1
00:00:04,437 --> 00:00:10,310
STRAIGHTFORWARD AND PROBABLY
THIS STATEMENT THAT WAS DONE

2
00:00:10,377 --> 00:00:16,249
MANY YEARS AGO BY A STATISTICIAN
AND TO ACCEPT IT WILL BE

3
00:00:16,316 --> 00:00:17,250
RECORDED.

4
00:00:18,084 --> 00:00:20,520
ALL MODELS ARE WRONG, BUT SOME
ARE USEFUL.

5
00:00:21,020 --> 00:00:24,724
PROBABLY TELLS US THAT THERE IS
FOR SURE ROOM FOR IMPROVEMENT.

6
00:00:26,593 --> 00:00:32,232
AND SO THE THE IDEA THAT WE
WANTED TO DISCUSS ALL TOGETHER

7
00:00:32,298 --> 00:00:38,238
IS WHETHER THERE IS A REASON TO
REALLY FOCUS ON BIDIRECTIONAL

8
00:00:38,304 --> 00:00:44,043
TRANSLATION AND ON ONE SIDE TO
UNDERSTAND HOW WE CAN BETTER

9
00:00:44,110 --> 00:00:46,379
CALIBRATE ANYONE MODELS.

10
00:00:46,446 --> 00:00:51,117
AND THESE ARE TWO WORDS I JUST
LEARNED AND I HOPE I KNEW THEM

11
00:00:51,184 --> 00:00:51,818
PROPERLY.

12
00:00:51,885 --> 00:00:52,852
SO HOW?

13
00:00:53,153 --> 00:00:57,457
BY LOOKING AT A LOT OF
PHYSIOLOGY IN PATIENTS AND

14
00:00:57,524 --> 00:01:02,729
DISEASE TRAJECTORIES, WE CAN
BETTER ADDRESS WHETHER OR NOT A

15
00:01:02,796 --> 00:01:08,468
SPECIFIC MODEL IS RECAPITULATING
THAT SPECIFIC PATTERN OF DISEASE

16
00:01:08,535 --> 00:01:13,339
PROGRESSION AND REFINE THE MODEL
ACCORDING TO THE HUMAN

17
00:01:13,406 --> 00:01:14,274
PATHOLOGY.

18
00:01:14,774 --> 00:01:20,580
AND ON THE OTHER SIDE, HAVING
ACCESS TO BRAIN SPECIMENS AND

19
00:01:20,647 --> 00:01:26,886
BIOFLUIDS FROM PATIENTS, WE CAN
EVENTUALLY CORROBORATE FINDINGS

20
00:01:26,953 --> 00:01:31,558
THAT ARE EMERGING FROM THE BASIC
SCIENCE WORK.

21
00:01:32,959 --> 00:01:38,531
SO IN THIS CIRCLE WE IDENTIFIED
SOME ASPECTS WE WOULD LIKE TO

22
00:01:38,598 --> 00:01:40,099
DISCUSS TOGETHER.

23
00:01:40,166 --> 00:01:45,772
SO METRICS AND TOOLS AND
PARAMETERS WE WOULD LIKE TO

24
00:01:45,839 --> 00:01:52,812
IMPLEMENT IN ORDER TO ADOPT THIS
FRAMEWORK AND THEY GO FROM BLOOD

25
00:01:52,879 --> 00:01:58,051
BIOMARKERS TO NEURO IMAGING
BIOMARKERS OF COURSE

26
00:01:58,117 --> 00:02:04,390
NEUROLOGICAL OUTCOME AND MORE
AND MORE NEUROPATHOLOGY ALSO

27
00:02:04,457 --> 00:02:10,630
INTENDED AS BIOPSY FOR VARIED
FINE MOLECULAR PHENOTYPING.

28
00:02:11,698 --> 00:02:17,871
OF COURSE, IN THIS BIO MECHANICS
PLAYS A MAJOR ROLE AND SO IN THE

29
00:02:17,937 --> 00:02:19,939
HETEROGENEITY OF TBI.

30
00:02:20,206 --> 00:02:25,345
CAN WE BETTER MODEL DIFFERENT
BIO MECHANICS ALSO IN THE

31
00:02:25,411 --> 00:02:31,017
PRECLINICAL SETTING AND PROBABLY
OR FOR SURE RODENTS ARE NOT

32
00:02:31,084 --> 00:02:35,688
ENOUGH TO REALLY MIMIC THE
COMPLEXITY OF ALSO THE

33
00:02:35,755 --> 00:02:40,793
STRUCTURAL BRAINS BRAIN
STRUCTURE AND SO LARGER ANIMAL

34
00:02:40,860 --> 00:02:46,299
WATERS COULD BE ESSENTIAL IN
ORDER TO IN IN THE PROCESS OF

35
00:02:46,366 --> 00:02:52,138
TRANSLATING FINDINGS FROM THE
CLINICAL SETTING TO THE CLINICAL

36
00:02:52,205 --> 00:02:52,906
SETTING.

37
00:02:52,972 --> 00:02:57,977
SO WITH WITH THIS SLIDE, I THINK
WE CAN ALREADY START A

38
00:02:58,044 --> 00:03:02,782
DISCUSSION AND MAYBE DOUG YOU
COULD START WITH THIS.

39
00:03:02,849 --> 00:03:07,754
AND YEAH, SO I MEAN I WONDER
WHAT PEOPLE THINK ABOUT THIS

40
00:03:07,820 --> 00:03:08,621
FRAMEWORK.

41
00:03:08,688 --> 00:03:12,158
SO THIS IS SOMETHING THAT
EVERYBODY'S TALKED ABOUT I

42
00:03:12,225 --> 00:03:16,329
THINK, BUT FEW PEOPLE DO THAT
TRUE TRANSLATION PRECLINICAL TO

43
00:03:16,396 --> 00:03:20,400
CLINICAL BY FIRST CALIBRATING
WHAT ASPECTS OF THE MODELS ARE

44
00:03:20,466 --> 00:03:21,801
CLINICALLY RELEVANT.

45
00:03:22,235 --> 00:03:23,736
YOU KNOW, HAVE YOU GONE THROUGH
THE MOTIONS?

46
00:03:23,803 --> 00:03:27,006
HAVE YOU WORKED WITH SOMEBODY,
HAVE YOU TALKED TO A PERSON IN

47
00:03:27,073 --> 00:03:27,740
BIO MECHANICS?

48
00:03:27,807 --> 00:03:30,810
AND JUST ON THE SIDE, WE'RE
HOPING TO EXPAND THE BIO

49
00:03:30,877 --> 00:03:34,547
MECHANICS REPRESENTATION HERE,
WHICH IS ALMOST ZERO RIGHT NOW.

50
00:03:34,614 --> 00:03:37,483
SO YOU KNOW THAT WE THINK THAT'S
GOING TO BE A VERY IMPORTANT

51
00:03:37,550 --> 00:03:37,884
ASPECT.

52
00:03:38,551 --> 00:03:41,087
BUT THEN ON THE OTHER, ON THE
FLIP SIDE, YOU HEARD WILLIE

53
00:03:41,154 --> 00:03:43,790
TALKING ABOUT A LITTLE EARLIER
THIS MORNING WHEN WE CAN TALK

54
00:03:43,856 --> 00:03:44,691
ABOUT IT MORE LATER.

55
00:03:44,757 --> 00:03:48,227
BUT YOU KNOW, HOW DO YOU
CORROBORATE YOUR DATA?

56
00:03:48,294 --> 00:03:50,496
I MEAN YOU KNOW YOUR, YOUR ROTOR
MODEL MAY HAVE DIFFERENT

57
00:03:50,563 --> 00:03:52,432
PHYSIOLOGY AND IT MIGHT HAVE
DIFFERENT OUTCOMES.

58
00:03:52,498 --> 00:03:56,069
SO HOW DO YOU FIND OUT IF THAT'S
GOING TO BE CLINICALLY RELEVANT

59
00:03:56,135 --> 00:03:58,204
AND NOT JUST A MODEL SPECIFIC
EVENT?

60
00:03:58,871 --> 00:04:02,342
SO THE IDEA, THE FRAMEWORK IS
CAN YOU FIRST, YOU KNOW,

61
00:04:02,408 --> 00:04:06,012
IDENTIFY OR VALIDATE THE
CLINICAL RELEVANCE OF YOUR MODEL

62
00:04:06,079 --> 00:04:09,849
AND THEN WHEN YOU GET DETAILS
THAT YOU CAN'T POSSIBLY DO IN

63
00:04:09,916 --> 00:04:13,620
CLINIC CLINICAL CIRCUMSTANCES,
THEN HOW DO YOU CORROBORATE

64
00:04:13,686 --> 00:04:13,953
THAT.

65
00:04:14,020 --> 00:04:18,024
SO YOU KNOW, WE'RE HAPPY TO, YOU
KNOW, HEAR EVERYBODY'S OPINION

66
00:04:18,091 --> 00:04:22,061
ON THAT AND YOU KNOW MAYBE ANY
IDEAS OF HOW WE COULD MAKE THIS

67
00:04:22,128 --> 00:04:22,895
HAPPEN MAYBE.

68
00:04:22,962 --> 00:04:24,030
CHERYL, DO YOU HAVE SOME IDEAS?

69
00:04:24,097 --> 00:04:33,973
LET ME GIVE YOU PUT ME ON THE
SPOT HERE DOUG.

70
00:04:35,108 --> 00:04:39,112
SO WELL IN TERMS OF SO LET ME
START OFF WITH BLOOD BIOMARKERS.

71
00:04:39,178 --> 00:04:41,981
WE'VE SPENT A LOT OF TIME
TALKING ABOUT BLOOD BIOMARKERS

72
00:04:42,048 --> 00:04:44,984
AND SOME OF THE ASSAYS THAT HAVE
BEEN DEVELOPED FOR HUMANS

73
00:04:45,051 --> 00:04:47,887
ACTUALLY DO WORK IN MOST MODELS,
BUT OTHER ONES DO NOT.

74
00:04:48,688 --> 00:04:52,458
SO I DO THINK THAT THERE IS AN
OPPORTUNITY FOR US TO MAKE SURE

75
00:04:52,525 --> 00:04:56,429
THAT WE HAVE AT LEAST A PANEL OF
OF BIOMARKERS THAT ARE SUITABLE

76
00:04:56,496 --> 00:04:58,097
FOR WORK IN MODEL SYSTEMS.

77
00:04:58,831 --> 00:05:02,435
I THINK UNDERSTANDING THE
TEMPORAL AND AND TRAJECTORIES OF

78
00:05:02,502 --> 00:05:06,105
OF BIOMARKER CHANGES WOULD BE A
WONDERFUL COMPANION TO THE

79
00:05:06,172 --> 00:05:09,642
CLINICAL STUDIES THAT COULD HELP
WITH THAT CALIBRATION.

80
00:05:10,576 --> 00:05:14,280
CERTAINLY NEUROPATHOLOGY, I
WOULD CERTAINLY AGREE THAT THIS

81
00:05:14,347 --> 00:05:18,184
IS AN EXCEPTIONALLY IMPORTANT
PART OF WHAT WE CAN WHAT WE CAN

82
00:05:18,251 --> 00:05:19,686
DO AND SHOULD BE DOING.

83
00:05:20,920 --> 00:05:26,659
AND THEN I ALSO THINK THAT THERE
IS A GREAT WITH WITH THE ADVENT

84
00:05:26,726 --> 00:05:32,265
OF TECHNOLOGIES LIKE SINGLE CELL
RNA SEQUENCING AND 3D SPATIAL

85
00:05:32,331 --> 00:05:37,704
METHODS TO BE ABLE TO IN AN
UNBIASED WAY KIND OF INTERROGATE

86
00:05:37,770 --> 00:05:42,942
WHAT HAPPENS IN THE INJURED
BRAIN FROM A MODEL SYSTEM THAT

87
00:05:43,009 --> 00:05:48,381
HAS THE OPPORTUNITY TO GIVE US A
VERY, VERY RICH DATA SET OF

88
00:05:48,448 --> 00:05:53,553
POTENTIAL PATHWAYS, HUBS OF
ACTIVITY OR PATHWAYS THAT ARE

89
00:05:53,619 --> 00:05:57,290
AFFECTED BY IN IN VARIOUS MODELS
OF TBI.

90
00:05:57,724 --> 00:06:01,894
HOW DO THESE COMPARE WITH CCI,
FLUID, PERCUSSION, WEIGHT, DROP

91
00:06:01,961 --> 00:06:03,029
BLAST, ETCETERA.

92
00:06:03,930 --> 00:06:06,399
I THINK THERE'S A LOT OF OF
OPPORTUNITY THERE.

93
00:06:06,933 --> 00:06:11,270
WHERE WE STILL NEED, I THINK A
LOT OF WORK IS HOW DO WE WORK

94
00:06:11,337 --> 00:06:15,775
WITH THE CLINICAL TEAMS, CAN WE
GET SURGICAL RESECTIONS OF OF

95
00:06:15,842 --> 00:06:20,413
HUMAN TISSUE THAT DOESN'T DON'T
REQUIRE LONG PERIODS FOR PEOPLE

96
00:06:20,480 --> 00:06:22,081
TO COME TO POSTMORTEM.

97
00:06:22,415 --> 00:06:23,750
WILLIE TALKED ABOUT THIS AS
WELL.

98
00:06:24,484 --> 00:06:28,020
FOR ME, THESE ARE THE LOW
HANGING FRUIT OF, OF TRYING TO

99
00:06:28,087 --> 00:06:32,158
GET TO MECHANISMS AND BE ABLE TO
TEST HYPOTHESES FUNCTIONALLY IN

100
00:06:32,225 --> 00:06:35,828
ANIMAL MODELS, VALIDATING A
TARGET AND A PATHWAY TO GO TO

101
00:06:35,895 --> 00:06:37,230
INTERVENTION STUDIES.

102
00:06:38,331 --> 00:06:41,768
THAT'S JUST MY 2 NOTES, YEAH.

103
00:06:42,335 --> 00:06:48,207
AND SO THE, THE IDEA OF THE NEXT
SLIDES WERE TO GIVE A FEW

104
00:06:48,274 --> 00:06:54,380
EXAMPLES OF STUDIES TRYING TO
COMPARE OR COMBINE PRECLINICAL

105
00:06:54,447 --> 00:07:00,653
AND CLINICAL APPROACHES IN ORDER
TO WORK TOWARDS CALIBRATION.

106
00:07:00,720 --> 00:07:05,558
AND THIS IS AN EXAMPLE FROM A
STUDY BY VIRGINIA NEWCOMB

107
00:07:05,625 --> 00:07:10,363
SHOWING CLEARLY THAT IN ABOUT
30% OF PATIENTS THERE IS

108
00:07:10,429 --> 00:07:15,635
PROGRESSIVE NEURODEGENERATION
THAT CAN BE TACKLED BY MRIDTI

109
00:07:15,701 --> 00:07:17,804
AND THE NUMBER OF TRACKS.

110
00:07:17,870 --> 00:07:23,109
THE DECREASE OVER TIME AND THIS
IS LINKED TO FUNCTIONAL

111
00:07:23,176 --> 00:07:28,848
IMPAIRMENT AND WHAT WAS FOUND
ALSO IN PRECLINICAL MODELS AND

112
00:07:28,915 --> 00:07:34,420
PARTICULARLY IN THE CONTROL
CORTICAL IMPACT TBI MODEL THAT

113
00:07:34,487 --> 00:07:40,092
WAS ORIGINALLY DESCRIBED RATHER
AS A VERY FOCAL INJURY WITH

114
00:07:40,159 --> 00:07:44,964
LIMITED DAMAGE BESIDES THE
CONTUSIONAL HEMISPHERE.

115
00:07:45,832 --> 00:07:50,603
THE THE CASE IS THAT IF YOU WAIT
LONG ENOUGH FOR YOU SEE THAT THE

116
00:07:50,670 --> 00:07:55,074
PATHOLOGY IS PROGRESSING AND
THERE IS ALSO A CLEAR DAMAGE IN

117
00:07:55,141 --> 00:07:56,375
SUBCORTICAL AREAS.

118
00:07:56,442 --> 00:08:01,280
AND THIS ALSO INVOLVED CLEARLY
WHITE MATTER CHANGES THAT CAN BE

119
00:08:01,347 --> 00:08:05,785
ADDRESSED SIMILAR TO WHAT HAS
BEEN DONE IN PATIENTS BY MRI

120
00:08:05,852 --> 00:08:06,652
APPROACHES.

121
00:08:06,719 --> 00:08:10,489
AND WHAT WE OBSERVED IS THAT BY
12 MONTHS THERE IS A DECREASE IN

122
00:08:10,556 --> 00:08:13,392
THE THICKNESS OF THE CORPUS
CALLOSUM ALSO IN THE

123
00:08:13,459 --> 00:08:14,493
CONTRALATERAL SIDE.

124
00:08:14,560 --> 00:08:19,098
AND THIS IS ASSOCIATED TO
COGNITIVE AND SENSORY MOTOR

125
00:08:19,165 --> 00:08:19,866
FUNCTION.

126
00:08:19,932 --> 00:08:24,770
SO TELLING US THAT POSSIBLY IF
YOU ARE WANTING IT, IF IF YOU'RE

127
00:08:24,837 --> 00:08:28,908
AIMING TO TACKLE WHITE MATTER
CHANGES EVEN THOUGH THE

128
00:08:28,975 --> 00:08:33,446
PROPORTION OF GREY AND WHITE
MATTER IN RODENTS IS OPPOSITE

129
00:08:33,512 --> 00:08:34,814
COMPARED TO HUMAN.

130
00:08:34,881 --> 00:08:40,152
SO IT CAN BE ARGUED THAT IT'S
NOT THE IDEAL SETTING IN ORDER

131
00:08:40,219 --> 00:08:45,391
TO DO THIS, BUT AT LEAST IN IN
TERMS OF DISEASE PROGRESSION

132
00:08:45,458 --> 00:08:49,228
THAT IS QUITE PARALLEL PROCESS
TAKING PART.

133
00:08:49,295 --> 00:08:54,533
AND AND THIS IS ANOTHER EXAMPLES
IN THE SETTING OF I MEAN LOOKING

134
00:08:54,600 --> 00:08:59,205
AT PATHOLOGY, IT WAS A VERY
PIONEER STUDIES BACK IN 95 BY

135
00:08:59,272 --> 00:09:00,172
DOUG SMITH.

136
00:09:00,640 --> 00:09:05,278
AND WHAT THEY SHOWED WAS IN FACT
THAT AGAIN THERE WAS A

137
00:09:05,344 --> 00:09:10,716
PROGRESSIVE ATROPHY AND THIS IS
CONSISTENT WITH WHAT OBSERVED IN

138
00:09:10,783 --> 00:09:15,788
PATIENTS MANY YEARS AFTER THE
INJURY AND IS UNDERPINNED MOST

139
00:09:15,855 --> 00:09:18,824
LIKELY BY ONGOING NEW
INFLAMMATION.

140
00:09:18,891 --> 00:09:23,829
SO THERE IS HERE AN OPPORTUNITY
TO GO BACK AGAIN TO THE MODELS

141
00:09:23,896 --> 00:09:28,701
AND SEE WHAT IS AND WHICH IS THE
MAIN ROLE OF THE PERSISTENT

142
00:09:28,768 --> 00:09:32,872
INFLAMMATORY INFLAMMATION IN
CONTRIBUTING TO INJURY

143
00:09:32,939 --> 00:09:33,739
EVOLUTION.

144
00:09:34,173 --> 00:09:38,811
SO WITH THIS, I I THINK WE
SHOULD, WE COULD START

145
00:09:38,878 --> 00:09:44,350
DISCUSSING ABOUT THE NEED TO
SHARE DATA AND HAVE ACCESS TO

146
00:09:44,417 --> 00:09:49,622
BRAIN BIOSPECIMENS FOR
NEUROPATHOLOGICAL ASSESSMENT AND

147
00:09:49,689 --> 00:09:51,857
FOR DEEPER PHENOTYPING.

148
00:09:52,291 --> 00:09:56,295
AND SO MAYBE REALLY YOU CAN
COMMENT ON THIS.

149
00:09:57,763 --> 00:09:58,030
THANK YOU.

150
00:09:59,231 --> 00:10:03,402
LET'S JUST BEFORE WE DO THIS,
LET ME JUST FIRST OF ALL ASK FOR

151
00:10:03,469 --> 00:10:07,406
A SHOW OF HANDS OF PEOPLE WHO'VE
RESEARCHED OR OR CONDUCTED

152
00:10:07,473 --> 00:10:10,576
RESEARCH IN ANIMAL MODELS OF TBI
IN SOME WAY.

153
00:10:13,512 --> 00:10:15,781
OK, NOW KEEP YOUR YOU CAN PUT
YOUR HAND UP HIGH.

154
00:10:15,848 --> 00:10:17,350
SORRY, I'M NOT GOING TO PICK AN
ENDER YET.

155
00:10:18,484 --> 00:10:19,185
NOW KEEP YOUR HAND UP.

156
00:10:19,251 --> 00:10:23,856
IF YOU'VE ALSO WORKED IN HUMAN
TISSUE FOR STUDYING TBI, YOU'D

157
00:10:23,923 --> 00:10:25,725
HAVE TO PUT TWO HANDS UP.

158
00:10:25,791 --> 00:10:28,294
JUST KEEP YOUR HAND DOWN.

159
00:10:28,361 --> 00:10:28,427
OK.

160
00:10:28,494 --> 00:10:29,261
SO THAT'S THAT'S GOOD.

161
00:10:29,328 --> 00:10:29,562
THAT'S GOOD.

162
00:10:29,628 --> 00:10:32,298
FOR THOSE WHO PUT THEIR HAND
DOWN AFTER ASHLEY WHO'D WORKED

163
00:10:32,365 --> 00:10:33,065
FOR HUMAN TISSUE.

164
00:10:33,132 --> 00:10:35,835
WHAT WHAT'S WHAT WAS THE BARRIER
TO ACTUALLY WORKING WITH HUMAN

165
00:10:35,901 --> 00:10:36,135
TISSUE?

166
00:10:36,202 --> 00:10:39,338
WHY WHY DID WHY DID MY NOT
PURSUED STUDIES IN HUMAN TISSUE?

167
00:10:39,405 --> 00:10:41,273
WHY HE WAS STUCK WITH JUST THE
ANIMAL MODEL.

168
00:10:44,443 --> 00:10:50,116
YEAH THERE THERE ARE SEVERAL
AREAS.

169
00:10:50,883 --> 00:11:00,593
SO AT LEAST GETTING EITHER,
YEAH, SO I THINK THERE ARE LACK

170
00:11:00,659 --> 00:11:08,901
OF REALLY ACCESSIBLE
REPOSITORIES FOR HUMAN TISSUE

171
00:11:08,968 --> 00:11:18,511
SOMETIMES BARRIERS AND SO OF
COURSE, SO WE NEED TO KIND OF

172
00:11:18,577 --> 00:11:21,380
GET AROUND THERE.

173
00:11:21,747 --> 00:11:24,350
HOW CAN WE WORK WITH THOSE
ORGANIZATIONS SO THAT THEY CAN

174
00:11:24,417 --> 00:11:27,086
DO THEIR WORK BUT WE CAN STILL
GET THE SPECIMENS WE NEED.

175
00:11:27,686 --> 00:11:31,357
YEAH PARDON.

176
00:11:36,095 --> 00:11:39,231
I WORK IN NEUROEMERGING AND
TRYING TO RELAY THE

177
00:11:39,298 --> 00:11:43,335
NEUROEMERGING HAS BEEN SO PRE
TRANSLATION OF THE CHEMICAL AND

178
00:11:43,402 --> 00:11:44,603
THEY WERE AT LEAST.

179
00:11:44,670 --> 00:11:47,540
I GO NOW TO THE STUDIES.

180
00:11:53,879 --> 00:11:54,113
YEAH.

181
00:11:54,180 --> 00:11:54,780
THESE THESE.

182
00:11:55,014 --> 00:11:55,648
SORRY STUART.

183
00:11:56,615 --> 00:11:57,483
ARE YOU GOING TO SAY SOMETHING?

184
00:11:57,550 --> 00:11:57,883
NO.

185
00:11:58,684 --> 00:11:58,784
NO.

186
00:11:58,851 --> 00:11:59,418
YOU COULD YOU COULD.

187
00:12:01,120 --> 00:12:01,387
YEAH.

188
00:12:01,454 --> 00:12:03,289
I'M A I'M A REFORMED RESEARCHER.

189
00:12:03,355 --> 00:12:05,257
I'M NOW JUST A BUREAUCRAT.

190
00:12:06,725 --> 00:12:08,060
IT'S TOO OFTEN FROM THE VA.

191
00:12:09,762 --> 00:12:13,499
YOU KNOW ONE THING IT'S ALWAYS
TROUBLED ME WITH GOING FROM THE

192
00:12:13,566 --> 00:12:16,469
ANIMAL TISSUE TO THE HUMAN
TISSUE IS THAT BEING.

193
00:12:16,535 --> 00:12:18,304
I KNOW THIS DOESN'T INCLUDE YOU
WILLIE.

194
00:12:18,370 --> 00:12:23,342
YOU HAVE MUCH BETTER METHODS BUT
BUT YOU KNOW IN THE LAB WE IT

195
00:12:23,409 --> 00:12:25,511
WAS, WE DID THEM IN SQUADS.

196
00:12:25,578 --> 00:12:27,012
IT WAS NICE AND PRECISE.

197
00:12:27,379 --> 00:12:30,282
FIXED THEM IT WAS YOU KNOW
EVERYTHING WAS DONE BY A

198
00:12:30,349 --> 00:12:30,816
PROTOCOL.

199
00:12:30,883 --> 00:12:31,750
VERY PRECISE.

200
00:12:33,285 --> 00:12:37,423
WELL HOW LONG DOES THE THE BRAIN
STAY IN THE IN THE DECEASED

201
00:12:37,490 --> 00:12:38,457
PERSON'S BODY.

202
00:12:39,291 --> 00:12:43,329
HOW LONG DOES THIS MAYBE GO INTO
A BUCKET OF FORMALIN THAT MAY OR

203
00:12:43,395 --> 00:12:46,532
MAY NOT BE AT ROOM TEMPERATURE
OR OR A COLD ROOM.

204
00:12:47,333 --> 00:12:50,936
AND THEN HOW LONG IS IT
PROCESSED SO IT'S FINALLY IN ITS

205
00:12:51,003 --> 00:12:53,739
FINAL STATE THAT YOU DO YOUR
ANALYSIS ON.

206
00:12:54,073 --> 00:12:58,611
SO THERE IS A WHOLE RANGE FROM
THE BEST PROBABLY YOUR LAB

207
00:12:58,677 --> 00:13:03,449
REALLY BUT THEN THERE'S OTHER
PLACES OR YOUR LOCAL CORONER'S

208
00:13:03,516 --> 00:13:06,619
OFFICE WHERE IT'S MAY NOT BE SO
EXACT.

209
00:13:07,920 --> 00:13:10,723
SO HOW CAN YOU DO SCIENCE ON
THAT THE THE THE THESE ARE THESE

210
00:13:10,789 --> 00:13:13,626
ARE FANTASTIC POINTS AND AND ALL
OF THESE POINTS WHERE WHEN WE

211
00:13:13,692 --> 00:13:16,295
SAT DOWN SOME YEARS AGO AND
TRIED TO FIGURE OUT WHAT WHAT

212
00:13:16,362 --> 00:13:17,930
HOW ARE THE WHAT ARE THE
SOLUTIONS.

213
00:13:17,997 --> 00:13:22,168
HOW DO WE BRING THE RESOURCES WE
HAVE THE THE HUMAN TISSUE

214
00:13:22,234 --> 00:13:26,572
ARCHIVES THE AVAILABILITY FOR
RESEARCH TO THE WIDER RESEARCH

215
00:13:26,639 --> 00:13:30,809
COMMUNITY AND ADDRESS SOME OF
THESE CHALLENGES AND AND OUR

216
00:13:30,876 --> 00:13:35,314
FIRST RUN AT THIS WAS WAS THIS
CONNECT TVI RESOURCE WHERE DOUG

217
00:13:35,381 --> 00:13:39,151
AND I AND OTHERS SET UP A
NETWORK A COLLABORATION OF

218
00:13:39,218 --> 00:13:43,455
COLLEAGUES WE KNEW HAD BRAIN
TISSUE FOR RESEARCH PURPOSES.

219
00:13:43,689 --> 00:13:46,358
SO SILOS OF EXCELLENT BRAIN
TISSUE WHICH IS AVAILABLE FOR

220
00:13:46,425 --> 00:13:49,261
RESEARCH AND AND WOULD ADDRESS
MANY OF THE QUESTIONS AND AND

221
00:13:49,328 --> 00:13:52,164
AND CERTAINLY DEALS WITH MANY OF
THE CHALLENGES IN TRAUMATIC

222
00:13:52,231 --> 00:13:55,100
BRAIN INJURY BUT THEY WERE THEY
WERE IN SILOS THEY WEREN'T SO

223
00:13:55,167 --> 00:13:55,801
EASY TO GET AT.

224
00:13:55,868 --> 00:13:58,571
SO IF YOU HAD A GREAT PROJECT
AND YOU'RE YOU'RE AN IDEA YOU

225
00:13:58,637 --> 00:14:01,307
WANTED TO PURSUE HOW HOW HOW
WOULD YOU HOW WOULD YOU GET TO

226
00:14:01,373 --> 00:14:04,043
PEOPLE THAT HAD THE TISSUE HOW
WOULD YOU FOLLOW UP ON THAT.

227
00:14:04,109 --> 00:14:07,880
SO SO THE IDEA IN CONNECT TBI IS
WE WE BROUGHT ALL OF THE

228
00:14:07,947 --> 00:14:11,817
RESEARCH ARCHIVES TOGETHER WE
YOU CREATED A A SHOP WINDOW A

229
00:14:11,884 --> 00:14:15,888
WAY IN TO INTERACT WITH WITH THE
ARCHIVES THAT ARE THERE THAT

230
00:14:15,955 --> 00:14:17,256
WERE THERE PRESENTLY.

231
00:14:17,323 --> 00:14:19,625
AND THEN WHAT WE'VE DONE IS
WE'VE GONE ALONG AS WE WE'VE

232
00:14:19,692 --> 00:14:22,094
WORKED ON STANDARDIZATION OF
PROTOCOLS SO THAT THAT WE CAN

233
00:14:22,161 --> 00:14:24,597
SEE THAT THE MATERIALS ARE
HANDLED MUCH THE SAME WAY IN THE

234
00:14:24,663 --> 00:14:27,233
DIFFERENT LABORATORIES THAT THE
STAINING PROCESSES ARE MUCH THE

235
00:14:27,299 --> 00:14:27,533
SAME.

236
00:14:28,167 --> 00:14:30,803
AND WE DID A BIT OF WORK AT THE
BEGINNING TO LOOK AT THE

237
00:14:30,869 --> 00:14:33,772
VARIABILITY AND PROTOCOLS EVEN
WITHIN LABS THAT WE'RE JOINING

238
00:14:33,839 --> 00:14:36,875
TOGETHER AND WHAT DIFFERENCE DID
THAT MAKE TO THE END RESULTS IN

239
00:14:36,942 --> 00:14:39,979
TERMS OF THE THE IMMUNOSTAINING
QUALITY AND AND AND AND IN TRUTH

240
00:14:40,045 --> 00:14:43,048
WE WERE ALL DOING MUCH THE SAME
BUT IN SLIGHTLY DIFFERENT WAYS,

241
00:14:43,115 --> 00:14:45,818
BUT THE END RESULTS WERE MUCH
THE SAME THAT DIDN'T REALLY

242
00:14:45,884 --> 00:14:46,385
IMPACT THEM.

243
00:14:46,452 --> 00:14:46,685
SO.

244
00:14:46,885 --> 00:14:50,522
SO THAT CREATES A GOOD NETWORK
AND FOR THOSE OF YOU WHO'VE NOT

245
00:14:50,589 --> 00:14:54,159
INTERACTED WITH CONNECT TVI,
THIS SLIDE IS, IS IS DESIGNED AS

246
00:14:54,226 --> 00:14:56,295
A AS A SUMMARY OF THE THE
PROJECT.

247
00:14:56,962 --> 00:15:00,299
THERE'S SEVERAL CORES THAT THAT
RUN ALONGSIDE THE BRAIN BANK

248
00:15:00,366 --> 00:15:03,469
CORE BEING THE THE CENTRAL
INITIATIVE TO BRING ALL THESE

249
00:15:03,535 --> 00:15:07,006
ARCHIVES TOGETHER AND ALSO TO
COORDINATE DONATIONS AND AND THE

250
00:15:07,072 --> 00:15:10,109
THE CENTRES, THE LABS THAT WE
HAVE WITH MATERIAL SPREAD

251
00:15:10,175 --> 00:15:13,579
THROUGH NORTH AMERICA, CANADA
AND ALSO OUR OWN LAB IN GLASGOW

252
00:15:13,646 --> 00:15:16,982
AND THAT THAT'S NOW THE HOPE IS
THAT THE OTHER RESOURCES AND

253
00:15:17,049 --> 00:15:20,619
SOURCES WILL COME TO US AND SAY
LOOK CAN WE GET ON BOARD, CAN WE

254
00:15:20,686 --> 00:15:23,689
WORK WITH THIS BUT AND WE'LL
WORK WITH THAT WITHIN THE

255
00:15:23,756 --> 00:15:26,859
AVAILABILITY OF THE FUNDS WE
HAVE AND RESOURCES WE HAVE.

256
00:15:26,925 --> 00:15:29,261
HAVING SAID THAT WE'RE WE'RE
WINDING DOWN AND WE'RE IN A

257
00:15:29,328 --> 00:15:30,429
FINAL YEAR OF THAT PROGRAM.

258
00:15:30,496 --> 00:15:33,632
WE'RE HOPING THAT THERE WILL BE
CONTINUANCE FUNDING IN IN

259
00:15:33,699 --> 00:15:37,036
ANOTHER MECHANISM AND I KNOW
RAQUEL EARLIER ON MENTIONED THAT

260
00:15:37,102 --> 00:15:40,339
THAT SHE WAS WAITING TO HEAR
ABOUT FUNDING AND SUDDENLY GOT

261
00:15:40,406 --> 00:15:43,776
AN E-MAIL WITHIN A MINUTE OF
SAYING IT WITH WITH THE FUNDING.

262
00:15:43,842 --> 00:15:46,845
SO I'LL JUST THROW THAT OUT
THERE IN CASE THE FUNDING

263
00:15:46,912 --> 00:15:50,516
FAIRIES WANT TO SEND AN E-MAIL
RIGHT NOW, ALTHOUGH IT'S SEVERAL

264
00:15:50,582 --> 00:15:52,017
WEEKS AWAY, SO MAYBE NOT.

265
00:15:53,419 --> 00:15:54,486
I MEAN WE WOULD HOPE THAT IT
WOULD CONTINUE.

266
00:15:54,553 --> 00:15:55,821
IT'S BEEN, IT'S BEEN HUGELY
SUCCESSFUL.

267
00:15:55,888 --> 00:15:59,091
SO, SO WE SET THIS UP WITH AN
ASPIRATION TO YOU KNOW BRING THE

268
00:15:59,158 --> 00:16:02,261
ARCHIVES TOGETHER AND ALLOW
PEOPLE A CENTRAL POINT OF ACCESS

269
00:16:02,328 --> 00:16:05,497
TO OUR TISSUE SUPPORT AND AND IF
NECESSARY SOME RESOURCE TO TO

270
00:16:05,564 --> 00:16:08,867
GET THE PROJECTS RUNNING WITH AN
EXPECTATION OF JUST IN THE LAST

271
00:16:08,934 --> 00:16:11,070
SIX MONTHS WE WOULD BE OPEN FOR
BUSINESS.

272
00:16:11,136 --> 00:16:15,240
SO INVITING INVESTIGATORS TO GET
IN TOUCH AND WE KNOW I THINK

273
00:16:15,307 --> 00:16:19,345
WE'VE HAD 1516 AND WE STARTED
EARLY SO WE WE WE WERE IN YEAR

274
00:16:19,411 --> 00:16:23,248
THREE WHEN WE STARTED SUPPORTING
PROGRAM AND WE'VE HAD 16

275
00:16:23,315 --> 00:16:25,851
EXTERNAL APPLICATIONS FOR FOR
FUNDING.

276
00:16:25,918 --> 00:16:27,252
SO IT'S IT'S WORKING.

277
00:16:27,319 --> 00:16:31,056
IT SEEMS TO HAVE ADDRESSED THAT
PROBLEM WITH THE ONE OTHER AREA

278
00:16:31,123 --> 00:16:34,693
IS ALSO WHEN YOU WORK IN YOUR
RAT OR MOUSE IN THE LAB BECAME

279
00:16:34,760 --> 00:16:36,261
CHARLES RIVER JACKSON LAB.

280
00:16:36,328 --> 00:16:41,367
YOU KNOW THE WHOLE LIFE HISTORY
OF THAT ANIMAL AND YOU DO YOUR

281
00:16:41,433 --> 00:16:42,000
INJURY.

282
00:16:42,634 --> 00:16:46,105
SOME LABS MAY DO MORE THAN ONE
BUT YOU GET TO THE HUMAN CASE

283
00:16:46,171 --> 00:16:49,241
AND IT'S LIKE WELL THEY MAY HAVE
HAD SOME CHILD ABUSE.

284
00:16:49,308 --> 00:16:53,846
THEY MAY PLAY THE RUGBY OR
HOCKEY AND ICE HOCKEY FOOTBALL

285
00:16:53,912 --> 00:16:58,851
AND THEY MAY HAVE A WHOLE SERIES
AND MAYBE THEY EVEN SERVED IN

286
00:16:58,917 --> 00:17:00,052
THE MILITARY.

287
00:17:00,119 --> 00:17:03,589
AND SO SO AND AND THESE AGAIN
THESE THESE ARE SO SO THE REAL

288
00:17:03,655 --> 00:17:07,126
WORLD OF OF MESSINESS OF OF
HUMANITY IS THAT IT IS MESSY AND

289
00:17:07,192 --> 00:17:10,896
NEUROPATHOLOGY IS MESSY WHICH IS
WHICH IS A LOT OF THE CHALLENGE

290
00:17:10,963 --> 00:17:14,600
THAT I AND MY COLLEAGUES SPEND
OUR TIME AS TRYING TO ARE SO THE

291
00:17:14,666 --> 00:17:18,137
MESSINESS OF OF REAL LIFE AND
AND AND THE YEAH SO GETTING TO

292
00:17:18,203 --> 00:17:21,740
YOUR QUESTION HOW CAN WE IT'S
NOT ONLY IS IT DIFFICULT TO GET

293
00:17:21,807 --> 00:17:24,576
BUT THERE IS THAT SO THE THE
PROS SO THE THE THE

294
00:17:24,643 --> 00:17:28,080
PROSPECTIVELY ACCRUED CASES
AMONGST CONNECT OF WHICH WE HAD

295
00:17:28,147 --> 00:17:31,850
AN ASPIRATION TO GET ABOUT 350 I
THINK BUT BUT WE WE'VE ACTUALLY

296
00:17:31,917 --> 00:17:34,787
OVER 1000 THAT HAVE BEEN
REGISTERED NOW WITHIN THE

297
00:17:34,853 --> 00:17:35,254
ARCHIVE.

298
00:17:35,320 --> 00:17:37,823
THE ASPIRATION IS THAT THEY THEY
WILL ALL HAVE STANDARDIZED

299
00:17:37,890 --> 00:17:40,058
CLINICAL INFORMATION CAPTURED,
ALBEIT MUCH OF LIKE A

300
00:17:40,125 --> 00:17:40,659
RETROSPECTIVE.

301
00:17:40,726 --> 00:17:44,430
BUT YOU KNOW FROM THE TOP THIS
MORNING THE, THE THE NEXT PHASE

302
00:17:44,496 --> 00:17:48,066
OF THIS IS IS WHAT YOU KNOW THE
GLOBAL MASTER PLAN I'VE BEEN

303
00:17:48,133 --> 00:17:51,703
WORKING TO FOR THE LAST DECADE
OR SO IS THAT WE EVERY SINGLE

304
00:17:51,770 --> 00:17:55,307
CLINICAL TRIAL STUDY THAT'S
GOING ON WILL INCLUDE THE, THE,

305
00:17:55,374 --> 00:17:57,342
THE, THE REQUEST OF
PARTICIPANTS.

306
00:17:57,409 --> 00:18:00,112
WILL YOU BE WILLING TO DATE YOUR
BRAIN AT SOME POINT AND THAT

307
00:18:00,179 --> 00:18:02,915
GIVES US THAT RICH PHENOTYPING
THAT WE'RE GETTING IN RESEARCH

308
00:18:02,981 --> 00:18:03,916
CAPACITY TO TAKE FOR.

309
00:18:04,716 --> 00:18:07,886
CAN I JUST FOLLOW UP ON ONE
THING THAT STU WAS SAYING?

310
00:18:08,620 --> 00:18:11,723
AND I WORK FOR THE US DEPARTMENT
OF DEFENSE, I'M JB PHILLIPS.

311
00:18:11,790 --> 00:18:15,394
AND I SEE HUNDREDS OF HUNDREDS
OF THOUSANDS OF PROPOSALS.

312
00:18:16,094 --> 00:18:20,399
SO I KIND OF KNOW WHAT THE
LANDSCAPE IS OF WHAT PEOPLE WANT

313
00:18:20,466 --> 00:18:22,968
TO DO TO GET TO SOLUTIONS FOR
TBI.

314
00:18:23,035 --> 00:18:28,340
AND MY QUESTION AND SEE IF YOU
GUYS ARE AFTER THIS, THE MOST

315
00:18:28,407 --> 00:18:33,078
COMPLEX HUMAN ON EARTH, COMPLEX
ANIMAL IS THE HUMAN.

316
00:18:33,579 --> 00:18:36,915
THE MOST COMPLEX ORGAN IN HUMAN
IS THE BRAIN.

317
00:18:38,016 --> 00:18:41,987
BUT WE'RE USING STANDARDIZED
ANIMALS WITH ONE TYPE OF

318
00:18:42,054 --> 00:18:46,525
CONTUSION AND I BET YOU ANY
CONCUSSION IN THIS ROOM IS NEVER

319
00:18:46,592 --> 00:18:51,163
THE SAME AMONGST PEOPLE WHERE
YOU'RE HIT, HOW HARD YOU'RE HIT

320
00:18:51,230 --> 00:18:52,664
AND HOW YOU RESPOND.

321
00:18:52,731 --> 00:18:56,835
SO THERE'S SO MUCH VARIABILITY
IN PEOPLE AND STILL WE RECRUIT

322
00:18:56,902 --> 00:19:00,939
THEM IN THE TRIALS WITH THE
GLASGOW COMA SCALE AND YOU HEARD

323
00:19:01,006 --> 00:19:03,842
THE PROBLEMS WITH THAT EARLIER
THIS WEEK.

324
00:19:04,309 --> 00:19:07,779
THAT'S SYMPTOM BASE AND YOU MAY
HAVE A LARGER CONTUSION, BUT YOU

325
00:19:07,846 --> 00:19:09,214
JUST YOU'RE FINE WITH IT.

326
00:19:09,515 --> 00:19:13,719
SO HOW DO WE GET AROUND AN
ANIMAL MODEL THAT NEEDS TO BE

327
00:19:13,785 --> 00:19:17,723
CONSISTENT WITH A CLOSE CORTICAL
IMPACT OR WHATEVER?

328
00:19:17,789 --> 00:19:23,595
AND THAT MAY ALIGN TO MAYBE 1
1/2% OF HUMAN TB IS I DON'T KNOW

329
00:19:23,662 --> 00:19:25,797
HOW WE GET AROUND THIS.

330
00:19:27,132 --> 00:19:30,402
SO THAT THAT'S A REALLY GOOD
POINT AND AND AND THAT'S THAT'S

331
00:19:30,469 --> 00:19:33,505
LIKE I THINK THE ASPIRATION OF
THIS SESSION IS THAT THE

332
00:19:33,572 --> 00:19:36,475
RECOGNIZING THE THE HUMAN
HETEROGENEITY BUT ALSO THAT

333
00:19:36,542 --> 00:19:39,378
MODELS HAVE TO BE RELEVANT TO TO
THAT HETEROGENEITY.

334
00:19:39,444 --> 00:19:42,814
SO SO THEY HAVE TO THEY HAVE TO
REPLICATE SOMETHING IN THE HUMAN

335
00:19:42,881 --> 00:19:45,951
CONDITION AND THAT'S THAT'S
REALLY BEEN THE ASPIRATION FOR

336
00:19:46,018 --> 00:19:49,221
THE ACTIVITY THAT WE'VE BEEN
INVOLVED IN FOR FOR THE 20 YEARS

337
00:19:49,288 --> 00:19:52,457
NOW IS TO ENSURE THAT THE MODEL
THAT WE'RE WORKING WITH SOME

338
00:19:52,524 --> 00:19:55,494
ASPECT OF IT THAT WE CAN WE CAN
SEE WITHIN OUR HUMAN TBI

339
00:19:55,561 --> 00:19:56,094
MATERIALS.

340
00:19:56,562 --> 00:19:59,831
I'M CONSCIOUSLY STUCK ON ON THAT
CONNECT TBI.

341
00:19:59,898 --> 00:20:02,200
ONE OTHER THING I JUST I'M I'M
DUTY BOUND TO MENTION IS TBI

342
00:20:02,267 --> 00:20:04,503
REPORTER WHICH IF YOU CLICK ON
THE LINK IT WILL TELL YOU

343
00:20:04,570 --> 00:20:06,004
EVERYTHING YOU NEED TO KNOW
ABOUT IT.

344
00:20:06,071 --> 00:20:08,407
BUT THAT'S GOING TO BECOME A
REALLY IMPORTANT PLATFORM FOR

345
00:20:08,473 --> 00:20:10,642
FOR ACCELERATING THIS KIND OF
RESEARCH GOING FORWARD.

346
00:20:12,911 --> 00:20:17,149
MAYBE IF I CAN ADD SOMETHING TO
TO THIS POINT, SO WHICH IS PART

347
00:20:17,215 --> 00:20:21,153
OF THE PROPOSAL WE ARE WORKING
ON AND DISCUSSING, I MEAN IN

348
00:20:21,219 --> 00:20:25,157
ORDER TO EMBRACE HETEROGENEITY
IN THE CLINICAL SETTING, BUT

349
00:20:25,223 --> 00:20:27,759
ALSO ENSURE CONSISTENCY OF THE
MODEL.

350
00:20:28,126 --> 00:20:30,996
SO ON ONE SIDE WE NEED TO
IDENTIFY WHICH MODEL IS

351
00:20:31,063 --> 00:20:34,666
REFLECTING WHICH PART OF THE
PATHOLOGY, BUT ON THE OTHER SIDE

352
00:20:34,733 --> 00:20:38,103
WE NEED TO HAVE SOME KIND OF
HETEROGENEITY WHICH POSSIBLY

353
00:20:38,170 --> 00:20:41,406
IT'S VERY DIFFICULT TO BE
MANAGED WITHIN A SINGLE LAB.

354
00:20:42,007 --> 00:20:47,946
SO ONE POSSIBILITY IS REALLY TO
TO CREATE A NETWORK OF LAB, EACH

355
00:20:48,013 --> 00:20:52,150
OF ONE WORKING WITH THEIR
ESTABLISHED MODEL.

356
00:20:52,718 --> 00:20:58,557
BUT IN THIS WAY WE WILL CREATE
HETEROGENEITY OF DIFFERENT TYPES

357
00:20:58,624 --> 00:21:04,262
OF INJURY AND IN ORDER TO HAVE
ACCESS THEN TO THE MATERIAL WE

358
00:21:04,329 --> 00:21:09,968
MAY DEVELOP WHAT WE ARE TRYING
TO TO FRAME AS A FEDERATED BIO

359
00:21:10,035 --> 00:21:15,307
REPOSITORY WHERE YOU CAN HAVE, I
MEAN WE WE DECENTRALIZED

360
00:21:15,374 --> 00:21:20,178
REGISTRY AND THE CENTRALIZED
COORDINATION SO THAT IN

361
00:21:20,245 --> 00:21:25,150
PRINCIPLE WE COULD DECIDE THAT
FOR THAT GIVEN, I MEAN

362
00:21:25,217 --> 00:21:30,689
THERAPEUTIC APPROACH OR IN ORDER
TO ADDRESS THAT PARTICULAR

363
00:21:30,756 --> 00:21:36,294
DISEASE TRAJECTORY, WE MAY WANT
TO ADDRESS IT IN THIS, THIS,

364
00:21:36,361 --> 00:21:38,130
THIS AND THIS MODEL.

365
00:21:38,196 --> 00:21:42,734
AND SO WE CAN CONNECT WITH
DIFFERENT LABS AND DO THE WORK

366
00:21:42,801 --> 00:21:47,472
IN A REASONABLE TIME FRAME AND
WITH THE LIMITED RESOURCES.

367
00:21:50,475 --> 00:21:53,945
YEAH, I WONDER IF YOU DON'T WANT
TO HAVE THE TBI MODEL,

368
00:21:54,012 --> 00:21:56,682
PRECLINICAL MODEL, GESTAPO AFTER
EVERYBODY.

369
00:21:56,748 --> 00:21:59,918
BUT YOU KNOW, WE WRITE THE FIRST
OR SECOND PARAGRAPH OF OF THE

370
00:21:59,985 --> 00:22:02,654
MANUSCRIPT AND SAY THIS MODEL IS
CLINICALLY RELEVANT.

371
00:22:02,721 --> 00:22:03,388
WELL, FORGET ABOUT THAT.

372
00:22:03,455 --> 00:22:04,356
HERE'S ALL THE DATA.

373
00:22:05,123 --> 00:22:08,493
I THINK ALL OF US WOULD REALLY
WANT TO SAY LET ME TELL YOU WHY

374
00:22:08,560 --> 00:22:11,897
IT'S CLINICALLY RELEVANT AND AND
THEN MOVE ON AND REALLY HAVE

375
00:22:11,963 --> 00:22:15,100
THAT KIND OF UNDERWRITERS
LIMITED KIND OF ENDORSEMENT THAT

376
00:22:15,167 --> 00:22:18,570
YES, THIS AT LEAST THAT ASPECT
HAS SOME CLINICAL RELEVANCY AND

377
00:22:18,637 --> 00:22:21,406
AND OF COURSE THERE'S
HETEROGENEITY CLINICALLY, BUT

378
00:22:21,473 --> 00:22:24,576
THERE ARE SOME VERY COMMON
THEMES OF NEUROPATHOLOGIES AND

379
00:22:24,643 --> 00:22:27,779
HUMAN TBI THAT I THINK MOST
PEOPLE ARE TRYING TO REPLICATE

380
00:22:27,846 --> 00:22:28,847
WITH THEIR MODELS.

381
00:22:29,114 --> 00:22:32,784
IT'S JUST A MATTER OF THEN THEY
MIGHT GET SCIENCY AND LET'S SAY

382
00:22:32,851 --> 00:22:35,954
LOOKING AFTER INFLAMMATION
PATHWAYS, WHAT IF THOSE ARE

383
00:22:36,021 --> 00:22:39,558
DIFFERENT BETWEEN THAT SPECIES
AND HUMANS THAT WE REALLY NEED

384
00:22:39,624 --> 00:22:40,392
TO KNOW ABOUT.

385
00:22:40,459 --> 00:22:44,596
SO I THINK IT'S IT'S A MATTER OF
WE REALLY HAVE TO KIND OF COME

386
00:22:44,663 --> 00:22:48,400
TO TERMS WITH YOU KNOW FOR
EXAMPLE 10 YEARS OR SO AGO THE

387
00:22:48,467 --> 00:22:52,070
DOD REFUSED TO FUND RODENT
MODELS JUST OUT OF A FEELING

388
00:22:52,137 --> 00:22:54,372
THAT THEY WEREN'T LIKELY
RELEVANT.

389
00:22:54,439 --> 00:22:54,673
SO.

390
00:22:54,740 --> 00:22:57,809
SO THIS IS SOME WAY TO KIND OF
ADDRESS THAT TO KIND OF OVERCOME

391
00:22:57,876 --> 00:22:58,110
THAT.

392
00:22:58,510 --> 00:23:02,280
WELL RODENTS ARE LIKE FULL TIME
BRAINS AND AND HAVE A WAY TO TO

393
00:23:02,347 --> 00:23:03,048
WORK ON THAT.

394
00:23:03,115 --> 00:23:06,351
SO I'D JUST LIKE TO OPEN UP THIS
TO THE FLOOR OF PEOPLE WHO USE

395
00:23:06,418 --> 00:23:09,321
PRECLINICAL MODELS AND MAYBE
EVEN YOUR OWN EXPERIENCE OF

396
00:23:09,387 --> 00:23:12,457
WHERE YOU, HOW DO YOU HANDLE
THAT FIRST OR SECOND PARAGRAPH?

397
00:23:12,524 --> 00:23:17,362
YOU KNOW, MAYBE I CAN, CAN I
CALL SOMEBODY OUT, DO YOU THINK

398
00:23:17,429 --> 00:23:22,300
MAYBE, LAURA, SO WHAT IF YOU
HAVE A NEUROSURGEON WHO'S USING

399
00:23:22,367 --> 00:23:27,372
A PRECLINICAL MODEL AND KNOWS
EXACTLY WHAT THE CLINICAL ASPECT

400
00:23:27,439 --> 00:23:28,273
LOOKS LIKE?

401
00:23:28,340 --> 00:23:29,007
SO DO YOU WANT TO PLEASE.

402
00:23:29,474 --> 00:23:39,017
I DON'T THINK SO.

403
00:23:39,084 --> 00:23:39,484
I'M NOT LYING.

404
00:23:39,885 --> 00:23:40,619
MAYBE THIS ONE ISN'T.

405
00:23:42,487 --> 00:23:47,025
YEAH, I THINK FOR ME I MEAN I DO
A LOT OF RESEARCH THAT ALSO IS

406
00:23:47,092 --> 00:23:51,596
LOOKING AT ELECTRICAL PROPERTIES
WHICH YOU GUYS DIDN'T HAVE ON

407
00:23:51,663 --> 00:23:54,399
THAT FIRST SLIDE THERE JUST AS A
BUT.

408
00:23:55,233 --> 00:23:58,670
BUT I THINK FOR ME AND I WAS
TALKING TO SOME PEOPLE ABOUT

409
00:23:58,737 --> 00:24:02,274
THIS I THINK LAST NIGHT, YOU
KNOW, WHEN I'M WRITING A GRANT

410
00:24:02,340 --> 00:24:05,977
OR THAT FIRST PARAGRAPH, I I
HAVE THE THE BENEFIT OF LIKE THE

411
00:24:06,044 --> 00:24:09,514
SECRET SAUCE OF LIKE I TALK
ABOUT LIKE MY CLINICAL STUFF.

412
00:24:10,515 --> 00:24:14,753
BUT IT IS HARD TO ACTUALLY DO
THAT TRANSLATION TO SAY WHY MY

413
00:24:14,820 --> 00:24:18,757
MODEL IS, IS, IS YOU KNOW I
HAVEN'T DONE THE CALIBRATION

414
00:24:18,824 --> 00:24:20,458
REALLY FOR A LOT OF IT.

415
00:24:20,892 --> 00:24:23,461
SO I CAN TALK ABOUT WHY IT'S
IMPORTANT TO ANSWER THE

416
00:24:23,528 --> 00:24:26,665
QUESTIONS AND LIKE THE SPECIFIC
QUESTION I'M ANSWERING BASED ON

417
00:24:26,731 --> 00:24:27,566
MY CLINICAL STUFF.

418
00:24:27,632 --> 00:24:30,468
BUT BUT YEAH, I ACTUALLY HAVEN'T
DONE A LOT OF THE CALIBRATION.

419
00:24:30,535 --> 00:24:32,938
SO LIKE I STILL HAVE ISSUES
WHERE I'LL SAY I'M GOING TO LOOK

420
00:24:33,004 --> 00:24:35,540
AT SOMETHING AT ONE DAY, THREE
DAYS AND SEVEN DAYS BECAUSE THIS

421
00:24:35,607 --> 00:24:36,741
IS WHAT I SEE IN MY PATIENTS.

422
00:24:36,808 --> 00:24:38,944
I KNOW THAT'S PROBABLY NOT THE
SAME IN A RAT, BUT LIKE I

423
00:24:39,010 --> 00:24:40,579
HAVEN'T DONE THE CALIBRATION
CELEBRATION.

424
00:24:40,645 --> 00:24:42,681
SO YEAH, I DON'T HAVE AN ANSWER
TO YOUR QUESTION REALLY.

425
00:24:44,149 --> 00:24:46,017
I MEAN BUT LIKE WHEN PEOPLE HERE
LIKE THAT.

426
00:24:46,084 --> 00:24:49,521
SO IF WE HAVE THE WHAT WE HAVE
FOR THE CONNECT CONNECTED BI IS

427
00:24:49,588 --> 00:24:52,557
REALLY TO HAVE A KIND OF A
FEDERATED A CONSENSUS THAT

428
00:24:52,624 --> 00:24:55,694
THERE'S CERTAIN CHRONIC
NEUROPATHOLOGIES IN THE CASES.

429
00:24:55,894 --> 00:24:59,264
BUT WITHIN THE UMBRELLA OF THAT
THERE ARE ACUTE CASES AND

430
00:24:59,331 --> 00:24:59,798
WHATNOT.

431
00:25:00,098 --> 00:25:03,068
AND THE IDEA WOULD BE THERE
CAN'T REALLY BE A SERVICE LIKE I

432
00:25:03,134 --> 00:25:03,401
CAN'T.

433
00:25:03,468 --> 00:25:06,438
IT'S HARD TO IMAGINE THAT YOU
KNOW, CENTRAL KIND OF, YOU KNOW,

434
00:25:06,504 --> 00:25:09,441
FISHER SCIENTIFIC RUNNING, YOU
KNOW, THESE THESE COORDINATED,

435
00:25:09,507 --> 00:25:12,344
YOU KNOW, COMPARISONS WOULD BE
MORE LIKE I I VIEW IT AS SOME

436
00:25:12,410 --> 00:25:14,913
MORE OF A MATCHMAKING
CIRCUMSTANCE WHERE THE TYPE OF

437
00:25:14,980 --> 00:25:17,682
PATHOLOGY YOU WANT TO STUDY IS
BRINGING YOU TOGETHER WITH

438
00:25:17,749 --> 00:25:19,050
SOMEBODY IN THAT NETWORK.

439
00:25:19,117 --> 00:25:21,853
SO YOU CAN PUT YOUR ANIMAL DATA
NEXT TO THE HUMAN DATA.

440
00:25:22,721 --> 00:25:27,559
YEAH, I THINK I MEAN FOR FOR
PATHOLOGY IT'S SOMEWHAT EASIER,

441
00:25:27,626 --> 00:25:28,059
RIGHT.

442
00:25:28,126 --> 00:25:29,194
WE CAN LOOK DOWN A MICROSCOPE.

443
00:25:29,261 --> 00:25:32,564
WE CAN SAY, HEY, I CAN SEE
INFLAMMATION AND THAT'S GOOD TO

444
00:25:32,631 --> 00:25:32,797
GO.

445
00:25:33,331 --> 00:25:36,301
AND AND SO THE QUESTION WE'RE
ASKING HERE IS HOW RELEVANT IS

446
00:25:36,368 --> 00:25:36,468
IT?

447
00:25:36,534 --> 00:25:39,771
SO LIKE TALK ABOUT A BETA OR TAU
IN A MOUSE MODEL, WE KNOW

448
00:25:39,838 --> 00:25:43,308
ACUTELY IT HAPPENS IN A HUMAN,
WE KNOW ACUTELY IT HAPPENS IN A

449
00:25:43,375 --> 00:25:43,708
RODENT.

450
00:25:43,775 --> 00:25:46,077
SO THAT'S ACTUALLY NOT A BAD
MODEL TO UNDERSTAND THE

451
00:25:46,144 --> 00:25:48,013
PATHOPHYSIOLOGY OF WHY THAT'S
HAPPENING.

452
00:25:48,313 --> 00:25:50,882
WE KNOW THAT CHRONICALLY IT'S
NOT REALLY HAPPENING IN MICE.

453
00:25:50,949 --> 00:25:52,517
AND SO THAT'S A BAD MODEL FOR
IT.

454
00:25:52,918 --> 00:25:55,287
AND SO WE ALL USE DIFFERENT
MODELS AND TWEAK DIFFERENT

455
00:25:55,353 --> 00:25:56,721
MODELS TO SEE WHAT'S HAPPENING.

456
00:25:56,988 --> 00:26:00,125
I THINK WE CAN YOU KNOW
UNDERSTANDING YOUR OWN MODEL AND

457
00:26:00,191 --> 00:26:03,561
AND REALLY LEARNING IT AND NOT
TRYING TO OVER PROMISE WHAT IT

458
00:26:03,628 --> 00:26:06,798
CAN DELIVER IS IS IMPORTANT LIKE
SAYING WHAT'S CLINICALLY

459
00:26:06,865 --> 00:26:07,899
RELEVANT ABOUT IT.

460
00:26:08,233 --> 00:26:12,170
YOU KNOW THIS MOUSE IS THE SAME
PATHOLOGY AND IT HAS MEMORY

461
00:26:12,237 --> 00:26:12,771
DEFICITS.

462
00:26:12,837 --> 00:26:15,874
THEREFORE I CAN DO EVERYTHING IN
THIS MODEL ISN'T THE RIGHT WAY

463
00:26:15,941 --> 00:26:16,675
TO GO ABOUT IT.

464
00:26:16,975 --> 00:26:19,844
UNDERSTANDING THE LIMITATIONS
AND SAY I'M NOT REALLY GOING TO

465
00:26:19,911 --> 00:26:22,881
STUDY, I'M NOT GOING TO PROMISE
TO STUDY SOMETHING AND AND DRAW

466
00:26:22,948 --> 00:26:25,717
OVER CONCLUSIONS FROM IT THAT
PROBABLY AREN'T TRUE IS ALSO

467
00:26:25,784 --> 00:26:26,251
IMPORTANT.

468
00:26:26,818 --> 00:26:30,088
BUT LIKE THE THINGS THAT THAT I
THINK ARE ALSO REALLY IMPORTANT

469
00:26:30,155 --> 00:26:33,058
WHEN IT COMES TO CLINICAL
TRANSLATABILITY ARE THE THINGS

470
00:26:33,124 --> 00:26:34,726
THAT ARE REALLY HARD TO MEASURE.

471
00:26:34,793 --> 00:26:37,062
WHERE WE'VE REALLY RUN INTO
TROUBLE WITH ANIMAL MODELS OF

472
00:26:37,128 --> 00:26:39,264
THINGS LIKE POST TRAUMATIC
EPILEPSY, SLEEP DISORDERS.

473
00:26:39,331 --> 00:26:42,367
THESE ARE THE THINGS THAT AFFECT
HUMANS ON A ON A HUGE SCALE.

474
00:26:42,667 --> 00:26:44,836
AND THEN WE'RE NOT REALLY
LOOKING INTO BECAUSE THEY'RE

475
00:26:44,903 --> 00:26:47,405
HARD AND THEY'VE THEY'VE BEEN
REALLY DIFFICULT TO DO IN MICE.

476
00:26:47,806 --> 00:26:50,875
AND THERE WAS A GREAT STUDY THAT
JUST CAME OUT OF A HIGHER STATE

477
00:26:50,942 --> 00:26:53,778
IN THE LAST COUPLE OF WEEKS
WHERE THEY'RE USING THE CC MICE

478
00:26:53,845 --> 00:26:56,681
AND THEY SCREENED A WHOLE BUNCH
OF THEM AND THEY SAID, HEY,

479
00:26:56,748 --> 00:26:59,384
THESE COUPLE OF OF OF OF
GENETICALLY DIFFERENT MICE ARE

480
00:26:59,451 --> 00:27:02,053
MUCH MORE SUSCEPTIBLE TO
EPILEPSY THAN THAN THAN AC 57

481
00:27:02,120 --> 00:27:05,090
MOUSE, WHICH SITS SOMEWHERE IN
THE MIDDLE OF THAT SCALE BY THE

482
00:27:05,156 --> 00:27:08,193
WAY, IT WASN'T WASN'T BY FAR THE
WORST, BUT IT CERTAINLY WASN'T

483
00:27:08,259 --> 00:27:08,693
THE BEST.

484
00:27:09,160 --> 00:27:12,564
AND SO YOU KNOW WE KEEP RUNNING
INTO THESE ISSUES OF, YOU KNOW,

485
00:27:12,630 --> 00:27:15,967
REMEMBER WHEN NIH SAID CAME OUT
WITH THE OUTRAGEOUS SUGGESTION

486
00:27:16,034 --> 00:27:19,437
WE HAD TO USE FEMALES IN OUR IN
OUR STUDIES AND WE'RE ALL LIKE,

487
00:27:19,504 --> 00:27:20,772
GOD, I CAN'T AFFORD THAT.

488
00:27:20,839 --> 00:27:22,674
LIKE NO, NO HUMAN CAN AFFORD
THIS.

489
00:27:23,074 --> 00:27:26,211
AND ALL OF A SUDDEN WE STARTED
LOOKING AND GOING, OH CRAP, THAT

490
00:27:26,277 --> 00:27:28,947
IS MASSIVELY DIFFERENT
INFLAMMATION BETWEEN A MALE AND

491
00:27:29,014 --> 00:27:31,049
FEMALE RODENT, NEVER MIND
ANYTHING ELSE.

492
00:27:31,416 --> 00:27:34,753
AND NOW WE'RE LOOKING AT GOING,
DO I HAVE TO SCREEN 32 DIFFERENT

493
00:27:34,819 --> 00:27:36,488
CC MICE TO FIND WHAT'S GOING ON?

494
00:27:36,888 --> 00:27:38,823
AND I THINK THE SAD ANSWER IS WE
PROBABLY DO.

495
00:27:38,890 --> 00:27:41,860
AND THE WAY TO DO THAT MIGHT BE
TO GET EVERYBODY TOGETHER AND

496
00:27:41,926 --> 00:27:44,729
SAY, OK, CAN WE TAKE THE SAME
MODELS, RUN IT ON ALL THESE

497
00:27:44,796 --> 00:27:47,565
DIFFERENT LABS AND SAY, HEY, I
FOUND A MASSIVE AMOUNT OF

498
00:27:47,632 --> 00:27:50,502
EPILEPSY IN MY MODEL, WHICH WE
SHOULD ALL MOVE FORWARD WITH

499
00:27:50,568 --> 00:27:53,371
THIS BECAUSE HAVING RELYING ON
ONE LAB TO DO ALL OF THESE

500
00:27:53,438 --> 00:27:55,507
DIFFERENT SCREENS IS, IS REALLY
DIFFICULT.

501
00:27:55,573 --> 00:28:00,845
SO ONE OF THE SHORTCOMINGS OF
THE EXPERIMENTAL MODELS IS THAT

502
00:28:00,912 --> 00:28:06,451
COMPARED TO HUMAN TBI, HUMAN TBI
IS USUALLY A SERIES OF IMPACTS,

503
00:28:06,518 --> 00:28:11,890
WHETHER WE SPEAK ABOUT TRAFFIC
ACCIDENTS OR FALLS OR VIOLENCE.

504
00:28:11,956 --> 00:28:16,528
AND SO THEY ARE A PRODUCT OF
SERIES OF IMPACTS.

505
00:28:16,594 --> 00:28:20,331
AND THAT IS SOMETHING THAT TO MY
UNDERSTANDING IS NOT CAPTURED IN

506
00:28:20,398 --> 00:28:23,735
EXPERIMENTAL TBI AND THAT MAKES
THIS ALSO VERY DIFFERENT.

507
00:28:27,772 --> 00:28:30,942
YEAH, OLLIE, I THINK THERE
THERE'S YOU KNOW THERE I THINK

508
00:28:31,009 --> 00:28:34,212
THERE ARE THERE ARE SOME MODELS
THAT CAN BE USED FOR TO TO

509
00:28:34,279 --> 00:28:37,248
MIMIC, YOU KNOW THE LESS
EXTENSIVE INJURY PARADIGMS.

510
00:28:37,615 --> 00:28:41,586
BUT I I WANT TO COME TO A POINT
WHERE I DON'T THINK CALIBRATION

511
00:28:41,653 --> 00:28:43,388
IS GOING TO BE ONE AND DONE.

512
00:28:44,656 --> 00:28:49,094
BECAUSE FOR EXAMPLE THE LIKE
THE, THE, THE, THE LIVING

513
00:28:49,160 --> 00:28:54,132
CONDITIONS OF THE ANIMALS CAN
RESULT IN VERY, VERY DIFFERENT

514
00:28:54,199 --> 00:28:58,903
INFLAMMATORY TONE IN THE BRAIN
EVEN FROM EXACTLY THE SAME

515
00:28:58,970 --> 00:28:59,571
STRAIN.

516
00:28:59,804 --> 00:29:03,007
BUT IN TWO DIFFERENT ANIMAL
FACILITIES, THEIR MICROBIOME CAN

517
00:29:03,074 --> 00:29:06,478
BE DIFFERENT AND SO YOU CAN GET
COMPLETELY DIFFERENT OUTCOMES OR

518
00:29:06,544 --> 00:29:09,914
TEMPORAL TRAJECTORIES OF SOME OF
THE THINGS THAT WE ACTUALLY DO

519
00:29:09,981 --> 00:29:10,849
WANT TO MEASURE.

520
00:29:11,216 --> 00:29:13,952
SO I JUST WANTED TO MAKE THE
POINT THAT I THINK CALIBRATION

521
00:29:14,018 --> 00:29:16,821
IS KIND OF A CONSISTENT THING,
GOT TO KEEP ON SORT OF TOP OF

522
00:29:16,888 --> 00:29:16,988
IT.

523
00:29:17,055 --> 00:29:21,693
BUT I THINK WE CAN GAIN A LOT BY
TRYING TO UNDERSTAND THE FACTORS

524
00:29:21,759 --> 00:29:26,030
THAT MODIFY THESE THESE THESE
TRAJECTORIES OR DIFFERENCES IN

525
00:29:26,097 --> 00:29:30,301
PEOPLE LIKE LABS THAT MIGHT BE
USING THE SAME STRAIN OR THE

526
00:29:30,368 --> 00:29:34,205
SAME MODEL, YOU KNOW, UNDER
UNDER SIMILAR CONDITIONS.

527
00:29:34,472 --> 00:29:37,208
SOMETIMES THE RESULTS ARE NOT
GOING TO BE COMPARABLE, BUT I

528
00:29:37,275 --> 00:29:39,844
THINK THERE'S GOING TO BE A LOT
OF INFORMATION ON ON ON

529
00:29:39,911 --> 00:29:41,179
UNDERSTANDING THAT AS WELL.

530
00:29:43,314 --> 00:29:46,484
AND HERE'S PROBABLY THE
OPPORTUNITY FOR THE THIS NETWORK

531
00:29:46,551 --> 00:29:49,954
IS TO SHARE THESE SAMPLES TO
THIS BIO REPOSITORY TO ACTUALLY

532
00:29:50,021 --> 00:29:53,258
EXPLORE SOME OF THESE BASIC
MECHANISMS, WHETHER IT BE THE

533
00:29:53,324 --> 00:29:56,928
MICROBIOME OR THE VARIABILITY IN
THE MODEL THAT WE CAN ACTUALLY,

534
00:29:56,995 --> 00:30:00,231
YOU KNOW BY HAVING SHARING AND
AND DOING WHATEVER TYPE OF

535
00:30:00,298 --> 00:30:03,701
SEQUENCING OR NFL BIOMARKERS,
YOU CAN SEE THE VARIABILITY IN

536
00:30:03,768 --> 00:30:04,369
THAT SYSTEM.

537
00:30:04,435 --> 00:30:07,238
SO PERHAPS WE HAVE THE SAMPLES
IN OUR FREEZERS ALREADY, IT'S

538
00:30:07,305 --> 00:30:10,241
JUST WE'RE NOT CONNECTING THEM
AND AND THAT'S MUCH LIKE CONNECT

539
00:30:10,308 --> 00:30:13,244
TBI, WE NEED TO CONNECT IT FOR
THE PRECLINICAL MODELS AS WELL.

540
00:30:13,878 --> 00:30:17,448
SO I THINK THAT THAT'S WHERE THE
OPPORTUNITY LIES IN MY, MY MIND

541
00:30:17,515 --> 00:30:17,916
ANYWAY.

542
00:30:19,017 --> 00:30:22,387
YEAH, THIS IS A QUICK POINT, YOU
KNOW THE DATA HARMONIZATION,

543
00:30:22,453 --> 00:30:22,754
RIGHT?

544
00:30:22,820 --> 00:30:24,689
YEAH, WE CANNOT MAKE EVERYTHING
IDENTICAL.

545
00:30:25,156 --> 00:30:25,456
SO.

546
00:30:25,523 --> 00:30:29,093
SO THERE ARE SOME PROJECTS THAT
ARE SHOWING SOME PROMISE LIKE

547
00:30:29,160 --> 00:30:32,263
THE OPTT THAT'S FUNDED BY DOD
PED KORANIC IS ANOTHER.

548
00:30:32,330 --> 00:30:35,066
I THINK IT'S FOCUSING ON
BIOMARKERS AND AND ALSO

549
00:30:35,133 --> 00:30:36,968
FUNCTIONAL OUTCOME AND ALL THAT.

550
00:30:37,202 --> 00:30:41,639
SO THE MORE RECENT EXAMPLE IS
TOP NT THAT YOU KNOW MARK,

551
00:30:41,706 --> 00:30:43,107
MYSELF AND OTHERS.

552
00:30:43,841 --> 00:30:45,510
HIPAA IS A PROGRAM OFFICER.

553
00:30:45,877 --> 00:30:50,715
SO IT'S LIKE 4 DIFFERENT LAB AND
THEN WE HAVE A CONSOURCE, YOU

554
00:30:50,782 --> 00:30:55,587
KNOW DATA ANALYSIS LAB, THREE
DIFFERENT ANIMAL MODELS, CCI FOR

555
00:30:55,653 --> 00:30:57,789
PERCUSSION AND ALSO CHIMERA.

556
00:30:57,855 --> 00:31:00,825
THEY'RE VERY DIVERSE AND BUT
THEY WE WE TRY TO DO IT

557
00:31:00,892 --> 00:31:02,493
REPEATEDLY IN DIFFERENT LABS.

558
00:31:02,560 --> 00:31:05,763
SO WE'RE FOCUSING ON BIOMARKERS
INCLUDING BIOMARKER AND ALSO

559
00:31:05,830 --> 00:31:06,831
IMAGING BIOMARKERS.

560
00:31:07,232 --> 00:31:10,501
SO, SO I THINK THAT'S THE WAY TO
STANDARDIZE AND AND WE FULLY

561
00:31:10,568 --> 00:31:13,972
EXPECT THAT NOT EVERYTHING WORKS
AND NOT EVERYTHING WORK IN ALL

562
00:31:14,038 --> 00:31:14,405
MODELS.

563
00:31:14,672 --> 00:31:17,709
SO WE WANT TO REALLY PUT YOU
KNOW SORT OF STRESS TEST AND SEE

564
00:31:17,775 --> 00:31:19,677
WHAT'S ROBUST AND WHAT'S LESS
ROBUST.

565
00:31:20,078 --> 00:31:20,345
SO.

566
00:31:20,411 --> 00:31:23,648
SO I THINK THAT'S THAT'S ONE WAY
TO I SEE MORE OPPORTUNITY, YOU

567
00:31:23,715 --> 00:31:26,184
KNOW, FOR THIS TYPE OF
CONSORTIUM STUDY IN THE P

568
00:31:26,251 --> 00:31:27,118
CLINICAL SETTING.

569
00:31:29,988 --> 00:31:32,490
THANK YOU SO MUCH FOR VALIDATING
MY THOUGHT PROCESS HERE.

570
00:31:33,691 --> 00:31:36,194
I'M MY WISH BY THE WAY, I FORGOT
TO INTRODUCE MYSELF IN THE

571
00:31:36,261 --> 00:31:36,594
MORNING.

572
00:31:36,794 --> 00:31:38,896
I'M A POSTDOC FELLOW WITH
PROFESSOR CHERYL WELLINGTON IN

573
00:31:38,963 --> 00:31:40,598
VANCOUVER, UNIVERSITY OF BRITISH
COLUMBIA.

574
00:31:40,965 --> 00:31:43,067
I JUST WANT TO SAY IT LOUD AGAIN
ONE MORE TIME.

575
00:31:43,134 --> 00:31:46,371
WHAT HAS BEEN I COULD HEAR IS
THE HETEROGENEITY THAT WE SEE IN

576
00:31:46,437 --> 00:31:49,674
HUMAN POPULATIONS AS WELL AS IN
ANIMAL POPULATIONS IS ACTUALLY

577
00:31:49,741 --> 00:31:50,408
OUR FRIEND.

578
00:31:50,475 --> 00:31:53,011
IT'S NOT SOMETHING TO KIND OF,
YOU KNOW, LET IT BE.

579
00:31:53,077 --> 00:31:56,014
BUT WITH THE ADVENT OF MACHINE
LEARNING, BIG DATA ANALYSIS,

580
00:31:56,080 --> 00:31:58,983
DATA HARMONIZATION, DATA MINING,
WE COULD ACTUALLY PICK UP

581
00:31:59,050 --> 00:32:01,619
PATTERNS THAT ARE BEYOND OUR
DAY-TO-DAY EXCEL SHEET

582
00:32:01,686 --> 00:32:04,255
COMPREHENSIONS AND MAKE US
WONDER THAT THINGS ARE SO

583
00:32:04,322 --> 00:32:06,057
DIFFERENT BETWEEN MODELS AND
ALL.

584
00:32:06,357 --> 00:32:09,827
AND I PERSONALLY FEEL WE DON'T
REALLY NEED TO ALIGN ALL MODELS

585
00:32:09,894 --> 00:32:13,197
ON THE SAME PAGE, RATHER EMPOWER
EACH MODEL TO LOOK AT EACH

586
00:32:13,264 --> 00:32:15,533
PATHOLOGY AS IT WAS STATED
EARLIER TODAY.

587
00:32:15,600 --> 00:32:18,503
SO I I BELIEVE AS SOON AS WE
START PUTTING IN DATA TOGETHER,

588
00:32:18,569 --> 00:32:21,005
WHETHER IT IS ABOUT THE
POSTMORTEM TISSUES THAT WE

589
00:32:21,072 --> 00:32:23,841
COLLECT, THE FEATURES, THE
ELEMENTS EVEN TO THE POINT HOW

590
00:32:23,908 --> 00:32:26,444
MANY MINUTES WAS IT LEFT IN
FORMULA IN 4% ETCETERA.

591
00:32:26,678 --> 00:32:30,181
YOU KNOW THE SUBTLE DETAILS, WE
WOULD START PICKING UP THOSE

592
00:32:30,248 --> 00:32:33,017
PATTERNS AND SEEING THOSE
CHANGES WITH TEMPORAL

593
00:32:33,084 --> 00:32:33,718
RESOLUTION.

594
00:32:33,918 --> 00:32:36,387
AND AND THAT'S PROBABLY THE WAY
TO GO IN MY HUMBLE OPINION.

595
00:32:38,289 --> 00:32:39,123
YEAH, YEAH.

596
00:32:39,190 --> 00:32:44,228
SO YOU ASKED FOR HAVING STANDARD
STANDARDIZED MODELS.

597
00:32:44,896 --> 00:32:50,335
THE VA IS FUNDING A INTERAGENCY
INITIATIVE CALLED PRECISE.

598
00:32:50,401 --> 00:32:55,473
IT'S THE PI IS IS CANDICE FLOYD
AND THAT IS THE GOAL OF THAT IS

599
00:32:55,540 --> 00:32:57,875
TO CATEGORIZE THE TBI MODELS.

600
00:32:58,109 --> 00:33:01,779
YOU MIGHT ACTUALLY HAVE SEEN
THEM AT AT SOCIETY FOR NEURO

601
00:33:01,846 --> 00:33:05,149
DRAMA MEETINGS AND THEY'RE
CATEGORIZING THE MODELS.

602
00:33:06,217 --> 00:33:09,887
THEY'RE GOING TO BE DOING A A
DETAILED PROCESS OF

603
00:33:09,954 --> 00:33:14,592
STANDARDIZING OR WHAT ARE THE
STANDARDS FOR THAT MODEL, HOW IT

604
00:33:14,659 --> 00:33:16,761
RELATES TO THE HUMAN INJURY.

605
00:33:17,128 --> 00:33:20,498
AND THAT'S ALL GOING TO BE OPEN
TO THE TO THE PUBLIC.

606
00:33:21,099 --> 00:33:25,737
SO THAT THAT INFORMATION ON HOW
TO DO THAT MODEL NOT WHAT'S THE

607
00:33:25,803 --> 00:33:30,108
CULTURE IN YOUR LAB BECAUSE I,
I, I WAS IN THAT AREA FOR A

608
00:33:30,174 --> 00:33:30,541
WHILE.

609
00:33:30,608 --> 00:33:34,212
I KNOW WE DID OUR INJURY THE WAY
THAT WE DID IT IN OUR LAB WHICH

610
00:33:34,278 --> 00:33:37,515
WAS NOT NECESSARILY SAME WAY YOU
DID CCI IN ANOTHER LAB.

611
00:33:38,616 --> 00:33:43,087
SO WE'RE WE'RE TRYING TO GET
THAT TOGETHER SO AT LEAST YOU

612
00:33:43,154 --> 00:33:47,458
CAN CHOOSE YOUR MODEL AND CHOOSE
THE PROTOCOL TO FOLLOW.

613
00:33:47,525 --> 00:33:50,895
SO IT IT WOULD BE SOME SORT OF
STANDARDIZATION TO THAT IN

614
00:33:50,962 --> 00:33:51,696
UNIFICATION.

615
00:33:52,930 --> 00:33:56,434
BUT THE THE FEAR IS THAT SO THE
SPINAL CORD INJURY FOLKS DID

616
00:33:56,501 --> 00:34:00,104
THIS YEARS AGO OF ASCUS AND THEY
DISCOVERED THAT THERE WAS THE

617
00:34:00,171 --> 00:34:03,541
SAME MODEL, THE SAME PARAMETERS
AND A COMPLETELY DIFFERENT

618
00:34:03,608 --> 00:34:05,376
OUTCOME AT AT EACH LABORATORY.

619
00:34:06,277 --> 00:34:09,113
BUT I DON'T THINK WE'RE WE'RE AT
A PLACE WHERE WE CAN HAVE

620
00:34:09,180 --> 00:34:10,181
REPLICATION OF MODELS.

621
00:34:10,248 --> 00:34:12,383
I THINK WE HAVE A TYPE OF MODEL,
YEAH.

622
00:34:12,450 --> 00:34:15,686
AND SO, AND BUT I STILL THINK
THAT IT'D BE IMPORTANT FOR EACH

623
00:34:15,753 --> 00:34:19,123
GROUP TO FIND A WAY TO CALIBRATE
THE CLINICAL RELEVANCE OF THAT

624
00:34:19,190 --> 00:34:20,792
TYPE OF MODEL, WHATEVER IT IS.

625
00:34:21,092 --> 00:34:21,359
YEAH.

626
00:34:21,692 --> 00:34:25,029
SO YEAH, I MEAN YOU REALIZE THAT
IT'S NOT A PERFECT WORLD THAT

627
00:34:25,096 --> 00:34:26,831
THERE'S GOING TO BE DIFFERENCES.

628
00:34:27,131 --> 00:34:31,302
YOU MIGHT HAVE A UNDETECTED
OUTBREAK OF ARVO IN YOUR IN YOUR

629
00:34:31,369 --> 00:34:34,872
RODENT COLONY THAT'S GOING TO
THROW OFF YOUR, YOUR

630
00:34:34,939 --> 00:34:36,541
INFLAMMATORY BIOMARKERS.

631
00:34:36,607 --> 00:34:39,076
BUT NOW YOU GOT TO START
SOMEWHERE.

632
00:34:43,414 --> 00:34:48,186
SO SINCE THE DISCUSSION WAS
DIRECTED TOWARDS HOW WE CAN

633
00:34:48,252 --> 00:34:51,589
SHARE MATERIALS EMBRACE
HETEROGENEITY.

634
00:34:52,056 --> 00:34:57,328
SO HERE IS SOMETHING WE WE
DISCUSSED LATELY AND HOW TO TO

635
00:34:57,395 --> 00:35:02,533
TO BUILD ON EXISTING WORK IN IN
IN LARGER COLLABORATIVE

636
00:35:02,600 --> 00:35:07,805
CONSORTIA AND IT HAS BEEN DONE
VERY MUCH IN THE CLINICAL

637
00:35:07,872 --> 00:35:08,539
SETTING.

638
00:35:08,606 --> 00:35:13,277
AND HERE ARE JUST EXAMPLES OF
HOW THERE ARE EXISTING NETWORKS

639
00:35:13,344 --> 00:35:18,249
AND PLATFORM THAT CAN ACCELERATE
DISCOVERING BY SHARING NOT ONLY

640
00:35:18,316 --> 00:35:22,887
KNOWLEDGE AND AND METADATA BUT
ALSO BIOMATERIALS AND HOW THE

641
00:35:22,954 --> 00:35:27,492
THE FIELD IS IS MOVING TOWARDS
THE IDEA THAT ALSO PHASE TWO

642
00:35:27,558 --> 00:35:31,929
STUDY SHOULD BE DESIGNED IN
ORDER TO ADDRESS A PARTICULAR

643
00:35:31,996 --> 00:35:34,198
PART OF PHYSIOLOGICAL ASPECT.

644
00:35:34,632 --> 00:35:39,337
AND I MEAN ADD ON TOP OF
CLINICAL OUTCOMES THAT WE HAVE

645
00:35:39,403 --> 00:35:44,208
ALWAYS RELIED ON SURROGATE
BIOMARKERS THAT CAN INFORM ON

646
00:35:44,275 --> 00:35:49,814
BATTLE PHYSIOLOGICAL CHANGES AND
SO PROVIDE A PLATFORM TO COLLECT

647
00:35:49,881 --> 00:35:54,252
DATA, CLINICAL DATA,
RADIOLOGICAL DATA, GENETIC AND

648
00:35:54,318 --> 00:35:59,690
SO ON AND ALLOW RESEARCHERS TO
TO EXPLORE THE BIOLOGICAL IMPACT

649
00:35:59,757 --> 00:36:03,327
OF INTERVENTION AND UNDERLYING
MECHANISM.

650
00:36:03,928 --> 00:36:08,733
AND IN THESE SLIDES THAT WAS
PROVIDED BY ADEL AND ME, HE MADE

651
00:36:08,799 --> 00:36:13,671
A STATEMENT THAT THIS MAY A WAY
TO FAIL FAST AND PROGRESS SOON

652
00:36:13,738 --> 00:36:17,542
IN ORDER TO SEE IF WE ARE
TARGETING THE SPECIFIC

653
00:36:17,608 --> 00:36:19,243
TRAJECTORY OR OR NOT.

654
00:36:19,844 --> 00:36:25,783
SO AND AND TO BUILD ON ON THAT
IN THE PRECLINICAL SETTING AS

655
00:36:25,850 --> 00:36:31,822
WAS JUST MENTIONED THERE ARE
ALSO VERY IMPORTANT EXAMPLES OF

656
00:36:31,889 --> 00:36:37,628
PLATFORMS THAT ARE LOOKING
TOWARDS SHARING DATA AND REFINE

657
00:36:37,695 --> 00:36:43,167
HOW WE PERFORM THE MODELS IN
TERMS OF A GOOD LABORATORY

658
00:36:43,234 --> 00:36:49,373
PRACTICE, COMMON DATA ELEMENTS
AND MAYBE CAN SET THE BASIS FOR

659
00:36:49,440 --> 00:36:51,509
MULTI CENTRE STUDIES.

660
00:36:52,076 --> 00:36:57,181
AND AND WHAT WE THOUGHT THAT ON
TOP OF THIS WHAT IS PROBABLY

661
00:36:57,248 --> 00:37:01,686
MISSING IN THE PRECLINICAL
SETTING COULD BE ROOM FOR

662
00:37:01,752 --> 00:37:06,757
SHARING NOT ONLY DATA BUT ALSO
BIOSPECIMENS AND BIOFLUIDS.

663
00:37:07,091 --> 00:37:12,997
SO WITH THIS IDEA OF A FEDERATED
PRECLINICAL BIO REPOSITORY AND

664
00:37:13,064 --> 00:37:18,502
ONE POSSIBILITY COULD BE TO
START WITH THE LIVING REGISTRY

665
00:37:18,569 --> 00:37:24,208
IN THE PRECLINICAL TBI ARENA TO
SEE WHICH ARE THE LABORATORY

666
00:37:24,275 --> 00:37:30,348
THAT WANT TO TO SHARE EXPERTISE,
MATERIALS AND METADATA AND REACH

667
00:37:30,414 --> 00:37:33,551
AND AND DEVELOP A GLOBAL
NETWORK.

668
00:37:33,618 --> 00:37:39,657
AND OF COURSE WE NEED TO ENSURE
THAT ALL THIS IS HAS BEEN WILL

669
00:37:39,724 --> 00:37:43,728
BE DONE IN THE HIGHEST LEVEL AS
POSSIBLE.

670
00:37:43,794 --> 00:37:49,333
SO THE IDEA IS TO CONNECT WITH
THE ALREADY ESTABLISHED NETWORK

671
00:37:49,400 --> 00:37:54,372
THAT HAVE DEVELOPED A GOOD
LABORATORY PRACTICE, STANDARD

672
00:37:54,438 --> 00:37:59,977
OPERATOR PROCEDURES AND TO COME
TO BE COMPLIANT TO COMMON DATA

673
00:38:00,044 --> 00:38:00,778
ELEMENTS.

674
00:38:00,845 --> 00:38:05,249
SO THIS CAN ONLY BE DONE BY
COLLABORATING WITH WITH ALREADY

675
00:38:05,316 --> 00:38:10,054
EXISTING ACTIVITIES AS MENTIONED
PRECISE, TBI, TOP AND TOBTT AND

676
00:38:10,121 --> 00:38:11,322
SO ON AND SO ON.

677
00:38:11,722 --> 00:38:15,893
BUT THIS COULD BE THE BASIS TO
DEVELOP WITHIN INTERVIEW THAT

678
00:38:15,960 --> 00:38:20,331
MERGES CLINICAL AND PRECLINICAL
EXPERIENCE A COMMON STRATEGY TO

679
00:38:20,398 --> 00:38:23,234
INTEGRATE PRECLINICAL AND
CLINICAL DATA.

680
00:38:23,868 --> 00:38:29,974
SO IN THIS IDEA OF A CENTRE WITH
NO WORDS BUT BUT PILLARS, WHAT

681
00:38:30,041 --> 00:38:35,646
WE WOULD NEED TO SEEK WOULD BE
RESOURCES FOR A CENTRALIZED

682
00:38:35,713 --> 00:38:37,014
COORDINATION.

683
00:38:37,081 --> 00:38:42,787
SO TO ENSURE OF COURSE THAT WHO
WANTS TO CONTRIBUTE CAN SEE HIS

684
00:38:42,853 --> 00:38:48,292
INTELLECTUAL PROPERTIES INSURED
AND DATA PRIVACY AND SO ON.

685
00:38:48,592 --> 00:38:54,665
BUT ALSO HAVE THE POSSIBILITY TO
HAVE THE MANAGEMENT OF LOGISTIC

686
00:38:54,732 --> 00:39:00,104
AND DISTRIBUTION ROLES SET UP
AND A SORT OF A PRECLINICAL

687
00:39:00,171 --> 00:39:05,876
MONITOR THAT WILL VISIT THE
DIFFERENT CENTRES IN ORDER TO BE

688
00:39:05,943 --> 00:39:11,515
SURE THAT ALL THE PROCEDURE ARE
HARMONIZED WITHIN DIFFERENT

689
00:39:11,582 --> 00:39:12,817
LABORATORIES.

690
00:39:13,517 --> 00:39:19,090
AND IDEALLY THIS COULD REALLY
CONTRIBUTE TO OF COURSE WE WITH

691
00:39:19,156 --> 00:39:24,795
WHAT IS ALREADY EXISTING TO TO
PROVIDE ADDITIONAL METADATA AND

692
00:39:24,862 --> 00:39:30,301
BIG DATA ANALYSIS AND TO BE THE
BASIS FOR CONDUCTING WHAT WE

693
00:39:30,367 --> 00:39:36,307
DISCUSSED BEFORE LIKE MULTI SIDE
PRECLINICAL STUDIES TO TAKE INTO

694
00:39:36,373 --> 00:39:41,645
ACCOUNT DIFFERENT MODELS,
DIFFERENT SETTING TO INVESTIGATE

695
00:39:41,712 --> 00:39:43,881
THE PARTICULAR APPROACH.

696
00:39:48,919 --> 00:39:51,722
THIS WAS GETTING INTO SOMETHING
THAT I WAS THINKING ABOUT, BUT

697
00:39:51,789 --> 00:39:53,691
AGAIN I'M NOT AT YOU GUYS ARE
THE EXPERTS.

698
00:39:53,758 --> 00:39:59,063
AND SO MY POINT IS USUALLY IN A
QUESTION IF YOU'RE GETTING THE

699
00:39:59,130 --> 00:40:04,235
CLINICAL DATA, I WAS THINKING
EARLIER ABOUT ALL THE CLINICAL

700
00:40:04,301 --> 00:40:08,939
NETWORKS, YOU GUYS KNOW THEM
FROM TRACK TO CARE TO THE

701
00:40:09,006 --> 00:40:13,844
LIGHTS, TRAUMA NETWORK TO
CONNECTING ALL OF THESE, IF YOU

702
00:40:13,911 --> 00:40:15,880
COULD GET SOME TYPE OF.

703
00:40:16,413 --> 00:40:20,484
AI, MACHINE LEARNING OR
SOMETHING TO TELL YOU THAT 20%

704
00:40:20,551 --> 00:40:24,855
OF 10,000 OF THESE TB IS ARE
SIMILAR, 20% OF THEN YOU CAN

705
00:40:24,922 --> 00:40:28,325
BUILD AN ANIMAL MODEL TO MEET
THAT 20% CAUSE.

706
00:40:28,392 --> 00:40:31,061
THE REST OF THEM ARE NOT REALLY,
THEY'RE KIND OF ALL OVER THE

707
00:40:31,128 --> 00:40:31,328
PLACE.

708
00:40:31,395 --> 00:40:35,666
BUT IF YOU CAN GET SOME HUMAN
DATA THAT IT'S SOMEWHAT SIMILAR

709
00:40:35,733 --> 00:40:39,436
TO SOME STANDARDS THAT YOU
DECIDE AND IT'S 20% OF THE

710
00:40:39,503 --> 00:40:43,674
POPULATION OR WHATEVER, THEN
THAT ANIMAL MODEL COULD ADDRESS

711
00:40:43,741 --> 00:40:47,978
20% OF THOSE OF THAT BECAUSE I
DON'T THINK WE'RE GOING TO GET

712
00:40:48,045 --> 00:40:49,814
ALL TB IS WITH ONE MODEL.

713
00:40:49,880 --> 00:40:52,850
YOU KNOW, I'M JUST TRYING TO
RELATE IT TO, BUT THAT'S

714
00:40:52,917 --> 00:40:56,320
PROBABLY EASIER SAID THAN DONE
TO GET ALL THAT CLINICAL DATA

715
00:40:56,387 --> 00:40:56,620
OUT.

716
00:40:58,255 --> 00:40:58,689
ALL RIGHT EVERYBODY.

717
00:40:58,756 --> 00:41:01,826
WELL THIS IS A PRETTY
INTERESTING AND THEN I THINK AND

718
00:41:01,892 --> 00:41:05,529
SOMEBODY'S INSPIRING BUT I THINK
IT BRINGS QUESTIONS TO A LOT OF

719
00:41:05,596 --> 00:41:08,933
US TO KIND OF HELP KIND OF YOU
KNOW YOU KNOW REFINE THE THE

720
00:41:08,999 --> 00:41:12,436
APPROACH AND A LOT OF THIS WORK
IS DONE THROUGH THE DIFFERENT

721
00:41:12,503 --> 00:41:15,339
WORKING GROUPS WHETHER IT'S
NERPATHOLOGY OR OR THE

722
00:41:15,406 --> 00:41:16,140
TRANSLATIONAL.

723
00:41:16,207 --> 00:41:18,809
SO IF YOU WANT TO BE PART OF
THAT PLEASE I MEAN IT'S YOUR

724
00:41:18,876 --> 00:41:20,945
EVERYBODY'S WELCOME AND REALLY
TRY TO WORK.

725
00:41:21,011 --> 00:41:25,015
I I THINK WE'RE REALLY CLOSE TO
BEING ABLE TO HAVE A FIRST START

726
00:41:25,082 --> 00:41:28,986
SOLUTION HERE IN KIND OF, YOU
KNOW, GETTING THAT THAT YOU KNOW

727
00:41:29,053 --> 00:41:32,957
WORK TOWARDS CLINICAL RELEVANCY
BOTH THE ONE DIRECTION AND THE

728
00:41:33,023 --> 00:41:33,390
OTHER.

729
00:41:33,757 --> 00:41:36,160
THINKING IS YOUR MODEL
CLINICALLY RELEVANT AND DO THE

730
00:41:36,227 --> 00:41:38,495
IS THE DATA FROM YOUR MODEL
CLINICALLY RELEVANT.

731
00:41:39,196 --> 00:41:41,732
SO I'M I'M AFRAID WE'RE KIND OF
RUNNING A LITTLE LATE.

732
00:41:41,799
SO THANK YOU ALL FOR YOUR
PARTICIPATION