1 00:00:08,865 --> 00:00:13,003 >> GOOD MORNING, EVERYONE. 2 00:00:13,003 --> 00:00:14,238 IT'S PAST 1:00 P.M. SO DR. KOOB 3 00:00:14,238 --> 00:00:19,076 WILL CALL THE MEETING TO ORDER. 4 00:00:19,076 --> 00:00:21,445 >> SO, GOOD AFTERNOON, EVERYONE. 5 00:00:21,445 --> 00:00:23,480 I WOULD LIKE TO WELCOME YOU ALL 6 00:00:23,480 --> 00:00:26,450 TO THE 169TH MEETING OF THE 7 00:00:26,450 --> 00:00:27,484 NATIONAL ADVISORY COUNCIL ON 8 00:00:27,484 --> 00:00:28,919 ALCOHOL ABUSE AND ALCOHOLISM. 9 00:00:28,919 --> 00:00:32,723 I'M GOING TO CALL ON EACH 10 00:00:32,723 --> 00:00:33,690 COUNCIL MEMBER. 11 00:00:33,690 --> 00:00:37,094 NANCY GONZALEZ IS NOT ABLE TO 12 00:00:37,094 --> 00:00:38,695 JOIN US. 13 00:00:38,695 --> 00:00:48,805 LEY 14 00:00:50,140 --> 00:00:50,707 LEYDEN. 15 00:00:50,707 --> 00:00:51,308 DAVID. 16 00:00:51,308 --> 00:00:52,809 >> INDIANA UNIVERSITY SCHOOL OF 17 00:00:52,809 --> 00:00:56,280 MEDICINE DEPARTMENT OF NEUROLOGY 18 00:00:56,280 --> 00:00:58,849 AND DIRECTOR OF OUR ALCOHOL 19 00:00:58,849 --> 00:01:02,019 RESEARCH CENTER HERE. 20 00:01:02,019 --> 00:01:04,921 >> DAVID SENT ME AN E-MAIL NOT 21 00:01:04,921 --> 00:01:07,090 TOO LONG AGO ABOUT A WEEK OR SO 22 00:01:07,090 --> 00:01:10,560 AGO AND HE HAS BEEN AWARDED A 23 00:01:10,560 --> 00:01:13,297 FULL RIDE FELLOWSHIP TO STUDY IN 24 00:01:13,297 --> 00:01:20,003 FRANCE, ALCOHOL. 25 00:01:20,003 --> 00:01:22,606 HE'LL BE WORKING WITH LAURA 26 00:01:22,606 --> 00:01:25,842 HASAN AT THE UNIVERSITY OF 27 00:01:25,842 --> 00:01:31,315 STRASBURG AND FLORENCE WARSPA IN 28 00:01:31,315 --> 00:01:32,382 PARIS. 29 00:01:32,382 --> 00:01:32,983 >> CONGRATULATIONS. 30 00:01:32,983 --> 00:01:33,317 >> THANK YOU. 31 00:01:33,317 --> 00:01:37,187 >> FRANCIS, ARE YOU ON? 32 00:01:37,187 --> 00:01:38,689 >> YES, I AM. 33 00:01:38,689 --> 00:01:40,724 HOW ARE YOU? 34 00:01:40,724 --> 00:01:42,693 FRANCIS LEVIN AT THE NEW YORK 35 00:01:42,693 --> 00:01:44,895 STATE PSYCHIATRIC INSTITUTE AND 36 00:01:44,895 --> 00:01:48,165 ALSO COLUMBIA UNIVERSITY MEDICAL 37 00:01:48,165 --> 00:01:50,200 CENTER AND CHIEF OF THE DIVISION 38 00:01:50,200 --> 00:01:55,272 ON SUBSTANCE USE DISORDERS AND 39 00:01:55,272 --> 00:01:56,673 GLAD WE'RE MEETING. 40 00:01:56,673 --> 00:01:57,908 >> WE ARE TOO, FRANCES. 41 00:01:57,908 --> 00:02:01,144 GREAT TO SEE YOU. 42 00:02:01,144 --> 00:02:01,912 MICHAEL. 43 00:02:01,912 --> 00:02:03,313 >> I'M MICHAEL LEWIS PROFESSOR 44 00:02:03,313 --> 00:02:06,316 OF PSYCHOLOGY AT HUNTER COLLEGE 45 00:02:06,316 --> 00:02:10,687 AND THE GRADUATE SCHOOL OF CITY 46 00:02:10,687 --> 00:02:14,591 UNIVERSITY OF NEW YORK. 47 00:02:14,591 --> 00:02:17,994 >> THANKS, MICHAEL. 48 00:02:17,994 --> 00:02:18,195 DAYNE. 49 00:02:18,195 --> 00:02:20,263 >> I'M ALSO GLAD YEAR ABLE TO 50 00:02:20,263 --> 00:02:20,897 MEET. 51 00:02:20,897 --> 00:02:24,167 I'M AT THE UNIVERSITY OF TEXAS 52 00:02:24,167 --> 00:02:25,836 AT AUSTIN AND WITH THE WAGNER 53 00:02:25,836 --> 00:02:26,870 CENTER FOR ALCOHOL AND ADDICTION 54 00:02:26,870 --> 00:02:29,239 RESEARCH AND THE DEPARTMENT OF 55 00:02:29,239 --> 00:02:34,211 NEUROSCIENCE. 56 00:02:34,211 --> 00:02:35,112 >> THANKS. 57 00:02:35,112 --> 00:02:37,214 I'M THE DIRECTOR GEORGE KOOB OF 58 00:02:37,214 --> 00:02:37,781 THE NATIONAL INSTITUTE ON 59 00:02:37,781 --> 00:02:39,750 ALCOHOL ABUSE AND ALCOHOLISM. 60 00:02:39,750 --> 00:02:42,285 I'LL GO THIS DIRECTION. 61 00:02:42,285 --> 00:02:43,520 SO TRISHA IS NEXT. 62 00:02:43,520 --> 00:02:46,723 >> DEPUTY DIRECTOR OF NIAAA. 63 00:02:46,723 --> 00:02:48,392 GLAD TO SEE EVERYONE. 64 00:02:48,392 --> 00:02:51,161 >> GOOD AFTERNOON, EVERYONE I'M 65 00:02:51,161 --> 00:02:54,698 KATHY YOUNG THE DIRECTOR OF 66 00:02:54,698 --> 00:02:57,067 DIVISION OF METABOLISM AND 67 00:02:57,067 --> 00:03:00,070 HEALTH S IN NIAA. 68 00:03:00,070 --> 00:03:02,406 >> I'M REPRESENTING THE DIVISION 69 00:03:02,406 --> 00:03:04,074 OF NEUROSCIENCE AND BEHAVIOR, 70 00:03:04,074 --> 00:03:09,346 MARK EGLI, NIAAA. 71 00:03:09,346 --> 00:03:13,884 >> I'M ACTING CHIEF OF THYROID 72 00:03:13,884 --> 00:03:18,955 DISORDERS AT THE NIAAA. 73 00:03:18,955 --> 00:03:23,126 >> I'M LAURA CHIEF OF THE 74 00:03:23,126 --> 00:03:25,595 RECOVERY BRANCH AND ACTING 75 00:03:25,595 --> 00:03:26,430 DIVISION DIRECTOR OF TREATMENT 76 00:03:26,430 --> 00:03:30,934 AND RECOVERY AT NIAAA. 77 00:03:30,934 --> 00:03:32,569 >> I DIRECT EPIDEMIOLOGY AND 78 00:03:32,569 --> 00:03:37,741 PREVENTION RESEARCH AT NIAAA. 79 00:03:37,741 --> 00:03:38,275 >> GOOD AFTERNOON. 80 00:03:38,275 --> 00:03:45,015 I'M PHILIPPE MARMILLOT DIRECTOR 81 00:03:45,015 --> 00:03:55,492 OF EXTRAMURAL ACTIVITIES AT 82 00:04:12,576 --> 00:04:14,244 >> OKAY. 83 00:04:14,244 --> 00:04:16,480 SO THIS IS GOING TO BE MY 84 00:04:16,480 --> 00:04:18,682 DIRECTOR'S RECORD OF REPORT FOR 85 00:04:18,682 --> 00:04:21,418 THE 169th MEETING OF THE NIAAA 86 00:04:21,418 --> 00:04:24,621 NATIONAL ADVISORY COUNCIL. 87 00:04:24,621 --> 00:04:27,958 WE HAVE SOME SAD NEWS AND A 88 00:04:27,958 --> 00:04:28,692 LITTLE BIT MORE SAD NEWS BECAUSE 89 00:04:28,692 --> 00:04:32,829 I'M GOING TO TALK ABOUT A NUMBER 90 00:04:32,829 --> 00:04:35,298 OF PROMINENT PEOPLE WHO'VE 91 00:04:35,298 --> 00:04:37,634 PASSED TO THE OTHER SIDE AND THE 92 00:04:37,634 --> 00:04:38,401 NUMBER OF PEOPLE THAT RETIRED 93 00:04:38,401 --> 00:04:39,169 THIS YEAR. 94 00:04:39,169 --> 00:04:40,537 SO WE'RE GOING TO GO THROUGH 95 00:04:40,537 --> 00:04:42,305 THAT FIRST AND THEN I'LL TELL 96 00:04:42,305 --> 00:04:43,106 YOU ABOUT SOME EXCITING RESEARCH 97 00:04:43,106 --> 00:04:49,746 AT THE END. 98 00:04:49,746 --> 00:04:52,983 SO WE LOST WARREN BICKELL. 99 00:04:52,983 --> 00:04:56,720 MANY KNEW OR KNOW OF WARREN. 100 00:04:56,720 --> 00:04:59,689 HIS CAREER WAS CHARACTERIZED BY 101 00:04:59,689 --> 00:05:02,692 A WONDERFUL BLEND OF 102 00:05:02,692 --> 00:05:03,760 PRODUCTIVITY AND INNOVATION IN 103 00:05:03,760 --> 00:05:06,696 THE FIELD OF ADDICTION AND HELD 104 00:05:06,696 --> 00:05:10,700 POSITIONS AT THE ALBERT EINSTEIN 105 00:05:10,700 --> 00:05:13,870 COLLEGE OF MEDICINE AND 106 00:05:13,870 --> 00:05:18,275 UNIVERSITY OF VERMONT AND 107 00:05:18,275 --> 00:05:20,010 VIRGINIA TECH. 108 00:05:20,010 --> 00:05:22,078 HIS RESEARCH ACCOMPLISHMENTS 109 00:05:22,078 --> 00:05:23,480 INCLUDING DEVELOPING 110 00:05:23,480 --> 00:05:25,415 BUPRENORPHINE AS THE MEDICATION 111 00:05:25,415 --> 00:05:28,885 FOR THE TREATMENT OF OPIOID USE, 112 00:05:28,885 --> 00:05:29,553 APPLYING BEHAVIORAL ECONOMICS TO 113 00:05:29,553 --> 00:05:32,222 THE STUDY OF ADDICTION AND 114 00:05:32,222 --> 00:05:34,190 STARTING A SEMINOLE ADDICTION 115 00:05:34,190 --> 00:05:34,791 RECOVERY REGISTRY. 116 00:05:34,791 --> 00:05:36,626 HE WAS A GREAT RESEARCHER AND 117 00:05:36,626 --> 00:05:37,694 CONTRIBUTOR TO THE FIELD AND THE 118 00:05:37,694 --> 00:05:44,467 ALCOHOL FIELD AS WELL. 119 00:05:44,467 --> 00:05:47,704 WE ALSO LOST FLOYD BLOOM. 120 00:05:47,704 --> 00:05:50,707 HE HAD A LONG AND DISTINGUISHED 121 00:05:50,707 --> 00:05:51,808 CAREER INCLUDING MAJOR ADVANCES 122 00:05:51,808 --> 00:05:53,009 IN THE FIELD OF NEUROSCIENCE. 123 00:05:53,009 --> 00:05:55,912 HE WAS ONE OF THE FIRST TO 124 00:05:55,912 --> 00:05:57,914 PROVIDE EVIDENCE THAT SIGNALLING 125 00:05:57,914 --> 00:06:02,686 IN THE BRAIN MAY BE CHEMICAL AS 126 00:06:02,686 --> 00:06:04,854 WELL AS ELECTRICAL AND 127 00:06:04,854 --> 00:06:08,391 IDENTIFIED CIRCUITS IN THE BRAIN 128 00:06:08,391 --> 00:06:11,061 AND DIRECTOR OF THE ARTHUR 129 00:06:11,061 --> 00:06:17,000 VINING CENTERS AT THE SALK AND 130 00:06:17,000 --> 00:06:18,234 AT SCRIPPS RESEARCH INSTITUTE 131 00:06:18,234 --> 00:06:20,170 LOOKING AT WHERE DRUGS PRODUCES 132 00:06:20,170 --> 00:06:23,707 ITS EFFECTS AT THE CELLULAR AND 133 00:06:23,707 --> 00:06:24,975 SYSTEMS LEVEL. 134 00:06:24,975 --> 00:06:26,710 HE WAS MY BOSS FOR 40 YEARS. 135 00:06:26,710 --> 00:06:31,648 HE RECRUITED ME TO THE SALK 136 00:06:31,648 --> 00:06:33,350 INSTITUTE AND MOVED WITH HIM TO 137 00:06:33,350 --> 00:06:34,684 SCRIPPS RESEARCH. 138 00:06:34,684 --> 00:06:36,886 FLOYD WAS ONE OF THE MOST 139 00:06:36,886 --> 00:06:44,628 PREEMINENT NEUROSCIENCE -- NEURO 140 00:06:44,628 --> 00:06:46,029 SCIENTIST AND FORMER PRESIDENT 141 00:06:46,029 --> 00:06:47,430 OF THE SOCIETY FOR NEUROSCIENCE 142 00:06:47,430 --> 00:06:50,734 EARLY ON AND CO-FOUNDER OF A BIO 143 00:06:50,734 --> 00:06:54,270 TECHNOLOGY COMPANY THAT , 144 00:06:54,270 --> 00:06:57,140 MANUFACTURES AND COMMERCIALIZES 145 00:06:57,140 --> 00:06:58,775 MEDICINES FOR THE TREATMENT OF 146 00:06:58,775 --> 00:07:02,345 CHRONIC DISEASES AND THAT 147 00:07:02,345 --> 00:07:05,015 COMPANY PRODUCED MANY LONG 148 00:07:05,015 --> 00:07:12,355 ACTING DRUGS INCLUDING THE 149 00:07:12,355 --> 00:07:15,425 MALTREXONE USED FOR TREATMENT 150 00:07:15,425 --> 00:07:21,131 DISORDER AND WE ALSO LOST 151 00:07:21,131 --> 00:07:22,699 CHARLO 152 00:07:22,699 --> 00:07:27,637 CHARLOTTE BOETTIGER. 153 00:07:27,637 --> 00:07:29,639 SHE WAS THE PROFESSOR OF 154 00:07:29,639 --> 00:07:30,740 NEUROSCIENCE AT THE ALCOHOL 155 00:07:30,740 --> 00:07:32,442 RESEARCH CENTER AND SHE USED A 156 00:07:32,442 --> 00:07:40,717 VARIETY OF APPROACHES TO EXAMINE 157 00:07:40,717 --> 00:07:42,619 ASSISTIVE LEARN AND SELECTION 158 00:07:42,619 --> 00:07:44,954 BIAS FOR IMMEDIATE AWARDS AND 159 00:07:44,954 --> 00:07:46,923 RETENTION TOWARDS 160 00:07:46,923 --> 00:07:49,159 ALCOHOL-RELATED INFORMATION. 161 00:07:49,159 --> 00:07:51,561 SHE WAS A HIGHLY PRODUCTIVE 162 00:07:51,561 --> 00:07:52,295 RESEARCHER AND STRONG ADVOCATE 163 00:07:52,295 --> 00:07:57,667 FOR ALCOHOL RESEARCH. 164 00:07:57,667 --> 00:08:02,706 WHERE HE ALSO LOST JAN FROEHLICH 165 00:08:02,706 --> 00:08:05,642 A PROFESSOR OF THE INDIANA 166 00:08:05,642 --> 00:08:08,978 UNIVER 167 00:08:08,978 --> 00:08:09,279 UNIVERSITY. 168 00:08:09,279 --> 00:08:11,114 AND SERVED AS THE SCIENTIFIC 169 00:08:11,114 --> 00:08:12,482 CO-DIRECTOR OF THE ALCOHOL 170 00:08:12,482 --> 00:08:14,684 RESEARCH CENTER IN INDIANA 171 00:08:14,684 --> 00:08:15,985 UNIVERSITY SCHOOL OF MEDICINE. 172 00:08:15,985 --> 00:08:18,254 SHE DEDICATED HER CAREER TO 173 00:08:18,254 --> 00:08:19,589 UNDERSTANDING HOW ALCOHOL AFFECT 174 00:08:19,589 --> 00:08:21,725 THE BRAIN AND HOW ADDICTION AND 175 00:08:21,725 --> 00:08:23,693 ALCOHOL USE DISORDER DEVELOP. 176 00:08:23,693 --> 00:08:25,161 SHE STUDIED THESE QUESTIONS 177 00:08:25,161 --> 00:08:28,531 THROUGH THE LENS OF HORMONAL, 178 00:08:28,531 --> 00:08:29,466 NEUROCHEMICAL AND GENETIC 179 00:08:29,466 --> 00:08:31,267 FACTORS AND WORKED TOWARDS THE 180 00:08:31,267 --> 00:08:32,836 DEVELOPMENT OF PHARMACO 181 00:08:32,836 --> 00:08:35,138 THERAPIES FOR ALCOHOL USE 182 00:08:35,138 --> 00:08:35,405 DISORDER. 183 00:08:35,405 --> 00:08:38,308 I KNEW JAN QUITE WELL. 184 00:08:38,308 --> 00:08:41,644 SHE WAS A REMARKABLE PERSON 185 00:08:41,644 --> 00:08:43,646 BECAUSE SHE ALWAYS TOLD YOU WHAT 186 00:08:43,646 --> 00:08:44,881 SHE THOUGHT AND YOU COULD DEPEND 187 00:08:44,881 --> 00:08:52,622 ON HER FOR THOSE OPINIONS. 188 00:08:52,622 --> 00:08:55,558 AND MARTIN KENT TRUSTY WAS 189 00:08:55,558 --> 00:08:57,560 BEFORE MY TIME, I KNOW THAT'S 190 00:08:57,560 --> 00:08:59,162 HARD TO BELIEVE. 191 00:08:59,162 --> 00:09:02,165 HE WAS NIAAA'S EXECUTIVE OFFICER 192 00:09:02,165 --> 00:09:04,367 FOR 29 YEARS GUIDING THE 193 00:09:04,367 --> 00:09:05,468 ADMINISTRATIVE AND MANAGEMENT 194 00:09:05,468 --> 00:09:08,571 AFFAIRS UNTIL HE RETIRED IN 195 00:09:08,571 --> 00:09:09,205 1999. 196 00:09:09,205 --> 00:09:10,707 AFTER RETIRING, NIAAA 197 00:09:10,707 --> 00:09:11,975 ESTABLISHED AN ANNUAL 198 00:09:11,975 --> 00:09:14,144 MERITORIOUS AWARD IN HIS NAME 199 00:09:14,144 --> 00:09:16,279 HONORING HIS LEADERSHIP AND 200 00:09:16,279 --> 00:09:16,746 CONTRIBUTIONS. 201 00:09:16,746 --> 00:09:18,681 IT'S GIVEN EACH YEAR TO A STAFF 202 00:09:18,681 --> 00:09:22,685 MEMBER IN RECOGNITION OF THE 203 00:09:22,685 --> 00:09:25,722 OUTSTANDING COMMITMENT TO AND 204 00:09:25,722 --> 00:09:27,090 EXCELLENCE IN MANAGEMENT OF 205 00:09:27,090 --> 00:09:27,357 NIAAA. 206 00:09:27,357 --> 00:09:30,994 IT'S ONE OF MY FAVORITE AWARDS 207 00:09:30,994 --> 00:09:33,029 BECAUSE IT AWARDS INDIVIDUALS 208 00:09:33,029 --> 00:09:35,064 WHO DON'T NECESSARILY GET THAT 209 00:09:35,064 --> 00:09:38,701 KIND OF RECOGNITION IN OUR 210 00:09:38,701 --> 00:09:40,136 ENTERPRISE. 211 00:09:40,136 --> 00:09:48,211 RETIREMENTS. 212 00:09:48,211 --> 00:09:50,079 RAYE LITTEN RETIRED AFTER ALMOST 213 00:09:50,079 --> 00:09:51,815 40 YEARS OF FEDERAL SERVICE WITH 214 00:09:51,815 --> 00:09:53,149 THE LAST 36 YEARS SPENT AT 215 00:09:53,149 --> 00:09:56,186 NIAAA. 216 00:09:56,186 --> 00:09:57,954 HE HAD MAJOR IMPACT ON THE 217 00:09:57,954 --> 00:09:59,255 MEDICATIONS DEVELOPMENT FIELD 218 00:09:59,255 --> 00:10:02,692 INCLUDING THE CREATION OF THE 219 00:10:02,692 --> 00:10:04,127 NIAAA CLINICAL INVESTIGATIONS 220 00:10:04,127 --> 00:10:04,894 GROUP. 221 00:10:04,894 --> 00:10:05,995 A HIGHLY SUCCESSFUL PROGRAM 222 00:10:05,995 --> 00:10:08,731 DESIGN TO TEST THE SAFETY AND 223 00:10:08,731 --> 00:10:09,933 EFFECTIVENESS OF PROMISING 224 00:10:09,933 --> 00:10:11,034 COMPOUNDS TO TREAT ALCOHOL USE 225 00:10:11,034 --> 00:10:14,237 DISORDER AND PROOF OF CONCEPT 226 00:10:14,237 --> 00:10:15,205 PHASE 2 CLINICAL TRIALS. 227 00:10:15,205 --> 00:10:19,709 HE SPEARHEADED THE ADVANCEMENT 228 00:10:19,709 --> 00:10:21,544 OF TWO U.S. FOOD AND DRUG 229 00:10:21,544 --> 00:10:23,146 ADMINISTRATION APPROVED OUTCOME 230 00:10:23,146 --> 00:10:24,681 MEASURES, USED IN MEDICATION 231 00:10:24,681 --> 00:10:26,182 DEVELOPMENT TRIALS. 232 00:10:26,182 --> 00:10:28,618 DR. LITTEN WAS ALSO INSTRUMENTAL 233 00:10:28,618 --> 00:10:30,320 IN THE DEVELOPMENT OF NIAAA'S 234 00:10:30,320 --> 00:10:33,690 RECOVERY, DEFINITIONS AND 235 00:10:33,690 --> 00:10:36,359 DEVELOPMENT OF NIAAA HEALTH CARE 236 00:10:36,359 --> 00:10:37,026 PROFESSIONALS CORE RESOURCE ON 237 00:10:37,026 --> 00:10:38,595 ALCOHOL. 238 00:10:38,595 --> 00:10:39,796 IN ADDITION TO HIS MANY 239 00:10:39,796 --> 00:10:42,699 ACCOLADES AND ACHIEVEMENTS HE'LL 240 00:10:42,699 --> 00:10:43,499 BE TRULY MISSED AS ABLE 241 00:10:43,499 --> 00:10:46,302 EXTRAORDINARY MENTOR, LEADER, 242 00:10:46,302 --> 00:10:46,970 SCHOLAR AND COLLEAGUE. 243 00:10:46,970 --> 00:10:51,975 WE WISH HIM ALL THE BEST UP HIS 244 00:10:51,975 --> 00:10:52,275 RETIREMENT. 245 00:10:52,275 --> 00:10:55,345 ANTONIO NURONA RETIRED AS THE 246 00:10:55,345 --> 00:10:58,281 DIRECTOR OF NEUROSCIENCE AND 247 00:10:58,281 --> 00:10:58,548 BEHAVIOR. 248 00:10:58,548 --> 00:11:01,451 HE HAD 35 YEARS OF FEDERAL 249 00:11:01,451 --> 00:11:01,684 SERVICE. 250 00:11:01,684 --> 00:11:05,188 DURING HIS TENURE AT NIAAA HE 251 00:11:05,188 --> 00:11:06,723 TRANSFORMED NEUROSCIENCE 252 00:11:06,723 --> 00:11:08,458 RESEARCH BY INTRODUCING NEW 253 00:11:08,458 --> 00:11:10,460 DOMAINS OF RESEARCH THAT OPENED 254 00:11:10,460 --> 00:11:13,663 THE DOOR FOR NEUROSCIENCE FOR 255 00:11:13,663 --> 00:11:14,430 DIAGNOSIS, PREVENTION AND 256 00:11:14,430 --> 00:11:16,399 TREATMENT OF ALCOHOL MISUSE AND 257 00:11:16,399 --> 00:11:17,467 ALCOHOL USE DISORDER. 258 00:11:17,467 --> 00:11:19,502 THESE EFFORTS CULMINATED IN A 259 00:11:19,502 --> 00:11:22,205 WIDE RANGE OF ADVANCEMENTS IN 260 00:11:22,205 --> 00:11:24,741 ALCOHOL RESEARCH AND TRAINING 261 00:11:24,741 --> 00:11:25,975 PROGRAMS AND INITIATIVES 262 00:11:25,975 --> 00:11:26,709 INCLUDING THE COLLABORATIVE 263 00:11:26,709 --> 00:11:29,379 STUDIES ON THE GENETICS OF 264 00:11:29,379 --> 00:11:30,613 ALCOHOLISM. 265 00:11:30,613 --> 00:11:32,682 THE INTEGRATIVE NEUROSCIENCE 266 00:11:32,682 --> 00:11:35,318 INITIATIVE AND THE NATIONAL 267 00:11:35,318 --> 00:11:36,719 CONSORTIUM ON ALCOHOL, NEURO 268 00:11:36,719 --> 00:11:40,156 DEVELOPMENT AND ADOLESCENCE AND 269 00:11:40,156 --> 00:11:42,959 ADULTHOOD AND THE CONSORTIUM ON 270 00:11:42,959 --> 00:11:46,462 THE NEUROBIOLOGY OF ADOLESCENT 271 00:11:46,462 --> 00:11:49,565 DRINKING AND ADULTHOOD, AND THE 272 00:11:49,565 --> 00:11:51,167 ADOLESCENT BRAIN COGNITIVE 273 00:11:51,167 --> 00:11:53,169 DEVELOPMENT STUDY, THE ABCD 274 00:11:53,169 --> 00:11:54,203 STUDY PART OF OUR EFFORT. 275 00:11:54,203 --> 00:11:54,771 WE'LL BE TALKING ABOUT THAT 276 00:11:54,771 --> 00:11:56,406 TOMORROW. 277 00:11:56,406 --> 00:11:58,708 SO WE WISH HIM ALL THE BEST FOR 278 00:11:58,708 --> 00:12:03,079 HIS RETIREMENT. 279 00:12:03,079 --> 00:12:04,414 THE LIST GOES ON QUITE A LONG 280 00:12:04,414 --> 00:12:06,683 WAYS AS MANY OF YOU PROBABLY 281 00:12:06,683 --> 00:12:07,951 FIGURED OUT. 282 00:12:07,951 --> 00:12:09,719 SO SO I'M GOING TO GO THROUGH 283 00:12:09,719 --> 00:12:11,955 THESE LISTS BECAUSE I'D LIKE TO 284 00:12:11,955 --> 00:12:14,691 HONOR THE THAT DID WORK AND 285 00:12:14,691 --> 00:12:18,394 SERVE WITH US AT NIAAA. 286 00:12:18,394 --> 00:12:20,663 GREGORY BLOS WAS A PUBLIC HEALTH 287 00:12:20,663 --> 00:12:22,265 ANALYST AND PROGRAM OFFICER IN 288 00:12:22,265 --> 00:12:25,234 THE DIVISION OF EPIDEMIOLOGY AND 289 00:12:25,234 --> 00:12:26,135 PREVENTION RESEARCH. 290 00:12:26,135 --> 00:12:27,503 HE RETIRED AFTER ALMOST 33 YEARS 291 00:12:27,503 --> 00:12:28,838 OF FEDERAL SERVICE. 292 00:12:28,838 --> 00:12:31,941 HE OVERSAW PROJECTS THAT 293 00:12:31,941 --> 00:12:34,210 EVALUATED HOW ALCOHOL POLICY 294 00:12:34,210 --> 00:12:35,645 IMPLEMENTATION INFLUENCE ALCOHOL 295 00:12:35,645 --> 00:12:37,447 DRINKING AT THE STATE AND LOCAL 296 00:12:37,447 --> 00:12:41,451 LEVEL AND LED EFFORTS ON THE 297 00:12:41,451 --> 00:12:42,618 ALCOHOL POLICY INFORMATION 298 00:12:42,618 --> 00:12:42,852 SYSTEM. 299 00:12:42,852 --> 00:12:44,253 A VALUABLE TOOL TO EVALUATE THE 300 00:12:44,253 --> 00:12:46,689 IMPACT OF STATE POLICIES ON 301 00:12:46,689 --> 00:12:47,256 ALCOHOL MISUSE AND RELATED 302 00:12:47,256 --> 00:12:55,465 CONSEQUENCES. 303 00:12:55,465 --> 00:13:00,436 AN INVENTORY SPECIALIST AFTER 27 304 00:13:00,436 --> 00:13:03,806 YEARS WITH THE CLINICAL AND 305 00:13:03,806 --> 00:13:06,676 BIOLOGICAL RESEARCH AND 306 00:13:06,676 --> 00:13:09,679 ADMINISTRATIVE SERVICES BRANCH. 307 00:13:09,679 --> 00:13:20,189 A COMPUTER SPECIALIST IN THE 308 00:13:43,413 --> 00:13:47,483 LAST YEARS WE HAD RESEARCH 309 00:13:47,483 --> 00:13:49,685 PROGRAMS. 310 00:13:49,685 --> 00:13:52,488 AN ADMINISTRATIVE OFFICER IN THE 311 00:13:52,488 --> 00:13:53,623 ADMINISTRATIVE SERVICES BRANCH 312 00:13:53,623 --> 00:13:55,058 RETIRED AFTER 30 YEARS OF 313 00:13:55,058 --> 00:13:56,592 SERVICE AT NIAAA. 314 00:13:56,592 --> 00:13:58,828 SHE SERVED IN MULTIPLE ROLES 315 00:13:58,828 --> 00:14:03,599 WITHIN THE BRANCH. 316 00:14:03,599 --> 00:14:06,469 A TRAVEL SPECIALIST IN THE NIAAA 317 00:14:06,469 --> 00:14:08,237 OFFICE OF THE DIRECTOR RETIRED 318 00:14:08,237 --> 00:14:10,673 AFTER 19 YEARS OF FEDERAL 319 00:14:10,673 --> 00:14:11,107 SERVICE. 320 00:14:11,107 --> 00:14:14,377 SHE JOINED NIAAA IN 2014. 321 00:14:14,377 --> 00:14:16,612 SHE TOOK CARE OF ALL MY TRAVEL 322 00:14:16,612 --> 00:14:20,750 IN ALL THESE 11 YEARS I'VE BEEN 323 00:14:20,750 --> 00:14:21,951 AT NIAAA AND NEVER ONCE LEFT ME 324 00:14:21,951 --> 00:14:24,187 STRANDED OR WITHOUT A HOTEL ROOM 325 00:14:24,187 --> 00:14:26,989 AND I DON'T THINK I EVEN HAD A 326 00:14:26,989 --> 00:14:31,794 DELAYED FLIGHT SO BLESS YOU. 327 00:14:31,794 --> 00:14:32,895 MICHAEL TODD KING IN THE OFFICE 328 00:14:32,895 --> 00:14:34,864 OF INTEGRATIVE NEUROSCIENCE IN 329 00:14:34,864 --> 00:14:37,400 THE DIVISION OF INTRAMURAL 330 00:14:37,400 --> 00:14:40,169 CLINICAL AND BIOLOGICAL RESEARCH 331 00:14:40,169 --> 00:14:41,170 RETIRED AFTER ALMOST 33 YEARS OF 332 00:14:41,170 --> 00:14:42,572 FEDERAL SERVICE. 333 00:14:42,572 --> 00:14:43,506 HE PREVIOUSLY WORKED WITH 334 00:14:43,506 --> 00:14:46,709 DR. BEACH IN THE LABORATORY ON 335 00:14:46,709 --> 00:14:47,510 METABOLIC CONTROL. 336 00:14:47,510 --> 00:14:49,212 KIMBERLY MARTIN, A TECHNICAL 337 00:14:49,212 --> 00:14:52,315 WRITER AND EDITOR IN THE OFFICE 338 00:14:52,315 --> 00:14:58,254 OF SCIENCE POLICY AND 339 00:14:58,254 --> 00:14:58,888 COMMUNICATIONS IS RETIRING AFTER 340 00:14:58,888 --> 00:15:01,891 18 YEARS TO NIH OVER ALL AND 341 00:15:01,891 --> 00:15:04,093 WROTE AND EDITED NIAAA 342 00:15:04,093 --> 00:15:04,994 RESOURCES, SOCIAL MEDIA CONTENT 343 00:15:04,994 --> 00:15:08,231 AND OTHER MATERIALS AND WAS THE 344 00:15:08,231 --> 00:15:10,700 LEAD FOR DEVELOPING NIAAA SHORT 345 00:15:10,700 --> 00:15:14,437 TAKE VIDEO SERIES. 346 00:15:14,437 --> 00:15:16,606 A COMPUTER SCIENTIST WESTBOUND 347 00:15:16,606 --> 00:15:17,607 THE INFORMATION TECHNOLOGY 348 00:15:17,607 --> 00:15:18,741 BRANCH IN THE DIVISION OF 349 00:15:18,741 --> 00:15:21,344 INTRAMURAL AND CLINICAL 350 00:15:21,344 --> 00:15:21,944 BIOLOGICAL RESEARCH RETIRED 351 00:15:21,944 --> 00:15:24,947 AFTER ALMOST 33 YEARS OF FEDERAL 352 00:15:24,947 --> 00:15:26,048 SERVICE. 353 00:15:26,048 --> 00:15:27,383 SHE PERFORMED DATA ANALYSIS FOR 354 00:15:27,383 --> 00:15:31,621 THE NIAAA CLINICAL PROGRAM AND 355 00:15:31,621 --> 00:15:37,360 PREVIOUSLY WORKED AT NIAAA 356 00:15:37,360 --> 00:15:41,230 INTRAMURAL LABORATORIES AND WE 357 00:15:41,230 --> 00:15:43,599 HAVE ANOTHER RETIREE AFTER 16 358 00:15:43,599 --> 00:15:45,434 YEARS AND COORDINATED NIAAA 359 00:15:45,434 --> 00:15:47,270 GREEN BANK ACTIVITIES AND SERVED 360 00:15:47,270 --> 00:15:49,372 IN THE JOINT ADDICTION AND 361 00:15:49,372 --> 00:15:49,972 MENTAL AGING DATA ACCESS 362 00:15:49,972 --> 00:16:00,149 COMMITTEE. 363 00:16:02,718 --> 00:16:04,420 WE HAVE ANOTHER RETIREE. 364 00:16:04,420 --> 00:16:06,889 FOLLOWING HER TIME AS A STAFF 365 00:16:06,889 --> 00:16:08,491 SCIENTIST IN THE SECTION ON 366 00:16:08,491 --> 00:16:10,793 LIVER BIOLOGY SHE JOINED THE 367 00:16:10,793 --> 00:16:14,330 DIVISION IN 2006. 368 00:16:14,330 --> 00:16:17,333 AND SHAPED A ROLE IN THE 369 00:16:17,333 --> 00:16:20,002 ASSOCIATED HEPATITIS NETWORK 370 00:16:20,002 --> 00:16:21,337 WHICH HAS HAD AND CONTINUES TO 371 00:16:21,337 --> 00:16:22,838 HAVE BROAD IMPACTS ON THE FIELD 372 00:16:22,838 --> 00:16:27,076 OF LIVER DISEASE AND CLINICAL 373 00:16:27,076 --> 00:16:29,278 PRACTICE. 374 00:16:29,278 --> 00:16:31,314 GREGORY ROA IN THE OFFICE OF 375 00:16:31,314 --> 00:16:32,415 SCIENCE POLICY AND 376 00:16:32,415 --> 00:16:34,684 COMMUNICATIONS RETIRED AFTER 377 00:16:34,684 --> 00:16:37,053 MORE THAN 18 YEARS WITH NIAAA 378 00:16:37,053 --> 00:16:38,020 AND ORGANIZED OUTREACH EFFORTS 379 00:16:38,020 --> 00:16:42,258 AND KEY TO A WIDE RANGE OF NIAAA 380 00:16:42,258 --> 00:16:44,360 COMMUNICATION ACTIVITIES 381 00:16:44,360 --> 00:16:45,361 INCLUDING WEBSITES, THE ALCOHOL 382 00:16:45,361 --> 00:16:47,563 TREATMENT NAVIGATOR, SPECTRUM 383 00:16:47,563 --> 00:16:49,932 AND THE NIH RECORD. 384 00:16:49,932 --> 00:16:51,667 BRENDA ROBERTSON A PROGRAM 385 00:16:51,667 --> 00:16:52,868 SPECIALIST IN THE DIVISION OF 386 00:16:52,868 --> 00:16:54,604 INTRAMURAL CLINICAL AND 387 00:16:54,604 --> 00:16:55,471 BIOLOGICAL RESEARCH RETIRED 388 00:16:55,471 --> 00:16:56,839 AFTER 33 YEARS IN FEDERAL 389 00:16:56,839 --> 00:16:58,674 SERVICE. 390 00:16:58,674 --> 00:17:02,678 SHE SERVED MANY ROLES FOR THE 391 00:17:02,678 --> 00:17:03,446 INTRAMURAL RESEARCH PROGRAM 392 00:17:03,446 --> 00:17:06,682 THROUGHOUT HER CAREER RECENTLY 393 00:17:06,682 --> 00:17:10,419 IN PROCUREMENT. 394 00:17:10,419 --> 00:17:14,824 AND A STATISTICIAN IN BIO METRIC 395 00:17:14,824 --> 00:17:16,225 IN THE DIVISION OF INTRAMURAL 396 00:17:16,225 --> 00:17:18,127 CLINICAL AND BIO MEDICAL 397 00:17:18,127 --> 00:17:19,829 RESEARCH RETIRED AFTER 33 YEARS 398 00:17:19,829 --> 00:17:21,330 OF FEDERAL SERVICE. 399 00:17:21,330 --> 00:17:25,268 AND MARY ELLIS SHIRLEY RETIRED 400 00:17:25,268 --> 00:17:25,935 FROM FEDERAL SERVICE AFTER 401 00:17:25,935 --> 00:17:33,376 JOINING NIAAA IN 2022 AND NIH IN 402 00:17:33,376 --> 00:17:35,077 2022 AND NIAAA IN 2006 AND 403 00:17:35,077 --> 00:17:37,947 OVERSAW GRANTS ON YOUNG ADULTS, 404 00:17:37,947 --> 00:17:39,382 OLDER POPULATIONS AND 405 00:17:39,382 --> 00:17:40,149 TRANSLATIONAL SCIENCE WITHIN THE 406 00:17:40,149 --> 00:17:42,318 DIVISION OF TREATMENT AND 407 00:17:42,318 --> 00:17:42,585 RECOVERY. 408 00:17:42,585 --> 00:17:44,754 DR. SHIRLEY WAS CO-CHAIR OF THE 409 00:17:44,754 --> 00:17:46,689 NIAAA CENTERS AND TRAINING 410 00:17:46,689 --> 00:17:51,994 COMMITTEE. 411 00:17:51,994 --> 00:17:54,130 A CHEMIST IN THE DIVISION OF 412 00:17:54,130 --> 00:17:57,099 INTRAMURAL AND CLINICAL AND 413 00:17:57,099 --> 00:17:58,701 BIOLOGICAL RESEARCH RETIRED 414 00:17:58,701 --> 00:18:02,471 AFTER 33 YEARS OF FEDERAL 415 00:18:02,471 --> 00:18:04,607 SERVICE HE WAS AN ESSENTIAL 416 00:18:04,607 --> 00:18:06,575 MEMBER OF THE CLINICAL CORPS 417 00:18:06,575 --> 00:18:07,610 TEAM AND AN ANALYST INVEST 418 00:18:07,610 --> 00:18:09,645 OFFICE OF POLICY AND 419 00:18:09,645 --> 00:18:11,714 COMMUNICATIONS RETIRED AFTER 25 420 00:18:11,714 --> 00:18:14,817 YEARS OF FEDERAL SERVICE. 421 00:18:14,817 --> 00:18:17,186 HE COORDINATED THE COMPLIANCE 422 00:18:17,186 --> 00:18:18,688 WITH THE POLICY OF INCLUSION OF 423 00:18:18,688 --> 00:18:22,925 WOMEN AND MINORITIES AND ENSURED 424 00:18:22,925 --> 00:18:24,894 NIAAA MATERIALS WERE ACCESSIBLE 425 00:18:24,894 --> 00:18:28,264 TO THOSE WITH DISABILITIES. 426 00:18:28,264 --> 00:18:29,832 AND A SENIOR RESEARCH PHYSICIAN 427 00:18:29,832 --> 00:18:32,535 IN THE LABORATORY OF 428 00:18:32,535 --> 00:18:33,803 NEUROIMAGING IN THE DIVISION OF 429 00:18:33,803 --> 00:18:35,438 INTRAMURAL CLINICAL AND 430 00:18:35,438 --> 00:18:36,872 BIOLOGICAL RESEARCH RETIRED 431 00:18:36,872 --> 00:18:38,674 AFTER 11 YEARS OF FEDERAL 432 00:18:38,674 --> 00:18:39,608 SERVICE. 433 00:18:39,608 --> 00:18:42,211 HE STUDIED THE NEURO PSYCHIATRIC 434 00:18:42,211 --> 00:18:44,513 MECHANISMS AND MANIFESTATIONS OF 435 00:18:44,513 --> 00:18:52,321 ALCOHOL AND DISORDER AND HYPER 436 00:18:52,321 --> 00:18:54,924 ACTIVITY DISORDER AND A 437 00:18:54,924 --> 00:18:56,258 BIOLOGIST WITH THE DIVISION OF 438 00:18:56,258 --> 00:18:59,829 INTRAMURAL CLINICAL AND 439 00:18:59,829 --> 00:19:00,463 BIOLOGICAL RESEARCH RETIRED 440 00:19:00,463 --> 00:19:05,067 AFTER 24 YEARS OF FEDERAL 441 00:19:05,067 --> 00:19:05,434 SERVICE. 442 00:19:05,434 --> 00:19:08,003 RECENT REDUCTIONS IN FORCE 443 00:19:08,003 --> 00:19:10,139 IMPACTED SIX MEMBERS IN THE 444 00:19:10,139 --> 00:19:11,440 NIAAA OFFICE OF SCIENCE POLICY 445 00:19:11,440 --> 00:19:12,274 AND COMMUNICATIONS AND FOUR 446 00:19:12,274 --> 00:19:14,877 STAFF MEMBERS AT NIAAA'S ETHICS 447 00:19:14,877 --> 00:19:21,317 AND MANAGEMENT ANALYSIS BRANCH. 448 00:19:21,317 --> 00:19:25,521 IN ADDITION FOUR STAFF MEMBERS 449 00:19:25,521 --> 00:19:27,189 WERE AFFECTED BY DISMISSALS. 450 00:19:27,189 --> 00:19:29,325 I HOPE BY GOING THROUGH THE 451 00:19:29,325 --> 00:19:32,528 LISTS AND HONORING THE PEOPLE 452 00:19:32,528 --> 00:19:39,135 WHO SERVED WITH US YOU REALIZE 453 00:19:39,135 --> 00:19:40,936 WE LOST MANY CONTRIBUTORS TO OUR 454 00:19:40,936 --> 00:19:44,540 PROGRAM OVER THE LAST 10 YEARS 455 00:19:44,540 --> 00:19:48,844 AND LONGER SECOND, THE REMAINING 456 00:19:48,844 --> 00:19:50,012 STAFF HAVE A LOT OF WORK TO DO 457 00:19:50,012 --> 00:19:50,713 AS A RESULT. 458 00:19:50,713 --> 00:19:52,214 I WANT YOU TO UNDERSTAND HOW 459 00:19:52,214 --> 00:19:55,117 MUCH WORK EVERYONE IS DOING AT 460 00:19:55,117 --> 00:19:58,754 NIAAA TO KEEP OUR MISSION ON 461 00:19:58,754 --> 00:19:59,121 TARGET. 462 00:19:59,121 --> 00:20:05,261 SO I WANT TO CONGRATULATE 463 00:20:05,261 --> 00:20:09,265 EVERYONE AT NIAAA PART OF OUR 464 00:20:09,265 --> 00:20:12,935 TEAM FOR ALL YOUR HARD WORK. 465 00:20:12,935 --> 00:20:14,003 THE TRANSITION IS CHALLENGING 466 00:20:14,003 --> 00:20:17,373 FOR EVERYONE AND WE'RE ALL 467 00:20:17,373 --> 00:20:21,677 WORKING HARD TO KEEP OURSELVES 468 00:20:21,677 --> 00:20:22,511 FOCUSED ON OUR MISSION. 469 00:20:22,511 --> 00:20:25,648 I THOUGHT IT WAS IMPORTANT TO 470 00:20:25,648 --> 00:20:33,689 LET YOU ALL KNOW ABOUT THOSE OF 471 00:20:33,689 --> 00:20:35,157 US WHO HAVE GONE ON TO WHAT I 472 00:20:35,157 --> 00:20:41,797 HOPE IS A VERY HAPPY RETIREMENT. 473 00:20:41,797 --> 00:20:45,034 INSTITUTE UPDATES ON MARCH 15 474 00:20:45,034 --> 00:20:46,669 THE PRESIDENT SIGNED A FULL YEAR 475 00:20:46,669 --> 00:20:47,837 CONTINUING RESOLUTION EXTENDING 476 00:20:47,837 --> 00:20:52,508 FUNDING AT THE FISCAL 2024 477 00:20:52,508 --> 00:20:54,343 LEVELS TO SEPTEMBER 30, 2025. 478 00:20:54,343 --> 00:20:59,782 THE FISCAL YEAR 2026 479 00:20:59,782 --> 00:21:02,117 APPROPRIATION FOR NIH AND NIAAA 480 00:21:02,117 --> 00:21:04,220 HAS NOT BEEN FINALIZED AND I 481 00:21:04,220 --> 00:21:05,454 WILL SAY NOTHING ELSE AT THE 482 00:21:05,454 --> 00:21:06,288 BUDGET AT THIS POINT BECAUSE 483 00:21:06,288 --> 00:21:07,623 WE'RE SIMPLY WAITING FOR 484 00:21:07,623 --> 00:21:10,359 CONGRESS TO DO WHAT CONGRESS 485 00:21:10,359 --> 00:21:13,329 ALWAYS DOES WHICH IS COME UP 486 00:21:13,329 --> 00:21:17,466 WITH A BUDGET BEFORE THE END OF 487 00:21:17,466 --> 00:21:20,002 THE FISCAL YEAR. 488 00:21:20,002 --> 00:21:26,342 WE DID PROMOTE THE BENEFITS OF 489 00:21:26,342 --> 00:21:29,411 JANUARY AND WE HELD A MEDIA TOUR 490 00:21:29,411 --> 00:21:32,147 WHERE I SPOKE TO 19TV AND RADIO 491 00:21:32,147 --> 00:21:35,384 OUTLETS HOW PEOPLE CAN ASSESS 492 00:21:35,384 --> 00:21:37,086 THEIR DRINKING. 493 00:21:37,086 --> 00:21:40,456 THE EVENT ALLEGEDLY REACH 21 494 00:21:40,456 --> 00:21:41,056 MILLION PEOPLE. 495 00:21:41,056 --> 00:21:42,791 IT'S SOMETHING WE'VE BEEN DOING 496 00:21:42,791 --> 00:21:49,999 FOR FIVE OR SIX YEARS NOW AND 497 00:21:49,999 --> 00:21:51,934 EVER YEAR THERE SEEMS TO BE MORE 498 00:21:51,934 --> 00:21:54,703 ACCEPTANCE AND ENTHUSIASM AND 499 00:21:54,703 --> 00:21:55,871 WANTING TO HEAR THE WORD ABOUT 500 00:21:55,871 --> 00:22:00,342 HOW AN INDIVIDUAL CAN ENGAGE IN 501 00:22:00,342 --> 00:22:01,143 RE-EVALUATING THEIR RELATIONSHIP 502 00:22:01,143 --> 00:22:01,744 WITH ALCOHOL. 503 00:22:01,744 --> 00:22:10,553 WE DID IT AGAIN THIS YEAR. 504 00:22:10,553 --> 00:22:13,923 WE RECOGNIZED DRY JANUARY ON 505 00:22:13,923 --> 00:22:15,958 SOCIAL MEDIA WITH INFLUENCERS TO 506 00:22:15,958 --> 00:22:16,992 RECOGNIZE THE IMPORTANCE OF 507 00:22:16,992 --> 00:22:18,694 TAKING A BREAK FROM ALCOHOL. 508 00:22:18,694 --> 00:22:21,597 AND IF YOU DON'T CARE ANY 509 00:22:21,597 --> 00:22:26,335 PARTICULAR PROGRAM, IT COULD BE 510 00:22:26,335 --> 00:22:35,477 SOBER OCTOBER, IT CAN BE 511 00:22:35,477 --> 00:22:38,314 MOCKTAILS AND DRY BARS IF YOU 512 00:22:38,314 --> 00:22:41,317 CAN RE-EVALUATE YOUR 513 00:22:41,317 --> 00:22:42,484 RELATIONSHIP WITH ALCOHOL IT CAN 514 00:22:42,484 --> 00:22:44,987 REDUCE THE BEHAVIOR AND MOVES 515 00:22:44,987 --> 00:22:46,689 THE GROUP THAT MOVES TO THE 516 00:22:46,689 --> 00:22:50,693 OTHER CATEGORY OF DRINKING 517 00:22:50,693 --> 00:22:54,330 EXCESSIVELY. 518 00:22:54,330 --> 00:22:57,032 SO WHAT'S AHEAD IS THE ANNUAL 519 00:22:57,032 --> 00:23:00,336 MEETING THAT WILL TAKE PLACE IN 520 00:23:00,336 --> 00:23:01,503 SEATTLE WASHINGTON ON THE 521 00:23:01,503 --> 00:23:04,473 EMPHASIS OF PREVENTION SCIENCE 522 00:23:04,473 --> 00:23:11,380 FOR ACTION LEVERAGE AND IN THE 523 00:23:11,380 --> 00:23:14,683 48th ANNUAL RESEARCH SCIENTIFIC 524 00:23:14,683 --> 00:23:19,154 MEETING WILL BE OCTOBER 24 TO 525 00:23:19,154 --> 00:23:27,730 25. 526 00:23:27,730 --> 00:23:29,264 AND JOIN THE ADVANCES IN SCIENCE 527 00:23:29,264 --> 00:23:29,798 AND HOPE TO EFFECT IN THE 528 00:23:29,798 --> 00:23:33,068 FUTURE. 529 00:23:33,068 --> 00:23:37,306 SO I PICKED OUT ONLY FOUR 530 00:23:37,306 --> 00:23:40,042 PRESENTATIONS TO TALK ABOUT 531 00:23:40,042 --> 00:23:40,242 TODAY. 532 00:23:40,242 --> 00:23:40,809 TWO ARE FROM OUR INTRAMURAL 533 00:23:40,809 --> 00:23:50,953 PROGRAM. 534 00:23:53,689 --> 00:23:56,558 I PICKED THEM BECAUSE THEY'RE 535 00:23:56,558 --> 00:23:57,292 AREAS WE DON'T PAY AS MUCH 536 00:23:57,292 --> 00:23:59,628 ATTENTION TO AND HOPE WE WILL 537 00:23:59,628 --> 00:24:00,529 WHERE WE'RE GOING IN THE FUTURE 538 00:24:00,529 --> 00:24:10,239 WHICH IS WITH A FOCUS ON ALCOHOL 539 00:24:10,239 --> 00:24:12,007 IT'S A CHRONIC DISEASE AND IS 540 00:24:12,007 --> 00:24:15,811 THE AFFECT ON LONGEVITY WHICH IS 541 00:24:15,811 --> 00:24:26,255 DR. BHATTACHARYA EMPHASIS. 542 00:24:40,569 --> 00:24:45,908 THE UPWARD OF TRAJECTORY OF LIFE 543 00:24:45,908 --> 00:24:48,844 EXPECTANCY EXPERIENCED A DECLINE 544 00:24:48,844 --> 00:24:59,321 IN THE UNITED STATES AND IT 545 00:25:02,758 --> 00:25:04,793 SCREENS FOR ALCOHOL USE TO 546 00:25:04,793 --> 00:25:07,262 EXAMINE CARDIOVASCULAR OUTCOMES 547 00:25:07,262 --> 00:25:11,533 OVER A FOUR-YEAR PERIOD. 548 00:25:11,533 --> 00:25:20,342 CONDUCTED BY A GROUP AND KAISER 549 00:25:20,342 --> 00:25:25,380 PERMANENTE IN NORTHERN 550 00:25:25,380 --> 00:25:25,681 CALIFORNIA. 551 00:25:25,681 --> 00:25:27,516 THE SAMPLING INCLUDED 42,000 552 00:25:27,516 --> 00:25:28,717 YOUNG AND MIDDLE AGED ADULT. 553 00:25:28,717 --> 00:25:31,320 AT THE FOUR-YEAR FOLLOW-UP THE 554 00:25:31,320 --> 00:25:34,423 RESEARCHERS FOUND AN INCREASED 555 00:25:34,423 --> 00:25:37,426 RISK FOR CORONARY HEART DISEASE 556 00:25:37,426 --> 00:25:40,062 AMONG MEN AND WOMEN WHO CONSUMED 557 00:25:40,062 --> 00:25:42,698 ALCOHOL ABOVE THE GUIDELINE 558 00:25:42,698 --> 00:25:44,233 RECOMMENDED LIMITS VERSUS AT OR 559 00:25:44,233 --> 00:25:45,734 ABOVE THE LIMITS. 560 00:25:45,734 --> 00:25:48,804 THE HIGHEST RISK WAS FOR MIDDLE 561 00:25:48,804 --> 00:25:51,507 AGE WOMEN. 562 00:25:51,507 --> 00:25:54,376 A COUPLE THINGS TO NOTE WEEKLY 563 00:25:54,376 --> 00:25:56,411 ALCOHOL OF THE LIMITS WAS 564 00:25:56,411 --> 00:25:58,680 ASSOCIATED WITH 26% HIGHER RISK 565 00:25:58,680 --> 00:26:02,618 OVER ALL FOR CORONARY HEART 566 00:26:02,618 --> 00:26:04,520 DISEASE. 567 00:26:04,520 --> 00:26:07,589 THERE WAS A 19% AND 43% MEN 568 00:26:07,589 --> 00:26:09,558 VERSUS WOMEN RISK OF CORONARY 569 00:26:09,558 --> 00:26:10,325 HEART DISEASE. 570 00:26:10,325 --> 00:26:11,226 SO SOMETHING WE'VE BEEN SEEING 571 00:26:11,226 --> 00:26:13,328 NOW OVER THE LAST FEW YEARS IS 572 00:26:13,328 --> 00:26:14,530 WOMEN ARE MORE ADVERSELY 573 00:26:14,530 --> 00:26:16,498 AFFECTED THAN MEN. 574 00:26:16,498 --> 00:26:17,699 YOU KNOW WHAT THE DIETARY 575 00:26:17,699 --> 00:26:19,434 GUIDELINES ARE BUT THEY'RE ON 576 00:26:19,434 --> 00:26:21,970 THE SLIDE IN THE PANEL. 577 00:26:21,970 --> 00:26:23,205 YOU CAN SEE IT WITHIN THE 578 00:26:23,205 --> 00:26:27,176 DIETARY GUIDELINES IS ONE TO 14 579 00:26:27,176 --> 00:26:32,080 WEEKS PER WEEK AND 1 TO 7 FOR 580 00:26:32,080 --> 00:26:33,182 WOMEN. 581 00:26:33,182 --> 00:26:36,985 HIGHER INCIDENTS FOR MEN ABOVE 582 00:26:36,985 --> 00:26:38,387 THE LIMITS AND WOMEN ABOVE THE 583 00:26:38,387 --> 00:26:44,760 LIMITS IS BIGGER THAN THE MEN'S. 584 00:26:44,760 --> 00:26:46,395 THEN ON THE BOTTOM PANEL WHILE 585 00:26:46,395 --> 00:26:48,397 THERE WAS A SIGNIFICANT 586 00:26:48,397 --> 00:26:50,199 ASSOCIATION BETWEEN HEAVY 587 00:26:50,199 --> 00:26:51,834 EPISODIC DRINKING AND CORONARY 588 00:26:51,834 --> 00:26:55,003 HEART DISEASE IN THE OVER ALL 589 00:26:55,003 --> 00:26:58,307 STUDY POPULATION IT WASN'T 590 00:26:58,307 --> 00:27:00,142 SIGNIFICANT BUT IF THEY DID A 591 00:27:00,142 --> 00:27:01,944 STRATIFIED ANALYSIS OF HEAVY 592 00:27:01,944 --> 00:27:04,346 EPISODIC DRINKING THERE WAS A 593 00:27:04,346 --> 00:27:06,281 HIGHER BUT STATISTICALLY 594 00:27:06,281 --> 00:27:07,883 NON-SIGNIFICANT EFFECT OF 595 00:27:07,883 --> 00:27:11,486 CORONARY HEART DISEASE AMONG MEN 596 00:27:11,486 --> 00:27:17,593 AND WOMEN. 597 00:27:17,593 --> 00:27:20,762 COMPARED TO THE NON-HEAVY 598 00:27:20,762 --> 00:27:21,797 EPISODIC DRINKING INDIVIDUALS. 599 00:27:21,797 --> 00:27:29,605 IF YOU LOOK AT THE BOTTOM PANEL 600 00:27:29,605 --> 00:27:31,740 WHEN PEOPLE WERE INVOLVED IN 601 00:27:31,740 --> 00:27:33,575 HEAVY EPISODIC DRINKING IN 602 00:27:33,575 --> 00:27:35,177 ADDITION TO THE WEEKLY LIMITS, 603 00:27:35,177 --> 00:27:37,512 THERE WAS AN INCREASE. 604 00:27:37,512 --> 00:27:38,614 IT WASN'T STATISTICALLY 605 00:27:38,614 --> 00:27:40,415 SIGNIFICANT BUT A STRONG HINT I 606 00:27:40,415 --> 00:27:44,853 THINK .054. 607 00:27:44,853 --> 00:27:47,623 WHILE MORE RESEARCH IS NEEDED TO 608 00:27:47,623 --> 00:27:49,491 UNDERSTAND CAUSALITY THEY CAN 609 00:27:49,491 --> 00:27:52,027 HELP IDENTIFY POPULATIONS THAT 610 00:27:52,027 --> 00:27:54,496 MAY HAVE THE HIGHEST RISK FOR 611 00:27:54,496 --> 00:27:55,831 DEVELOPING CORONARY HEART 612 00:27:55,831 --> 00:27:56,765 DISEASE BASED ON THE ALCOHOL 613 00:27:56,765 --> 00:28:07,142 CONSUMPTION PATTERNS. 614 00:28:09,845 --> 00:28:20,222 AND INTERESTINGLY ENOUGH, 615 00:28:22,291 --> 00:28:32,768 PARTHAT IN TISSUE INJURY DID A 616 00:28:33,468 --> 00:28:37,272 STUDY IN CHRONIC ALCOHOL 617 00:28:37,272 --> 00:28:39,841 CONSUMPTION ACCELERATING AGING. 618 00:28:39,841 --> 00:28:42,344 THE STUDY SUGGESTS HEAVY ALCOHOL 619 00:28:42,344 --> 00:28:45,914 USE MAY ACCELERATE BIOLOGICAL 620 00:28:45,914 --> 00:28:46,682 AGING UNDERSTANDING THE HEALTH 621 00:28:46,682 --> 00:28:53,655 SPAN OF GROWING ADULTS 8-65 IS 622 00:28:53,655 --> 00:28:56,892 IMPORTANT AND THE STUDY WAS TO 623 00:28:56,892 --> 00:28:59,761 IDENTIFIED SIX MONTHS OF ALCOHOL 624 00:28:59,761 --> 00:29:02,698 CONSUMPTION ON HEMODYNAMIC AND 625 00:29:02,698 --> 00:29:03,498 CARDIOVASCULAR MEASURES. 626 00:29:03,498 --> 00:29:04,733 TO GIVE A BRIEF VIEW. 627 00:29:04,733 --> 00:29:06,802 THESE ARE YOUNG AND AGING RATS, 628 00:29:06,802 --> 00:29:10,772 LESS THAN THREE MONTHS OLD AND 629 00:29:10,772 --> 00:29:13,508 ONES THAT WERE FISHER RATS, 24 630 00:29:13,508 --> 00:29:15,077 TO 26 MONTHS OLD. 631 00:29:15,077 --> 00:29:16,645 THAT'S THE STRAIN USUALLY USED 632 00:29:16,645 --> 00:29:23,452 FOR STUDYING AGING IN RATS AND 633 00:29:23,452 --> 00:29:26,355 DIVED 634 00:29:26,355 --> 00:29:31,193 DIVIDED AND THEY GOT A 5% PER 635 00:29:31,193 --> 00:29:35,163 VOLUME LIQUID DIET AND OBTAINED 636 00:29:35,163 --> 00:29:38,800 ALCOHOL LEVEL OF PEAK OVER 130, 637 00:29:38,800 --> 00:29:48,377 140 MILLIGRMILLIGRAMS PER DECILD 638 00:29:48,377 --> 00:29:51,480 ACCELERATED AGING BY IMPAIRING 639 00:29:51,480 --> 00:29:53,749 MITOCHONDRIAL FUNCTION, 640 00:29:53,749 --> 00:29:58,320 INCREASING OXIDATIVE STRESS, 641 00:29:58,320 --> 00:29:59,755 TRIGGERING, INFLAMMATION AND 642 00:29:59,755 --> 00:30:01,289 FIBROSIS AND APOPTOSIS 643 00:30:01,289 --> 00:30:03,458 PARTICULARLY IN AN AGING ANIMAL 644 00:30:03,458 --> 00:30:04,493 VERSUS A YOUNG ANIMAL. 645 00:30:04,493 --> 00:30:06,461 ALL THE THINGS MENTIONED ON THE 646 00:30:06,461 --> 00:30:08,663 DIAGRAM ARE SEPARATE SECTIONS IN 647 00:30:08,663 --> 00:30:11,033 THE PAPER WITH DATA AND GRAPHS 648 00:30:11,033 --> 00:30:14,669 THAT ARE SIGNIFICANT RELATIVE TO 649 00:30:14,669 --> 00:30:17,439 THE MEASURES. 650 00:30:17,439 --> 00:30:21,043 SO IT'S REALLY QUITE AN 651 00:30:21,043 --> 00:30:25,047 EXTRAORDINARY THOROUGH STUDY OF 652 00:30:25,047 --> 00:30:25,781 CHRONIC ALCOHOL AND 653 00:30:25,781 --> 00:30:26,481 CARDIOVASCULAR MEASURES IN BOTH 654 00:30:26,481 --> 00:30:32,954 YOUNG AND OLDER ANIMALS. 655 00:30:32,954 --> 00:30:35,023 IT ALSO SUGGESTS THE LONG-TERM 656 00:30:35,023 --> 00:30:37,125 USE CAN AFFECT CARDIOVASCULAR 657 00:30:37,125 --> 00:30:39,628 AGING AND DIMINISH THE FUNCTIONS 658 00:30:39,628 --> 00:30:40,595 ASSOCIATED WITH AGING. 659 00:30:40,595 --> 00:30:44,466 YOU CAN SEE IN THE DIAGRAM, THIS 660 00:30:44,466 --> 00:30:47,302 INTERACTION BETWEEN HEMODYNAMIC 661 00:30:47,302 --> 00:30:49,471 ALTERATION AND HYPERTENSION IS 662 00:30:49,471 --> 00:30:52,074 SOMETHING KATHY YOUNG AND I 663 00:30:52,074 --> 00:30:55,877 TALKED A LOT ABOUT AND MANY 664 00:30:55,877 --> 00:30:57,579 HEARD ME SAY THIS BEFORE BUT AT 665 00:30:57,579 --> 00:31:01,550 MAYO CLINIC LAST YEAR I HAD A 666 00:31:01,550 --> 00:31:09,124 CLINICIAN TELL ME NOW WHEN HE 667 00:31:09,124 --> 00:31:12,294 HAS A NEW PATIENT THAT COMES IN 668 00:31:12,294 --> 00:31:13,895 WITH HYPERTENSION HE ASKS ABOUT 669 00:31:13,895 --> 00:31:14,896 ALCOHOL AND THAT'S THE FIRST 670 00:31:14,896 --> 00:31:19,801 LINE OF TREATMENT TO CUT BACK ON 671 00:31:19,801 --> 00:31:22,037 ALCOHOL INTAKE AND THE 672 00:31:22,037 --> 00:31:23,171 INFLAMMATION AND ACTIVATION AND 673 00:31:23,171 --> 00:31:24,906 YOU END UP WITH SEVERE 674 00:31:24,906 --> 00:31:26,675 CARDIOVASCULAR EVENTS. 675 00:31:26,675 --> 00:31:31,913 I'M REALLY GLAD THE GROUP AT THE 676 00:31:31,913 --> 00:31:35,083 INTRAMURAL GROUP IS WORKING ON 677 00:31:35,083 --> 00:31:45,427 THE SUBJECT MATTER. 678 00:31:47,829 --> 00:31:52,567 THIS IS A COOL PAPER BY HOLLY 679 00:31:52,567 --> 00:32:03,111 JOSEPH AND KASHUBU DID THIS WORK 680 00:32:12,888 --> 00:32:19,127 IN INDIA BUT WAS ALSO DONE IN 681 00:32:19,127 --> 00:32:21,663 NORAH VOLKOW'S LABORATORY AND IT 682 00:32:21,663 --> 00:32:25,300 WAS A COLLABORATIVE EFFORT AND 683 00:32:25,300 --> 00:32:35,844 THE STUDY AIMED TO LOOKED AT THE 684 00:32:41,216 --> 00:32:41,783 HUMAN CONNECTOME PROJECT DATA 685 00:32:41,783 --> 00:32:45,320 FOR IMAGING AND THE ALCOHOL 686 00:32:45,320 --> 00:32:45,587 MEASURES. 687 00:32:45,587 --> 00:32:47,822 TASTE AND SMELL CAN PLAY A ROLE 688 00:32:47,822 --> 00:32:49,391 IN ALCOHOL CRAVING WHICH IS 689 00:32:49,391 --> 00:32:52,060 ALREADY ESTABLISHED USING 690 00:32:52,060 --> 00:32:56,598 RESTING STATE FUNCTIONAL MRI AND 691 00:32:56,598 --> 00:32:57,632 THE RESEARCHERS IDENTIFIED 692 00:32:57,632 --> 00:33:00,835 SPECIFIC FUNCTIONAL NETWORKS 693 00:33:00,835 --> 00:33:03,004 ASSOCIATED WITH SMELL AND TASTE 694 00:33:03,004 --> 00:33:05,106 ING WITH DIFFERENT DRINKING 695 00:33:05,106 --> 00:33:05,373 PATTERNS. 696 00:33:05,373 --> 00:33:07,442 ON THE LEFT HAND PANEL YOU CAN 697 00:33:07,442 --> 00:33:08,877 SEE FOR EXAMPLE WITHIN THE 698 00:33:08,877 --> 00:33:12,547 OLFACTORY NETWORK, THERE WAS A 699 00:33:12,547 --> 00:33:14,382 POSITIVE ASSOCIATION BETWEEN 700 00:33:14,382 --> 00:33:18,720 TOTAL PAST WEEK WINE CONSUMPTION 701 00:33:18,720 --> 00:33:21,690 AND THE VISUAL CONNECTION AND 702 00:33:21,690 --> 00:33:26,194 TOTAL INTAKE SHOWED AN AFFECT 703 00:33:26,194 --> 00:33:28,797 WITH THE PARIETAL NUCLEUS 704 00:33:28,797 --> 00:33:29,331 CONNECTIVITY. 705 00:33:29,331 --> 00:33:33,435 THAT'S A MOUTHFUL BUT NATS THE 706 00:33:33,435 --> 00:33:34,202 CONNECTIVITY ESTABLISHED. 707 00:33:34,202 --> 00:33:37,606 YOU SEE THE DARK BLUE LINE WITH 708 00:33:37,606 --> 00:33:45,413 THE OLLI -- OLFACTORY CONNECTION 709 00:33:45,413 --> 00:33:47,082 NETWORK AND IT HAD PREDICTIVE 710 00:33:47,082 --> 00:33:48,650 VALUE FOR WINE CONSUMPTION AND 711 00:33:48,650 --> 00:33:52,988 THE VENTRAL ATTENTION NETWORK 712 00:33:52,988 --> 00:33:55,257 FRONTAL PARIETAL NUCLEUS TASTE 713 00:33:55,257 --> 00:33:56,825 NETWORK HAD PREDICTIVE VALUE FOR 714 00:33:56,825 --> 00:33:58,193 ALCOHOL CONSUMPTION. 715 00:33:58,193 --> 00:33:59,494 THOSE ARE ILLUSTRATED ON THE TWO 716 00:33:59,494 --> 00:34:08,069 BOTTOM GRAPHS. 717 00:34:08,069 --> 00:34:09,404 FUTURE STUDIES ARE NEEDED TO 718 00:34:09,404 --> 00:34:11,406 EXPLORE THE RESULTS FOR 719 00:34:11,406 --> 00:34:13,808 BIOLOGICALLY INFORMED 720 00:34:13,808 --> 00:34:15,877 INTERVENTION AND TREATMENT 721 00:34:15,877 --> 00:34:17,746 STRATEGIES BUT ALSO IT'S WORTH 722 00:34:17,746 --> 00:34:19,247 NOTING THE CONNECTIONS 723 00:34:19,247 --> 00:34:22,717 IDENTIFIED WITHIN THE OLFACTORY 724 00:34:22,717 --> 00:34:24,486 AND OTHER NETWORKS ARE 725 00:34:24,486 --> 00:34:26,721 CONSISTENT WITH THE PREMISE THAT 726 00:34:26,721 --> 00:34:34,729 THE CHEMO SENSORY SYSTEMS AFFECT 727 00:34:34,729 --> 00:34:43,438 ALSO SENSORY FUNCTION LIKE 728 00:34:43,438 --> 00:34:46,708 ATTENTION AND IT HAS PROPOSITION 729 00:34:46,708 --> 00:34:53,948 FOR LEADING US AND WHO WILL 730 00:34:53,948 --> 00:34:56,117 PROGRESS IN WHAT DIRECTION WITH 731 00:34:56,117 --> 00:35:01,356 THEIR ALCOHOL USE PROBLEM. 732 00:35:01,356 --> 00:35:11,800 IT'S NOVEL AND INNOVATIVE. 733 00:35:14,769 --> 00:35:16,237 THE LAST ONE IS IMPORTANT TO ME 734 00:35:16,237 --> 00:35:16,938 BECAUSE FOR MANY YEARS WE'VE 735 00:35:16,938 --> 00:35:18,907 BEEN SUPPORTING RESEARCH ON THE 736 00:35:18,907 --> 00:35:22,711 AFFECTS OF LOOKING AT AROUND 737 00:35:22,711 --> 00:35:27,849 TESTING THE HYPOTHESIS THAT 738 00:35:27,849 --> 00:35:30,719 CHOLINE MAY BE ABLE TO HELP 739 00:35:30,719 --> 00:35:33,521 BECAUSE MUCH IT'S ANTI-OXIDANT 740 00:35:33,521 --> 00:35:37,092 REACTIVE PROPERTIES AND MAY HELP 741 00:35:37,092 --> 00:35:40,595 IN TREATMENT OF FETAL ALCOHOL 742 00:35:40,595 --> 00:35:43,431 SPECTRUM DISORDER AND THERE WAS 743 00:35:43,431 --> 00:35:46,735 RESEARCH THE SUPPLEMENTATION MAY 744 00:35:46,735 --> 00:35:57,278 HAVE POSITIVE MEMORY AFFECTS AND 745 00:35:57,812 --> 00:35:58,947 THIS COMBINES DATA IN THREE 746 00:35:58,947 --> 00:36:00,882 DOUBLE BLINDED RANDOMIZED 747 00:36:00,882 --> 00:36:11,426 TREATMENT IN PRE-AGED CHILDREN. 748 00:36:16,297 --> 00:36:20,368 THIS WAS DONE AT THE MAYO CLINIC 749 00:36:20,368 --> 00:36:21,636 IN WISCONSIN AND THE 750 00:36:21,636 --> 00:36:25,807 PARTICIPANTS WERE RECRUITED FROM 751 00:36:25,807 --> 00:36:27,275 FASD INCLUDING THE MINNESOTA 752 00:36:27,275 --> 00:36:29,043 CLINIC AND SUPPORT GROUPS FOR 753 00:36:29,043 --> 00:36:30,979 FAMILIES RAISING CHILDREN WITH 754 00:36:30,979 --> 00:36:33,281 FETAL ALCOHOL SPECTRUM DISORDER. 755 00:36:33,281 --> 00:36:34,716 THOUGH IT WAS NOT REQUIRED FOR 756 00:36:34,716 --> 00:36:36,351 INCLUSION, ALL PARTICIPANTS WERE 757 00:36:36,351 --> 00:36:38,720 LIVING WITH ADOPTIVE FAMILIES OR 758 00:36:38,720 --> 00:36:41,089 IN PERMANENT PLACEMENTS. 759 00:36:41,089 --> 00:36:41,956 THERE WERE NONE IN FOSTER 760 00:36:41,956 --> 00:36:51,566 TRANSITIONAL CARE. 761 00:36:51,566 --> 00:36:53,635 DIAGNOSES WERE MADE USING 762 00:36:53,635 --> 00:36:55,136 CRITERION AND INFORMATION FROM 763 00:36:55,136 --> 00:36:59,808 THE CHILD'S MEDICAL RECORDS AND 764 00:36:59,808 --> 00:37:00,475 DYSMORPHOLOGY CONDUCTED BY A 765 00:37:00,475 --> 00:37:01,509 STUDY PHYSICIAN. 766 00:37:01,509 --> 00:37:02,477 IN ADDITION BECAUSE THE 767 00:37:02,477 --> 00:37:05,914 INSTITUTE OF MEDICINE CRITERIA 768 00:37:05,914 --> 00:37:07,282 DO NOT SPECIFICALLY CHARACTERIZE 769 00:37:07,282 --> 00:37:08,049 COGNITIVE FUNCTION THEY APPLIED 770 00:37:08,049 --> 00:37:11,920 THE CENTERS FOR DISEASE CONTROL 771 00:37:11,920 --> 00:37:14,856 AND CENTRAL NERVOUS SYSTEM FOR 772 00:37:14,856 --> 00:37:17,926 FETAL ALCOHOL DISORDER. 773 00:37:17,926 --> 00:37:21,196 IN THE END THEY IDENTIFIED 774 00:37:21,196 --> 00:37:22,730 APPROXIMATELY 104 INDIVIDUALS 775 00:37:22,730 --> 00:37:25,600 WITH HIGHLY PROBABLE FETAL 776 00:37:25,600 --> 00:37:27,435 ALCOHOL SPECTRUM DISORDER. 777 00:37:27,435 --> 00:37:30,705 YOU REMEMBER THAT FETAL ALCOHOL 778 00:37:30,705 --> 00:37:36,945 SPECTRUM DISORDER INCLUDES 779 00:37:36,945 --> 00:37:38,580 DEVELOPMENTAL DISORDER AND 780 00:37:38,580 --> 00:37:41,216 PARTIAL SYNDROME AND FETAL 781 00:37:41,216 --> 00:37:41,950 ALCOHOL SYNDROME AMONG OTHERS. 782 00:37:41,950 --> 00:37:45,553 WE DON'T REALLY HAVE A CONCRETE 783 00:37:45,553 --> 00:37:46,788 DEFINITION YET OF FETAL ALCOHOL 784 00:37:46,788 --> 00:37:47,655 SPECTRUM DISORDER BUT THE FIELD 785 00:37:47,655 --> 00:37:52,193 IS WORKING ON A CONSENSUS 786 00:37:52,193 --> 00:37:52,494 DEFINITION. 787 00:37:52,494 --> 00:37:55,663 AFTER THE NINE-MONTH FOLLOW-UP 788 00:37:55,663 --> 00:37:58,566 VISIT CHOLINE VISIT IMPROVED 789 00:37:58,566 --> 00:38:02,570 EARLY NON-VERBAL MEMORIES 790 00:38:02,570 --> 00:38:03,605 ELICITED WITH THE TASK COMPARED 791 00:38:03,605 --> 00:38:06,040 WITH PLACEBO. 792 00:38:06,040 --> 00:38:10,178 SO REMEMBER, THESE WERE 2 TO 793 00:38:10,178 --> 00:38:10,478 6-YEAR-OLDS. 794 00:38:10,478 --> 00:38:13,648 THE AVERAGE AGE WAS SOMEWHERE 795 00:38:13,648 --> 00:38:22,090 AROUND 4 --. 796 00:38:22,090 --> 00:38:24,592 THIS WAS NOT VERBAL. 797 00:38:24,592 --> 00:38:27,061 THERE WERE GIVEN TOYS TO PLAY 798 00:38:27,061 --> 00:38:29,430 WITH AND GIVEN AN ORDER AND THEY 799 00:38:29,430 --> 00:38:34,702 WERE SUPPOSED TO REMEMBER THE 800 00:38:34,702 --> 00:38:36,037 ORDER. 801 00:38:36,037 --> 00:38:38,439 IF THEY PAIRED THE TOYS PROPERLY 802 00:38:38,439 --> 00:38:40,775 AS SEEN BEFORE, THAT IS WHAT WAS 803 00:38:40,775 --> 00:38:41,209 MEASURED. 804 00:38:41,209 --> 00:38:42,043 I DON'T KNOW. 805 00:38:42,043 --> 00:38:45,480 LAURA MAY BE ABLE TO TELL ME 806 00:38:45,480 --> 00:38:51,019 MORE ABOUT THE TASK BUT IT 807 00:38:51,019 --> 00:38:52,587 SOUNDS COMPLICATED BUT I'D LIKE 808 00:38:52,587 --> 00:38:54,589 TO SEE IT IN ACTION BUT THESE 809 00:38:54,589 --> 00:38:55,557 WERE FOR 4-YEAR-OLDS. 810 00:38:55,557 --> 00:38:58,726 YOU CAN SEE THE INCREASE AT THE 811 00:38:58,726 --> 00:39:01,896 NINE MONTH TEST, VISIT IN THE 812 00:39:01,896 --> 00:39:05,600 CHOLINE GROUP THAT WAS QUITE 813 00:39:05,600 --> 00:39:05,867 DRAMATIC. 814 00:39:05,867 --> 00:39:16,411 THE GRAPH ON THE RIGHT AND THE 815 00:39:18,379 --> 00:39:18,880 YOUNGER CHILDREN SHOWED A 816 00:39:18,880 --> 00:39:20,181 GREATER IMPROVEMENT WITH THE 817 00:39:20,181 --> 00:39:22,784 FULLY ADJUSTED MODEL TOOK IT 818 00:39:22,784 --> 00:39:24,052 INTO ACCOUNT AND THAT WAS ALSO 819 00:39:24,052 --> 00:39:32,760 SIGNIFICANT. 820 00:39:32,760 --> 00:39:33,294 OVER 821 00:39:33,294 --> 00:39:37,298 OVER ALL CHOLINE SHOWED NO 822 00:39:37,298 --> 00:39:41,069 AFFECT ON INTELLIGENCE QUOTIENT. 823 00:39:41,069 --> 00:39:45,173 THERE WAS NO ADVERSE EFFECT FROM 824 00:39:45,173 --> 00:39:46,708 CHOLINE SUPPLEMENTATION AND 825 00:39:46,708 --> 00:39:48,610 THERE WAS A FISHY BODY ORDER AND 826 00:39:48,610 --> 00:39:50,311 IT WAS DOSE DEPENDENT. 827 00:39:50,311 --> 00:39:54,182 I GUESS IF THE BODY ORDER GOT 828 00:39:54,182 --> 00:39:57,785 TOO STRONG, THEN MAYBE CHILDREN 829 00:39:57,785 --> 00:40:01,222 HAVE TO MODERATE THEIR DOSE BUT 830 00:40:01,222 --> 00:40:10,465 IN ANY EVENT THE AUTHORS SAID 831 00:40:10,465 --> 00:40:11,766 THERE'S LONG-TERM BENEFITS TO 832 00:40:11,766 --> 00:40:15,870 MODIFY TRAJECTORY IN EARLY 833 00:40:15,870 --> 00:40:17,271 CHILDHOOD AND EVEN A COURSE AT 834 00:40:17,271 --> 00:40:22,710 THE CRITICAL MOMENTS IN THE 835 00:40:22,710 --> 00:40:24,479 DEVELOPMENT OF THE INDIVIDUALS 836 00:40:24,479 --> 00:40:26,981 CAN LEAD TO EFFECTS THAT CAN 837 00:40:26,981 --> 00:40:30,018 SNOWBALL IN A POSITIVE AWAY 838 00:40:30,018 --> 00:40:32,153 LATER ON. 839 00:40:32,153 --> 00:40:34,956 DID I SCREW IT UP OR IS THAT A 840 00:40:34,956 --> 00:40:35,657 FAIR ARGUMENT? 841 00:40:35,657 --> 00:40:39,293 PHIL IS THE COORDINATOR OF OUR 842 00:40:39,293 --> 00:40:42,063 FETAL ALCOHOL SPECTRUM DISORDER 843 00:40:42,063 --> 00:40:52,407 EXTRAMURAL PROGRAM. 844 00:41:17,131 --> 00:41:18,633 AND THIS HELPS UNDERSTAND THE 845 00:41:18,633 --> 00:41:20,768 TREATMENT OPTIONS AND YOU CAN 846 00:41:20,768 --> 00:41:24,072 LEARN ALCOHOL USE DISORDER IS A 847 00:41:24,072 --> 00:41:26,708 SPECTRUM DISORDER AND THEN 848 00:41:26,708 --> 00:41:27,375 HEALTH CARE PROFESSIONAL CORE 849 00:41:27,375 --> 00:41:29,744 RESOURCE COVERS THE BASICS OF 850 00:41:29,744 --> 00:41:30,311 WHAT EVERY HEALTH CARE 851 00:41:30,311 --> 00:41:33,381 PROFESSIONAL NEEDS TO KNOW ABOUT 852 00:41:33,381 --> 00:41:36,084 ALCOHOL KWLUGDP INCLUDING 853 00:41:36,084 --> 00:41:46,561 STRATEGIES FOR INTERVENTION. 854 00:41:51,065 --> 00:41:52,834 I WANTED TO ADVERTISE THE NATIVE 855 00:41:52,834 --> 00:41:54,102 COMMUNITIES ALCOHOL AND 856 00:41:54,102 --> 00:42:02,710 PREVENTION REVIEW THAT WE PUT UP 857 00:42:02,710 --> 00:42:06,347 IN NOVEMBER AND EDUCATE IN 858 00:42:06,347 --> 00:42:08,015 IDENTIFYING EFFECTIVE 859 00:42:08,015 --> 00:42:08,883 SCIENTIFICALLY ALCOHOL 860 00:42:08,883 --> 00:42:10,284 INTERVENTIONS FOR COMMUNITIES. 861 00:42:10,284 --> 00:42:14,622 IT WAS IN PARTNERSHIP WITH 862 00:42:14,622 --> 00:42:15,990 SCIENTIFIC EXPERTS HAVING 863 00:42:15,990 --> 00:42:18,059 EXTENSIVE EXPERIENCE CONDUCTING 864 00:42:18,059 --> 00:42:20,194 RESEARCH WITH NATIVE COMMUNITIES 865 00:42:20,194 --> 00:42:22,063 AND EVALUATING NEARLY 40 866 00:42:22,063 --> 00:42:24,031 INTERVENTIONS INCLUDING NATIVE 867 00:42:24,031 --> 00:42:26,067 POPULATIONS FROM PUBLISHED 868 00:42:26,067 --> 00:42:26,734 PEER-REVIEWED RESEARCH. 869 00:42:26,734 --> 00:42:29,871 THERE'S INFORMATION THERE ON 870 00:42:29,871 --> 00:42:31,939 PREVENTION OF ALCOHOL MISUSE AND 871 00:42:31,939 --> 00:42:33,541 TREATMENT OF DISORDER AND 872 00:42:33,541 --> 00:42:34,108 PREVENTION OF FETAL ALCOHOL 873 00:42:34,108 --> 00:42:44,085 SPECTRUM DISORDER. 874 00:42:44,085 --> 00:42:45,787 WE WANT TO BE YOUR CREDIBLE 875 00:42:45,787 --> 00:42:47,188 SOURCE FOR ALCOHOL INFORMATION 876 00:42:47,188 --> 00:42:49,190 AND HEALTH AND HOPE IT CONTINUE 877 00:42:49,190 --> 00:42:51,859 TO BE AND UPDATE THESE 878 00:42:51,859 --> 00:42:52,126 RESOURCES. 879 00:42:52,126 --> 00:42:53,928 I WANT TO GIVE A SPECIAL THANKS 880 00:42:53,928 --> 00:42:57,331 TO EVERYBODY THAT CONTRIBUTED TO 881 00:42:57,331 --> 00:43:00,067 THESE SLIDES AND A LOT OF WORK 882 00:43:00,067 --> 00:43:04,939 BY DEVIN PLOT AND LAURA AND 883 00:43:04,939 --> 00:43:07,942 LAUREN AND TRISH POWELL. 884 00:43:07,942 --> 00:43:12,113 THANK YOU VERY MUCH AND -- AM I 885 00:43:12,113 --> 00:43:15,082 SUPPOSED TO TAKE QUESTIONS OR AM 886 00:43:15,082 --> 00:43:15,850 I OVER? 887 00:43:15,850 --> 00:43:16,784 WHERE ARE WE? 888 00:43:16,784 --> 00:43:24,292 >> WE HAVE PLENTY OF TIME FOR 889 00:43:24,292 --> 00:43:27,161 DISCUSSION. 890 00:43:27,161 --> 00:43:28,429 >> DOES ANYBODY HAVE QUESTIONS 891 00:43:28,429 --> 00:43:38,906 THAT I CAN ACTUALLY ANSWER? 892 00:43:42,076 --> 00:43:45,513 >> WE HAVE A QUESTION. 893 00:43:45,513 --> 00:43:46,347 >> THANK YOU FOR SHARING THE 894 00:43:46,347 --> 00:43:50,318 BIOS OF ALL THE FOLKS WHO WORKED 895 00:43:50,318 --> 00:43:53,120 FOR SUCH A LONG TIME AT NIAAA. 896 00:43:53,120 --> 00:43:56,257 IT WAS WONDERFUL TO LEARN MORE 897 00:43:56,257 --> 00:43:58,659 ABOUT THEM AND FOR YOU TO 898 00:43:58,659 --> 00:43:59,760 RECOGNIZE THEM SO THANK YOU. 899 00:43:59,760 --> 00:44:01,028 >> YOU'RE WELCOME. 900 00:44:01,028 --> 00:44:01,863 IF YOU LOOK AT THE DIRECTOR'S 901 00:44:01,863 --> 00:44:04,498 REPORT YOU'LL SEE EVERYTHING I 902 00:44:04,498 --> 00:44:06,133 TALKED ABOUT IS IN THE 903 00:44:06,133 --> 00:44:07,001 DIRECTOR'S REPORT AND EVEN 904 00:44:07,001 --> 00:44:12,139 EXPANDED A BIT IN THERE. 905 00:44:12,139 --> 00:44:17,879 OTHER COMMENTS OR QUESTIONS? 906 00:44:17,879 --> 00:44:18,713 WE'LL HAVE TIME FOR DISCUSSION 907 00:44:18,713 --> 00:44:22,717 LATER AFTER WE GO THROUGH SOME 908 00:44:22,717 --> 00:44:32,960 OF THE TALKS. 909 00:44:50,978 --> 00:44:52,046 >> THEY'RE ROBUST IN THEIR 910 00:44:52,046 --> 00:44:53,347 ABILITY TO MEASURE MEMORY. 911 00:44:53,347 --> 00:44:55,082 >> I WONDERED IF YOU HEARD OF 912 00:44:55,082 --> 00:44:56,117 THAT ONE. 913 00:44:56,117 --> 00:44:58,219 I HAD NEVER HEARD OF IT BEFORE 914 00:44:58,219 --> 00:44:58,920 BUT APPARENTLY THEY HAVE TOYS 915 00:44:58,920 --> 00:45:02,323 THEY HAVE TO ARRANGE IN A 916 00:45:02,323 --> 00:45:06,227 SEQUENCE OF THEME. 917 00:45:06,227 --> 00:45:08,596 LIKE CATCHING A BALL OR 918 00:45:08,596 --> 00:45:09,630 SOMETHING LIKE THAT. 919 00:45:09,630 --> 00:45:12,934 THERE'S A LOT OF MANIPULATIVES 920 00:45:12,934 --> 00:45:15,102 INVOLVES WHEN TESTING LITTLE 921 00:45:15,102 --> 00:45:15,303 KIDS. 922 00:45:15,303 --> 00:45:18,139 YOU HAVE TO PRESENT THEM IN 923 00:45:18,139 --> 00:45:22,109 ORDER. 924 00:45:22,109 --> 00:45:22,810 OBVIOUSLY WE'VE NEVER TESTED 925 00:45:22,810 --> 00:45:23,010 KIDS. 926 00:45:23,010 --> 00:45:28,215 OTHER QUESTIONS OR COMMENTS? 927 00:45:28,215 --> 00:45:33,854 WHERE ARE WE AT IN THE SCHEDULE? 928 00:45:33,854 --> 00:45:34,422 >> WE HAVE A COMMENT OR 929 00:45:34,422 --> 00:45:44,598 QUESTION. 930 00:45:58,112 --> 00:46:00,748 AFTER NOTING THE OLFACTORY 931 00:46:00,748 --> 00:46:05,753 SYSTEM DOES MORE THAN OLFACTION 932 00:46:05,753 --> 00:46:09,991 AND PARTICIPATES IN MOTOR 933 00:46:09,991 --> 00:46:11,292 BEHAVIOR GOES TO SHOW YOU THE 934 00:46:11,292 --> 00:46:13,194 BRAIN DOES MORE THAN ONE THING 935 00:46:13,194 --> 00:46:14,962 AND IT'S A VERY INTEGRATED 936 00:46:14,962 --> 00:46:18,132 CIRCUIT. 937 00:46:18,132 --> 00:46:27,775 IT WAS GREAT TO SEE. 938 00:46:27,775 --> 00:46:30,144 >> IN DROSOPHILA NOW THEY KNOW 939 00:46:30,144 --> 00:46:34,715 MOST THE CONNECTIONS. 940 00:46:34,715 --> 00:46:43,057 I BELIEVE THAT'S CORRECT. 941 00:46:43,057 --> 00:46:44,992 KNOWING THEY INVADE MY FRUIT 942 00:46:44,992 --> 00:46:48,596 TREES I CAN TELL YOU THEY HAVE A 943 00:46:48,596 --> 00:46:51,732 WELL DEVELOPED OLFACTORY SYSTEM. 944 00:46:51,732 --> 00:46:57,038 ANY OTHER THOUGHTS OR COMMENTS? 945 00:46:57,038 --> 00:46:59,473 WELL, WE CAN TAKE A 15 MINUTE 946 00:46:59,473 --> 00:47:01,575 BREAK AND BE 15 MINUTES AHEAD OF 947 00:47:01,575 --> 00:47:01,809 TIME. 948 00:47:01,809 --> 00:47:03,244 IS THAT OKAY OR DO I WANT TO 949 00:47:03,244 --> 00:47:07,114 KEEP GOING, PHILIPPE? 950 00:47:07,114 --> 00:47:10,251 >> YES, A 15-MINUTE BREAK AND 951 00:47:10,251 --> 00:47:11,385 THE NEXT PRESENTATION IS 952 00:47:11,385 --> 00:47:18,626 SCHEDULED AT 2:30 BUT I THINK -- 953 00:47:18,626 --> 00:47:20,528 >> LET'S STAY ON SCHEDULE. 954 00:47:20,528 --> 00:47:22,263 PEOPLE AT INTRAMURAL PROBABLY 955 00:47:22,263 --> 00:47:22,930 WANT TO HEAR HIM. 956 00:47:22,930 --> 00:47:24,765 MAYBE WE'LL JUST TAKE A LONGER 957 00:47:24,765 --> 00:47:25,166 BREAK. 958 00:47:25,166 --> 00:47:26,700 >> I THINK THAT'S A GOOD IDEA. 959 00:47:26,700 --> 00:47:30,371 >> LET'S DO IT THAT WAY. 960 00:47:30,371 --> 00:47:34,708 SO YOU'RE ON AT 2:30. 961 00:47:34,708 --> 00:47:42,983 IS THAT CORRECT? 962 00:47:42,983 --> 00:47:46,253 OKAY TELL EVERYBODY AT FISHER'S 963 00:47:46,253 --> 00:47:48,122 LANE YOU'RE ON AT 2:30. 964 00:47:48,122 --> 00:47:49,790 I KNOW YOU WON'T BUT MAYBE 965 00:47:49,790 --> 00:47:50,401 SOMEBODY WILL. WE'LL SEE EVERYBODY AT 2:30. 966 00:47:56,390 --> 00:47:58,225 >> WE FORGOT TO INTRODUCE TWO 967 00:47:58,225 --> 00:48:01,762 KEY MEMBERS OF NIAAA. 968 00:48:01,762 --> 00:48:04,598 OUR TWO DAVIDS, DAVID GOLDMAN 969 00:48:04,598 --> 00:48:06,734 AND DAVID LOVINGER. 970 00:48:06,734 --> 00:48:09,003 DO YOU WANT TO SAY SOMETHING? 971 00:48:09,003 --> 00:48:11,305 >> HELLO, GLAD YEAR ABLE TO GET 972 00:48:11,305 --> 00:48:13,007 TOGETHER FOR COUNCIL. 973 00:48:13,007 --> 00:48:15,442 I'M THE SCIENTIFIC OF THE 974 00:48:15,442 --> 00:48:18,178 DIVISION OF INTRAMURAL CLINICAL 975 00:48:18,178 --> 00:48:19,780 AND BIOLOGICAL RESEARCH AT 976 00:48:19,780 --> 00:48:20,147 NIAAA. 977 00:48:20,147 --> 00:48:23,551 GOOD TO SEE, Y'ALL. 978 00:48:23,551 --> 00:48:27,621 >> THANKS, DAVE. 979 00:48:27,621 --> 00:48:34,828 AND DAVID GOLDMAN AND THANK YOU 980 00:48:34,828 --> 00:48:36,096 FOR REMINDING ME TO TELL 981 00:48:36,096 --> 00:48:36,897 EVERYBODY THE DIRECTOR'S REPORT 982 00:48:36,897 --> 00:48:37,665 IS ON THE WEBSITE. 983 00:48:37,665 --> 00:48:47,775 DAVID. 984 00:48:52,379 --> 00:48:55,683 IT'S A REAL PLEASURE FOR ME TO 985 00:48:55,683 --> 00:49:02,156 INTRODUCE DR. RESAT CINAR FROM 986 00:49:02,156 --> 00:49:05,626 FIBROTIC DISORDERS AT NIAAA 987 00:49:05,626 --> 00:49:07,161 SINCE JANUARY 2021. 988 00:49:07,161 --> 00:49:10,831 HE TRAINED AS A PHARMACIST AND 989 00:49:10,831 --> 00:49:14,668 PHARMACOLOGIST IN TURKEY. 990 00:49:14,668 --> 00:49:16,870 HE OBTAINED HIS Ph.D. BY 991 00:49:16,870 --> 00:49:19,273 STUDYING MOLECULAR PHARMACOLOGY 992 00:49:19,273 --> 00:49:25,145 OF THE CV1 RECEPTORS AND OPIOID 993 00:49:25,145 --> 00:49:26,146 RECEPTOR SIGNALLING. 994 00:49:26,146 --> 00:49:28,616 AFTER COMPLETING HIS Ph.D. HE 995 00:49:28,616 --> 00:49:32,653 JOINED THE LAB AT NIAAA AS A 996 00:49:32,653 --> 00:49:36,457 POSTDOCTORAL FELLOW AND THEN 997 00:49:36,457 --> 00:49:39,093 BECAME A STAFF SCIENTIST AND 998 00:49:39,093 --> 00:49:40,527 CURRENTLY A TENURE TRACK 999 00:49:40,527 --> 00:49:43,364 INVESTIGATOR AT NIAAA. 1000 00:49:43,364 --> 00:49:50,170 HIS RESEARCH HAS DEMONSTRATED 1001 00:49:50,170 --> 00:49:52,606 GOALS OF THE CANNABINOID SYSTEM 1002 00:49:52,606 --> 00:49:54,208 IN DISORDERS SUCH AS LUNG AND 1003 00:49:54,208 --> 00:49:54,775 LIVER. 1004 00:49:54,775 --> 00:49:59,847 HE'S CONTRIBUTED IN 1005 00:49:59,847 --> 00:50:01,749 MULTI-TARGETED STRATEGICS TO 1006 00:50:01,749 --> 00:50:03,817 DEVELOP MORE EFFICIENT AND SAFER 1007 00:50:03,817 --> 00:50:05,519 MODALITIES FOR COMPLEX, 1008 00:50:05,519 --> 00:50:06,787 PROGRESSIVE DISORDERS. 1009 00:50:06,787 --> 00:50:10,057 HIS RESEARCH IDENTIFIED DUAL 1010 00:50:10,057 --> 00:50:20,601 INHIBITION OF RE -- RECEPTORS 1011 00:50:23,537 --> 00:50:26,173 AND INVOLVED IN NOVEL 1012 00:50:26,173 --> 00:50:28,008 PERIPHERALLY RESTRICTED HYBRID 1013 00:50:28,008 --> 00:50:31,211 COMPOUNDS, CB1 RESTRICTER AND 1014 00:50:31,211 --> 00:50:34,648 AMP K AS THIRD GENERATION CV1 1015 00:50:34,648 --> 00:50:37,685 RECEPTOR ANTAGONIST. 1016 00:50:37,685 --> 00:50:40,120 THIS NOVEL CLASS HAS THERAPEUTIC 1017 00:50:40,120 --> 00:50:42,256 POTENTIAL IN OBESITY, DIABETES, 1018 00:50:42,256 --> 00:50:43,557 ALCOHOL USE DISORDER AND 1019 00:50:43,557 --> 00:50:46,660 FIBROTIC DISORDER AND TWO OF THE 1020 00:50:46,660 --> 00:50:49,463 LEAD COMPOUNDS. 1021 00:50:49,463 --> 00:50:52,566 HAVE BEEN TRANSLATED TO CLINICAL 1022 00:50:52,566 --> 00:50:52,833 TESTING. 1023 00:50:52,833 --> 00:50:56,170 HIS RESEARCH FOCUSES ON 1024 00:50:56,170 --> 00:50:59,673 UNDERSTAN 1025 00:50:59,673 --> 00:51:05,612 UNDERSTANDING PATH LOGIC 1026 00:51:05,612 --> 00:51:08,749 MECHANISMS AND ALCOHOL INDUCED 1027 00:51:08,749 --> 00:51:10,984 INJURY AND IDENTIFIED 1028 00:51:10,984 --> 00:51:14,021 THERAPEUTIC TARGETS AND DEVELOP 1029 00:51:14,021 --> 00:51:16,724 EFFECTIVE PHARMACO THERAPIES. 1030 00:51:16,724 --> 00:51:18,192 THERE'S ALWAYS A WARM SPOT FOR 1031 00:51:18,192 --> 00:51:22,196 RESEARCHERS WHO TRAINED IN 1032 00:51:22,196 --> 00:51:31,538 PHARMACY. 1033 00:51:31,538 --> 00:51:33,073 ANOTHER WARM SPOT IN MY HEART 1034 00:51:33,073 --> 00:51:38,145 FOR SOMEONE WHO STUDIES THE 1035 00:51:38,145 --> 00:51:39,747 LIVER. 1036 00:51:39,747 --> 00:51:40,981 YOU'LL YOURS, RESAT. 1037 00:51:40,981 --> 00:51:42,816 >> THANK YOU FOR THE 1038 00:51:42,816 --> 00:51:44,151 INTRODUCTION AND INVITATION. 1039 00:51:44,151 --> 00:51:47,421 I'M HERE TO SHARE IN OUR 1040 00:51:47,421 --> 00:51:50,858 RESEARCH THE INTERNAL PROGRAM OF 1041 00:51:50,858 --> 00:51:52,760 THE NIAAA. 1042 00:51:52,760 --> 00:51:55,496 MY TITLE IS UNDERSTANDING THE 1043 00:51:55,496 --> 00:51:58,899 AFFECT OF ALCOHOL MISUSING IN 1044 00:51:58,899 --> 00:52:04,171 WOUND HEALING AND WE CAN TRY TO 1045 00:52:04,171 --> 00:52:05,606 FOCUS ON THERAPEUTIC TARGETS. 1046 00:52:05,606 --> 00:52:08,876 THIS IS ALSO ONE OF THE LESS 1047 00:52:08,876 --> 00:52:18,185 STUDIES INTERACTION WITH 1048 00:52:18,185 --> 00:52:20,154 ALCOHOL. 1049 00:52:20,154 --> 00:52:25,459 WE HAVE AN ESTABLISHED MECHANISM 1050 00:52:25,459 --> 00:52:28,695 AND FOCUSSING ON LUNG DISEASE 1051 00:52:28,695 --> 00:52:33,167 AND I WILL TRY TO OF GIVE 1052 00:52:33,167 --> 00:52:36,603 EVIDENCE HOW THE TWO DISEASE MAY 1053 00:52:36,603 --> 00:52:41,942 INFORM EACH OTHER OR SHED 1054 00:52:41,942 --> 00:52:44,578 PATHOLOGICAL MECHANISMS AND 1055 00:52:44,578 --> 00:52:47,815 SHARE SOME RECENT RESEARCH WITH 1056 00:52:47,815 --> 00:52:54,922 A POSTDOC IN MY LAB. 1057 00:52:54,922 --> 00:52:56,824 NOW MANY MAY KNOW THE LATEST 1058 00:52:56,824 --> 00:52:58,192 EVIDENCE AND PREVALENCE OF 1059 00:52:58,192 --> 00:53:01,428 ALCOHOL DRINKING INCREASED BASED 1060 00:53:01,428 --> 00:53:06,400 ON THE DATA AND AN IMPORTANT 1061 00:53:06,400 --> 00:53:08,635 POINT IS BASED ON THE SURVEY, 1062 00:53:08,635 --> 00:53:13,240 MORE THAN HALF THE UNITED STATES 1063 00:53:13,240 --> 00:53:16,343 POPULATION AGE 18 AND OLDER HAS 1064 00:53:16,343 --> 00:53:19,780 DRINKING AND A QUARTER OF THE 1065 00:53:19,780 --> 00:53:24,051 POPULATION ALMOST A QUARTER HAS 1066 00:53:24,051 --> 00:53:25,752 BINGE DRINKING EXPERIENCE AND 1067 00:53:25,752 --> 00:53:29,556 ABOUT 10% OF THE POPULATION HAVE 1068 00:53:29,556 --> 00:53:31,658 ALCOHOL USE DISORDER. 1069 00:53:31,658 --> 00:53:33,727 IS THIS IS CONCERNING IF YOU 1070 00:53:33,727 --> 00:53:34,361 CONSIDER THE NEGATIVE HEALTH 1071 00:53:34,361 --> 00:53:36,897 IMPACT OF ALCOHOL IN DIFFERENT 1072 00:53:36,897 --> 00:53:37,130 ORGANS. 1073 00:53:37,130 --> 00:53:41,101 MY FOCUS IS ON LUNG BUT I WILL 1074 00:53:41,101 --> 00:53:51,545 FOCUS ON MY TALK AND THE 1075 00:53:55,115 --> 00:54:01,321 PSYCHIATRIST WHO ALSO ONE OF THE 1076 00:54:01,321 --> 00:54:03,190 PERSONS INTRODUCED THE ALCOHOL 1077 00:54:03,190 --> 00:54:06,894 USE DISORDER CONCEPT DESCRIBED 1078 00:54:06,894 --> 00:54:08,095 THE ALCOHOL LUNG DISEASE AS 1079 00:54:08,095 --> 00:54:09,663 FATAL MORE THAN 200 YEARS AGO. 1080 00:54:09,663 --> 00:54:12,599 THE LAST 200 YEARS THERE'S A 1081 00:54:12,599 --> 00:54:15,769 REMARKABLE ADVANCEMENT OF THE 1082 00:54:15,769 --> 00:54:22,843 MEDICAL PRACTICE WITH THE MOST 1083 00:54:22,843 --> 00:54:24,411 IMPORTANT IS THE ANTIBIOTICS AND 1084 00:54:24,411 --> 00:54:26,179 THE RULES HAVE CHANGED IN THE 1085 00:54:26,179 --> 00:54:34,621 LAST 200 YEARS BUT STILL ALCOHOL 1086 00:54:34,621 --> 00:54:35,722 PREDISPOSED THE ALCOHOL WITH THE 1087 00:54:35,722 --> 00:54:38,659 PNEUMONIA AND SEPSIS AND THIS IS 1088 00:54:38,659 --> 00:54:42,029 ALL CAUSE MORTALITY. 1089 00:54:42,029 --> 00:54:44,231 BASED ON THE CAN CLINICAL 1090 00:54:44,231 --> 00:54:46,199 EVIDENCE, INDIVIDUALS WITH 1091 00:54:46,199 --> 00:54:49,803 ALCOHOL MISUSE HAVE ALMOST 1092 00:54:49,803 --> 00:54:50,237 DOU 1093 00:54:50,237 --> 00:54:54,942 DOUBLED INCIDENTS ADDRESSING THE 1094 00:54:54,942 --> 00:54:55,609 SYNDROME AND IT'S OFTEN 1095 00:54:55,609 --> 00:55:03,617 RESULTING IN MORTALITY. 1096 00:55:03,617 --> 00:55:04,851 IF YOU CHECK THE PUBLISHED 1097 00:55:04,851 --> 00:55:07,421 EVIDENCE WE CAN CONCLUDE OR SEE 1098 00:55:07,421 --> 00:55:08,622 EVIDENCE THAT HEAVY ALCOHOL 1099 00:55:08,622 --> 00:55:16,029 DRINKING PROMOTES WHAT IS 1100 00:55:16,029 --> 00:55:18,498 HAPPENING IN LUNGS AND THERE'S 1101 00:55:18,498 --> 00:55:20,233 OXIDATIVE STRESS AND ALCOHOL 1102 00:55:20,233 --> 00:55:24,705 CAUSES REPETIVE INJURIES. 1103 00:55:24,705 --> 00:55:29,576 AND LINING THE LUNGS FOR SECOND 1104 00:55:29,576 --> 00:55:29,810 INJURY. 1105 00:55:29,810 --> 00:55:30,911 THERE'S MULTIPLE EVIDENCE IT 1106 00:55:30,911 --> 00:55:32,179 AFFECTS THE IMMUNE SYSTEM. 1107 00:55:32,179 --> 00:55:33,513 I WANT TO EMPHASIZE THE UNIQUE 1108 00:55:33,513 --> 00:55:37,384 ROLE OF LUNG. 1109 00:55:37,384 --> 00:55:41,421 LUNG IS EXPOSED TO VIRUS, 1110 00:55:41,421 --> 00:55:42,255 BACTERIA, AIR POLLUTION. 1111 00:55:42,255 --> 00:55:46,293 THIS ORGAN HAS A LOT OF EXTERNAL 1112 00:55:46,293 --> 00:55:50,630 FACTOR CAN CAUSE MULTIPLE INJURY 1113 00:55:50,630 --> 00:55:52,866 AND INFLAMMATION AND WHY 1114 00:55:52,866 --> 00:55:56,236 INTEGRITY OF THE LUNG IMMUNITY 1115 00:55:56,236 --> 00:56:01,875 IS CRITICAL FOR HEALTHY 1116 00:56:01,875 --> 00:56:03,777 PHYSIOLOGICAL FUNCTION OF LUNG. 1117 00:56:03,777 --> 00:56:06,146 CONSIDERING THIS ONE OF THE 1118 00:56:06,146 --> 00:56:07,948 IMPORTANT QUESTIONS IS HOW DOES 1119 00:56:07,948 --> 00:56:10,183 THE ALCOHOL AFFECT THE LUNG THAT 1120 00:56:10,183 --> 00:56:17,024 BECOMES IMPORTANT QUESTION. 1121 00:56:17,024 --> 00:56:22,629 TO ADDRESS THIS WE TRIED TO 1122 00:56:22,629 --> 00:56:25,599 ANALYZE TRANSCRIPTOMICS DATA 1123 00:56:25,599 --> 00:56:29,069 WHICH IS POPULATION BASED LUNG 1124 00:56:29,069 --> 00:56:30,303 TRANSCRIPTOME DATA AVAILABLE 1125 00:56:30,303 --> 00:56:40,781 THROUGH THE DATABASE AND WE 1126 00:56:42,449 --> 00:56:46,753 IDENTIFIED 328 ALCOHOL DRINKERS 1127 00:56:46,753 --> 00:56:48,388 AND THEIR AGE WAS SIMILAR. 1128 00:56:48,388 --> 00:56:50,057 IN THIS POPULATION WE ALSO FOUND 1129 00:56:50,057 --> 00:56:50,624 DIFFERENT LEVELS OF ALCOHOL 1130 00:56:50,624 --> 00:56:54,594 DRINKING. 1131 00:56:54,594 --> 00:56:57,998 FROM LESS THAN ONE OR MORE THAN 1132 00:56:57,998 --> 00:57:01,501 FOUR OR IN BETWEEN. 1133 00:57:01,501 --> 00:57:03,270 S FIRST WE CZECHED THE EFFECT 1134 00:57:03,270 --> 00:57:06,807 AND HERE WE FOUND REGARDLESS OF 1135 00:57:06,807 --> 00:57:10,043 THE SEX OR ALCOHOL DOSE THE 1136 00:57:10,043 --> 00:57:12,979 GENES SIGNIFICANTLY ALTERED WITH 1137 00:57:12,979 --> 00:57:14,081 ALCOHOL DRINKING. 1138 00:57:14,081 --> 00:57:15,148 THAT WAS QUITE SURPRISING 1139 00:57:15,148 --> 00:57:16,650 BECAUSE THE LOWER LEVEL OF 1140 00:57:16,650 --> 00:57:18,018 ALCOHOL CAN DO SOMETHING IN THE 1141 00:57:18,018 --> 00:57:21,588 LUNG BUT WINCE ONCE WE CHECK THE 1142 00:57:21,588 --> 00:57:27,928 DOSE RESPONSE INCREASE ALCOHOL 1143 00:57:27,928 --> 00:57:29,362 CONSUMPTION AND INCREASING THE 1144 00:57:29,362 --> 00:57:36,837 GENES ONLY IN MEN BUT NOT WOMEN. 1145 00:57:36,837 --> 00:57:39,106 THAT SUGGESTED MEN ARE MORE 1146 00:57:39,106 --> 00:57:42,442 SENSITIVE TO ALCOHOL AFFECT TO 1147 00:57:42,442 --> 00:57:47,647 DYSREGULATING THE LUNG IMMUNITY. 1148 00:57:47,647 --> 00:57:50,317 AS A NEXT STEP WE WANT TO CHECK 1149 00:57:50,317 --> 00:57:52,919 THE HEAVY ALCOHOL DRINKER'S LUNG 1150 00:57:52,919 --> 00:57:56,523 AND SEE WHAT PATHWAYS ARE 1151 00:57:56,523 --> 00:57:56,756 ALTERED. 1152 00:57:56,756 --> 00:57:57,023 . 1153 00:57:57,023 --> 00:58:04,831 WE FOUND THESE WERE 1154 00:58:04,831 --> 00:58:06,199 SIGNIFICANTLY DOWN RELATED. 1155 00:58:06,199 --> 00:58:09,002 AND THIS IS ALSO HAPPENING OR 1156 00:58:09,002 --> 00:58:12,539 APPEARED IN MALE OR MEN NOT 1157 00:58:12,539 --> 00:58:12,739 WOMEN. 1158 00:58:12,739 --> 00:58:16,376 AND THESE PATHWAYS ARE NATURAL 1159 00:58:16,376 --> 00:58:20,313 KILLER CELLS MAYBE WITH 1160 00:58:20,313 --> 00:58:21,915 CYTOTOXICITY AND SIGNALLING AND 1161 00:58:21,915 --> 00:58:25,252 THESE ARE BASICALLY ALL 1162 00:58:25,252 --> 00:58:29,489 INVOLVING THE MOST EVENTS AND 1163 00:58:29,489 --> 00:58:31,158 INFLAMMATION INJURY PROCESS. 1164 00:58:31,158 --> 00:58:32,325 THAT SOMEHOW SET GROUND FOR US 1165 00:58:32,325 --> 00:58:33,827 FROM THE HUMAN DATA BUT WE NEED 1166 00:58:33,827 --> 00:58:37,497 TO UNDERSTAND THE FUNCTIONAL AND 1167 00:58:37,497 --> 00:58:40,967 TRANSLATI 1168 00:58:40,967 --> 00:58:44,404 TRANSLATIONAL RELEVANCE USING 1169 00:58:44,404 --> 00:58:47,874 ANIMAL STUDIES AND DECIDED TO 1170 00:58:47,874 --> 00:58:52,579 TRY FIRST CHRONIC DRINKING WHICH 1171 00:58:52,579 --> 00:58:56,283 WAS INTRODUCED BY DR. BENGOL AND 1172 00:58:56,283 --> 00:58:59,586 THIS MODEL WE BASICALLY CHECKED 1173 00:58:59,586 --> 00:59:05,859 THE IMMUNE CELLS BY FLOW 1174 00:59:05,859 --> 00:59:09,095 CYTOMETRY AND LEVELS DECREASE IN 1175 00:59:09,095 --> 00:59:13,133 MALE ANIMALS NINE HOURS AFTER 1176 00:59:13,133 --> 00:59:16,937 BUT RESTORING BACK AND 1177 00:59:16,937 --> 00:59:20,707 MACROPHAGE WAS DECREASED 1178 00:59:20,707 --> 00:59:21,841 PREDOMINANTLY IN MALE AND 1179 00:59:21,841 --> 00:59:23,877 SHOWING THE UP REGULATION. 1180 00:59:23,877 --> 00:59:25,579 THIS WAS MYELOID CELLS. 1181 00:59:25,579 --> 00:59:28,181 THIS IS THE INNATE IMMUNE CELLS. 1182 00:59:28,181 --> 00:59:30,150 WE ALSO CHECKED THE ADAPTIVE 1183 00:59:30,150 --> 00:59:34,187 IMMUNE CELLS WHICH ARE LYMPHOIDS 1184 00:59:34,187 --> 00:59:40,927 AND FOUND MULTIPLE LYMPHOID 1185 00:59:40,927 --> 00:59:45,232 CELLS LIKE TC17 CELLS OR NATURAL 1186 00:59:45,232 --> 00:59:47,901 KILLER CELLS ARE DOWN REGULATED. 1187 00:59:47,901 --> 00:59:50,170 THERE'S A RATE RESPONSE MUCH 1188 00:59:50,170 --> 00:59:53,340 MORE DOMINANT THAN THE 24 HOURS 1189 00:59:53,340 --> 00:59:55,642 BUT THIS IS ALSO PREDOMINANTLY 1190 00:59:55,642 --> 01:00:01,982 SEEN IN THE MALE SUBJECTS. 1191 01:00:01,982 --> 01:00:07,587 WE FOUND THE 17 T CELLS AND TOLD 1192 01:00:07,587 --> 01:00:10,657 MAYBE THE MODEL IS GOOD TO 1193 01:00:10,657 --> 01:00:17,063 ESTABLISH OR SEE THE TRANSLATION 1194 01:00:17,063 --> 01:00:18,965 BUT IN THE MORTALITY CAUSES IS 1195 01:00:18,965 --> 01:00:20,567 THE ALCOHOL RELATED LIVER 1196 01:00:20,567 --> 01:00:25,772 DISEASE. 1197 01:00:25,772 --> 01:00:28,575 THE NEXT QUESTION IS MAYBE IT 1198 01:00:28,575 --> 01:00:30,010 CAUSES THE UNIVERSAL INJURY IN 1199 01:00:30,010 --> 01:00:32,245 ALL ORGANS AND NOWADAYS WE HAVE 1200 01:00:32,245 --> 01:00:35,482 A SYSTEM BIOLOGY APPROACH WE CAN 1201 01:00:35,482 --> 01:00:40,820 SEE MORE SYSTEM IC INFORMATION F 1202 01:00:40,820 --> 01:00:42,022 THE TISSUE ON DIFFERENT ORDERS 1203 01:00:42,022 --> 01:00:44,024 AND DECIDED TO COMPARE SIDE BY 1204 01:00:44,024 --> 01:00:46,793 SIDE, LUNG AND LIVER FROM SAME 1205 01:00:46,793 --> 01:00:50,630 ANIMAL AND HERE WE USED THE SAME 1206 01:00:50,630 --> 01:00:58,204 ANIMAL MODEL IS WE ALSO WANT TO 1207 01:00:58,204 --> 01:01:02,142 SEE CHRONIC EFFECT. 1208 01:01:02,142 --> 01:01:08,615 AND HERE WE CHECKED THE 1209 01:01:08,615 --> 01:01:11,751 DIFFERENTIALLY EXPRESSED GENES. 1210 01:01:11,751 --> 01:01:13,186 THERE'S MORE SIGNIFICANT AT 1211 01:01:13,186 --> 01:01:16,022 RATION BUT IF YOU CHECK THE 1212 01:01:16,022 --> 01:01:19,125 LIVER -- ALTERATION BUT IF YOU 1213 01:01:19,125 --> 01:01:22,929 CHECK THE LIVER HAS MORE 1214 01:01:22,929 --> 01:01:25,665 EXPRESSED GENES COMPARED TO THE 1215 01:01:25,665 --> 01:01:32,305 LUNG BUT THE CHANGE WE CAN PRO 1216 01:01:32,305 --> 01:01:34,808 LONG DOWN REGULATE TO THE 1217 01:01:34,808 --> 01:01:38,078 PATHWAYS DOWN REGULATED AND 1218 01:01:38,078 --> 01:01:39,512 REMAIN DOWN REGULATED AFTER 14 1219 01:01:39,512 --> 01:01:39,713 DAYS. 1220 01:01:39,713 --> 01:01:43,083 ON THE OTHER HAND, LIVER HAS 1221 01:01:43,083 --> 01:01:44,417 ONLY FIVE PERSONS AF NINE HOURS 1222 01:01:44,417 --> 01:01:50,190 AND THERE'S A DELAYED DOWN 1223 01:01:50,190 --> 01:01:53,593 REGULATION BUT THEN IT'S 1224 01:01:53,593 --> 01:01:54,194 RESTORED. 1225 01:01:54,194 --> 01:01:58,198 14 DAYS EVEN SOME PATHWAYS ARE 1226 01:01:58,198 --> 01:02:00,166 UP REGULATED. 1227 01:02:00,166 --> 01:02:02,502 IT WAS SURPRISING SUGGESTING THE 1228 01:02:02,502 --> 01:02:04,504 ORGAN-SPECIFIC EFFECT OF ALCOHOL 1229 01:02:04,504 --> 01:02:08,375 AND THIS IS ACTUALLY SUPPORTING 1230 01:02:08,375 --> 01:02:11,177 OUR FINDING THAT LUNG MAY BE 1231 01:02:11,177 --> 01:02:14,481 MORE SENSITIVE FOR 1232 01:02:14,481 --> 01:02:15,682 ALCOHOL-REGULATED DYSREGULATION 1233 01:02:15,682 --> 01:02:17,684 AND WE WERE FORTUNATE TO SEE 1234 01:02:17,684 --> 01:02:22,188 WITH THE GTEX DATA WE IDENTIFIED 1235 01:02:22,188 --> 01:02:27,660 A PATIENT AND TRIED TO MATCH THE 1236 01:02:27,660 --> 01:02:30,230 LUNG AND LIVER SAMPLES FROM THE 1237 01:02:30,230 --> 01:02:34,200 SAME PATIENT AND THIS IS THE 1238 01:02:34,200 --> 01:02:43,977 SAME AND WE FOUND HUMAN LUNG 1239 01:02:43,977 --> 01:02:45,745 TRANSCRIPTOME AND THE MOUSE 1240 01:02:45,745 --> 01:02:46,079 TRANSCRIPTOME. 1241 01:02:46,079 --> 01:02:49,783 YOU SEE HERE THE PATHWAYS ARE 1242 01:02:49,783 --> 01:02:54,621 SIMILAR WE ALREADY IDENTIFIED T 1243 01:02:54,621 --> 01:02:56,356 CELLS AND K CELLS. 1244 01:02:56,356 --> 01:03:00,026 IT ALSO CONVINCED US MAYBE THE 1245 01:03:00,026 --> 01:03:02,796 MODEL IS RECAPITULATING THE 1246 01:03:02,796 --> 01:03:06,199 SIMILAR ALTERATIONS IN THE HUMAN 1247 01:03:06,199 --> 01:03:15,942 LUNG. 1248 01:03:15,942 --> 01:03:19,312 THEN TO IDENTIFY THE MOST 1249 01:03:19,312 --> 01:03:20,447 SIGNIFICANT CHANGE OR WHAT MAY 1250 01:03:20,447 --> 01:03:23,516 BE UPREGULATED FOR ALL THE 1251 01:03:23,516 --> 01:03:24,751 CHANGE WE WANT TO USE THE 1252 01:03:24,751 --> 01:03:27,821 SYSTEMIC BIOLOGY APPROACH. 1253 01:03:27,821 --> 01:03:33,259 HERE WE TRIED TO SEE WHAT IS 1254 01:03:33,259 --> 01:03:34,727 ALTERED IN HUMAN LUNG AND MOUSE 1255 01:03:34,727 --> 01:03:34,994 LUNG. 1256 01:03:34,994 --> 01:03:38,264 HERE WE DECIDED TO CHECK ALL THE 1257 01:03:38,264 --> 01:03:45,271 TIME POINTS WHETHER WE SEE 1258 01:03:45,271 --> 01:03:48,775 SIMILAR ALTERATIONS IN HUMAN AND 1259 01:03:48,775 --> 01:03:59,285 THEY'RE HAPPENING IN AND SOME 1260 01:04:01,120 --> 01:04:03,223 ARE IN IMMUNE REGULATED 1261 01:04:03,223 --> 01:04:03,490 PATHWAYS. 1262 01:04:03,490 --> 01:04:06,926 WE GENERATED THE EXPRESSION AND 1263 01:04:06,926 --> 01:04:12,532 TRIED TO SEE THE MAJOR DRIVERS 1264 01:04:12,532 --> 01:04:14,234 AND IDENTIFIED G1. 1265 01:04:14,234 --> 01:04:18,805 G1 NETWORK IS UP REGULATED WHICH 1266 01:04:18,805 --> 01:04:20,340 CONSISTS OF METABOLIC PATHWAYS 1267 01:04:20,340 --> 01:04:22,709 AND G3 IS DOWN REGULATED WHICH 1268 01:04:22,709 --> 01:04:31,684 IS IMMUNE REGULATED PATHWAYS. 1269 01:04:31,684 --> 01:04:34,888 CHECKING THE DATA SHOWED THE 1270 01:04:34,888 --> 01:04:37,390 DRIVERS OF THE ALTERATION IN 1271 01:04:37,390 --> 01:04:39,058 LUNGS WITH CHRONIC ALCOHOL 1272 01:04:39,058 --> 01:04:40,026 INTAKE IN HUMAN. 1273 01:04:40,026 --> 01:04:43,096 WE TRIED TO EXPLORE IN DETAILS 1274 01:04:43,096 --> 01:04:46,232 THE PATHWAYS AND IT NOTICED 1275 01:04:46,232 --> 01:04:54,707 CHECK ALCOHOL HAS MULTIPLE 1276 01:04:54,707 --> 01:04:58,645 METABOLIC CHANGE IN ORGAN AND 1277 01:04:58,645 --> 01:05:02,949 THERE'S SIGNIFICANT ALTERATIONS 1278 01:05:02,949 --> 01:05:08,755 AND WE DID TARGETED METABOLOMICS 1279 01:05:08,755 --> 01:05:11,558 TO SEE HOW IT'S ALTERED BUT WE 1280 01:05:11,558 --> 01:05:14,594 ALSO WANT TO SEE IF WE CAN 1281 01:05:14,594 --> 01:05:15,461 IDENTIFY A DIFFERENCE BETWEEN 1282 01:05:15,461 --> 01:05:18,131 THE JUST SINGLE ACUTE PINCH 1283 01:05:18,131 --> 01:05:20,767 VERSUS THE CHRONIC PLUS SINGLE 1284 01:05:20,767 --> 01:05:28,608 AND HERE YOU CAN SEE SINGLE 1285 01:05:28,608 --> 01:05:32,011 SHOWS THE SINGLE PINCH AND 1286 01:05:32,011 --> 01:05:37,050 OTHERS NOTICE HERE IT INCREASES 1287 01:05:37,050 --> 01:05:40,019 AMINO ACID LEVELS. 1288 01:05:40,019 --> 01:05:47,493 THAT ALSO ASK IS EVIDENT AND SEE 1289 01:05:47,493 --> 01:05:49,996 THE MOST SIGNIFICANTLY AT RATED 1290 01:05:49,996 --> 01:05:50,229 PATHWAY. 1291 01:05:50,229 --> 01:05:51,898 WE THOUGHT MAYBE WE NEED TO 1292 01:05:51,898 --> 01:05:54,167 FOLLOW THE EVIDENCE TO FURTHER 1293 01:05:54,167 --> 01:06:04,377 EXPLORATION. 1294 01:06:08,414 --> 01:06:12,285 AND BRANCH AMINO ACIDS WE TAKE 1295 01:06:12,285 --> 01:06:13,620 THEM BY DIET OR BY DEGRADATION 1296 01:06:13,620 --> 01:06:22,528 OF THE PROTEINS WE TAKE THIS ONE 1297 01:06:22,528 --> 01:06:33,039 HOUR BEFORE TISSUE COLLECTION 1298 01:06:34,240 --> 01:06:39,345 AND WE SEE THE LEUCINE LEVELS IN 1299 01:06:39,345 --> 01:06:39,545 SERUM. 1300 01:06:39,545 --> 01:06:41,481 THEY'RE TRANSPORTED TO THE LUNG 1301 01:06:41,481 --> 01:06:52,091 BY AMINO TRANSPORTERS THEIR 1302 01:06:52,392 --> 01:06:53,626 EXPRESSION WAS TWO TO FOUR FOLD 1303 01:06:53,626 --> 01:06:56,062 INCREASE AND WE COULD ONLY SEE 1304 01:06:56,062 --> 01:06:57,697 FOURFOLD INCREASE IN THE LUNG 1305 01:06:57,697 --> 01:07:01,300 AND THAT SUGGESTED THERE ARE 1306 01:07:01,300 --> 01:07:06,773 HIGHER CLEARANCE OF THIS IN THE 1307 01:07:06,773 --> 01:07:08,975 LUNG AND THE DEGRADATION 1308 01:07:08,975 --> 01:07:09,242 INCREASED. 1309 01:07:09,242 --> 01:07:12,445 ONCE WE CHECKED IN HUMAN AND 1310 01:07:12,445 --> 01:07:16,215 MOUSE LUNG INDIVIDUALS ENZYMES 1311 01:07:16,215 --> 01:07:19,719 IN THE DEGRADATION PATHWAY, WE 1312 01:07:19,719 --> 01:07:23,890 CAN SEE IN MOUSE AND HUMAN 1313 01:07:23,890 --> 01:07:27,360 SIGNIFICANT UPREGULATION OF THE 1314 01:07:27,360 --> 01:07:27,894 ENZYME. 1315 01:07:27,894 --> 01:07:33,299 OUR STUDY DEMONSTRATED IT 1316 01:07:33,299 --> 01:07:34,567 INCREASED DEGRADATION IN MOUSE 1317 01:07:34,567 --> 01:07:36,536 AND HUMAN. 1318 01:07:36,536 --> 01:07:39,439 HOW WE FOUND THIS AMINO ACID 1319 01:07:39,439 --> 01:07:40,173 QUITE INTERESTING SINCE THEY'RE 1320 01:07:40,173 --> 01:07:43,609 ESSENTIALLY WHAT OUR BODY NEEDS 1321 01:07:43,609 --> 01:07:45,912 AND WE WANT TO SEE WHAT PATHWAYS 1322 01:07:45,912 --> 01:07:47,747 THEY MAY BE INVOLVING. 1323 01:07:47,747 --> 01:07:56,689 ONE OF THE CRITICAL PATHWAYS IS 1324 01:07:56,689 --> 01:08:00,460 MTOR SIGNALLING BUT IT'S A 1325 01:08:00,460 --> 01:08:08,434 MASTER REGULATOR OF METABOLISM 1326 01:08:08,434 --> 01:08:11,237 AND CRITICAL FOR MITOCHONDRIAL 1327 01:08:11,237 --> 01:08:11,471 GENESIS. 1328 01:08:11,471 --> 01:08:15,575 AS THE FIRST STEP WE CHECKED THE 1329 01:08:15,575 --> 01:08:17,577 MTOR SIGNALLING AND CHRONIC 1330 01:08:17,577 --> 01:08:18,845 ALCOHOL IS REDUCING THE MTOR 1331 01:08:18,845 --> 01:08:26,953 ACTIVATION. 1332 01:08:26,953 --> 01:08:31,190 THEN WE WANT TO SEE A 1333 01:08:31,190 --> 01:08:33,359 PHARMACOLOGIC INTERVENTION TO 1334 01:08:33,359 --> 01:08:36,529 SEE HOW IT INVOLVES THE DE 1335 01:08:36,529 --> 01:08:38,164 REGULATION. 1336 01:08:38,164 --> 01:08:42,535 WE HAVE A SELECTIVE MTOR 1337 01:08:42,535 --> 01:08:46,906 INHIBITOR AND FDA APPROVED USED 1338 01:08:46,906 --> 01:08:52,678 BUT HERE AS YOU SEE WE DON'T 1339 01:08:52,678 --> 01:08:56,048 REDUCE FURTHER LIPOCYTE 1340 01:08:56,048 --> 01:09:01,087 REDUCTION BUT SOME OF THE IMMUNE 1341 01:09:01,087 --> 01:09:04,524 CELLS ARE FURTHER DOWN REGULATED 1342 01:09:04,524 --> 01:09:09,629 BUT THIS SUGGEST ED IT'S DOWN 1343 01:09:09,629 --> 01:09:11,631 REGULATED THE MTOR SIGNALLING 1344 01:09:11,631 --> 01:09:14,200 AND THEY MAY BE UPSTREAM 1345 01:09:14,200 --> 01:09:18,171 REGULATOR OF THE IMMUNE 1346 01:09:18,171 --> 01:09:22,675 REGULATION. 1347 01:09:22,675 --> 01:09:24,977 KNOW IF YOU PUT THE EVIDENCE 1348 01:09:24,977 --> 01:09:27,947 TOGETHER IT SUGGESTS THE CHANGE 1349 01:09:27,947 --> 01:09:34,620 IN THE LUNG AND SWITCH DOING 1350 01:09:34,620 --> 01:09:37,790 DOWN REGULATION AND IT'S AN 1351 01:09:37,790 --> 01:09:39,258 INTERESTING APPROACH AND MAY BE 1352 01:09:39,258 --> 01:09:41,460 WE CAN SUPPLEMENT THEM. 1353 01:09:41,460 --> 01:09:44,463 MAYBE SUPPLEMENTING THE AMINO 1354 01:09:44,463 --> 01:09:49,135 ACID SIMPLY RESTORES THE MTOR 1355 01:09:49,135 --> 01:09:54,006 ACTIVITY AND MAYBE WE CAN ALSO 1356 01:09:54,006 --> 01:09:57,109 RESTORE THE DYSREGULATION AND WE 1357 01:09:57,109 --> 01:10:06,919 FOUND PROTOCOL AND WE TRIED ONE 1358 01:10:06,919 --> 01:10:10,189 AND WE WERE ABLE TO INCREASE THE 1359 01:10:10,189 --> 01:10:13,359 BRANCHING AMINO ACID THREEFOLD 1360 01:10:13,359 --> 01:10:15,995 COMPARED TO THE UNTREATED GROUP 1361 01:10:15,995 --> 01:10:19,732 BUT COULD NOT RESTORE MTOR 1362 01:10:19,732 --> 01:10:25,071 ACTIVITY OR IMMUNE CELLS. 1363 01:10:25,071 --> 01:10:31,978 NOW, TO SUMMARIZE THIS PART WE 1364 01:10:31,978 --> 01:10:34,780 FOUND WE CHECKED THE BASAL 1365 01:10:34,780 --> 01:10:36,549 ALCOHOL AFFECT WITHOUT ANY 1366 01:10:36,549 --> 01:10:38,017 SECONDARY CHALLENGE BUT CHRONIC 1367 01:10:38,017 --> 01:10:44,790 ALCOHOL DRINKING AS A SEXUALLY 1368 01:10:44,790 --> 01:10:49,262 DYSMORPHIC EFFECT AND MALES ARE 1369 01:10:49,262 --> 01:10:52,632 MORE PRONE TO THE ALCOHOL AND 1370 01:10:52,632 --> 01:10:54,967 LUNG IS MORE SENSITIVE TO 1371 01:10:54,967 --> 01:10:56,469 ALCOHOL EFFECT THAN LIVER FOR 1372 01:10:56,469 --> 01:11:06,479 IMMUNE DYSREGULATION. 1373 01:11:06,479 --> 01:11:08,614 ALCOHOL AFFECTS CHANGE IN THE 1374 01:11:08,614 --> 01:11:11,817 HUMAN AND MOUSE LUNG AND IN THE 1375 01:11:11,817 --> 01:11:13,552 MTOR SIGNALLING MIGHT BE ONE OF 1376 01:11:13,552 --> 01:11:17,490 THE UP STREAM REGULATOR OF 1377 01:11:17,490 --> 01:11:20,626 ALCOHOL INDUCED DYSREGULATION. 1378 01:11:20,626 --> 01:11:26,165 BUT IT SEEMS MTOR MAY NOT BE 1379 01:11:26,165 --> 01:11:30,036 IDEAL TARGETS TO ACTIVATE TO 1380 01:11:30,036 --> 01:11:34,907 CORRECTING THIS IMMUNE 1381 01:11:34,907 --> 01:11:36,309 DYSREGULATION BECAUSE IT MAY 1382 01:11:36,309 --> 01:11:38,177 ALSO INVOLVE PROMOTING THE 1383 01:11:38,177 --> 01:11:43,549 CARCINOGENESIS. 1384 01:11:43,549 --> 01:11:45,718 WE NEED TO FIND MORE UP STREAM 1385 01:11:45,718 --> 01:11:49,388 MORE SELECTIVE TARGETS AND NEED 1386 01:11:49,388 --> 01:11:53,893 TO UNDERSTAND BETTER UP STREAM 1387 01:11:53,893 --> 01:11:55,061 PATHWAYS REGULATING THIS. 1388 01:11:55,061 --> 01:11:57,997 AND WE'LL SWITCH GEARS BUT WE 1389 01:11:57,997 --> 01:12:06,472 ALSO FOUND ALCOHOL CRIN DUCING 1390 01:12:06,472 --> 01:12:11,010 MACROPHAGE POLYMERIZATION AND 1391 01:12:11,010 --> 01:12:18,184 OBSERVED THE MACROPHAGES 1392 01:12:18,184 --> 01:12:20,353 ACQUIRING THE PHENOTYPE AND 1393 01:12:20,353 --> 01:12:24,357 ACTIVATE THE MARKER. 1394 01:12:24,357 --> 01:12:27,626 WHY THIS IS IMPORTANT? 1395 01:12:27,626 --> 01:12:31,897 LET ME EXPLAIN WITH THE 1396 01:12:31,897 --> 01:12:32,531 MACROPHAGE POLYMERIZATION. 1397 01:12:32,531 --> 01:12:35,668 WITH HEALTHY PEOPLE IF YOU HAVE 1398 01:12:35,668 --> 01:12:38,804 INFECTION OR INJURY, THE HOST 1399 01:12:38,804 --> 01:12:42,108 DEFENSE MECHANISM REQUIRE OF THE 1400 01:12:42,108 --> 01:12:42,375 PHENOTYPE. 1401 01:12:42,375 --> 01:12:46,212 THESE ARE GENERALLY PRO 1402 01:12:46,212 --> 01:12:47,279 INFLAMMATORY AND ONCE THEY'RE 1403 01:12:47,279 --> 01:12:50,182 ACTIVATED AFTER THE THREAT IS 1404 01:12:50,182 --> 01:12:52,885 ELIMINATED THEY'RE DOWN 1405 01:12:52,885 --> 01:12:58,457 REGULATED AND THE INFLAMMATORY 1406 01:12:58,457 --> 01:13:02,161 RESPONSE IS REQUIRED FOR HEALTHY 1407 01:13:02,161 --> 01:13:09,435 WOUND HEALING. 1408 01:13:09,435 --> 01:13:12,838 THIS SYSTEM REMAINS ELEVATED BUT 1409 01:13:12,838 --> 01:13:18,411 IT BECOMES PROFIBROTIC. 1410 01:13:18,411 --> 01:13:21,313 THERE'S MULTIPLE EVIDENCE THAT A 1411 01:13:21,313 --> 01:13:26,185 MONOCYTE DRIVE AND CONTRIBUTE TO 1412 01:13:26,185 --> 01:13:36,362 FIBROSIS. 1413 01:13:36,562 --> 01:13:38,864 CAN WE UNDERSTAND PATHOGENIC 1414 01:13:38,864 --> 01:13:40,599 MECHANISMS AND ALCOHOL INDUCED 1415 01:13:40,599 --> 01:13:42,802 LUNG INJURY? 1416 01:13:42,802 --> 01:13:46,205 THAT CAN BE BOLD QUESTION BUT WE 1417 01:13:46,205 --> 01:13:51,777 WANT TO TRY TO USE THE SYSTEMS 1418 01:13:51,777 --> 01:13:52,812 BIOLOGY APPROACH. 1419 01:13:52,812 --> 01:13:54,814 NOW, I WANT TO BRIEFLY MENTIONED 1420 01:13:54,814 --> 01:13:57,917 WHAT ARE THE FIBROTIC LUNG 1421 01:13:57,917 --> 01:13:58,184 DISEASES? 1422 01:13:58,184 --> 01:14:01,487 WE KNOW LUNG PLAYS A CRITICAL 1423 01:14:01,487 --> 01:14:02,855 ROLE FOR OXYGEN SUPPLY AND IT'S 1424 01:14:02,855 --> 01:14:07,693 HAPPENING IN ALVEOLI AND THE 1425 01:14:07,693 --> 01:14:10,496 WHITE SPACE IS AIR SACKS AND THE 1426 01:14:10,496 --> 01:14:12,798 OXYGEN EXCHANGE HERE BUT IN THE 1427 01:14:12,798 --> 01:14:16,836 FIBROTIC OR FIBROPROLIFERATION 1428 01:14:16,836 --> 01:14:18,437 ALVEOLI GETS THICKER OR SCARRING 1429 01:14:18,437 --> 01:14:20,573 AND YOU CAN SEE THIS HISTOLOGY 1430 01:14:20,573 --> 01:14:23,909 OR PATHOLOGY. 1431 01:14:23,909 --> 01:14:30,316 BLUE IS THE EXTRA CELLULAR 1432 01:14:30,316 --> 01:14:31,617 MATRIX DEPOSITION. 1433 01:14:31,617 --> 01:14:34,186 AS A RESULT OF THE CHANGE YOU 1434 01:14:34,186 --> 01:14:36,589 CAN APPRECIATE THE INDIVIDUALS 1435 01:14:36,589 --> 01:14:38,491 CAN LOSE THE LUNG CAPACITY AND 1436 01:14:38,491 --> 01:14:42,194 THE DECLINE AFTER THREE TO FIVE 1437 01:14:42,194 --> 01:14:42,928 YEARS MORE TRALT CAN OCCUR. 1438 01:14:42,928 --> 01:14:46,031 WHY THIS IS IMPORTANT BECAUSE 1439 01:14:46,031 --> 01:14:51,070 ALSO PREVALENCE AND MORTALITY 1440 01:14:51,070 --> 01:14:53,439 LUNG DISEASE INCREASED AND ONE 1441 01:14:53,439 --> 01:14:55,341 OF THE RECENT EVIDENCE BASED ON 1442 01:14:55,341 --> 01:14:56,575 THE GLOBAL BURDEN OF THIS 1443 01:14:56,575 --> 01:14:59,945 DISEASE DATA PUBLISHED IN 2019 1444 01:14:59,945 --> 01:15:02,448 CHRONIC RESPIRATORY DISEASE IN 1445 01:15:02,448 --> 01:15:05,251 THE FIRST TIME IN HISTORY IS THE 1446 01:15:05,251 --> 01:15:06,552 LEADING CAUSE OF DEATH WITH $4 1447 01:15:06,552 --> 01:15:13,792 MILLION DEATHS. 1448 01:15:13,792 --> 01:15:16,862 ONE OF THE DATA COMPARED THE 20 1449 01:15:16,862 --> 01:15:27,406 YEAR TREND AND THE REF LANCE HAS 1450 01:15:30,242 --> 01:15:33,012 HIGHER MORTALITY THERE'S LESS 1451 01:15:33,012 --> 01:15:34,780 DEATH BECAUSE OF THE ASTHMA 1452 01:15:34,780 --> 01:15:35,881 MEDICATIONS OR ANTIBIOTICS. 1453 01:15:35,881 --> 01:15:39,985 IT SHOWS UNMET MEDICAL NEED FOR 1454 01:15:39,985 --> 01:15:41,287 FIBROTIC LUNG DISEASE AS 1455 01:15:41,287 --> 01:15:42,555 EVIDENCE FROM INCREASED 1456 01:15:42,555 --> 01:15:43,088 PREVALENCE AND REMARKABLE 1457 01:15:43,088 --> 01:15:47,092 MORTALITY. 1458 01:15:47,092 --> 01:15:48,827 WHAT ARE THE MECHANISMS IN 1459 01:15:48,827 --> 01:15:49,028 LUNGS? 1460 01:15:49,028 --> 01:15:51,931 THIS IS IMPORTANT TO UNDERSTAND 1461 01:15:51,931 --> 01:15:54,433 DISEASE AND ALSO DEVELOPING 1462 01:15:54,433 --> 01:15:56,101 TARGETS AND STRATEGY. 1463 01:15:56,101 --> 01:16:06,011 IN MY LAB WE TRIES TO ALSO DO AN 1464 01:16:06,011 --> 01:16:09,348 APPROACH TO THE MULTI-OMICS 1465 01:16:09,348 --> 01:16:12,017 APPROACH USING THE FIBROSIS 1466 01:16:12,017 --> 01:16:15,654 ANIMAL MODEL AND HUMAN LUNG 1467 01:16:15,654 --> 01:16:17,590 PATIEN 1468 01:16:17,590 --> 01:16:18,591 PATIENTS AND HEALTHY LUNG 1469 01:16:18,591 --> 01:16:20,859 SAMPLES AND THE PARAMETERS 1470 01:16:20,859 --> 01:16:24,797 INCLUDING PULMONARY FUNCTION 1471 01:16:24,797 --> 01:16:25,231 TEST. 1472 01:16:25,231 --> 01:16:27,399 IT'S IMPORTANT BECAUSE IN CLINIC 1473 01:16:27,399 --> 01:16:30,069 IT'S THE ONLY MARKER TO MONITOR 1474 01:16:30,069 --> 01:16:33,672 THE PROGRESSION OF THE DISEASE. 1475 01:16:33,672 --> 01:16:38,143 IF YOU WANT TO DESIGN A CLINICAL 1476 01:16:38,143 --> 01:16:41,614 TRIAL THEY'LL ASK YOU TO SHOW 1477 01:16:41,614 --> 01:16:45,818 THE DECLINE OR MONITOR THE 1478 01:16:45,818 --> 01:16:46,085 CAPACITY. 1479 01:16:46,085 --> 01:16:49,855 WE INTEGRATED MORE THAN 13,000 1480 01:16:49,855 --> 01:16:52,625 GENES PULMONARY FUNCTION 1481 01:16:52,625 --> 01:16:54,693 PARAMETERS AND 200,000 LINKS AND 1482 01:16:54,693 --> 01:16:58,163 IDENTIFIED 5G NETWORKS. 1483 01:16:58,163 --> 01:17:04,870 AND AGAIN IT WAS IMPORTANT. 1484 01:17:04,870 --> 01:17:09,975 ONCE WE TRIED TO SEE THE 10 MOST 1485 01:17:09,975 --> 01:17:13,112 SIGNIFICANT GENES CO-REGULATED 1486 01:17:13,112 --> 01:17:14,013 WITH THE FUNCTION. 1487 01:17:14,013 --> 01:17:17,316 THE NI VH1 AND 2 WERE THERE AND 1488 01:17:17,316 --> 01:17:20,653 WE WERE NOT EXPECTING TO SEE 1489 01:17:20,653 --> 01:17:20,853 THEM. 1490 01:17:20,853 --> 01:17:31,130 BUT THIN ANOTHER STUDY WITH THE 1491 01:17:31,130 --> 01:17:32,498 SEQUENCING STUDY FOUND IN THE 1492 01:17:32,498 --> 01:17:38,170 HUMAN LUNG FIBROBLAST AND DURING 1493 01:17:38,170 --> 01:17:41,240 FIBROSIS THE LEVELS WERE DOWN 1494 01:17:41,240 --> 01:17:44,643 RELTHED AND IF THERE IS A 1495 01:17:44,643 --> 01:17:48,714 FIBROSIS RESOLUTION, ALDH HAS TO 1496 01:17:48,714 --> 01:17:56,155 BE A RISK AND ALSO THIS STUDY 1497 01:17:56,155 --> 01:17:57,956 HIGHLIGHTS THE IMPORTANCE OF 1498 01:17:57,956 --> 01:17:59,491 ALCOHOL METABOLISM AND WOUND 1499 01:17:59,491 --> 01:18:00,259 HEALING RESPONSE. 1500 01:18:00,259 --> 01:18:03,529 IN OTHER FOLLOW-UP STUDY 1501 01:18:03,529 --> 01:18:06,565 CONFIRMED IF YOU DELETE IT 1502 01:18:06,565 --> 01:18:08,634 AGGREGATED LUNG FIBROSIS THROUGH 1503 01:18:08,634 --> 01:18:11,437 MITOCHONDRIAL DYSFUNCTION AND 1504 01:18:11,437 --> 01:18:13,972 AGING FIBROBLASTS. 1505 01:18:13,972 --> 01:18:16,175 BASED ON THE EVIDENCE WE THINK 1506 01:18:16,175 --> 01:18:20,646 HEAVY ALCOHOL DRINKING MAY CAUSE 1507 01:18:20,646 --> 01:18:25,284 WOUND HEALING RESPONSE IN LUNGS. 1508 01:18:25,284 --> 01:18:28,520 AND THERE'S A THOUSAND REASONS 1509 01:18:28,520 --> 01:18:31,023 WHY THE ALCOHOL IS CAUSING 1510 01:18:31,023 --> 01:18:32,291 INJURIES WITH PERTURBATION IN 1511 01:18:32,291 --> 01:18:33,826 THE WOUND HEALING RESPONSE. 1512 01:18:33,826 --> 01:18:36,662 WITH THE HYPOTHESIZED DRIVEN 1513 01:18:36,662 --> 01:18:38,163 APPROACH INFORMED US SHARED 1514 01:18:38,163 --> 01:18:40,632 MECHANISMS IN ALCOHOL-RELATED 1515 01:18:40,632 --> 01:18:42,568 LUNG DISEASE AND FIBROTIC LUNG 1516 01:18:42,568 --> 01:18:45,471 DISEASE MAY EXIST. 1517 01:18:45,471 --> 01:18:51,710 IT MEANS WE NEED TO LOOK FOR 1518 01:18:51,710 --> 01:18:55,280 INTERACTION OF THE TWO 1519 01:18:55,280 --> 01:18:55,581 PATHOLOGIES. 1520 01:18:55,581 --> 01:18:57,716 WE TAKE THE INTEGRATIVE OMICS 1521 01:18:57,716 --> 01:18:59,118 APPROACH AND WE IDENTIFY OR 1522 01:18:59,118 --> 01:19:01,720 DEVELOP A FRAMEWORK FOR 1523 01:19:01,720 --> 01:19:04,957 IDENTIFYING TARGETS BECAUSE OUR 1524 01:19:04,957 --> 01:19:08,293 AIM IS IDEAL TARGETS THEY SHOULD 1525 01:19:08,293 --> 01:19:13,899 CAUSE CHANGE AT THE SAME TIME. 1526 01:19:13,899 --> 01:19:16,802 HERE WE FOUND THE THERAPEUTIC 1527 01:19:16,802 --> 01:19:20,606 TARGET FOR PULMONARY FIBROSIS 1528 01:19:20,606 --> 01:19:27,846 BECAUSE IT EARLIER WE SHOWED CV1 1529 01:19:27,846 --> 01:19:29,081 COMPARED TO THE HEALTHY LUNG 1530 01:19:29,081 --> 01:19:30,682 THERE'S A REMARKABLE INCREASE OF 1531 01:19:30,682 --> 01:19:35,954 C1 EXPRESSION. 1532 01:19:35,954 --> 01:19:43,562 AND THE ACTIVATOR NAMED AND 1533 01:19:43,562 --> 01:19:44,663 INCREA 1534 01:19:44,663 --> 01:19:47,099 INCREASED IN PATIENTS AND THE 1535 01:19:47,099 --> 01:19:49,168 INCREASE WAS NEGATIVELY 1536 01:19:49,168 --> 01:19:50,169 CORRELATED WITH PULMONARY 1537 01:19:50,169 --> 01:19:59,378 FUNCTION DECLINE. 1538 01:19:59,378 --> 01:20:04,082 IT MAY HAVE A BIOMARKER THE LAST 1539 01:20:04,082 --> 01:20:05,717 COUPLE YEARS WE ALSO TRIED TO 1540 01:20:05,717 --> 01:20:06,919 UNDERSTAND THE SPECIFIC OF CV1 1541 01:20:06,919 --> 01:20:17,229 IN THE PATHOLOGY. 1542 01:20:18,230 --> 01:20:22,301 WE IDENTIFIED THE CC1 RECEPTOR 1543 01:20:22,301 --> 01:20:26,171 IS RESPONSIBLE FOR THE ALVEOLI 1544 01:20:26,171 --> 01:20:30,976 AND RESPONSIBLE FOR CD2O6 1545 01:20:30,976 --> 01:20:33,979 EXPRESSION WHICH MAKES 1546 01:20:33,979 --> 01:20:36,114 FIBROBLASTS FIBROTIC SORRY, 1547 01:20:36,114 --> 01:20:39,451 MACROPHAGES PROFIBROTIC AND 1548 01:20:39,451 --> 01:20:45,958 CONTRIBUT 1549 01:20:45,958 --> 01:20:47,226 CONTRIBUTING WITH THE MARKERS 1550 01:20:47,226 --> 01:20:48,527 AND WE THOUGHT WE SHOULD 1551 01:20:48,527 --> 01:20:50,996 INVESTIGATE THE ROLE IN ALCOHOL 1552 01:20:50,996 --> 01:20:51,897 INDUCED LUNG INJURY. 1553 01:20:51,897 --> 01:21:00,906 THE SAME ANIMAL MODELS WE FOUND 1554 01:21:00,906 --> 01:21:04,843 IT INCREASED IN THE LUNG AND 1555 01:21:04,843 --> 01:21:08,614 ONLY INCREASED NINE HOURS, 24 1556 01:21:08,614 --> 01:21:13,685 HOURS RETURNING BACK BUT THE 1557 01:21:13,685 --> 01:21:14,253 GENE EXPRESSION WAS HIGHLY 1558 01:21:14,253 --> 01:21:20,726 ELEVATED. 1559 01:21:20,726 --> 01:21:23,228 NOW IN THE PREVIOUS SLIDE I WAS 1560 01:21:23,228 --> 01:21:26,164 TALKING ABOUT MACROPHAGE AND YOU 1561 01:21:26,164 --> 01:21:29,735 CAN ASK ABOUT THE STATUS OR 1562 01:21:29,735 --> 01:21:31,737 EXCREMENTAL MODEL. 1563 01:21:31,737 --> 01:21:36,742 WE CHECKED WITH THE FLOW 1564 01:21:36,742 --> 01:21:37,009 CYTOMETRY. 1565 01:21:37,009 --> 01:21:38,977 YOU SEE THE CD 1 LUNG EXPRESSION 1566 01:21:38,977 --> 01:21:42,447 INCREASED WITH FIBROSIS. 1567 01:21:42,447 --> 01:21:45,651 SIMILARLY ALCOHOL INCREASES THE 1568 01:21:45,651 --> 01:21:48,654 CD 1 EXPRESSION AND THAT'S 1569 01:21:48,654 --> 01:21:59,064 RETURNING BACK 24 HOURS. 1570 01:21:59,898 --> 01:22:02,267 WE WANT TO EXPLORE MORE THE V1. 1571 01:22:02,267 --> 01:22:06,171 I THINK ONE OF THE IDEAL MODELS 1572 01:22:06,171 --> 01:22:11,410 OR GROUP IS VOLUNTARY DRINK 1573 01:22:11,410 --> 01:22:13,211 MODELS IN NON-HUMAN PRIORITIES 1574 01:22:13,211 --> 01:22:16,815 AND ILD PATIENTS. 1575 01:22:16,815 --> 01:22:25,891 WE WERE FORTUNATE TO ESTABLISH 1576 01:22:25,891 --> 01:22:26,692 COLLABORA 1577 01:22:26,692 --> 01:22:27,926 COLLABORATION AND DEVELOPED A 1578 01:22:27,926 --> 01:22:31,830 DRINKING MODEL IN NON-HUMAN 1579 01:22:31,830 --> 01:22:42,374 PRIMATES AND THEY COLLECTED THE 1580 01:22:42,975 --> 01:22:46,945 LAVAGE AT THE BASELINE AND THE 1581 01:22:46,945 --> 01:22:53,652 ESCALATED THE DOSE AND AT THE 1582 01:22:53,652 --> 01:23:02,194 END THEY LET THE MONKEYS GO I 1583 01:23:02,194 --> 01:23:06,164 THINK 22 HOURS A DAY. 1584 01:23:06,164 --> 01:23:09,935 AT THE END IT COLLECTED AND WHAT 1585 01:23:09,935 --> 01:23:18,210 WE FOUND INCREASE IN THE LAVAGE. 1586 01:23:18,210 --> 01:23:21,513 THIS WAS THE SAME OBSERVATION WE 1587 01:23:21,513 --> 01:23:25,050 FOUND WITH THE MOUSE MODEL BUT 1588 01:23:25,050 --> 01:23:26,685 ONCE WE CHECKED LONG-TERM 1589 01:23:26,685 --> 01:23:29,888 VOLUNTARY DRINKING THERE'S 1590 01:23:29,888 --> 01:23:40,432 REMARKABLE ALMOST 22 INCREASE WE 1591 01:23:44,670 --> 01:23:47,372 WERE INTERESTED IN THE STATUS OF 1592 01:23:47,372 --> 01:23:50,175 THE HUMAN WE WERE FORTUNATE TO 1593 01:23:50,175 --> 01:23:53,478 ESTABLISH COLLABORATION FROM THE 1594 01:23:53,478 --> 01:23:55,714 COLORADO PULMONARY ALCOHOL 1595 01:23:55,714 --> 01:23:57,049 RESEARCH COLLABORATIVE AND 1596 01:23:57,049 --> 01:24:00,819 ASSESSED SAMPLES BUT DESIGN A 1597 01:24:00,819 --> 01:24:07,492 STUDY TO SELECT SAMPLES OF 40 1598 01:24:07,492 --> 01:24:09,261 HEALTHY INDIVIDUALS AND HAVE 1599 01:24:09,261 --> 01:24:13,131 BLOOD ALCOHOL -DRINKERS AND HAVE 1600 01:24:13,131 --> 01:24:15,867 AUD PATIENTS EITHER SMOKERS OR 1601 01:24:15,867 --> 01:24:18,970 NON-SMOKERS BUT WE WERE ALSO 1602 01:24:18,970 --> 01:24:27,979 DISCUSSING OBVIOUSLY THEY'RE NOT 1603 01:24:27,979 --> 01:24:28,680 DRINKING ALCOHOL AND THOUGHT 1604 01:24:28,680 --> 01:24:35,787 MAYBE THOUGHT IT MAY BE A MATTER 1605 01:24:35,787 --> 01:24:37,556 FOR OUR MEASUREMENT. 1606 01:24:37,556 --> 01:24:40,892 THAT'S WHY WE STRATIFIED THE 1607 01:24:40,892 --> 01:24:50,168 GROUPS SELECTING PATIENTS FROM 1608 01:24:50,168 --> 01:25:00,712 THE FOUND NON-SMOKERS AND WITH 1609 01:25:03,448 --> 01:25:06,518 ALCOHOL PATIENTS THERE'S A 1610 01:25:06,518 --> 01:25:17,028 SIGNIFICANT INCREASE OF A BR 1611 01:25:23,368 --> 01:25:27,539 BRONCHIAL LAVAGE AND ALL THIS 1612 01:25:27,539 --> 01:25:30,175 SUGGES 1613 01:25:30,175 --> 01:25:33,478 SUGGESTED THE CHRONIC ALCOHOL 1614 01:25:33,478 --> 01:25:41,486 DRINKING IN LUNGS AND WE'RE 1615 01:25:41,486 --> 01:25:43,455 WORKING ON THE ACTIVATION MAY 1616 01:25:43,455 --> 01:25:46,491 CONTRIBUTE INJURY PROCESS IN THE 1617 01:25:46,491 --> 01:25:57,002 LUNG AND IT REQUIRES FURTHER 1618 01:25:58,537 --> 01:26:02,174 INVESTIGATION BUT WE'RE WORKING 1619 01:26:02,174 --> 01:26:07,712 ON THIS. 1620 01:26:07,712 --> 01:26:11,349 I'D LIKE TO THANK MY LAB MEMBERS 1621 01:26:11,349 --> 01:26:20,025 INVOLVED IN THE STUDIES AND 1622 01:26:20,025 --> 01:26:21,459 COLLABORATIONS AND JUDY IS 1623 01:26:21,459 --> 01:26:25,630 INSTRUMENTAL IN HELPING WITH THE 1624 01:26:25,630 --> 01:26:28,466 MASS SPEC MEASUREMENTS AND NIAAA 1625 01:26:28,466 --> 01:26:32,003 LEADERSHIP AND THE CONTINUOUS 1626 01:26:32,003 --> 01:26:33,271 SUPPORT IN THE INTRAMURAL 1627 01:26:33,271 --> 01:26:41,613 PROGRAM AND AND HELP WITH 1628 01:26:41,613 --> 01:26:43,248 RESEARCH AND COLLABORATORS. 1629 01:26:43,248 --> 01:26:43,481 THANKS. 1630 01:26:43,481 --> 01:26:44,883 I'LL BE ABLE TO ADDRESS IF YOU 1631 01:26:44,883 --> 01:26:55,160 HAVE QUESTIONS. 1632 01:26:56,895 --> 01:26:57,229 >> GREAT TALK. 1633 01:26:57,229 --> 01:26:57,896 I ALWAYS HAVE A HUNDRED 1634 01:26:57,896 --> 01:27:08,073 QUESTIONS. 1635 01:27:10,976 --> 01:27:12,744 IS POLLUTION ACTIVATED? 1636 01:27:12,744 --> 01:27:21,086 WHAT ABOUT CIGARETTE SMOKING, IS 1637 01:27:21,086 --> 01:27:23,622 THERE A VIRAL OR BACTERIAL 1638 01:27:23,622 --> 01:27:24,055 COMPONENT. 1639 01:27:24,055 --> 01:27:26,825 YOU DIDN'T TELL US WHAT CAUSES 1640 01:27:26,825 --> 01:27:28,827 LUNG FIBROSIS AND THEN ALCOHOL 1641 01:27:28,827 --> 01:27:36,868 CLEARLY INTERACTS I'M ASSUMING. 1642 01:27:36,868 --> 01:27:39,404 THERE'S SOME EVIDENCE AND ARDS 1643 01:27:39,404 --> 01:27:42,574 IS CAUSING A SOMEWHAT OF A 1644 01:27:42,574 --> 01:27:43,141 FIBROTIC CONDITION BUT IT'S 1645 01:27:43,141 --> 01:27:50,181 RESOLVED. 1646 01:27:50,181 --> 01:27:53,852 AND COVID WE LOST PATIENTS DUE 1647 01:27:53,852 --> 01:27:55,320 TO THE REMARKABLE FIBROTIC 1648 01:27:55,320 --> 01:27:57,389 PROCESS IN A SHORT TIME AND 1649 01:27:57,389 --> 01:27:59,691 BASICALLY THE LUNG CANNOT GO 1650 01:27:59,691 --> 01:28:02,928 WITH THAT AMOUNT OF FIBROTIC 1651 01:28:02,928 --> 01:28:03,695 PROCESS. 1652 01:28:03,695 --> 01:28:07,132 PEOPLE DIED BECAUSE LUNG 1653 01:28:07,132 --> 01:28:13,805 FIBROTIC PROCESS PEOPLE CALL IT 1654 01:28:13,805 --> 01:28:15,106 LUNG FIBROSIS. 1655 01:28:15,106 --> 01:28:17,342 MOST DIE BECAUSE OF THE SAME 1656 01:28:17,342 --> 01:28:18,810 REASON BECAUSE OF A RESPIRATORY 1657 01:28:18,810 --> 01:28:20,145 INFECTION AND WERE HOSPITALIZED 1658 01:28:20,145 --> 01:28:30,655 BUT THEY DIE OF THE SITUATION. 1659 01:28:48,640 --> 01:28:50,175 AND CIGARETTE IS ASSOCIATED AND 1660 01:28:50,175 --> 01:28:53,545 PEOPLE ARE TRADING IT WITH SOME 1661 01:28:53,545 --> 01:28:57,148 OF THE AREA PEOPLE LIVE WITH THE 1662 01:28:57,148 --> 01:28:58,183 AIR POLLUTION HAVE SIGNIFICANT 1663 01:28:58,183 --> 01:29:08,326 DECLINE. 1664 01:29:24,209 --> 01:29:26,211 I TRIED TO TAKE EVIDENCE THAT 1665 01:29:26,211 --> 01:29:36,421 MAKES SENSE. 1666 01:29:52,871 --> 01:29:55,173 >> DOES ANYONE ONLINE HAVE A 1667 01:29:55,173 --> 01:29:55,440 QUESTION? 1668 01:29:55,440 --> 01:29:56,107 >> IT'S A VERY INTERESTING TALK. 1669 01:29:56,107 --> 01:30:03,415 THANK YOU. 1670 01:30:03,415 --> 01:30:05,984 >> IS THERE INFORMATION ON THE 1671 01:30:05,984 --> 01:30:07,886 ALCOHOL-RELATED FIBROTIC DISEASE 1672 01:30:07,886 --> 01:30:11,556 ON ATHLETIC PERFORMANCE. 1673 01:30:11,556 --> 01:30:12,924 FROM A PREVENTION POINT OF VIEW 1674 01:30:12,924 --> 01:30:14,859 IT SEEMS IF THERE'S SOME 1675 01:30:14,859 --> 01:30:16,928 RELATIONSHIP THAT WOULD BE A 1676 01:30:16,928 --> 01:30:19,998 POWERFUL PREVENTION TOOL BECAUSE 1677 01:30:19,998 --> 01:30:23,068 PEOPLE PARTICULARLY YOUNG PEOPLE 1678 01:30:23,068 --> 01:30:24,602 WANT TO INCREASE THEIR ATHLETIC 1679 01:30:24,602 --> 01:30:26,171 PERFORMANCE. 1680 01:30:26,171 --> 01:30:27,972 SO IS THERE A RELATIONSHIP COULD 1681 01:30:27,972 --> 01:30:31,943 THERE BE A RELATIONSHIP BETWEEN 1682 01:30:31,943 --> 01:30:35,346 SAY HOW FAST AND HOW LONG PEOPLE 1683 01:30:35,346 --> 01:30:36,548 CAN RUN. 1684 01:30:36,548 --> 01:30:38,817 ARE THERE PEOPLE WHO ARE RUNNERS 1685 01:30:38,817 --> 01:30:43,555 A MILE, HALF MILE, QUARTER MILE, 1686 01:30:43,555 --> 01:30:44,889 WHATEVER, CROSS COUNTRY. 1687 01:30:44,889 --> 01:30:47,692 AND THE OTHER THING THAT STRUCK 1688 01:30:47,692 --> 01:30:58,203 ME IS WHETHER OR NOT SMOKING 1689 01:30:59,871 --> 01:31:02,107 WHETHER THE SMOKING AND ALCOHOL 1690 01:31:02,107 --> 01:31:04,642 FIBROSIS WHEN YOU PUT THE TWO 1691 01:31:04,642 --> 01:31:07,812 TOGETHER WHETHER THE IMPACT IS 1692 01:31:07,812 --> 01:31:13,384 ADDITIVE OR LESS THAN ADDITIVE? 1693 01:31:13,384 --> 01:31:15,620 >> I'LL START WITH THE SECOND 1694 01:31:15,620 --> 01:31:16,488 QUESTION. 1695 01:31:16,488 --> 01:31:18,690 EXCELLENT QUESTION. 1696 01:31:18,690 --> 01:31:25,697 WE'LL START BUT THE DATA THE 1697 01:31:25,697 --> 01:31:27,799 SMOKING MAY HAVE A CONTRIBUTORY 1698 01:31:27,799 --> 01:31:30,201 ROLE AND MAY TAKE THE 1699 01:31:30,201 --> 01:31:32,770 EXPERIMENTAL MODEL AND LOOK AT 1700 01:31:32,770 --> 01:31:42,113 THE DATA TO UNDERSTAND I 1701 01:31:42,113 --> 01:31:43,648 MENTIONED THE LUNG DECLINE. 1702 01:31:43,648 --> 01:31:47,051 THE LUNG CAPACITY IS CRITICAL 1703 01:31:47,051 --> 01:31:54,192 FOR THIS -- IT'S ONE CAPACITY. 1704 01:31:54,192 --> 01:31:57,428 ONE THING IS BASED ON THE 1705 01:31:57,428 --> 01:31:59,731 CURRENT EVIDENCE, IF IT HAS A 1706 01:31:59,731 --> 01:32:01,499 VITAL INFECTION OR SOMETHING 1707 01:32:01,499 --> 01:32:05,670 GOING ON AS THE SECONDARY 1708 01:32:05,670 --> 01:32:07,772 INJURY, I THINK ALCOHOL 1709 01:32:07,772 --> 01:32:10,542 CONSUMPTION BECAUSE IT CAUSE 1710 01:32:10,542 --> 01:32:11,843 DELAY OR PERTURBATION THEY'LL 1711 01:32:11,843 --> 01:32:13,678 NOT BE READY FOR THE EVENT 1712 01:32:13,678 --> 01:32:16,948 BECAUSE THE RECOVERY TIME CAN BE 1713 01:32:16,948 --> 01:32:17,215 DELAYED. 1714 01:32:17,215 --> 01:32:20,618 I DON'T -- I CANNOT RECALL ANY 1715 01:32:20,618 --> 01:32:21,753 EPIDEMIOLOGICAL DATA BECAUSE 1716 01:32:21,753 --> 01:32:24,322 THESE ARE YOUNG PEOPLE BUT I GOT 1717 01:32:24,322 --> 01:32:25,456 INTERESTED AND WAS LOOKING AT 1718 01:32:25,456 --> 01:32:28,993 THE DATA PARTICULARLY FOR THE 1719 01:32:28,993 --> 01:32:32,297 BRANCHING AMINO ACID PART 1720 01:32:32,297 --> 01:32:34,365 BECAUSE MANY BODY BUILD ARE 1721 01:32:34,365 --> 01:32:35,934 USING THE BRANCH CHAIN AMINO 1722 01:32:35,934 --> 01:32:38,203 ACIDS AS A SUPPLEMENT. 1723 01:32:38,203 --> 01:32:39,170 AND MANY COLLEGE STUDENTS CAN 1724 01:32:39,170 --> 01:32:41,239 HAVE A BINGE DRINKING AND BEFORE 1725 01:32:41,239 --> 01:32:44,976 OR AFTER THEY CAN HAVE A 1726 01:32:44,976 --> 01:32:45,443 PHYSICAL ACTIVITY. 1727 01:32:45,443 --> 01:32:48,646 THEY CAN HAVE BRANCH AMINO ACID 1728 01:32:48,646 --> 01:32:52,250 SO WE WERE THINKING SINCE WE 1729 01:32:52,250 --> 01:32:54,485 FOUND THE UTILIZATION IS 1730 01:32:54,485 --> 01:32:55,620 IMPORTANT IN THE LUNG, WHETHER 1731 01:32:55,620 --> 01:33:02,193 IT MAY HAVE SOME ASSOCIATION OR 1732 01:33:02,193 --> 01:33:05,697 NOT AND IT COULD BE INTERESTING 1733 01:33:05,697 --> 01:33:08,967 TO INFORMING US AS AN EVIDENCE. 1734 01:33:08,967 --> 01:33:14,372 AT OUR DATA SHOWED IT'S CRITICAL 1735 01:33:14,372 --> 01:33:18,343 BUT WE CANNOT RESTORE ANYTHING 1736 01:33:18,343 --> 01:33:22,213 BUT THEY'RE ALL GREAT QUESTIONS 1737 01:33:22,213 --> 01:33:24,616 AND PEOPLE CAN INFORM US IN THE 1738 01:33:24,616 --> 01:33:26,684 PICTURE. 1739 01:33:26,684 --> 01:33:29,020 >> THERE'S A QUESTION FROM 1740 01:33:29,020 --> 01:33:29,921 FRANCES LEVIN FROM COLUMBIA. 1741 01:33:29,921 --> 01:33:40,331 >> THIS IS A GREAT TALK. 1742 01:33:42,267 --> 01:33:46,004 I THINK YOU SAID THE CB1 1743 01:33:46,004 --> 01:33:46,971 ANTAGONIST MAY HAVE SOME UTILITY 1744 01:33:46,971 --> 01:33:50,208 AND IF I GOT THAT WRONG YOU CAN 1745 01:33:50,208 --> 01:33:54,212 CORRECT ME BUT THE PROBLEM WITH 1746 01:33:54,212 --> 01:33:56,948 SUICIDAL IDEATION WITH THE 1747 01:33:56,948 --> 01:33:58,449 ANTAGONIST BUT WONDERING IF 1748 01:33:58,449 --> 01:34:00,685 THERE'S A FORM THAT DOESN'T 1749 01:34:00,685 --> 01:34:01,386 ACROSS THE BLOOD BRAIN BARRIER 1750 01:34:01,386 --> 01:34:05,123 AND I'VE LOOKED AT SIGNALLING 1751 01:34:05,123 --> 01:34:06,658 SPECIFIC NEGATIVE MODULATOR THE 1752 01:34:06,658 --> 01:34:09,761 CB1 RECEPTOR AND WHETHER THAT 1753 01:34:09,761 --> 01:34:10,194 MIGHT HAVE UTILITY. 1754 01:34:10,194 --> 01:34:12,096 YOU ARE ALWAYS THINKING ABOUT 1755 01:34:12,096 --> 01:34:14,198 OKAY WHAT DO YOU DO ABOUT THIS 1756 01:34:14,198 --> 01:34:17,869 PROBLEM. 1757 01:34:17,869 --> 01:34:20,138 CERTAINLY DRINKING LESS IS ONE 1758 01:34:20,138 --> 01:34:22,273 OPTION BUT HOW CAN YOU HELP THEM 1759 01:34:22,273 --> 01:34:23,141 BUT I THOUGHT THE TALK WAS 1760 01:34:23,141 --> 01:34:26,210 GREAT. 1761 01:34:26,210 --> 01:34:34,185 THANK YOU. 1762 01:34:34,185 --> 01:34:36,821 >> THE ANTAGONIST IS NOW IN THE 1763 01:34:36,821 --> 01:34:38,323 PHRASE II TRIALS BUT WE'LL SEE 1764 01:34:38,323 --> 01:34:48,733 THE SAFETY AND EFFICACY. 1765 01:34:53,037 --> 01:34:54,639 WE'RE TRYING TO LOOK AT THE 1766 01:34:54,639 --> 01:34:56,974 BIOLOGY IN THE EXACT CELL TYPES 1767 01:34:56,974 --> 01:35:02,213 BUT WE ALSO DEVELOP A STRATEGY 1768 01:35:02,213 --> 01:35:12,690 AND CAN INHALE TO THE LUNG 1769 01:35:18,262 --> 01:35:22,200 ALVEOLI AND RETAINED IN THE LUNG 1770 01:35:22,200 --> 01:35:25,803 AND HAVE A STRATEGY TO ENSURE 1771 01:35:25,803 --> 01:35:26,704 THE SYSTEMIC SAFETY. 1772 01:35:26,704 --> 01:35:29,207 THAT COULD BE AN APPROACH WE CAN 1773 01:35:29,207 --> 01:35:39,350 PURSUE. 1774 01:35:42,720 --> 01:35:45,022 >> YOU CAN FIND IT EASILY BY 1775 01:35:45,022 --> 01:35:54,499 SENDING AN E-MAIL. 1776 01:35:54,499 --> 01:35:58,669 >> THE FIRST IS THE GUT THEN 1777 01:35:58,669 --> 01:36:01,839 LIVER AND WHATEVER WE HAVE SEEN 1778 01:36:01,839 --> 01:36:03,708 IN THE STUDIES ARE SECONDARY 1779 01:36:03,708 --> 01:36:05,877 EFFECTS OF ALCOHOL AND CHRONIC 1780 01:36:05,877 --> 01:36:06,177 CONDITIONS. 1781 01:36:06,177 --> 01:36:09,147 SO IF YOU WANT TO TREAT ALCOHOL 1782 01:36:09,147 --> 01:36:13,918 USE DISORDERS SO WE WILL TREAT 1783 01:36:13,918 --> 01:36:17,155 FIRST OR GO FOR GUT-LIVER DAMAGE 1784 01:36:17,155 --> 01:36:21,626 TO SEE FIRST HERE AND THEN GO TO 1785 01:36:21,626 --> 01:36:28,933 LUNG, RIGHT? 1786 01:36:28,933 --> 01:36:30,802 AND I DON'T KNOW IF YOU LOOKED 1787 01:36:30,802 --> 01:36:32,570 AT THE EFFECT OF ALCOHOL ON 1788 01:36:32,570 --> 01:36:32,904 LUNG. 1789 01:36:32,904 --> 01:36:36,874 >> NICE BIG PICTURE QUESTION. 1790 01:36:36,874 --> 01:36:40,111 BASICALLY, ANY MEDICATION 1791 01:36:40,111 --> 01:36:42,914 REDUCING ALCOHOL INTAKE 1792 01:36:42,914 --> 01:36:45,049 ALLEVIATES THE SECONDARY 1793 01:36:45,049 --> 01:36:45,917 COMPLICATIONS. 1794 01:36:45,917 --> 01:36:48,986 ALSO SOME OF THE INDIVIDUALS 1795 01:36:48,986 --> 01:36:51,556 DEVELOPING THE LUNG DISEASE 1796 01:36:51,556 --> 01:36:53,157 DON'T HAVE ANOTHER COMPLICATIONS 1797 01:36:53,157 --> 01:37:03,568 AND TARGETED THERAPIES 1798 01:37:07,538 --> 01:37:10,141 >> DO YOU THINK ACUTE ALCOHOL 1799 01:37:10,141 --> 01:37:12,076 CONDITION AFFECTS LUNGS? 1800 01:37:12,076 --> 01:37:13,911 >> I TALKED ABOUT ACUTE EFFECT 1801 01:37:13,911 --> 01:37:15,646 BUT RIGHT NOW WE ARE TRYING TO 1802 01:37:15,646 --> 01:37:17,582 ESTABLISH THE MODEL AND THEN 1803 01:37:17,582 --> 01:37:19,684 BRIDGING THE TRANSLATION. 1804 01:37:19,684 --> 01:37:21,419 I THINK THAT WILL BE INTERESTING 1805 01:37:21,419 --> 01:37:24,021 TO FOLLOW ACUTE OR CHRONIC 1806 01:37:24,021 --> 01:37:25,022 INTERVENTION AND CHALLENGE WITH 1807 01:37:25,022 --> 01:37:25,656 THE SECONDARY INJURIES. 1808 01:37:25,656 --> 01:37:30,361 THANK YOU. 1809 01:37:30,361 --> 01:37:31,896 >> THAT WAS SUPER. 1810 01:37:31,896 --> 01:37:34,165 WE'LL MOVE ON TO OUR NEXT TALK 1811 01:37:34,165 --> 01:37:34,599 FROM DAYNE MAYFIELD. 1812 01:37:34,599 --> 01:37:44,809 ARE YOU ON? 1813 01:37:54,285 --> 01:37:56,087 DO YOU WANT TO LOAD YOUR SLIDES. 1814 01:37:56,087 --> 01:37:58,089 HE'S A PROFESSOR IN THE 1815 01:37:58,089 --> 01:37:59,290 DEPARTMENT OF NEUROSCIENCE AND 1816 01:37:59,290 --> 01:38:05,796 FOUNDING MEMBER OF THE WAGNER 1817 01:38:05,796 --> 01:38:08,299 CENTER FOR ALCOHOL AND ADDICTION 1818 01:38:08,299 --> 01:38:12,937 AND PART OF THE INITIATIVE ON 1819 01:38:12,937 --> 01:38:15,373 ALCOHOLISM NEURO IMMUNE A 1820 01:38:15,373 --> 01:38:16,173 MULTI-DISCIPLINARY EFFORT 1821 01:38:16,173 --> 01:38:18,476 STUDYING BRAIN MECHANISMS THAT 1822 01:38:18,476 --> 01:38:21,579 UNDER LIE ALCOHOL MISUSE AND 1823 01:38:21,579 --> 01:38:23,047 STRESS AND ANXIETY. 1824 01:38:23,047 --> 01:38:24,315 HE BRINGS DEEP KNOWLEDGE OF THE 1825 01:38:24,315 --> 01:38:26,217 MOLECULAR AND CELLULAR 1826 01:38:26,217 --> 01:38:31,022 MECHANISMS IN THE CENTRAL 1827 01:38:31,022 --> 01:38:34,225 NERVOUS SYSTEM AND MAY 1828 01:38:34,225 --> 01:38:36,594 CONTRIBUTE TO OTHER SUBSTANCES. 1829 01:38:36,594 --> 01:38:37,995 HIS WORK HAS LED TO NEW DRUG 1830 01:38:37,995 --> 01:38:39,830 TARGETS AND BIOMARKERS OF 1831 01:38:39,830 --> 01:38:41,799 ALCOHOL AND OTHER SUBSTANCE 1832 01:38:41,799 --> 01:38:42,033 MISUSE. 1833 01:38:42,033 --> 01:38:46,237 THIS IS A HUMBLE DESCRIPTION SO 1834 01:38:46,237 --> 01:38:50,207 I ACTUALLY WENT TO LOOK AT THE 1835 01:38:50,207 --> 01:38:55,179 MORE SEM NAL PAPERS AND 1836 01:38:55,179 --> 01:38:57,582 MOLECULAR PSYCHOLOGY AND ALCOHOL 1837 01:38:57,582 --> 01:39:00,618 USE IN THE HUMAN BRAIN. 1838 01:39:00,618 --> 01:39:03,054 IN THE JOURNAL OF NEUROSCIENCE 1839 01:39:03,054 --> 01:39:11,729 HE LOOKED AT EPIDEMIOLOGIC 1840 01:39:11,729 --> 01:39:14,999 MODIFICATIONS AND LOOKED AT 1841 01:39:14,999 --> 01:39:16,801 SINGLE CELL TRANSCRIPTOME 1842 01:39:16,801 --> 01:39:18,102 PROFILING OF THE HUMAN ALCOHOL 1843 01:39:18,102 --> 01:39:18,736 DEPENDENT BRAIN. 1844 01:39:18,736 --> 01:39:21,072 HE'S ALWAYS BEEN AT THE CUTTING 1845 01:39:21,072 --> 01:39:25,042 EDGE OF WHERE MOLECULAR BIOLOGY 1846 01:39:25,042 --> 01:39:26,844 MEETS ALCOHOL NEUROSCIENCE AND I 1847 01:39:26,844 --> 01:39:33,684 HOPE THE TOPIC IS GLIAL CELL 1848 01:39:33,684 --> 01:39:35,653 DIVERSITY IN ANIMAL MODELS AND 1849 01:39:35,653 --> 01:39:39,423 MOVED BEYOND NEURONS. 1850 01:39:39,423 --> 01:39:40,825 IT'S ALWAYS YOURS. 1851 01:39:40,825 --> 01:39:51,335 >> HOPEFULLY YOU CAN HEAR ME. 1852 01:39:53,704 --> 01:39:57,074 I'LL TALK ABOUT WORK WE'RE DOING 1853 01:39:57,074 --> 01:40:02,213 IN BRAIN SINCE WE HAVE A GLIAL 1854 01:40:02,213 --> 01:40:04,515 FOCUS AND IMMUNE SYSTEMS ARE THE 1855 01:40:04,515 --> 01:40:06,884 MAJOR TOPIC HERE, ONE OF THE 1856 01:40:06,884 --> 01:40:09,320 THINGS WE DON'T KNOW IS HOW DO 1857 01:40:09,320 --> 01:40:11,055 IMMUNE SIGNALS GET FROM THE 1858 01:40:11,055 --> 01:40:12,289 PERIPHERY TO THE BRAIN. 1859 01:40:12,289 --> 01:40:14,492 DO THEY ORIGINATE IN THE BRAIN? 1860 01:40:14,492 --> 01:40:15,760 THERE'S A LOT OF UNANSWERED 1861 01:40:15,760 --> 01:40:18,929 QUESTIONS AND THE DISCUSSION WE 1862 01:40:18,929 --> 01:40:29,473 PREVIOUSLY HAD REALLY POINT TO 1863 01:40:32,810 --> 01:40:41,952 THE QUESTIONS. 1864 01:40:41,952 --> 01:40:44,188 I WANT TO POINT OUT WHAT REALLY 1865 01:40:44,188 --> 01:40:45,890 DRIVES THE WORK THAT WE'RE ALL 1866 01:40:45,890 --> 01:40:47,625 TALKING ABOUT THAT WE'RE ALL 1867 01:40:47,625 --> 01:40:50,194 DOING AND THAT IS HERE IN THE 1868 01:40:50,194 --> 01:41:00,337 FUNDING. 1869 01:41:05,576 --> 01:41:06,177 AND NOTHING WOULD ROLL WITHOUT 1870 01:41:06,177 --> 01:41:07,445 THIS SO I WANT TO MAKE SURE TO 1871 01:41:07,445 --> 01:41:10,581 GET THE PLUG IN NOW. 1872 01:41:10,581 --> 01:41:17,221 AS GEORGE MENTION ED I WANT TO 1873 01:41:17,221 --> 01:41:18,255 TALK ABOUT THE LARGE COLLECTIVE 1874 01:41:18,255 --> 01:41:20,057 EFFORT AND THIS IS A GROUP OF 1875 01:41:20,057 --> 01:41:23,227 INVESTIGATORS ACROSS THE COUNTRY 1876 01:41:23,227 --> 01:41:33,738 WITH ALL KINDS OF EXPERTS AND 1877 01:41:35,639 --> 01:41:41,078 COLLABORATORS ARE PART OF THE 1878 01:41:41,078 --> 01:41:43,981 WORK I DO AT THE INDIANA SCHOOL 1879 01:41:43,981 --> 01:41:46,751 OF MEDICINE AND ALLISON GOAD AT 1880 01:41:46,751 --> 01:41:49,353 THE MOUNT SINAI SCHOOL OF 1881 01:41:49,353 --> 01:41:49,754 MEDICINE. 1882 01:41:49,754 --> 01:41:53,891 IN THE WAGNER CENTER WAS 1883 01:41:53,891 --> 01:41:54,558 DIRECTED WITH A RICH 1884 01:41:54,558 --> 01:41:56,527 ENENVIRONMENT THAT ALLOWS US TO 1885 01:41:56,527 --> 01:41:58,195 DO A LOT OF WORK THAT WOULD BE 1886 01:41:58,195 --> 01:42:05,970 HARD TO DO ELSEWHERE. 1887 01:42:05,970 --> 01:42:08,706 GRADUATE STUDENTS AND 1888 01:42:08,706 --> 01:42:10,107 TECHNICIANS HAVE ALL BEEN GREAT 1889 01:42:10,107 --> 01:42:11,609 AND THEY'RE TO THE ONES THAT DO 1890 01:42:11,609 --> 01:42:14,245 THE WORK AND I JUST GET TO TAKE 1891 01:42:14,245 --> 01:42:24,088 CREDIT FOR IT. 1892 01:42:24,088 --> 01:42:27,057 I APPRECIATE THE HARD WORK AND 1893 01:42:27,057 --> 01:42:30,828 THEY APPRECIATED PHARMACY AND 1894 01:42:30,828 --> 01:42:31,162 PHARMACOLOGY. 1895 01:42:31,162 --> 01:42:35,533 I WILL SAY THAT I WAS TRAINED IN 1896 01:42:35,533 --> 01:42:37,902 THE '80s AS A PHARMACOLOGIST. 1897 01:42:37,902 --> 01:42:39,937 MOST OF WHAT I WAS DOING BACK IN 1898 01:42:39,937 --> 01:42:42,206 THOSE DAYS WAS INVESTIGATING 1899 01:42:42,206 --> 01:42:44,809 SINGLE MOLECULES WHETHER IT'S AT 1900 01:42:44,809 --> 01:42:47,645 A GENE LEVEL OR PROTEIN LEVEL 1901 01:42:47,645 --> 01:42:49,780 AND HAMMERING TO UNDERSTAND HOW 1902 01:42:49,780 --> 01:42:50,381 ALCOHOL MIGHT IMPACT THOSE 1903 01:42:50,381 --> 01:42:59,990 PARTICULAR MOLECULES. 1904 01:42:59,990 --> 01:43:06,130 AFTER 10 OR 15 YEARS I GOT 1905 01:43:06,130 --> 01:43:09,200 INTERESTED IN MORE SYSTEMS LEVEL 1906 01:43:09,200 --> 01:43:13,237 APPROACHES AT THE TIME THE 1907 01:43:13,237 --> 01:43:15,172 GENOMICS FIELD WERE STARTING TO 1908 01:43:15,172 --> 01:43:16,473 EXPLODE AND STARTED TO 1909 01:43:16,473 --> 01:43:18,209 APPRECIATE COMPLEX DISEASE 1910 01:43:18,209 --> 01:43:21,212 STATES LIKE ALCOHOL USE DISORDER 1911 01:43:21,212 --> 01:43:23,247 AND IN A SLIGHTLY DIFFERENT WAY 1912 01:43:23,247 --> 01:43:24,982 AND IT'S SUMMARIZED IN THE SLIDE 1913 01:43:24,982 --> 01:43:27,818 WHETHER IT'S ALCOHOL USE 1914 01:43:27,818 --> 01:43:30,654 DISORDER OR OTHER PSYCHIATRIC 1915 01:43:30,654 --> 01:43:31,822 DISEASES. 1916 01:43:31,822 --> 01:43:34,024 WE ARE TRYING TO LEARN ABOUT 1917 01:43:34,024 --> 01:43:36,727 WHAT ARE THE MOLECULES AND 1918 01:43:36,727 --> 01:43:38,362 SYSTEMS THAT CONTRIBUTE TO A 1919 01:43:38,362 --> 01:43:40,531 HEALTHY STATE VERSUS A 1920 01:43:40,531 --> 01:43:42,666 PRE-DISEASE STATE AND FINALLY A 1921 01:43:42,666 --> 01:43:44,001 DISEASED STATE AND AN 1922 01:43:44,001 --> 01:43:46,637 UNDERSTANDING OF THESE PROCESSES 1923 01:43:46,637 --> 01:43:47,738 REALLY REQUIRES KNOWLEDGE OF A 1924 01:43:47,738 --> 01:43:51,108 LOT OF DIFFERENT DATA TYPES. 1925 01:43:51,108 --> 01:43:52,943 SO EACH OF THESE TWO DIMENSIONAL 1926 01:43:52,943 --> 01:43:56,247 LAYERS ARE COMPOSED OF DIFFERENT 1927 01:43:56,247 --> 01:43:59,216 TYPES OF DATA WHETHER IT'S 1928 01:43:59,216 --> 01:44:00,317 EPIDEMIOLOGIC DATA AND PROTEOME 1929 01:44:00,317 --> 01:44:01,852 AND SO ON AND THIS STARTS TO 1930 01:44:01,852 --> 01:44:06,156 BUILD A MORE COMPLETE PICTURE OF 1931 01:44:06,156 --> 01:44:11,262 A COMPLEX DISEASE STATE AND IT 1932 01:44:11,262 --> 01:44:12,630 IMPACTS MANY PROTEINS AND MANY 1933 01:44:12,630 --> 01:44:14,198 DIFFERENT GENES AND ALL AT THE 1934 01:44:14,198 --> 01:44:15,199 SAME TIME. 1935 01:44:15,199 --> 01:44:18,736 SO THIS IS ONE OF THE THINGS 1936 01:44:18,736 --> 01:44:27,211 THAT REALLY MOVED ME INTO A 1937 01:44:27,211 --> 01:44:28,979 SYSTEMS LEVEL STUDY APPROACH OF 1938 01:44:28,979 --> 01:44:29,213 ALCOHOL. 1939 01:44:29,213 --> 01:44:30,047 IF YOU LOOK AT ALCOHOL USE 1940 01:44:30,047 --> 01:44:32,616 DISORDER AND HERE I'M SHOWING 1941 01:44:32,616 --> 01:44:34,818 THE MODEL OF THE THREE STAGES OF 1942 01:44:34,818 --> 01:44:35,386 ADDICTION. 1943 01:44:35,386 --> 01:44:38,322 THIS IS SOMETHING THAT GUIDES A 1944 01:44:38,322 --> 01:44:43,394 LOT OF THE WORK IN THE HUMAN 1945 01:44:43,394 --> 01:44:44,895 BRAIN AND I THINK EVERYONE HAS 1946 01:44:44,895 --> 01:44:47,298 SHOWN THE PICTURE OR TALK AT 1947 01:44:47,298 --> 01:44:49,767 SOME POINT AND CAPTURES THE 1948 01:44:49,767 --> 01:44:51,235 DIFFERENT ASPECTS OF ALCOHOL USE 1949 01:44:51,235 --> 01:44:56,573 DISORDER WHETHER PREOCCUPATION, 1950 01:44:56,573 --> 01:44:57,875 INTOXICATION OR NEGATIVE AFFECT 1951 01:44:57,875 --> 01:44:59,243 AND THE BRAIN REGIONS INVOLVED. 1952 01:44:59,243 --> 01:45:00,411 THEY'RE VERY DIFFERENT 1953 01:45:00,411 --> 01:45:01,011 CONSTRUCTED AND HAVE TO BE 1954 01:45:01,011 --> 01:45:09,687 THOUGHT OF IN DIFFERENT WAYS. 1955 01:45:09,687 --> 01:45:11,889 AND THEY CONTRIBUTE TO THE 1956 01:45:11,889 --> 01:45:14,325 ADDICTION CYCLE AND I'VE 1957 01:45:14,325 --> 01:45:17,394 UTILIZED POSTMORTEM BRAIN FROM 1958 01:45:17,394 --> 01:45:19,029 DONORS COMPARED TO THE 1959 01:45:19,029 --> 01:45:19,697 NEUROTYPICAL CONTROLS FOR MANY 1960 01:45:19,697 --> 01:45:22,266 YEARS TO GET AN IDEA OF THE 1961 01:45:22,266 --> 01:45:24,835 HUMAN SIDE OF THIS EQUATION BUT 1962 01:45:24,835 --> 01:45:27,738 WE ALSO USE ANIMAL MODELS. 1963 01:45:27,738 --> 01:45:29,840 WE USE GENETIC MODELS AND ANIMAL 1964 01:45:29,840 --> 01:45:33,444 MODELS OF VOLUNTARY CONSUMPTION 1965 01:45:33,444 --> 01:45:36,313 AND WE IN MY LAB WE TRY TO FOCUS 1966 01:45:36,313 --> 01:45:39,016 ON THESE TRANSLATION EVENTS AND 1967 01:45:39,016 --> 01:45:42,820 WHAT I'VE LEARNED IN HUMAN BRAIN 1968 01:45:42,820 --> 01:45:44,922 I WANT TO MAKE SURE THE ANIMAL 1969 01:45:44,922 --> 01:45:48,359 MODELS ARE ACTUALLY VALID MODELS 1970 01:45:48,359 --> 01:45:50,194 TO STUDY THESE PLAYERS AND VICE 1971 01:45:50,194 --> 01:45:52,329 VERSA, THE ANIMAL MODELS ARE 1972 01:45:52,329 --> 01:45:54,365 INFORMING AND PROVIDING 1973 01:45:54,365 --> 01:46:00,037 TRANSLATIONAL VALUE TO THE HUMAN 1974 01:46:00,037 --> 01:46:02,206 AUD CONDITION. 1975 01:46:02,206 --> 01:46:08,812 SO THE ANIMAL MODELS AND HUMAN 1976 01:46:08,812 --> 01:46:11,181 BRAIN ARE THE STARS OF THE SHOW. 1977 01:46:11,181 --> 01:46:12,750 AND MANY YEARS I'LL CALL THE 1978 01:46:12,750 --> 01:46:14,518 TURN OF THE CENTURY BECAUSE IT 1979 01:46:14,518 --> 01:46:16,286 MAKES IT SEEM LIKE A LONG TIME 1980 01:46:16,286 --> 01:46:17,855 AGO BUT WAS ONLY 25 YEARS AGO. 1981 01:46:17,855 --> 01:46:19,123 WHEN WE STARTED DOING 1982 01:46:19,123 --> 01:46:22,192 TRANSCRIPTOME WORK IN HUMAN 1983 01:46:22,192 --> 01:46:29,533 BRAIN WE SAW SOMETHING WE DIDN'T 1984 01:46:29,533 --> 01:46:32,836 EXPECT AND KNEW WE'D FINE NEURON 1985 01:46:32,836 --> 01:46:36,073 COUPLE RECEPTOR CHANGES BUT WHAT 1986 01:46:36,073 --> 01:46:41,145 WE SAW WITH ARE GENES AND MANY 1987 01:46:41,145 --> 01:46:43,947 GENES THAT ARE KNOWN TO BE 1988 01:46:43,947 --> 01:46:47,217 INVOLVED IN THE IMMUNITY DEFENSE 1989 01:46:47,217 --> 01:46:49,453 AND OTHER IMMUNE SYSTEMS AND WE 1990 01:46:49,453 --> 01:46:51,288 DIDN'T REALLY FOCUS ON THIS A 1991 01:46:51,288 --> 01:46:54,558 LONG TIME WE DON'T KNOW IF IT 1992 01:46:54,558 --> 01:46:55,826 WAS FACTUAL OR REAL BECAUSE THE 1993 01:46:55,826 --> 01:46:57,928 BRAIN IS A CLEAN ORGAN AND 1994 01:46:57,928 --> 01:47:02,199 DIDN'T KNOW WHY THE SIGNALS WERE 1995 01:47:02,199 --> 01:47:05,202 PRESENT IN DATA. 1996 01:47:05,202 --> 01:47:06,603 AFTER A NUMBER OF OTHER STUDIES 1997 01:47:06,603 --> 01:47:12,109 AND A FEW ARE HIGHLIGHTED ON THE 1998 01:47:12,109 --> 01:47:14,111 PAGE MOST ARE NEXT GENERATION 1999 01:47:14,111 --> 01:47:17,581 SEQUENCING FROM BULK BRAIN, BUT 2000 01:47:17,581 --> 01:47:20,651 ALL OF THEM CONTAIN IMMUNE 2001 01:47:20,651 --> 01:47:20,951 RESPONSES. 2002 01:47:20,951 --> 01:47:23,253 I WANT TO SHOW A LARGER STUDY. 2003 01:47:23,253 --> 01:47:26,890 THIS IS PART OF THE NEUROIMMUNE 2004 01:47:26,890 --> 01:47:27,558 AND COLLABORATIVE EFFORTS THAT 2005 01:47:27,558 --> 01:47:29,093 WE'VE DONE. 2006 01:47:29,093 --> 01:47:33,097 THIS IS A FEW YEARS AGO AT THE 2007 01:47:33,097 --> 01:47:35,165 TIME WE INTEGRATED MULTI-OMIC 2008 01:47:35,165 --> 01:47:38,102 DATA FROM A LARGE COHORT OF 2009 01:47:38,102 --> 01:47:41,105 POSTMORTEM BRAIN. 2010 01:47:41,105 --> 01:47:45,476 WE UTILIZED TRANSCRIPTOME 2011 01:47:45,476 --> 01:47:47,711 INFORMATION AND INTEGRATED GWAS 2012 01:47:47,711 --> 01:47:51,482 FROM ALCOHOL DEPENDENCE FROM THE 2013 01:47:51,482 --> 01:47:53,750 PGC AS WELL AS U.K. BIO BANK AND 2014 01:47:53,750 --> 01:47:56,053 ALCOHOL CONSUMPTION DATA AS WELL 2015 01:47:56,053 --> 01:48:00,224 AS THE DATA FROM 461 POSTMORTEM 2016 01:48:00,224 --> 01:48:01,525 BRAIN PART OF THE PROJECT. 2017 01:48:01,525 --> 01:48:09,500 IT'S A LARGE INTEGRATIVE EFFORT 2018 01:48:09,500 --> 01:48:14,204 TO TO UNDERSTAND THE IMPORTANT 2019 01:48:14,204 --> 01:48:22,212 PLAYERS IN HUMAN BRAIN. 2020 01:48:22,212 --> 01:48:25,649 THE IMMUNE RESPONSE WAS THERE 2021 01:48:25,649 --> 01:48:30,187 AND A STRONG SIGNAL THE MORE 2022 01:48:30,187 --> 01:48:35,826 PRONOUNCED THE SIGNALS WERE, G 2023 01:48:35,826 --> 01:48:37,928 WAS ENRICHMENT AND MODULES 2024 01:48:37,928 --> 01:48:39,196 RELATED TO IMMUNE RESPONSE. 2025 01:48:39,196 --> 01:48:42,199 IT'S PRETTY CONVINCING THE 2026 01:48:42,199 --> 01:48:43,967 IMMUNE SIGNALS ARE REAL. 2027 01:48:43,967 --> 01:48:47,204 THEY'RE ALL ASSOCIATED WITH 2028 01:48:47,204 --> 01:48:53,477 ALCOHOL USE AND SO THESE ARE 2029 01:48:53,477 --> 01:48:54,211 CORRELATED WITH LIFE TIME 2030 01:48:54,211 --> 01:48:59,550 ALCOHOL CONSUMPTION. 2031 01:48:59,550 --> 01:49:02,019 WE AND OTHERS STARTED TO FOCUS 2032 01:49:02,019 --> 01:49:04,821 IN ON NEURO IMMUNE SIGNALLING AS 2033 01:49:04,821 --> 01:49:06,657 BEING INVOLVED IN EXCESSIVE 2034 01:49:06,657 --> 01:49:10,194 ALCOHOL CONSUMPTION AND WE AND 2035 01:49:10,194 --> 01:49:13,330 OTHERS DEVELOPED THIS 2036 01:49:13,330 --> 01:49:15,032 NEUROIMMUNE HYPOTHESIS THAT 2037 01:49:15,032 --> 01:49:16,934 BASICALLY STATES OVER ACTIVATION 2038 01:49:16,934 --> 01:49:19,136 OF THE IMMUNE SIGNALLING WITH 2039 01:49:19,136 --> 01:49:21,538 ALCOHOL CONSUMPTION WE KNOW TOLL 2040 01:49:21,538 --> 01:49:23,340 WIDE RECEPTORS AND OTHER 2041 01:49:23,340 --> 01:49:26,210 RECEPTORS AND PATHWAYS ARE 2042 01:49:26,210 --> 01:49:31,114 INVOLVED AND INITIATING P 2043 01:49:31,114 --> 01:49:32,482 PROINFLAMMATORY RESPONSES AND 2044 01:49:32,482 --> 01:49:34,318 ALTERED IN RESPONSE TO CHRONIC 2045 01:49:34,318 --> 01:49:34,785 ALCOHOL. 2046 01:49:34,785 --> 01:49:39,323 SO THE PLOT ON THE RIDE 2047 01:49:39,323 --> 01:49:42,192 SUMMARIZES A LOT OF THIS 2048 01:49:42,192 --> 01:49:43,493 INFORMATION AND IT'S SHOWING 2049 01:49:43,493 --> 01:49:45,562 THAT WHETHER IT'S LIFE TIME 2050 01:49:45,562 --> 01:49:47,764 ALCOHOL CONSUMPTION ACROSS THE X 2051 01:49:47,764 --> 01:49:50,200 AXIS AND LIFE TIME CONSUMPTION 2052 01:49:50,200 --> 01:49:54,204 IN HUMANS OR REPEATED BINGE 2053 01:49:54,204 --> 01:49:59,309 DRINKING IN AN ANIMAL MODEL OR 2054 01:49:59,309 --> 01:50:02,212 INTERMITTENT VAPOR 2055 01:50:02,212 --> 01:50:03,580 ADMINISTRATION LEAD TO THE 2056 01:50:03,580 --> 01:50:05,682 INCREASE IN NEUROIMMUNE 2057 01:50:05,682 --> 01:50:06,783 EXPRESSION OVER TIME RESULTING 2058 01:50:06,783 --> 01:50:08,919 IN INCREASED LIFE TIME 2059 01:50:08,919 --> 01:50:11,855 CONSUMPTION OF ALCOHOL OR 2060 01:50:11,855 --> 01:50:15,058 INCREASED ALCOHOL CONSUMPTION IN 2061 01:50:15,058 --> 01:50:15,559 ANIMAL MODELS. 2062 01:50:15,559 --> 01:50:16,660 IT'S BEEN THE DRIVER FOR A 2063 01:50:16,660 --> 01:50:18,195 NUMBER OF YEARS FOR A LOT OF THE 2064 01:50:18,195 --> 01:50:19,796 WORK WE'VE DONE. 2065 01:50:19,796 --> 01:50:23,500 SO, FOR TODAY'S TALK, I CAN'T 2066 01:50:23,500 --> 01:50:29,539 TALK ABOUT ALL THE GLIAL CELLS 2067 01:50:29,539 --> 01:50:32,709 BUT GIVEN WHAT WE'VE SEEN WE 2068 01:50:32,709 --> 01:50:35,178 KNOW THE IMMUNE SIGNALLING IN 2069 01:50:35,178 --> 01:50:38,615 BRAIN HAS MORE THAN JUST NEURONS 2070 01:50:38,615 --> 01:50:43,253 INVOLVED SO I'LL TALK 2071 01:50:43,253 --> 01:50:44,388 SPECIFICALLY ABOUT MICROGLIA 2072 01:50:44,388 --> 01:50:47,758 TODAY FOR THE TALK AND A LOT OF 2073 01:50:47,758 --> 01:50:50,193 IS KNOWN IN THE ALCOHOL FIELD 2074 01:50:50,193 --> 01:50:54,064 ABOUT THE ROLE OF GLIAL CELLS, 2075 01:50:54,064 --> 01:50:58,201 MICROGLIAL CELLS IN AUD, CHRONIC 2076 01:50:58,201 --> 01:50:59,970 ALCOHOL LEADS TO 2077 01:50:59,970 --> 01:51:02,205 PRO-INFLAMMATORY STATES FOR THE 2078 01:51:02,205 --> 01:51:03,373 CELLS AND ALSO CAUSES NEURONAL 2079 01:51:03,373 --> 01:51:07,477 DAMAGE DEGRADATION. 2080 01:51:07,477 --> 01:51:14,184 ALSO IMMUNE SIGNALLING RELEASES 2081 01:51:14,184 --> 01:51:15,218 CHEMOKINE ACTIVATE OTHER IMMUNE 2082 01:51:15,218 --> 01:51:19,222 SYSTEMS IN THE BRAIN THAT ALTER 2083 01:51:19,222 --> 01:51:19,656 ALCOHOL CONSUMPTION. 2084 01:51:19,656 --> 01:51:26,196 SO WE DO KNOW A LOT ABOUT 2085 01:51:26,196 --> 01:51:28,098 MICROGLIA AT A SPECIFIC CELL 2086 01:51:28,098 --> 01:51:28,298 LEVEL. 2087 01:51:28,298 --> 01:51:30,901 WE DON'T KNOW HOW THIS MIGHT BE 2088 01:51:30,901 --> 01:51:31,868 IMPACTING IMMUNE SIGNALLING AND 2089 01:51:31,868 --> 01:51:35,072 WE DON'T KNOW EXACTLY WHERE 2090 01:51:35,072 --> 01:51:36,840 MICROGLIA SIGNALLING COMES FROM. 2091 01:51:36,840 --> 01:51:42,179 DOES IT ORIGINATE FROM BRAIN OR 2092 01:51:42,179 --> 01:51:52,389 NOT. 2093 01:51:52,389 --> 01:51:54,191 AND A LOT OF THE WORK WE'VE DONE 2094 01:51:54,191 --> 01:51:58,862 FOR YEARS HAS TAKEN THIS SORT OF 2095 01:51:58,862 --> 01:52:01,665 DICHOTOMY APPROACH WHERE 2096 01:52:01,665 --> 01:52:05,736 MICROGLIA ARE GOOD OR BAD AND 2097 01:52:05,736 --> 01:52:08,905 RESTING VERSUS ACTIVATED AND 2098 01:52:08,905 --> 01:52:09,606 THAT'S GREAT. 2099 01:52:09,606 --> 01:52:11,508 WE'RE USUALLY MORPHOLOGICAL 2100 01:52:11,508 --> 01:52:12,442 CHARACTERISTICS AND IT'S A GOOD 2101 01:52:12,442 --> 01:52:18,415 WAY TO CLASSIFY CELLS. 2102 01:52:18,415 --> 01:52:20,684 IT'S EASY TO QUANTITATE AND 2103 01:52:20,684 --> 01:52:21,985 OBSERVE AND THAT'S FINE BUT WITH 2104 01:52:21,985 --> 01:52:26,189 THE SYSTEM LEVELS APPROACHES THE 2105 01:52:26,189 --> 01:52:27,691 GLIAL CELLS ARE EXISTING IN 2106 01:52:27,691 --> 01:52:30,193 MULTIPLE STATES. 2107 01:52:30,193 --> 01:52:31,595 THEY TRANSITION BETWEEN THESE 2108 01:52:31,595 --> 01:52:35,132 STATES SO RATHER THAN A SIMPLE 2109 01:52:35,132 --> 01:52:38,201 DICHOTOMY, THE IMPACT THAT 2110 01:52:38,201 --> 01:52:41,371 ALCOHOL HAS ON GLIAL CELLS AND 2111 01:52:41,371 --> 01:52:44,040 MICROGLIA ESPECIALLY RESULTS IN 2112 01:52:44,040 --> 01:52:46,209 SHIFTS IN STATES THAT ULTIMATELY 2113 01:52:46,209 --> 01:52:50,213 REDUCES THE DIFFERENT FUNCTION 2114 01:52:50,213 --> 01:52:56,887 FOR THE CELL. 2115 01:52:56,887 --> 01:53:00,023 ONE OTHER PIECE OF INFORMATION 2116 01:53:00,023 --> 01:53:09,633 AND WE DIDN'T KNOW WHAT 2117 01:53:09,633 --> 01:53:12,369 MICROGLIA DID IN THE CONTEXT OF 2118 01:53:12,369 --> 01:53:14,204 ANIMAL MODELS AND THE CIV 2119 01:53:14,204 --> 01:53:17,307 DEPENDENCE MODEL WHERE REPEATED 2120 01:53:17,307 --> 01:53:19,709 BOUTS OF ALCOHOL VAPOR REDUCE 2121 01:53:19,709 --> 01:53:21,244 THE ESCALATION AND VOLUNTARY IN 2122 01:53:21,244 --> 01:53:22,946 TAKE OF ALCOHOL. 2123 01:53:22,946 --> 01:53:25,015 WE WERE CURIOUS DOES 2124 01:53:25,015 --> 01:53:26,583 MANIPULATION OF MICROGLIA ALTER 2125 01:53:26,583 --> 01:53:29,152 THE IMPORTANT PHENOTYPE AND THE 2126 01:53:29,152 --> 01:53:31,388 PHENOTYPE'S IMPORTANT BECAUSE 2127 01:53:31,388 --> 01:53:32,622 THE COMMON FEATURE IS THE 2128 01:53:32,622 --> 01:53:34,424 DEPENDENCE COMPONENT AND I 2129 01:53:34,424 --> 01:53:37,727 WANTED TO RELATE THAT TO THE 2130 01:53:37,727 --> 01:53:42,866 HUMAN AUD DONORS. 2131 01:53:42,866 --> 01:53:47,304 THE SIMPLE EXPERIMENT WASN'T 2132 01:53:47,304 --> 01:53:49,172 SIMPLE BUT LONG AND HARD AND 2133 01:53:49,172 --> 01:53:51,641 USED THE COLONY STIMULATING ONE 2134 01:53:51,641 --> 01:53:54,744 RECEPTOR INHIBITOR TO BASICALLY 2135 01:53:54,744 --> 01:53:57,047 ELIMINATE MICROGLIA AND LOOK AT 2136 01:53:57,047 --> 01:54:01,551 THE IMPACT IT HAD ON MICROGLIA 2137 01:54:01,551 --> 01:54:03,620 PERFORATION AND 2138 01:54:03,620 --> 01:54:04,254 ELECTROPHYSIOLOGICAL RESPONSES 2139 01:54:04,254 --> 01:54:07,991 AND ALCOHOL RELATED PHENOTYPES. 2140 01:54:07,991 --> 01:54:09,292 AND SO THE IMPORTANT THING I 2141 01:54:09,292 --> 01:54:11,061 WANT TO THROW YOUR ATTENTION TO 2142 01:54:11,061 --> 01:54:13,563 HERE WILL BE THE PHENOTYPES THAT 2143 01:54:13,563 --> 01:54:16,800 WE SAW IN THESE ANIMALS 2144 01:54:16,800 --> 01:54:18,235 NON-DEPENDENT ANIMALS THAT DID 2145 01:54:18,235 --> 01:54:20,504 NOT GO THROUGH CHRONIC 2146 01:54:20,504 --> 01:54:21,638 INTERMITTENT ALCOHOL. 2147 01:54:21,638 --> 01:54:26,209 THEY DID THEIR USUAL DRINKING 2148 01:54:26,209 --> 01:54:33,483 AND THEY WOULD DRINK THE SAME 2149 01:54:33,483 --> 01:54:35,619 AMOUNT OF ALCOHOL AND ALMOST 2150 01:54:35,619 --> 01:54:38,855 COMPLETE DEPLETION OF MICROGLIA 2151 01:54:38,855 --> 01:54:41,291 DID NOTHING TO NON-DEPENDENT 2152 01:54:41,291 --> 01:54:45,028 DRINKING ANIMALS BUT IN THE 2153 01:54:45,028 --> 01:54:55,105 DEPENDENT COHORT ELIMINATION 2154 01:54:55,105 --> 01:54:57,641 RESULTED IN THIS CLASSIC 2155 01:54:57,641 --> 01:55:01,044 INCREASE THAT WAS BLOCKED BY 2156 01:55:01,044 --> 01:55:03,380 ELIMINATION OF MICROGLIA. 2157 01:55:03,380 --> 01:55:04,147 WE KNOW THERE'S SOMETHING 2158 01:55:04,147 --> 01:55:05,081 SPECIAL ABOUT THIS PARTICULAR 2159 01:55:05,081 --> 01:55:07,651 CELL TYPE. 2160 01:55:07,651 --> 01:55:09,653 SO WE'VE FOCUSSED A LOT ON 2161 01:55:09,653 --> 01:55:20,196 MICROGLIA IN THE LAST FEW YEARS. 2162 01:55:23,033 --> 01:55:26,069 FOR A MIXTURE OF ALL BRAIN CELL 2163 01:55:26,069 --> 01:55:26,570 TYPES. 2164 01:55:26,570 --> 01:55:27,837 BRAIN WAS COMPOSED OF DIFFERENT 2165 01:55:27,837 --> 01:55:31,041 CELLS AND STATES OF CELLS AND SO 2166 01:55:31,041 --> 01:55:33,276 FOR THE LAST SEVERAL YEARS WE'VE 2167 01:55:33,276 --> 01:55:35,779 BEEN UTILIZING SINGLE CELLS AND 2168 01:55:35,779 --> 01:55:38,181 NUCLEUS APPROACHES AS WELL AS 2169 01:55:38,181 --> 01:55:41,685 SPATIAL APPROACHES TO START TO 2170 01:55:41,685 --> 01:55:44,487 TEASE A PART THE IMPACT OF 2171 01:55:44,487 --> 01:55:45,288 CELLS. 2172 01:55:45,288 --> 01:55:46,656 WE SEE THE MULTIPLE SUB CLASSES 2173 01:55:46,656 --> 01:55:57,367 OF CELLS CAN BE OBSERVE D IT THS 2174 01:56:00,870 --> 01:56:02,672 IS A VERY POWERFUL APPROACH WE 2175 01:56:02,672 --> 01:56:05,408 CAN USE IN OUR ALCOHOL STUDIES. 2176 01:56:05,408 --> 01:56:06,743 ULTIMATELY WE WANT TO DISCOVER 2177 01:56:06,743 --> 01:56:10,180 CELL TYPES OR STATES IMPORTANT 2178 01:56:10,180 --> 01:56:11,548 AND HOW THE CELLS CHANGE OVER 2179 01:56:11,548 --> 01:56:15,952 TIME BUT REALLY WE WANT TO KNOW 2180 01:56:15,952 --> 01:56:19,022 WHAT ARE THE OVER ALL 2181 01:56:19,022 --> 01:56:20,624 CROSS-SPECIES OVERLAPS BETWEEN 2182 01:56:20,624 --> 01:56:24,728 THE TRANSCRIPTOMES. 2183 01:56:24,728 --> 01:56:27,263 SO GEORGE MENTIONED THIS EARLY 2184 01:56:27,263 --> 01:56:31,267 STUDY WE DID WITH HUMAN 2185 01:56:31,267 --> 01:56:36,172 POSTMORTEM BRAIN USING 2186 01:56:36,172 --> 01:56:36,706 TRANSCRIPTOME PROFILING. 2187 01:56:36,706 --> 01:56:40,610 IT WAS A SMALL COHORT AND PROOF 2188 01:56:40,610 --> 01:56:50,820 OF CONCEPT. 2189 01:56:54,691 --> 01:56:56,860 WE CAN LOOK AT A CLUSTER OF 2190 01:56:56,860 --> 01:56:59,796 CELLS THAT REPRESENT THE CELL 2191 01:56:59,796 --> 01:57:08,538 TYPES IN BRAIN THIS IS SHOWN IN 2192 01:57:08,538 --> 01:57:10,507 EXAMPLES OF INDIVIDUAL GENES 2193 01:57:10,507 --> 01:57:14,044 SHOWN AS THE VIOLIN PLOTS AS A 2194 01:57:14,044 --> 01:57:14,878 FUNCTION OF DIFFERENT CELL TYPES 2195 01:57:14,878 --> 01:57:15,578 IN BRAIN. 2196 01:57:15,578 --> 01:57:20,050 BOTH OF THESE ARE KNOWN TO BE 2197 01:57:20,050 --> 01:57:30,593 ALCOHOL RESPONSIVE AND SHOWING 2198 01:57:33,863 --> 01:57:37,500 THE DATA FROM THE AUD AND GREEN 2199 01:57:37,500 --> 01:57:39,703 IS FROM CONTROLS. 2200 01:57:39,703 --> 01:57:50,246 YOU SEE THE EXPRESSION LEVEL AND 2201 01:57:51,781 --> 01:57:53,950 CASE CONTROL AND A SPECIAL 2202 01:57:53,950 --> 01:57:56,720 PATTERN WHERE MICROGLIA EXPRESS 2203 01:57:56,720 --> 01:57:57,721 RATHER THAN THE OTHERS. 2204 01:57:57,721 --> 01:58:07,997 IN ADDITION TO THE SPECIFIC CELL 2205 01:58:07,997 --> 01:58:09,199 TYPE IDENTIFIERS IT WAS CLEAR 2206 01:58:09,199 --> 01:58:11,167 WHAT WE WERE MISSING IN OUR 2207 01:58:11,167 --> 01:58:14,237 SEQUENCING WAS THE MICROGLIA 2208 01:58:14,237 --> 01:58:22,846 SIGNAL AND WE WERE MISSING A LOT 2209 01:58:22,846 --> 01:58:26,616 OF INFORMATION ABOUT MICROGLIA. 2210 01:58:26,616 --> 01:58:31,888 MOVING TO JUSTIFYING THE COST OF 2211 01:58:31,888 --> 01:58:33,723 THE LARGER EXPERIMENT. 2212 01:58:33,723 --> 01:58:36,760 WE DID PROFILE AN ADDITIONAL 2213 01:58:36,760 --> 01:58:37,660 COHORT OF INDIVIDUALS. 2214 01:58:37,660 --> 01:58:41,264 THIS IS A LARGE COHORT. 2215 01:58:41,264 --> 01:58:43,466 THIS WAS 73 INDIVIDUAL DONORS. 2216 01:58:43,466 --> 01:58:52,075 ALL THIS WORK IS DONE ENDORSAL 2217 01:58:52,075 --> 01:58:55,378 ENDORSAL -- IN DORSAL LATERAL 2218 01:58:55,378 --> 01:58:58,948 BRAIN AND THIS IS REPRESENTED 2219 01:58:58,948 --> 01:59:02,185 ACROSS THE 73 SAMPLES ARE 2220 01:59:02,185 --> 01:59:05,722 PRESENTATIONS OF DSM5 SEVERITY. 2221 01:59:05,722 --> 01:59:08,858 THERE'S A RICH SET OF CLINICAL 2222 01:59:08,858 --> 01:59:09,492 INFORMATION AVAILABLE FOR ALL 2223 01:59:09,492 --> 01:59:11,795 AND I'M LISTING A FEW YEAR. 2224 01:59:11,795 --> 01:59:13,730 WE DO HAVE VERY STRICT INCLUSION 2225 01:59:13,730 --> 01:59:17,433 CRITERIA FOR OUR CASES SO 2226 01:59:17,433 --> 01:59:28,144 THERE'S NO COMORBIDITYIES AND TE 2227 01:59:32,615 --> 01:59:36,786 ALCOHOL DRINK EERS HAVE FEW 2228 01:59:36,786 --> 01:59:38,087 COMORBIDITIES FOR THIS COHORT. 2229 01:59:38,087 --> 01:59:42,692 WITH 73 INDIVIDUAL CASES, THIS 2230 01:59:42,692 --> 01:59:51,701 RESULTS IN SOME 650,000 TO 2231 01:59:51,701 --> 01:59:54,137 700,000 TRANSCRIPTOME. 2232 01:59:54,137 --> 01:59:54,904 THIS RESULTS IN A LOT OF DATA. 2233 01:59:54,904 --> 02:00:03,913 I'M NOT GOING TO TALK ABOUT THE 2234 02:00:03,913 --> 02:00:08,117 DATA PROCESSING BUT THE STUDY IS 2235 02:00:08,117 --> 02:00:12,021 DOING JUST THAT. 2236 02:00:12,021 --> 02:00:15,058 IDENTIFYING THE DATA AND MAKING 2237 02:00:15,058 --> 02:00:22,932 SURE THERE'S NO DOWN STREAM AND 2238 02:00:22,932 --> 02:00:24,634 THE DOWN STREAM ANALYSIS IS WHAT 2239 02:00:24,634 --> 02:00:26,469 I'LL TALK ABOUT AND THE 2240 02:00:26,469 --> 02:00:29,038 EXPRESSION GENE NETWORK THE WAY 2241 02:00:29,038 --> 02:00:29,739 IT EXPRESSES IN ANALYSIS AND SO 2242 02:00:29,739 --> 02:00:39,816 ON. 2243 02:00:42,252 --> 02:00:45,488 WITH WE IDENTIFIED 32 DISTINCT 2244 02:00:45,488 --> 02:00:49,959 CELL TYPE CLUSTERS SHOWN IN THE 2245 02:00:49,959 --> 02:00:50,159 SPACE. 2246 02:00:50,159 --> 02:00:51,761 WHICH THIS IS A SIMPLE WAY TO 2247 02:00:51,761 --> 02:00:52,762 DISPLAY A LOT OF DATA. 2248 02:00:52,762 --> 02:00:56,366 YOU CAN SEE IT IN TWO 2249 02:00:56,366 --> 02:01:00,670 DIMENSIONS. 2250 02:01:00,670 --> 02:01:02,572 THE SUB CLUSTERS OF CELLS ARE 2251 02:01:02,572 --> 02:01:03,339 SHOWN AND THIS IS MULTIPLE SUB 2252 02:01:03,339 --> 02:01:09,712 CLUSTERS. 2253 02:01:12,248 --> 02:01:14,083 ASTROCYTES AND IF YOU LOOK AT 2254 02:01:14,083 --> 02:01:15,752 THE PROPORTION OF CELL TYPES 2255 02:01:15,752 --> 02:01:16,819 THEY FOLLOW WHAT WE HAVE KNOWN 2256 02:01:16,819 --> 02:01:26,262 FOR BRAIN FOR A WHILE. 2257 02:01:26,262 --> 02:01:28,598 AND EXCITATORY NEURON HAVE THE 2258 02:01:28,598 --> 02:01:32,035 HIGHEST PROPORTION AND 2259 02:01:32,035 --> 02:01:33,336 DENDROCYTES AND ASTROCYTES. 2260 02:01:33,336 --> 02:01:41,711 ALL THE PROPORTIONS ARE THOUGHT 2261 02:01:41,711 --> 02:01:45,014 OF AND THE PROPORTIONS ARE NOT 2262 02:01:45,014 --> 02:01:46,816 ALTERED BY AUD STATE. 2263 02:01:46,816 --> 02:01:49,752 ONE OF THE THINGS WE'RE ALWAYS 2264 02:01:49,752 --> 02:01:53,790 CONCERNED ABOUT IS IF WE HAVE A 2265 02:01:53,790 --> 02:01:56,292 HIGHLY DECEASED BRAIN WE'LL LOSE 2266 02:01:56,292 --> 02:01:56,993 REPRESENTATION OF CELLS BECAUSE 2267 02:01:56,993 --> 02:01:59,329 THEY'LL HAVE DIED OFF AND THAT 2268 02:01:59,329 --> 02:02:02,432 WAS NOT EVIDENT IN THE DATA. 2269 02:02:02,432 --> 02:02:06,135 THAT'S ALSO SHOWN HERE IF YOU 2270 02:02:06,135 --> 02:02:10,773 TALK THE MAP AND SPLIT IT AUD 2271 02:02:10,773 --> 02:02:13,409 AND CONTROL DONORS THE CLUSTER 2272 02:02:13,409 --> 02:02:16,946 OF CELLS ARE REPRESENTED BY AUD 2273 02:02:16,946 --> 02:02:18,181 DONORS AND NEUROTYPICAL 2274 02:02:18,181 --> 02:02:28,358 CONTROLS. 2275 02:02:31,961 --> 02:02:33,796 WE HAVE A COHORT OF INDIVIDUALS 2276 02:02:33,796 --> 02:02:37,667 AND THE OTHER GLIAL CELLS WERE 2277 02:02:37,667 --> 02:02:38,201 HIGHLY DYSREGULATED. 2278 02:02:38,201 --> 02:02:39,702 THERE'S NOT TIME TO GO INTO ALL 2279 02:02:39,702 --> 02:02:41,838 THE FINDINGS. 2280 02:02:41,838 --> 02:02:44,073 THIS WORK SINCE WE DIDN'T GET TO 2281 02:02:44,073 --> 02:02:46,542 PRESENT THIS IN FEBRUARY, THE 2282 02:02:46,542 --> 02:02:48,277 MANUSCRIPT CAME OUT BETWEEN 2283 02:02:48,277 --> 02:02:49,512 FEBRUARY AND NOW AND IS 2284 02:02:49,512 --> 02:02:50,246 AVAILABLE ONLINE IF YOU WANT TO 2285 02:02:50,246 --> 02:02:59,222 LOOK AT IT. 2286 02:02:59,222 --> 02:03:03,292 THE GLIAL CELLS ARE THE MOST 2287 02:03:03,292 --> 02:03:04,761 DYSREGULATED AND SHOWN HERE FOR 2288 02:03:04,761 --> 02:03:09,198 ALL CELL TYPES WHERE THE UPWARD 2289 02:03:09,198 --> 02:03:11,000 DEFLECTED BARS SHOWING 2290 02:03:11,000 --> 02:03:12,535 UPREGULATION OF DIFFERENTIAL 2291 02:03:12,535 --> 02:03:14,537 EXPRESSION THE DOWNWARD 2292 02:03:14,537 --> 02:03:15,671 DEFLECTIONS ARE DOWN REGULATED 2293 02:03:15,671 --> 02:03:17,573 GENES FOR THE MAJOR CELL 2294 02:03:17,573 --> 02:03:17,840 CLASSES. 2295 02:03:17,840 --> 02:03:21,778 EACH OF THE BARS ARE DIVIDED 2296 02:03:21,778 --> 02:03:28,384 INTO SUB CLUSTERS OF CELLS AND 2297 02:03:28,384 --> 02:03:32,221 IT'S CLEAR ASTROCYTES HAVE BY 2298 02:03:32,221 --> 02:03:34,223 FAR THE GREATEST NUMBER OF 2299 02:03:34,223 --> 02:03:35,091 DYSREGULATED GENES FOLLOWED BY 2300 02:03:35,091 --> 02:03:40,263 THE ADENDROCYTES AND MICROGLIA 2301 02:03:40,263 --> 02:03:41,931 AND THEY WERE THE MOST 2302 02:03:41,931 --> 02:03:42,465 DYSREGULATED IN TERMS OF 2303 02:03:42,465 --> 02:03:49,806 DIFFERENTIAL EXPRESSION. 2304 02:03:49,806 --> 02:03:52,275 NOW IT TAKE A DEEP DIVE IN THE 2305 02:03:52,275 --> 02:03:55,578 MICROGLIA POPULATION AND WHERE I 2306 02:03:55,578 --> 02:03:58,581 WANTED TO GET WITH THE DATA SET. 2307 02:03:58,581 --> 02:03:59,315 LET'S FOCUS ON WHAT'S 2308 02:03:59,315 --> 02:04:02,185 HIGHLIGHTED IN THE SQUARE. 2309 02:04:02,185 --> 02:04:04,420 THE MICROGLIA POPULATION SUB 2310 02:04:04,420 --> 02:04:06,389 CLUSTERED INTO TWO DIFFERENT 2311 02:04:06,389 --> 02:04:08,624 POPULATIONS I'M CALLING THOSE 2312 02:04:08,624 --> 02:04:11,861 MG1 AND MG2. 2313 02:04:11,861 --> 02:04:16,699 NOT TO BE CONFUSED WITH THE 2314 02:04:16,699 --> 02:04:19,802 CLASSIFICATION SCHEMES I TALKED 2315 02:04:19,802 --> 02:04:20,870 ABOUT EARLIER. 2316 02:04:20,870 --> 02:04:24,574 THAT'S A DIFFERENT AND THIS IS A 2317 02:04:24,574 --> 02:04:27,777 CLUSTER NAME THAT WAS APPLIED TO 2318 02:04:27,777 --> 02:04:34,083 THE CLUSTER. 2319 02:04:34,083 --> 02:04:37,687 IF YOU LOOK AT THE AUD DONORS IN 2320 02:04:37,687 --> 02:04:39,522 TERMS OF THE PROPORTION OR 2321 02:04:39,522 --> 02:04:41,657 CONTRIBUTIONS TO MG1 AND MG2, 2322 02:04:41,657 --> 02:04:43,993 YOU SEE THE CONTROL SAMPLES HAD 2323 02:04:43,993 --> 02:04:46,028 A MUCH GREATER PROPORTION OF THE 2324 02:04:46,028 --> 02:04:49,232 LARGER MG1 CLUSTER COMPARED TO 2325 02:04:49,232 --> 02:04:53,903 AUD WHILE THE AUD SAMPLES HAD A 2326 02:04:53,903 --> 02:04:57,773 HIGHER PROPORTION OF THE MG2 2327 02:04:57,773 --> 02:05:03,479 CLASSIFICATION. 2328 02:05:03,479 --> 02:05:06,682 AS A CLUSTER THE MICROGLIA 2329 02:05:06,682 --> 02:05:09,752 CLUSTER OF CELLS SEEMS TO BE 2330 02:05:09,752 --> 02:05:20,530 CHANGING OR TRANSITION TRANSITIF 2331 02:05:20,530 --> 02:05:21,797 YOU LOOK AT THE INDIVIDUAL 2332 02:05:21,797 --> 02:05:23,366 CLUSTER, THIS IS WHERE WE 2333 02:05:23,366 --> 02:05:25,234 STARTED TO FIND THINGS THAT WERE 2334 02:05:25,234 --> 02:05:29,305 NOT EXPECTED IN THE DATA 2335 02:05:29,305 --> 02:05:29,605 NECESSARILY. 2336 02:05:29,605 --> 02:05:32,175 SO THIS IS A LITTLE BIT OF A 2337 02:05:32,175 --> 02:05:33,910 COMPLICATED PLOT BUT HERE I'M 2338 02:05:33,910 --> 02:05:38,181 BREAKING DOWN EACH OF THE GLIAL 2339 02:05:38,181 --> 02:05:41,450 CLUSTERS 1 AND 2 AND SHOWING 2340 02:05:41,450 --> 02:05:45,488 REPRESENTATION OF CANONICAL 2341 02:05:45,488 --> 02:05:48,357 MARKERS ASSOCIATED WITH 2342 02:05:48,357 --> 02:05:50,593 MICROGLIA OR INFLAMMATORY CELL 2343 02:05:50,593 --> 02:05:51,761 STATES. 2344 02:05:51,761 --> 02:05:58,634 AND SO THE COLOR CODES HERE THE 2345 02:05:58,634 --> 02:06:01,170 HOMEOSTATIC AND PRO-INFLAMMATORY 2346 02:06:01,170 --> 02:06:02,438 AND PAINTED ON THE RIGHT SIDE SO 2347 02:06:02,438 --> 02:06:05,074 YOU SEE THE CANONICAL MARKERS 2348 02:06:05,074 --> 02:06:05,775 AND EXPRESSION LEVEL FOR EACH OF 2349 02:06:05,775 --> 02:06:06,776 THE MARKERS. 2350 02:06:06,776 --> 02:06:09,946 AND THE STRIKING THING HERE IS 2351 02:06:09,946 --> 02:06:14,183 THAT WITH HOMEOSTATIC MARKERS, 2352 02:06:14,183 --> 02:06:18,054 THE MG1 CLUSTER IS PRIMARILY 2353 02:06:18,054 --> 02:06:19,855 ASSOCIATED WITH HOMEOSTASIS 2354 02:06:19,855 --> 02:06:23,292 WHEREAS THE MG2 HAS A 2355 02:06:23,292 --> 02:06:24,527 COMBINATION OF INFLAMMATORY 2356 02:06:24,527 --> 02:06:26,495 MARKERS, WHICH WOULD BE 2357 02:06:26,495 --> 02:06:26,796 EXPECTED. 2358 02:06:26,796 --> 02:06:29,498 THAT'S NOT NEW, BUT WHAT WE 2359 02:06:29,498 --> 02:06:32,602 DIDN'T EXPECT IS TO HAVE 2360 02:06:32,602 --> 02:06:33,769 REPRESENTATION OF 2361 02:06:33,769 --> 02:06:35,771 DISEASE-ASSOCIATED MACROPHAGES 2362 02:06:35,771 --> 02:06:39,775 THE DAM SIGNATURE AND 2363 02:06:39,775 --> 02:06:41,477 BORDER-ASSOCIATED MACROPHAGE 2364 02:06:41,477 --> 02:06:42,411 THAT I'LL CALL DAB HERE AND THIS 2365 02:06:42,411 --> 02:06:44,747 IS IMPORTANT. 2366 02:06:44,747 --> 02:06:46,215 WE DON'T KNOW WHERE THESE 2367 02:06:46,215 --> 02:06:47,250 SIGNALS ORIGINATE. 2368 02:06:47,250 --> 02:06:49,885 THIS CAN COME BACK TO AS THE 2369 02:06:49,885 --> 02:06:51,287 PREVIOUS TALK AND THE SIGNALS IN 2370 02:06:51,287 --> 02:06:53,990 THE PERIPHERY WITH MACROPHAGE 2371 02:06:53,990 --> 02:06:55,291 INVOLVEMENT ARE THESE SIGNALS 2372 02:06:55,291 --> 02:06:57,860 THAT ARE MAYBE ORIGINATING IN 2373 02:06:57,860 --> 02:07:00,129 THE PERIPHERY AND GETTING TO THE 2374 02:07:00,129 --> 02:07:00,429 BRAIN. 2375 02:07:00,429 --> 02:07:01,364 WE DON'T KNOW. 2376 02:07:01,364 --> 02:07:03,299 THAT'S SOMETHING WE'RE WORKING 2377 02:07:03,299 --> 02:07:03,466 ON. 2378 02:07:03,466 --> 02:07:06,469 IT'S VERY CLEAR FROM WHAT WE'RE 2379 02:07:06,469 --> 02:07:09,605 SEEING HERE AND THIS WAS PRETTY 2380 02:07:09,605 --> 02:07:15,878 MUCH UNEXPECTED THAT THE MIC 2381 02:07:15,878 --> 02:07:17,613 MICROGLIA MARKERS TELL US ABOUT 2382 02:07:17,613 --> 02:07:21,917 THE GENE EXPRESSION SIGNATURES 2383 02:07:21,917 --> 02:07:32,261 WITHIN THE CLUSTERS. 2384 02:07:33,362 --> 02:07:38,134 AND IF YOU LOOK AT ENRICHMENTS 2385 02:07:38,134 --> 02:07:41,237 OF GENE ONCOLOGIES WITHIN THE 2386 02:07:41,237 --> 02:07:44,573 CLUSTERS, THE GREEN REPRESENTING 2387 02:07:44,573 --> 02:07:46,509 WHAT'S PRIMARILY IMMUNOSTATIC 2388 02:07:46,509 --> 02:07:47,677 MICROGLIA ASSOCIATED WITH 2389 02:07:47,677 --> 02:07:51,881 CONTROL INDIVIDUALS. 2390 02:07:51,881 --> 02:07:56,052 THESE ARE ENRICHED WITH PATHWAYS 2391 02:07:56,052 --> 02:07:58,387 KNOWN TO BE INVOLVED WITH 2392 02:07:58,387 --> 02:08:00,122 HOMEOSTASIS AND SIGNALLING AND A 2393 02:08:00,122 --> 02:08:03,859 TRANS MEMBRANE IMMUNE SIGNALLING 2394 02:08:03,859 --> 02:08:04,427 ADAPTER. 2395 02:08:04,427 --> 02:08:07,830 ALL OF THESE ARE DONE BY 2396 02:08:07,830 --> 02:08:09,665 HOMEOSTATIC MARKERS. 2397 02:08:09,665 --> 02:08:14,203 WHEREAS THE MT2 CLUSTER IS 2398 02:08:14,203 --> 02:08:17,340 ASSOCIATED MORE WITH CYTOKINE 2399 02:08:17,340 --> 02:08:19,008 SIGNALLING AND IMMUNE RESPONSE 2400 02:08:19,008 --> 02:08:21,143 AS YOU SEE FROM THE ONTOLOGIES 2401 02:08:21,143 --> 02:08:22,178 WITH IMMUNE SYSTEM DEVELOPMENT 2402 02:08:22,178 --> 02:08:32,521 AND DISEASE STATES. 2403 02:08:40,629 --> 02:08:42,198 THERE'S A CLEAR TRANSMISSION 2404 02:08:42,198 --> 02:08:45,701 ASSOCIATED WITH AUD. 2405 02:08:45,701 --> 02:08:47,370 I'M GOING TO MOVE NOW TO GENE 2406 02:08:47,370 --> 02:08:49,872 COEXPRESSION AND GO TO A MORE 2407 02:08:49,872 --> 02:08:58,581 SYSTEMS LEVEL LOOK AT THESE 2408 02:08:58,581 --> 02:09:01,350 CLUSTERS AND FOR THOSE THAT 2409 02:09:01,350 --> 02:09:03,786 DON'T KNOW ABOUT CO-EXPRESSION 2410 02:09:03,786 --> 02:09:04,053 NETWORKS. 2411 02:09:04,053 --> 02:09:06,188 THE BASIC IDEA IS YOU TAKE A SET 2412 02:09:06,188 --> 02:09:07,823 OF TRANSCRIPTS. 2413 02:09:07,823 --> 02:09:09,892 IF YOU PULL ALL THE MICROGLIA 2414 02:09:09,892 --> 02:09:12,561 TRANSCRIPTS AND ORGANIZE THEM 2415 02:09:12,561 --> 02:09:17,933 INTO GROUPS OF GENES WITH 2416 02:09:17,933 --> 02:09:19,535 SIMILAR EXPRESSION PATTERNS, AB 2417 02:09:19,535 --> 02:09:21,537 AND C FOR EACH IN THE CASE AND 2418 02:09:21,537 --> 02:09:25,274 YOU CAN IDENTIFY THE GENE 2419 02:09:25,274 --> 02:09:25,508 MODULES. 2420 02:09:25,508 --> 02:09:32,915 THE IDEA IS THEY USUALLY HAVE 2421 02:09:32,915 --> 02:09:34,784 DIFFERENT FUNCTIONS AND START TO 2422 02:09:34,784 --> 02:09:36,519 IDENTIFY THE GENE MODULES 2423 02:09:36,519 --> 02:09:37,686 CO-EXPRESSED WITH ONE ANOTHER. 2424 02:09:37,686 --> 02:09:40,156 WITHIN THE MODULES THERE ARE KEY 2425 02:09:40,156 --> 02:09:42,124 GENES THE ONES SHOWN IN GOLD. 2426 02:09:42,124 --> 02:09:43,492 THESE ARE GENES HIGHLY CONNECTED 2427 02:09:43,492 --> 02:09:45,828 TO THE OTHERS. 2428 02:09:45,828 --> 02:09:49,131 SO THESE ARE THE DRIVER GENES 2429 02:09:49,131 --> 02:09:54,203 FOR EACH OF THESE WHERE YOU CAN 2430 02:09:54,203 --> 02:09:56,238 DO CORRELATIONS WITH PHENOTYPES 2431 02:09:56,238 --> 02:10:00,209 AND SHOWN IN THE CARTOON IS YOU 2432 02:10:00,209 --> 02:10:03,679 CAN CORRELATE THE CO-EXPRESSION 2433 02:10:03,679 --> 02:10:04,780 MODELS WITH THINGS LIKE ALCOHOL 2434 02:10:04,780 --> 02:10:08,384 AND GENDER AND DSM5 STATUS TO 2435 02:10:08,384 --> 02:10:10,553 GET AN IDEA OF SETS OF GENES 2436 02:10:10,553 --> 02:10:13,689 THAT FUNCTION TOGETHER AND MAY 2437 02:10:13,689 --> 02:10:19,028 DRIVE SOME OF THESE CELLS WE'RE 2438 02:10:19,028 --> 02:10:20,596 TALKING ABOUT. 2439 02:10:20,596 --> 02:10:23,165 CO-EXPRESSION NETWORK ANALYSIS 2440 02:10:23,165 --> 02:10:27,870 RESULTED IN EIGHT SEPARATE 2441 02:10:27,870 --> 02:10:30,372 MICROGLIA EXPRESSION MODULES 2442 02:10:30,372 --> 02:10:34,477 SHOWN IN 1-M8 AND SEPARATED BY 2443 02:10:34,477 --> 02:10:38,047 AUD STATUS AND THE RED CIRCLES 2444 02:10:38,047 --> 02:10:42,017 IN THE STOP PLOT REPRESENT THE 2445 02:10:42,017 --> 02:10:47,490 GENE VALUES AND IT'S THE FIRST 2446 02:10:47,490 --> 02:10:50,960 COMPONENT OF THE CLUSTERS SO IT 2447 02:10:50,960 --> 02:10:57,833 GIVES YOU AN EXPRESSION AND YOU 2448 02:10:57,833 --> 02:11:00,503 SEE THE UP REGULATION OF AUD 2449 02:11:00,503 --> 02:11:03,873 RESULTED IN THREE MODULES UP 2450 02:11:03,873 --> 02:11:11,514 REGULATED GENE EXPRESSION. 2451 02:11:11,514 --> 02:11:13,382 IF YOU LOOK AT THE CLINICAL 2452 02:11:13,382 --> 02:11:14,650 VARIABLES COLLECTED AND I'M 2453 02:11:14,650 --> 02:11:17,086 SHOWING SIX HERE WHERE EACH OF 2454 02:11:17,086 --> 02:11:18,454 THE MODULES OF GENES ARE 2455 02:11:18,454 --> 02:11:21,857 CORRELATED WITH SEX, LIVER, 2456 02:11:21,857 --> 02:11:22,658 CLASS AND TOTAL DRINKING YEARS 2457 02:11:22,658 --> 02:11:27,029 AND SO ON AND YOU SEE A NUMBER 2458 02:11:27,029 --> 02:11:30,699 ARE HIGHLY CORRELATED WITH TOTAL 2459 02:11:30,699 --> 02:11:33,235 DRINKING YEARS RATHER THAN 2460 02:11:33,235 --> 02:11:34,737 INTAKE PER DAY OF ALCOHOL. 2461 02:11:34,737 --> 02:11:37,306 SO THE LONGER AN INDIVIDUAL 2462 02:11:37,306 --> 02:11:38,007 DRINKS, THE HIGHER THE 2463 02:11:38,007 --> 02:11:45,447 RELATIONSHIP IN THE COHORTS. 2464 02:11:45,447 --> 02:11:47,950 I WANT TO FOCUS ON TWO OF THESE. 2465 02:11:47,950 --> 02:11:50,019 THERE'S INFORMATION IN ALL THE 2466 02:11:50,019 --> 02:11:50,886 MODULES BUT I ONLY HAVE TIME TO 2467 02:11:50,886 --> 02:11:54,189 YOU CAN TA ABOUT TWO. 2468 02:11:54,189 --> 02:12:03,499 I'LL TALK MORE ABOUT AND WE'LL 2469 02:12:03,499 --> 02:12:07,436 LOOK AT 103 GENES AND I WANT TO 2470 02:12:07,436 --> 02:12:15,844 FOCUS ON THOSE BECAUSE THESE WE 2471 02:12:15,844 --> 02:12:18,180 DIDN'T EXPECT TO SEE IN THE 2472 02:12:18,180 --> 02:12:28,490 PARTICULAR STUDY. 2473 02:12:34,330 --> 02:12:36,098 IF YOU LOOK AT THE CRITERIA FOR 2474 02:12:36,098 --> 02:12:42,004 MODERATE AND SEVERE AND THE 2475 02:12:42,004 --> 02:12:49,345 MODULE 2 GENES OERCORRELATE TO D 2476 02:12:49,345 --> 02:12:51,380 TO MODERATE AND MODULE 3 IS 2477 02:12:51,380 --> 02:12:53,882 ASSOCIATED WITH SEVERE DRINKING. 2478 02:12:53,882 --> 02:12:54,516 SO MODULE 3 STANDS OUT IN THIS 2479 02:12:54,516 --> 02:13:02,925 CASE. 2480 02:13:02,925 --> 02:13:06,195 IF YOU CONSIDER THE DISEASE 2481 02:13:06,195 --> 02:13:08,097 ASSOCIATED MACROPHAGE POPULATION 2482 02:13:08,097 --> 02:13:10,165 AND START TO ASK QUESTIONS WHICH 2483 02:13:10,165 --> 02:13:11,934 PARTICULAR CLUSTERS ARE THESE 2484 02:13:11,934 --> 02:13:13,335 REGULATED IN, WHAT WILL THE HUB 2485 02:13:13,335 --> 02:13:19,875 GENES AND CONNECTIONS AND WHAT 2486 02:13:19,875 --> 02:13:21,944 DOES IT TELL US ABOUT THE MOTHER 2487 02:13:21,944 --> 02:13:23,512 YOU'LL SIGNATURE? 2488 02:13:23,512 --> 02:13:27,916 WHAT I'M DRAWING HERE THE 2489 02:13:27,916 --> 02:13:30,519 ORIGINAL MICROGLIAL STRUG TURE 2490 02:13:30,519 --> 02:13:33,956 IS IN MG1 AND 2 DIVIDED INTO AUD 2491 02:13:33,956 --> 02:13:44,500 STATUS AND CONTROL AND AND THIS 2492 02:13:48,704 --> 02:13:50,406 IS 70 GENES WORTH OF DATA AND 2493 02:13:50,406 --> 02:13:52,808 PLOTTED ON TOP OF CLUSTERS TO 2494 02:13:52,808 --> 02:13:54,610 SEE WHICH CLUSTERS THEY'RE 2495 02:13:54,610 --> 02:13:55,277 INVOLVED WITH. 2496 02:13:55,277 --> 02:13:56,478 THE FUNCTIONS ASSOCIATED WITH 2497 02:13:56,478 --> 02:13:59,214 THE DISEASE ASSOCIATED 2498 02:13:59,214 --> 02:14:04,319 MACROPHAGE INCLUDED F1, L2, CD83 2499 02:14:04,319 --> 02:14:08,891 AND IL1 BETA AND THEY SUBJECT 2500 02:14:08,891 --> 02:14:10,793 STRONG UP REGULATION OF 2501 02:14:10,793 --> 02:14:12,895 DISEASE-ASSOCIATED BORDERS 2502 02:14:12,895 --> 02:14:15,798 MACROPHAGE IN AUDs. 2503 02:14:15,798 --> 02:14:26,341 AND AGAIN THIS WAS NOT EXPECTED 2504 02:14:29,278 --> 02:14:33,515 AND GOT IMMUNE MOLECULES AND THE 2505 02:14:33,515 --> 02:14:35,284 CAPPA B. 2506 02:14:35,284 --> 02:14:39,154 THE MODULE 2 DOES CONTAIN A 2507 02:14:39,154 --> 02:14:46,228 STRONG SIGNATURE OF GENES NOVEL 2508 02:14:46,228 --> 02:14:48,564 TO THE ALCOHOL FIELD AND CONTAIN 2509 02:14:48,564 --> 02:14:50,099 RELEVANT KNOWN MARKERS. 2510 02:14:50,099 --> 02:14:52,568 AND MODULE 3 I WANT TO POINT 2511 02:14:52,568 --> 02:14:54,169 OUT. 2512 02:14:54,169 --> 02:15:00,142 THIS IS A WHITE MATTER WHITE 2513 02:15:00,142 --> 02:15:00,843 MATTER ASSOCIATED STATE AND 2514 02:15:00,843 --> 02:15:02,644 SOMETHING I WANT TO POINT OUT 2515 02:15:02,644 --> 02:15:06,181 BECAUSE THIS HAS BEEN ASSOCIATED 2516 02:15:06,181 --> 02:15:11,086 WITH PARKINSON'S DISEASE AND 2517 02:15:11,086 --> 02:15:13,555 THESE MACROPHAGES ARE KNOWN TO 2518 02:15:13,555 --> 02:15:18,594 BE INVOLVED WITH DISEASE-RELATED 2519 02:15:18,594 --> 02:15:28,804 SIGNATURES. 2520 02:15:29,671 --> 02:15:33,742 AND A BIOMARKER IN HUMANS AND WE 2521 02:15:33,742 --> 02:15:35,778 HAVE CLUSTERS OF MICROGLIA. 2522 02:15:35,778 --> 02:15:46,321 THESE ARE TWO OF THE FEATURES OF 2523 02:15:47,856 --> 02:15:51,660 THE GENE COEXPRESSION IN HUMAN 2524 02:15:51,660 --> 02:15:51,927 MICROGLIA. 2525 02:15:51,927 --> 02:15:55,731 IF YOU LOOK AT THIS AT THE WHEEL 2526 02:15:55,731 --> 02:15:59,735 OF MICROGLIA AND THE HOMEOSTATIC 2527 02:15:59,735 --> 02:16:01,503 MICROGLIA AND DISEASE STATES, 2528 02:16:01,503 --> 02:16:05,073 YOU SEE AUD IS REALLY RESULTING 2529 02:16:05,073 --> 02:16:12,714 IN STATE TRANSITIONS FROM THE 2530 02:16:12,714 --> 02:16:13,816 HOMEOSTATIC MICROGLIA PHENOTYPE 2531 02:16:13,816 --> 02:16:17,152 TO OTHER STATES OF MICROGLIA 2532 02:16:17,152 --> 02:16:19,588 WHICH IS INTERESTING BECAUSE WE 2533 02:16:19,588 --> 02:16:22,224 NEED TO LEARN MORE ABOUT WHERE 2534 02:16:22,224 --> 02:16:23,192 THESE ORIGINATE. 2535 02:16:23,192 --> 02:16:24,359 ARE THESE ORIGINATING IN THE 2536 02:16:24,359 --> 02:16:26,195 BRAIN OR MAKING THEIR WAY INTO 2537 02:16:26,195 --> 02:16:30,999 THE BRAIN. 2538 02:16:30,999 --> 02:16:33,969 SO THAT'S THE HIGH-LEVEL SUMMARY 2539 02:16:33,969 --> 02:16:37,606 FOR THE HUMAN DATA. 2540 02:16:37,606 --> 02:16:39,942 WE ALWAYS WANT TO GO BACK TO 2541 02:16:39,942 --> 02:16:46,014 ANIMAL MODELS AND ASK QUESTIOS 2542 02:16:46,014 --> 02:16:47,249 IDENTIFY FROM THE HUMAN AUD 2543 02:16:47,249 --> 02:16:50,185 DONORS OR CHECK TO MAKE SURE 2544 02:16:50,185 --> 02:16:57,359 THAT OUR ANIMAL MODELS ARE 2545 02:16:57,359 --> 02:16:59,561 TRANSLATING TO HUMAN AND WANT TO 2546 02:16:59,561 --> 02:17:02,231 SHOW AN INTEGRATING STUDY WITH 2547 02:17:02,231 --> 02:17:06,168 ANOTHER SINGLE CELL STUDY 2548 02:17:06,168 --> 02:17:14,643 PUBLISHED IN THE LAB LAST YEAR. 2549 02:17:14,643 --> 02:17:17,212 THESE ARE ANIMALS TREATED WITH 2550 02:17:17,212 --> 02:17:18,947 THE ALCOHOL DRINKING PARADIGM 2551 02:17:18,947 --> 02:17:20,816 THAT RESULTS IN ALCOHOL 2552 02:17:20,816 --> 02:17:21,116 DEPENDENCE. 2553 02:17:21,116 --> 02:17:24,820 THESE WERE PROVIDED BY MARISSA 2554 02:17:24,820 --> 02:17:27,723 ROBERTO'S GROUP AT SCRIPPS. 2555 02:17:27,723 --> 02:17:32,027 WE PROFILES PREFRONTAL CORTEX 2556 02:17:32,027 --> 02:17:34,162 AND INTEGRATED THE SIGNAL CELL 2557 02:17:34,162 --> 02:17:38,166 DATA FROM MOUSE AND HUMAN. 2558 02:17:38,166 --> 02:17:41,203 HERE THIS WAS ROUGHLY 150,000 2559 02:17:41,203 --> 02:17:44,473 TOTAL NUCLEI. 2560 02:17:44,473 --> 02:17:54,883 THIS WAS PUBLISHED AND 2561 02:17:58,287 --> 02:18:01,123 APPROACHES WITH SINGLE CELL 2562 02:18:01,123 --> 02:18:02,190 TECHNOLOGY. 2563 02:18:02,190 --> 02:18:05,727 WE UTILIZED ANCHOR BASED 2564 02:18:05,727 --> 02:18:08,363 UTILIZATION AND WE USED THE 2565 02:18:08,363 --> 02:18:10,198 PLOTS, BLUE REPRESENTS NUCLEI 2566 02:18:10,198 --> 02:18:13,702 FROM MOUSE POPULATIONS, THE RED 2567 02:18:13,702 --> 02:18:24,179 FROM HUMAN AND THEY CLUSTER 2568 02:18:25,480 --> 02:18:27,115 SEPARATE AND WE CAN START TO 2569 02:18:27,115 --> 02:18:28,016 INTEGRATE THE DATA. 2570 02:18:28,016 --> 02:18:32,254 THIS IS DONE BY IDENTIFYING THE 2571 02:18:32,254 --> 02:18:34,022 CELLS IN EACH SPECIES THAT HAVE 2572 02:18:34,022 --> 02:18:36,892 THE GREATEST AMOUNT OF 2573 02:18:36,892 --> 02:18:37,225 SIMILARITIES. 2574 02:18:37,225 --> 02:18:38,627 IF YOU TAKE PAIR OF CELLS ONE 2575 02:18:38,627 --> 02:18:42,197 FROM MOUSE AND IDENTIFY CELLS 2576 02:18:42,197 --> 02:18:48,003 THAT OVERLAP IN THE EXPRESSION 2577 02:18:48,003 --> 02:18:50,639 PATTERNS CAN BE USED AS ANCHORS 2578 02:18:50,639 --> 02:18:53,809 TO BUILD THE ORTHOLOGOUS GENE 2579 02:18:53,809 --> 02:18:58,013 NETWORKS TO PULL TOGETHER CELLS 2580 02:18:58,013 --> 02:19:02,184 THAT ARE REPRESENTING EACH CELL 2581 02:19:02,184 --> 02:19:03,518 TYPE FROM EACH SPECIES. 2582 02:19:03,518 --> 02:19:09,691 SO AFTER DOING THIS YOU CAN SEE 2583 02:19:09,691 --> 02:19:11,360 FOR THE DATA SET THERE WAS A 2584 02:19:11,360 --> 02:19:12,995 GOOD OVERLAP BETWEEN MOUSE AND 2585 02:19:12,995 --> 02:19:14,629 HUMAN FROM THE ANCHOR-BASED 2586 02:19:14,629 --> 02:19:17,733 APPROACH AND CAN START TO ASK 2587 02:19:17,733 --> 02:19:19,534 QUESTI 2588 02:19:19,534 --> 02:19:20,435 QUESTIONS AND IDENTIFIED 2589 02:19:20,435 --> 02:19:22,738 CLUSTERS OF CELLS IN HUMANS IN 2590 02:19:22,738 --> 02:19:28,043 THE TRANSCRIPTOME OR RELEVANT IN 2591 02:19:28,043 --> 02:19:38,387 MICE AND VICE VERSA. 2592 02:19:44,559 --> 02:19:52,034 AND 13 SPECIES AND THEY'RE 2593 02:19:52,034 --> 02:19:53,802 REPRESENTED ALMOST EQUALLY. 2594 02:19:53,802 --> 02:19:54,936 MOST CLUSTERS THOUGH A SEEM TO 2595 02:19:54,936 --> 02:19:56,872 BE MOUSE ONLY. 2596 02:19:56,872 --> 02:19:59,141 OF COURSE YOU WOULD EXPECT THIS 2597 02:19:59,141 --> 02:20:00,642 BECAUSE NOT ALL MOUSE CELLS WILL 2598 02:20:00,642 --> 02:20:02,077 BE SIMILAR TO HUMAN CELLS SO 2599 02:20:02,077 --> 02:20:06,815 IT'S NOT UNEXPECTED. 2600 02:20:06,815 --> 02:20:17,359 IS IS -- CLUSTER 12 AND 27 AND 2601 02:20:25,834 --> 02:20:27,936 CLUSTER 12 IS REPRESENTED BY ALL 2602 02:20:27,936 --> 02:20:29,704 THE CONDITIONS IN THE STUDIES. 2603 02:20:29,704 --> 02:20:31,940 THE HUMAN AUD AND THEIR 2604 02:20:31,940 --> 02:20:34,142 CONTROLS, MOUSE CONTROL, MOUSE 2605 02:20:34,142 --> 02:20:36,912 VAPOR, ALL COLOR CODED AND SO 2606 02:20:36,912 --> 02:20:37,979 THERE'S NEAR EQUAL CONTRIBUTIONS 2607 02:20:37,979 --> 02:20:41,216 OF ALL THE CELLS. 2608 02:20:41,216 --> 02:20:46,321 THIS IS TRUE FOR MANY OF THE 2609 02:20:46,321 --> 02:20:49,057 CLUSTERS AND I WANT TO FOCUS ON 2610 02:20:49,057 --> 02:20:52,027 CLUSTER 27, WHICH YOU CAN SEE IS 2611 02:20:52,027 --> 02:20:55,831 MOSTLY A CONTRIBUTION FROM THE 2612 02:20:55,831 --> 02:20:56,231 AUD. 2613 02:20:56,231 --> 02:21:00,535 NOW, THIS SUGGEST THERE'S 2614 02:21:00,535 --> 02:21:03,138 SOMETHING ABOUT THE MICROGLIA 2615 02:21:03,138 --> 02:21:05,140 CELL NOT FOUND IN OUR MOUSE 2616 02:21:05,140 --> 02:21:05,507 MODEL. 2617 02:21:05,507 --> 02:21:06,475 I'M POINTING THIS OUT BECAUSE 2618 02:21:06,475 --> 02:21:08,477 AGAIN WE NEED TO ALWAYS MAKE 2619 02:21:08,477 --> 02:21:09,945 SURE THAT WHEN WE ARE THINKING 2620 02:21:09,945 --> 02:21:13,048 ABOUT OUR TRANSLATION EVENTS 2621 02:21:13,048 --> 02:21:13,949 THEY'RE RELEVANT. 2622 02:21:13,949 --> 02:21:18,186 IF YOU LOOK AT THIS HUMAN ONLY 2623 02:21:18,186 --> 02:21:23,892 POPULATION WE SEE IT'S HIGHLY 2624 02:21:23,892 --> 02:21:27,696 OVERLAPPED WITH THE MG2 CLUSTER 2625 02:21:27,696 --> 02:21:34,603 I TALKED A LOT ABOUT EARLIER. 2626 02:21:34,603 --> 02:21:36,571 THIS HAD CYTOKINE SIGNALLING. 2627 02:21:36,571 --> 02:21:38,106 THIS IS AN EXAMPLE OF A 2628 02:21:38,106 --> 02:21:39,508 SITUATION WHERE WE WANT TO 2629 02:21:39,508 --> 02:21:41,109 REALLY LOOK CAREFULLY IF YOU'RE 2630 02:21:41,109 --> 02:21:43,712 GOING TO STUDY SOME OF THE 2631 02:21:43,712 --> 02:21:44,479 PATHWAYS WITHIN THE CELL TYPE 2632 02:21:44,479 --> 02:21:47,082 AND MAKE SURE THAT YOU HAVE 2633 02:21:47,082 --> 02:21:47,916 TRANSLATIONAL VALUES. 2634 02:21:47,916 --> 02:21:51,019 SO JUST WANTED TO POINT THIS OUT 2635 02:21:51,019 --> 02:21:52,821 BECAUSE THE INTEGRATION OF 2636 02:21:52,821 --> 02:21:53,522 EXPERIMENTS ARE IMPORTANT 2637 02:21:53,522 --> 02:21:56,124 BECAUSE IT DOES REALLY TELL US 2638 02:21:56,124 --> 02:21:57,325 SOMETHING ABOUT WHAT TO STUDY 2639 02:21:57,325 --> 02:22:07,702 AND WHAT NOT TO STUDY. 2640 02:22:12,140 --> 02:22:13,675 MICROGLIA STRUCTURES WERE FOUND 2641 02:22:13,675 --> 02:22:21,950 TO BE RICH WITH MARKERS AND THE 2642 02:22:21,950 --> 02:22:24,819 MACROPHAGE MARKERS WERE NOT 2643 02:22:24,819 --> 02:22:27,022 ANTICIPATED SO THAT'S A NEW 2644 02:22:27,022 --> 02:22:28,156 FINDING. 2645 02:22:28,156 --> 02:22:31,693 MICROGLIA LOSE THEIR HOMEOSTATIC 2646 02:22:31,693 --> 02:22:38,366 CONTROL IN THE AUD CASES AND 2647 02:22:38,366 --> 02:22:40,168 OBTAIN A MORE INFLAMMATORY STATE 2648 02:22:40,168 --> 02:22:41,403 YOU MIGHT EXPECT FROM AUD. 2649 02:22:41,403 --> 02:22:46,975 THERE'S ENRICHED TARGETS LIKE 2650 02:22:46,975 --> 02:22:53,315 TLR SIGNALLING AND IT FITS WITH 2651 02:22:53,315 --> 02:22:55,817 HYPOTHESIS OF ALCOHOL 2652 02:22:55,817 --> 02:22:57,719 CONSUMPTION. 2653 02:22:57,719 --> 02:23:03,358 THE DISEASE-LIKE SIGNATURES AND 2654 02:23:03,358 --> 02:23:05,427 RECRUITMENT AS WE SAID THIS IS 2655 02:23:05,427 --> 02:23:07,762 ONE OF THE ONGOING QUESTIONS WE 2656 02:23:07,762 --> 02:23:08,029 HAD. 2657 02:23:08,029 --> 02:23:09,764 WHERE ARE THE SIGNALS COMING AND 2658 02:23:09,764 --> 02:23:12,901 WE'RE DEVELOPING STRATEGIES TO 2659 02:23:12,901 --> 02:23:15,971 IDENTIFY INFILTRATION OF 2660 02:23:15,971 --> 02:23:17,639 LYMPHOCYTES OR MACROPHAGE FROM 2661 02:23:17,639 --> 02:23:20,008 THE PERIPHERY THAT MAY EXPLAIN 2662 02:23:20,008 --> 02:23:23,044 THE DIFFERENCES OR IDENTIFY THE 2663 02:23:23,044 --> 02:23:23,979 CELLS THAT MIGHT TRANSITION FROM 2664 02:23:23,979 --> 02:23:26,181 WITHIN THE BRAIN ITSELF. 2665 02:23:26,181 --> 02:23:36,524 WE JUST DON'T KNOW. 2666 02:23:43,331 --> 02:23:45,467 I POINTED OUT WHETHER YOU CAN 2667 02:23:45,467 --> 02:23:47,402 STUDY ANIMAL MODELS RELEVANT TO 2668 02:23:47,402 --> 02:23:47,902 AUD. 2669 02:23:47,902 --> 02:23:48,503 WITH THAT I'LL STOP AND TAKE 2670 02:23:48,503 --> 02:23:58,680 QUESTIONS. 2671 02:24:11,893 --> 02:24:13,561 >> THAT WAS GREAT AND I ALWAYS 2672 02:24:13,561 --> 02:24:14,763 TAKE THE PREROGATIVE OF ASKING 2673 02:24:14,763 --> 02:24:18,033 THE FIRST QUESTION. 2674 02:24:18,033 --> 02:24:18,800 YOU GAIN THE INFLAMMATORY STATE 2675 02:24:18,800 --> 02:24:23,471 AND I HAVE THE IMPRESSION THAT 2676 02:24:23,471 --> 02:24:26,641 THERE'S A SENSITIZATION IN 2677 02:24:26,641 --> 02:24:29,911 INFLAMMATORY STATES THAT ARE 2678 02:24:29,911 --> 02:24:33,181 ASSOCIATED WITH THE BRAIN AND I 2679 02:24:33,181 --> 02:24:34,849 WONDER ARE THERE ANY CLUES YET 2680 02:24:34,849 --> 02:24:38,186 FROM THE MORE SOPHISTICATED 2681 02:24:38,186 --> 02:24:46,761 ANALYSES OF HOW ONCE IT GETS 2682 02:24:46,761 --> 02:24:48,330 STARTED THERE'S INFLAMMATION AND 2683 02:24:48,330 --> 02:24:52,400 MICROGLIA ACTIVATE AND CYTOKINES 2684 02:24:52,400 --> 02:24:57,806 AND THEY FEEDBACK AND FURTHER 2685 02:24:57,806 --> 02:24:59,774 ACTIVATE IS THERE A HINT HOW 2686 02:24:59,774 --> 02:25:00,575 IT'S TAKING PLACE IN THE SYSTEMS 2687 02:25:00,575 --> 02:25:02,777 ONCE THEY GET STARTED? 2688 02:25:02,777 --> 02:25:04,946 >> YEAH, SO SOME OF THE WORK 2689 02:25:04,946 --> 02:25:07,816 THERE WAS NOT TIME TO TALK ABOUT 2690 02:25:07,816 --> 02:25:12,554 AND THIS IS ALSO IN WORK WE'RE 2691 02:25:12,554 --> 02:25:19,327 INTERESTED IN PERIODIC 2692 02:25:19,327 --> 02:25:22,497 ACTIVATION OF PROTEINS BECAUSE 2693 02:25:22,497 --> 02:25:28,169 WITH THE INTERMITTENT ACTIVATION 2694 02:25:28,169 --> 02:25:31,973 WE SEE OVER TIME AN INCREASE IN 2695 02:25:31,973 --> 02:25:35,944 ALCOHOL CONSUMPTION THAT IS 2696 02:25:35,944 --> 02:25:38,713 PROBABLY RELATED TO A 2697 02:25:38,713 --> 02:25:41,416 SENSITIZATION EVENT LIKE YOU'RE 2698 02:25:41,416 --> 02:25:43,284 TALKING. 2699 02:25:43,284 --> 02:25:46,221 ONE HIT, ONE ACTIVATION ENOUGH. 2700 02:25:46,221 --> 02:25:50,225 IT TAKES UP TO SO REPEAT BOUTS 2701 02:25:50,225 --> 02:25:58,166 OF ACTIVATION AND AFTER THAT 2702 02:25:58,166 --> 02:25:59,968 THERE'S A SICKNESS RESPONSE AND 2703 02:25:59,968 --> 02:26:01,169 MOLECULAR TOLERANCE. 2704 02:26:01,169 --> 02:26:04,139 SO THE ANIMALS ARE RELATIVELY 2705 02:26:04,139 --> 02:26:07,842 NORMAL AT THE END OF THE CHRONIC 2706 02:26:07,842 --> 02:26:09,711 ADMINISTRATION PARADIGM PLUS WE 2707 02:26:09,711 --> 02:26:18,052 ALLOW A FEW WEEKS OFF FOR THE 2708 02:26:18,052 --> 02:26:18,887 ANIMALS MAINTAIN THEIR STATE 2709 02:26:18,887 --> 02:26:20,221 WITH THE ALCOHOL CONSUMPTION AND 2710 02:26:20,221 --> 02:26:26,194 THAT'S SOMETHING WE'RE WORKING 2711 02:26:26,194 --> 02:26:30,965 TO FINALIZE THE PATHWAYS AND 2712 02:26:30,965 --> 02:26:32,066 WILL BRING THE BLOOD BRAIN 2713 02:26:32,066 --> 02:26:33,334 BARRIER INTO THE PICTURE BECAUSE 2714 02:26:33,334 --> 02:26:35,370 IT'S A FEATURE COMMON BETWEEN 2715 02:26:35,370 --> 02:26:36,604 THE TRANSCRIPTOMIC SIGNATURES 2716 02:26:36,604 --> 02:26:45,747 AND THE ANIMAL MODELS. 2717 02:26:45,747 --> 02:26:49,150 WHAT WE DON'T KNOW IS DOES THIS 2718 02:26:49,150 --> 02:26:49,884 HAPPEN EARLY? 2719 02:26:49,884 --> 02:26:51,553 IS THE BLOOD BRAIN BARRIER 2720 02:26:51,553 --> 02:26:58,193 DYSFUNCTION ACCUMULATED OVER 2721 02:26:58,193 --> 02:27:04,966 TIME? 2722 02:27:04,966 --> 02:27:06,334 THOSE ARE THINGS WE'RE TRYING TO 2723 02:27:06,334 --> 02:27:08,903 DO TO GET AT THE QUESTION. 2724 02:27:08,903 --> 02:27:09,671 >> SO IS THERE ANOTHER QUESTION 2725 02:27:09,671 --> 02:27:19,881 FROM ANYONE? 2726 02:27:21,082 --> 02:27:25,119 DOES IT ANYONE ONLINE HAVE A 2727 02:27:25,119 --> 02:27:25,386 QUESTION? 2728 02:27:25,386 --> 02:27:27,822 CAN YOU HEAR ME? 2729 02:27:27,822 --> 02:27:31,860 >> THIS IS MICHAEL LEWIS. 2730 02:27:31,860 --> 02:27:32,527 HAVE YOU SEEN EVIDENCE IN THE 2731 02:27:32,527 --> 02:27:34,729 STUDIES WHERE IF YOU TERMINATE 2732 02:27:34,729 --> 02:27:36,397 THE ALCOHOL EXPOSURE THERE IS 2733 02:27:36,397 --> 02:27:39,834 EVIDENCE OF RECOVERY OF ANY OF 2734 02:27:39,834 --> 02:27:42,070 THESE FUNCTIONS IT MIGHT LEAD TO 2735 02:27:42,070 --> 02:27:46,207 PERHAPS THERAPEUTIC APPROACHES 2736 02:27:46,207 --> 02:27:56,284 TO TREATMENT OF ALCOHOLISM. 2737 02:27:56,284 --> 02:27:59,654 >> THAT'S WHAT WE SET OUT TO DO 2738 02:27:59,654 --> 02:28:00,655 WITH HUMAN DONORS. 2739 02:28:00,655 --> 02:28:02,724 THE PROBLEM IS WE HAVE A VARIETY 2740 02:28:02,724 --> 02:28:04,659 OF ABSTINENCE PERIOD IN THE 2741 02:28:04,659 --> 02:28:06,060 HUMANS BUT DON'T HAVE THE SAMPLE 2742 02:28:06,060 --> 02:28:09,831 SIZE TO GET TO WHAT HAPPENS WITH 2743 02:28:09,831 --> 02:28:13,034 EXTENDED WITHDRAWAL AND WE CAN 2744 02:28:13,034 --> 02:28:17,772 DO THAT WITH THE ANIMAL MODELS. 2745 02:28:17,772 --> 02:28:19,874 IT BECOMES FINANCIALLY 2746 02:28:19,874 --> 02:28:21,442 CHALLENGING TO DO MULTIPLE TIME 2747 02:28:21,442 --> 02:28:26,180 POINTS AFTER INDUCTION OF 2748 02:28:26,180 --> 02:28:27,448 DEPENDENTS. 2749 02:28:27,448 --> 02:28:28,283 THERE'S CHALLENGES THERE. 2750 02:28:28,283 --> 02:28:33,922 NATS A THAT'S A GREAT QUESTION 2751 02:28:33,922 --> 02:28:35,390 AND PURSUED TO GET AT THE 2752 02:28:35,390 --> 02:28:35,857 THERAPEUTIC EVIDENCE. 2753 02:28:35,857 --> 02:28:40,261 FOR A LONG TIME WE WERE 2754 02:28:40,261 --> 02:28:42,196 UTILIZING SIGNATURES FROM 2755 02:28:42,196 --> 02:28:46,200 DIFFERENT WITHDRAWAL PERIODS TO 2756 02:28:46,200 --> 02:28:56,311 TRY TO PREDICT DRUGS TO LOOK AT 2757 02:28:56,311 --> 02:28:57,679 SIGNATURES TO REDUCE DRINKING 2758 02:28:57,679 --> 02:29:02,183 BUT IT'S EXPENSIVE AND TIME 2759 02:29:02,183 --> 02:29:02,450 CONSUMING. 2760 02:29:02,450 --> 02:29:04,285 THANK YOU FOR THE QUESTION. 2761 02:29:04,285 --> 02:29:06,054 >> I WAS MAINLY AIMED AT THE 2762 02:29:06,054 --> 02:29:08,122 ANIMAL STUDIES TO LOOK FOR IN 2763 02:29:08,122 --> 02:29:08,656 HUMANS WITH THIS BUT IT'S 2764 02:29:08,656 --> 02:29:14,028 EXCELLENT WORK. 2765 02:29:14,028 --> 02:29:24,072 IT'S WONDERFUL. 2766 02:29:24,072 --> 02:29:25,807 >> WE'LL HAVE TO MOVE ON BUT 2767 02:29:25,807 --> 02:29:28,276 PEOPLE CAN FIND YOU THROUGH 2768 02:29:28,276 --> 02:29:30,178 E-MAIL AND IF YOU WANT PRE 2769 02:29:30,178 --> 02:29:31,279 PRINTS, PLEASE FEEL FREE. 2770 02:29:31,279 --> 02:29:34,182 CAN YOU STOP SHARING YOUR 2771 02:29:34,182 --> 02:29:43,958 SCREEN? 2772 02:29:43,958 --> 02:29:46,194 WE'LL HAVE CONCEPT CLEARANCE. 2773 02:29:46,194 --> 02:29:55,370 HERE WE GO. 2774 02:29:55,370 --> 02:29:56,938 >> GOOD AFTERNOON. 2775 02:29:56,938 --> 02:29:58,940 THIS IS NOT GOING TO BE A 2776 02:29:58,940 --> 02:29:59,574 SCIENTIFIC PRESENTATION BUT A 2777 02:29:59,574 --> 02:30:05,313 HIGHER LEVEL PRESENTATION OF A 2778 02:30:05,313 --> 02:30:06,180 CONCEPT. 2779 02:30:06,180 --> 02:30:09,350 AS GEORGE MENTIONS CARRIES ON 2780 02:30:09,350 --> 02:30:09,984 THEMATICALLY WITH WHAT WE'VE 2781 02:30:09,984 --> 02:30:11,586 BEEN DISCUSSING THIS AFTERNOON. 2782 02:30:11,586 --> 02:30:19,527 SO I'M HERE TODAY TO DISCUSS THE 2783 02:30:19,527 --> 02:30:21,462 RENEWAL OF THE INITIATIVE ON THE 2784 02:30:21,462 --> 02:30:24,165 ALCOHOLISM IN FISCAL 2027. 2785 02:30:24,165 --> 02:30:26,467 THAT IS TO SUPPORT TWO 2786 02:30:26,467 --> 02:30:28,503 COLLABORATIVE RESEARCH 2787 02:30:28,503 --> 02:30:29,671 CONSORTIUMS CURRENTLY THERE ARE 2788 02:30:29,671 --> 02:30:35,009 TWO CONSORTIUMS COMPRISED OF 22 2789 02:30:35,009 --> 02:30:38,179 PROJECTS HOUSED AT 13 DIFFERENT 2790 02:30:38,179 --> 02:30:41,849 RESEARCH INSTITUTIONS. 2791 02:30:41,849 --> 02:30:45,887 AND OUR FOCUS WILL BE BRAIN BODY 2792 02:30:45,887 --> 02:30:46,821 MECHANISM PERPETUATING EXCESSIVE 2793 02:30:46,821 --> 02:30:49,624 ALCOHOL DRINKING AND RELATED 2794 02:30:49,624 --> 02:30:52,827 ALCOHOL-USE DISORDER PHENOTYPES. 2795 02:30:52,827 --> 02:31:00,935 RESEARCH GOALS LOOK AT CAUSAL 2796 02:31:00,935 --> 02:31:05,707 INFLUENCES ON FOCUS ON 2797 02:31:05,707 --> 02:31:07,842 TRAJECTORIES AND WE HAD A SLIDE 2798 02:31:07,842 --> 02:31:09,577 FROM INITIAL ALCOHOL EXPOSURE TO 2799 02:31:09,577 --> 02:31:11,979 THE DEVELOP OF PATHOLOGICAL 2800 02:31:11,979 --> 02:31:14,015 DRINKING WE SOME INDIVIDUALS. 2801 02:31:14,015 --> 02:31:16,751 TRANSLATABLE TARGETS, MARKERS 2802 02:31:16,751 --> 02:31:27,328 AND WE WILL PROMOTE INNOVATION 2803 02:31:41,642 --> 02:31:44,979 IN TWO DIFFERENT WAYS. 2804 02:31:44,979 --> 02:31:47,014 BOTH IN ADAPTING TOOLS AND 2805 02:31:47,014 --> 02:31:49,417 TECHNOLOGIES FROM THE NIH BRAIN 2806 02:31:49,417 --> 02:31:50,084 INITIATIVE, NIH COMMON FUND AND 2807 02:31:50,084 --> 02:31:57,759 OTHER ADVANCED RESOURCES. 2808 02:31:57,759 --> 02:32:01,496 IN TERMS OF HYPOTHESES TO REVEAL 2809 02:32:01,496 --> 02:32:03,097 PERIPHERAL INFLUENCES ON BRAIN 2810 02:32:03,097 --> 02:32:05,600 FUNCTION RELATED TO ALCOHOL 2811 02:32:05,600 --> 02:32:08,736 MISUSE AND AUD. 2812 02:32:08,736 --> 02:32:14,408 ALL LONG THE INITIATIVE HAS AND 2813 02:32:14,408 --> 02:32:16,477 RIGOR AS SUPPORTED BY NIH. 2814 02:32:16,477 --> 02:32:19,747 IT EMPHASIZES REPLICATION ACROSS 2815 02:32:19,747 --> 02:32:22,183 PROJECTS AND USE OF STANDARDIZED 2816 02:32:22,183 --> 02:32:23,217 AND COORDINATED BEHAVIORAL AND 2817 02:32:23,217 --> 02:32:26,287 NEURAL FUNCTIONAL MEASURES AND 2818 02:32:26,287 --> 02:32:34,529 PROTOCOLS. 2819 02:32:34,529 --> 02:32:36,831 AND INTEGRATION IS A KEY THING. 2820 02:32:36,831 --> 02:32:37,999 IT'S BEEN BENEFICIAL IN 2821 02:32:37,999 --> 02:32:41,369 ACCELERATING DISCOVERY. 2822 02:32:41,369 --> 02:32:48,376 SO THE CONSORTIUM HAS HYPOTHESIS 2823 02:32:48,376 --> 02:32:50,211 AND ANALYSES FROM MOLECULAR TO 2824 02:32:50,211 --> 02:32:52,413 SYSTEMS LEVEL AND COORDINATED 2825 02:32:52,413 --> 02:32:55,483 USE OF RESOURCES AND 2826 02:32:55,483 --> 02:32:56,017 CROSS-SPECIES TRANSLATION. 2827 02:32:56,017 --> 02:33:06,527 WE HAVE SOME EXAMPLES OF THAT. 2828 02:33:12,099 --> 02:33:17,371 AND THE MECHANISM SUCH THAT EACH 2829 02:33:17,371 --> 02:33:19,340 CONSORTIUM INCLUDES RESOURCE 2830 02:33:19,340 --> 02:33:21,108 SUPPORTED UNDER THE U24 2831 02:33:21,108 --> 02:33:24,278 MECHANISM AND INDIVIDUAL 2832 02:33:24,278 --> 02:33:27,682 PROJECTS SUPPORTED BY THE UL1 2833 02:33:27,682 --> 02:33:27,949 MECHANISM. 2834 02:33:27,949 --> 02:33:31,018 THIS IS JUST A CARTOON. 2835 02:33:31,018 --> 02:33:34,655 IT'S NOT ILLUSTRATING SPECIFIC 2836 02:33:34,655 --> 02:33:45,199 PROJECTS BUT AND THIS EMPHASIZES 2837 02:33:53,341 --> 02:33:55,309 MECHANISMS AND NEURAL PATHWAY 2838 02:33:55,309 --> 02:33:56,477 MECHANISMS AND THE LARGER 2839 02:33:56,477 --> 02:33:59,614 CIRCLES ILLUSTRATE THE 2840 02:33:59,614 --> 02:34:02,984 AFFILIATED CONSORTIUM. 2841 02:34:02,984 --> 02:34:07,722 THEY COLLABORATE THROUGH JOINT 2842 02:34:07,722 --> 02:34:10,191 MEETINGS AND THE INDIVIDUAL 2843 02:34:10,191 --> 02:34:14,128 PROJECTS COLLABORATE WITHIN EACH 2844 02:34:14,128 --> 02:34:17,298 THEMATIC CONSORTIUM AS INDICATED 2845 02:34:17,298 --> 02:34:22,169 BY THE SPOKES IN THE 2846 02:34:22,169 --> 02:34:26,173 ILLUSTRATION. 2847 02:34:26,173 --> 02:34:27,942 THEY COLLABORATE ALONG THE 2848 02:34:27,942 --> 02:34:28,242 CONSORTIUMS. 2849 02:34:28,242 --> 02:34:37,318 IT'S COMMON FOR THEM TO OCCUR. 2850 02:34:37,318 --> 02:34:38,653 I'M WILLING TO ENTERTAIN 2851 02:34:38,653 --> 02:34:39,720 CONVERSATIONS AND I'M LOOKING 2852 02:34:39,720 --> 02:34:50,264 FOR AN ENDORSEMENT FROM COUNCIL. 2853 02:34:58,239 --> 02:35:01,609 >> THERE'S FOCUS AND ARE YOU 2854 02:35:01,609 --> 02:35:03,744 PLANNING TO HAVE NEW ONES OR 2855 02:35:03,744 --> 02:35:10,985 WANT TO CONTINUE TO WORK? 2856 02:35:10,985 --> 02:35:12,687 THEY'RE DIRECTLY RELEVANT TO OUR 2857 02:35:12,687 --> 02:35:14,789 INTEREST IN LOOKING AT 2858 02:35:14,789 --> 02:35:17,625 HOMEOSTATIC MECHANISMS LINKING 2859 02:35:17,625 --> 02:35:20,761 BRAIN TO THE BODY. 2860 02:35:20,761 --> 02:35:21,662 SO THERE'S CERTAINLY GOING TO BE 2861 02:35:21,662 --> 02:35:21,963 EMPHASIZED. 2862 02:35:21,963 --> 02:35:32,239 THAT'S THE PLAN. 2863 02:35:34,575 --> 02:35:37,778 >> WE HAVE ONE MORE CONCEPT? 2864 02:35:37,778 --> 02:35:40,614 >> WOULD ANYBODY ON COUNCIL LIKE 2865 02:35:40,614 --> 02:35:42,450 TO ENDORSE THE CONCEPT. 2866 02:35:42,450 --> 02:35:42,917 >> I WILL. 2867 02:35:42,917 --> 02:35:43,684 >> THANKS, MIKE. 2868 02:35:43,684 --> 02:35:44,051 >> I WILL TOO. 2869 02:35:44,051 --> 02:35:54,295 >> THANK YOU. 2870 02:36:19,687 --> 02:36:21,455 WE'VE HAD GUIDANCE ON HOW TO DO 2871 02:36:21,455 --> 02:36:24,525 NOTICES OF FUNDING 2872 02:36:24,525 --> 02:36:24,859 OPPORTUNITIES. 2873 02:36:24,859 --> 02:36:28,295 SO MARK EGLI HAS SUBMITTED 2874 02:36:28,295 --> 02:36:36,437 WHAT'S CALLED A FORECAST FOR 2875 02:36:36,437 --> 02:36:39,040 THESE, FIRST REVIEWED AND THEN 2876 02:36:39,040 --> 02:36:41,942 APPROVED AT COUNCIL BY HHS 2877 02:36:41,942 --> 02:36:46,414 BEFORE WE MOVE FORWARD THE 2878 02:36:46,414 --> 02:36:48,649 CONCEPT CLEARANCE. 2879 02:36:48,649 --> 02:36:50,484 THE ONES YOU'RE SEEING TODAY 2880 02:36:50,484 --> 02:36:52,520 HAVE BEEN CLEARED BY HEALTH AND 2881 02:36:52,520 --> 02:36:58,826 HUMAN SERVICES FOR THE RECORD. 2882 02:36:58,826 --> 02:37:00,428 >> GOOD AFTERNOON I'M IN THE 2883 02:37:00,428 --> 02:37:04,532 DIVISION OF NATAL SCIENCE AND 2884 02:37:04,532 --> 02:37:06,067 BEHAVIOR. 2885 02:37:06,067 --> 02:37:10,337 WITH DR. LIONS IN THE AUDIENCE 2886 02:37:10,337 --> 02:37:12,039 IN THE BACK. 2887 02:37:12,039 --> 02:37:17,178 I'M HERE TO PRESENT THE 2888 02:37:17,178 --> 02:37:17,545 PROPOSAL. 2889 02:37:17,545 --> 02:37:19,580 WE JUST HEARD TWO FANTASTIC 2890 02:37:19,580 --> 02:37:21,282 TALKS ON ALCOHOL EFFECTS ON THE 2891 02:37:21,282 --> 02:37:22,550 IMMUNE SYSTEM OF THE DIFFERENT 2892 02:37:22,550 --> 02:37:26,887 PARTS OF THE BRAIN AND BODY 2893 02:37:26,887 --> 02:37:29,156 WHICH STARTS TO BOND TO THE 2894 02:37:29,156 --> 02:37:31,192 CELLULAR AND SYSTEMS LEVEL AND 2895 02:37:31,192 --> 02:37:35,796 LET'S ZOOM OUT AND LOOK AT THE 2896 02:37:35,796 --> 02:37:38,532 AFFECT OF ALCOHOL ON THE BRAIN 2897 02:37:38,532 --> 02:37:42,169 AND I'LL GIVE A BIG OVERVIEW OF 2898 02:37:42,169 --> 02:37:52,613 THIS THIS IS A MULTI-SITE 2899 02:38:10,631 --> 02:38:13,868 CONSORTIUM WITH MECHANISMS 2900 02:38:13,868 --> 02:38:18,172 FUNDED THE UL 1 MECHANISM AND 2901 02:38:18,172 --> 02:38:22,543 ONE DATA ANALYSIS SITE IT'S IN 2902 02:38:22,543 --> 02:38:26,113 THE UNDERSTANDING THE FUNCTIONAL 2903 02:38:26,113 --> 02:38:28,582 CONSEQUENCES OF EARLY ONSET 2904 02:38:28,582 --> 02:38:30,084 ALCOHOL USE AND THE BINGE 2905 02:38:30,084 --> 02:38:31,051 DRINKING AND PROGRESSION TO 2906 02:38:31,051 --> 02:38:33,521 ALCOHOL USE DISORDER AND HOW THE 2907 02:38:33,521 --> 02:38:34,054 CONSEQUENCES MANIFEST IN 2908 02:38:34,054 --> 02:38:44,231 ADULTHOOD. 2909 02:38:45,466 --> 02:38:45,866 AND CAN THEY CREATE 2910 02:38:45,866 --> 02:38:50,171 REPRESENTATIVE SAMPLE. 2911 02:38:50,171 --> 02:38:53,974 THE PRIMARY FOCUS IS TO EXAMINE 2912 02:38:53,974 --> 02:38:56,443 HOW ALCOHOL EXPOSURE AFFECTS 2913 02:38:56,443 --> 02:38:57,945 ADULT BRAIN STRUCTURE, FUNCTION 2914 02:38:57,945 --> 02:39:02,183 AND COGNITIVE AND MENTAL HEALTH 2915 02:39:02,183 --> 02:39:03,317 OUTCOMES. 2916 02:39:03,317 --> 02:39:06,053 TO ACHIEVE THIS THEY HAVE 2917 02:39:06,053 --> 02:39:07,221 LONGITUDINAL DESIGN AND THEY 2918 02:39:07,221 --> 02:39:13,627 FOLLOWED THE COHORT OF 831 2919 02:39:13,627 --> 02:39:16,130 PERSONS 12 TO 21 YEARS AS THEY 2920 02:39:16,130 --> 02:39:19,333 TRANSITION TO ADULTHOOD AND WE 2921 02:39:19,333 --> 02:39:21,235 HAVE A DATA SPANNING 12 TO 32 2922 02:39:21,235 --> 02:39:31,212 YEARS WHICH IS VERY IMPRESSIVE. 2923 02:39:31,212 --> 02:39:34,215 IT HAS AN ASSESSMENT APPROACH 2924 02:39:34,215 --> 02:39:44,725 AND MEASURES AND ASSESSMENT 2925 02:39:44,725 --> 02:39:47,061 APPROACHES INCLUDING ANALYSIS OF 2926 02:39:47,061 --> 02:39:52,233 PHYSICAL ACTIVITIES AND RHYTHMS 2927 02:39:52,233 --> 02:39:55,603 AND COMPONENTS OF DEVELOPMENT IN 2928 02:39:55,603 --> 02:39:58,172 ADDITION TO ALCOHOL USE. 2929 02:39:58,172 --> 02:40:03,077 IT ALSO EMPLOYEES OBJECTIVE 2930 02:40:03,077 --> 02:40:07,147 ASSESSMENT METHODS WITH SLEEP 2931 02:40:07,147 --> 02:40:07,615 TRACKING. 2932 02:40:07,615 --> 02:40:10,551 SINCE THE START OF 2022 FUNDING 2933 02:40:10,551 --> 02:40:14,054 CYCLE IT HAS MADE SIGNIFICANT 2934 02:40:14,054 --> 02:40:20,761 PROGRESS SOME ARE HIGHLIGHTED 2935 02:40:20,761 --> 02:40:29,203 HERE AND 77 PEER-LE -- 2936 02:40:29,203 --> 02:40:31,972 PEER-REVIEWED PAPERS AND IT HAS 2937 02:40:31,972 --> 02:40:37,111 MADE DATA ACCESSIBLE WHICH HAS 2938 02:40:37,111 --> 02:40:40,147 ENABLED SECONDARY ANALYSIS BY 2939 02:40:40,147 --> 02:40:43,851 OTHER RESEARCHERS. 2940 02:40:43,851 --> 02:40:46,553 THERE'S STANDARDIZED DATA 2941 02:40:46,553 --> 02:40:49,356 HARMONIZATION AND PROVIDED EARLY 2942 02:40:49,356 --> 02:40:49,857 CAREER INVESTIGATORS. 2943 02:40:49,857 --> 02:40:52,593 AND IT ALSO REACHED THE PUBLIC 2944 02:40:52,593 --> 02:40:53,827 THROUGH VARIOUS NATIONAL MEDIA 2945 02:40:53,827 --> 02:40:55,929 OUTLETS WHICH CONTRIBUTED TO 2946 02:40:55,929 --> 02:41:06,473 PUBLIC AWARENESS AND EDUCATION. 2947 02:41:10,244 --> 02:41:17,418 IT'S TIMELY AND THEY ARE 2948 02:41:17,418 --> 02:41:18,319 IMPACTED BY THREE STAGES. 2949 02:41:18,319 --> 02:41:23,057 THE PRE-DRINKING ONSET BY AGE 12 2950 02:41:23,057 --> 02:41:23,590 OR LATER. 2951 02:41:23,590 --> 02:41:26,160 SECOND TRANSITION TO THE YOUNG 2952 02:41:26,160 --> 02:41:28,562 ADULTHOOD WHICH IS A CRITICAL 2953 02:41:28,562 --> 02:41:34,168 PERIOD FOR BINGE DRINKING AND 2954 02:41:34,168 --> 02:41:38,172 THE MEASURING OUT PHASE. 2955 02:41:38,172 --> 02:41:39,740 IT CREATES A RARE BASELINE OF 2956 02:41:39,740 --> 02:41:43,444 DATA FOR UNDERSTANDING ADULT 2957 02:41:43,444 --> 02:41:53,954 DRINKING PATTERNS CAN LOOK AT 2958 02:41:56,857 --> 02:41:59,126 DRINKING RATES AND THE 2959 02:41:59,126 --> 02:42:00,961 BEHAVIORAL DATA ALLOWS 2960 02:42:00,961 --> 02:42:02,196 INVESTIGATORS TO DEVELOP AND 2961 02:42:02,196 --> 02:42:03,764 VALIDATE PREDICTIVE MODELS OF 2962 02:42:03,764 --> 02:42:06,066 ADULT DRINKING PATTERNS. 2963 02:42:06,066 --> 02:42:07,968 THIS IS CRUCIAL FOR IDENTIFYING 2964 02:42:07,968 --> 02:42:10,170 EARLY RISK FACTORS AND INFORMING 2965 02:42:10,170 --> 02:42:17,845 INTERVENTION STRATEGIES. 2966 02:42:17,845 --> 02:42:18,545 THAT CONCLUDES MY PRESENTATION 2967 02:42:18,545 --> 02:42:20,214 AND I LOOK FORWARD TO YOUR 2968 02:42:20,214 --> 02:42:22,082 QUESTIONS AND ENDORSEMENT. 2969 02:42:22,082 --> 02:42:22,416 >> THANK YOU. 2970 02:42:22,416 --> 02:42:29,690 THAT'S GREAT. 2971 02:42:29,690 --> 02:42:31,525 SO COUNCIL MEMBERS, ANY 2972 02:42:31,525 --> 02:42:32,593 QUESTIONS, COMMENTS OR 2973 02:42:32,593 --> 02:42:34,194 ENDORSEMENTS OF THE CONCEPT 2974 02:42:34,194 --> 02:42:38,165 CLEARANCE? 2975 02:42:38,165 --> 02:42:38,766 I'LL ENDORSE IT. 2976 02:42:38,766 --> 02:42:40,634 >> DITTO. 2977 02:42:40,634 --> 02:42:41,402 >> THANK YOU. 2978 02:42:41,402 --> 02:42:43,537 >> THANK YOU, ALL VERY MUCH. 2979 02:42:43,537 --> 02:42:46,206 ANY QUESTIONS? 2980 02:42:46,206 --> 02:42:49,343 DAVID? 2981 02:42:49,343 --> 02:42:51,979 >> I'M CHIMING IN TO ENDORSE 2982 02:42:51,979 --> 02:42:54,181 IT'S BEEN A VERY PRODUCTIVE 2983 02:42:54,181 --> 02:42:54,815 PROJECT. 2984 02:42:54,815 --> 02:42:56,884 >> OKAY. 2985 02:42:56,884 --> 02:42:58,018 SO THANK YOU. 2986 02:42:58,018 --> 02:43:01,088 I THINK WE'RE FINISHED WITH 2987 02:43:01,088 --> 02:43:01,889 COUNCIL. 2988 02:43:01,889 --> 02:43:04,725 WE DESIGNATED SOME TIME FOR 2989 02:43:04,725 --> 02:43:09,563 COUNCIL DISCUSSION I'M GOING TO 2990 02:43:09,563 --> 02:43:12,266 OPEN IT UP FOR ANY QUESTIONS YOU 2991 02:43:12,266 --> 02:43:15,836 HAVE FOR ME, FOR ANYONE OF OUR 2992 02:43:15,836 --> 02:43:18,472 STAFF THAT ARE HERE WE CAN TAKE 2993 02:43:18,472 --> 02:43:22,176 01 MINUTES FOR THIS. 2994 02:43:22,176 --> 02:43:25,979 -- 10 MINUTES FOR THIS. 2995 02:43:25,979 --> 02:43:30,851 FOR THOSE GOING TO APA, FRANCES, 2996 02:43:30,851 --> 02:43:35,656 I'LL SEE YOU AT THE ADDICTION 2997 02:43:35,656 --> 02:43:39,960 PSYCHIATRY GROUP. 2998 02:43:39,960 --> 02:43:41,228 ANYWAY, I'LL BE THERE. 2999 02:43:41,228 --> 02:43:43,931 ARE THERE QUESTIONS FROM ANYONE 3000 02:43:43,931 --> 02:43:45,899 ON COUNCIL? 3001 02:43:45,899 --> 02:43:46,200 PLEASE? 3002 02:43:46,200 --> 02:43:50,170 >> I GUESS I'D LIKE TO ASK IF 3003 02:43:50,170 --> 02:43:55,042 ANY OF THE RECENT CHANGES WITH 3004 02:43:55,042 --> 02:44:00,047 HHS DOES HHS SEE THE MISSION OF 3005 02:44:00,047 --> 02:44:01,348 NIAAA CHANGING IN A FUNDAMENTAL 3006 02:44:01,348 --> 02:44:05,219 WAY AND WHAT THE EMPHASIZES ARE 3007 02:44:05,219 --> 02:44:09,122 GOING TO BE MOVING FORWARD. 3008 02:44:09,122 --> 02:44:11,925 >> AS OF NOW MY DISCUSSIONS WITH 3009 02:44:11,925 --> 02:44:13,827 BHATTACHARYA AND I OUTLINED OUR 3010 02:44:13,827 --> 02:44:17,631 MISSION TO HIM AND HAD A 3011 02:44:17,631 --> 02:44:21,068 ONE-ON-ONE WITH THE DIRECTOR OF 3012 02:44:21,068 --> 02:44:27,574 NIH AND I THINK I'VE ASKED HIM 3013 02:44:27,574 --> 02:44:28,642 REPEATEDLY ABOUT WHAT I CAN 3014 02:44:28,642 --> 02:44:30,978 PRESENT AT MEETINGS LIKE COUNCIL 3015 02:44:30,978 --> 02:44:39,720 AND THEN RSA AND HE EXPLICITLY 3016 02:44:39,720 --> 02:44:41,588 STATED AS LONG AS WE'RE TALK OUR 3017 02:44:41,588 --> 02:44:42,856 SPECIFIC AIMS AND WHERE WE'RE 3018 02:44:42,856 --> 02:44:46,460 GOING WE SHOULD SPEAK TO OUR 3019 02:44:46,460 --> 02:44:46,693 MISSION. 3020 02:44:46,693 --> 02:44:49,363 I HAVEN'T SEEN ANY EVIDENCE OF 3021 02:44:49,363 --> 02:44:52,232 CHANGING DIRECTION OF OUR 3022 02:44:52,232 --> 02:44:53,233 MISSION IN THAT REGARD. 3023 02:44:53,233 --> 02:44:56,336 SO OUR MISSION STATEMENT REMAINS 3024 02:44:56,336 --> 02:44:57,704 THE STATEMENT BASICALLY TO 3025 02:44:57,704 --> 02:44:59,172 UNDERSTAND THE AFFECTS OF 3026 02:44:59,172 --> 02:45:02,342 ALCOHOL MISUSE AND SPECIFICALLY 3027 02:45:02,342 --> 02:45:06,346 IN THE DOMAINS OF ETIOLOGY AND 3028 02:45:06,346 --> 02:45:10,183 PREVENTION AND TREATMENT AND 3029 02:45:10,183 --> 02:45:14,154 ORGAN DAMAGE. 3030 02:45:14,154 --> 02:45:16,156 I ALWAYS LEAVE SOMETHING OUT, 3031 02:45:16,156 --> 02:45:16,356 TRISH. 3032 02:45:16,356 --> 02:45:16,990 WHAT IS IT? 3033 02:45:16,990 --> 02:45:18,926 >> DIAGNOSIS AND RECOVERY. 3034 02:45:18,926 --> 02:45:23,997 >> THERE YOU GO, THANK YOU. 3035 02:45:23,997 --> 02:45:26,567 >> IT'S A LONG LIST BUT NO, THE 3036 02:45:26,567 --> 02:45:28,635 ANSWER IS OUR MISSION REMAINS 3037 02:45:28,635 --> 02:45:34,174 THE SAME. 3038 02:45:34,174 --> 02:45:36,543 >> THANK YOU. 3039 02:45:36,543 --> 02:45:39,613 >> THANK YOU FOR THAT. 3040 02:45:39,613 --> 02:45:40,180 WE'VE BEEN WONDERING ABOUT 3041 02:45:40,180 --> 02:45:50,490 THINGS LIKE THAT. 3042 02:45:54,161 --> 02:45:57,464 >> WELL, WE HAVE A LOT OF THINGS 3043 02:45:57,464 --> 02:46:00,500 THAT REMAIN TO BE WORKED OUT. 3044 02:46:00,500 --> 02:46:09,042 THERE IS A LOT OF EFFORTS GOING 3045 02:46:09,042 --> 02:46:12,179 IN THAT REGARD BUT CAN'T REALLY 3046 02:46:12,179 --> 02:46:14,815 COMMENT ON ANYTHING OTHER THAN 3047 02:46:14,815 --> 02:46:16,383 SOME OF THE CHANGES YOU HEARD 3048 02:46:16,383 --> 02:46:16,717 OF. 3049 02:46:16,717 --> 02:46:24,858 PEER REVIEW WILL NOW BE AT CSR. 3050 02:46:24,858 --> 02:46:26,693 WE DON'T KNOW WHAT THE BUDGET 3051 02:46:26,693 --> 02:46:28,528 WILL BE LIKE BECAUSE IT'S ONLY 3052 02:46:28,528 --> 02:46:29,329 THE BEGINNING OF THE PROCESS SO 3053 02:46:29,329 --> 02:46:37,371 CONGRESS WON'T BE WEIGHING IN 3054 02:46:37,371 --> 02:46:39,406 AND THIS IS SOMETHING THAT 3055 02:46:39,406 --> 02:46:40,374 OCCURS EVERY YEAR NOT JUST 3056 02:46:40,374 --> 02:46:40,841 TRANSITION YEARS. 3057 02:46:40,841 --> 02:46:42,743 WE ARE ACCEPTING APPLICATIONS 3058 02:46:42,743 --> 02:46:44,778 FOR ACTIVE FUNDING 3059 02:46:44,778 --> 02:46:45,112 OPPORTUNITIES. 3060 02:46:45,112 --> 02:46:46,213 YOU ALREADY HEARD ABOUT TWO 3061 02:46:46,213 --> 02:46:46,747 CONCEPT CLEARANCES WE PUT 3062 02:46:46,747 --> 02:46:56,890 FORWARD. 3063 02:46:58,225 --> 02:47:00,360 SOME HAVE BEEN ALIGNED WITH 3064 02:47:00,360 --> 02:47:03,497 PRIORITIES AND RE-READ FOR 3065 02:47:03,497 --> 02:47:04,131 CHANGING PRIOR TO SUBMISSION 3066 02:47:04,131 --> 02:47:05,499 RAND ADJUST FOUR APPLICATIONS 3067 02:47:05,499 --> 02:47:08,702 ACCORDINGLY AND YOU CAN PASS THE 3068 02:47:08,702 --> 02:47:10,170 WORD ON TO COLLEAGUES IN THIS 3069 02:47:10,170 --> 02:47:20,313 REGARD. 3070 02:47:22,182 --> 02:47:23,784 IT'S TO WHAT HAS CHANGED AND 3071 02:47:23,784 --> 02:47:26,820 WHAT'S ALREADY HAPPENING. 3072 02:47:26,820 --> 02:47:34,461 THE PAUSE WAS LONGER THAN NORMAL 3073 02:47:34,461 --> 02:47:37,030 BUT GO THROUGH THESE TRANSITIONS 3074 02:47:37,030 --> 02:47:39,032 EVERY FOUR YEARS AND BACK UP AND 3075 02:47:39,032 --> 02:47:40,834 RUNNING WITH GRANTS AND AS YOU 3076 02:47:40,834 --> 02:47:43,937 KNOW WE HAD CLOSED SESSION TODAY 3077 02:47:43,937 --> 02:47:46,206 AND GRANTS ARE GOING OUT AND 3078 02:47:46,206 --> 02:47:48,575 HAVE A PAY PLAN END OF THIS 3079 02:47:48,575 --> 02:47:50,177 WEEK. 3080 02:47:50,177 --> 02:47:58,051 WE'RE MOVING FORWARD. 3081 02:47:58,051 --> 02:48:00,687 >> I WONDER IF COUNCIL FUNCTIONS 3082 02:48:00,687 --> 02:48:01,555 WILL REMAIN THE SAME? 3083 02:48:01,555 --> 02:48:04,725 >> WE'RE WAITING ON GUIDANCE FOR 3084 02:48:04,725 --> 02:48:11,264 THAT, MICHAEL. 3085 02:48:11,264 --> 02:48:13,033 WE DID LOSE A FEW COUNCIL 3086 02:48:13,033 --> 02:48:15,235 MEMBERS AND WAITING ON SOME 3087 02:48:15,235 --> 02:48:15,869 SLATES TO BE APPROVED SO THERE'S 3088 02:48:15,869 --> 02:48:22,175 A BACKLOG TO 2023. 3089 02:48:22,175 --> 02:48:22,943 WE'RE JUST WAITING FOR THAT 3090 02:48:22,943 --> 02:48:28,381 >> THANK YOU. 3091 02:48:28,381 --> 02:48:31,551 ANY OTHER QUESTIONS? 3092 02:48:31,551 --> 02:48:31,752 DAYNE? 3093 02:48:31,752 --> 02:48:32,819 >> YEAH, THANKS. 3094 02:48:32,819 --> 02:48:34,688 I WANT TO ASK ANOTHER QUESTION 3095 02:48:34,688 --> 02:48:35,689 YOU DON'T KNOW THE ANSWER TO I'M 3096 02:48:35,689 --> 02:48:38,425 SURE BUT I'M GOING TO TRY 3097 02:48:38,425 --> 02:48:38,658 ANYWAY. 3098 02:48:38,658 --> 02:48:41,094 ONE OF THE PLACES WE ALWAYS GO 3099 02:48:41,094 --> 02:48:42,896 TO FIND NEW INFORMATION OR THE 3100 02:48:42,896 --> 02:48:47,434 NIH WEBSITES AND OF COURSE 3101 02:48:47,434 --> 02:48:50,036 THEY'RE NOT CURRENTLY UPDATED. 3102 02:48:50,036 --> 02:48:52,739 IS THERE ANY ANY INDICATION OF 3103 02:48:52,739 --> 02:49:00,280 WHEN INFORMATION COULD BE ADDED 3104 02:49:00,280 --> 02:49:02,115 WHERE THE LABS ARE TRYING TO 3105 02:49:02,115 --> 02:49:04,017 COLLECT INFORMATION AS THE GO-TO 3106 02:49:04,017 --> 02:49:04,551 SOURCE. 3107 02:49:04,551 --> 02:49:05,652 WONDERING IF THERE'S ANY HINT ON 3108 02:49:05,652 --> 02:49:06,353 WHEN SOME OF THAT MIGHT BE 3109 02:49:06,353 --> 02:49:11,625 UPDATED. 3110 02:49:11,625 --> 02:49:14,194 >> WE'RE WAITING ON GUIDANCE 3111 02:49:14,194 --> 02:49:16,029 FROM THAT. 3112 02:49:16,029 --> 02:49:25,038 DAYNE, WE SERVE ALSO THE PUBLIC. 3113 02:49:25,038 --> 02:49:26,173 WE HAVE AN EMPHASIS TO CONTINUE 3114 02:49:26,173 --> 02:49:31,845 IN SOME FASHION. 3115 02:49:31,845 --> 02:49:33,446 WE'RE WAITING TO SEE WHAT 3116 02:49:33,446 --> 02:49:34,614 EVOLVES BUT THE OTHER INSTITUTES 3117 02:49:34,614 --> 02:49:36,550 ARE IN THE SAME SITUATION. 3118 02:49:36,550 --> 02:49:38,652 THEY HAVE CLIENTS WHO ARE ALSO 3119 02:49:38,652 --> 02:49:42,189 WAITING FOR UPDATES ON THE 3120 02:49:42,189 --> 02:49:47,961 LATEST TRANSLATABLE OBSERVATIONS 3121 02:49:47,961 --> 02:49:50,564 IF IT COULD BE THE EYE OR THE 3122 02:49:50,564 --> 02:49:56,770 EAR OR MUSCLES. 3123 02:49:56,770 --> 02:49:58,171 ETCETERA, BY THE WAY, THAT WAS A 3124 02:49:58,171 --> 02:50:08,481 REALLY GOOD TALK. 3125 02:50:18,191 --> 02:50:23,163 I KNOW YOU WERE BEING WATCHED 3126 02:50:23,163 --> 02:50:24,698 LIKE AN EGRIT SO MAY BE 3127 02:50:24,698 --> 02:50:25,432 APPROACHED THERE. 3128 02:50:25,432 --> 02:50:26,533 >> THERE WAS CROSS TALK THERE. 3129 02:50:26,533 --> 02:50:28,268 >> SO TOMORROW WE HAVE THE 3130 02:50:28,268 --> 02:50:30,170 COLLABORATIVE RESEARCH ON 3131 02:50:30,170 --> 02:50:40,480 ADDICTIONS AT NIH. 3132 02:50:45,418 --> 02:50:48,255 IT'S PUBLIC AND OPEN AND LEE 3133 02:50:48,255 --> 02:50:50,190 HOOD DOES TEM KNOLL WORK IN 3134 02:50:50,190 --> 02:50:53,593 SYSTEMS BIOLOGY AS THE SPEAKER 3135 02:50:53,593 --> 02:50:55,829 THERE WHICH SHOULD DOVETAIL 3136 02:50:55,829 --> 02:50:57,230 REALLY WELL WITH WHAT YOU HEARD 3137 02:50:57,230 --> 02:50:58,164 TODAY. 3138 02:50:58,164 --> 02:51:00,433 ANYONE WHO WANTS TO CONTINUE AND 3139 02:51:00,433 --> 02:51:05,405 SEE A PERSON WHO ADDRESSES IT AT 3140 02:51:05,405 --> 02:51:09,042 MULTIPLE LEVELS AND HAS DONE 3141 02:51:09,042 --> 02:51:12,812 MOST OF HIS CAREER, IT'S ANOTHER 3142 02:51:12,812 --> 02:51:14,114 WAY OF FINDING ANOTHER VIEW 3143 02:51:14,114 --> 02:51:15,448 POINT FROM 30,000 FEET OF HOW 3144 02:51:15,448 --> 02:51:16,616 YOU INTEGRATE INFORMATION AND 3145 02:51:16,616 --> 02:51:17,017 SCIENCE. 3146 02:51:17,017 --> 02:51:19,586 I'M VERY MUCH LOOKING FORWARD TO 3147 02:51:19,586 --> 02:51:22,856 THAT TALK AS WELL MYSELF. 3148 02:51:22,856 --> 02:51:25,492 SO IT'S ONLINE. 3149 02:51:25,492 --> 02:51:27,794 HOW DO THEY ACCESS AND FINE IT? 3150 02:51:27,794 --> 02:51:38,171 IS IT ON OUR WEBSITE? 3151 02:51:40,640 --> 02:51:41,708 IT SHOULD BE ON THE NIH VIDEO 3152 02:51:41,708 --> 02:51:51,952 LINK WEBSITE. 3153 02:51:54,187 --> 02:51:56,222 WE HIGHLIGHT RECOMMEND IT AND 3154 02:51:56,222 --> 02:51:58,158 WE'LL BE WITH OUR BRETHREN AT 3155 02:51:58,158 --> 02:51:58,758 NIDA TOMORROW. 3156 02:51:58,758 --> 02:52:02,395 AND TOBACCO. 3157 02:52:02,395 --> 02:52:05,832 I ALWAYS LEAVE OUT NCI. 3158 02:52:05,832 --> 02:52:10,070 I LEAVE OUT TOBACCO -- WHAT DO 3159 02:52:10,070 --> 02:52:14,407 THEY CALL THEMSELVES? 3160 02:52:14,407 --> 02:52:16,876 IT'S A BIG OUTFIT BUT THEY HAVE 3161 02:52:16,876 --> 02:52:18,178 A NAME. 3162 02:52:18,178 --> 02:52:27,053 I FORGET IT. 3163 02:52:27,053 --> 02:52:29,789 IT'S THE TOBACCO SECTION OF THE 3164 02:52:29,789 --> 02:52:30,223 NATIONAL INSTITUTE. 3165 02:52:30,223 --> 02:52:38,164 ANY OTHER THOUGHTS OR QUESTION 3166 02:52:38,164 --> 02:52:41,201 OR COMMENTS? 3167 02:52:41,201 --> 02:52:43,570 >> TWO QUESTIONS. 3168 02:52:43,570 --> 02:52:46,072 FOR BOTH THE SPEAKERS, HAVE YOU 3169 02:52:46,072 --> 02:52:47,974 TRIED TO DO THIS SYSTEM APPROACH 3170 02:52:47,974 --> 02:52:50,477 AT TWO DIFFERENT TIME POINTS 3171 02:52:50,477 --> 02:52:52,879 JUST TO -- BECAUSE I KNOW THE 3172 02:52:52,879 --> 02:53:02,155 IMMUNE SYSTEM IMPACT REGULATION. 3173 02:53:02,155 --> 02:53:04,858 IT'S A HUGE DIFFERENCE IF YOU DO 3174 02:53:04,858 --> 02:53:12,465 THE MORNING OR EVENING AND CAN 3175 02:53:12,465 --> 02:53:15,035 YOU REPEAT WHAT YOU SAID ABOUT 3176 02:53:15,035 --> 02:53:15,769 THE BRAIN. 3177 02:53:15,769 --> 02:53:17,470 >> GO AHEAD BECAUSE IT'S FRESH 3178 02:53:17,470 --> 02:53:18,905 IN YOUR MIND AND YOU MAY HAVE TO 3179 02:53:18,905 --> 02:53:22,509 REPEAT THE OTHER QUESTION FOR 3180 02:53:22,509 --> 02:53:23,376 DAYNE. 3181 02:53:23,376 --> 02:53:25,979 >> FOR THE TIME PERIOD, IT WAS 3182 02:53:25,979 --> 02:53:27,380 ACTUALLY YOU WERE INTERESTED IN 3183 02:53:27,380 --> 02:53:29,215 THE TIME COURSE IN THE MOUSE 3184 02:53:29,215 --> 02:53:30,784 STUDY BECAUSE ONE SNAPSHOT MAY 3185 02:53:30,784 --> 02:53:32,952 NOT BE ENOUGH ESPECIALLY IF 3186 02:53:32,952 --> 02:53:33,553 YOU'RE COMPARING IT THE LIVER 3187 02:53:33,553 --> 02:53:37,857 AND LUNG. 3188 02:53:37,857 --> 02:53:40,326 WE NEED TO INFORMATION THIS 3189 02:53:40,326 --> 02:53:41,861 INFLAMMATORY OR PROGRESSIVE 3190 02:53:41,861 --> 02:53:42,095 DISEASE. 3191 02:53:42,095 --> 02:53:46,900 IN THE HUMAN DATA WE JUST GET A 3192 02:53:46,900 --> 02:53:54,174 SNAPSHOT BUT THE DATA SHOWS AND 3193 02:53:54,174 --> 02:53:58,878 FOR THE SECOND QUESTION FOR 3194 02:53:58,878 --> 02:53:59,746 EVERYBODY APPRECIATED WHAT WAS 3195 02:53:59,746 --> 02:54:01,514 IN THE BRAIN AND I LIKE TO MAKE 3196 02:54:01,514 --> 02:54:05,685 THE ANALOGY BECAUSE OUR BODY 3197 02:54:05,685 --> 02:54:07,287 OPERATES THE SAME PRINCIPLE TO 3198 02:54:07,287 --> 02:54:08,988 CONSERVE ENERGY. 3199 02:54:08,988 --> 02:54:11,891 WE KNOW IN THE BRAIN THERE'S 3200 02:54:11,891 --> 02:54:17,997 CASES AND THERE'S NEURO 3201 02:54:17,997 --> 02:54:21,434 TRANSMISSION AND IT MAY WORK IN 3202 02:54:21,434 --> 02:54:23,369 THE SAME PRINCIPLE IN THE IMMUNE 3203 02:54:23,369 --> 02:54:25,305 SYSTEM AND THAT IS IMMEDIATELY 3204 02:54:25,305 --> 02:54:26,673 RELEASED AND THAT IS MADE IN THE 3205 02:54:26,673 --> 02:54:26,940 BEGINNING. 3206 02:54:26,940 --> 02:54:29,175 IT CAN BE NEEDED TO PRIME THE 3207 02:54:29,175 --> 02:54:31,010 IMMUNE SYSTEM. 3208 02:54:31,010 --> 02:54:32,479 THEN PROLONG ACTIVATION IS THE 3209 02:54:32,479 --> 02:54:33,012 PROBLEM. 3210 02:54:33,012 --> 02:54:34,814 I THINK THAT IS WHAT WE'RE 3211 02:54:34,814 --> 02:54:36,382 OBSERVING AND THE TIME COURSE 3212 02:54:36,382 --> 02:54:39,986 STUDY ONCE WE CONDUCT IT THAT IS 3213 02:54:39,986 --> 02:54:41,788 THE OBSERVATION WE FIND. 3214 02:54:41,788 --> 02:54:44,257 >> AND DAYNE, DID YOU WANT TO 3215 02:54:44,257 --> 02:54:48,161 ANSWER THE TIME COURSE PIECE? 3216 02:54:48,161 --> 02:54:48,595 >> I'M SURE. 3217 02:54:52,866 --> 02:54:54,467 SO HE WE BRIDGED THE TIME SERIES 3218 02:54:54,467 --> 02:54:58,171 QUESTION AND ANIMAL MODELS A 3219 02:54:58,171 --> 02:54:58,738 COUPLE TIMES. 3220 02:54:58,738 --> 02:55:02,075 THIS HAS BEEN DONE IN ANIMALS 3221 02:55:02,075 --> 02:55:04,244 SUBJECTED SO THE CHRONIC 3222 02:55:04,244 --> 02:55:04,878 INTERMITTENT ALCOHOL DEPENDENCE 3223 02:55:04,878 --> 02:55:07,947 INDUCTION MODEL. 3224 02:55:07,947 --> 02:55:14,854 SO IF WE LOOK AT THE TIME FROM 3225 02:55:14,854 --> 02:55:16,122 INTOXICATION THROUGH VARIOUS 3226 02:55:16,122 --> 02:55:17,857 LEVELS OF ABSTINENCE FROM TWO 3227 02:55:17,857 --> 02:55:20,894 DAYS TO A WEEK OR WHATEVER, WE 3228 02:55:20,894 --> 02:55:22,829 HAVE ONLY DONE THAT WITH BULK 3229 02:55:22,829 --> 02:55:28,535 SEQUENCING NOT SINGLE CELL. 3230 02:55:28,535 --> 02:55:32,005 I CAN TELL YOU IT BECOMES TRICKY 3231 02:55:32,005 --> 02:55:35,842 TO TEASE THINGS AAPART BECAUSE 3232 02:55:35,842 --> 02:55:38,444 YOU DO LOSE SOME OF THE 3233 02:55:38,444 --> 02:55:41,881 DYSREGULATION YOU SEE DURING 3234 02:55:41,881 --> 02:55:43,850 INTOXICATION HOWEVER THE 3235 02:55:43,850 --> 02:55:46,186 DIRECTIONAL CHANGES OF 3236 02:55:46,186 --> 02:55:53,226 INDIVIDUAL GENES REALLY ARE VERY 3237 02:55:53,226 --> 02:55:53,960 PATTERN SPECIFIC. 3238 02:55:53,960 --> 02:55:55,395 THEY MAY BE INITIALLY AND THEN 3239 02:55:55,395 --> 02:55:57,797 THEY GO VERY NEGATIVE AT THE END 3240 02:55:57,797 --> 02:56:00,767 OR MAY START OUT UNCHANGED AND 3241 02:56:00,767 --> 02:56:05,505 THEN OVER TIME THEY BECOME VERY 3242 02:56:05,505 --> 02:56:06,172 ACTIVATED. 3243 02:56:06,172 --> 02:56:11,844 AND WE'VE USED APPROACHES TO 3244 02:56:11,844 --> 02:56:12,979 APPROACH THAT WAY. 3245 02:56:12,979 --> 02:56:14,914 IF WE CAN DO THAT WITH A SINGLE 3246 02:56:14,914 --> 02:56:18,184 CELL WORK IT WOULD BE 3247 02:56:18,184 --> 02:56:22,889 INFORMATIVE I THINK WITH THE 3248 02:56:22,889 --> 02:56:23,489 PLATFORMS BECOMING AVAILABLE 3249 02:56:23,489 --> 02:56:26,159 MAYBE WE'LL BE ABLE TO DO THAT 3250 02:56:26,159 --> 02:56:27,894 BUT RIGHT NOW WE JUST CAN'T BUT 3251 02:56:27,894 --> 02:56:30,330 WE'VE PUBLISHED A COUPLE PAPERS 3252 02:56:30,330 --> 02:56:31,898 WITH THE TIME COURSE AND BULK 3253 02:56:31,898 --> 02:56:38,171 SEQUENCING IN ANIMALS. 3254 02:56:38,171 --> 02:56:39,439 >> OKAY. 3255 02:56:39,439 --> 02:56:40,907 ANYMORE COMMENTS OR QUESTIONS 3256 02:56:40,907 --> 02:56:42,141 REAL QUICKLY? 3257 02:56:42,141 --> 02:56:52,085 WE CAN TAKE MAYBE ONE MORE. 3258 02:56:52,085 --> 02:56:53,886 >> I HAVE AN ANOTHER QUESTION 3259 02:56:53,886 --> 02:56:55,488 FOR DR. MAYFIELD. 3260 02:56:55,488 --> 02:56:58,558 I ENJOYED YOUR PRESENTATION. 3261 02:56:58,558 --> 02:57:03,029 MY QUESTION IS YOU'RE SHOWING 3262 02:57:03,029 --> 02:57:05,698 THE ALCOHOL DRINKING DURATION 3263 02:57:05,698 --> 02:57:06,733 AND THAT WAS AS FAR AS I SEE 3264 02:57:06,733 --> 02:57:10,169 THAT WAS THE ONLY ONE THAT WAS 3265 02:57:10,169 --> 02:57:11,537 NOT CORRELATED WITH THE ALCOHOL 3266 02:57:11,537 --> 02:57:12,472 AND DRINKING DURATION. 3267 02:57:12,472 --> 02:57:14,574 DO YOU THINK IT'S REALLY 3268 02:57:14,574 --> 02:57:16,809 SENSITIVE THAT ANY KIND OF 3269 02:57:16,809 --> 02:57:17,644 ALCOHOL DURATION CAN BE ENOUGH 3270 02:57:17,644 --> 02:57:22,181 TO ACTIVATE THE SYSTEM? 3271 02:57:22,181 --> 02:57:26,185 AND ANOTHER FOLLOW-UP POINT IS 3272 02:57:26,185 --> 02:57:28,388 THE PHENOTYPE HAS A MACROPHAGE 3273 02:57:28,388 --> 02:57:30,690 PHENOTYPE THAT MADE ME THINK 3274 02:57:30,690 --> 02:57:33,760 MAYBE THERE ARE SHARED 3275 02:57:33,760 --> 02:57:36,429 MECHANISMS WITH THE OTHER 3276 02:57:36,429 --> 02:57:38,131 NEURODEGENERATIVE DISEASE. 3277 02:57:38,131 --> 02:57:41,000 ARE YOU PLANNING TO CHECK DATA 3278 02:57:41,000 --> 02:57:44,570 FROM OTHER DISEASE TO SEE THE 3279 02:57:44,570 --> 02:57:45,405 SIMILAR SIGNATURES? 3280 02:57:45,405 --> 02:57:46,839 YOU HAVE WONDERFUL SIGNATURES 3281 02:57:46,839 --> 02:57:47,940 FROM DIFFERENT CLUSTERS. 3282 02:57:47,940 --> 02:57:51,544 >> I THINK WE'RE TALKING ABOUT 3283 02:57:51,544 --> 02:57:54,180 THE MODULE RELATIONSHIP TABLE 3284 02:57:54,180 --> 02:58:04,691 SHOWING THE ASSUMPTION OF THE 3285 02:58:18,237 --> 02:58:19,138 PHENOTYPES AND THE 3286 02:58:19,138 --> 02:58:20,106 CLASSIFICATION MAKES IT HARD TO 3287 02:58:20,106 --> 02:58:21,708 DO BECAUSE SOME OF THE 3288 02:58:21,708 --> 02:58:25,445 INDIVIDUALS HAVE VARYING 3289 02:58:25,445 --> 02:58:29,315 ABSTINENCE PERIODS THAT REALLY 3290 02:58:29,315 --> 02:58:31,417 HURT THE OVER ALL CORRELATION. 3291 02:58:31,417 --> 02:58:33,753 IT'S A LITTLE BIT MUDDY TO DO 3292 02:58:33,753 --> 02:58:33,953 THAT. 3293 02:58:33,953 --> 02:58:37,156 THAT'S WHY I BROKE IT DOWN AFTER 3294 02:58:37,156 --> 02:58:40,660 THAT PARTICULAR SLIDE INTO 3295 02:58:40,660 --> 02:58:51,070 HERE'S A SPECIFIC STATE 3296 02:58:52,271 --> 02:58:54,273 STRUCTURE AND THAT MAY BE MORE 3297 02:58:54,273 --> 02:58:55,575 INFORMATIVE AND IN ANIMAL MODELS 3298 02:58:55,575 --> 02:58:59,011 IT'S A DIFFERENT STORY. 3299 02:58:59,011 --> 02:59:01,848 IT'S VERY CLEAR WITH THE 3300 02:59:01,848 --> 02:59:03,516 CORRELATIONS IN TERMS OF THE 3301 02:59:03,516 --> 02:59:06,185 CELL TYPE OR SIGNATURE WITH HOW 3302 02:59:06,185 --> 02:59:10,723 MUCH AN ANIMAL IS DRINKING. 3303 02:59:10,723 --> 02:59:11,991 HUMANS, THERE'S SO MUCH 3304 02:59:11,991 --> 02:59:13,292 VARIATION AS YOU KNOW VERY WELL. 3305 02:59:13,292 --> 02:59:14,293 IT'S HARD TO GET A GOOD CLEAN 3306 02:59:14,293 --> 02:59:21,234 SIGNAL. 3307 02:59:21,234 --> 02:59:31,778 AND ONE MORE FOLLOW-UP TO THAT I 3308 02:59:34,414 --> 02:59:38,184 HAD IN MY DECK AT THE END I 3309 02:59:38,184 --> 02:59:40,019 FIGURED SOMEONE WOULD ASK BUT 3310 02:59:40,019 --> 02:59:42,155 USING SPATIAL GENOMIC APPROACHES 3311 02:59:42,155 --> 02:59:45,024 YOU CAN IDENTIFY THE BORDER 3312 02:59:45,024 --> 02:59:48,728 ASSOCIATED MACROPHAGE POPULATION 3313 02:59:48,728 --> 02:59:54,167 LINING THE PERIHEMISPHERIC STATE 3314 02:59:54,167 --> 03:00:01,974 AND THESE ARE SOME OF THE CELLS 3315 03:00:01,974 --> 03:00:07,880 INFILTRATING THE PARENCHYMAL 3316 03:00:07,880 --> 03:00:08,915 PORTION OF THE BRAIN AND DON'T 3317 03:00:08,915 --> 03:00:10,850 KNOW HOW THEY'RE GETTING THREE 3318 03:00:10,850 --> 03:00:11,484 MAYBE THE BLOOD BRAIN BARRIER 3319 03:00:11,484 --> 03:00:13,252 AND WITH SOME APPROACHES WE CAN 3320 03:00:13,252 --> 03:00:16,823 START TO RESOLVE WHERE AT LEAST 3321 03:00:16,823 --> 03:00:19,292 SOME OF THE GLIAL TYPE CELLS ARE 3322 03:00:19,292 --> 03:00:23,463 ORIGINATING ESPECIALLY THE 3323 03:00:23,463 --> 03:00:32,605 MACROPHAGE AND LYMPHOCY 3324 03:00:32,605 --> 03:00:32,905 POPULATION. 3325 03:00:32,905 --> 03:00:35,842 WHETHER IT'S IN LUNG, LIVER OR 3326 03:00:35,842 --> 03:00:39,178 GUT, EVENTUALLY IT MAKES IT'S 3327 03:00:39,178 --> 03:00:42,148 WAY TO THE BRAIN. 3328 03:00:42,148 --> 03:00:45,918 I HAVEN'T THOUGHT ABOUT IT MUCH 3329 03:00:45,918 --> 03:00:46,986 IN THE CONTEXT OF LUNG SO THAT 3330 03:00:46,986 --> 03:00:50,022 WAS VERY INTERESTING. 3331 03:00:50,022 --> 03:00:53,392 >> OKAY. 3332 03:00:53,392 --> 03:00:54,861 YOU CAN CONTINUE TO COMMUNICATE. 3333 03:00:54,861 --> 03:00:56,195 I HOPE YOU DO. 3334 03:00:56,195 --> 03:01:00,833 I'M COMPLETELY INTRIGUED WITH 3335 03:01:00,833 --> 03:01:02,502 THE POSSIBILITY THE LUNG IS THE 3336 03:01:02,502 --> 03:01:03,636 FIRST THING THAT SIGNALS THERE'S 3337 03:01:03,636 --> 03:01:05,304 A PROBLEM. 3338 03:01:05,304 --> 03:01:09,509 WE'LL SEE HOW THAT EVOLVES. 3339 03:01:09,509 --> 03:01:09,709 OKAY. 3340 03:01:09,709 --> 03:01:13,045 AS DAVID GOLDMAN SENT ME AN 3341 03:01:13,045 --> 03:01:14,747 E-MAIL AND SAID, I NEGLECTED TO 3342 03:01:14,747 --> 03:01:17,016 TELL YOU EARLIER A WRITTEN 3343 03:01:17,016 --> 03:01:20,620 REPORT WAS PREPARED BY THE NIAAA 3344 03:01:20,620 --> 03:01:21,888 OFFICE OF SCIENCE POLICY AND 3345 03:01:21,888 --> 03:01:24,757 COMMUNICATIONS CALLED THE 3346 03:01:24,757 --> 03:01:27,126 DIRECTOR'S REPORT. 3347 03:01:27,126 --> 03:01:30,029 MY SLIDES AND THE WRITTEN REPORT 3348 03:01:30,029 --> 03:01:31,464 WILL BE AVAILABLE ON THE NIAAA 3349 03:01:31,464 --> 03:01:31,697 WEBSITE. 3350 03:01:31,697 --> 03:01:35,935 IT'S GOING TO BE PUT UP THERE. 3351 03:01:35,935 --> 03:01:37,803 IF YOU MISSED ANYTHING FROM MY 3352 03:01:37,803 --> 03:01:41,007 PART OF THE DISCUSSIONS TODAY, 3353 03:01:41,007 --> 03:01:42,842 IT'S THERE. 3354 03:01:42,842 --> 03:01:44,477 NOW I'LL TURN IT OVER TO 3355 03:01:44,477 --> 03:01:47,079 PHILIPPE TO TALK ABOUT 3356 03:01:47,079 --> 03:01:49,415 CONSIDERATION OF FUTURE MEETING 3357 03:01:49,415 --> 03:01:50,416 MINUTES AND COUNCIL REPORT AND 3358 03:01:50,416 --> 03:01:54,420 FUTURE MEETING DATES. 3359 03:01:54,420 --> 03:01:57,723 I THINK HE CAN DO THAT IN FIVE 3360 03:01:57,723 --> 03:01:58,124 MINUTES. 3361 03:01:58,124 --> 03:02:01,227 >> I'D LIKE TO SUBMIT FOR 3362 03:02:01,227 --> 03:02:02,161 APPROVAL BY COUNCIL THREE 3363 03:02:02,161 --> 03:02:02,828 DOCUMENTS. 3364 03:02:02,828 --> 03:02:06,599 THE MINUTES FOR THE SEPTEMBER 12 3365 03:02:06,599 --> 03:02:07,800 COUNCIL MEETING. 3366 03:02:07,800 --> 03:02:08,901 THE COUNCIL STANDARD OPERATING 3367 03:02:08,901 --> 03:02:12,939 PROCEDURE AND THE REPORT ON THE 3368 03:02:12,939 --> 03:02:15,074 INCLUSION OF THE CLINICAL 3369 03:02:15,074 --> 03:02:15,341 APPROACH. 3370 03:02:15,341 --> 03:02:16,909 THESE DOCUMENTS WERE PROVIDED TO 3371 03:02:16,909 --> 03:02:20,546 COUNCIL IN THE ELECTRONIC 3372 03:02:20,546 --> 03:02:23,683 COUNCIL BOOK AND BEFORE ASKING 3373 03:02:23,683 --> 03:02:26,252 FOR A VOTE I'D ASK FOR COMMENTS 3374 03:02:26,252 --> 03:02:26,819 ON ANY ORGANIZATION OF THE 3375 03:02:26,819 --> 03:02:35,127 DOCUMENTS? 3376 03:02:35,127 --> 03:02:37,630 HEARING NONE I'D LIKE TO 3377 03:02:37,630 --> 03:02:38,497 ENTERTAIN A MOTION TO APPROVE 3378 03:02:38,497 --> 03:02:43,436 THE THREE DOCUMENTS. 3379 03:02:43,436 --> 03:02:43,736 >> SO MOVED. 3380 03:02:43,736 --> 03:02:50,776 >> SECOND? 3381 03:02:50,776 --> 03:02:51,577 >> SECOND. 3382 03:02:51,577 --> 03:02:53,079 >> ALL IN FAVOR ? 3383 03:02:53,079 --> 03:02:58,150 THOSE OPPOSED? 3384 03:02:58,150 --> 03:02:59,552 ANY AB TENSION? 3385 03:02:59,552 --> 03:03:03,356 THE MOTION CARRIES. 3386 03:03:03,356 --> 03:03:04,357 THANK YOU VERY MUCH AND I WOULD 3387 03:03:04,357 --> 03:03:10,162 LIKE ALSO TO SHARE THE UPCOMING 3388 03:03:10,162 --> 03:03:14,133 DATES FOR THE NEXT COUNCIL SO 3389 03:03:14,133 --> 03:03:17,036 IT'S ON THE SCREEN. 3390 03:03:17,036 --> 03:03:20,539 FOR THE NIAAA COUNCIL THE DATE 3391 03:03:20,539 --> 03:03:22,174 OF 2025 WILL BE SEPTEMBER 4. 3392 03:03:22,174 --> 03:03:27,847 FOR 2026, FEBRUARY 5, MAY 5, 3393 03:03:27,847 --> 03:03:32,051 SEPTEMBER 17, 2027 WOULD BE 3394 03:03:32,051 --> 03:03:34,453 FEBRUARY 4, 11 AND SEPTEMBER 16. 3395 03:03:34,453 --> 03:03:36,522 FOR THE FUTURE MEETING DAVIS THE 3396 03:03:36,522 --> 03:03:40,426 CRAN JOINT ADVISORY COUNCIL OF 3397 03:03:40,426 --> 03:03:43,362 NIAAA, NIDA AND NCI IN 2026 MAY 3398 03:03:43,362 --> 03:03:52,505 6, AND 2027, MAY 12. 3399 03:03:52,505 --> 03:03:54,540 BACK TO YOU, DR. KOOB. 3400 03:03:54,540 --> 03:03:57,543 >> SO I THINKS IT'S UP TO ME TO 3401 03:03:57,543 --> 03:03:58,144 ADJOURN THE MEETING. 3402 03:03:58,144 --> 03:03:59,912 THE MEETING IS NOW ADJOURNED. 3403 03:03:59,912 --> 03:04:03,049 THANK YOU ALL, ESPECIALLY 3404 03:04:03,049 --> 03:04:03,683 COUNCIL MEMBERS FOR JOINING US 3405 03:04:03,683 --> 03:04:07,420 TODAY. 3406 03:04:07,420 --> 03:04:09,689 THERE'S ONLY SIX OF YOU BUT YOU 3407 03:04:09,689 --> 03:04:11,023 CARRY A LOT OF IMPORTANCE TO US 3408 03:04:11,023 --> 03:04:14,260 AND I REALLY APPRECIATE YOUR 3409 03:04:14,260 --> 03:04:17,063 INTERACTIONS AND COMMENTS TODAY 3410 03:04:17,063 --> 03:04:18,164 AND QUESTIONS. 3411 03:04:18,164 --> 03:04:21,701 WE'LL SEE YOU IN SEPTEMBER AND 3412 03:04:21,701 --> 03:04:22,334 WE'LL SEE YOU TOMORROW AT CRAN. 3413 03:04:22,334 --> 03:04:22,401