730 01:30:47,640 --> 01:30:48,680 FUNCTION AS WELL. 1731 01:30:48,680 --> 01:30:51,600 I WILL NOW RETURN TO THE STORY I 1732 01:30:51,600 --> 01:30:53,720 STARTED AND WHICH WAS THIS END 1733 01:30:53,720 --> 01:30:56,800 OWE TYPING OF THE UREKA COHORT 1734 01:30:56,800 --> 01:31:00,560 AND I SHOWED YOU THE PATHWAYS TO 1735 01:31:00,560 --> 01:31:04,760 THE LOW FUNCTION GROUP AND LET 1736 01:31:04,760 --> 01:31:08,560 ME SPEND IF THE MINUTE ON THE 1737 01:31:08,560 --> 01:31:11,600 MEDIUM WHICH AGAIN I SAID AT THE 1738 01:31:11,600 --> 01:31:14,560 OUTSET RESEMBLED A LOW NON A 1739 01:31:14,560 --> 01:31:21,280 TOPIC ASTHMA AND WE CAN SEE IF 1740 01:31:21,280 --> 01:31:23,560 YOU JUST LOOK GLOBALLY THERE'S A 1741 01:31:23,560 --> 01:31:24,760 DISTINCT PATTERN AND THE SIGNALS 1742 01:31:24,760 --> 01:31:26,120 IN THIS GROUP ARE CERTAINLY A 1743 01:31:26,120 --> 01:31:28,200 LITTLE BIT WEAKER OR A LITTLE 1744 01:31:28,200 --> 01:31:35,200 BIT MORE HETEROGENEOUS BUT A FEW 1745 01:31:35,200 --> 01:31:42,320 AND ONE BEING THAT THIS AND 1746 01:31:42,320 --> 01:31:43,960 RELATIVE AND LOWER EXPRESSION OF 1747 01:31:43,960 --> 01:31:46,680 AN INTEGRITY AND LUKE OWE SIGHT 1748 01:31:46,680 --> 01:31:51,840 MIGRATION PATHWAY AND PATHWAY IN 1749 01:31:51,840 --> 01:31:54,880 WHICH CAR TIN AND SIMILAR AND 1750 01:31:54,880 --> 01:31:56,640 RELATIVE OVER EXPRESSION OF THIS 1751 01:31:56,640 --> 01:32:01,320 INJURY RESPONSE PATHWAY AND 1752 01:32:01,320 --> 01:32:02,120 INCLUDING SIGNALING AND A COUPLE 1753 01:32:02,120 --> 01:32:08,360 OF OTHER SIGNALING PATHWAYS. 1754 01:32:08,360 --> 01:32:18,840 SO A HIGH WHEEZE GROUP AND WE 1755 01:32:19,520 --> 01:32:22,400 CAN SEE HERE IN A NETWORK OF 1756 01:32:22,400 --> 01:32:26,680 NETWORKS WHERE WE LINK IN THE 1757 01:32:26,680 --> 01:32:27,760 RELATIVE ASSOCIATION OF THE 1758 01:32:27,760 --> 01:32:28,920 DIFFERENT PATHWAYS WE 1759 01:32:28,920 --> 01:32:29,240 IDENTIFIED. 1760 01:32:29,240 --> 01:32:31,720 YOU CAN SEE AT A BROAD SCALE THE 1761 01:32:31,720 --> 01:32:33,520 MULTIPLE THINGS THAT ARE OVER 1762 01:32:33,520 --> 01:32:36,120 EXPRESSED AND HIGH WHEEZE HIGH A 1763 01:32:36,120 --> 01:32:38,000 TP LOSS OF LUNG FUNCTION 1764 01:32:38,000 --> 01:32:40,760 INCLUSIVE THE TWO I SHOWED AND 1765 01:32:40,760 --> 01:32:42,520 TWO OTHERS AND OTHERS YOU CAN 1766 01:32:42,520 --> 01:32:44,560 SEE HERE. 1767 01:32:44,560 --> 01:32:45,640 AND AGAIN A VERY DIFFERENT STORY 1768 01:32:45,640 --> 01:32:48,080 IN THE MEDIUM WITH LOW ATP OF 1769 01:32:48,080 --> 01:32:49,920 THE TWO I TALKED ABOUT AND ALSO 1770 01:32:49,920 --> 01:32:54,520 RELATIVE IMPAIRMENT OF AN ANTI 1771 01:32:54,520 --> 01:32:58,280 OXIDANT GENE EXPRESSION PATHWAY 1772 01:32:58,280 --> 01:33:02,440 AND I'LL TURN IT TO ONE ON GOING 1773 01:33:02,440 --> 01:33:03,920 PROJECT WHICH IS WORKING WITH 1774 01:33:03,920 --> 01:33:06,200 JIM THE CHARACTERIZATION NOW OF 1775 01:33:06,200 --> 01:33:07,720 RHINITIS PHENOTYPES IN THESE 1776 01:33:07,720 --> 01:33:09,840 CHILDREN AND SO JIM SHOWED THIS 1777 01:33:09,840 --> 01:33:13,560 USING THE SAME PORT OF METHOD OF 1778 01:33:13,560 --> 01:33:16,680 THE CHILDREN CAN BE GROUPED BY 1779 01:33:16,680 --> 01:33:18,560 THEIR 11 YEAR TRAJECTORY OF 1780 01:33:18,560 --> 01:33:20,280 UPPER AIRWAY SYMPTOMS AS EITHER 1781 01:33:20,280 --> 01:33:22,680 THOSE WITH PERSISTENT DISEASE 1782 01:33:22,680 --> 01:33:26,000 FROM EARLY LIFE AND THOSE WITH 1783 01:33:26,000 --> 01:33:27,440 DECREASING INCREASING AND THOSE 1784 01:33:27,440 --> 01:33:30,640 WITH RELATIVELY LOW SYMPTOMS AND 1785 01:33:30,640 --> 01:33:34,480 WE CAN APPLY THE SAME SORT OF 1786 01:33:34,480 --> 01:33:36,280 SEEK ANALYSIS AND IN FACT WE CAN 1787 01:33:36,280 --> 01:33:39,200 APPLY THE SAME MODULES WE HAD 1788 01:33:39,200 --> 01:33:40,720 IDENTIFIED AND THIS IS ON GOING 1789 01:33:40,720 --> 01:33:44,160 SO WHY WANT TO GET TO INTO IT 1790 01:33:44,160 --> 01:33:46,320 BUT NOTICE A NUMBER OF PATHWAYS 1791 01:33:46,320 --> 01:33:49,880 RELEVANT TO EACH OF THESE ONE 1792 01:33:49,880 --> 01:33:53,000 THING THAT STOOD OUT 1793 01:33:53,000 --> 01:33:54,000 IMMEDIATELY, EXCUSE ME, IS THAT 1794 01:33:54,000 --> 01:33:58,840 THIS EARLY PERSISTENT RHINITIS 1795 01:33:58,840 --> 01:34:01,160 PHENOTYPE SEEMS TO STAND OUT IN 1796 01:34:01,160 --> 01:34:05,040 THEIR RELATIVE LOW EXPRESSION OF 1797 01:34:05,040 --> 01:34:08,240 A VARIETY OF LET'S CALL THEM 1798 01:34:08,240 --> 01:34:10,080 ANTIMICROBIAL PLUS INNATE AND 1799 01:34:10,080 --> 01:34:13,640 ADAPTIVE IMMUNE RESPONSE 1800 01:34:13,640 --> 01:34:15,080 PATHWAYS AS OPPOSED TO STANDING 1801 01:34:15,080 --> 01:34:21,560 OUT TYPE 2 INFLAMMATION. 1802 01:34:21,560 --> 01:34:23,240 WITH THAT I'LL CONCLUDE. 1803 01:34:23,240 --> 01:34:24,760 I GUESS I SHOULD ACTUALLY SAY 1804 01:34:24,760 --> 01:34:26,200 ABOVE ALL THIS THAT BASICALLY 1805 01:34:26,200 --> 01:34:29,840 THE USE OF IN PARTICULAR AIRWAY 1806 01:34:29,840 --> 01:34:31,480 PROFILING HAS BEEN EXTREMELY 1807 01:34:31,480 --> 01:34:33,200 VALUABLE AND UNDERSTANDING THE 1808 01:34:33,200 --> 01:34:36,240 ACTUAL BIOLOGY BEHIND THE VERY 1809 01:34:36,240 --> 01:34:39,880 NICE CLINICAL TRAJECTORIES AND 1810 01:34:39,880 --> 01:34:41,080 WE'VE SEEN SIGNALS IN BLOOD AS 1811 01:34:41,080 --> 01:34:43,840 WELL AND SORT OF AS CAROLE 1812 01:34:43,840 --> 01:34:44,880 ALLUDED TO ITS NOT QUITE AS 1813 01:34:44,880 --> 01:34:46,920 VALUES ABLE AS LOOKING AT THE 1814 01:34:46,920 --> 01:34:48,240 TARGET ORGAN. 1815 01:34:48,240 --> 01:34:51,320 BUT HERE, WITHIN YOUR URECA, 1816 01:34:51,320 --> 01:34:53,320 WE'VE SEEN SPECIFIC MOTH HE CAN 1817 01:34:53,320 --> 01:34:57,000 YOU LAR PATHWAYS AND MAUD USE BY 1818 01:34:57,000 --> 01:34:58,320 PHENOTYPE AND MAUD USE QUITE A 1819 01:34:58,320 --> 01:35:01,840 FEW MODULE INCREASED IN THIS 1820 01:35:01,840 --> 01:35:03,080 HIGH WHEEZE HIGH LOSS OF LUNG 1821 01:35:03,080 --> 01:35:05,080 FUNCTION INCLUSIVE OF THE ONES I 1822 01:35:05,080 --> 01:35:07,360 LISTED HERE AND A DECREASE IN 1823 01:35:07,360 --> 01:35:12,480 ASPECTS OF INNATE IMMUNITY AND 1824 01:35:12,480 --> 01:35:14,840 COMBINING AND LEVERAGING THE 1825 01:35:14,840 --> 01:35:16,280 EXPERTISE OF CAROLE AND HER 1826 01:35:16,280 --> 01:35:18,880 GROUP LOOKING AT GENETIC 1827 01:35:18,880 --> 01:35:20,360 VARIANTS AND ALLOWED US TO 1828 01:35:20,360 --> 01:35:23,280 IDENTIFY A FAIRLY IMPORTANT 1829 01:35:23,280 --> 01:35:27,240 VARIANT IN THE MUC5AC AND 1830 01:35:27,240 --> 01:35:33,360 ASSOCIATING WITH GENE EXPRESSION 1831 01:35:33,360 --> 01:35:35,040 AND GAINING IN SIGHT INTO THIS 1832 01:35:35,040 --> 01:35:39,400 GROUP WHERE WE SEE INCREASES EGF 1833 01:35:39,400 --> 01:35:42,480 AN RELATIVE DECREASE IN 1834 01:35:42,480 --> 01:35:43,800 INTEGRITY AND LUKE OWE SIGHT 1835 01:35:43,800 --> 01:35:49,040 MIGRATION OF ACTIVITY ACTIVATION 1836 01:35:49,040 --> 01:35:49,680 PATHWAYS. 1837 01:35:49,680 --> 01:35:54,120 WITH THAT I'LL CONCLUDE SUPPORT 1838 01:35:54,120 --> 01:35:59,960 FROM NIAID AND PARTICULAR AND 1839 01:35:59,960 --> 01:36:02,280 JIM OF THE WHOLE GROUP AT 1840 01:36:02,280 --> 01:36:07,720 MADISON WHO HAVE RUN ICCAC AND 1841 01:36:07,720 --> 01:36:10,680 CAUSE AND SCOTT IN MY GROUP WHO 1842 01:36:10,680 --> 01:36:12,080 CONTRIBUTED A LOT TO THESE 1843 01:36:12,080 --> 01:36:13,880 ANALYSIS AND STUDENT AND WHO IS 1844 01:36:13,880 --> 01:36:17,720 WORKING ON THE RHINITIS DATA AND 1845 01:36:17,720 --> 01:36:23,640 THE INVESTIGATORS AND EUREKA 1846 01:36:23,640 --> 01:36:24,240 STUDY FAMILIAR LOOSE WHO HAVE 1847 01:36:24,240 --> 01:36:26,680 BEEN DOING THIS FOR SO MANY 1848 01:36:26,680 --> 01:36:27,000 YEARS. 1849 01:36:27,000 --> 01:36:32,760 WITH THAT I'LL END AND TAKE ANY 1850 01:36:32,760 --> 01:36:33,000 QUESTIONS. 1851 01:36:33,000 --> 01:36:35,840 >> QUESTIONS FOR MATT ON THAT 1852 01:36:35,840 --> 01:36:39,080 I'M REALLY INTERESTED TO SEE HOW 1853 01:36:39,080 --> 01:36:44,560 THE RHINITIS PHENOTYPE SHAPOUS 1854 01:36:44,560 --> 01:36:45,840 AND BETWEEN THE END OWE TYPES 1855 01:36:45,840 --> 01:36:48,560 FOR THE POPULATIONS THERE VERSUS 1856 01:36:48,560 --> 01:36:51,840 THE OS MOW PHENOTYPES? 1857 01:36:51,840 --> 01:36:57,520 >> THIS IS HOT OFF THE PRESS 1858 01:36:57,520 --> 01:36:58,960 YEAH, I THINK WE HAD A MEETING 1859 01:36:58,960 --> 01:37:00,920 THAT WAS GOING TO BE THIS WEEK 1860 01:37:00,920 --> 01:37:06,720 IT'S DELAYED A WEEK OR SOMETHING 1861 01:37:06,720 --> 01:37:08,960 BUT EVERYBODY CAN PUT THIS 1862 01:37:08,960 --> 01:37:10,160 TOGETHER AND I HAVE NOT 1863 01:37:10,160 --> 01:37:14,200 PERSONALLY SEEN THE OVERLAP OF 1864 01:37:14,200 --> 01:37:15,880 THE RHINITIS PHONE OWE TYPES BY 1865 01:37:15,880 --> 01:37:19,640 RESPIRATORY PHONE OWE TYPES THAT 1866 01:37:19,640 --> 01:37:25,880 WOULD BE TRANSRIPTOME. 1867 01:37:25,880 --> 01:37:27,560 >> I JUST HAVE A QUICK COMMENT 1868 01:37:27,560 --> 01:37:29,320 IT WILL TAKE TOO MUCH TIME TO 1869 01:37:29,320 --> 01:37:33,320 DISCUSS I HAD QUESTIONS FOR BOTH 1870 01:37:33,320 --> 01:37:35,040 CAROLE AND MATT BUT I'M VERY 1871 01:37:35,040 --> 01:37:39,480 INTERESTED IN THIS FINDINGS WITH 1872 01:37:39,480 --> 01:37:44,960 NISH AND THEN, IN MATT'S DATA I 1873 01:37:44,960 --> 01:37:49,400 ALSO SEE AM A IT'S A COMMENT AND 1874 01:37:49,400 --> 01:37:51,680 OUR COLLEAGUES HERE HAVE JUST 1875 01:37:51,680 --> 01:37:57,840 HAVE ISSUES A FEW MONTHS AGO IN 1876 01:37:57,840 --> 01:37:59,920 SCIENCING MACROPHAGES AND 1877 01:37:59,920 --> 01:38:01,920 HOMEOSTATIC FUNCTION IS 1878 01:38:01,920 --> 01:38:04,080 REGULATED WHICH CON STRAINS CYTO 1879 01:38:04,080 --> 01:38:07,680 SIGN EXPRESSION AS RISK TO 1880 01:38:07,680 --> 01:38:08,720 EXPRESSION AND I DON'T KNOW 1881 01:38:08,720 --> 01:38:10,800 WHETHER THERE'S A PARALLEL IN 1882 01:38:10,800 --> 01:38:12,360 THE FEMALE CELLS AND THAT IS 1883 01:38:12,360 --> 01:38:13,880 SOMETHING THAT COULD BE LOOKED 1884 01:38:13,880 --> 01:38:17,080 AT AND I WAS JUST WONDERING EVEN 1885 01:38:17,080 --> 01:38:20,000 IF YOUR WORLD QUICK SORT OF 1886 01:38:20,000 --> 01:38:24,800 LOOKS HAVE YOU SEEN ANY INVERSE 1887 01:38:24,800 --> 01:38:27,960 RELATIONSHIP BETWEEN THE TWO? 1888 01:38:27,960 --> 01:38:29,600 >> IT'S A GOOD QUESTION AND I'LL 1889 01:38:29,600 --> 01:38:33,480 SAY A WORD OR TWO AND I NOTICE 1890 01:38:33,480 --> 01:38:34,880 THAT ALSO AND SOMETIMES IT'S 1891 01:38:34,880 --> 01:38:37,400 GOOD TO HEAR OURSELVES PRESENT 1892 01:38:37,400 --> 01:38:40,720 TO ONE ANOTHER AND I SAW THAT 1893 01:38:40,720 --> 01:38:41,680 ASSOCIATION AS WELL AND WE HAVE 1894 01:38:41,680 --> 01:38:46,960 NOT DONE A LOT OF WORK LOOKING 1895 01:38:46,960 --> 01:38:49,760 AT FOR EXAMPLE HOW TWO GENES ARE 1896 01:38:49,760 --> 01:38:51,360 TOO MUCH AND WE'LL ASSOCIATE 1897 01:38:51,360 --> 01:38:53,800 WITH ONE ANOTHER SO THAT USEFUL 1898 01:38:53,800 --> 01:38:55,680 TO DO WITHIN THE FRAMEWORK AND 1899 01:38:55,680 --> 01:38:59,080 I'LL SAY YOU KNOW THIS IDEA OF 1900 01:38:59,080 --> 01:39:00,640 CAROLE HAS DONE THIS SORT OF 1901 01:39:00,640 --> 01:39:02,680 GENOME WIDE WITHIN THE WE'RE 1902 01:39:02,680 --> 01:39:05,000 EQUAL A COHORT AND MINING THAT 1903 01:39:05,000 --> 01:39:09,440 FOR ASSOCIATIONS AMONG TWO GENES 1904 01:39:09,440 --> 01:39:11,480 OR CANNING VALUABLE SO I CAN'T 1905 01:39:11,480 --> 01:39:15,400 ANSWER THE BIOLOGY YOU ARE 1906 01:39:15,400 --> 01:39:17,400 ASKING THERE AND WE SHOULD 1907 01:39:17,400 --> 01:39:18,960 PRIORITIZE BUT THIS DATA SET AND 1908 01:39:18,960 --> 01:39:25,120 FRAMEWORK ALLOWS US TO LOOK AT 1909 01:39:25,120 --> 01:39:29,320 THAT LEFT OF DETAILS AMONG 1910 01:39:29,320 --> 01:39:29,800 GENES. 1911 01:39:29,800 --> 01:39:31,040 AND MY BRIEF QUESTION I'LL ASK 1912 01:39:31,040 --> 01:39:33,160 YOU THIS NOT ENOUGH TIME, HAVE 1913 01:39:33,160 --> 01:39:34,760 YOU SEEN THIS IS SOMETHING WE 1914 01:39:34,760 --> 01:39:38,040 HAVE SEEN IN THE COHORT IN 1915 01:39:38,040 --> 01:39:41,800 SEVERE ASTHMA WE'RE SEEING IT 1916 01:39:41,800 --> 01:39:44,960 AND A VERY INTERESTING 1917 01:39:44,960 --> 01:39:46,720 RELATIONSHIP BETWEEN HIS TMP AND 1918 01:39:46,720 --> 01:39:48,520 TYPE ONE ASK TYPE TWO INTER 1919 01:39:48,520 --> 01:39:49,720 NEURONS AND HAVE YOU SEEN THAT 1920 01:39:49,720 --> 01:39:53,560 IN YOUR DATA AT ALL? 1921 01:39:53,560 --> 01:39:55,280 >> INCLUDING THE T CELLS IF. 1922 01:39:55,280 --> 01:39:56,880 >> I DON'T THINK WE'VE LOOKED AT 1923 01:39:56,880 --> 01:40:00,240 THAT RELATIONSHIP IN OUR DATA. 1924 01:40:00,240 --> 01:40:04,960 WORE SEEING AN OPPOSITE 1925 01:40:04,960 --> 01:40:05,200 EFFECTOR? 1926 01:40:05,200 --> 01:40:07,160 >> IT'S POSITIVE RELATIONSHIP. 1927 01:40:07,160 --> 01:40:13,960 >> YEAH, THIS IS NOT A TH2 1928 01:40:13,960 --> 01:40:14,160 FOCUS. 1929 01:40:14,160 --> 01:40:16,120 >> YEAH, EXACTLY. 1930 01:40:16,120 --> 01:40:18,080 >> IT'S VERY INTRIGUING. 1931 01:40:18,080 --> 01:40:19,920 >> I WOULD BE INTERESTED TO TALK 1932 01:40:19,920 --> 01:40:20,120 MORE. 1933 01:40:20,120 --> 01:40:23,080 >> YEAH. 1934 01:40:23,080 --> 01:40:26,160 SAME HERE. 1935 01:40:26,160 --> 01:40:29,000 >> ANY OTHER FINAL QUESTIONS I 1936 01:40:29,000 --> 01:40:31,360 THINK WE'RE JUST ABOUT AT THE 1937 01:40:31,360 --> 01:40:32,680 TIME WE WERE ALLOTTED. 1938 01:40:32,680 --> 01:40:38,880 BUT IF THERE'S ANY ADDITIONAL 1939 01:40:38,880 --> 01:40:40,040 QUESTIONS, PLEASE POP YOUR HAND 1940 01:40:40,040 --> 01:40:45,200 UP OR JUST SPEAK OUT. 1941 01:40:45,200 --> 01:40:46,480 IF NOT I WANT TO THANK YOU THE 1942 01:40:46,480 --> 01:40:49,000 THREE OF YOU AGAIN FOR REALLY 1943 01:40:49,000 --> 01:40:49,680 GREAT TALKS. 1944 01:40:49,680 --> 01:40:52,080 IT WAS A WONDERFUL ADDITION TO 1945 01:40:52,080 --> 01:40:55,680 COUNCIL THIS AFTERNOON. 1946 01:40:55,680 --> 01:40:57,000 AND I THINK WE'LL TURN THINGS 1947 01:40:57,000 --> 01:41:02,840 BACK OVER TO YOU. 1948 01:41:02,840 --> 01:41:05,000 >> GREAT. 1949 01:41:05,000 --> 01:41:07,000 THANK YOU. 1950 01:41:07,000 --> 01:41:12,240 PATRICE AND THANK YOU CAROLE, 1951 01:41:12,240 --> 01:41:13,120 JENN AND MATT FOR THOSE 1952 01:41:13,120 --> 01:41:17,040 PRESENTATION AND KEEPING US ON 1953 01:41:17,040 --> 01:41:17,240 TIME. 1954 01:41:17,240 --> 01:41:23,240 WE HAVE FOUR CONCEPT CLEARANCES 1955 01:41:23,240 --> 01:41:25,240 FOR DISCUSSION AND CONSIDERATION 1956 01:41:25,240 --> 01:41:27,040 BY COUNCIL AND WE'LL START WITH 1957 01:41:27,040 --> 01:41:34,560 THE FIRST OF THOSE IS CHAO JIANG 1958 01:41:34,560 --> 01:41:36,280 WILL PRESENT THE CONFERENCE 1959 01:41:36,280 --> 01:41:46,800 CLEARING ON HUMAN IMMUNOLOGY. 1960 01:41:51,680 --> 01:41:55,440 I SEE YOUR SLIDES BUT I DON'T 1961 01:41:55,440 --> 01:41:56,400 HEAR YOU. 1962 01:41:56,400 --> 01:42:06,840 POSSIBLE YOU ARE ON MUTE. 1963 01:42:07,880 --> 01:42:10,600 >> HI, JOE, I'M MUTED BUT WE'RE 1964 01:42:10,600 --> 01:42:13,800 STILL NOT GETTING SOUND RIGHT 1965 01:42:13,800 --> 01:42:13,960 NOW. 1966 01:42:13,960 --> 01:42:16,840 ARE YOU USING A HEADSET? 1967 01:42:16,840 --> 01:42:21,560 CHECK YOUR AUDIO SETTING ON THE 1968 01:42:21,560 --> 01:42:22,000 BOTTOM LEFT. 1969 01:42:22,000 --> 01:42:32,520 >> WE'RE STILL NOT HEARING YOU. 1970 01:42:32,760 --> 01:42:32,880 OK. 1971 01:42:32,880 --> 01:42:35,480 >> THAT'S GOOD. 1972 01:42:35,480 --> 01:42:37,160 WE CAN SEE YOU NOW BUT WE ONLY 1973 01:42:37,160 --> 01:42:40,600 GOT SOUND FOR A FEW MOMENTS. 1974 01:42:40,600 --> 01:42:41,560 CAN YOU HEAR ME NOW? 1975 01:42:41,560 --> 01:42:43,320 >> YES, GREAT. 1976 01:42:43,320 --> 01:42:49,200 I'M GOING TO RESUME AND SHARE 1977 01:42:49,200 --> 01:42:50,960 THE SCREEN AND SORRY ABOUT THE 1978 01:42:50,960 --> 01:42:51,560 TICK UP. 1979 01:42:51,560 --> 01:42:53,040 >> THANK YOU. 1980 01:42:53,040 --> 01:42:56,160 >> SORRY ABOUT THAT. 1981 01:42:56,160 --> 01:42:58,960 AND GOOD AFTERNOON. 1982 01:42:58,960 --> 01:43:00,840 MY NAME CHAO AND I'M A PROGRAM 1983 01:43:00,840 --> 01:43:02,880 OFFICER IN THE BASIC IMMUNOLOGY 1984 01:43:02,880 --> 01:43:03,960 BRANCH AND TODAY I WILL TALK 1985 01:43:03,960 --> 01:43:07,960 ABOUT THE RENEWAL OF COOPERATED 1986 01:43:07,960 --> 01:43:16,840 CENTERS OF HUMAN IMMUNOLOGY OF 1987 01:43:16,840 --> 01:43:21,800 PCHI. 1988 01:43:21,800 --> 01:43:23,840 IT HAS BEEN RENEWED THREE TIMES 1989 01:43:23,840 --> 01:43:26,680 AND THE CURRENT FAMILY CYCLE 1990 01:43:26,680 --> 01:43:30,080 STARTED IN 2019 AND CCHI IS 1991 01:43:30,080 --> 01:43:31,640 DESIGNED TO SUPPORT MECHANISTIC 1992 01:43:31,640 --> 01:43:34,280 AND HYPOTHESIS TESTING STUDIES 1993 01:43:34,280 --> 01:43:36,320 AND TO UNDERSTAND HUMAN IMMUNE 1994 01:43:36,320 --> 01:43:45,400 RESPONSES TO INFECTION AND THE 1995 01:43:45,400 --> 01:43:48,160 PROGRAM SUPPORTS THE CENTRALIZED 1996 01:43:48,160 --> 01:43:50,600 INFRASTRUCTURE TO COORDINATE 1997 01:43:50,600 --> 01:43:52,040 MULTI-DISCIPLINARY RESEARCH AND 1998 01:43:52,040 --> 01:43:54,520 THE DEVELOPMENT AND APPLICATIONS 1999 01:43:54,520 --> 01:43:56,720 OF INNOVATIVE TECHNOLOGIES AND 2000 01:43:56,720 --> 01:43:59,840 THE PROMOTING PUBLIC DATA 2001 01:43:59,840 --> 01:44:00,200 ACCESS. 2002 01:44:00,200 --> 01:44:03,240 SO THE CURRENT FUNDING MECHANISM 2003 01:44:03,240 --> 01:44:06,320 IS U19 CO-OPERATIVE AGREEMENT 2004 01:44:06,320 --> 01:44:08,880 AND WE HAVE EIGHT ACTIVE AWARDS 2005 01:44:08,880 --> 01:44:11,040 NOW AND THESE STUDIES COVERED A 2006 01:44:11,040 --> 01:44:15,920 BROAD SPECTRUM OF HUMAN IMMUNE 2007 01:44:15,920 --> 01:44:17,440 RESPONSES AND TO INFECTIONS, 2008 01:44:17,440 --> 01:44:20,920 VACCINES AND IMMUNO 2009 01:44:20,920 --> 01:44:21,520 THERAPEUTICS. 2010 01:44:21,520 --> 01:44:24,360 SO, IN THE PAST THROW YEARS, 2011 01:44:24,360 --> 01:44:26,160 OVER 300 PEER REVIEWED 2012 01:44:26,160 --> 01:44:28,040 PUBLICATIONS HAVE BEEN 2013 01:44:28,040 --> 01:44:30,280 ATTRIBUTED TO THE CCHI PROGRAM 2014 01:44:30,280 --> 01:44:32,040 AND SOME RESEARCH HIGHLIGHTS ARE 2015 01:44:32,040 --> 01:44:37,560 SHOWN ON THIS SLIDE. 2016 01:44:37,560 --> 01:44:39,240 YOU CAN TELL THEY IDENTIFY NEW 2017 01:44:39,240 --> 01:44:43,880 CELL POPULATIONS AND NEW 2018 01:44:43,880 --> 01:44:47,080 MECHANISMS OF IMMUNE REGULATION 2019 01:44:47,080 --> 01:44:49,200 AND SO WHEN COVID-19 PANDEMIC 2020 01:44:49,200 --> 01:44:51,880 HIT IN 2020, WHICH WAS BUILDING 2021 01:44:51,880 --> 01:44:54,960 THE FIRST YEAR OF THESE U19 2022 01:44:54,960 --> 01:45:02,240 AWARDS, ALL THE CC HI CENTERS 2023 01:45:02,240 --> 01:45:04,840 QUICKLY PIVOTED THEIR RESEARCH 2024 01:45:04,840 --> 01:45:09,520 TO THE COVID STUDIES WITH THE 2025 01:45:09,520 --> 01:45:10,160 DISCIPLINARY INFRASTRUCTURE AND 2026 01:45:10,160 --> 01:45:10,840 SO HE IS PHYSICAL INDICATED 2027 01:45:10,840 --> 01:45:14,880 TECHNOLOGIES IN PLACE, 2028 01:45:14,880 --> 01:45:17,120 CCHI/PIs HAVE BEEN HIGHLY 2029 01:45:17,120 --> 01:45:18,200 PRODUCTIVE AND MADE A 2030 01:45:18,200 --> 01:45:20,320 CONTRIBUTION TO THE FUNDAMENTAL 2031 01:45:20,320 --> 01:45:25,320 UNDERSTANDING OF COVID-19 2032 01:45:25,320 --> 01:45:25,600 IMMUNITY. 2033 01:45:25,600 --> 01:45:27,920 SO IN TERMS OF TECHNOLOGY 2034 01:45:27,920 --> 01:45:30,440 DEVELOPMENT, CCHI SUPPORTED THE 2035 01:45:30,440 --> 01:45:32,360 APPLICATIONS AND THE FURTHER 2036 01:45:32,360 --> 01:45:35,880 DEVELOPMENT OF TISSUE IMAGING 2037 01:45:35,880 --> 01:45:37,400 TECHNOLOGIES AND THE CRUSTER 2038 01:45:37,400 --> 01:45:42,640 BASED TCR REP TO BE ANALYSIS 2039 01:45:42,640 --> 01:45:43,320 TOOLS. 2040 01:45:43,320 --> 01:45:46,400 SPACIAL TRANSCRIPT TOMICS HAVE 2041 01:45:46,400 --> 01:45:49,480 SINGLE CELL SEQUENCING TO 2042 01:45:49,480 --> 01:45:50,880 IDENTIFY SPATIALLY SEPARATED 2043 01:45:50,880 --> 01:45:52,240 COMPARTMENTS IN TISSUE AND 2044 01:45:52,240 --> 01:45:54,360 SEVERAL X VIVO PLATFORMS TO 2045 01:45:54,360 --> 01:45:57,000 STUDY HUMAN IMMUNE RESPONSES, 2046 01:45:57,000 --> 01:46:00,160 HAVE ALSO BEEN DEVELOPED SUCH AS 2047 01:46:00,160 --> 01:46:04,640 STANFORD HUMAN COUNCIL ORGANOIDS 2048 01:46:04,640 --> 01:46:08,600 THAT RECAPITULATE FEATURES IN 2049 01:46:08,600 --> 01:46:10,800 VITRO AND LABS AT A CULTURE OF 2050 01:46:10,800 --> 01:46:13,880 HUMAN LUNG TISSUE AND THE 3D 2051 01:46:13,880 --> 01:46:16,480 FILE PRINTING OF BREATH ABLE 2052 01:46:16,480 --> 01:46:18,640 LONG MODEL THOSE ARE GREAT TOOLS 2053 01:46:18,640 --> 01:46:21,120 FOR STUDYING THE INTERACTIONS 2054 01:46:21,120 --> 01:46:24,600 BETWEEN IMMUNE CELLS AND ALLOW 2055 01:46:24,600 --> 01:46:29,000 EPITHELIUM POST INFECTION AND 2056 01:46:29,000 --> 01:46:34,440 THE VACCINATION. 2057 01:46:34,440 --> 01:46:36,000 IT'S TRAINING SERVICES TO 2058 01:46:36,000 --> 01:46:40,480 BENEFIT ALL LABORATORY WITHIN 2059 01:46:40,480 --> 01:46:45,440 THE KNELT WORK. 2060 01:46:45,440 --> 01:46:49,800 HERE ARE PAPERS BY THE CCHIPI 2061 01:46:49,800 --> 01:46:51,680 AND IDENTIFIED OF PEER 2062 01:46:51,680 --> 01:47:02,200 EXPRESSING REGULATORY CDAP AND 2063 01:47:08,400 --> 01:47:12,240 RYE MODELING O OF THE INNATE 2064 01:47:12,240 --> 01:47:16,840 IMMUNITY IN RESPONSE TO 2065 01:47:16,840 --> 01:47:27,200 INFLUENZA VACCINES. 2066 01:47:30,440 --> 01:47:33,200 IS THE IMMUNE SARS-CoV-2 BY 2067 01:47:33,200 --> 01:47:35,120 THE LA JOLLA GROUP THAT SHOWED 2068 01:47:35,120 --> 01:47:37,320 CROSS REACTIVE IMMUNE MEMORY 2069 01:47:37,320 --> 01:47:47,840 UNEXPOSED TO HEALTHY PEOPLE WE 2070 01:47:54,800 --> 01:48:03,000 DO WE CONTINUE THE CCHI PROGRAM. 2071 01:48:03,000 --> 01:48:05,320 MANY KNOWLEDGE GAPS STILL EXIST. 2072 01:48:05,320 --> 01:48:07,200 WE HAVE OUR LARGE BODY OF DATA 2073 01:48:07,200 --> 01:48:11,440 USING THE SYSTEM BIOLOGY 2074 01:48:11,440 --> 01:48:11,760 APPROACH. 2075 01:48:11,760 --> 01:48:13,560 IT'S CHALLENGING TO EXTRACT 2076 01:48:13,560 --> 01:48:16,000 KNOWLEDGE FROM THESE DATA AND 2077 01:48:16,000 --> 01:48:17,440 TRANSLATE THEM INTO BETTER 2078 01:48:17,440 --> 01:48:20,040 UNDERSTANDING OF IMMUNE 2079 01:48:20,040 --> 01:48:21,000 MECHANISMS. 2080 01:48:21,000 --> 01:48:22,480 THEREFORE, WE THINK IT'S 2081 01:48:22,480 --> 01:48:24,760 IMPORTANT TO CONTINUE TO SUPPORT 2082 01:48:24,760 --> 01:48:27,240 FUNDING PROGRAMS LIKE CCHI. 2083 01:48:27,240 --> 01:48:30,080 IF THIS RENEW CONCEPT IS 2084 01:48:30,080 --> 01:48:32,040 APPROVED, WE WANT TO CONTINUE TO 2085 01:48:32,040 --> 01:48:35,160 FOCUS ON DEFINING MOLECULAR 2086 01:48:35,160 --> 01:48:39,320 MECHANISMS OF HUMAN HUMAN IMMUE 2087 01:48:39,320 --> 01:48:41,720 REGULATION AND SUPPORT 2088 01:48:41,720 --> 01:48:42,960 CENTRALIZED THE INFRASTRUCTURE 2089 01:48:42,960 --> 01:48:47,040 TO PROMOTE AND COORDINATE 2090 01:48:47,040 --> 01:48:47,600 MULTI-DISCIPLINARY RESEARCH. 2091 01:48:47,600 --> 01:48:50,400 WHICH HAS BEEN PROVED TO BE 2092 01:48:50,400 --> 01:48:51,960 SUCCESSFUL IN REDIRECTING 2093 01:48:51,960 --> 01:48:54,120 RESEARCH FOCUS UNDER URGENT 2094 01:48:54,120 --> 01:48:59,440 PUBLIC-HEALTH SITUATIONS. 2095 01:48:59,440 --> 01:49:01,000 WE WANT TO SUPPORT DEVELOPMENT 2096 01:49:01,000 --> 01:49:03,440 OF INNOVATIVE TECHNOLOGIES TO 2097 01:49:03,440 --> 01:49:08,360 FACILITATE IMMUNE STUDIES IN 2098 01:49:08,360 --> 01:49:08,680 HUMANS. 2099 01:49:08,680 --> 01:49:13,040 SO WE WANT TONE COURAGE ANALYZE 2100 01:49:13,040 --> 01:49:16,160 THE CONSEQUENCES OF INFECTION 2101 01:49:16,160 --> 01:49:17,920 AND VACCINATION IN POPULATION 2102 01:49:17,920 --> 01:49:19,360 WITH CO-MORBIDITY AND TO LOOK AT 2103 01:49:19,360 --> 01:49:26,680 THE IMPACTS OF PRO EXISTING 2104 01:49:26,680 --> 01:49:27,600 IMMUNITY ON SUBSEQUENT INFECTION 2105 01:49:27,600 --> 01:49:29,640 OR VACCINATION AND A STUDY 2106 01:49:29,640 --> 01:49:34,400 FOCUSING ON MECHANISMS OF IMMUNE 2107 01:49:34,400 --> 01:49:36,160 DISEASES. 2108 01:49:36,160 --> 01:49:38,360 IDENTICAL TO THE CURRENT 2109 01:49:38,360 --> 01:49:44,440 ITERATION, WE WERE ALLOWED SMALL 2110 01:49:44,440 --> 01:49:45,880 MECHANISTIC CLINICAL TRIALS AND 2111 01:49:45,880 --> 01:49:47,760 PERMIT ANIMAL STUDIES THAT 2112 01:49:47,760 --> 01:49:49,920 EXTEND OR GUIDE MECHANISTIC 2113 01:49:49,920 --> 01:50:00,200 ANALYSIS OF HUMAN SAMPLES AND SO 2114 01:50:00,200 --> 01:50:03,520 CO-OPERATIVE AND MECHANISMS AND 2115 01:50:03,520 --> 01:50:06,840 SO, I'LL STOP HERE AND I'M HAPPY 2116 01:50:06,840 --> 01:50:17,200 TO TAKE ANY QUESTIONS. 2117 01:50:19,360 --> 01:50:22,720 LET ME JUST REMIND COUNCIL 2118 01:50:22,720 --> 01:50:23,640 MEMBERS OR MEMBERS OF THE PUBLIC 2119 01:50:23,640 --> 01:50:30,720 WHO ARE IN THE CALL TO RAISE 2120 01:50:30,720 --> 01:50:41,200 YOUR HAND OR GO ON VIDEO AND 2121 01:50:45,040 --> 01:50:51,480 WHEN YOU SPEAK GO ON VIDEO. 2122 01:50:51,480 --> 01:50:56,280 >> I HAVE A QUESTION, I SEE 2123 01:50:56,280 --> 01:51:01,080 UNDER SCOPE, THIS IMPACT OF THE 2124 01:51:01,080 --> 01:51:04,520 EXISTING AND INFECTION AND 2125 01:51:04,520 --> 01:51:08,200 VACCINATION AND THIS COMES TO 2126 01:51:08,200 --> 01:51:10,800 MIND THE ASSOCIATION OF THESE 2127 01:51:10,800 --> 01:51:11,680 STUDIES WITH MACHINE LEARNING 2128 01:51:11,680 --> 01:51:17,600 AND ARTIFICIAL INTELLIGENCE AND 2129 01:51:17,600 --> 01:51:20,200 INCORPORATE AND THIS WITH ALSO 2130 01:51:20,200 --> 01:51:24,640 MORE COMPUTATIONAL EFFORTS AND 2131 01:51:24,640 --> 01:51:26,680 TO HARNESS ON VAST AMOUNTS OF 2132 01:51:26,680 --> 01:51:29,040 PREDICTIONS AND THINGS THAT OF 2133 01:51:29,040 --> 01:51:29,280 NATURE. 2134 01:51:29,280 --> 01:51:33,520 >> THAT'S A GOOD SUGGESTION AND 2135 01:51:33,520 --> 01:51:37,520 THE CCHI GROUP AT THIS TYPE OF 2136 01:51:37,520 --> 01:51:40,240 EFFORT IS ON GOING RIGHT NOW AND 2137 01:51:40,240 --> 01:51:44,600 HOWEVER, I THINK WE NEED 2138 01:51:44,600 --> 01:51:50,160 ENCOURAGE MORE LIKE STUDIES AND 2139 01:51:50,160 --> 01:51:57,520 THERE ARE COVID REALLY BROWN UP 2140 01:51:57,520 --> 01:52:07,880 THE OPPORTUNITY OF USING MACHINE 2141 01:52:07,880 --> 01:52:09,560 LEARNING PROGRAMS TO PREDICT 2142 01:52:09,560 --> 01:52:11,440 OUTCOMES, ON THE OTHER HAND, I 2143 01:52:11,440 --> 01:52:14,040 THINK THAT'S WHAT BCHI IS 2144 01:52:14,040 --> 01:52:19,160 PERFECTLY FOR IS TO SUBSEQUENT 2145 01:52:19,160 --> 01:52:23,000 TO DO THE MECHANISTIC STUDY TO 2146 01:52:23,000 --> 01:52:24,520 VALIDATE THAT PREDICTION IN 2147 01:52:24,520 --> 01:52:26,400 EITHER THE HUMAN COHORT OR 2148 01:52:26,400 --> 01:52:30,360 PRIMARY HUMAN CELLS OR EVEN 2149 01:52:30,360 --> 01:52:31,080 ANIMAL MODEL. 2150 01:52:31,080 --> 01:52:31,640 >> THANK YOU. 2151 01:52:31,640 --> 01:52:34,920 >> THANK YOU. 2152 01:52:34,920 --> 01:52:45,360 >> SO IF THERE ARE NO OTHER 2153 01:52:53,800 --> 01:52:54,360 COMMENTS OR QUESTIONS. 2154 01:52:54,360 --> 01:52:57,000 IN THE INTEREST OF TIME, WE'LL 2155 01:52:57,000 --> 01:52:59,640 ASK YOU FOR AN ON BLOCK 2156 01:52:59,640 --> 01:53:01,280 RECOMMENDATION AT THE END OF THE 2157 01:53:01,280 --> 01:53:04,680 FOUR PRESENTATIONS. 2158 01:53:04,680 --> 01:53:07,520 AND IN THAT CASE WE CAN MOVE ON 2159 01:53:07,520 --> 01:53:09,240 TO MERCY, YOU ARE GOING TO 2160 01:53:09,240 --> 01:53:12,560 PRESENT THE IMMUNITY IN OLDER 2161 01:53:12,560 --> 01:53:23,000 ADULTS CONCEPT CLEARANCE. 2162 01:53:41,160 --> 01:53:43,320 >> GOOD AFTERNOON, I'LL BE 2163 01:53:43,320 --> 01:53:45,800 PRESENTING THIS CONCEPT ON 2164 01:53:45,800 --> 01:53:55,200 IMMUNITY IN OLDER ADULTS FO FY2. 2165 01:53:55,200 --> 01:53:58,720 SO AS WE KNOW, RELATED TO AGE 2166 01:53:58,720 --> 01:54:04,560 DECLINES IN IMMUNE FUNCTION AND 2167 01:54:04,560 --> 01:54:06,240 THEY ARE ARE A VARIETY OF 2168 01:54:06,240 --> 01:54:13,520 DECLINES THAT ARE SEEN LOOKING 2169 01:54:13,520 --> 01:54:16,120 AT INNATE SYSTEMS AS WELL AS 2170 01:54:16,120 --> 01:54:19,960 VACCINE EFFICIENCY AND DIVERSITY 2171 01:54:19,960 --> 01:54:23,760 AND IT'S LOW GRADE CHRONIC 2172 01:54:23,760 --> 01:54:27,960 INFLAMMATION THAT CONTINUES IN 2173 01:54:27,960 --> 01:54:32,600 OLDER AGE AND SO THE -- JUST TO 2174 01:54:32,600 --> 01:54:36,360 GIVE YOU A QUICK BACKGROUND OF 2175 01:54:36,360 --> 01:54:41,760 THIS PROGRAM, IT BEGAN IN 2009 2176 01:54:41,760 --> 01:54:48,480 AND THE -- WITH REJUVENATION IN 2177 01:54:48,480 --> 01:54:55,760 ANIMAL MODELS FOCUSING ON THE 2178 01:54:55,760 --> 01:55:00,600 THYMIC AND THE STUDIES AND THEN 2179 01:55:00,600 --> 01:55:04,200 IN THE SUBSEQUENT ITERATION OF 2180 01:55:04,200 --> 01:55:06,880 THIS PROGRAM, IT WAS THEN WHERE 2181 01:55:06,880 --> 01:55:12,400 WE INCLUDE HUMAN STUDIES, IT WAS 2182 01:55:12,400 --> 01:55:14,200 SPECIFICALLY FOR THE ELDERLY 2183 01:55:14,200 --> 01:55:15,920 WHERE WE HAD HUMAN STUDIES AS 2184 01:55:15,920 --> 01:55:21,280 WELL AS ANIMAL STUDIES AND THEN, 2185 01:55:21,280 --> 01:55:31,800 IN ALL THE AND WE HAVE A VARIETY 2186 01:55:39,920 --> 01:55:43,440 OF CO-SPONSORS AND CURRENTLY 2187 01:55:43,440 --> 01:55:47,440 ONLY NIA AND NIAID ARE THE ONES 2188 01:55:47,440 --> 01:55:51,080 THAT IN THE PROGRAM AND THE ONE 2189 01:55:51,080 --> 01:55:57,440 SUNSHINE AND AVAILABLE FOR 2190 01:55:57,440 --> 01:55:59,080 ANYTHING. 2191 01:55:59,080 --> 01:56:02,760 SO SOME OF THE KEY 2192 01:56:02,760 --> 01:56:06,600 ACCOMPLISHMENTS ASSOCIATED WITH 2193 01:56:06,600 --> 01:56:10,840 THIS PROGRAM, AGE ASSOCIATED 2194 01:56:10,840 --> 01:56:20,640 WITH AGE AND INDEPENDENT AND AND 2195 01:56:20,640 --> 01:56:26,920 PHENOTYPE BY A SMALL PREPORTION 2196 01:56:26,920 --> 01:56:30,840 OF -- THAT COULD INCLUDE UP 2197 01:56:30,840 --> 01:56:34,000 REGULATION OF MARKERS OR 2198 01:56:34,000 --> 01:56:37,760 INCREASED REACTIVE ISSUES AND 2199 01:56:37,760 --> 01:56:39,320 THEN INTEGRATION OF VARIOUS 2200 01:56:39,320 --> 01:56:42,000 CHANGES THAT UNDER LIE HEALTHY 2201 01:56:42,000 --> 01:56:46,600 VERSUS DYSFUNCTIONAL OR 2202 01:56:46,600 --> 01:56:48,120 DIS-REGULATED CONDITIONS THAT 2203 01:56:48,120 --> 01:56:53,520 WOULD ALSO HELP TO CREATE USEFUL 2204 01:56:53,520 --> 01:56:54,360 IMMUNE HEALTH GRADE. 2205 01:56:54,360 --> 01:56:58,160 THIS COULD INCLUDE ACCELERATED 2206 01:56:58,160 --> 01:57:01,000 OR PREMATURE PHENOTYPES WITH 2207 01:57:01,000 --> 01:57:02,680 CHRONOLOGICAL VERSUS BIOLOGICAL 2208 01:57:02,680 --> 01:57:03,640 AGE AND CURRENTLY THE 2209 01:57:03,640 --> 01:57:05,440 INVESTIGATORS IN THE PROGRAM 2210 01:57:05,440 --> 01:57:07,080 HAVE ACCOMPLISHED ALMOST 50 2211 01:57:07,080 --> 01:57:11,280 RESEARCH PUBLICATIONS. 2212 01:57:11,280 --> 01:57:13,040 AND I'D LIKE TO JUST GIVE A FEW 2213 01:57:13,040 --> 01:57:14,760 EXAMPLES OF FINDINGS FROM THE 2214 01:57:14,760 --> 01:57:15,440 PROGRAM. 2215 01:57:15,440 --> 01:57:19,240 AND THE FIRST ONE IS WHERE 2216 01:57:19,240 --> 01:57:22,040 AUTOIMMUNE C TELLS AND THE SO IN 2217 01:57:22,040 --> 01:57:25,640 THIS CASE, A STUDY FROM THE LAB 2218 01:57:25,640 --> 01:57:30,040 REPORTED A DEFECT IN THE DNA 2219 01:57:30,040 --> 01:57:34,280 REPAIR MECHANISM IN T CELLS THAT 2220 01:57:34,280 --> 01:57:37,240 BANKRUPTED IN REPAIR AND ON THE 2221 01:57:37,240 --> 01:57:39,640 MRE11A AND THOSE EFFECTIVE IN T 2222 01:57:39,640 --> 01:57:45,000 CELLS IN PATIENTS WITH RA AND 2223 01:57:45,000 --> 01:57:47,000 THE ARTHRITIS AND THEY SHOWED 2224 01:57:47,000 --> 01:57:48,920 THAT THE LOSS OF FUNCTION OF 2225 01:57:48,920 --> 01:57:54,840 THIS NEW NUCLEUS RESULTED IN 2226 01:57:54,840 --> 01:57:59,680 MITOCHONDRIAL FAILURE AND TISSUE 2227 01:57:59,680 --> 01:58:06,120 MTDNA AND PROMOTING TISSUE 2228 01:58:06,120 --> 01:58:06,560 INFORMATION. 2229 01:58:06,560 --> 01:58:13,240 AND ANOTHER GROUP, IDENTIFIED 2230 01:58:13,240 --> 01:58:23,600 AND CELL EYE EXPRESS IT SHOWED 2231 01:58:23,600 --> 01:58:25,960 THE FACTORS THAT DEFINE THIS 2232 01:58:25,960 --> 01:58:27,600 POPULATION AND THEN OLDER AND 2233 01:58:27,600 --> 01:58:30,800 YOUNGER ADULTS AND SO WE FIND 2234 01:58:30,800 --> 01:58:32,960 THAT THE YOUNG ADULT HAD THE 2235 01:58:32,960 --> 01:58:35,360 POPULATION OF MEMORY T CELLS 2236 01:58:35,360 --> 01:58:38,760 WHICH WERE CHARACTERIZED BY 2237 01:58:38,760 --> 01:58:39,840 SEVERAL TRANSCRIPTION FACTORS 2238 01:58:39,840 --> 01:58:42,320 TWO AND THROW AND EOMES FOR 2239 01:58:42,320 --> 01:58:45,640 EXAMPLE AND WE HAVE THE OLDER 2240 01:58:45,640 --> 01:58:48,960 POPULATION THEY FOUND THAT THE 2241 01:58:48,960 --> 01:58:53,680 MEMORY T-CELL POPULATION HAD NO 2242 01:58:53,680 --> 01:58:55,280 AMOUNTS OF, THEY ACTUALLY SAW 2243 01:58:55,280 --> 01:58:57,000 THE DECREASE IN THE POPULATION 2244 01:58:57,000 --> 01:59:04,680 OF THE CD PRODUCT CELLS AND THEN 2245 01:59:04,680 --> 01:59:15,240 FROM THE GROUPS, THEY FOUND THAT 2246 01:59:44,400 --> 01:59:49,760 THESE CD8 CELLS TO BE MORE MK 2247 01:59:49,760 --> 02:00:00,320 LIKE AND AND THE RENEWAL OF THE 2248 02:00:01,680 --> 02:00:05,480 PROGRAM IN 24, THE PROPOSED 2249 02:00:05,480 --> 02:00:08,240 SUPPORTING STUDIES WHICH DEFINE 2250 02:00:08,240 --> 02:00:10,720 MECHANISMS THAT CONTRIBUTE IN 2251 02:00:10,720 --> 02:00:13,840 THE DYSFUNCTION AND LOOK AT VERY 2252 02:00:13,840 --> 02:00:17,360 STRATEGIES INCLUDING IMPROVING 2253 02:00:17,360 --> 02:00:19,640 HOSTING IMMUNE FUNCTION AND 2254 02:00:19,640 --> 02:00:23,520 INFECTIONS IN OLDER ADULTS AND 2255 02:00:23,520 --> 02:00:25,480 WE ALSO WANT TO ENCOURAGE FOLKS 2256 02:00:25,480 --> 02:00:29,360 TO USE SAMPLES FROM HUMAN 2257 02:00:29,360 --> 02:00:31,360 COHORTS THAT ARE ESTABLISHED OR 2258 02:00:31,360 --> 02:00:34,800 FROM CURRENTLY INDEPENDENTLY 2259 02:00:34,800 --> 02:00:37,240 CLIN TAL TRIALS OR THEY COULD 2260 02:00:37,240 --> 02:00:38,400 ALSO ESTABLISH NEW COHORTS TO 2261 02:00:38,400 --> 02:00:41,760 STUDY THE HUMAN FUNCTION AND FOR 2262 02:00:41,760 --> 02:00:43,880 THE FUTURE EMPHASIS AND ALSO 2263 02:00:43,880 --> 02:00:45,800 ENCLOUD LOCKING AT MECHANISMS 2264 02:00:45,800 --> 02:00:49,080 AND IMPACT OF VARIOUS ANALYTICS 2265 02:00:49,080 --> 02:00:53,680 WHICH ARE DRUGS THAT DESTROY AND 2266 02:00:53,680 --> 02:00:58,840 LOCK AT EPI GENETIC CHANGES AND 2267 02:00:58,840 --> 02:01:00,840 VACCINE AND RESPONSES TO 2268 02:01:00,840 --> 02:01:02,160 MECHANISMS OF AGING AND THEN IN 2269 02:01:02,160 --> 02:01:05,440 THE PAST FEW YEARS, THERE'S ALSO 2270 02:01:05,440 --> 02:01:07,520 BEEN VARIOUS TOOLS DEVELOPED TO 2271 02:01:07,520 --> 02:01:09,280 MONITOR IMMUNE HEALTH AND 2272 02:01:09,280 --> 02:01:14,960 LOOKING AT AGE OR AIAS WHICH 2273 02:01:14,960 --> 02:01:16,840 HAVE DIFFERENT TOOLS THAT FOLKS 2274 02:01:16,840 --> 02:01:19,880 HAVE COME UP WITH BASED ON THIS 2275 02:01:19,880 --> 02:01:23,760 STUDY LOOKING AT THE AND 2276 02:01:23,760 --> 02:01:26,280 EXPRESSION OR OTHER IMMUNO 2277 02:01:26,280 --> 02:01:29,560 METRICS OR ALSO LOOKING AT AND 2278 02:01:29,560 --> 02:01:34,880 WHETHER IT'S AGING RELATED AND 2279 02:01:34,880 --> 02:01:40,240 AGING INDEPENDENT AND SO WE AND 2280 02:01:40,240 --> 02:01:41,000 CONTINUE OUR PARTNERSHIP WITH 2281 02:01:41,000 --> 02:01:44,080 THE AGING INSTITUTE AND WE'D 2282 02:01:44,080 --> 02:01:48,440 LIKE TO HAVE THIS MECHANISM BE 2283 02:01:48,440 --> 02:01:50,440 THE MECHANIC IN THE NEXT 2284 02:01:50,440 --> 02:01:53,640 ITERATION AND SO IF YOU HAVE ANY 2285 02:01:53,640 --> 02:01:58,600 QUESTIONS WE'LL BE TO THANK YOU, 2286 02:01:58,600 --> 02:02:03,760 VERY MUCH. 2287 02:02:10,800 --> 02:02:12,240 >> I'M SORRY, I AM NOT ABLE TO 2288 02:02:12,240 --> 02:02:15,520 TURN ON MY VIDEO. 2289 02:02:15,520 --> 02:02:24,240 IT WOULD INCLUDE CLINICAL. 2290 02:02:24,240 --> 02:02:25,400 >> YES, IT WOULD. 2291 02:02:25,400 --> 02:02:28,680 >> OK. 2292 02:02:28,680 --> 02:02:37,720 >> YOU ARE PLANNING TO BRING THE 2293 02:02:37,720 --> 02:02:44,760 GROUPS TOGETHER PERIODICALLY WE 2294 02:02:44,760 --> 02:02:46,200 WILL BRING THE GROUPS TOGETHER 2295 02:02:46,200 --> 02:02:49,240 AND WE'LL HAVE ENCOURAGE 2296 02:02:49,240 --> 02:02:52,200 COLLABORATION AND ACROSS VARIOUS 2297 02:02:52,200 --> 02:02:53,360 CENTERS OR GROUPS BASICALLY, 2298 02:02:53,360 --> 02:03:03,840 THAT'S WHAT WE'D LIKE TO DO. 2299 02:03:21,080 --> 02:03:23,760 CONRAD, LET'S MOVE ON. 2300 02:03:23,760 --> 02:03:24,320 MAINTAINING DAY AFTER 2301 02:03:24,320 --> 02:03:26,520 VACCINATION AND INFECTION. 2302 02:03:26,520 --> 02:03:29,240 >> I HAD A LITTLE TROUBLE WITH 2303 02:03:29,240 --> 02:03:30,160 THE SHARING. 2304 02:03:30,160 --> 02:03:32,560 I DON'T KNOW WHY, SO ERIC IS 2305 02:03:32,560 --> 02:03:35,560 GOING TO BRING IT UP. 2306 02:03:35,560 --> 02:03:36,880 THANK YOU, ERIC. 2307 02:03:36,880 --> 02:03:38,480 AND I'M JUST GOING TO ADVANCE 2308 02:03:38,480 --> 02:03:44,520 THE SLIDES VERBALLY WITH HIM. 2309 02:03:44,520 --> 02:03:46,280 THIS IS INITIATIVE IS 2310 02:03:46,280 --> 02:03:48,560 MAINTAINING IMMUNITY AFTER 2311 02:03:48,560 --> 02:03:48,920 IMMUNIZATION. 2312 02:03:48,920 --> 02:03:51,920 IT WAS INITIATED IN 2019 AND 2313 02:03:51,920 --> 02:03:55,760 THIS IS A RENEWAL OF THAT 2314 02:03:55,760 --> 02:03:56,240 INITIATIVE. 2315 02:03:56,240 --> 02:03:57,400 NEXT SLIDE, PLEASE. 2316 02:03:57,400 --> 02:04:01,000 SO THE BACKGROUND. 2317 02:04:01,000 --> 02:04:02,480 THE DURABILITY OF VACCINES 2318 02:04:02,480 --> 02:04:04,120 PROTECTION VARIES AS WE VARY 2319 02:04:04,120 --> 02:04:07,440 WELL KNOW NOW. 2320 02:04:07,440 --> 02:04:08,400 AND SMALLPOX VACCINES CAN 2321 02:04:08,400 --> 02:04:12,400 PRODUCE LIFETIME OF IMMUNITY AND 2322 02:04:12,400 --> 02:04:18,200 THE SARS-CoV-2 VACCINE AND 2323 02:04:18,200 --> 02:04:22,360 SOME PERTUSSIS VACCINES CAN ONLY 2324 02:04:22,360 --> 02:04:23,560 PROTECT FOR A FEW YEARS AND 2325 02:04:23,560 --> 02:04:25,200 MONTHS AND WE WANT TO DEFINE WHY 2326 02:04:25,200 --> 02:04:27,120 THAT IS AND SO A BETTER 2327 02:04:27,120 --> 02:04:28,160 UNDERSTANDING OF THE IMMUNE 2328 02:04:28,160 --> 02:04:29,520 MECHANISMS AND THE COMPONENTS 2329 02:04:29,520 --> 02:04:31,680 THAT LEAD TO THE SUSTAINED 2330 02:04:31,680 --> 02:04:35,280 IMMUNITY CAN HELP TO DESIGN IN 2331 02:04:35,280 --> 02:04:39,320 VACCINES.DOU DESIGN OF FUTURE 2332 02:04:39,320 --> 02:04:45,160 THIS IS MENTIONED BEFORE, THAT S 2333 02:04:45,160 --> 02:04:46,480 SUPPORTING GRANTS AND WE 2334 02:04:46,480 --> 02:04:48,120 CURRENTLY HAVE SEVEN THEM. 2335 02:04:48,120 --> 02:04:56,000 AND NEXT SLIDE. 2336 02:04:56,000 --> 02:04:59,080 SO FAR SINCE 2019 WE'VE HAD 54 2337 02:04:59,080 --> 02:05:01,880 PUBLICATION AND A LOT OF THEM IN 2338 02:05:01,880 --> 02:05:03,520 HIGH I AM IMPACT JOURNALS AND I 2339 02:05:03,520 --> 02:05:05,640 THOUGHT I WOULD MENTION A FEW 2340 02:05:05,640 --> 02:05:08,120 HIGHLIGHTS OF THE THINGS THAT 2341 02:05:08,120 --> 02:05:10,840 WE'VE DONE AND THAT ISOLATION 2342 02:05:10,840 --> 02:05:14,480 AND CHARACTERIZATION OF 2343 02:05:14,480 --> 02:05:22,480 INFLUENZA ANTIBODIES AND IT 2344 02:05:22,480 --> 02:05:25,240 SEEMS TO PROTECT AGAINST 2345 02:05:25,240 --> 02:05:28,600 INFLUENZA INFECTION AND MOUSE 2346 02:05:28,600 --> 02:05:38,800 MODELS AND. 2347 02:05:46,720 --> 02:05:51,720 >> WE KNOW MORE ABOUT THIS THIS 2348 02:05:51,720 --> 02:05:53,480 WAS A LITTLE WHILE AGO AND IT'S 2349 02:05:53,480 --> 02:05:54,840 IMPORTANT TO CHARACTERIZE BUT 2350 02:05:54,840 --> 02:06:01,720 THIS IMMUNE RESPONSE IS. 2351 02:06:01,720 --> 02:06:12,160 AND WHICH IS TALKING ABOUT 2352 02:06:15,520 --> 02:06:25,240 VACCINATION AND AND IT SEEMS TO 2353 02:06:25,240 --> 02:06:29,440 CONCERN COMPONENTS OF THE T-CELL 2354 02:06:29,440 --> 02:06:33,840 RESPONSE AND EVEN A LITTLE BIT 2355 02:06:33,840 --> 02:06:36,760 OF THE HUMORAL IMMUNE TONS AND 2356 02:06:36,760 --> 02:06:38,360 JUST ANOTHER FINDING IS 2357 02:06:38,360 --> 02:06:42,480 PROTECTIVE IMMUNITY REQUIRES 2358 02:06:42,480 --> 02:06:45,440 BOTH NAIVE AND MEMORY B CELLS 2359 02:06:45,440 --> 02:06:49,240 AND INFLUENZA BACK SCENES 2360 02:06:49,240 --> 02:06:52,480 INDUCED LIP SNOWED CENTERS 2361 02:06:52,480 --> 02:06:56,480 STRUCTURES AND THIS INVOLVES 2362 02:06:56,480 --> 02:06:58,680 CROSS HYBRID IMMUNITY AND NOT 2363 02:06:58,680 --> 02:07:09,240 HYBRID IMMUNITY AND BECAUSE THIS 2364 02:07:09,680 --> 02:07:15,760 IS SOMETHING THAT IS A NEW 2365 02:07:15,760 --> 02:07:26,240 ANTIGEN I JUST WANTED TO SHOW 2366 02:07:28,600 --> 02:07:30,080 YOU WHAT THESE JOURNALS, THESE 2367 02:07:30,080 --> 02:07:33,680 WERE IN AND THESE FINDINGS AND 2368 02:07:33,680 --> 02:07:34,520 NEXT SLIDE. 2369 02:07:34,520 --> 02:07:37,120 SO, THE RENEWAL. 2370 02:07:37,120 --> 02:07:38,520 IS THE OBJECTIVES ARE TO DEFINE 2371 02:07:38,520 --> 02:07:41,240 THE IMMUNE COMPONENTS THAT ARE 2372 02:07:41,240 --> 02:07:42,160 STIMULATED AFTER VACCINATION IT 2373 02:07:42,160 --> 02:07:46,040 WAS THE ORIGINAL AND WE'RE STILL 2374 02:07:46,040 --> 02:07:48,480 PURSUING THAT AND DETERMINE HOW 2375 02:07:48,480 --> 02:07:49,800 THESE RELATE TOWN DUCK AND 2376 02:07:49,800 --> 02:07:52,400 MAINTENANCE OF PERSISTENT IMMUNE 2377 02:07:52,400 --> 02:07:52,640 RESPONSES. 2378 02:07:52,640 --> 02:07:55,160 AND MAKE THAT CONNECTION TO BE 2379 02:07:55,160 --> 02:07:58,000 FOCUSED ON THAT CONNECT AND THEN 2380 02:07:58,000 --> 02:07:59,920 WE'RE TRYING TO HOPE TO GET 2381 02:07:59,920 --> 02:08:02,080 PROJECTS WHICH WOULD DEFINE 2382 02:08:02,080 --> 02:08:03,400 DIFFERENCES BETWEEN HUMOR ALL 2383 02:08:03,400 --> 02:08:05,640 AND CELLULAR IMMUNE RESPONSE AND 2384 02:08:05,640 --> 02:08:08,520 WORE GOING TO ASK FOR THAT AND 2385 02:08:08,520 --> 02:08:10,960 COMPARED TO INFECTION AND THE 2386 02:08:10,960 --> 02:08:12,920 RESPONSE AFTER INFECTION 2387 02:08:12,920 --> 02:08:14,120 COMPARED TO VACCINATION. 2388 02:08:14,120 --> 02:08:16,680 AND TO SEE HOW THAT EFFECTS THE 2389 02:08:16,680 --> 02:08:18,920 DURABILITY OF IMMUNITY. 2390 02:08:18,920 --> 02:08:21,400 AND TO REEMPHASIZE IMPORTANT 2391 02:08:21,400 --> 02:08:23,760 EMERGING AREAS THAT WE HAVE NOT 2392 02:08:23,760 --> 02:08:24,800 DISCOVERED AS MUCH IN OUR 2393 02:08:24,800 --> 02:08:26,440 CURRENT PROGRAMS FOR EXAMPLE, 2394 02:08:26,440 --> 02:08:28,040 TISSUE RESIDENT MEMORY, VERY 2395 02:08:28,040 --> 02:08:32,840 IMPORTANT, RIGHT, AND THE IMMUNO 2396 02:08:32,840 --> 02:08:34,760 MA TAB LOAM AND THE FUNDING 2397 02:08:34,760 --> 02:08:37,880 MECHANISM IS GOING TO BE UO1 2398 02:08:37,880 --> 02:08:40,040 CO-OPERATIVE AGREEMENT AND RO1 2399 02:08:40,040 --> 02:08:40,760 SIZE GRANTS AND WE ANTICIPATE 2400 02:08:40,760 --> 02:08:43,520 ABOUT MAKING ABOUT FIVE TO EIGHT 2401 02:08:43,520 --> 02:08:43,880 AWARDS. 2402 02:08:43,880 --> 02:08:48,680 AND I THINK THAT'S THE LAST 2403 02:08:48,680 --> 02:08:49,000 SLIDE. 2404 02:08:49,000 --> 02:08:52,960 I'LL TAKE ANY QUESTIONS THAT YOU 2405 02:08:52,960 --> 02:09:00,040 HAVE NOW. 2406 02:09:00,040 --> 02:09:03,480 SORRY FOR THE BACKGROUND LAWN 2407 02:09:03,480 --> 02:09:03,960 MOW ARE NOISE. 2408 02:09:03,960 --> 02:09:05,960 I DON'T KNOW IF YOU HEAR THAT. 2409 02:09:05,960 --> 02:09:16,440 IT HAPPENED ALL OF A SUDDEN. 2410 02:09:18,960 --> 02:09:25,960 >> WELL IT'S ALL QIU ET O QUIE. 2411 02:09:25,960 --> 02:09:28,760 WE'LL MOVE ON TO CENTERS OF 2412 02:09:28,760 --> 02:09:33,080 EXCELLENCE, DAVID, YOU ARE UP. 2413 02:09:33,080 --> 02:09:40,160 >> THANK YOU. 2414 02:09:40,160 --> 02:09:41,160 THIS SHOULD BE SHOWING. 2415 02:09:41,160 --> 02:09:44,360 >> IT IS AND WE CAN HEAR YOU 2416 02:09:44,360 --> 02:09:44,920 THIS TIME. 2417 02:09:44,920 --> 02:09:45,880 THANK YOU. 2418 02:09:45,880 --> 02:09:47,200 OK, SO GOOD AFTERNOON, I WILL 2419 02:09:47,200 --> 02:09:49,320 PRESENT THE RENEWAL OF THE 2420 02:09:49,320 --> 02:09:52,200 AUTOIMMUNITY CENTERS OF 2421 02:09:52,200 --> 02:09:56,440 EXCELLENCE ABBREVIATED ACE. 2422 02:09:56,440 --> 02:10:00,040 THE PROGRAM PURPOSE IS TO 2423 02:10:00,040 --> 02:10:01,600 EXCELERATE TRANSITION OF LAB TO 2424 02:10:01,600 --> 02:10:03,120 THE CLINIC OF NEW THERAPIES 2425 02:10:03,120 --> 02:10:04,560 AUTOIMMUNE DISEASES AND IMPROVE 2426 02:10:04,560 --> 02:10:07,520 THE FUNDAMENTAL UNDERSTANDING OF 2427 02:10:07,520 --> 02:10:08,800 OUR CURRENT THERAPIES AND THE 2428 02:10:08,800 --> 02:10:11,280 APPROACH IS TO FOSTER 2429 02:10:11,280 --> 02:10:12,840 COLLABORATIONS BETWEEN BASIC AND 2430 02:10:12,840 --> 02:10:16,280 CLINICAL SCIENTIST AND IF SIL 2431 02:10:16,280 --> 02:10:17,840 CO-OPERATIVE CLINICAL TRIALS IN 2432 02:10:17,840 --> 02:10:19,240 AUTOIMMUNE DISEASES. 2433 02:10:19,240 --> 02:10:21,920 THIS SHOWS THE HISTORY OF THE 2434 02:10:21,920 --> 02:10:23,640 ACE IT WAS INITIATED IN 1999 2435 02:10:23,640 --> 02:10:26,960 WITH FOUR CENTERS AND EXPANDED 2436 02:10:26,960 --> 02:10:30,480 IN 2004 AND RENEWED AGAIN IN 2437 02:10:30,480 --> 02:10:32,560 2014 AND BROKEN INTO TWO 2438 02:10:32,560 --> 02:10:34,200 MECHANISMS, UM1 FOR THE CLINICAL 2439 02:10:34,200 --> 02:10:38,720 AND BASIC U19. 2440 02:10:38,720 --> 02:10:40,200 19 RENEWED IN 2019 2441 02:10:40,200 --> 02:10:42,200 WITH EXTREME CLINICAL PROJECTS. 2442 02:10:42,200 --> 02:10:45,400 ANIMAL MODELS ARE NOT PERMITTED 2443 02:10:45,400 --> 02:10:47,320 AND THE CURRENT CYCLE HAS 10 2444 02:10:47,320 --> 02:10:47,560 CENTERS. 2445 02:10:47,560 --> 02:10:50,560 FIVE CLINICAL AND FIVE BASIC AND 2446 02:10:50,560 --> 02:10:54,560 THOSE ARE COORDINATED 2447 02:10:54,560 --> 02:10:56,560 COMPOSEDDED OF PI AND 2448 02:10:56,560 --> 02:10:58,120 REPRESENTATIVE OF THE STATISTICS 2449 02:10:58,120 --> 02:11:00,080 AND CLINICAL CENTER AND THERE 2450 02:11:00,080 --> 02:11:02,040 ARE TWO ANNUAL STEERING 2451 02:11:02,040 --> 02:11:03,120 COMMITTEE MEETINGS, ONE 2452 02:11:03,120 --> 02:11:05,960 INCLUDING ALL INVESTIGATORS AND 2453 02:11:05,960 --> 02:11:10,080 A SINGLE FUNDS MANAGEMENT CORE 2454 02:11:10,080 --> 02:11:11,600 AT ONE CENTER SUPPORTS THE 2455 02:11:11,600 --> 02:11:13,520 NETWORK ACTIVITIES INCLUDING 2456 02:11:13,520 --> 02:11:15,240 CLINICAL PROJECTS NOW CLINICAL 2457 02:11:15,240 --> 02:11:17,280 PROJECTS IS A CLINICAL TRIAL AND 2458 02:11:17,280 --> 02:11:18,840 TOGETHER WITH A MECHANIC NICE 2459 02:11:18,840 --> 02:11:20,960 TICK STUDIES AND ALSO 2460 02:11:20,960 --> 02:11:24,880 COLLABORATIVE PROJECTS MORE ON 2461 02:11:24,880 --> 02:11:28,040 THE ACES RESPOND TO THE PANDEMIC 2462 02:11:28,040 --> 02:11:30,040 AS FOUNDING MEMBERS OF PRISM 2463 02:11:30,040 --> 02:11:31,560 WHICH IS A TOGETHER 2464 02:11:31,560 --> 02:11:32,360 TRANSPORTATION BRANCH 2465 02:11:32,360 --> 02:11:39,360 INVESTIGATORS STUDYING COVID IN 2466 02:11:39,360 --> 02:11:41,800 CHILDREN. 2467 02:11:41,800 --> 02:11:46,600 LEADING SUBJECT ON THOSE AND 2468 02:11:46,600 --> 02:11:48,360 CENTERS COMPETED SUCCESSFULLY 2469 02:11:48,360 --> 02:11:51,640 FOR ADMINISTRATIVE SUPPLEMENTS 2470 02:11:51,640 --> 02:11:54,280 OF COVID AND AS I MENTIONED THE 2471 02:11:54,280 --> 02:11:54,880 COLLABORATIVE PROJECT. 2472 02:11:54,880 --> 02:11:56,480 THIS IS A SECOND PROGRAM CYCLE 2473 02:11:56,480 --> 02:11:58,120 WHICH APPLICANTS DESCRIBED THEIR 2474 02:11:58,120 --> 02:11:59,760 PLANS FOR COLLABORATIVE PROJECTS 2475 02:11:59,760 --> 02:12:01,320 AND HOW THEY WOULD CONTRIBUTE 2476 02:12:01,320 --> 02:12:03,760 AND HOW THEY WOULD BENEFIT FROM 2477 02:12:03,760 --> 02:12:04,480 THE GROUP. 2478 02:12:04,480 --> 02:12:06,160 AND THESE PROJECTS WERE 2479 02:12:06,160 --> 02:12:08,320 COORDINATED SUCCESSFULLY POST 2480 02:12:08,320 --> 02:12:09,840 AWARD WITH ALL CENTERS 2481 02:12:09,840 --> 02:12:13,000 PARTICIPATING IN THESE THREE 2482 02:12:13,000 --> 02:12:14,640 COLLABORATIVE PROJECTS 2483 02:12:14,640 --> 02:12:15,840 ONE INBIOMARKERS AND THE THIRD 2484 02:12:15,840 --> 02:12:20,000 ON IMMUNE RESPONSES AND 2485 02:12:20,000 --> 02:12:27,240 PERIPHERAL TISSUES. 2486 02:12:27,240 --> 02:12:30,720 THEY INCLUDE THESE FOUR 2487 02:12:30,720 --> 02:12:33,160 ENROLLING AND TO THE FIRST IS 2488 02:12:33,160 --> 02:12:37,040 BLOCKING SLAM F7 AND IGG4 2489 02:12:37,040 --> 02:12:38,840 RELATED DISEASES AND THE SECOND 2490 02:12:38,840 --> 02:12:43,000 USES A ANTIBODY IN EARLY 2491 02:12:43,000 --> 02:12:45,320 RELAXING MULTIPLE SCLEROSIS AND 2492 02:12:45,320 --> 02:12:51,640 THE THIRD IS KINASE AND PHOTO 2493 02:12:51,640 --> 02:12:52,600 SENSITIVITY AND LIEU US AND THE 2494 02:12:52,600 --> 02:12:56,080 FOURTH IS A STUDY IN SYSTEMIC 2495 02:12:56,080 --> 02:12:57,400 LUPUS AND THE FIFTH IN 2496 02:12:57,400 --> 02:13:03,440 DEVELOPMENT IS TO TREAT JUVENILE 2497 02:13:03,440 --> 02:13:03,880 IDIOPATHIC ARTHRITIS. 2498 02:13:03,880 --> 02:13:05,880 SO IN TERMS OF CHALLENGES FROM 2499 02:13:05,880 --> 02:13:07,880 THAT AND ACCOMPLISHMENTS 2500 02:13:07,880 --> 02:13:09,280 INCLUDE, AGAIN, THE DEVELOPMENT 2501 02:13:09,280 --> 02:13:10,720 OF THE FOUR CLINICAL PROJECTS 2502 02:13:10,720 --> 02:13:14,120 AND ONE IN DEVELOPMENT AND ONE 2503 02:13:14,120 --> 02:13:17,520 OF FOUR AREN ROLLING AND ONE IN 2504 02:13:17,520 --> 02:13:18,720 DEVELOPING AND SUPPORTING ON 2505 02:13:18,720 --> 02:13:21,160 GOING LEGACY CLINICAL TRIALS AND 2506 02:13:21,160 --> 02:13:25,200 I WON'T GO INTO THOSE. 2507 02:13:25,200 --> 02:13:26,520 WE HAVE ESTABLISHED AN 2508 02:13:26,520 --> 02:13:29,120 INEFFICIENT FUNDS MANAGEMENT 2509 02:13:29,120 --> 02:13:31,120 CORE AGAIN AND FOSTER 2510 02:13:31,120 --> 02:13:32,560 COLLABORATIONS, THIS IS A 2511 02:13:32,560 --> 02:13:33,520 FORMULATED COLBORATIVE 2512 02:13:33,520 --> 02:13:37,400 RESEARCH AGENDA AND THIS IS A 2513 02:13:37,400 --> 02:13:39,160 FIVE-YEAR PLAN POSTED WITH THE 2514 02:13:39,160 --> 02:13:41,680 ENTIRE PROGRAM, POSTED ON THE 2515 02:13:41,680 --> 02:13:43,480 PUBLIC ACE WEBSITE AND UPDATED 2516 02:13:43,480 --> 02:13:44,760 ANNUALLY WITH PROGRESS REPORTS 2517 02:13:44,760 --> 02:13:46,560 AGAIN PUBLICLY. 2518 02:13:46,560 --> 02:13:48,800 AND AS I SHOWED YOU, THEY 2519 02:13:48,800 --> 02:13:50,360 INITIATED THREE COLLABORATIVE 2520 02:13:50,360 --> 02:13:53,680 PROJECTS INCLUDING ALL CENTERS. 2521 02:13:53,680 --> 02:13:55,200 THEY HAVE MAINTAINED HIGH 2522 02:13:55,200 --> 02:13:56,600 SCIENTIFIC PRODUCTIVITY AND 2523 02:13:56,600 --> 02:13:58,760 THERE HAVE BEEN 162 ORIGINAL 2524 02:13:58,760 --> 02:14:02,880 PAPERS AND REVIEW ARTICLES MANY 2525 02:14:02,880 --> 02:14:06,560 IN HIGH-IMPACT JOURNALS AND THAT 2526 02:14:06,560 --> 02:14:13,680 IS THROUGH APR OF 202020. 2527 02:14:13,680 --> 02:14:15,560 AND 35 PUBLICATIONS OF COVID-19. 2528 02:14:15,560 --> 02:14:17,520 IN ELSE TESTIFY CHARGES EMERGING 2529 02:14:17,520 --> 02:14:20,320 INCLUDING THE PANDEMIC, THESE 2530 02:14:20,320 --> 02:14:21,800 RESPONDED TO THE PANDEMIC BY 2531 02:14:21,800 --> 02:14:23,360 JOINING WITH COLLABORATE FROM 2532 02:14:23,360 --> 02:14:29,600 THE TRANSPLANTATION COMMITTEE TO 2533 02:14:29,600 --> 02:14:30,920 FORM PRISM ON SARS-CoV-2 2534 02:14:30,920 --> 02:14:35,440 STUDYING THE MULTI SYSTEM 2535 02:14:35,440 --> 02:14:36,360 INFLAMMATORY INDROP IN CHILDREN 2536 02:14:36,360 --> 02:14:37,640 OR MIS-C. 2537 02:14:37,640 --> 02:14:40,040 THIS PROGRAM IS PERFORMING 2538 02:14:40,040 --> 02:14:42,680 IN-DEPTH IMMUNE ANALYSIS IN MORE 2539 02:14:42,680 --> 02:14:45,760 THAN 240 CHILDREN WITH COVID. 2540 02:14:45,760 --> 02:14:46,360 THE ACE ALSO DEVELOPED A TRIAL 2541 02:14:46,360 --> 02:14:51,920 AND STUDY OF COVID VACCINES AND 2542 02:14:51,920 --> 02:14:53,560 IN AUTOIMMUNE SUBJECTS THAT 2543 02:14:53,560 --> 02:14:57,960 SHOWN ACBO-1 RIGHT THERE AND 2544 02:14:57,960 --> 02:14:59,800 IT'S RANDOMIZED ADAPTIVE TRIAL 2545 02:14:59,800 --> 02:15:02,200 THAT IS COMPLICATED ACTUALLY. 2546 02:15:02,200 --> 02:15:05,720 I'M NOT DIRECTLY INVOLVED WITH 2547 02:15:05,720 --> 02:15:07,360 THAT. 2548 02:15:07,360 --> 02:15:09,240 ACVO2 IS A SMALLER STUDY AND 2549 02:15:09,240 --> 02:15:11,240 MORE LIKE A MECHANIC NICE TICK 2550 02:15:11,240 --> 02:15:13,040 TRIAL PART OF THE PROJECTS. 2551 02:15:13,040 --> 02:15:16,320 AND AGAIN, COUPLE OF THE CENTERS 2552 02:15:16,320 --> 02:15:18,160 HAD SUCCESSFULLY COMPETED FOR 2553 02:15:18,160 --> 02:15:20,680 ADMIN SUPPLEMENTS IN COVID. 2554 02:15:20,680 --> 02:15:22,360 IN TERMS OF CHALLENGES 2555 02:15:22,360 --> 02:15:25,960 REMAINING, OUR PLANS FORT 2556 02:15:25,960 --> 02:15:27,960 RENEWAL, WE HOPED TO FURTHER 2557 02:15:27,960 --> 02:15:31,560 STRENGTHEN ANALYSIS OF CLINICAL 2558 02:15:31,560 --> 02:15:35,880 TRIALS BY FORMING A DEDICATED 2559 02:15:35,880 --> 02:15:38,840 MESSNESS TICK STUDY TEAM THAT 2560 02:15:38,840 --> 02:15:40,240 WOULD HELP KEEP CURRENT THE USE 2561 02:15:40,240 --> 02:15:44,960 OF SAMPLES LEVERAGING THE NET 2562 02:15:44,960 --> 02:15:46,720 EXPERTISE AND PROMOTE SECONDARY 2563 02:15:46,720 --> 02:15:48,280 ANALYSIS OF CLINICAL TRIALS 2564 02:15:48,280 --> 02:15:50,280 SAMPLES AND WE THINK WE CAN 2565 02:15:50,280 --> 02:15:53,080 ASSIST IN THAT AND FOSTER THAT 2566 02:15:53,080 --> 02:15:55,200 BY HAVING A COORDINATED 2567 02:15:55,200 --> 02:15:56,920 COLLECTION AND PROVISION OF 2568 02:15:56,920 --> 02:16:02,160 CLINICAL TRIALS SAMPLES THROUGH 2569 02:16:02,160 --> 02:16:05,200 A ACE REPOSITORY CORE THAT WOULD 2570 02:16:05,200 --> 02:16:06,880 BE INSTRUCT ACTUALLY NEW AND 2571 02:16:06,880 --> 02:16:08,800 DEVELOP SAMPLE SET COLLECTION 2572 02:16:08,800 --> 02:16:11,520 AND ANALYSIS. 2573 02:16:11,520 --> 02:16:14,400 NOW, THE RENEWAL STRUCTURALLY 2574 02:16:14,400 --> 02:16:16,720 LOOKED LIKE THIS TWO SEPARATE 2575 02:16:16,720 --> 02:16:21,640 MECHANISMS A UM1 AND UM19. 2576 02:16:21,640 --> 02:16:23,640 UM1 NEITHER OF THE TWO ACTUALLY 2577 02:16:23,640 --> 02:16:25,760 ON THEIR OWN CHANGED MUCH BUT 2578 02:16:25,760 --> 02:16:29,080 ALL THE APPLICANTS ARE OBLIGED 2579 02:16:29,080 --> 02:16:34,080 TO PROPOSE A CO COLLABORATIVE AD 2580 02:16:34,080 --> 02:16:40,080 ADMINISTRATIVE CORE NOT NEW AND 2581 02:16:40,080 --> 02:16:43,680 AND ACE AND THAT WOULD BE NEW 2582 02:16:43,680 --> 02:16:47,120 AND MANAGEMENT ONE NETWORK A 2583 02:16:47,120 --> 02:16:48,480 HARD AND THEY WOULD BE OBLIGED 2584 02:16:48,480 --> 02:16:54,480 TO APPLY. 2585 02:16:54,480 --> 02:16:56,240 I HOPE YOU'VE HEARD ME AND I'M 2586 02:16:56,240 --> 02:17:06,720 HAPPY TO TAKE ANY QUESTIONS. 2587 02:17:25,440 --> 02:17:34,400 >> THANK YOU, IT LOOKS GOOD. 2588 02:17:34,400 --> 02:17:35,680 >> SORRY. 2589 02:17:35,680 --> 02:17:38,880 MY VIDEO IS LIKE TURNED OFF SO I 2590 02:17:38,880 --> 02:17:40,240 CAN'T TURN IT ON. 2591 02:17:40,240 --> 02:17:42,560 >> THAT'S OK. 2592 02:17:42,560 --> 02:17:43,760 I UNDERSTAND. 2593 02:17:43,760 --> 02:17:47,640 SO, I DON'T SEE ANY OTHER 2594 02:17:47,640 --> 02:17:51,880 QUESTIONS OR HANDS UP SO, AT 2595 02:17:51,880 --> 02:17:54,240 THIS POINT WE'RE A BIT AHEAD OF 2596 02:17:54,240 --> 02:17:59,040 SCHEDULE WHICH IS FINE AND WE 2597 02:17:59,040 --> 02:18:02,640 CAN ASK FOR AN RECOMMENDATION 2598 02:18:02,640 --> 02:18:05,680 AND MOTION AND A SECOND FOR ALL 2599 02:18:05,680 --> 02:18:11,280 OF THE CONCEPT CLEARANCES. 2600 02:18:11,280 --> 02:18:13,440 >> SO MOVED. 2601 02:18:13,440 --> 02:18:15,680 >> SECOND. 2602 02:18:15,680 --> 02:18:17,160 >> OK. 2603 02:18:17,160 --> 02:18:19,160 DOES THAT TAKE CARE OF ALL OF 2604 02:18:19,160 --> 02:18:21,000 THE OFFICIAL BUSINESS. 2605 02:18:21,000 --> 02:18:22,400 >> THE COUNCIL MEMBERS WILL NEED 2606 02:18:22,400 --> 02:18:25,000 TO GO INTO THE ECD AND APPROVE 2607 02:18:25,000 --> 02:18:26,600 THE RESEARCH CONCEPT CLEARANCE 2608 02:18:26,600 --> 02:18:28,920 AND THAT WILL DO IT. 2609 02:18:28,920 --> 02:18:30,800 >> TERRIFIC. 2610 02:18:30,800 --> 02:18:31,400 OK. 2611 02:18:31,400 --> 02:18:36,360 WELL, IN THAT CASE, WE CAN 2612 02:18:36,360 --> 02:18:39,280 WRAP-UP AS SOON AS YOU ALL DO 2613 02:18:39,280 --> 02:18:42,520 THAT AND LOOK FORWARD TO, I 2614 02:18:42,520 --> 02:18:46,000 HOPE, SEEING YOU IN-PERSON 2615 02:18:46,000 --> 02:18:48,960 FAIRLY SOON. 2616 02:18:48,960 --> 02:18:49,160 AND -- 2617 02:18:49,160 --> 02:18:52,520 >> WILL THE FALL MEETING BE 2618 02:18:52,520 --> 02:18:52,920 IN-PERSON? 2619 02:18:52,920 --> 02:18:58,240 >> WE DON'T KNOW YET. 2620 02:18:58,240 --> 02:19:01,960 I THINK IT'S -- HOPEFULLY WE 2621 02:19:01,960 --> 02:19:05,440 WILL BE BEYOND COVID TRAVEL 2622 02:19:05,440 --> 02:19:07,440 RESTRICTIONS AND MEETING 2623 02:19:07,440 --> 02:19:09,240 RESTRICTIONS THEN AND WE'LL SEE. 2624 02:19:09,240 --> 02:19:14,640 I THINK THE EXPERIENCE WITH 2625 02:19:14,640 --> 02:19:18,880 COVID AND DOING THESE REMOTELY 2626 02:19:18,880 --> 02:19:24,640 BY WEB, HAS BEEN GOOD ENOUGH OUR 2627 02:19:24,640 --> 02:19:27,000 EXPECTATION IS THAT FOR THE 2628 02:19:27,000 --> 02:19:30,600 WINTER MEETING AND JANUARY IN 2629 02:19:30,600 --> 02:19:34,200 TRAVEL IS AN ISSUE WE WILL DO 2630 02:19:34,200 --> 02:19:38,040 THOSE REMOTE LEROUX TEENLY GOING 2631 02:19:38,040 --> 02:19:42,120 FORWARD AND WE'LL SEE ABOUT THE 2632 02:19:42,120 --> 02:19:46,240 FALL AND MAY AND JUNE COUNCIL AS 2633 02:19:46,240 --> 02:19:46,560 THIS UNFOLDS. 2634 02:19:46,560 --> 02:19:47,240 >> OK. 2635 02:19:47,240 --> 02:19:47,560 >> THANK YOU. 2636 02:19:47,560 --> 02:19:50,920 >> IF ANY OF YOU HAVE THOUGHTS 2637 02:19:50,920 --> 02:19:52,720 OR SUGGESTIONS ABOUT HOW WELL 2638 02:19:52,720 --> 02:19:55,440 THIS IS WORKING AND WHETHER IT'S 2639 02:19:55,440 --> 02:19:57,880 A GOOD IDEA TO MEET IN-PERSON 2640 02:19:57,880 --> 02:20:00,360 MORE FREQUENTLY AND THEN ONCE A 2641 02:20:00,360 --> 02:20:02,400 YEAR OR THE TIMES SAY OF TERM 2642 02:20:02,400 --> 02:20:08,440 TRAVEL IS VALUABLE TO YOU, WE'RE 2643 02:20:08,440 --> 02:20:09,520 HAPPY TO HEAR YOUR COMMENTS 2644 02:20:09,520 --> 02:20:11,480 EITHER RIGHT NOW OR PRIVATELY BY 2645 02:20:11,480 --> 02:20:11,720 E-MAIL. 2646 02:20:11,720 --> 02:20:13,880 >> WE DID GET ACTUALLY A SURVEY 2647 02:20:13,880 --> 02:20:18,480 TO RESPOND TO SO, WE DID. 2648 02:20:18,480 --> 02:20:20,880 >> I MISSED THE SURVEY BUT I 2649 02:20:20,880 --> 02:20:26,240 SAID ONCE A YEAR MAY B BALANCE E 2650 02:20:26,240 --> 02:20:27,080 PROS AND CONS. 2651 02:20:27,080 --> 02:20:29,080 THE TIME SAVED IN TRAVEL IS 2652 02:20:29,080 --> 02:20:30,840 WELCOME BUT IT'S REALLY NICE TO 2653 02:20:30,840 --> 02:20:35,200 BE ABLE TO INTERNET ARE ACT. 2654 02:20:35,200 --> 02:20:36,920 THE DIFFERENT GROUPS ACROSS WE 2655 02:20:36,920 --> 02:20:38,160 WOULD SEE EACH OTHER IN THE 2656 02:20:38,160 --> 02:20:41,520 HOTEL OR AT LUNCH AND THOSE WERE 2657 02:20:41,520 --> 02:20:43,520 VALUABLE EXPERIENCES. 2658 02:20:43,520 --> 02:20:46,040 I THINK MEANINGFUL ALL AROUND IN 2659 02:20:46,040 --> 02:20:47,760 ADDITION TO INTERACTING WITH YOU 2660 02:20:47,760 --> 02:20:49,400 GUYS AT NIH. 2661 02:20:49,400 --> 02:20:53,520 >> YEAH, I AGREE. 2662 02:20:53,520 --> 02:20:55,760 GWEN, I TOOK IT YOU WERE SAYING 2663 02:20:55,760 --> 02:21:01,360 MEET IN-PERSON ONCE AND THAT 2664 02:21:01,360 --> 02:21:02,960 MIGHT BE FREQUENT ENOUGH OR WERE 2665 02:21:02,960 --> 02:21:03,280 YOU SAYING? 2666 02:21:03,280 --> 02:21:08,280 >> THAT MIGHT BE FREQUENT 2667 02:21:08,280 --> 02:21:08,520 ENOUGH. 2668 02:21:08,520 --> 02:21:10,600 THERE ARE PROS AND CONS TO EACH 2669 02:21:10,600 --> 02:21:13,120 APPROACH. 2670 02:21:13,120 --> 02:21:14,880 I'M NOT SURE ROBIN THINKS ABOUT 2671 02:21:14,880 --> 02:21:16,800 IT BUT ONCE OR TWICE A YEAR 2672 02:21:16,800 --> 02:21:17,120 WOULD BE NICE. 2673 02:21:17,120 --> 02:21:21,200 >> I TOTAL TOTE AGREE. 2674 02:21:21,200 --> 02:21:22,760 I HAVE THE SAME OPINION. 2675 02:21:22,760 --> 02:21:23,360 >> GOOD. 2676 02:21:23,360 --> 02:21:24,040 >> ALL RIGHT. 2677 02:21:24,040 --> 02:21:25,680 >> BIG QUESTION IS WILL IT BE 2678 02:21:25,680 --> 02:21:26,720 THE WINTER THAT IS THE WORSE 2679 02:21:26,720 --> 02:21:28,120 TIME TO TRAVEL, RIGHT, BECAUSE I 2680 02:21:28,120 --> 02:21:30,520 WAS SUPPOSED TO GO TO AAI THAT'S 2681 02:21:30,520 --> 02:21:34,920 WHAT I GOT COVID IN MAY I WOULD 2682 02:21:34,920 --> 02:21:36,560 HAVE BET MAY WOULD HAVE BEEN THE 2683 02:21:36,560 --> 02:21:38,280 SAFEST MONTH OF THE YEAR. 2684 02:21:38,280 --> 02:21:39,880 IT'S REALLY HARD TO TELL. 2685 02:21:39,880 --> 02:21:43,400 >> SAME THING HAPPENED AT ETS 2686 02:21:43,400 --> 02:21:45,560 SEVERAL PEOPLE CAME DOWN AND I'M 2687 02:21:45,560 --> 02:21:51,320 OFF TO ASPEN FOR A WEEK AND THE 2688 02:21:51,320 --> 02:22:00,520 HONG KONG AND THE VIRUS IS 2689 02:22:00,520 --> 02:22:01,760 CHANGING FASTER THAN THE 2690 02:22:01,760 --> 02:22:03,160 VACCINES AND THE VIRUS WILL TELL 2691 02:22:03,160 --> 02:22:04,560 US WHEN IT'S DONE WITH US. 2692 02:22:04,560 --> 02:22:05,560 >> YEAH, EXACTLY. 2693 02:22:05,560 --> 02:22:07,320 >> I WANTED TO ASK THE QUESTION 2694 02:22:07,320 --> 02:22:10,480 BUT I DON'T KNOW THAT WE KNOW 2695 02:22:10,480 --> 02:22:13,960 THE ANSWER BUT ON ONE HAND WE 2696 02:22:13,960 --> 02:22:15,280 HEARD THAT CORONAVIRUS IMMUNITY 2697 02:22:15,280 --> 02:22:16,640 JUST TENDS TO BE SHORT AND THAT 2698 02:22:16,640 --> 02:22:19,400 IS HISTORICALLY TRUE, RIGHT, 2699 02:22:19,400 --> 02:22:23,640 EVEN BEFORE SARS-CoV-2 BUT THE 2700 02:22:23,640 --> 02:22:25,640 NASAL VACCINE IS GETTING A LOT 2701 02:22:25,640 --> 02:22:29,480 OF DISCUSSION, WILL IT BE 2702 02:22:29,480 --> 02:22:30,280 BETTER? 2703 02:22:30,280 --> 02:22:31,600 I DON'T THINK WE KNOW THE ANSWER 2704 02:22:31,600 --> 02:22:31,880 TO THAT. 2705 02:22:31,880 --> 02:22:34,480 >> NOT AT ALL. 2706 02:22:34,480 --> 02:22:39,800 >> WELL HOPEFULLY FOR ONE NASAL 2707 02:22:39,800 --> 02:22:42,520 VACCINE SOMETIMES FAIRLY SOON 2708 02:22:42,520 --> 02:22:43,960 AND ABOUT SHORT TERM IMMUNITY 2709 02:22:43,960 --> 02:22:47,840 BUT IT'S GOING TO TAKE A LONG 2710 02:22:47,840 --> 02:22:51,000 TIME AND WILL REQUIRE THE VIRUS 2711 02:22:51,000 --> 02:22:55,000 CONTINUES TO TRANSMIT AND BE 2712 02:22:55,000 --> 02:22:57,760 CIRCULATING WIDELY TO KNOW 2713 02:22:57,760 --> 02:23:01,720 WHETHER THERE'S EVEN A REAL 2714 02:23:01,720 --> 02:23:02,320 PROTECTION. 2715 02:23:02,320 --> 02:23:02,880 >> YES. 2716 02:23:02,880 --> 02:23:04,280 >> THE HOSPITALIZATIONS DID NOT 2717 02:23:04,280 --> 02:23:06,320 RISE AND THERE'S A HUGE RISE 2718 02:23:06,320 --> 02:23:08,320 LOCALLY INFECTION AND IN FACT, 2719 02:23:08,320 --> 02:23:10,240 IT ALSO JUST EVEN UNIVERSITY 2720 02:23:10,240 --> 02:23:13,400 ALMOST EVERYONE I KNOW GOT COVID 2721 02:23:13,400 --> 02:23:19,080 THIS MAY AND REALLY 2722 02:23:19,080 --> 02:23:19,720 HOSPITALIZATIONS DIDN'T RISE AND 2723 02:23:19,720 --> 02:23:28,680 I THINK THAT'S A GOOD SIGN. 2724 02:23:28,680 --> 02:23:30,560 >> IT'S PREVENTING SEVERE 2725 02:23:30,560 --> 02:23:30,840 DISEASES. 2726 02:23:30,840 --> 02:23:35,480 >> YEAH, BUT IT'S TRUE. 2727 02:23:35,480 --> 02:23:40,120 WE'RE HEARING OF A LOT OF PEOPLE 2728 02:23:40,120 --> 02:23:45,720 WHO HAVE MILD STAY AT HOME 2729 02:23:45,720 --> 02:23:47,720 DISEASE BUT SYMPTOMS TWO TO FOUR 2730 02:23:47,720 --> 02:23:48,760 WEEKS BEFORE THEY'RE BACK TO 2731 02:23:48,760 --> 02:23:50,400 THEIR NORMAL EXERCISE LEVEL AND 2732 02:23:50,400 --> 02:23:52,560 THE LIKE SO THAT IS A HIGH PRICE 2733 02:23:52,560 --> 02:23:52,960 TO PAY. 2734 02:23:52,960 --> 02:23:54,080 >> YEAH. 2735 02:23:54,080 --> 02:23:56,520 >> ABSOLUTELY. 2736 02:23:56,520 --> 02:23:58,360 >> ALL RIGHT. 2737 02:23:58,360 --> 02:24:00,360 WELL, THANK YOU ALL AND I THINK 2738 02:24:00,360 --> 02:24:03,280 WE'LL JUST WRAP-UP HERE. 2739 02:24:03,280 --> 02:24:04,440 LOOK FORWARD TO HOPEFULLY SEEING 2740 02:24:04,440 --> 02:24:05,720 YOU IN THE FALL. 2741 02:24:05,720 --> 02:24:06,320 >> THANK YOU. 2742 02:24:06,320 --> 00:00:00,000 >> THANK YOU, EVERYBODY.