THIS YEAR'S WORKSHOP IS
ADVASING OUTCOME MEASURE
DEVELOP AM AND ANALYTICAL
APPROACHES SO THE PAIN ANIMALS
WORKSHOP WAS SET UP WITH THE
DIVISION TO DIGS CUSS THE
MEASUREMENT OF PAIN IN ANIMALS.
AND THE GOAL REALLY OF THE
WORKSHOP IS TO BE A FORM OF
DISCUSSION AND EXCHANGE OF IDEAS
AND HOPEFULLY YOU'VE MET A FEW
PEOPLE AND YOU REALIZE IT'S
QUITE A MIXED GATHERING HERE.
WE HAVE INDIVIDUALS FROM REG LA
THORY EAMTIONS, WE HAVE
INDIVIDUALS FROM INDUSTRY BOTH
ON THE VETERINARY AND HUMAN SIDE
OF INDUSTRY.
WE HAVE FOLK FROM THE NIH, FROM
PRIVATE PRACTICE, VETERINARY
PRACTICE FROM ACADEMIA AND SO,
IN A SENSE IT'S KIND OF AN
UNCOMFORTABLE MIX, ISN'T IT IN
BECAUSE YOU'RE NOT NECESSARILY
SURROUNDED BY YOUR REGULAR
COLLEAGUES, YOUR REGULAR FRIENDS
BUT I THINK THAT UNCOMFORTABLE
MIX HOPEFULLY WILL BECOME
COMFORTABLE AND I THINK THAT'S
REALLY IMPORTANT BECAUSE WE'RE
REALLY, WE'RE ALL INVOLVED IN
THE SAME THING.
WE'RE ALL INVOLVED IN ANIMAL
RESEARCH, ON THE VETERINARY
CLINICAL SIDE, ON THE RESEARCH
SIDE, DEVELOPMENT OF
THERAPEUTICS AND WE'RE ALL
STRUGGLING WITH THE SAME
QUESTIONS, WE'RE STRUGGLING WITH
HOW DO WE MEASURE PAIN IN OUR
MODEL, IN OUR PATIENTS >> IN
OUR CLINICAL MODELS.
SO HOPEFULLY THERE WILL BE
PLENTY OF EXCHANGE AND
PRESENTATION OF IDEAS.
HOPEFULLY YOU MAY LISTEN TO A
LECTURE ON A SPECIES YOU MAY
NEVER EVER WORK ON, BUT
HOPEFULLY WHEN YOU LISTEN TO
THAT, YOU MAY TAKE AWAY A FEW
IDEAS AND MODEL TO YOUR
DEPARTMENT AND HOPEFULLY WE WILL
INFLUENCE TRANSLATIONAL AND
VETERINARY RESEARCH EMPLOY SO
VERY STRONG AIM OF THIS WORKSHOP
IS TO DEVELOP OUR ABILITY IN
PAIN AND ANIMALS SO THAT ANIMALS
ARE BETTER MODELS SO THAT WE CAN
ADVANCE HUMAN PAIN THERAPEUTIC
DEVELOPMENT.
AT THE SAME TIME UNDERSTAND MORE
ABOUT HOW TO MEASURE AND
THEREFORE CONTROL PAIN IN
ANIMALS.
AND SO THOSE THINGS VERY MUCH
ARE INTERWOVEN HERE IN THIS
THEME AND HOPEFULLY WILL IMPROVE
HUMAN AND ANIMAL HEALTH WELFARE
AND WELBEING.
THE PRESENTATIONS AS WE GO
THROUGH THE DAY ARE THE AGENDA
GIVES YOU THE TIME OF THE
SPEAKERS.
SPEAKERS PLEASE PAY TEAPGZ TO
THAT.
WE WILL NOT TAKE QUESTIONS AFTER
EACH DISCUSSION BUT INSTEAD WE
WILL SAVE THOSE FOR THE PANEL
DISCUSSIONS AT THE END OF EACH
SESSION.
I WANT TO ACKNOWLEDGE THE
ORGANIZING COMMITTEE HERE.
THESE ARE INDIVIDUAL WHO IS CAME
TOGETHER TO MAKE THIS HAPPEN,
THEY'RE A DIVERSE ORGANIZING
COMMITTEE AND I THINK THAT
REALLY THEN SPEAKS TO THE
RICHNESS OF THE PROGRAM AND
EVERYONE HAS PULLED THEIR WEIGHT
HERE.
I DO WANT TO CALL OUT MARIE GILL
WHO LATE LAST NIGHT WAS DOING A
STELLAR JOB OF PICKING UP ALL
THE MESS THAT THE REST OF US HAD
LEFT BEHIND AND BRENGING THIS
TOGETHER.
SO THANK YOU VERY MUCH.
NONAPOPTOTIC A MEETING LIKE
THIS, ALTHOUGH AUTOAIR
RELATIVELY SMALL MEETING COSTS
10S OF THOUSANDS OF DOLLARS TO
PUT ON, MAYBE 70, $80,000, YOU
THIS WOULD NOT HAVE HAPPENED,
YOU DON'T PAY REGISTRATION FEES
BECAUSE WE'RE HERE AT THE NIH,
THAT'S AN IMPORTANT PART OF THIS
BUT THERE'S I LOT OF COSTS THAT
GO ON TO PUT ON A MEETING LIKE
THIS.
SO EXTREMELY GRATEFUL TO THE MAY
DAY FUND, IN PARTICULAR
CHRISTINE SPELMAN WHO HAS TALKED
TO THE BOARD AND BEEN A GREAT
SUPPORTER AND THE NIH ARE
PROVOIDING THE ROOM AND THE AV
SUPPORT AT NO CHARGE.
>> WE HAVE ADEGRADATIONAL
SUPPORT FROM THE MORRIS ANIMAL
FOUNDATION AND THE PAIN
EDUCATION CENTER AND COMPARATIVE
PAIN RESEARCH FROM NC STATE.
SO THANK TO YOU ALL OF OUR
SPONSORS.
THERE WILL BE CONTINUED
EDUCATION CERTIFICATE FOR THOSE
WHO WOULD LAKE THEM EMPLOY THEY
WILL BE ISSUED SHORTLY AFTER THE
WORKSHOP.
IF YOU DON'T RECEIVE YOUR
CERTIFICATE, BY THE END OF NEXT
WEEK, PLEASE CONTACT DANE AND
THAT'S HIS WORK E-MAIL THERE, CE
REGIVATION AT NCSU.EDU.
ALL RIGHT, JUST A COUPLE OF
HOUSEKEEPING THINGS HERE.
SO WE ARE IN THE--I CAN'T WORK
THAT.
WE ARE IN THE AUDITORIUM THERE,
THAT'S WHERE THE PRESENTATIONS
ARE TAKING PLACE.
YOU PROBABLY FIGURED OUT
REGISTRATION IS JUST OUTSIDE,
COFFEE IS JUST BEYOND THAT,
THAT'S WHERE THE BOX LURCHS WILL
BE AT LUNCH TIME.
IF YOU KEEP GOING BEHIND THAT,
THERE'S A ROOM E1 AND E2, THERE
WILL BE 2 PRESENTATIONS AT LUVEN
TIME IN THERE.
THEY WILL BE SEQUENTIAL, THEY
WILL BE IN YOUR ASCRENDA AND YOU
CAN GRAB A BOX LUNCH AND PARK
YOURSELF IN E1, E2 ASK LISTEN TO
THOSE PRESENTATIONS.
LATER ON AT THE END OF THE DAY,
WE WILL HAVE A RECEPTION, HEAVY
OR'ORDEAURK Vs, AND THEN GO
BACK INTO THE STAIRS INTO THE
AUDITORIUM WITH A BASIC OF
WINDOWS, THERE WILL BE POSTERS
THERE, WINE, BEER, APPETIZERS, A
CHANCE TO ENGAGE WITH COLLEAGUES
AND OTHER ATTENDEES.
SO WE'RE GOING TO KICKOFF THIS
MORNING THE THEME OF THIS
MORNING'S UPDISTRICT ATTORNEYS
ON VALIDATED APPROACHES TO
MEASURING PAIN AND THAT WILL
MORPH INTO A DISCUSSION ABOUT
THE APPLICATION OF ARTIFICIAL
IPT GREATER TELEIENCE AND
MACHINE LEARNING.
AND IT'S MY PLEASURE NOW TO
INTRODUCE THE FIRST
PRESENTATION.
THIS IS THE MICHELLE SHARKEY PAW
LECTURE, MICHELLE SHARKEY,
UNFORT MATILY DIED IN 2022, SHE
WAS A TEAM MEMBER, FRIEND ASK
INTEGRAL PART OF THE
ORGANIZATION OF THE PAW MEETINGS
RIGHT FROM THE START.
FOR OVER 20 YEARS MESHLE WORKED
AT THE CENTER FOR VEDINARY
MEDICINE AND WAS A VERY STRONG
ADVOCATE FOR THE DEVELOPMENT OF
ANALGESICS FOR ANIMALS, THE
DEVELOPMENT BEHIND THAT, OF PAIN
ASSESSMENT TOOLS.
SHE WAS AN ABSOLUTELY WONDERFUL
PERSON.
YOU WILL HEAR IN DCORRELATED
TTIAFTER THE ACCIDENT
PRESENTATION IN A MOMENT, YOU
WILL HEAR SNIPITS THAT SPEAK TO
HER PERSONALITY BUT SHE WAS
ALWAYS ABSOLUTELY DELIGHTFUL, SO
HIGHLY ORGANIZED IT WAS UNREAL.
SHE REALLY MOVED OUR MEETINGS
FORWARD AND MADE THE PAW
MEETINGS HAPPEN.
SO SHE'S VERY MUCH MISSED.
AND SHE WAS INSTRUMENTAL IN
STARTING THE PAIN ANIMALS
WORKSHOP.
SO AT 10 AMAND I DO REMEMBER THE
TIME AT 10 AMON THE 23rd OF
DECEMBER IN 2015, I HAD A CALL
WITH MICHELLE WITH THIS IDEA OF
TALKING ABOUT THE PAIN IN
ANIMALS WORKSHOP.
SHE WAS REALLY EXCITED,
ABSOLUTELYON BOARD AND SHE
REALLY PICKED IT UP AND DROVE IT
FORWARD FROM THAT POINT ALLOWING
THE 50 MEETING TO BE HELD IN
2017.
SO IT'S AN HONOR TO HAVE A
MEMORIAL LECTURE IN HER HONOR,
AND THERE'S NO 1 BETTER TO
PRECEPT THIS THAN DOTTIE BROWN.
DOTTIE SPEPT MOST OF HER CAREER
AT THE UNIVERSITY OF
PENNSYLVANIA WHERE SHE WAS A
SURGEON, EPIDEMIOLOGIST AND
CLINICAL PAIN RESEARCHER.
IF YOU DON'T KNOW DOTTIE BROWN,
YOU'VE PROBABLY HEARD OF THE
CBPI, THEY'RE ALMOST SYNONYMOUS.
SHE MOVED THAT FORWARD, SHE
DEVELOPED THAT AND SHE REALLY
SPEARHEADED US TALKING ABOUT
OWNER ASSESSMENT TOOLS ACCIDENT
CAREGIVER ASSESSMENT TOOLS AS A
MEASUREMENT OF THE IMPACT OF
PAIN.
FROM THE UNIVERSITY OF
PENNSYLVANIA SHE MOVED TO
[INDISCERNIBLE] WHERE SHE HEADED
UP MORE TRANSLATIONAL INITIATIVE
AND SHE MOVED TO MARS PET
HEALTHCARE WHERE SHE LEADS UP
SCIENTIFIC INNOVATION GLOBALLY.
SHE--BECAUSE OF THAT MOVE AND A
CONFLICT THAT CAME UP IN TERMS
OF SCHEDULING, SHE CANNOT BE
HERE TODAY BUT SHE HAS RECORDED
A PRESENTATION AND I'M GOING TO
DO MY BEST TO BRING THAT UP.
SHE'S GOTTEN IT.
>> I'M SO SORRY I'M NOT ABLE TO
BE THERE WITH YOU IN PERSON-
-NGOOD MORNING EVERYONE,
I'M SO SORRY THAT I'M NOT ABLE
TO BE THERE WITH YOU IN PERSON
TODAY, BUT I AM REALLY, REALLY
TRULY HONORED TO BE ABLE TO
DELIVER THIS FIRST MICHELLE
SHARKEY MEMORIAL LECTURE.
MANY OF YOU KNEW MICHELLE AS A
REALLY KEY FIGURE IN THE SUCCESS
OF THIS PAIN AND ANIMAL WORKSHOP
WHICH STARTED BACK IN 2017.
FOR US ON THE PLANNING COMMITTEE
MICHELLE WAS THE FLU THAT HELD
OUR TEAM TOGETHER, SHE KEPT US
ON TRACK WITH AGENDA AND
MINUTES, SHE WAS REALLY GOOD AT
HEARDING ANIMALS BUT MORE
IMPORTANTLY SHE KEPT US FOCUS ON
OUR MISSION, SHE CAME ON TO
EVERY CALL WITH A CHEERY HIGH
GANG, MOW MATTER WHAT WAS GOING
ON IN HER LIFE, SHE FELT LIKE
PERFECT FOCUS ON WAS ON THE TEAM
AND ON THE TEAM'S GOALS AND SHE
ALWAYS FINISHED EVERY SINGLE
CALL BY THANKING EVERYONE FOR
THEIR TIME AND FOR THEIR
CONTRIBUTIONS.
SHE CONNECTED INDIVIDUALLY WITH
EVERYONE IN ONLY THE MOST
POSITIVE AND UPLIFTING WAYS.
AND OF COURSE, MICHELLE'S FAMILY
KNEW HER BEST AND HER BROTHER
CHUB WAS KIND ENOUGH TO SHARE
WITH US INSIGHTS INTO MICHELLE'S
LOVE AND PASSION FOR WHAT SHE
DID.
HER BROTHER WROTE DR. MICHELLE
SHARKY TOOK GREAT PRIDE IN THE
PAIN AND ANIMAL WORKSHOP AND WAS
1 OF THE PEOPLE WHO HELPED TO
GET IT STARTED.
LAST FEBRUARY MICHELLE DIED
AFTER A LONG VALIANT BALGT
AGAINST CANCER.
AS HER TIME GREW SHORT, SHE SAID
SHE WOULD LIKE TO HAVE PAWS
CITED IN HER OBITIARY.
ALWAYS A STRONG DETERMINED
WOMAN, DR. SHARKY KEPT HER
CANCER BATTLE PRIVATE.
SHE LOVED HER JOB AND VALUED HER
COLLEAGUESA THE FDA SO MUCH THAT
SHE CONTINUED HER WORK TO THE
VERY END OF HER LIFE, NOT
WANTING TO SEPARATE HERSELF FROM
HER COLLEAGUES OR THEIR MISSION.
MICHELLE ALWAYS WANTED TO BE A
VETERINARIAN, HER FAMILIES
REMEMBERS HER AS A YOUNG CHILD
RAPPING THE PAWS OF THE FAMILY
DOG IN TOILET PAPER EMPLOY WHILE
MICHELLE WAS ALWAYS MORE
COMFORTABLE IN THE BACKGROUND,
NAMING THIS PAWS LECT NUR HER
HONOR WOULD UNDOUBTED HE BRING A
BIG BOWFUL SMILE WE ALL REMEMBER
TO HER FACE.
SO, THANKS SO MUCH TO MICHELLE'S
FAMILY FOR SHARING THEIR
BEAUTIFUL WORDS WITH US IN
ADDITION TO BEING A ROLELY
IMPORTANT AND SPECIAL PERSON TO
THE REASON THAT WE SIT HERE
TODAY, MICHELLE WAS IMPORTANT IN
MY OWN PERSONAL JOURNEY AND THE
SEARCH FOR BETTER WAYS TO
IDENTIFY AND TREAT CHRONIC PAIN
IN OUR COMPANION ANIMALS WHICH I
WILL SHARE IN A BIT LATER.
WHAT I WOULD LIKE TO DO ON THE
NEXT HALF HOUR OR SO IS LOOK
BACK TO WHERE WE STARTED IN OUR
SEARCH FOR WAYS TO MEASURE AND
IMPACT CHRONIC PAIN ACROSS
SPECIES.
WHERE WE ARE NOW, AND THINK
ABOUT WHERE WE'RE GOING IN THE
FUTURE.
FOR ME PERSONALLY AS I THOUGHT
BACK ON THIS, I CONSIDER THIS
JOURNEY AS 1 OF THE YELLOW BRICK
ROAD.
AS WE ALL KNOW THE YELLOW BRICK
ROAD WAS A KEY FEATURE IN THE
WIZARD OF OZ WHICH DOROTHY AND
HER FRIENDS USE TO FOLLOW TO THE
EMERALD CITY AND OVERTIME THE
CONCEPT OF THE YELLOW BRICK ROAD
HAS EVOLVED TO REPRESENT A
COURSE OF ACTION THAT A PERSON
TAKES BELIEVING IT WILL LEAD TO
GOOD THINGS AND THAT HAS ALWAYS
REALLY RESONATE WIDE ME.
I THINK SOMETIMES WHEN THE ROAD
IS REALLY LOPPING, AND WHEN THE
JOURNEY'S REALLY HARD, IT'S
DIFFICULT TO SEE HOW FAR WE'VE
COME, PARTICULARLY WHEN WE'RE
WORKING REALLY, REALLY HARD IN
THE MOMENT.
I THINK NOW'S REALLY A PERFECT
TIME TO ELECTRIC BACK AS WE'RE
COMING YOU--LOOK BACK AS WE'RE
COMING UP ON A DECADE FROM
BEGINNING THE FIRST PAWS
WORKSHOP, SO I WILL DATE MYSELF
MANY TIMES OVER THIS, BUT I WILL
TART WITH MY OWN PERSONAL
PERSPECTIVE ON THIS JOURNEY AND
BRING YOU GO TO US TOGETHER TO
THINK ABOUT WHERE WE ARE NOW AND
WHERE WE'RE GOING.
SO THIS IS THE 30,000-FOOT VIEW
OF THE JOURNEY OF DEVELOPMENT
FOR OFTIO ARTHRITIS PAIN MANAGE
AM WHICH IS WHERE MOST CHRONIC
PAIN MANAGEMENT PAIN HAS BEEN
FOCUSED BECAUSE IT'S SO
PREVALENT IN DOGS.
THIS SPANS THE FULL SPECTRUM
FROM WHEN THERE WAS NOTHING
APPROVED FOR USE TO TODAY WHERE
MORE NOVEL MODES OF ACTION ARE
NOW BECOMING AVAILABLE.
SO I FIRST STARTED ON THIS
JOURNEY WAY BACK IN THE OTC
TIME, SO THE OVERTHE COUNTER
TIMES, PRIOR TO THE FIRST
NONSTEROIDAL BEING APPROVED FOR
DOGS IN 1996.
AND THIS IS A TIME WHEN WE WERE
REALLY TREATING ONLY THE MOST
AFFECTED ANIMALS.
WE TALKED TO OWNERS A LOT ABOUT
THINGS LIKE CONTROLLED EXERCISE
AND SWIMMING, WE TRIED TO HELP
OWNERS NAVIGATE TO A SAFE PLACE
POSSIBLE, ADMINISTER ASPIRIN AND
WRITE PREARE SCRIPGZS FOR PEROX
CAM, AT THE TIME FROM A
THERAPEUTIC TANNED POINT, THIS
WAS THE BEST WE COULD DO AND
UNFORTUNATELY MANY DOGS HAD
THEIR OFTIO ARTHRITIS PAIN GO ON
NOT ADEQUATELY TREATED AND MANY
TIMES NOT AT ALL AND PART OF
THIS LACK OF TREATMENT WAS DUE
TO THE LACK OF TRULY SAFE AND
EFFECTIVE THERAPEUTICS AND PART
WAS DUE TO THE LACK OF
RECOGNITION OF THE PREVALENCE OF
OFTIO ARTHRITIS AND THE SIGNS OF
CHRONIC PAIN C
HRONIC PAIN IN OUR PATIENTS.
IT WAS THE POINT AT WHICH THE
VIABILITY OF A PAIN THERAPEUTIC
DROVE THE DESIRE TO UNDERSTAND
THE TRUE PREVALENCE OF THE STEEZ
AND THE BEST WAY TO RECK MYSELF
IT IN OUR PATIENTS.
THERE WAS A RELATIVELY QUICK
SUCCESS OF APPROVALS OF
ADDITIONAL NONSTEROIDALS AND
THERE WERE EDUCATIONAL PROGRAMS
ON HOW TO RECOGNIZE CHRONIC PAIN
IN DOGS THAT WERE LAUNCHED BY
THE COMPANIES THAT WERE
DEVELOPING THE DRUGS.
AND PRACTICE CHANGED, THE
OWNER'S MIND SET OF OH SHE'S
JUST LYING DOWN BECAUSE HE'S
GETTING OLDER, KIND OF SLOW LE
SHIFTED TO PROACT OFLY MAKING
APPOINTMENTS BECAUSE I THINK MY
DOG HAS ARTHRITIS.
VETERINARIANS BEGAN MAKING
DECISIONS ABOUT WHICH NSIDES TO
USE AND WHICH NSAID TO USE AND
HOW TO DECIDE WHEN A SWITCH WAS
NEEDED.
AND IT WASN'T JUST DAILY
PRACTICALIS THAT CHANGED.
RESEARCH CHANGED AS WELL MUCH
WHEN A PROVEN THERAPEUTIC BECAME
AVAILABLE, IT BECAME POSSIBLE TO
DO REALLY ROBUST STUDIES
EVALUATING THE EFFECTIVENESS OF
METHODS TO DIAGNOSE AND TREAT
AND MONITOR DISEASE.
ON THE GRAPH ON THE RIGHT, YOU
CAN SEE THE RELATIVELY LOW
INCIDENCE OF PAPERS THAT WERE
MEPGZING THE PREVALENCE OF K908
PRIOR TO 1996 AND HOW THE YEAR
OVER YEAR INCIDENTS DRAMATICALLY
INCREASES AFTER 1996 TO OVER
300% IN THE EARLY 2000S, AND
THAT KIND OF SETTLES BACK TO THE
ESTATEITATE WHERE WE ARE NOW OF
ABOUT WOP 30% YEARLY INCREASES,
SO A REALLY EXCITING TIME TO BE
A PRACTITIONER AND SCIENTIST
INTERESTED IN THE MEASUREMENT
AND MANAGEMENT OF CHRONIC PAIN.
FOR ME DURING THIS TIME BECAME
IF INVOLVED IN SETTING UP
TRANSLATIONAL RESEARCH PROGRAM.
SO IN COLLABORATION WITH THE
FOLKS AT THE UNIVERSITY SCHOOL
OF PENNSYLVANIA WE WERE LOOKING
TO FOCUS ON THE USE OF
NEUROTOXINS FOR BONE CANCER PANE
AND IT WAS A RESPONSE TO THIS
REALIZE THAT THERE WAS A LACK OF
A FULL SET OF CLINICALLY
APPROPRIATE ANIMAL MODELS FOR
BOTH BASIC SCIENCE TRANSLATIONAL
RESEARCH AND CLINICAL TRIALS SO
OF PROMISING AGENTS.
WE WERE STUDYING DOG FIST
OSTEOSARCOMA AS A PRECLINICAL
MODEL OF HUMAN CANCER PAIN AND
WE DID MORE STUDIES IN CLINICAL
ANIMALS AND THEN AS WE MOVED TO
STUDIES IN DOGS WITH BONE
CANCER, 1 OF THE BIG QUESTIONS
HOW ARE WE GOING TO MEASURE
OUTCOME?
HOW WILL WE KNOW IF THE
NEUROTOXINS HAD A BENEFICIAL
EFFECT IN WE'VE DON'T THIS AND
GAIN ANALYSIS ASK USED A VISUAL
AN LOG SCALE AS EFFICACY OUTCOME
MEASURES, BUT WE ACTUALLY RAN
INTO SOME ISSUES WITH EACH OF
THESE APPROACHES.
FOR DIFFERENT REASONS THE
THERMAL SUSCEPTIVE TESTING AND
THE GAIN ANALYSIS WEREN'T
FEASIBLE AT SCALE, THE TERMAL
TESTING ISSUES EQUIPMENT WASN'T
AVAILABLE FOR THE LARNL AND
GIANT BREED DOGS ON THE STUDY
AND GAIN ANALYSIS WAS DIFFICULT
FOR CANCER USING THE TECHNOLOGY
THAT WAS AVAILABLE AT THE TIME.
A LOT OF DOGS HAD DIFFICULTY
GOING BACK AND FORTH OVER THE
FORCE PLATE MULTIPLE TIMES TO
GET THE NUMBER OF PASSES NEEDED
TO DO VALID TRIALS.
SO WE REALIZED WE WERE GOING TO
NEED ANOTHER APPROACH TO
MEASURING OUTCOME, SO AS PART OF
AN NIH GRANT TO EVALUATE
NEUROTOXINS IN DOGS WITH OFTIO
ARGT RIGHT WE ADDED A NAME TO
FESTER DEVELOP A VALIDATED TOOL
THAT WOULD ALLOW US TO RELIABLY
CAPTURE THE DOG'S BEHAVIORS AND
ACTIVITIES IN ITS HOME
ENVIRONMENT, SO GUY QUANTIFYING
THE OWNER'S ASSESS AM OF PAIN
OUTCOME IN THEIR DOG, WE KNEW
THE RELATIVELY RAP EDUCATIONAL
DEC PROGRESSION OF OSTEOSARCOMA
WOULD MAKE DEVELOPING THE TOOL
IN THAT POPULATION VERY
DIFFICULT, SO WE DECIDED TO
FIRST DEVELOP THE INSTRUMENT IN
DOGS WITH A MORE CHRONIC PAIN
STATE, SO DOGS WITH
OSTEOARTHRITIS AND VALIDATED IN
DOGS WITH BONE CANCER AS A
SUBSEQUENT STEP AND THIS IS
WHERE WE ARRIVEDDA THE CANINE
BRIEF PAIN INVENTORY.
AT THE TIME, SO, AGAIN, 20 YEARS
AGO, I KNEW THAT THIS AREA OF
RESEARCH DEVELOPING AND
VALIDATING HEALTH ARK
ASSESSESMENT INSTRUMENTS WAS NEW
TO ME BUT WHAT I DID FOCUS ON
THE TRULY FULLY COMPREHEND WAS
THAT THIS AREA OF SCIENCE WAS
NOT KNOWN OR UNDERSTOOD BY THE
VETERINARY COMMUNITY AS A WHOLE
AND THIS BECAME VERY REAL, VERY
QUICKLY, WHEN I SUBMITTED THIS
FIRST CBPI MANUSCRIPT FOR
PUBLICATION, THE REVOWS THAT
INITIALLY CAME BACK, CAN
GENERALLY BE SUMMARIZED BOY THE
1 REVIEWER WHO WROTE AND I
QUOTE: THIS IS THE MOST
RIDICULOUS WASTE OF TIME THAT I
HAVE EVER SEEN.
AND LAUGHABLE WAS AN ADJECTIVE
USED BY ANOTHER REVIEWER, SO
THERE WAS CLEARLY A HUGE
AWARENESS AND EDUCATION GAP THAT
NEEDED TO BE FILLED BEFORE WE
COULD GET TO ACCEPTANCE OF THIS
MANUSCRIPT.
REVIEWERS KEPT BEING ADDED TO
THE MANUSCRIPT AND EACH RESPONSE
BACK TO THE REVIEWERS GOT LONGER
AND LONGER ISSUES EACH TIME
ADDED MORE REFERENCES TO SUPPORT
EVERY SENTENCE IN THE
MANUSCRIPT.
IT'S KIND OF CRAZY.
AT 1 POINT THERE WERE OVER 250
REFERENCES LISTED IN THE ARLAND
SOME OF THE REVIEWS GOT CRAZIER
AS WELL.
MY PERSONAL FAVORITE WAS THE
REVIEWER WHO SPENT 5 PAGES
EXPLAINING HOW MISGUIDED THIS
WORK WAS AND REFERRED ME TO THE
SPACE PROGRAM WHERE CHIMPS HAD
BEEN SENT INTO SPACE AND
EVERYONE THOUGHT THEY WERE
ENJOYING THEMSELVES BECAUSE THEY
WERE SMILING BUT IN ACTUALITY
THEY WERE NOT HAPPY AND IF YOU
CAN'T JUDGE THE FEELINGS OF THE
MONKEY THEN YOU DEFINITELY CAN'T
JUDGE THE FEELINGS OF A DOG.
AND THAT REVIEW I HAD FRAMED AND
WAS HANGING IN MY OFFICE
ACTUALLY FOR QUITE A WHILE.
THERE WERE TIMES THAT I TRULY
FEARED I WOULD NEVER GET THE
MANUSCRIPT PUBLISHED IN THE
VETERINARY LITERATURE AND HAVING
THIS INSTRUMENTED ACCEPTED AS
VALID BY THE VETERINARY
COMMUNITY WAS KEY TO THE
PROGRESSION OF MY ENTIRE
TRANSLATIONAL RESEARCH PROGRAM,
SO STRESSFUL TIMES FOR ME.
IN THE END OF COURSE IT DID GET
PUBLISHED, IT TOOK ME 2 YEARS
AND OVER A DOZEN DIFFERENT
REVIEWERS TO FINDALLY HAVE IT
ACCEPTED.
INTERESTINGLY HOWEVER WHEN THE
PAPER WAS FINALLY PUBLISHED SOME
SORT OF TIME WARP OCCURRED AND
MAGICALLY THE REVIEW PROCESS
ONLY TOOK A MONTH BUT YOU HAVE
TO CHOOSE YOUR BALGTS.
SO I HAVE SAY AS PAINFUL AS THE
PROCESS WAS, IT HIGHLIGHTED THE
AREAS ON WHICH WE REALLY NEEDED
TO FOCUS IN ORDER TO HAVE
VETERINARY MEDICINE EMBRACE THIS
SEEMINGLY KNEW AREA OF RESEARCH.
AND THERE WERE 3 MAJOR
OBJECTIONS THAT NEEDED TO BE
OVERCOME.
THE FIRST MAJOR OBJECTION OF
COURSE WAS JUST THIS GENERAL
MISCONCEPTION THAT SUBJECTIVE
STATES CAN'T BE MEASURED ISSUES
CAN'T BE QUANTIFIED AND WE'VE
ALL BEEN EXPOSED TO THE
MEASUREMENT OF SUBJECTIVE
STATES.
WE CAN THINK ABOUT IQ TESTS AND
PERSONALITY TESTS AND WHEN IT AM
CANS TO MEASURING SUBJECTIVE
HEALTH STATES WE CAN NOW
RECOGNIZE THERE'S AN ENTIRE BODY
OF SCIENCE AROUND THE METHOD
LOGICAL DEVELOPMENT AND
VALIDATION OF RELIABLE
INSTRUMENTS.
THE SECOND OBJECTION WAS BUT OUR
PATIENTS CAN'T SPEAK SO ONCE
FOLKS KIND OF ACQUIESCE TO THE
IDEA THAT OKAY, THE SCIENCE
EXISTS AND SUBJECTIVE HEALTH
STATES CAN BE MEASURED, THE NEXT
CONCERN WAS THAT THE FIELD WAS
ALL BASED ON SELF-REPORT IN
HUMANS AND OUR PATIENTS CAN'T
SPEAK.
SO HERE WE HAVE TO REFER TO ALL
THE LITERATURE ON HEALTH
ASSESSMENTS AND PEDIATRIC
POPULATIONS AND SOME COGNITIVELY
IMPAIRED ADULT POPULATIONS AND
CLEARLY IN THESE AREAS VALID AND
RELIABLE BEHAVIOR BASED TOOLS
HAVE BEEN DEVELOPED TO MEASURE
HEALTH OUTCOMES IN THESE
NONVERBAL GROUPS.
AND THE THIRD BIG OBJECTION WAS
BUT OWNERS ARE NOT TRAINED
OBSERVERS OF PAIN.
SO THIS HARKENS BACK TO THE
MEASUREMENT OF ACUTE PAIN.
SO THE HISTORY OF AND THE
LITERATURE AROUND PAIN IN
VETERINARY MEDICINE IS MUCH
LONGER THAN CHRONIC PAIN.
AND WHEN YOU LOOK AT THOSE
PAPERS VERY COMMONLY IN THE
METHOD SECTION, IT WILL TALK
ABOUT A TRAINED OBSERVER
EVALUATING POST OPERATIVE
PATIENTS FOR PAIN AND THEN
INTERVENING WHEN APPROPRIATE.
AND IT MAKES TOTAL SENSE IN THIS
SITUATION, YOU KNOW VETERINARY
PROFESSIONALS ARE GOING TO BE
THE 1S WITH THE GREATEST
EXPERIENCE, THE GREATEST
EXPERTISE AND UNDERSTANDING WHAT
AND IMMEDIATELY POST OPERATIVE
ANIMAL LOOKS LIKE AS ITS COMING
OUT OF ANESTHES RAW DATA AND
RECOVERING FROM SURGERY.
HOWEVER, MOST FOLKS NOW ACCEPT
THAT WHEN IT AM CANS TO CHRONIC
PAIN, CONDITIONS LIKE
OSTEOARTHRITIS OR CANCER PAIN,
THE BEHAVIORS THAT THE ANIMALS
EXPRESS, MOST INDICATIVE OF
THEIR PAIN ARE OCCURRING AT HOME
IN THEIR ROUTINE ENVIRONMENT AND
WE NOW RECOGNIZE THAT MANY OF
THESE BEHEAEVERS INDICATIVE OF
CHRONIC PAIN THAT THE OWNERS SEE
AT HOME ARE NOT JUST SOMETHING
THAT CAN BE EVALUATED IN THE
CLINIC.
PARTICULARLY WHEN ANIMALS ARE
EXCITED AND DISTRACTED AND SO
THE CONCEPT THAT OWNERS ARE
INDEED A MOST KNOWLEDGEABLE
OBSERVER OF CHRONIC PAIN
CONDITIONS AND THEIR PET IS
FAIRLY WELL ACCEPTED THESE DAYS
ABOUT YOU THERE WAS A FAIR
AMOUNT OF PUSH BACK ON THIS 1
FOR QUITE A WHILE.
WHEN I STARTED SPEAKING ABOUT
THE DEVELOPMENT OF THE CBPI,
THERE WERE OFTEN COMMENTS THAT
WOULD COME IN THE QUESTION AND
ANSWER SESSION WHERE
VETERINARIANS WOULD GIVE
EXAMPLES WHERE AN OWNER'S
ASSESSMENT OF PAIN IN THEIR DOG
WITH OSTEOARTHRITIS WAS
DIFFERENT FROM WHAT THE
VETERINARIAN THEMSELVES
ASSESSED.
SOME OF THESE CAN BE DIFFERENCES
BECAUSE WE KNOW IN ORDER TO GET
RELIABLE ASSESSMENTS, THE SAME
PERSON NEEDS TO BE DOING THOSE
ASSESSMENTS BUT MOST OF THE
COMMENTS CAME THAT BELIEVING AT
SOME LEVEL THAT AN OWNER COULD
NOT GIVE AN APPROPRIATE
ASSESSMENT AND I UNDERSTAND THE
CONCERN AND I HAVE MY OWN
INSTANCES WHERE I STRUGGLED A
BIT, WITH WHAT AN OWNER MAY BE
SAYING VERSUS WHAT I WAS SEEING
IN THE CLINIC, BUT I GOT OVER
THIS PRETTY QUICKLY WHEN I
STARTED ASKING OWNERS TO SHARE
VIDEOS OF WHAT THEY WERE SEEING
AT HOME.
SO HERE'S 1 EXAMPLE, THIS DOG
WAS ENROLLED IN A STUDY I WAS
RUNNING WHERE WE WERE EVALUATING
THE EFFICACY OF AN
INTERARTICULAR NEUROTOXIN FOR
THE MANAGEMENT OF OSTEOARTHRITIS
PAIN.
THIS IS A DOG WITH SEVERE
OSTEOARTHRITIS OF THE STIFLE AND
THE TOP VIDEO IS THE
PRETREATMENT ARK ASSESSESMENT.
YOU CAN SEE THE DOGS REALLY
AFFECTED AND YOU CAN SEE HE
DOESN'T USE THE LEG MUCH AT ALL
AND THE BECOME VIDEO IS THE DOG
2 WEEKS AFTER THE INTRAARTICULAR
NEUROINJECTION, AND YOU CAN SEE
THE DOG DOESN'T LOOK DRASTICALLY
DIFFERENT.
AFTER THE VISIT WAS COMPLETE AND
ALL OF OUR ARK ASSESSESMENTS
WERE DONE, I LOOKED AT THE CBPI
THAT THE OWNER COMPLETED AND SHE
MARKED THE DOG AS MARKEDLY
BETTER COMPARED TO BASE LINE
ASSESSMENT WHICH WAS NOT WHAT I
SAW IN THE CLINIC, SO I JUST
ASKED OWNER IF SHE WOULD BE
WILLING TO TAKE VIDEO OF WHAT
HER DOG WAS DOING AT HOME ARE
THE BEHAVIORS SHE WAS SEEING
THAT WERE LEADING HER TO GIVE
THE RESPONSES THAT SHE DID.
SO THAT SAME AFTERNOON SHE SENT
ME THIS VIDEO OF THE DOG IN HER
BACKYARD.
I WATCHED THIS VIDEO MULTILE
TIMES TO MIC SURE I UNDERSTOOD
WHICH DOG WAS THE DOG THAT WAS
IN THE CLINICAL STUDY AND I HAD
TO CALL THE OWNER AND CONFIRM
WHAT I THOUGHT WHICH WAS THAT,
THE DOG WITHOUT THE BALL IS
ACTUALLY THE DOG IN OUR STUDY,
AND YOU CAN PICK IT UP A LITTLE
BIT IN THE VIDEO, CAN YOUEE
THERE'S A LITTLE STUMBLE OUT IN
THE YARD AND THERE'S CLEARLY
LIKE A LIMP AND A LITTLE HAD BOB
WHEN HE HITS THE PAVEMENT ISSUE
THE TAKE AWAY OF COURSE BEING
THAT WHAT WE SEE IN THIS VIDEO
AS AN INDICATION OF HOW THE DOG
IS DOING IS NOTHING LIKE THE ARK
ASSESSESMENT THAT WE DID IN THE
HOSPITAL, SO WE'VE COME AROUND
TO THE UNDERSTANDING THAT WHEN
EVALUATING CHRONIC PAIN AND MANY
OTHER CHRONIC CONDITIONS IN OUR
SPECIES IT'S HOW THE ANIMAL
DOING AT HOME OR IN ITS ROUTINE
ENVIRONMENT THAT WE NEED TO
MEASURE AND MANY TIMES THE OWNER
IS BEST SUITED TO PROVIDE THAT
INFORMATION.
SO BY THE EARLY 2010S, I THINK
WE GOTTEN OVER MOST OF THESE
FUNDAMENTAL HURDLES AROUND THE
DEVELOPMENT OF HOW ARK
ASSESSESMENT INSTRUMENTS.
THERE IS ACCEPTANCE THAT THERE
IS A SCIENCE TO MEASURING
SUBJECTIVE HEALTH STATES THAT WE
CAN DO IT EVEN THOUGH OUR
PATIENTS ARE NONVERBAL, AND THAT
WHEN IT COMES TO CHRONIC
CONDITIONS, GETTING THE
INFORMATION FROM THE AT-HOME
ENVIRONMENT WHICH CAN BE
QUANTIFYING THE OWNER'S
ASSESSMENT IS IMPORTANT AND IT'S
POSSIBLE.
AND SO WITH THOSE MAJOR HURDLES
PASS, KIND OF A WHOLE MIEW SET
OF WHAT FOR ME WERE UNXEBTED
QUESTIONS TARTED BEING ASKED.
AS I WAS MAKING PRESENTATIONS
ABOUT THE CANINE PAIN INVENTORY
AND SOME OF ITS USE IN MY
CLINICAL TRIALS, FOR EXAMPLE IN
2017 AT THE--I'M SORRY IN 2007
AT THE [INDISCERNIBLE], AT THE
END OF MY PRESENTATION ON THE
DEVELOPMENT OF CBPI, SOMEONE
STOOD UP AND INTRODUCE
THEMSELVES AS BEING FROM THE CBM
AND AT THAT TIME I WASN'T
INTERACTING AT ALL, SO I DO NOT
REMEMBER WHO THAT WAS, BUT HER
QUESTION WAS WHO DO YOU THINK
SHOULD PAY FOR THIS KIND OF WORK
IN MEANING FOR THE DEVELOPMENT
AND VALIDATION OF HEALTH ARK
ASSESSESMENT TRIEWMENTS.
SO THIS WAS A COMPLETELY
UNEXPECTED QUESTION FOR ME IN
THE MOMENT.
I JUST EXPLAINED HOW WE GARNERED
THE FUNDING THROUGH NIH BY
LEVERAGING THIS TRANSLATIONAL
MEDICINE APPROACH, BUT THAT
WOULDN'T NECESSARILY BE POSSIBLE
THROUGHOUT ALL INDICATIONS AND
THIS LED TO A FASCINATING BACK
AND FOGGER IN THE AUDIENCE AMONG
THE PERSON FROM THE CBM WHO
ASKED THE QUESTION, SOME FOLKS
FROM INDUSTRY WHO CLEARLY WERE
VERY VESTED IN THE ANSWER AS
WELL AS SOME FOLKS FROM
FOUNDATIONS AND IT WAS
INTERESTING, ULTIMATELY EACH
THOUGHT THE OTHER HAD SOME
RESPONSIBILITY IN FUNDING THE
DEVELOPMENT OF THESE KINDS OF
OUTCOME ARK ASSESSESMENT
INSTRUMENTS AND ULTIMATELY THE
MODERATOR HAD TO STEP IN AND
BRING IT BACK TO THE PODIUM BUT
WHAT WAS REALLY INTERESTING
ABOUT THIS CONVERSATION AND WHAT
IT DID WAS HIGHLIGHT HOW TIME
AND RESOURCE INTENSIVE THE
DEVELOPMENT OF A RELIABLE AND
VALID OUTCOME ASSESSMENT
INSTRUMENT CAN BE PARTICULARLY
IN A SPACE WHERE 1 DOESN'T
ALREADY EXIST.
ANOTHER QUESTION THAT SPARKED A
REALLY FIERCE DEBATE IN THE
MOMENT WAS SOMETHING AGAIN THAT
I WASN'T EXPECTING WHEN SOMEONE
STOOD UP AND ASKED SO WHICH IS
BETTER, YOUR INSTRUMENT MEANING
THE CBPI OR GAIN ANALYSIS.
THIS WAS ANOTHER QUESTION THAT
WAS PRIZING TO ME BECAUSE IT
NEVER OCCURRED THAT PROPOSING
ANOTHER TOOL LIKE THE KRRK BPI
WOULD BE PERSPEEFED AS COMPETING
WITH A VERY WELL VALIDATED AND
HIGHLY USEFUL TOOL WHICH HAD
BEEN AROUND IN THE CHRONIC PAIN
SPACE SUCH AS PAIN ANALYSIS.
AND THIS DEBATE GOT QUITE HEATED
AT TIMES.
BUT I THINK WE GOT TO THE PAIN
WHERE WE UNDERSTAND AND MEASURE
THINGS WITH OWNER ANALYSIS AND
AGAIN ANALYSIS IS CLEARLY THE
GOLD STANDARD FOR MEASURING
LAMENESS AND IF YOU WANT TO
MEASURE LAME PS AND YOU HAVE
ACCESS TO GAIN ANALYSIS,
ABSOLUTELY IT'S THE WAY TO GO,
IF YOU WANT TO MEASURE WHAT'S
HAPPENING IN THE ANIMAL'S HOME
ENVIRONMENT WHEN AN OWNER
ASSESSMENT MAY BE WHAT YOU WOULD
CHOOSE.
THEY BOTH WORK WELL, THEY BOTH
HAVE PROS AND CONS AND THE
CHOICE OF INSTRUMENT WILL BE
BASED ON THE GOALS OF THE STUDY
AND THE RESOURCES AVAILABLE TO
DID IT.
SO I THINK WE'VE MOSTLY GOTTEN
PAST THIS HURDLE.
IT STILL LINGERS A LITTLE BIT
TODAY, MAYBE LESS IN THE CONTEXT
OF GENERATED ANALYSIS.
I THINK MORE IN THE CONTEXT OF
NOW HAVING MULTIPLE VALIDATED
OWNER ASSESSMENTS AVAILABLE.
SO NOW IT WOULDN'T BE UNUSUAL TO
GET THE QUESTION, WHICH IS
BETTER, THE LOAD OR THE API, OR
THE COI, OR THE CBPI, AGAIN,
WITH THE IDEA THAT THERE'S 1
PERFECT TOOL TO USE IN EVERY
SITUATION.
AND WE KNOW THAT WHILE ALL OF
THESE TOOLS MIGHT BE IN KIND OF
VARYING POINTS OF VALIDATION,
THEY'RE ALL OWNER ASSESSMENTS
BUT IN THE END THEY'RE NOT
MEASURING EXACTLY THE SAME
THING, THEY'RE ASKING ABOUT
DIFFERENT BEHEAEVERS AND
DIFFERENT PERSPECTIVES THOSE
BEHAVIORS, SOME FOCUS ON PAIN,
OTHERS ON MOBILITY, OR FUNCTION,
AND IT'S THROUGH THINGS LIKE
THIS PAIN AND ANIMAL WORKSHOP
THAT WE'VE REALLY BEEN ABLE TO
COME TOGETHER AS A GROUP OF
SCIENTISTS AND CLINICIANS, WHO
ARE INTERESTED IN PAIN
MEASUREMENT AND PAIN MANAGED TO
REALIZE THERE'S NEVER GOING TO
BE 1 PERFECT TOOL WHEN IT COMES
TO MEASURING PAIN ACROSS THE
BOARD.
IT'S A MULTIDIMENSIONAL COMPLEX
CONDITION THAT VARIES BASED ON
THE UNDERLYING DISEASE, THE
POPULATION IN YOUR CLINIC OR THE
POPULATION THAT MAY BE IN YOUR
CLINICAL TODAY ASK WE NEED
MULTIPLE VALID AND RELIABLE
TOOLS TO BE ABLE TO PROGRESS THE
PROGRESSION FORWARD IN THE
MEASUREMENT AND MANAGEMENT OF
CROPPIC PAIN IN OUR PATIENTS.
SO TO ME IT FELT LIKE THESE PAIN
IN ANIMAL WORKSHOPS CAME AT THE
RIGHT TIME.
THE FIRST 1 WAS 2017 WHICH WAS
10 YEARS AFTER THE FIRST CBPI
PAPERS AND WE'VE GOTTEN OVER
THOSE EARLY MISCONCEPTIONS AND
HURDLES.
AND WE WERE READY TO DIG INTO
THE NUTS AND BOLTS AND SAY OKAY,
WHERE DO WE GO FROM HERE.
AND YOU CAN SEE THE DEPTH OF
COMMITMENT AND SCIENTIFIC
ROBUSTNESS THAT WAS POURED INTO
REALLY MOVING THE PROFESSIONAL
FFD THROUGH THESE PAIN AND
ANIMAL WORKSHOPS.
ALL THE WORKSHOPS HAD THE SAME 2
BASIC OBJECTIVES.
SO TO ADVANCE TRANSLATION AS
WELL ASVIATEINARY RESEARCH.
FROM THE VETERINARY MEDICINE
PERSPECTIVE, WE REALIZE THAT
CHRONIC PAIN IS 1 OF THE MOST
POORLY UNDERSTAND AND RELATIVELY
UNDERDIGITEXTED CONDITIONS IN
THE PROFESSIONAL.
AND FROM A TRANSLATIONAL
RESEARCH STANDPOINT, WE KNOW
THAT THERE'S BEEN A LACK OF
TRANSLATION OF BASIC RESEARCH
INTO NEW AND APPROVED
THERAPEUTICS FOR THE TREATMENT
OF PAIN AND WE WANT TO
INVESTIGATE HEALTH STUDIES
ACROSS HUMAN AND VETERINARY
MEDICINE CAN CONTRIBUTE TO
IMPROVING HEALTH FOR ALL OF OUR
SPECIES.
SO THE FIRST WORKSHOP DISSED THE
STATUS OF CHRONIC PAIN
MEASUREMENT IN ANIMALS FROM THE
THERAPEUTIC DRUG DEVELOPMENT AND
THERAPEUTIC RESEARCH AND IT
TOUCHED ON OUTCOME ARK
ASSESSESMENT INCLUDING CLINICAL
METROLOGY INSTRUMENTS, GAIT
ANALYSIS AND ACTIVITY
MONITORING, AS WELL AS THE
POTENTIALLY VALUABLE APPROACHES
OF QUANTITATIVE SENSORY TESTING,
NOKRRK ICEPTIVE WITHDRAWAL
MEASURES AND PLACEBO EFFECTS AND
NEUROPATHIN PAINS, IT WAS A
BROAD LIST OF PRIORITIES FOR
FUTURE RESEARCH WAS GENERATED.
AND SO THE PRIORITIES THAT CAME
OUT OF THAT FIRST WORKSHOP
AROUND THE CLINICAL METROLOGY
TRIEWMENTS ARE BASICALLY
CATEGORRORRIZED AS WHAT WE NEED
TO DO WITH OUR CURRENTLY
AVAILABLE INSTRUMENTS.
WHAT DO WE HAVE TO DO TO DEVELOP
SOPs FOR THE APPROPRIATE USE
OF OUR INSTRUMENTS ONCE THEY'RE
VALIDATED AND WHAT ARE THE BEST
STUDY DESIGNS FOR USING CMIs.
SO IF YOU LOOK IN THAT FIRST
BUCKET OF PRIORITY ANDS QUICKLY
KIND OF SCAN THE LITERATURE FOR
WHAT'S COME UP SINCE THAT FIRST
WORKSHOP IN 2017, YOU CAN SEE
THERE'S BEEN A FAIR AMOUNT OF
ACTIVITY FOR A LOT OF THESE
DIFFERENT BULLET POINTS.
WE CAN SEE PUBLICATIONS AROUND
MEASURING PAIN AND NONMUSK LO
SKELETAL CONDITIONS SO MOST
CANCER, CANCER NEUROPATHIN PAIN,
WE ALSO SEE PUB LIAISON KAIGS
ABOUT ANALGESICS PARTICULARLY
INTRAARTICULAR.
AS WELL AS UNDERSTANDING ON
CLINICAL DIFFERENCES AND SUCCESS
FAILURE CRITERIA WHICH ARE
THINGS THAT WE WILL TALK ABOUT
MORE IN THIS WORKSHOP.
WHEN IT COMES TO THE SECOND
BUCKET, SO DEVELOPING THE USE OF
STANDARD OPERATING PROCEDURES
FOR THE USE OF CMIs, IT'S A
BIT DIFFICULT TO,A ASSESSES WHAT
KIND OF PROGRESS HAS BEEN MADE
HERE.
THERE'S CLEARLY A NEED FOR
STANDARD METHODOLOGY ON HOW WE
INCORPORATE CMIs PROTOCOLS BUT
IT'S NOT CLEAR THAT THERE ARE
WELL ACCEPTED WIDELY AVAILABLE
GUIDELINES FOR HOW WE DO THIS IN
GENERAL OR HAD EASILY
IDENTIFIABLE AND AVAILABLE
SOPs OR HAND BOOKS OR
INSTRUCTIONS WITH SIGNIFICANT
DETAIL ABOUT HOW TO USE MOST OF
THESE INSTRUMENTS INDIVIDUALLY.
SO IT SEEMS LIKE THERE'S WORK TO
DO FOR THIS BUCKET.
AND WHEN IT COMES TO THAT LAST
BUCKET AND WHAT'S THE OPTIMAL
STUDY DESIGN FOR THE USE OF
CMIs, WE SEE INTERESTING
ARTICLES FOCUSING ON STUDY
DESIGN ASSOCIATED ELEMENTS LIKE
RESPONSE BIAS OR RECALL BIAS SO
SOME INTERESTING MOVEMENT IN
THIS AREA, BUT I THINK THERE'S A
LOT MORE THAT NEEDS TO BE DONE
FOR US TO REALLY UNDERSTAND
OPTIMAL CLINICAL DESIGNS FOR
CMIs IN VETERINARY MEDICINE.
WHEN IT COMES TO THE PRIORITIES
FOR ACTIVITY MONITORING THAT
CAME OUT OF THAT FIRST WORKSHOP
IN 2017, THE FIRST BUCKET WAS
AROUND THE CURRENTLY AVAILABLE
ACTIVITY MONITORS.
THE SECOND BUCKET WAS PRIORITIES
FOR THE DEVELOPMENT OF NEW
MONITORS AND KIND OF THIS
MISCELLANEOUS BUCKET OF OTHER
THINGS TO THINK ABOUT TO MOVE
THE FIELD FORWARD FOR ACTIVITY
MONITORING IN OUR VETERINARY
SPECIES.
WHEN YOU SCAN THE LITERATURE TO
SEE WHO'S HAPPENED SINCE THAT
MEETING, IT LOOKS LIKE THERE'S
ACTIVITY AVAILABLE IN THE
MONITORS AND HOW BEST TO CAPTURE
THE SPECIFIC PAIN, DETERMINING
OUTPUTS TO USE, ARE THERE
PROCEDURES SPECIFIC TO SPECIFIC
PAIN DEHAD A FEWS, THERE'S A LOT
OF FOCUS FOR EXAMPLE ON NIGHT
TIME ACTIVITY AND HOW WELL
ANIMALS ARE SLEEPING.
SO A LOT OF REALLY NICE MOVEMENT
FOR THIS FIRST BUCKET.
THERE'S ALSO INTERESTING
MOVEMENT FOR THE SECOND BUCKET.
WE'RE DEVELOPING ACTIVITY
MONITORS, FOCUSING ON SMALL
ANIMALS, MAKING SURE WE HAVE
MONITORS FOR CATSAs WELL AS
DOGS, THESE ARE THE AREAS THAT
SEEM TO BE PRETTY ACTIVE.
AND THAT LAST BUCKET WHERE WE'RE
LOOKING AT SOPs AND BEST
APPROACHES FOR THINGS LIKE AT
THAT TIMISTICAL EVALUATION OF
THE DATA.
THE 2021 PAIN AND ANIMAL
WORKSHOP DID A DEEP DIVE INTO
ACCEL ROMETRY AROUND SOME OF
THESE DETAILS SO WE KNOW THAT
THERE'S ACTIVITY IN THIS AREA
BECAUSE THIS GROUP, THIS
WORKSHOP WAS DRIVING THAT
CONVERSATION FORWARD 4 YEARS
AFTER THE INITIAL WORKSHOP.
WHEN IT CAME TO WHAT PRIORITIES
COME UP AROUND GAIT ANALYSIS,
YOU KNOW FROM THAT 2017
WORKSHOP, AGAIN THERE WAS A
FOCUS ON WHAT DO WE NEED TO KNOW
AROUND OUR CURRENTLY AVAILABLE
TECHNIQUES AS WELL AS KIND OF
THE CATCH ALL BUCKET FOR OTHER
PRIORITIES.
FOR THAT FIRST BUCKET OF
CURRENTLY AVAILABLE TECHNIQUES,
THERE'S CLEARLY LOTS OF ACTIVITY
FOCUSING ON HOW TO INSURE WE'RE
GETTING THE BEST DATA AS WELL AS
UNDERSTANDING THE DIFFERENCES
AND THE VARIOUS TOOLS WE USE TO
COLLECT DATA AND A FOCUS ON
WHICH PARAMETERS MAY BE THE MOST
APPROPRIATE OUTCOMES.
AND JUST LIKE ACCEL ROMETRY, THE
2021 PAIN IN ANIMAL WORKSHOP DID
A DEEP DIVE INTO GAIT ANALYSIS
AND OTHER DETALES THAT ARE IN
THE SECOND BUCKET SO WE KNOW
THERE'S ACTIVITY TBH THIS AREA
BECAUSE AGAIN THIS GROUP WAS
DRIVING THE CONVERSATION FORWARD
4 YEARS AFTER THAT INITIAL
WORKSHOP.
WHEN IT CAME TO THE PRIORITIES
FOR QUANTITATIVE SENSORY
TESTING, AGAIN THERE WERE THOSE
THAT FOCUSED ON CURRENT
METHODOLOGY AND QUITE A DETAILED
LIST OF QUESTIONS ASSOCIATED
WITH UNDERSTANDING SENSORY
PHENOTYPES.
THERE HASN'T BEEN A TON OF
ACTIVITY IN THIS AREA, IN
VETERINARY MEDICINE AS LEAST
RELATIVE RIGHT, TO THE OTHER
PRIORITIES THAT WERE IDENTIFIED.
IT LOOKS LIKE WE'RE REALLY STILL
SEEKS TO UNDERSTAND WHETHER
DIRECT TREATMENT RELATED CHANGES
AND SENSORY PROCESSING CAN BE
DOCUMENTED OR WHETHER ANY OF
THESE PARAMETERS CAN BE USED TO
REALLY DEFEIGN A PHENOTYPE THAT
CAN PREDICT RESPONSE TO THE
ANALGESICS FOR EXAMPLE, SO
THERE'S A LOT TO THINK ABOUT AND
I THINK A LOT OF OPPORTUNITY
HERE FOR US TO POTENTIALLY MAKE
PROGRESS.
AND FINALLY THE PRIORITIES
AROUND PLACEBO EFFECTS.
THERE WERE 2 BUCKETS.
ONE FOCUSED ON AN OPPORTUNITY TO
PULL DATA FROM THE MULTITUDE OF
PLACEBO CONTROL TRIALS THAT ARE
HAPPENING IN VETERINARY MEDICINE
TO DO A REALLY DEEP DIVE INTO
TRULY UNDERSTANDING WHICH
PATIENT AND TODAY DESIGN FACTORS
CAN IMPACT THE PLACEBO RESPONSE.
THE SECOND BUCKET REALLY RAISED
QUESTIONS AROUND WHAT ARE THOSE
ELEMENTS OF A STUDY THAT MAY BE
IMPACTING MA SEEB O RESPONSE
THAT WE HAVEN'T REALLY BEEN
FOCUSED ON IN VETERINARY
MEDICINE, THINGS LIKE HOW
CONSENT FORMS ARE WORDED OR WHAT
THE CHARACTERISTICS OF A SITE
MIGHT BE FOR EXAMPLE.
BOTH OF THESE BUCKETS STILL SEEM
LIKE VERY BIG AREAS OF AN
OPPORTUNITY.
IT'S NOT CLEAR THERE IS A
SIGNIFICANT MOVEMENT ON THESE
PRIORITIES SPECIFICALLY SO IT'LL
BE INTERESTING FOR THIS GROUP TO
HAVE THAT CONVERSATION TO IS
THIS AN AREA THAT PEOPLE ARE
ACTUALLY MOVING FORWARD OR IS
THERE STILL AN OPPORTUNITY TO
GET GALVANIZE BEHIND THESE
CONCEPTS.
PLACEBO EFFECTS DO POP UP AGAIN
IN THE 2019 WORKSHOP, BUT NOT
NECESSARILY AROUND THOSE
PARTICULAR TOPICS.
SO CLEARLY PLACEBO EFFECTS ARE
FRONT OF MIND FOR EVERYONE
WORKING IN THE PAIN SPACE BUT IT
SEEMS THERE ARE STILL A LOT OF
OPPORTUNITY TO DEVISE A
STRATEGIC PLANENTLY TOW TACKLE
THE ISSUES.
IN THE END FOR THE 2017
WORKSHOP, THERE WERE 3 MAJOR
PUBLICATIONS THAT CAME OUT.
THE FIRST DESCRIBED THE
FUNCTIONS THAT HAPPENED AT THE
WORKSHOP ISSUE THE SECOND LISTED
OUT THE PRIORITIES THAT I
MENTIONED HERE TODAY AND THE
THIRD FOCUSED ON THE
TRANSLATIONAL MEDICINE ASPECT
AND HOW VETERINARY SPECIES CAN
REALLY HELP INFORM HUMAN HEALTH,
SO A LOT OF REALLY NICE
SUBSTANTIVE OUTPUT FROM THAT
VERY FIRST 2017 WORKSHOP THAT WE
CAN NOW LOOK BACK ON 6 YEARS
LATER.
THE SECOND WORKSHOP IN 2019
BROADENED THE DISCUSSION TO
INCLUDE FARM ANIMALS, SPECIES,
DISCUSSING THE ADVANCES AND ROAD
PLOKS TO THE MEASUREMENT OF
ACUTE PAIN, AND THE POTENTIAL
FOR SPONTANEOUS CONDITIONS AND
ANIMALS TO CONTRIBUTE TO
TRANSLATIONAL ACUTE PAIN
RESEARCH FOR HUMAN THERAPEUTICS.
BOTH SUBJECTIVE AND OBLIGATIONS
YECTIVE MEASURES WERE DISCUSSED
ENCLOUDING QUESTIONNAIRES,
FACIAL EXPRESSIONS SCALES,
ACTIVITY MONITORING, KINETIC
LIMB EVALUATION, COMPLEX
BEHAVIORIAL TESTS AND
PHYSIOLOGIC MEASURES REALLY
ACROSS SPECIES.
IT WAS REALLY BEING TO SEE WHERE
THERE WAS A LOT OF OVERLAP AMONG
SPECIES FOR EXAMPLE, THERE WERE
MANY SPECIES WHERE FACIAL
EXPRESSION SKILLS WERE BEING
DEVELOPED, MUCH LIKE KINETIC
LIMB EVALUATION AND THESE ARE
AREAS THAT ARE CLEARLY
CONTINUING TO BE VERY ACTIVE
ACROSS SPECIES INCLUDING HUMANS,
SO IT'LL BE VERY INTERESTING TO
SEE HOW ALL OF THIS DEVELOPS
MOVING FORWARD, NOW THAT WORE
JUST ABOUT 4 YEARS OUT FROM THAT
PARTICULAR WORKSHOP.
THE 2021 WORKSHOP WAS A BIT
DIFFERENCE IN THAT THE PRIOR TO
THERE WAS A DEEPER DIVE INTO A
MORE SELECTIVE NUMBER OF TOPICS.
THE PRIOR WORKSHOPS HAD TAKEN A
BROAD FOCUS AND DIDN'T GO TOO
DEEP INTO ANY 1 AREA SO IT WAS
NICE TO CARRY THE CONVERSATION
FORWARD WITH A COUPLE OF TOPICS
AND DIVE A BIT DEEPER.
AND THE 2 TOPICS THAT WERE
CONTINUATIONS OF DISCUSSIONS
FROM THE PRIOR WORKSHOPS AS
MENTIONED WERE ACCEL ROMETRY AND
GAIT ANALYSIS.
SO CLEARLY A LOT OF ACTIVITY IN
THESE 2 AREAS CONTINUES AS YOU
SCAN THE LITERATURE ON A REGULAR
BASIS APPROXIMATE SEE PUB
LIAISON KAIGS GOING FORWARD,As
WELL AS WHAT'S BEING DRIVEN
DIRECTLY BY THESE WORKSHOPS.
ONE NEW TOPIC BROACHED IN 2021
WAS THE CONCEPT OF BIOMARKERS
FOR PAIN, SO THE ABILITY TO
DOCUMENT THE PRESENCE AND THE
SEVERITY OF PAIN WITH 1 SIMPLE
OBJECTIVE TEST IS THE HOLY GRAIL
RIGHT OF PAIN MEASUREMENT, THE
HUMAN SPACE IN PARTICULAR HAS
BEEN LOOKINGA THE THIS FOR MANY
YEARS AND I THINK WE'VE COME
GENERALLY AROUND TO THE IDEA
THAT IT'S UNLIKELY THAT SUCH A
COMPLEX PHYSIOLOGICALITATE IS
GOING TO BE CONSISTENTLY
MEASURED WITH JUST 1 SIMPLE TEST
AND THERE'S A LOT OF FOCUS ON
ALGORITHMS NOW, USING AI AND
MACHINE LEARNING TO PUT TOGETHER
VARIOUS POTENTIAL BIOMARKERS TO
LOOK FOR SOME SORT OF COMPOSITE
THAT MAY BE ABLE TO IDENTIFY
PAIN OR ANIMALS OR PEOPLE WHO
ARE AT RISK FOR PAIN FOR
EXAMPLE.
AND THIS IS AN AREA THAT CLEARLY
HAS AN ENORMOUS AMOUNT OF
ACTIVITY IN THE LITERATURE,
VETERINARY MEDICINE IS A
RELATIVELY NEW PLAYER TO THIS
FIELD, IT WILL BE REALLY BEING
AND IMPORTANT TO SEE HOW WE CAN
LEVERAGE THIS SEARCH FOR THE
HOLY GRAIL BIOMARKER OR A SET OF
BIOMARKERS IN OUR VETERINARY
SPECIES WITH WHEN'S BEEN
HAPPENING IN THE HUMAN WORLD FOR
QUITE A WHILE EMPLOY SO MUCH
MORE TO COME HERE FOR SURE
EMPLOY SO IF WE THEN LOOK BACK
AT THE TIMELINE OF PAIN
MANAGEMENT FOR CANINE
OSTEOARTHRITIS, IT'S REMARKABLE
TO SEE HOW MUCH HAS BEEN
ACCOMPLISHED IN THE VETERINARY
COMMUNITY.
AND THE IMPORTANCE WE BROUGHT OF
VETERINARY MEDICINE TO
TRANSLATIONAL RESEARCH IN HUMAN
HEALTH.
THERE'S STILL MUCH MORE FOR US
TO LEARN PARTICULARLY THROUGH
COLLABORATION, DATA SHARING AND
OPEN COMMUNICATION AND THESE
PAIN IN ANIMAL WORKSHOPS HAVE
BEEN REALLY INTEGRAL TO THE MOST
RECENT WAVE OF KNOWLEDGE IN
AWARENESS EMPLOY SO
INTERESTINGLY I WAS PUTTING THE
STACK TOGETHER, 1 TECHNOLOGY
TRANSFER THAT STRUCK ME IS THE 1
AREA THAT THERE HAS BEEN VERY
LITTLE FOCUS ON IS VETERINARY
ASSESSMENTS.
THE FOI FOR THAT FIRST NSAID
APPROVAL IPT GREATER CLUEDED
GAIT ANALYSIS AND VET
ASSESSMENT, OPENER ARK
ASSESSESMENT AND CLEARLY WE'RE
TALKING ABOUT VET ASSESSMENTS
TODAY AND GAIT AND OWNER
ANALYSIS AND HOW DO WE DO IT
BETTER AND THAT'S VALUABLE FOR
THE VETERINARY COMMUNITY AND
TRANSLATIONAL RESEARCH BUT
INTERESTINGLY WE'VE REALLY NOT
BEEN FOCUSING ON THE VETERINARY
ASSESSMENT PARTICULARLY FOR
CHRONIC PAIN.
SO AS I WRAP UP THIS
PRESENTATION, A PROVEOCATION, IS
THERE A VALUE TO A FOCUS OF
VETERINARY ARK ASSESSES OF PAIN
IN OR HAVE WE MOVED TO A
CONSENSUS THAT THESE OTHER
APPROACHES TO CHRONIC PAIN
MEASUREMENT WILL PROVIDE MORE
INSIGHT IN THE LONG RUN EMPLOY
SO JUST A PROVOCATION AS WE
THINK ABOUT THIS WORKSHOP WILL
INFLUENCE THE PRIORITIES OF THE
FUTURE.
SO NOW I WOULD LIKE TO BRING IT
BACK TO WHERE WE TARTED ON THIS
JOURNEY AND MY PERSONAL
CONNECTION TO MICHELLE WHEN WE
WERE ON IT.
WHEN I LOOK BACK ON MY DECADE OF
CHAOS, WHEN I WAS TRYING TO GET
THE CBPI PAPER PUBLISHED AND
THEN AFTER PUBLICATION, YOU KNOW
DEFENDING THE SCIENCE AND THE
UTILITY OF THE INSTRUMENTS AND
YOU KNOW WADING THROUGH
ACCUSATIONS AROUND WHICH WAS
BETTER AND WHO SHOULD PAY AND I
REMEMBER THE EXACT MOMENT I MET
MICHELLE IN PERSON AND IT WAS AT
THE 2017 WORKSHOP AND OBVIOUSLY
COMMUNICATING BEFORE THEN BUT I
HADN'T MET HER ONE-ON-ONE IN
PERSON, AND SHE CAME UP TO ME
AND SHE PAUSED AND SHE LOOKED ME
IN THE EYE AND SHE SAID, THANK
YOU FOR MAKING US BETTER.
AND THIS THAT MOMENT I FELT THIS
HUGE WEIGHT OF THE DECADE OF
CHAOS FOR ME LIFTING AND I WAS
JUST HAD THIS FEELING OF GOING
BACK TO OUR MISSION AND WHY WE
DO WHAT WE DO BECAUSE MAKING THE
SCIENCE BETTER, MAKING THE
PROFESSION BETTER, MAKING THE
LIVES OF ANIMAL AND PEOPLE
BETTER THAT'S WHERE WHY WE DO
WHAT WE DO AND I WILL NEVER
FORGET THAT MOMENT AND THE PEACE
THAT MICHELLE GAVE ME AS I MOVED
INTO THE NEXT PHASE OF MY
CAREER.
WITH JUST THOSE FEW WORDS IT WAS
TRULY A GIFT.
SO AS I'M WRACHING UP, I WILL
TAKE A PLAY OUT OF THE MICHELLE
SHARKY PLAY BOOK AND SAY, TO ALL
OF YOU FOLKS THAT HAVE BEEN
MEETINGS, SPEARHEADING THESE
WORKSHOPS, DUNCAN IN PARTICULAR,
TO THE MANY SPEAKERS AND
SPONSORS AND EVERYONE WHO COMES
TO THESE WORKSHOPS AND ENGAGES
IN THE CONVERSATION AND THE
DEBATE, I JUST WANT TO SAY THANK
YOU FOR MAKING US BETTER BECAUSE
IN THE END WE'RE DOING IT ALL
FOR THEM SO THANK YOU.
[ APPLAUSE ]
>> GOOD MORNING, IT'S MY
PLEASURE TO WORK DR. E, EVANG
ILISSA, HER TOPIC AND PAIN
SCORING IN FARM ANIMALS, SHE
RECEIVED HER UNIVERSITY DEGREE
FROM BRAZIL AND ALSO OBTAINED
MERMASTER'S DEGROO FROM THE
UNIVERSITY OF SAO P A OLO,
BEFORE EARNING A Ph.D. FROM
THE UNIVERSITY OF MONTREAL IN
CANADA, SURRENTLY WORKED AS A
RESEARCHIST AT LAB RAARE TOYS
IN--LABORATORIES IN CANADA SO
WELCOME, EVANG ELISTA.
[ APPLAUSE ]
NTHANK YOU.
THANK YOU ALL FOR BEING HERE,
WHEN I ATTENDED THE FIRST MEET
NOTHING FALL OF 2017, I COULD
NOT IMAGINE I WOULD BE HERE
SPEAKING TO THE AUDIENCE SO I'M
REALLY HONORED AND THANKFUL FOR
THE ORGANIZING COMMITTEE AND
TODAY I WILL TALK ON MEASUREMENT
PROPERTIES IN FARM ANIMALS.
MOST OF MY RESEARCH I'VE DONE
WITH CAT ANDS DOGS BUT I DID
PARTICIPATE IN THIS BIG
SYSTEMATIC REVIEW THAT WE DID
WITH FARM ANIMAL ANDS THAT LED
TO A NEW FIELD OF DISCOVERY AND
RAISED SOME INTERESTED, TOO.
FIRST, I WOULD LIKE TO DISCLOSE
THAT ALTHOUGH I WORK I AM GOING
TO PRESENT HERE WAS DONE WHILE I
WAS A Ph.D. AT THE UNIVERSITY
OF MONTREAL, NOW I WORK FOR
CHARLES RIVER AND TODAY I DO NOT
SPEAK TO THEIR BEHALF EMPLOY AS
A BRIEF INTRODUCTION INTO THE
SUBJECT ISSUES THE SOCIETY
FIELDS OF ANIMAL PRODUCTION IS
CONITANTLY CHEANCHING AND NOW
THERE'S MORE CONCERN ABOUT PAIN
AND WELFARE.
IT'S WELL DETERMINED THAT PAIN
CAUSES FEAR, SUFFERING AND
STRESS WHICH CAN NEGATIVELY
IMPACT ANIMAL WELFARE AND
DECREASE PRODUCTIVITY.
THE CURRENT PAIN INSTRUMENTS
THAT WE HAVE THAT ARE AVAILABLE
RELY ON THE EVALUATION OF
BEHAVIOR, OR FACIAL EXPRESSIONS
AND SOME OTHER MORE OBJECTIVE
MOTHERS OF EVALUATING OR
RESPONSE TO AICAL BAITED PAINFUL
STIMULUS SUCH AS SENSORY TESTING
AND OTHER PARAMETERS AS
DOTTIE JUST MENTIONED, GAIT
ANALYSIS, LAMENESS AND ET
CETERA.
TODAY I WILL FOCUS ON THE
BEHAVIOR AND FACIAL EXPRESSIONS
IN FARM ANIMALS AND IN WHICH
FARM ANIMALS WE WILL TALK ABOUT
MAINLY KALGT, BUFFALOS, SHEEP,
GOATS, PIGS APPROXIMATE AND
POULTRY, THESE WERE CONSIDERED
THE MOST IMPORTANT FOR ANIMAL
PROTEIN, HORSES WERE NOT INCLUDE
THE STUDY WE DID BECAUSE THEY'RE
A DIFFERENT DPROWP.
ALTHOUGH THEY'RE ALSO RAISED IN
FARMS AND USED FOR PROTEIN
PRODUCTION, TOO, HERE WE FOCUS
ONLY ON THE OTHER MOST RELEVANT
SPECIES.
THIS IS A SYSTEMATIC REVIEW, A
RECENT SISATTIC REVIEW THAT
POIGNED OUT THE METHOD LOGICAL
CHARACTERISTICS OR THE ASSAY
BUILDS IN THE FARM ANIMALS.
THAT'S THE REFERENCE HERE THAT
WAS PUBLISHED EARLIER THIS YEAR
IN THE JOURNAL.
THESE INSTRUMENTS THEY WERE
SYSTEMATICALLY ASSESSED USING A
APPRAISAL TOOL THAT WOULD REGARD
THE MEASURE AM PROPERTIES WE
WILL DOIF A BIT MORE INTO THAT,
IN PERFORMING SUCH SYSTEMATIC
REVIEWS, IT'S IMPORTANT OF
OUTCOME MEASUREMENT SUCH AS
PAIN, SCORING INSTRUMENTS SUCH
AS PAIN SCALES, IT'S IMPORTANT
BECAUSE IT HELPS SELECTING THE
MOST SUITABLE INSTRUMENT FOR
EACH SPECIES OR FOR EACH TIME OF
PAIN, FOR EXAMPLE ACUTE PAIN
VERSUS CHRONIC PAIN EXPSM IT
HELPS TO IESHES DENTIFY THE
GAP'S KNOWLEDGE, WHICH WILL THEN
BE USED TO DESEEN NEW STUDIES OR
IMPROVE THE PREVIOUS EXISTING
SYSTEMS.
THESE MEASUREMENT PROPERTIES I'M
MENTIONING THEY'RE MAINLY
VALIDITY AND RELIABILITY.
HERE I WILL USE THE TAXONOMY OR
DEFINITION FROM THE COSMIC
INITIATIVE WHICH IS THE
CONSENSUS BASED STANDARDS FOR
SELECTION OF HEALTH MEASUREMENT
STRIEWPTS THEY STARTED THIS
INITIATIVE WITH PATIENT OUTCOME
REPORTED MEASURES BUT HERE IS A
LITTLE BIT--ADAPTATION FOR OUR
VERY GOOD PEASHTS ABOUT YOU WE
CAN STILL USE THIS SET OF
GUIDELINES ESTABLISHED FOR
ASSESSING THE PAIN ASSESSMENT
INSTRUMENTS.
RELIABILITY WILL INCLUDE TEST,
RETEST OF THE SCALE.
INTERAND INTERCONSIST ENSEL,
ACCURACY OF THE SCALE, ET CETERA
WHILE VALIDITY WOULD INCLUDE THE
CONTENT, CONSTRUCT AND CRITERION
VALIDITY.
IN THIS DEFINITION, THE
CONSIDERED RESPONSIVENESS AS A
SEPARATE DOMAIN WHICH WOULD BE
THE RESPONSE FOR EXAMPLE, TO AN
INCREASE OR DECREASE IN THE PAIN
STATUS AFTER ANALGESIC TREATMENT
FOR EXAMPLE.
SOME AUTHORS DO INCLUDE THE
RESPONSIVENESS INSIDE THE
CONSTRUCT VALIDITY BUT HERE IT
WAS RATED SEPARATELY.
AND THERE'S ANOTHER 1 CALLED
INTERPRETABILITY THAT IS NOT AN
ACTUAL MEASURE AM PROPERTY OF AN
INSTRUMENT BUT IT'S AN IMPORTANT
CHARACTERISTIC BECAUSE IT HELPS
DEFINING A CLINICAL--ASSIGNING A
CLINICAL MEANING A SCORE OR
DETERMINING A CORE.
FOR EXAMPLE, DETERMINING A SCORE
FOR RESCUE ANNAL GEEZIA.
A KEEMATTIC REVIEW SUCH AS THIS
1 WILL FOLLOW THE STANDARD STEPS
FOR IT.
FIRST REGISTERING THE PROTOCOL,
EITHER PUBLISHING OR IN A
SPECIFIC DATABASE.
THEN IN THE LITERATURE SEARCH
LOOKING FOR ALL THE RELEVANT
REFERENCES, DETERMINING KEY
TERMS FOR SEARCH, KREENING ALL
THE STUDIES FOUND FOR
ELIGIBILITY, THEN ALL RELEVANT
DATA WAS EXTRACTED WITH A
COLLECTION TABLE THE MOST
IMPORTANT PART OF THE SYSTEMATIC
REVIEW WILL BE THE ANALYSIS AND
INTERPRETATION OF THESE RESULTS
AND THIS DATA AND THEN THE
RECORDING ACCORDING TO SPECIFIC
GUIDELINE.
DURING THE ANALYSIS ISSUES THE
INTERPRETATION OF THE DATA, THE
QUALITY OF THE EVIDENT WAS
GRADED ACCORDING TO THE COSMIN
GUIDELINES, THIS WAS INITIALLY
DEVELOPED FOR PATIENT REPORTED
OUTCOME TISSUES AND THEN IT WAS
ADAPTED FOR EXAMPLE, WHICH DID
NOT INCLUDE METHODS OF
INTERVIEWING THE PATIENT
REGARDING THEIR PAIN.
HERE OUR PAIN INSTRUMENTS, IT'S
THE ASSESSMENT USUALLY BY THE
VETERINARIAN THAT OOH SIGNS A
SCORE ACCORDING TO THE OBSERVED
BEHAVIORING OR THE OBSERVED
CHARACTERISTICS OF THE ANIMAL.
AND THIS METHODOLOGY WAS ALSO
PREVIOUSLY USE INDEED ANOTHER
SYSTEMATIC REVIEW TO GRADE ALL
THE SCALES OR FACIAL EXPRESSION
SCALES IN OTHER NONHUMAN MAMMAL
SPECIES.
WHEN WE TALK ABOUT METHOD
LOGICAL QUALITY, I'M REFERRING
TO THE ROBUSTNESS OF THE DESIGN
OF THE STUDY AND THE STATISTICAL
APPROACH.
I KNOW THAT'S THE PART THAT A
LOT OF PEOPLE PASS THROUGH, THEY
READ QUICKLY WHEN READING A
PAPER BUT THAT'S VERY IMPORTANT
TO KNOW AND HOW TO ASSESS THIS
METHODOLOGY AND HOW CAN YOU
INTERPRET THE FINDINGS ACCORDING
TO WHAT HAS BEEN DONE BEHIND IT.
WE ARK ASSESSESSED A SET OF
CRITERIA TR THE DEVELOPMENT OF
THIS SCALES INCLUDING DESIGN OF
THE STUDIES, THE STEPS TO TURN
THE SINGLE IERK TEMS, SINGLE
BEHAVIORS OBSERVED ABOUT A
COMPREHENSIVE INSTRUMENT THAT
MEASURES PAIN.
THEN THE PRESSUREMENTS HERE ARE
MENTIONED AS THE INTERNAL
CONSISTENCY WHICH IS ASSESSES
HOW THE ITEMS IN THE SCALE ARE
INTERRELATED AMONGST EACH OTHER.
THE RELIABILITY INTERAND
INTROOBSERVER, THE SAME OBSERVER
OR EVALUATOR DURING--IN
DIFFERENT OCCASIONS FOR EXAMPLE
OVER TIME OR THE RELIABILITY
BETWEEN DIFFERENT OBSERVERS WITH
DIFFERENT CHEASHTISTICS OR
DIFFERENT EXPERIENCE.
MEASUREMENT ERROR OR ACCURACY OF
THE SCALE.
HOW CONPILOT PROJECT DENT CAN
YOU BE THAT THAT INSTRUMENT
WORKS OR NOT?
HOW WAS THE STUDY BEHIND IT, WAS
IT WELL DEVELOPED TO ACTUALLY
ARK ASSESSES PAIN OR IS IT
MEASURING SOMETHING ELSE, ET
CETERA.
LIKE THE RESPONSIVENESS TO
ANALGESICS AND THE CROSS
CULTURAL VALIDITY IF THIS
INSTRUMENT WAS TESTED BY ANOTHER
GROUP OR IN A DIFFERENT LANGUAGE
OR SETTING THAN THE ORIGINAL 1.
HERE'S AN EXAMPLE OF THIS
GRADING SYSTEM USED TO RATE EACH
OF THE STUDIES.
THIS CRITERIA HERE IF WE LOOK AT
THE COLUMN IN THE MITSD,
HIGHLIGHTED FOR THE GENERAL
DESEEN OF THE STUDY, WAS THERE A
CLEAR DESCRIPTION PROVIDED OF
THE CONSTRUCT TO BE MEASURED.
FOR EXAMPLE, HERE THE CONSTRUCT
IS PAIN.
IS IT CLEAR THAT THIS INSTRUMENT
IS MEASURING PAIN.
MOST OF THE LOW SCORES ASSIGNED
ARE DUE TO REPORTING AND IN HERE
IN THIS PART ALL THESE STUDIES
WERE RATED FOR THE METHOD
LOGICAL QUALITIES AS VERY GOOD,
ADEQUATE, DOUBTFUL OR
INADEQUATE.
IF THE DESCREPGZ OF THE
CONSTRUCT WAS CLEAR, THE TYPE OF
PAIN, THE MODEL, IF IT WAS
SURGICAL STIMULUS, IF IT WASN'T
NATURALLY OCCURRING TYPE OF PAIN
OR NOT.
AND THE OTHER EXAMPLE IN THE
CONTENT VALIDITY WAS ESTABLISHED
AND HOW WAS IT ESTABLISHED.
WAS THERE AN INDEX CALCULATED.
WAS THERE EXPERT OPINION, WAS
THERE A HISTOGRAM PERFORMED
BEFORE THE ASSEM MYELIN OF THESE
ITEMS INTO THE CURRENT SYSTEM OR
THE FINAL SCALE.
AFTER THAT, FIRST PART WAS
RELATED TO THE METHODS AND THEN
THERE WAS THE QUALITY OF
FINDINGS.
NOW WE WILL RATE THE QUALITY OF
THE METHOD ANDS THE FINDINGS,
THE RESULTS THAT WERE PUBLISHED.
FOR EACH CALCULATION, LET'S SAY
FOR RELIABILITY.
IF THE CO EFFICIENT WAS HIGHER
THAN .7, IN THAT CASE THE RESULT
WOULD BE CONSIDERED EFESHT OR
POSITIVE OR THE OTHER WAY
AROUND, LOWER THAN .7 NEGATIVE
OR INDETERMINANT.
IN THIS THEY WERE RATED AS
POSITIVE, NEGATIVE OR
ENDETERMINANT.
IN THE END WE WILL GATHER THE
FESTER PART OF THE BIOLOGICAL
QUALITY, QUALITY OF FINDINGS TO
SUMMARIZE THE STRENGTH OF THE
EVIDENCE RELATED TO THAT
TRIEWMENT.
THE STRENGTH OF THE EVIDENCE WAS
RATED AS HIGH, MODERATE, LOW AND
VERY LOW.
AND IN CASE OF HIGH STRENGTH
EVIDENCE WOULD BE CONSISTENT
FINDINGS AND MULTIPLE STUDIES
OFAT LEAST ADEQUATE OR 1 OF VERY
GOOD QUALITY.
SO IN THE METHOD LOGICAL QUALITY
OF THE STUDY WAS LOW, USUALLY
THE STRENGTH OF EVIDENCE WOULD
BE LOWERED.
IN THE STUDY LITERATURE
RESEARCH, MORE THAN 800 STUDIES
WERE DONE, 209 DUPLICATES
REMOVED, THE ABNORMALITIES TRACT
WERE STUDIED AND AGAIN MOST OF
THEM WERE EXCLUDED.
THEY DID NOT MEET THE INCLUSION
CRITERIA.
FORTY-EIGHT STUDIES WERE
ASSESSED FOR FULL TEXT ELIGIBLE
BY 2 INDEPENDENT OBSERVERS AND
25 EXCLUDED IN THE REASONS.
YOU CAN SEE HERE.
THIS 23 STUDIES THAT WERE
FINALLY INCLUDED IN THE REVIEW,
THEY WERE REFERRING TO 20
INSTRUMENTS FOR PAIN ASSESSMENT
IN FARM ANIMALS.
MOSTLY, ACTUALLY FOR THIS 3 MAIN
SPECIES OR GROUPS OF ANIMALS,
BEEF AND THEIR KALGT, PIGS AND
SHEEP, THESE ARE THE 3 MAIN
SPECIES FOR WHICH THERE WERE
INSTRUMENTS PUBLISHED.
THERE WERE 12 BEHAVIOR BASED
PAIN SCALES, 7 WHICH WERE FACIAL
EXPRESSIONS OR GRIMACE SKILLS.
AND 1 CONSIDERED MIXED THAT
WOULD CONSIDER BOTH THE BEHAVIOR
AND FACIAL EXPRESSION IN COWS.
HERE ARE LISTED THE NAMES OF ALL
THE INSTRUMENTS.
THE MAJORITY OF THEM WAS
DEVELOPED FOR ACUTE PAIN.
AND THERE WERE A FEW THAT WERE
AMRIED FOR A SPECIFIC TYPE OF
PAIN.
FOR EXAMPLE, THE PAIN SCORING
SYSTEM FOR VENTRICULAR SYSTEM
DEVICES IMPLANTED IN SHEEP.
SO THAT WOULD BE APPLIED FOR A
SPECIFIC CONTEXT OR A SPECIFIC
MODEL OF PAIN.
THERE ARE OTHERS FOR ABDOMINAL
PAIN OR CASTRATION.
SO EACH 1 IS A SETTING OR
CONTEXT IN WHICH IT SHOULD BE
APPLIED.
THEY RANGED A LOT IN LENGTH OR
IN COMPLEXITY OF EACH SCALE FROM
1 TO THE OTHERS.
THEY WERE USUALLY 6 ITEMS LONG
BUT RAIRVELG FROM 3 TO 22 ITEMS
RESEARCH THEY WERE SCALES TO BE
EVALUATED LIKE A GRIMACE SCALE,
AND THERE WERE 22 WITH
DESCRIPTION OF SPECIFIC
BEHAVIORS.
THE FINAL SCORE IN ALL OF THEM
WAS CALCULATED BY THE SUM OF THE
INDIVIDUAL ITEMS IN A CUT OFF OR
AN INTERVENTIONAL CORE THRESHOLD
FOR ANNAL GEEZIA WAS REPORTED IN
ONLY 5 INSTRUMENTS.
REGARDING THE MEASUREMENT
PROPERTIES THE LAST 2 PAIN
SCALES FOR CATTLE, PIGS AND
SHEEP, THEY PRESENTED OVERALL
HIGH STRENGTH OF EVIDENT.
AS STUDIES BEHIND THE SCALE
SHOWED ROBUST METHODOLOGY AND A
STEADY SCORE FOR THE DEVELOPMENT
AND VALIDATION STEPS.
THERE WERE OTHER INSTRUMENTS FOR
SHEEP, PIGS, CATTLE, THAT
PRESENTED MODERATE STRENGTH BUT
MOST OTHER STUDIES PRESENTED LOW
STRENGTH OF EVIDENCE.
IN THOSE CASES, THE SMALL
NUMBER
OF STUDIES, INADEQUATE
METHODOLOGY, DESEEN OR
CONFLICTING OR INDETERMINANT
FINDINGS.
THESE ARE THE 3 INSTRUMENTS WE
HAVE NOW DAYS FOR CATTLE, PIGS
AND SHEEP WHICH PRESENTED BY
QUALITY EVIDENCE LEADING TO
DEVELOPMENT.
THE PAIN SCALE FOR KALGT HAS 5
ITEMS INCLUDING LOCOMOTION,
ACTIVITY, APPETITE, INTERACTIVE
BEHAVIOR AND OTHER MISCELLANEOUS
BEHAVIORS.
WE HAVE A TOTAL SCORE OF 10.
IT WAS DETERMINED THAT THE
CUT-OFF SCORE FOR RESCUE
ANAGEEZIA OF 3 OR 4 IN THE
ORIGINAL VERSION OR ITALIAN
VERSION TRANSLATION WAS ALSO
RETESTED FOR THIS INTERVENTIONAL
THRESHOLD.
FOR PIGS, 6 ITEMS WITH A TOTAL
OF 18 AND SIMILARLY FOR SHEEP,
IT'S 6 ITEMS LONG TAKEN BO
CONSIDERATION THE INTERACTION,
LOCOMOTION, HAD POSITION FOSTER,
ACTIVITY AND APPETITE.
IN CONCLUSION, THIS STUDY SHOWED
A LOT OF VARIABILITY IN THE
GAPS.
AND ALTHOUGH THE STUDY IS BEHIND
EITHER THE NUMBER OF ANIMALS
ISSUES THE DEMOGRAPHIC OF THIS
ANIMAL, SEX, AGE, IF IT WAS ONLY
1 BREED OR DIFFERENT BREEDS OF
ANIMALS INCLUDED IN THE STUDIES,
ALSO IN HOW THIS IERK TEMS WERE
SELECTED TO COMOPPOSITE
BEHAVIORIAL PHENOTYPE THE FINAL
METHOD OR THE FINAL PAIN SCALE
AND THE REPORTED LEVEL OF
VALIDITY AND RELIABILITY.
THE CROSS CULTURAL VALIDITY AND
TESTING OF ANOTHER GROUP BY A
RESEARCHER WAS ONLY PERFORMED 11
SCALE WHICH WAS THE
[INDISCERNIBLE] PAIN SCALE FOR
KALGT.
AND THE CONSTRUCT AND CRITERIA
AND RELIABILITY ARE THE MOST
STUDIED MEASUREMENT PROPERTIES
WITH VARIABLE STRENGTH OF
EVIDENCE HERE.
STUDIES SUCH AS THIS SYSTEMATIC
REVIEW, THEY HELP US IDENTIFY
THE GAPS IN KNOWLEDGE AND WHERE
MORE STUDIES ARE REQUIRED AND
AND HOW YOU CAN DESIGN NEW
STUDIES TO SUPPLY THIS NICHE.
FOR INSTANCE, THE TRIEWMENTS
WITH VERY LOW STRENGTH OF
EVIDENCE, WHICH RECEIVED LOW
SCORES DUE TO THE STUDIES OR
METHODOLOGY, BUT MOSTLY
REPORTING AND I WOULD LIKE TO
STRESS HERE, THIS IMPORTANCE OF
USING WRITING AND REPORTING
GUIDELINES DURING THE
PUBLICATION PROCESS.
SOMETIMES IT'S NOT THAT IT HAS
NOT BEG YOUR PARDON DONE, IT'S
JUST THE REPORTING HAS NOT BEEN
CLEAR SO YOU CAPTAIN DETERMINE
THE EVIDENT FOR STUDY FOR THAT
EXAMPLE.
KALGT, PIGS, AND SHEEP ARE THE
SPECIES FOR WHICH SEVERAL PAIN
SCALES WERE DEVELOPED FOR USE
AND INSTRUMENTS WITH REPORDED
VALDATION ARE REPORTED FOR
BUFFALOS, GOATS, CAMEL
EDUCATIONALS AND AVIAN SPECIES.
I WOULD LIKE TO THANK THE
LIBRARIAN AT THE FACULTY OF
IMMEDIATE, WHO HELPED WITH THE
KEY WORDS AND THE SEARCH AND THE
TERMS AND OUR RESEARCH LAB
INVOLVED IN THIS STUDIES .
THANK YOU.
[ APPLAUSE ]
>> THANK YOU VERY MUCH DR. EVANG
ELISTA, APPRECIATE IT.
THERE WILL BE AN OPPORTUNITY FOR
QUESTIONS DURING THE PANEL
DISCUSSION AT THE END OF THE
SESSION.
WE HAVE DR. BARATT, AND THEN THE
BREAK WILL FOLLOW, YES?
SO WE HAVE WELCOME DR. DAN
BARRATT, TO THE PODIUM, SHE'S A
CLINICAL RESEARCHER IN THE
CLINICAL FORMACOLOGY AND DRUG
DISPOSITION IN THE UNIVERSITY OF
ADELAIDE, THAT DOESN'T ROLL OFF
THE TONGUE.
DAN HAS PRECISION MEDICINE AND
FOCUSING ON THE DISCOVERY AND
DEVELOPMENT OF BIOMARKERS OF
PAIN AND ANALGESIC RESPONSE TO
SUPPORT PRECISION PAIN MEDICINE.
WELCOME, DAN.
APPRECIATE YOU BEING HERE.
[ APPLAUSE ]
>> THANK YOU FOR THE
INTRODUCTION AND THE INI HAVE
VITATION TO BRUCE BLOOD-BASED
BIOMARKERS IN PAIN ANNAL GEESIA
AND HUMANS AND LIVESTOCK.
I THOUGHT IT WOULD BE A GOOD
PLACE TO START WHERE WE LEFT OFF
AT THE LAST PAWS WORKSHOP IN
2021.
AND SO BACK THEN WE ESTABLISHED
IN LIVESTOCK THERE WERE 2 KEY
NEEDS OR KEY CONTEXTS OF USE FOR
OBJECTIVE PAIN BIOMARKERS IN
LIVESTOCK.
ONE IS IN TRIALS TO GET DRUGGED
APPROVED FOR PAIN IN FOOD
ANIMALS AND AT LEAST IN
AUSTRALIA THERE'S ALSO A DESIRE
FOR SCALABLE FIELDABLE AND MORE
AFFORDABLE SOLUTIONS FOR
INTEGRATING MARKETING AND PAIN
ARE BEING PART OF OUR BROADER
PRODUCTION SYSTEMS.
WE ALREADY HEARD TODAY ABOUT
THEY'RE NOT BEING 1 PERFECT TOOL
TO USE AND THERE'S A NEED TO
COMBINE MULTIPLE TOOLS TOGETHER
AND SELECT THE RIGHT TOOLS FOR
THE JOB FOR PARTICULAR PAIN
CONTEXT.
AND THE RESEARCH I'M TALKING
ABOUT TODAY IS TRYING TO ADD
BLOOD BASED BIOMARKERS TO THAT
SET OF VALUABLE TOOLS.
AND ON THE LAST SESSION WE HAD A
SESSION ON BLOOD BASED
BIOMARKERS THAT IS ELECTRICKING
TO HARNESS OUR PERIPHERAL AND
CENTRAL NEURONAL AND IMMUNE
SYSTEMS WHEREBY WE CAN USE BLOOD
AND CELLULAR AND SOLUBLE
COMPONENTS TO GIVE US INDICATION
NOT ONLY OF WHAT'S HAPPENING IN
THE PERIPHERY BUT ALSO WHAT HEY
HAPPENING IN BRAIN AND SPOKENNAL
CORD, WHICH IS OF COURSE
IMPORTANT FOR PAIN.
SO IN THAT SESSION WE HEARD
ABOUT MORE THAN 10 YEARS AGO
NOW, HOW WE COULD DETECT BLOOD
GENE EXPRESSION CHANGES THAT
CORRELATED REALLY NICELY WITH
THE DEGREE OF ALODENIA,
GENERATED BY A GREAT RESTRICTION
IN RATS AND WE CAN DO GENE ASSAY
THAT'S ABLE TO DIFFERENTIATE
PAIN PATIENTS FROM HEALTHY
CONTROLS AND PROFESSOR
[INDISCERNIBLE] RAN US THROUGH
HIS WORK THAT WERE ABLE TO
DIFFERENTIATE BETWEEN LOW PAIN
AND HIGH PAIN STATES WITHIN
INDIVIDUALS AS WELL AS
DIFFERENTIATE PAIN IN HEALTHY
CONTROLS AS WELL.
AND THEN, DR. [INDISCERNIBLE]
INTRODUCES TO THESE CIRCULATING
BIOMARKERS IN VET SPECIES AND
THESE ARE PARTICULARLY
INTERESTING IN BIOMARKERS
BECAUSE THEY'RE KEY REGULATORS
OF PROTEIN EXPRESSION BOTH
WITHIN A CELL BYPASSING TO THE
MRNA PREVENTING TRANSLATION, BUT
ALSO BETWEEN CELLS THROUGH THE
RELEASE OF THESE MICRORNAs
INSIDE OF EXOSTUDIES OF MULTIPLE
ENDOCRINES.
AND IMPORTANTLY FOR US THEY CAN
BE DETECTED AND QUANTIFIED IN
ACCESSIBLE BIOFLUIDS LIKE SALIVA
AND BLOOD AND IMPORTANTLY ALSO
RELATIVELY STABLE IN NEEZ
BIOLOGICAL SAMPLES PARTICULARLY
COMPARED TO SAY MESSENGER RNA
BECAUSE OF THIS THEY'VE SHOWN
GOOD POTENTIAL AS A NUMBER OF
BIOLOGICAL CONDITIONS.
AND THE DOCTOR RAN US THROUGH
HER RESEARCH LOOKINGA THE THAT
SAN FRANCISCO LIVA AND PLASMA
MARKER RNAs HAVE BEEN ABLE TO
DIFFERENTIATE BETWEEN SHAM AND
MALE CASTRATED PIGLETS, AND ALSO
TWEEP POST AND POST SURMINGRY IN
SLIDERS AND IN SOME CASES WITH
SPECIFICITY INDICATED BY THESE
HIGH AREAS THAT RECEIVE
OPERATING CHARACTERISTIC CODES.
AND SO THESE CIRCULATING
MICRORNAs THAT HAVE BEEN THE
FOCUS OF COLLABORATIVE RESEARCH
BETWEEN PROFESSOR HANZ
[INDISCERNIBLE] AND HIS TEAM
HERE AND US AT THE UNIVERSITY OF
ADELAIDE, STUDYING RNAs IN
PIGLETS AND CATTLE.
I WILL RUN THROUGH THESE TODAY.
THE FIRST WAS IN KALGT, IN AN
EXISTING TRIAL AT KSU OF TOPICAL
LIDOCAINE AND INTRAVENOUS MEL OX
CAM FOR CASTRATION AND DEHORN
NOTHING CALVES.
AND THIS STUDY HAD 5 GROUPS.
ONE GROUP WITHOUT CASTRATION
WITH DEHORNING, WE HAD A
DEHORNING GROUP WITH NO
TREATMENT AND THEN DIFFERENT
COMBINATIONS OF MEL OX CAM AND
LIDOCAINE.
THE PROCEDURE WAS OUT TO HOURS
AND WEEKS FOLLOWING DEHORNING
AND CASTRATION AND THE KANSAS
TEAM HAD SERUM AVAILABLE FOR
THOSE ANIMALS FOR WHICH THEY
EXTRACTED EXOSTUDIES OF STUDIESE
ENDOCRINES AND RAN RNASEQ TO
MARK THE RNAs AND TO THE BRIEF
THE ANALYSIS OF THAT MICRORNA
WAS TO ITENTIFY MICRORNAs THAT
MIGHT MAKE GOOD CANDIDATE ANDS
FOLLOWING DEHORNING AND
CASTRATION, AND PARTICULARLY
LOOKING TOWARDS THE END PRODUCT
WILL NOT BE USING RNASEQ, IT
WILL NOT USE MORE TARGETED
TECHNOLOGIES SO TRYING TO FIND
INDIVIDUAL CANDIDATES RATHER
THAN COMPLEX SIGNATURES WITHIN
THE SEQUENCING DATA SO OUR
ANALYSIS SOUGHT TO MATCH THAT
CONTEXT OF USE LOOKING TOWARDS
USING THESE IN TRIALS TO GET
DRUGS APPROVED FOR PAIN IN KALGT
AND HARNESSING THE POWER OF THE
REPEATED MEASURES TAKEN AND THE
VARIABILITY WITHIN THE GROUP
THAT WAS OBSERVED.
SO HERE WE SEE, THESE ARE THE
RESULTS OF VISUAL AN LOG SCALE
OF THE PAINY BEHAVIOR SO THIS
SHOWS HERE, IN PLAQUE THE
AVERAGE IS ACROSS ALL THE
ANIMALS WITHIN EACH GROUP AND WE
SEE A VERY CLEAR BEHAVIORIAL
RESPONSE AROUND 6-12 HOURS
FOLLOWING PROCEDURE, AND THERE
WAS ANT OBVIOUS EFFECT OF
LIDOCAINE OR MELOXICAM WITH
THESE BEHAVIORS AND WE USE THIS
TO GUIDE OUR ANALYSIS WITH
RNAs AND WE,A PROACH THAT FROM
3 DIRECTIONS, SO FOR EACH
MICRORNA, WE ASSISTED FOR HOW
WELL IT CORRELATED WITH THE
VISUAL ANALOGUE SCALES IN
REALTIME, HOW WELL THEY TRACT
WITHIN AN ANIMAL AND CHAIMPLES
IN PAIN BEHAVIORS AND AFTER THE
ACCIDENT ASSESSESSED EACH
MICRORNA HOW ABOUT IT
DIFFERENTIATED PAIN VERSUS NO
PAIN STATES WITHIN AN INDIVIDUAL
ANIMAL AS WELL AS PERFORMING THE
MORE TRADITIONAL FOR GENE
EXPRESSION ANALYSIS, DIFIENTIAL
JEEP ANALYSIS APPROACH STARTING
WITH FIRSTLY SEEING WHETHER
THERE WAS A DIFFERENCE BETWEEN
CONTROL AND PLACEBO GROUP AT
EACH TIME POINT AND IF THAT WAS
SIGNIFICANT EXAMINING WHETHER IT
WAS A REVERSAL ON LIDOCAINE.
SO WITH OUR TALK CANDIDATES IS
THAT WE SEE THEM COME TO THE TOP
OF THOSE LISTS FOR THOSE
ANALYSIS BUT THE DIFFERENT YALE
YEEP EXPRESSION ANALYSIS ALLOWED
US TO IDENTIFY POTENTIAL
CANDIDATES THAT DON'T
NECESSARILY FOLLOW THAT EXIST
SAME TEMPORAL PROFILE OF THE
BEHAVIOR.
AND WE WILL SEE EXAMPLES OF
BOTH.
NICELY WE SAW GOOD OVERLAP
BETWEEN THE CORRELATION AND
CLASSIFICATION BASED
ASSESSMENTS, AS WELL WITH THE
DIFFERENTIAL GENE EXPRESSION
WHICH ALSO WAS ABLE TO IDENTIFY
ADDITIONAL RAPID AND LATE
RESPONSE MICRORNAs WHICH
DIDN'T NECESSARILY FOLLOW THIS
TEMPORAL PAIN PROFILE EMPLOY SO
FOCUSING ON THOSE OVERLAPPING
MICRORNAs, HERE, WE HAVE THOSE
POSITIVE AND CORRELATED, AND
TONS OF HIGH PAIN AND WE HAD THE
NEGATIVELY CORRELATED
MICROREFRESH YOUR RECOLLECTION
NAs WELL AS RAPID AND LIGHT
RESPONSE MICRORNAs AS WELL AND
NOT SURPRISINGLY WITHIN THOSE
GROUPS WE HAVE HIGH CORRELATION,
SO WE HAVE CLUSTERS OF
MICRORNAs THAT FOLLOW EACH
OTHER.
SO SOME OF OUR STAND OUT
EXAMPLES OF THOSE, 1 OF THESE IS
THE MIR143, WE SEE THE
EXPRESSION PROFILES IN THE
DIFFERENT GROUPS SO PARTICULARLY
HERE IN THE PLACEBO GROUP WE SEE
THE CLEAR SPIKE EXPRESSION AT 12
HOURS WHICH CORRELATES REALLY
NICELY WITHIN EACH ANIMAL WITH
HIS PROFILE OF HIS VISUAL
ANALOGUE SCALE.
THIS MICRORNA ALSO DID VERY WELL
IN DIFFERENTIATING THE PAIN AND
NO PAIN STATES WITHIN THE
ANIMALS AS WELL.
AND FOR EACH OF THESE WE HAVE
CORRELATED MICRORNAs THAT
SHOWED THESE PROFILES AS WELL,
SO WE HAD THE RAPID RESPONSE, SO
THE GOOD EXAMPLE HERE WAS THE
MEAN, AND 9, AND 9 B, THIS IS
EARLY SPARK EXPRESSION AND WOO
HAVE AN EXAMPLE OF THE LIGHT
RESPONDING RIKE ROUGH ATOM
RNETWORK As SO WE HAVE THE INN
CREASE THE SAME LATER ON, WEEKS
FOLLOWING THE PROCEDURE.
AND SO NOT ONLY DO THESE TOP
CANDIDATES HERE IN TERMS OF
DIFFERENCE WITH DIFFERENTIAL
RESPONSE IN LIGHT CHANGE, WE
ALSO SEE AN EFFECT OR REVERSAL
WITH PARTICULARLY
MELOXICAM TREATMENT BUT NOT
LIDOCAINE.
SO IN TERMS HOW THESE MIGHT BE
MORE FAMILIAR WITH IN 2021, 22,
MIRIAM MARTIN AND HANZ AND THEIR
TEAM PUB LESHED AN ASSESS OF
MULTIPLE POTENTIAL BIOMARKERS
AND FOR SPECIFICITY FOR
DIFFERENTIATING PAIN IN CATTLE
USING THESE OPERATING
CHARACTERISTIC CURVES AND THE
AREA UNDERNEATH THEM SO THIS IS
JUST A GRAPHICAL SUMMARY OF
THEIR FINDINGS FOR THE
CASTRATION AND DEHORNING AND WE
SEE CORTISOL DOES A DPD YOB
EARLY ON AND TESTING PERFORMED
VERY WELL, TOO WHERE IT WAS
ASSESSED AND COVER INDEED THAT
PUBLICATION, PERFORMED POORLY OR
ACCEPTABLY DEPENDING ON THE TIME
POINT YOU LOOK AT.
SO FOCUSING ON THE TIME POINTS
THAT WERE COVERED IN THE
MICRORNA TRIAL, WE SEE OUR EARLY
RESPONSE, RAPID RESPONSE, 9999
B, PERFORMING 6-12 HOURS, OUR
LIGHT RESPONSE MIR, 122
PERFORMING QUITE WELL BY EARLY
AND LATE OR AS WELL AND FOR EACH
OF THESE EXAMPLES THERE ARE
CORRELATED MICRORNAs IN THAT
CATEGORY THAT PERFORM AS WELL.
NODDING OFF OW WELL THE TEAM DID
WITH THE VISUAL ANALOGUE SCALES
AND DIFREBTIATING THE PLACEBO
FROM CONTROL ANIMALS AS WELL.
PARTICULARLY COMPARED TO
PREVIOUS STUDIES.
SO IN TERMS OF THE BIOLOGICAL
CONTEXT SO IN CATTLE, THE NUMBER
OF THESE MICRORNAs ARE
ASSOCIATED WITH THE INNATE
IMMUNE RESPONSE INVITRO, SOME
ALSO HAVE BEEN IDENTIFIED AS
CHANGING EXPRESSION IN SERUM IN
HEAT STRESS KALGT AS WELL, SO IN
TERMS OF WHY YOU MIGHT SEE THESE
FOLLOWING DEHORNING AND
CASTRATION, CAN YOU SEE HOW THEY
MIGHT BE ELEVATING RESPONSE TO
DNLING ASSOCIATED MOLECULAR
PATTERNS INDUCE BY INJURIES.
SO IN TERMS OF HUMANS, IN TERMS
OF LINKS TWOAN THE HUMAN
PREVALENCE OF MICRORNAs,
CIRCULATING DEC BIOMARKERS
IDENTIFIED AS CANDIDATES FOR
ENDOMEET REOISEIS AND RHEUMATOID
ARTHRITIS.
MIR21 IS CONSIDERED A LIVER
MICRORNA AND ASSOCIATE WIDE
LIVER INJURED IN MULTILE SPECIES
AND SOME OF THESE RAPID RESPONSE
MEETINGS HAVE BEEN INDICATE
INDEED THE WOUND HEALING EFFECTS
OF THESE ENWROIMS BUT IT'S
IMPORTANT TO POINT OUT THESE ARE
NO MEANS IN CATTLE, THESE HAVE
BEEN ASSOCIATED WITH SO THEY'RE
NOT SPECIFIC TO THESE FUNCTIONS
AND PHENOTYPES.
AS YOU DO OVERREPRESENTATION
ANALYSIS, AND WE VISIT BOTH THE
MICRORNA LEVEL AND THE TARGET
JEEP LEVEL AND IMPORTANTLY
BECAUSE WE'RE LOOKING THEA
TARGET YEEPS IN MICRORNA, WE USE
THAT,A PROACH THERE RATHER THAN
THE STANDARD GEOMETRIC TEST.
AND WHILE NO SINGLE PAIN PATHWAY
JUMPED OUT AT THE TOP OF THOSE
LISTS WE DID SEE INTERESTING
OVERLAP IN TERMS OF YEEP SETS
THAT WERE ENRICHED FOR
MULTIPLE--MULTILE--TARGETING OF
MULTIPLE RNAs, PARTICULARLY
PATHWAYS INVOLVED IN THE
REGULATION OF GLUCOSE LEVELS BUT
ALSO IMMUNITY AND INFLAMMATION
AND ALSO WOUND HEALING.
SO THAT WAS THE FIRST STUDY IN
KALGT.
WE ALSO LOOKED AT SERUM MIKE ARE
RNAs IN BIGLETS ISSUES THIS
WAS CONDUCTED AT KANSAS STATE
UNIVERSITY, THIS WAS FOR
CASTRATION IN BOTH MALE AND
FEMALE PIG WILLS.
IN THERE TRIAL THERE WERE 4
GROUPS, WE HAD A CONTROL GROUP
WITH ETHYL CHLORIDE BY ITSELF
AND FIRO+ EC, NOTICE IN THIS
TRIAL ALL PIG WILLS UNDER WENT
TAIL DOCKING AND WE WERE
INTERPRETING THESE CHANGES IN
PREGZ FROM PRETO POST PROCEDURE
AND THE MARKER RNA WERE
GENERATED THROUGH KSU THROUGH
NEXT GENERATION SEQUENCING AND
THESE WERE AT 2 BASE POINTS AND
24 HOURS FOLLOWING THE
PROCEDURE.
AND AT THE EPPED OF THE DAY WE
HAD BETWEEN BASE LINE AND 24
HOUR DATA, FOR 32 PIGLETS WERE
GROUP AND WE ANALYZED FEMALE
ANDS MALES SEPARATELY AND DID
THAT IN A STEP WISE APPROACH
STARTING WITH LOOKING FOR, OKAY,
THERE WAS A TIME EFFECT, A
DIFFERENCE BETWEEN PREAND POST
PROCEDURE CONTROL ANIMAL ANDS IF
THERE WAS, WAS THERE ANY
TREATMENT EFFECTS OR ANY REVERSE
OF THAT EMPLOY AND IN EACH CASE,
WHERE MICRORNA WAS
SIGNIFICANT,LY ELECTRICKEDDA HOW
WELL DIFFERENTIATING THESE
CONTROLS OR BETWEEN THE
FIROCOXIB, AND THE CONTROL
PIBLET.
WE DID MORE TESTING, MORE
FEMALES THAN MALES AND SUBSET OF
THOSE DEMON TRAITED AT LEAST
NORMALLY SOME REVERSAL IN
EXPRESSION WITH FIROCOXIB
TREATMENT.
A COUPLE STAND OUTS THERE, WE
HAD AMIRAKA 15 A AND 101 WHICH
DECREASE FROM PREON POST
PROCEDURE AND THIS WAS ONLY
SIGNIFICANT IN FEMALES BUT THEN
WE ALSO HAVE THESE NOVEL 6 AND
NOVEL 7 MICRORNATHAT IS INCREASE
SIGNIFICANTLY FROM PRETO POST
PROCEDURE AND THESE WERE IN MALE
AND FEMALE PIGGINGLIES AND FOR A
SUBSET OF THESE IN MIR 101 AND
ALSO AT 6, WE SAW A SIGNIFICANT
DIFFERENCE BETWEEN CONTROL
ANIMALS AND FIROCOXIB, TREATMENT
AS WELL.
AND THE UNDERS UNDER THE CURVE
REFLECT THAT PERFECT OR NEAR
PERFECT SEPARATION BETWEEN
PREAND POST PROIED SEEDURE IN
THE CRETION AND ANIMAL CONTROLS
WHERE THE AREAS YOU SHOULD THE
CURVES REFLEKS THAT OVERLAPPING
EXPRESSION.
SO, THAT COULD BE EITHER LACK OF
SENSITIVITY OF THE BIOMARKER
SAID ITSELF AND THEINAL GEESIC
ITSELF OR THAT FIROCOXIB IS JUST
AS A VARIABLE AND THAT'S WITH
RESPECT TO BOTH THINGS.
INTERESTING WE HAD OVERLAP WITH
THE BOVINE MICRORNA SO THESE
SEQUENCES ARE IN SEQUENCE TO THE
MIR 1246, WHICH WAS 1 OF THE
LATE RESPONSE CHANGE THAT ALSO
SHOWED A REVERSE WITH MELOXICAM
IN THE CATTLE STUDY.
WE ALSO LOOKED TO SEE WHETHER
ANY OF THE SLOBBERING IDENTIFIED
IN MALE PIG WILLS REPLICATED
ACROSS BUT WE DEPARTMENT SAY
THAT THE PIG WILLS CHANGE THEIR
193 B65 OR 27 B, WE DIDN'T SEE
THAT IN THE SERUM EXOSTUDIES OF
MULTIPLE ENDOCRINES COMPARED TO
WHAT WE'VE SEEN IN THE SALIVA.
SO PROMISING EARLY FINDING
THERE, OBVIOUSLY STILL A LOT OF
REPLICATION AND VALIDATION WORK
TO DO AND WE'RE WORK ON THAT.
SOME OF THE KEY CHAL ERVEG ENCHS
WE HAVE SO FAR IN MOVING
FORWARD, 1 OF WHICH IS IN TERMS
OF REPLICATION BETWEEN STUDIES,
PARTICULARLY BETWEEN DIFFERENT
RESEARCH GROUPS SO WE'VE SEEN
EXAMPLES WHERE DIFFERENT
EXTRACTION METHODS AND QUALITY
CONTROLS, PREP, HOW THE RNA IS
EXTRACTED, LIBRARY PREP ANDS
SEQUENCING PLATFORMS THEY USE
AND POST SEQUENCING THE DECISION
IS MADE ABOUT THE
BIO-INFORMATICS PIPELINE AND
STATISTICAL ANALYSIS OR MAKE IT
DIFFICULT TO COMPARE STUDIES AND
SEREPLICATION IN THE TOP
CANDIDATE MICRORNAs THAT MIGHT
COME OUT.
TRUSTEES ARE ALSO DISCUSSIONS
AROUND THE VALIDATION QPC R,
THAT IS NOW WITH THE NEXT STUDY,
TO VALIDATE THOSE SEQUENCING
FINDINGS THERE THERE ARE ALSO
THE BEST WAY OF DOING THAT QRTPC
R PARTICULARLY ABOUT WHAT
CONTROLS WE WILL HAVE WITHIN
THOSE EXPERIMENTS WHETHER WELL
CELEGANCES SPIKE SUGGEST REALLY
ENOUGH FOR THOSE.
THE OTHER 1 WHICH YOU MIGHT HAVE
PICKED UP ON IS 1 CHALLENGE IS
DEMON TRAITS SPECIFICITY HERE TO
PAIN OR DEASSOCIATED STRESS FOR
THE PROCEDURES AND WOUND HEALING
BECAUSE ALL OF THE CURRENT
APPROACH IN FOOD ANIMALS USE
THIS NATURALLY OCCURRING IN
MODELS OR WHICH INVOLVE TISSUE
DAMAGE AND OFTEN WE HAVE CARE
EFFICACY SO IT CAN BE DIFFICULT
TO DIFFERENTIATE THOSE 2 SO
THERE'S DISCUSSION TO BE HAD
ABOUT WHAT COMPLIMENTARY MODELS
WE MIGHT BE ABLE TO EMPLOY THAT
MAY BE NOT NECESSARILY VETINARLY
OR PRODUCTION RELEVANT BUT MY
HOPE IS NOT IT'S NOT TO SOME OF
THESE QUESTION ANDSTY TEASE THAT
OUT AND GIVE US MORE CONFIDENCE
IN THE PAIN NO PAIN HIGH GROUND
TRUTH TO TEST THESE BIOMARKERS.
HOW ARE WE DOING WITH TIME?
STILL GOOD.
PERFECT.
SO I WOULD LIKE TO FINISH UP
WITH TALKING ABOUT SOME OF THE
WORK WE'RE DOING DOWN IN
AUSTRALIA, WHICH AT THE
UNIVERSITY OF ADLAID WITH MARK
HUTCHINS SON'S TEAM, WE'VE JUST
TAKEN OUR 2 FLOCKS OF LAMBS
THROUGH LAMBS THROUGH FROM
MARKING TO HABITAT 12 MONTHS.
IN HERE WE HAVE DEFINITE
COMBINATIONS OF KNOWN MARKING
VERSUS VARIATIONS ON MICE AND
RING TAU DOCKING AND WITH OR
WITHOUT CASTRATION IN THE IN THE
MALES.
AND THE LAMBS WERE ASSISTED AT
BASE LINE AND VARIOUS TIME
POINTS OUT TO 12 MONTHS.
WE HAVE VIDEO FOR BEHEAEVERRIAL
ASSESSMENTS AND WE'VE ALSO DONE
MECHANICAL NOCICEPTIV TESTING.
IN TERMS OF VIDEO AND
VALIDATION, WE HAVE A STUDENT
WORKING TO ASSESS THE PAIP
BEHAVIOR AND SHE HAS INTERESTING
PRELIMINARY RESULTS FROM THAT
SHOWING CLEAR BEHAVIORIAL
RESPONSES IN RING DOCKED FEMALE
ANDS CAST RATED MALES BUT NO
SIGNIFICANT BEHAVIOR IN KNIFE
KNOCKED ANIMALS AND THOSE SEEM
TO BE GONE BY 4 HOURS POST
PROCEDURE.
IN ARK DITION TO THAT WE HAVE
OUR BLOOD SAMPLES TO LOOK AT,
PLASMA RNA, TRANSCRIPTOME AND
EPIGENOME LOOKING AT THE COLOR
OF PAIN, AND MULTISPECTRAL
ANALYSIS DOING THE SHAPED
VERSION OF THAT HUMAN
PHENOTYPING TEST THAT WEB
CONNECTED USE TO DIFFERENTIATE
BETWEEN PAIN PATIENTS AND
CONTROLS.
WE TOOK SAMPLES AS WELL TO
CONDUCT ANALYSIS ON CORTISOL,
AND HYDROCORTISONE, AND AT 12
MONTHS WE CLEBTED BRAINS AND
SPINAL CORDS SO THE TEAM VERY
BUSY AT THE MOMENT SLICING AND
STAINING THOSE TO LOOK THEA
CHAIRVELGS IN THE CELLULAR AND
MORPH O LONLICAL LEVELS IN THE
BRAIN.
SO ALTOGETHER WE'RE TRYING TO
GENERATE HERE, AN INTEGRATED
PICTURE OF THE ACUTE TO
LONG-TERM MOLECULAR TO CELLULAR
TO SYSTEMS TO BEHAVIORIAL
CONSEQUENCES OF THESE PAINFUL
PROCEDURES IN SHEEP.
SO HOPEFULLY IN 2ER YOAN
MONCADAS TIME WE'LL HAVE SOMEONE
FROM THE TEAM HERE TO PRECEPT
HAD SOME OF THOSE RESULS FROM
THAT TRIAL.
AND THAT'S IT FOR ME.
THANK YOU.
[ APPLAUSE ]
NTHANK YOU SPEAKERS.
WE WILL TAKE A BREAK BUT BEFORE
WE DO DR. JULIA BACHMAN FROM THE
NIH HEAL INITIATIVE, WILL GIVE A
PLUG FOR 2 HEAL FUNDING
OPPORTUNITIES.
NETWORK SO SORRY TO DELAY YOUR
KAFIN INTAKE BY JUST A MOMENT.
I WANT TO QUICKLY INTRODUCE
MYSELF AND IF RELEVANT FUNDING
OPPORTUNITIES WE THINK YOU MIGHT
BE INTERESTED IN.
I AM JULIA, I AM WITH THE HEAL
IPT GREATERRISHIAATIVE HELPING
END ADDITION LONG-TERM WHICH IS
THE TREPPED TO STEM THE OPIOID
EPIDEMIC BY BEDDING TREATMENT
MANAGEMENT AND PAIN.
WE HAVE 2 FUNDING OPEN
OPPORTUNITIES FOR THE
DEVELOPMENT AND RIGOROUS
VALIDATION OF ANIMAL MODELS AND
PAIN RELATED OUTCOME MEASURES,
SO AS A PART OF THESE FUNDING
OPPORTUNITIES, SOMETHING WE'RE
REALLY ENCOURAGING IS REALLY
STRESSING THE RIGOROUS
VALIDATION, SO THERE WERE SLIDES
EARLIER OUTLINING SOME GREAT
ELEMENTS OF METHOD LOGICAL
QUALITY AND RIGOR AS WELL AS
DIFFERENT TYPES OF VALIDITY AND
RELIABILITY, SO ALL OF THESE ARE
KEY PARAMETERS THAT WE ARE
HOPING INVESTIGATORS EXPLORE AS
PART OF THESE FUNDING TIEWPTS.
ANOTHER IMPORTANT THING TO
MENTION IS WE'RE ENCOURAGING
INDEPENDENT REPLICATION, ARK
ASSESSING PAIN AS A
MULTIDEDIMENSIONAL EXPERIENCE
AND ALSO ENCOURAGING
MULTIDISCIPLINARY TEAMS AND
CLINICIANS BIOSTATISTICIANS, ALL
WORKING TOGETHER, IMPORTANT
PERSPECTIVES TO BRING TO THESE
PROJECTS AND AS DUNCAN MENTIONED
EARLIER, A LOT OF THAT DIFFERENT
EXPERTISE IS IN THIS ROOM TODAY,
SOPHISTICATED I WOULD ENCOURAGE
TO YOU TALK TO EACH OTHER, TALK
TO US, MY COLLEAGUES, THE DOCTOR
AND SHOULD BE HERE FOR AT LEAST
PART OR ALL OF THIS MEETING
TODAY AND TOMORROW, AND YOU'RE
WELCOME TO CONTACT US AFTER THE
FACT, IF YOU HAVE IDEAS AND WANT
TO TALK ABOUT THE PROJECT AS IT
RELATES TO THESE FUNDING
OPPORTUNITIES.
THANK YOU.
[ APPLAUSE ]
AND WE'LL BREAK UNTIL 10:50.
THANK YOU.
SO WE'RE READY TO START OFF
OUR NEXT SESSION, SESSION BEFORE
LUNCH.
SWITCHING GEARS A LITTLE BIT AND
FOCUSING ON ARTIFICIAL
INTELLIGENCE AND VETERINARY
MEDICINE, OUR FIRST SPEAKER IS
DR. P A RMINDER BASRAN, FROM
CORNELL UNIVERSITY.
HE RECEIVED HIS Ph.D. FROM THE
UNIVERSITY OF CALGARY AND THE
LAB IS NAMED THE VETERINARY
ARTIFICIAL INTELIENCE AND
DIAGNOSTIC IMAGES AND THERAPY OR
THE VADER LAB, AND HAS 3 MAIN
FOCUSING IN VETERINARY
RADIATION, TREATMENT PLAN,
MEDICAL IMAGE PROCESSING AND
ANALYSIS AND WE'RE EXCITED TO
HAVE DR. BASRAN TALK TO US A
LITTLE BIT ABOUT SOME OF HIS
WORK WITH AI AND VETERINARY
MEDICINE.
SO WELCOME, THANK YOU.
[ APPLAUSE ]
MTHANK YOU FOR THE INTRODUCTION
AND THANKS FOR THE COMMITTEE FOR
INVITING ME HERE.
MY GOAL TODAY IS TO--SO QUICK
SHOW OF HANDS, WHO KNOWS
ANYTHING ABOUT ARTIFICIAL
INTELIENCE.
A LITTLE BIT.
OKAY, GREAT.
THIS IS FOR THE REST OF YOU.
MOST OF THE IMAGES THAT I'M
GOING TO SHOW HAVE BEEN
GONEERATED THROUGH WHAT'S CALLED
STABLE DIFFUSION SO IF THEY LOOK
WEIRD IT'S BECAUSE THEY'RE MADE
BY AN AI SYSTEM.
HERE'S THE OUTLINE FOR TODAY AND
LET'S JUMP RIGHT INTO IT.
ARTIFICIAL INTELLIGENCE, WHAT
ARE THEY?
THEY ARE ILTELEIGENCE AGENTS
THAT PERCEIVE THE ENVIRONMENT,
TAKE ACTION, YOU BET INPUT AND
YOU GENERATE USEFUL OUTPUT,
THEY'RE PERVASIVE, THEY'RE
EVERYWHERE, GOOGLE,
RECOMMENDATION, SPEECH
RECOGNITION, FRAUD DETECTION, SO
FORTH.
WE USED TO THINK THIS WAS A
CLEVER USE OF FORM OF AI AND WE
DON'T EVEN THINK OF THAT BEING
USEFUL ANYMORE.
WHAT IS,A I AND MACHINE LEARNING
I WILL TRY TO DEMYSTIFY IT A BIT
LEARNING, CAN YOU THINK OF
MACHINE LEARNING AS A SUBSET OF
ARTIFICIAL INTELLIGENCE, SO
IMAGINE HAVE YOU A VERY LARGE
DATA SET AND YOUR GOAL IS TO
TROO I TO DRAW CONNECTIONS
BETWEEN THIS LARGE DATA SET AND
SOME KNOWN OUTPUTS, MAYBE FOR
EXAMPLE, HAVE YOU A WHOLE BUNCH
OF BLOOD SERUM DATA AND YOU WANT
TO PREDICT SOME KIND OF SCORE.
THAT WOULD BE A SUPERVISED
PROBLEM OF CONTINUOUS VARIABLES,
I. E. THE CONCENTRATION OF THESE
DIFFERENT ELEMENTS AND YOU WOULD
USE A REGRESSION MODEL TO
GENERATE AN OUTPUT.
THE KEY DIFFERENCE HERE IS THAT
THE LEVEL OF SOPHISTICATION IN
THESE LEVEL OF ALGORITHMS IS
DEEP AND RICH SUCH THAT THEY CAN
HANDLE TREMENDOUSLY EPPED
OMOUNTS OF DATA AND THERE ARE A
PLETHORA OF DIFFERENT ALGORITHMS
TO BE USED BETWEEN THE DATA AND
THE OUTPUT THAT YOU WANT.
YOU MAY ALSO HAVE DISCREET
VARIABLES.
YOU MAY HAVE A WHOLE BUNCH OF
MEDICAL IMAGES THAT YOU WANT TO
CLASSIFY OR DETERMINE IF A DOG
HAS SOME SORT OF HEART DISEASE
OR IF IT HAS METASTASIS AND SO
FORTH.
AGAIN, THIS IS A SUPERVISED
PROBLEM WHERE YOU CAN STRUCTURED
INPUT DATA AND HAVE SOME
STRUCTURED OUTPUT.
AND YOU MAY ALSO HAVE SITUATIONS
WHERE YOU DON'T KNOW WHAT THE
DATA IS TELLING YOU AND YOU WANT
IT TO TELL WHAT YOU'S GOING ON.
SO YOU CAN USE DEDUCTIVE
REASONING THROUGH WHAT ARE
CALLED UNSUPERICIZED MACHINE
LEARNING METHODS AND YOU CAN USE
VARIABLES FOR THESE PROBLEMS.
THE GENERAL APPROACH FOR ANY
KIND OF MACHINE LEARNING FOLLOWS
SOMETHING LIKE THIS WHERE YOU
TYPICALLY WOULD HAVE VERY, VERY
LARGE CHUNKS AND PIECES OF DATA
TO SAY THAT WE'RE GOING TO
GENERATE A SUPERVISED MACHINE
LEARNING ALGORITHM, WE WANT TO
PREDICT SOMETHING FROM THIS LARM
DATA SET BUT WE TAKE A GOOD
CHUNK OF THAT DATA AND MAYBE 70,
80% OF IT, AND USE THAT TO TRAIN
A MODEL.
THE REST OF THAT 20% WE PUT
ASIDE AND KEEP IT IN A CORNER.
WITH THAT 70-80% OF THAT DATA WE
THEN EXPLORE DIFFERENT--WE CAN
ATTEST DIFFERENT MACHINE
LEARNING ALGORITHMS TO TRY TO
PREDICT THIS OUTCOME THAT WE'RE
INTERESTED IN.
AND GENERALLY THIS MEANS WE HAVE
TO CREATE A LOSS FUNCTION.
WE ARE TO DEFINE A METRIC WHICH
TAKES THE PREDICTION AND THE
MEASURED OUTPUT AND MEASURE THAT
AND PRESUMABLY THE ALGORITHM
PERFORMS BETTER AS THAT LOSS
FUNCTION STARTS TO GO DOWN.
SO WE DO THIS ARK PROACH
THROUGHOUT--USING ALL THOSE
SOPHISTICATED ALGORITHMS TO
BUILD A MODEL THAT HAS A LOW
LOSS FUNCTION.
YOU CAN THROW DIFFERENT KINDS OF
DATA SETS, CAN YOU HAVE
MULTIINSTITUTIONAL DATA SETS AND
THEY WILL ALL PERFORM
DIFFERENTLY BASED ON THE MODEL
YOU COLLECTED.
ONCE YOU HAVE THE MODEL, YOU
HAVE THE TEST DATA ISSUES THING
YOU PUT ARK SIDE, THAT'S THE
DAILY BASIS THEA YOU USE TO
EVALUATE THE MODEL ITSELF.
WHAT KINDS OF FORMS OF AI ARE
THERE?
YOU CAN THINK OF THEM IN 3 WAYS,
I WILL GO INTO DETAIL ON HOW
EACH OF THESE AI METHODS WORK.
HAVE YOU COMPUTER VISION, YOU
HAVE NATURAL LANGUAGE PROCESSING
THAT ARE CONNECTED TO THESE LONG
LANGUAGE MODELS YOU MAY HAVE
HEARD OF AND THEN SPEECH REG
NITION.
IN COMPUTER VISION, WHAT WE'RE
TRYING TO DO IS GENERALLY
SIMULATE WHAT'S HAPPENING INSIDE
A YOU HAD MAP BRAIN.
AND IF YOU HAVE A PICTURE OF FOR
EXAMPLE, A DOG, WHAT WE
TYPICALLY THINK HAPPENS, IS THAT
A SERIES OF NODE ANDS
CONNECTIONS TWOAN THE NODES AND
BRAINS WITHIE DIFFERENT PATTERNS
AND WEIGHTS, ALL COLLECTIVELY
REPRESENT WHAT WE THINK OF AS
BEING A DOG.
AND WHAT COMPUTER VISION TRIES
TO DO IS EMULATE THAT KIND OF
BEHAVIOR WITHIN A COMPUTER.
NOW THIS IS A FIELD OF COMPUTER
VISION REALLY DIDN'T TAKE OFF
UNTIL THE ESTABLISHMENT OF A
DATABASE AND SO IT'S REALLY
INTERESTING TO HEAR THE
IMPORTANCE OF STANDARDIZED DATA
BECAUSE IT WAS THIS IMAGE NET
DATABASE THAT REALLY BLEW--BLEW
UP THE WHOLE FIELD OF COMPUTER
VISION EMPLOY IT WAS A PROFESSOR
THAT SAID WE ARE 15 DIFFERENT
COMPUTERS WITH 15 DIFFERENT DATA
SETS COLLECTING MULTIPLE
OBLIGATIONS YECTS AND THE
PROFESSOR SAID I'M GOING TO GET
1.2 MILLION HIGH RESOLUTION
CLASSIFICATIONS AND PROVIDE THE
DATA SET FOR IT TO COMPARE.
AND IT WAS THIS IMPETUS TO
COMPARE DIFFERENT COMPUTER
APPROACHES.
ANOTHER REALLY IMPORTANT THING
THAT HAPPENED WAS THE INVENTION
OF WHAT'S CALLED THE
CONVOLUTIONAL NETWORK, THERE'S A
GRAD STUDENT BY THE NAME OF
[INDISCERNIBLE] WHO YOU MAY HAVE
HEARD OF LEAVING GOOGLE AND
RESIGNING AND CAUSING THE BIG
FUSS.
IT'S THIS FELLOW HERE.
HE DECIDED TO CREATE A NEURAL
NETWORK BASED ON IMAGES.
AND THIS IS WHAT IT FIRST LOOKS
LIKE, THIS IS THE FIRST COMPUE
TUITIONAL NEURAL NETWORK WHICH
SUBJECTED TO AN XREA IMAGE OF A
NORWEGIAN FOREST CAT.
THESE ARE TRUE IN DETAIL, - IT
IS TAKEN ME HOURS TO CREATE THIS
BUT THE BOTTOM LINE HERE WHAT
IT'S TRYING TO DO IS IT'S TAKING
AN IMAGE AND IT'S GOING TO
CLASSIFY IT, PROVIDE
PROBABILITIES FOR EACH OF THE
THOUSAND OBJECTS THAT IT CAN
CLASSIFY, SO IN THIS CASE, IT'S
TAKEN THIS IMAGE, AND IT'S
CLASSIFIED IT AS A SPENDLE,
17.7%.
I'M GOING TO GO INTO MORE DETAIL
AS TO HOW THIS ACTUALLY HAPPENS.
IT TAKES THIS IMAGE, AND THEN IT
RESAMPLES IT DOWN INTO A COMMON
SIZE, 22, AND THEN IT PERFOR THE
PURPOSES CONVOLUNTEERSULATION
FILTERS.
IT YOU THINK OF THEM AS
PLURIPOTENT C
ELLSINESS--BLIEWRINESS OR
IMAGES PUT ON THE IMAGE THAT
EXTRACT CERTAIN FEATURES OF THAT
IMAGE.
IN THIS CASE, THERE ARE 96
DIFFERENT FILTERS OR 96
DIFFERENT IMAGES THAT ARE
RESULTING AND IT'S ALSO SCHURCHG
DOWN IN SIZE TO 55 BY 55.
SO HERE'S THE ORIGINAL IMAGE,
SHRINK DOWN AND HERE ARE THE
CONVOLUTIONAL FILTERS.
AND THEN IT GOES THROUGH
FILTERING, IT GOES THROUGH DATA
NORMALIZATION AND ACTIVELY
SUPPRESSING OR HEIGHTENING
CERTAIN SIGNALS WITHIN THAT
IMAGE WHICH ARE KNOWN AS THESE
IMAGES.
THIS IS THE UNIT AND SO FORTH,
THIS SAN EXAMPLE OF 1 OF THOSE
IMAGES OF THOSE 27 BY 27 IMAGES.
IT REPEAT THIS IS PROCESS OVER
AND OVER AGAIN UNTIL YOU
EFFECTIVELY HAVE A STRING OF
NUMBERS AND THOSE STRINGS OF
NUMBERS ARE CHARACTERIZING THAT
ORIGINAL IMAGE FROM THOSE
STRINGS OF NUMBERS IT GETS FED
INTO A THAT YOU'RAL NETWORK,
THIS COMPLICATED PATTERN OF
CONNECTED NODES AND OF
INFORMATION THAT PASS BETWEEN
THE NODES AND IT'S THE WEIGHT
BETWEEN THOSE NODES THAT ARE
URKNIQUE TO IDENTIFY OBLIGATIONS
YECT.
AND THROUGH ALL OF THOSE FILTER
BEING, YOU GET THE STRING OF
NUMBERS, IT GOES THROUGH THE
NETWORK AND IT PROVIDES
ROBBABILITYS FOR EACH OF THOSE
THOUSAND OBLIGATIONS YECTS.
NOTICE THAT THE PAPER IS ABOUT
1.07% FROM THIS ORIGINAL IMAGE.
SO HOW MIGHT THIS BE USE INDEED
PAIN ASSESSMENTS IN WELL YOU CAN
SEE HOW YOU MIGHT BE ABLE TO DO
THIS.
THIS' --THERE'S A VERY SIMPLE
TRICK FOR LEARNING I WILL SHOW.
IMAGINE YOU HAVE THE ALEX NETAND
YOU CAN KNOW IT CAN CLASSIFY A
THOUSAND OBLIGATIONS YEKS.
SO HERE'S A PATIENTS PICTURE OT
AND IT WILL PREDICT PROBABILITY
FOR THOSE THOSE THOUSAND
OBLIGATIONS YECTS SO IT SAYS 90%
IS THE CAT, SO IT CAN ALSO
REPLACE THE FINAL LAYER OF THOSE
THOUSAND OBLIGATIONS YECT ANDS
SAY, WHY DON'T INSTEAD I PUT IN
A CLASSIFICATION LIKE IN OUR
LAB, SCORING HYPER KERATOSEIS
AND [INDISCERNIBLE].
AND WE HAVE A SCORE OF 1-4 AND
NOW IN STED OF USING THESE
ORIGINAL IMAGES WE USE TO
CLASSIFY OBJECTS WE SHOW IMAGES
OF THE SETTING OF DIFFERENT
CLASSIFICATIONS--BASICALLY 2
APPROACHES, 1 CAN EXTRACT
FEATURES FROM THE IMAGES
THEMSELVES OR ALSO USE SOME SORT
OF INTERMEDIATE REPRESENTATION
FROM FEATURES TO ARK ASSESSES IN
KIND OF SCORE OR PAIN SCORE.
WHAT'S NATURAL LANGUAGE
PROCESSING
PROCESSING?
IT'S A MACHINE LEARNING SYSTEM
CAPABLE OF SORTING AND
CLASSIFYING TEXT DATA.
NATURAL LANGUAGE PROCESSING HAS
BEEN USED IRPT CHANGEABLILY WITH
TERMS SUCH AS TEXT MINING AND
INFORMATION EXTRACTION CAN IT
CAN BE REALLY USEFUL FOR
STANDARDIZING THINGS LIKE
REPORTS AND INPUTS FROM HUMANS.
RESPIRATORY HOW DOES THIS THING
WORK IN IMAGINE YOU HAVE A
SENTENCE THAT LOOKS LIKE THIS.
SO FOR THOSE THAT MIGHT HAVE
DONE ULTRASOUNDS IN CATS MIGHT
SEE A STATEMENT THAT LOOKS LIKE
THIS.
THE FIRST STEP A NATURAL
LANGUAGE PROCESSING SYSTEM DID
IS GO THROUGH THE PROCESS OF
TOKENNIZATION, BREAKING UP ALL
THOSE LITTLE THINGS INTO
DIFFERENT WORDS.
SO HERE I SHOW EACH OF THOSE
WORDS WITH SPELLING MISTAKES AND
ALL.
NOW WHAT IT DID IS WHAT'S CALLED
THE TOP REMOVAL.
IT WILL THROW OUT WORDS THAT ARE
NOT ADDING MUCH VALUE TO THIS
ENTIRE SET OF THESE PIECES OF
WORS, THINGS LIKE OF, OF, AND SO
FORTH.
THEP IT GOES THROUGH SPEECH
TAGGING, SUCH AS NOUNS AND
VERBS, SHOWN IN DIFFERENT COLORS
AND THEN THERE IS A STEP CALLED
NAMED ENTITY RECOGNITION,
IDENTIFYING NAMES OF PEOPLE AND
PLACES.
SO WE'RE LUMPING CERTAIN THINGS
LIKE ULTRASOUND EXAM, MUSKULARIS
AND SO FORTH OF DIFFERENT
SECTIONS OF THIS ORIGINAL
SENTENCE AND THEN THERE'S
SENTIMENT ANALYSIS AND I WILL
SKIP THIS PART.
AND THEN THERE'S THIS PART,
DETERMINING THE GRAMMATICAL
STRUCTURE OF THE SENTENCE
CREATED OR PROVIDED.
AND THEN THERE'S A PROCESS
CALLED LAMETTIZATION AND
STEMMING, THAT'S REDUCING WORDS
TO ITS ELEMENTAL FORM,
EXAMINATION COULD MEAN EXAMS,
WE'RE TALKING ABOUT THE SAME
THING, WE'RE TALKING ABOUT AN
EXAM.
AND THEN OF COURSE, THE FINAL
TEXT CLASSIFICATION AND THIS
DEPENDS ON WHAT YOUR SPECIFIC
TASK IS, SO IF YOUR TASK IS TO
TRY TO UNDERSTAND WHAT THE EXAM
IS, HAVE YOU CLASSIFICATIONS OF
THOSE DIFFERENT WORDS BASED ON
THE CATEGORIES YOU CREATED SO IN
THIS CASE, I THEY'RE ASSOCIATED
WITH THE WORD EXAM AND ANOTHER
SET OF WORDS THAT ARE ASSOCIATED
WITH A FINDING AND A CONTRA
INDICATION OR INDDICATION IN
THIS CASE AND A DIAGNOSIS.
SO CAN YOU START TO SEE HOW ALL
OF THESE DIFFERENT WORDS WHEN
STRUNG TOGETHER CAN START TO BE
USED TO DEVELOP TO BE ABLE TO
HAVE A MACHINE LEARNING SYSTEM,
EXTRACT MEANING FOR WHAT IS
MEANT.
I REALLY LIKE THOSE WORDS, THESE
ARE LARGE LANGUAGE SO EVERYONE'S
FAMILIAR WITH THE CHATGPT AND
ALL THESE SYSTEMS THAT ARE
AFLOAT IN THE INTERNET, BUT
EFFECTIVELY WHAT THEY ARE IS
IMENERATING HUMAN LIKE TEXT
RESPONSES BASED ON WHAT THOSE
INPUTS ARE, SO WE ARE TAKING ALL
OF THOSE THINGS IN NATURAL
LANGUAGE PROCESSING TO DETERMINE
WHAT THAT SENTENCE MEANT AND
THEN THROUGH AN INCREDIBLE
COLLECTION OF TRAINED DATA,
IT--THIS NEURAL METE YORK CAN
PREDICT WHAT COMBINATIONS OF
WORKS MAKE A REASONABLE RESPONSE
TO THAT INPUT SET OF WORDS.
SO THERE'S NO SENTIENCE GOING
ON, THING'S NOT ALIVE.
IT'S REALLY JUST TAKING THIS
STRUCTURED INPUT AND GENERATING
AN OUTPUT WHICH WE AS HUMANS CAN
TRY TO THINK WE UNDERSTAND.
THESE THINGS CAN BE EXTREMELY
USEFUL FOR THINGS LIKE
STANDARDIZED REPORTING, SO
IMAGINE IF YOUR A RADIOLOGIST
AND YOU WORK IN A CENTER WHICH
HAS 3 OTHER RADIOLOGISTS, YOU
MAY ALL HAVE DIFFERENT WAYS OF
REPORTING YOUR RADIOLOGY REPORT.
IT WOULD BE REALLY NICE TO
STANDARDIZE ALL THAT
INFORMATION, SOME WOULD SAY AND
SO THESE KINDS OF SYSTEMS CAN
CAN DO THIS KIND OF WORK.
WE CAN STANDARDIZE A LOT OF THE
WORK, TAKE UNSTRUCTURED DAILY
BASIS THEA AND CREATE IT INTO A
TRUCTURED DATA SET.
ANOTHER TECHNOLOGY TRANSFER
THESE CAN DO IS TO SEARCH AND
QUERY LARGE DATABASES AND LOOK
FOR TRENDS WITHIN DATABASES,
SUCH THAT IT WOULD BE USED FOR
OTHER KINDS OF RESEARCH AND WORE
ALSO SEEING IN HUMAN MEDICINE,
HOW THESE SYSTEMS CAN BE USED TO
DETECT CERTAIN SETS OF KEY WORS
WHEN PHRASED TOGETHER COULD
INDICATE ALARMS LIKE SEPSIS FOR
EXAMPLE EMPLOY WHAT'S SPEECH
RECOGNITION, THERE ARE 4 STEPS
INVOFFED, THE FESTER STEP IS
ACOUSTIC ANALYSIS, IT'S TAKING
SOME KIND OF SOUND WAVE WHICH
DIGITIZED AND ANALYZING THAT
SOUND WAVE AND LOOKING FOR
PACIFIC FEATURES CAN WHICH MAY
BE ASSOCIATE WIDE A WORD.
SO IN THIS CASE, IT'S TAKING
SOME PATTERN OF SIGNATURES FALS
OF SOUNDS AND AND ASSOCIATING IN
THIS CASE WITH THE WORD DOG
EMPLOY THEN THERE'S OFTEN A
LANGUAGE MODEL THAGOREAN HAPPENS
AFTER THIS, SO 1 CAN--EXCUSE ME,
SCATTER DIFFERENT PORTIONS OR
DIFFERENT WORDS IN A SENTENCE
BUT THEY EFFECTIVELY MEAN THE
SAME THING.
SO YOU WOULD WANT TO BE ABLE TO
MODEL THIS BEHAVIOR, IF SOMEONE
SPEAKS SHIETLY DIFFERENTLY OR
HAS A DIFFERENT LANGUAGE BUT
EFFECTIVELY, THERE'S A COMMON
MEANING THAT'S ASSOCIATED WITH
THAT COLLECTION OF WORDS.
THEN THERE'S TRAINING AND
ADAPTION, LOOKING AT THE
ASSORTMENT SO IN THIS CASE WE
HAVE VAIDER, WE HAVE BUCK, MAYBE
BUCK IS NOT A DOG, MAYBE IT'S A
DEER, SO YOU WOULD WANT TO HAVE
SOME WAY FOR CORRECTING THIS.
WHERE ARE THESE THINGS USED
TODAY IN TERMS OF PAIN
ASSESSMENT.
THIS IS A NICE PAPER I CAME
ACROSS LOOKING AT DOGS THAT ARE
BARKING AND EXTRACTING MEANING
FROM THEM AND TRYING TO
UNDERSTAND IF THERE WAS A
CONNECTION BETWEEN THE BARK AND
A PARTICULAR STATE OF THE DOG
EMPLOY AND I WOULD ENCOURAGE YOU
TO TAKE A ELECTRIC AT THIS
BECAUSE THERE ARE ALL SORTS OF
EXAMPLES SHOWN HERE FOR THIS
KIND OF APPROACH TO DOLPHINS OR
ELEPHANTS AND O FORTH WHERE
THEY'VE TAKEN SPEECH RECOGNITION
TOOLS TO SEE IF THEY CAN
UNDERSTAND WHAT THE ANIMALS ARE
SAYING.
AND THIS IS THE BASIC APPROACH,
SO WHAT HAPPENS IS YOU HAVE A
MICROPHONE, THEY TAKE THE DATA,
YOU GET THE ACOUSTIC SIGNAL,
THAL CASE, THEY STUDIED 8 DOGS
AND YOU COLLECT THESE BARKING
SOUNDS AND THEN THEY HAVE
ASSOCIATIONS OF WHAT TYPE OF
INSTANCE WE MIGHT BE--THE DOG IS
BARKING EMPLOY SO FOR EXAMPLE, 1
WOULD TAKE THE DOG TO A PARK,
TAKE THE LEASH, TIE THE LEASH TO
A POST, AND THEN WALK AWAY, AND
THEN RECORD THE BARKING AND THAT
WOULD REPRESENT ALONE, AND THAT
WOULD BE ALONE BARKS, PUT IT
INTO A DATA SET, AND SAME THING
WITH THESE SCORES.
YOU TAKE THE DATA.
HAVE YOU A CLASSISK, YOU HAVE A
METHOD, A WAY OF CONNECTING
THOSE AUDIO SIGNALS WITH THOSE
DISCREET OUTPUTS.
AND THEY WERE ABLE TO FIND SOME
PRETTY INTERESTING RESULTS.
SO THERE'S CONFUSION MATRIX FOR
THIS, YOU CAN SEE THE DIAGONAL
SHOWING THE TRUE PREDICTIVE
CLASS AND THE M., THE TRUE
CLASSES AND YOU CAN SEE THAT IN
SOME INSTANCES IT DOESN'T DO TOO
WELL BUT FOR SOME THINGS IT DOES
REPRETTY WELL.
SO IF FIGHT, IT SHOWS A STRONG
SIGNAL, IN OTHER WORDS THE AI
ALGORITHM IS ABLE TO DETECT THAT
SIGNAL, AND ASSOCIATE THAT WITH
THIS THING CALLED FIGHT.
SO WHAT OTHER CHALLENGES WE SEE
HERE.
I HAVE 4 OR 5 SLIDES HERE WHERE
I SEE CHALLENGES AND PAIN
ASSESSMENT.
THE FIRST 1 IS CLARITY AND
TRANSPARENCY OF AI FEATURES AND
DECISIONS ISSUES THE ABILITY TO
TO LEARN FROM THESE PROCESSES
AND SYSTEMS ARE PIVOTAL IN A
CLASSICAL SESSION, THIS IS
IMPORTANT IF VETERINARY MEDICINE
WHERE THERE'S A HEFTY RELIANCE
OR VISUAL AND SIGNAL ASSESS AMS
FOR ANIMALS STATES.
ANOTHER IMPORTANT CONSIDERATION
IS LEVERAGING DATA SOURCES AND
WE HEARD EARLIER ABOUT USING
DIFFERENT TYPES OF CATASETS BUT
LEVERAGING THOSE MULTIPLE DATA
SOURCES FOR ENHANCED
PERFORMANCE.
INCORPORATING A WIDE RANGE OF
DATA RELATED PAIN ALONGSIDE AN
INTEGRATING ARK DITIONAL
FUNCTIONS SUCH AS DETECTING HEAD
POACHES, FACIAL AND OCCLUSION
HAS THE POTENTIAL TO ENHANCE THE
RESILIENCE AND EFFECTIVENESS OF
THESE OTHER DETECTION SYSTEMS.
OBTAINING MULTIPLE DATA SOURCES
IS ITSELF A PRETTY MUCH A
CHALLENGE IN VETERINARY MEDICINE
WHERE IT DID NOT HAVE RESOURCES
AVAILABLE AS THEY DO IN HUMAN
HEALTHCARE ASK WHEN THEY ARE
AVAILABLE, THEY MAY NOT BE
SUITABLE FOR GENERATING RELIABLE
DATA NEEDED FOR MODELING.
ANOTHER IMPORTANT ADDRESS IS
ADDRESSING THESE CHALLENGES
THROUGH COLLABORATION.
WE HAVE TO WORK WITH
VETERINARIANS BASIC BIOLOGISTS,
DATA SCIENTISTS AND OTHERS TO
INSURE THE MODELS ARE ASHES -
-ADAPTABLE AND ADOPTABLE.
THIS IS A REALLY INTERESTING
PART OF THIS PROBLEM IS
CONSIDERING THE TIME BASED
ATTRIBUTES OF PAIN EPISODES AND
THE INFLUENCES OF PAIN
MEDICATION AND HOW WE CAN MODEL
THOSE THINGS.
JUST EXPLORING GENERALIZABILITY
ACROSS DIFFERENT COHORTS, I HAVE
APOLOGIZE FOR THIS WEIRD MESSAGE
THAT [INDISCERNIBLE] CREATED,
BUT THE POINT HERE IS THAT WE
HAVE TO REALLY HAVE A GOOD
HANDLE ON THE RANGE OF YOUTH
OFNESS OF THESE AI MODEL ANDS
THIS IS NOT AN EASY THING TO DO.
AGAIN JUST BRIEFLY WE HAVE
ISSUES OF STANDARDIZATION OF THE
DAILY BASIS THEA CAPTURE, DATA
SHARING, WE HAVE TO THINK ABOUT
THAT, RESPONSIBLE USES OF AI,
WHEN IS IT SAFE TO USE THIS
TECHNOLOGY AND THEN A WHOLE
GAMUT OF ETHICAL ISSUES THAT I
DIDN'T EACH DELVE INTO.
THAT PRETTY MUCH SUMMARIZES THE
TALK THAT I HAD FOR TODAY AND I
LEAVE YOU WITH THIS FINAL
PICTURE OF STABLE DIFFUSION'S
RESPONSE TO ANDROID'S DREAM OF
SHEEP IN PAIN IN THE IN THE
STYLE OF PLAYED RUNNER AND IT IS
REALLY QUITE A WEIRD PICTURE
THAT MAYBES YOU THINK.
THANK YOU.
[ APPLAUSE ]
SHAMELESS SELF-PROMOTION, WE
HAVE A SYMPOSIUM ON ARTIFICIAL
INTELIENCE IN VETERINARY
MEDICINE THAT'S GOING TO BE THE
FIRST OF ITS KIND ON
APRIL 19th, THE 21st AT
CORNELL UNIVERSITY IN ITHACA.
>> THANK YOU VERY MUCH
DR. BASRAN, THAT WAS AN
EXCELLENT PRESENTATION ON
INTRODUCING US TO AI AND ITS
POTENTIAL USES FOR PAIN
ASSESSMENT.
THE LAST SPEAKER WE HAVE BEFORE
THE PANEL BEFORE LUNCH, IS
DR. EDWADDERA BORTOLUZWRRKS I,
SHE HOLDS A VETERINARY MEDICINE
DEGREE FROM THE FEDERAL
UNIVERSITY OF [INDISCERNIBLE]
BRAZIL AND COMPLETED HER MASTERS
AND Ph.D. STUDIES AT K-ITATE.
HER INTERESTS ENCLUED ANIMAL
BEHAVIOR AND THE WELFARE OF
DOMESTIC SPECIES EMPHASIZING
DEVELOPMENT OF NEW WELFARE
METRICS USING ARTIFICIAL
INTELIENCE AND MACHINE LEARNING
AND HER TITLE OF HER TALK IS
APPLICATION OF AIML TO LARGE
ANIMALS FOR PAIN MEASUREMENT SO
WELCOME EDUARDA.
[APPLAUSE ]
>> HELLO, THANK YOU SO MUCH FOR
HAVING ME HERE TODAY.
I AM REALLY TBLAD I GOT TO STAY
HERE AFTER THE PRESENTER THAT
JUST PRESENTED BECAUSE HE KIND
OF EXPLAINED A LITTLE BIT OF THE
THINGS THEY WILL TALK ABOUT SO
THAT IS VERY HELPFUL.
SO FIRST THINGS FIRST, WE NEED
TO TALK ABOUT HOW WE MEASURE
PANE AND YOU SAW DIFFERENT WAYS
WE DO THAT THROUGHOUT THE
PRESENTATIONS THIS MORNING BUT 1
OF THE WAYS WE WERE INTERESTED
IN MAIN IS ABOUT ANIMAL WELFARE
SO 1 OF THE COMMON FRAMEWORKS WE
USE FOR ANIMAL WELFARE IS THE 3
CIRCLES FROM FRAZIER, AND I WILL
BE FOCUSING ONASTIVEITATES OF
THOSE ANIMALS SO THE 3 CIRCLES
WILL INCLUDE BASIC HEALTH AND
FUNCTION, NATURAL LIVE XG THEN
AFFECTIVE STATES.
SO THE TERM AFFECTIVE STATES
REFERS TO EMOTIONS AND FEELINGS
THAT ARE EXPERIENCED AS PLEASANT
AND UNPLEASANT.
SO IT WILL RANGE FROM A SCORE OF
POSITIVE AND NEGATIVE AND
INCLUDES THINGS LIKE PAIN,
DISTRESS AND PLEASURE.
AND AS YOU ALL KNOW THAT GETS A
LITTLE BAD RAP WHEN WE DO
STATISTICS BECAUSE THEY ARE
CONSIDERED SUBJECTIVE MEASURES
AND WE HAVE THIS PUSH BACK FROM
RESEARCHERS WHEN WE ARE GOING TO
GO AND PUBLISH LIKE YOU SAW IN
THE FIRST TALK BY DR. BROWN.
SO THE BIGGEST CHALLENGE WE FACE
WITH ANIMAL IS THERE AN
INABILITY TO VERBALIZE THEIR
PAIN.
WE LACK A GOLD STANDARD TO
IDENTIFY THEIR AFFECTIVEITATES
AND FOR THAT WE RELY A LOT ON
BEHAVIOR, BODY POSTURES AND
FACIAL GRIMACES.
SO AS YOU GUYS KNOW, THOSE
MEASURES CAN BE VERY SUBJECTIVE
AND THEY ARE EFFECTIVE BY THE
HUMAN EMPATHY.
ALSO THE KNOWLEDGE OF THE
SPECIES, AND THE NORMAL BEHAVIOR
OF THOSE ANIMALS AND ALSO, THE
TRAINING THAT IS USED TO MAKE
THOSE ASSESSMENT IN USING THOSE
SCORES SO 1 EXAMPLE I BROUGHT TO
YOU WAS A STUDY DONE BY THOMPSON
IN 2012 WHERE THEY COMPARE HOW
FARMERS AND VETERINARIANS WOULD
ASSESS A LAMENESS IN DAIRY COWS
AND WHAT THEY FOUND THAT WAS A
HIGH VARIABILITY IN PAIN SCORES.
THEY SAW THAT THE FARMERS WERE
ACTUALLY MORE EMPATHETIC TOWARDS
THE ANIMALS THAT THEY SAW EVERY
DAY, COMPARED TO THE
VETERINARIAN, SO THEY TEND TO
SCORE A LAMENESS OR PAIN OF
LAMENESS A LITTLE HIGHER THAN
THE VETERINARIANS.
SO WHY TO USE ARTIFICIAL
INTELIENCE AND MACHINE LEARNING
AND THAT IS HARD BECAUSE THE
MAIN GOAL IS JUST TRYING TO
TRANSFORM MANAGE THAT IS VERY
SUBJECTIVE THAT ARE AROUND
ANIMALS CAN MAYBE TELL YES, THIS
ANIMAL WAS FEELING PANE BUT WE
NEED TO HAVE A WAY TO
TRAPEZIUSALATE THAT WHEN WE ARE
GOING TO DO OUR STATISTIC
ANALYSIS OR WHEN WE'RE GOING TO
EXPLAIN TO OTHER RESEARCHERS
WHAT WE ARE SEEING IN THOSE
ANIMALS.
THE OTHER BIG THING WE NEED TO
THINK ABOUT IN ARTIFICIAL
INTELIENCE AND, AND HELP TO
THOSE PEOPLE THAT ARE DOING THE
ANIMAL HUSBANDRY EVERY DAY.
SO BY DOING, USING ARTIFICIAL
INTELIENCE AND MACHINE LEARNING,
WE HAVE AN OPPORTUNITY TO
INCREASE THE VALIDITY OF OUR
DATA BY IMPROVING THE QUALITY OF
THE MEASUREMENT WE ARE TAKING.
WE ALSO INCREASE THE RELIABILITY
BETWEEN DIFFERENT LAB GROUPS.
AS WE KNOW THE TRAINING CAN BE
DIFFERENT AND THOSE PAIN SCORES
CAN BE COMPLETELY DIFFERENT
BETWEEN LABORATORIES, SO HAVING
THAT TOOL OF ARTIFICIAL
INTELIENCE AND MACHINE LEARNING
CAN ACTUALLY HELP US WITH THAT.
AND THEN WE CAN ALSO DECREASE
BIAS, ESPECIALLY BEING A
VETERINARIAN WORKING WITH
ANIMALS AS SOMETIMES YOU GET
ASHES TACHED TO ANIMALS AND YOU
MIGHT SCORE THEM DIFFERENTLY
BECAUSE OF THAT EMPATHETIC
FEELING YOU FEEL FORWARDS THEM.
OKAY, SO THERE'S A LOT OF
RESEARCH THAT HAS BEEN DONE ON
ARTIFICIAL INTELIENCE AND THE
MACHINE SIDE OF THINGS
ESPECIALLY IN INFANTS AND PEOPLE
THAT CANNOT VERBALIZE THEIR PAIN
EMPLOY THEY ARE VERY AHEAD OF US
IF WE COMPARE VETERINARY
MEDICINE, THEY HAVE A LOT OF
RESEARCH BEING DONE IN THE LAST
COUPLE OF YEARS.
AND THIS IS JUST A COUPLE
EXAMPLES OF THINGS THAT THEY
HAVE USED FOR, THE SECTION OF
PAIN, AND ALSO, PAIN RELATED TO
BACK PAIN AND USING THE
ARTIFICIAL INTELIENCE AND
MACHINE LEARNING TOWARDS GRIMACE
AND ALSO THE BEHAVIOR OF THE
HUMAN PATIENTS.
HOWEVER, WHEN WE LOOK INTO LARGE
ANIMALS WE ARE VERY FAR BEHIND
AND THE MAIN SPECIES WE HAVE
RESEARCH ON IS SHEEP, HORSES AND
PIGS.
AND THAT THERE'S A LOT OF
VARIABILITY IN THAT DATA AND HOW
THEY COLLECT THOSE RESULTS AND
HOW THEY ANALYZE THEIR DATA.
SOME OF THEM ARE LOOKING INTO
SHOULDITATES OF PAIN BY LOOKING
AT FACIAL GRIMACE AND THEY CAN
JUST USE BEHAVIOR AS NORMAL PAIN
THAT IS OCCURRING IN THE ANIMALS
AND THEY CAN ALSO INDUCE PAIN TO
TRAIN THEIR MODELS TO CLASSIFY
THOSE ANIMALS AS FEELING PAIN OR
NOT.
BUT IN ANOTHER AREA THAT HAS
BEEN USED A LOT INCLUDING PIGS
IS USING WHAT WE CALL THE
EMOTIONS AND THE WAY WE MEASURE
EMOTIONS IS THROW THE BEHAVIOR
OF THOSE ANIMALS.
SO THEY CAN BE DONE USING BODY
POSTURES, ALSO THE FACIAL
GRIMACE BUT IN THE BIG PICTURE,
JUST ELECTRICKING AT OUR VIDEO
AND THEIR BEHAVIOR.
SO I WANTED TO BRING SOME
EXAMPLES FOR YOU OF HOW WE CAN
USE THOSE ASSESSMENTS, AND WHAT
HAS BEEN DONE BEFORE SO CAN YOU
HAVE AN IDEA OF WHERE WE'RE
GOING WITH THAT.
SO THE FIRST RESEARCH ARTICLE
BROUGHT TO YOU WAS DONE IN
BRAZIL, SO DEAR TO MY HEART AND
IT WAS ENTITLED PAIN ASSESSMENT
IN HORSES USING AUTOMATIC FACIAL
RECOGNITION THROUGH DEEP
LEARNING AND LEARNING BASE
MODELING.
SO THIS PUBLICATION WAS DONE
PLUS 1 AND THE AUTHOR USED 3000
IMAGE TO CREATE A DATA SET FOR
TRAINING AND TESTING OF
CONVOLUTIONAL NEURAL NETWORK TO
AUTOMATICALLY ASSESS GRIMACE
SCALE IN HORSES THAT WERE
SUBMITTED TO CASTRATION.
SO THE WAY THAT THEY DID THAT IS
THEY HAD CAMERAS OVERHEAD AS CAN
YOU SEE AND WHEN THE ANIMAL'S
APPROACH THE AREA THE CAMERA
WOULD TAKE A PICTURE OF THE FIES
OF THE HORSE AS CAN YOU SEE IN
THE IMAGE, AND THEY FIND THE 3
DIFFERENT AREAS OF ABOUT THAT
THEY USE ON THE GRIMACE SCALE.
SO THE FIRST PART OF TRAINING
THIS MODEL WAS TO ACTUALLY FIND
THE FACE OF THE HORSE, AND THEN
FIND THOSE AREAS WHERE THEY HAD
INTEREST.
SO THEY LOOK FOR THE EARS, THE
EYES AND THE NOSE AND MOUTH OF
THAT ANIMAL.
AND THEY HAD A PRETTY GOOD
ACCURACY ON FINDING THE EARS, ON
FINDING 93%, AND FOLLOWING WITH
THE NOSTRILS OF 74.5 AND THEN
FOLLOWED BY THE EYES.
SO THE NEXT THING THAT THEY DID
WAS THEY GAVE THE SCORES TO
THOSE ANIMAL ANDS THEY TRAIN THE
MODEL TO PREDICT IN WHICH CORE
THE ANIMAL WAS GOING TO FALL
INTO.
AND BY DOING THAT, THEY DIVIDED
THE ANIMALS INTO PRESENTING
PAIN, PRESENTING PAIN MODERATELY
AND OBVIOUSLY PRESENTING PAIN.
SO WHEN THEY DID THAT BY USING
HOSE GRIMACE SCORES THEY ACHIEE
A 75.8% ACCURACY ON THOSE
ANIMALS SO THEY THOUGHT THEY
COULD IMPROVE ACCURACY OF HOW
THEY DETECT PAIN AND THEY
DECIDED TO COMBOYNE THOSE AND
MODERATE AND PRESENT THEY
COMBOYNE THOSE 2 TOGETHER AND
THEY END UP WITH A BINOMIAL TYPE
OF DATA WHERE THEY HAD PAIN AND
NO PAIN.
AND WHEN THEY DID THAT THEY
IMPROVE THEIR ACCURACYS BY
88.3%.
SO, IT WAS A LITTLE BITTER OF
WHAT THEY HAD BEFORE BUT THEY
WERE ABLE TO USE THAT GRIMACE
SCALE IN A MORE OBJECTIVE WAY
THAN WHAT WE WOULD DO WHEN WE
WERE JUST SCORING BY A HUMAN
EMPLOY THE NEXT 1 IS QUITE GOOD
BECAUSE THE PRESENTER BEFORE ME
ALREADY KIND OF SHOWED THIS 1,
THIS WAS DONE IN SHEEP AND IT
WAS ENTITLED TOWARDS AUTOMATIC
MONITORING OF DISEASE PROGRESS
IN SHEEP: A HIERARCHICAL MODEL
FOR SHEEP FACIAL EXPRESSIONS
ANALYSIS FROM VIDEO.
THIS IS A NEAT STUDY THEY HAD TO
DEVELOP, THEY HAD TO DEVELOP A
ROBUST SHEEP FACIAL DETECTION
MODEL, SO THE FIRST THING WAS
HAVING BIG HERDS OF SHEEP AND
FINDING THE FACE OF THOSE
ANIMALS USING BINDING BOXES.
SO JUST LOOKING FOR THOSE IMAGE
AND TRYING TO FIND WHERE THE
SHEEP WAS AT AND WHERE THEIR
HEAD WAS AT.
THEY DO THAT BY USING CONTINUOUS
DETECTION AND ANALYSIS OF VIDEO
SO THEY HAD A LOT OF VIDEOS OF
THOSE ANIMALS AND THEY
CONTINUOUSLY FOUND THOSE FACES
OF THOSE ANIMALS.
AND THE GOOD THING THAT THEY DID
HERE WAS THEY ACCOUNTED FOR, HAD
ROTATION AND SELF-OCCLUSION
WHICH CAN BE VERY BIG WHEN WE
TALK ABOUT MACHINE LEARNING AND
ARTIFICIAL INTELLIGENCE WHEN YOU
DON'T HAVE THE EYE PRESENTING
ITSELF ON THE IMAGE, HOW YOU
CLASSIFY THAT ANIMAL.
SO FOR THIS PROMULGATE
ECTOMYOSIN THEY WERE ABLE TO
THEY WERE ABLE TO ACCOUNT FOR
THAT OCCLUSION, MAYBE THERE'S
AN ANIMAL IN FRONT OF ANOTHER 1
SO THERE'S AN OVERLAP OF HEADS
IN THE IMAGE THEY HAD AND THEN
THEY ALSO USE A TEMPORAL NATURE
OF FACIAL XREGS SO THEY COULD
FOLLOW THOSE ANIMALS THROUGH
TIME.
THEY USE A PAIN SUMMATION MODEL
ISSUE UTILIZING REGIONS OF
INTEREST LIKE THEY DID IN THE
PREVIOUS STUDY AND I'M GOING TO
SHOW YOU JUST KIND OF A LITTLE
BIT OF HOW THEY DID THAT.
SO THE FIRST THING WAS TO FIND
THE FACE OF THE SHEEP AS CAN YOU
SEE BY THE PURPLE BOX SO THAT
WAS THE FIRST THING THAT THEY
DID WAS CREATE THE MODTOLL FIND
THOSE HEADS AND THEN THEY WERE
ABLE TO PUT LANDMARKS
SPONTANEOUS ACTIVITY THE FACE OF
THE SHEEP SO I KNOW IT'S QUITE
SMALL BUT THOSE PURPLE DOTS
REPRESENT ALL OF THE AREAS, THE
LANDMARKS THAT THEY DID, TO FIND
THE FACE OF SHEEP AND ALSO
ACCOUNT FOR THAT, MAYBE
OCCLUSION OR TILT OF THE HEAD.
ONCE THEY DID THAT, THEN THEY
WERE ABLE TO FIND THOSE REGIONS
OF INTEREST SO THEY LOOKED FOR
THE 2 EARS, THE NOSE, BOTH EYE
ANDS THEN THE POSITION OF THE
HEAD.
AND THEN THEY RUN THAT THROUGH A
CLASSIFIER TYPE OF MODEL THAT
WOULD PREDICT IF THE ANIMAL WAS
IN PAIN OR NOT IN PAIN BASED ON
ALL OF THAT.
SO WHEN YOU LOOK AT THE RESULTS,
YOU CAN SEE THAT THEY USE ALL
THEIR APPROACHES TO LOOK FOR THE
PRECISION AND RECALL AND FOR
THOSE OF YOU THAT ARE MORE
ACCUSTOMED TO EPIDEMIOLOGICAL
DATA OUR PRECISION WOULD BE OUR
PROZZATIVE PREDICTIVE VALUE AND
OUR RECALL WOULD BE OUR
SENSITIVITY.
AND THE F1 SCORE IS GOING TO BE
A COMBINATION BETWEEN THE 2
WHERE THEY MODEL HOW THE
PRECISION AND RECALL IS DONE TO
FIND OUT IF THE ANIMALS WERE IN
PANE OR NOT.
SO AS CAN YOU SEE, WHEN THEY
WHEN THEY USE EACH 1 OF THOSE,
THEY ACHIEVE A GREAT PRECISION
BUT WHEN THEY COMBINE THE
REGIONS OF INTEREST, THE POSE OF
THE HEAD AND THE GEOMETRY OF THE
FACIAL, THEY ACTUALLY HAD A
BETTER PRECISION OF 83%, RECALL
OF 68% AND AN ACCURACY OF 78%.
SO THE LAST STUDY I WANT TO
PRESENT TO YOU IS ACTUALLY DONE
DURING MY Ph.D.
WE USE AN EVALUATED PRECISION
LIVESTOCK TECHNOLOGY AND WE
COMPARED TO THAT PRECISION
TECHNOLOGY TO HUMAN SCORING OF
NURSERY PIGS THAT WERE
CHALLENGED USING LPS.
SO THIS WAS DONE WITH THE
UNIVERSITY OF NEBRASKA AND WHAT
WE USE WAS A CAMERA THAT WAS ON
TOP OF THE PANS AND IT WAS ABLE
TO IDENTIFY EACH INDIVIDUAL
ANIMAL USING THEIR EAR TAGS.
SO THAT IS A CHALLENGE HAD WE
USE ARTIFICIAL INTELLIGENCE IS
BEING ABLE TO TELL WHICH ANIMAL
IS WHAT WHEN WE'RE TALKING ABOUT
HERDS.
SO THIS IS WHAT THIS PROJECT WAS
DONE BY USING THOSE EAR TAGS.
AND THEN BY DOING SO, WE WERE
ABLE TO ANNOTATE AND TO TRAIN
OUR MODEL TO FIND BEHAVIORS OF
THOSE ANIMALS THAT WE HAD
INTEREST ON BASED ON SICKNESS.
SO THEN WE WERE ABLE TO IAT THE
PRESENT TIMIFY THE ANIMALS WERE
PRESENTING CLINICAL SICKNESS OR
NOT AND THEN COMPARING TO A
VETERINARIAN STAND NOTHING FRONT
OF THE PIN AND CHECKING IF THE
ANIMAL PRESENTED SICKNESS OR
NOT.
SO THE GOLD STAND ORDER WOULD
RECEIVE WELL, PS OR THEY DIDN'T
RECEIVE LPS.
AND WE USE QUITE A HIGH DOSE OF
LPS, SO THEY PRESENTED A LOT OF
THOSE BEHAVIORS OF PAIN, JUST
STRUGGLING LOOKING AT THE FLANK
AND THEN WE USE, WE COMPARE THAT
GOLDEN STANDARD WITH THE GOLD
STANDARD, SORRY WITH 6 CORES
THAT WERE DONE BY THE HUMAN
OBSERVER AND THE BEHAVIORS
COMING FROM OUR PRECISION
TECHNOLOGY THAT I WILL BE
REFERRING AS NO TRACK.
SO JUST TO SHOW YOU RESULTS ON
THE LPS AND ON THE Y-AXIS WE
HAVE THE AREA UNDER THE KUIVE
FOR BOTH NEW TRACK IN RED AND
SICKNESS SCORES DONE BY HUMANS
IN IMROAN.
AND YOU CAN SEE THAT THE NUTRACK
DID QUITE A BIT BETTER THAN US
IN IDENTIFYING WHICH PIGLETS
WERE PRESENTING SICKNESS AND
THEN WHAT HAPPENED WAS BY DAY 3,
BECAUSE THEY START TO RECOVER,
THE HUMAN HAD A REALLY HARD TIME
TO
IDENTIFY ANIMALS THAT WERE SICK
BEFORE BUT WHEN WE LOOK AT THE
NUTRACK, THEY HAD CURVE OF 0.9
WHICH IS FAIRLY GOOD IN
IDENTIFYING THOSE ANIMALS.
SO MOVING ON TO THINGS THAT ARE
JUST NOW COMING UP.
WE HAVE SYNTHETIC DATA BEING
GENERATED AND THIS IS IMPORTANT
BECAUSE WE NEED A LOT OF DATA TO
TRAIN A MODEL, WE NEED A LOT OF
VIDEOS, IMAGES AND IT'S
SOMETHING HARD TO DO.
SO THIS PROJECT WAS DONE IN IOWA
AND THEY GENERATED SEN
ILLEGALSENTHETIC DATA TO TRAIN
THEIR DEEP LEARNING MODEL AND
WHAT THEY HAD DONE FIRST WAS TO
DO THE SYNTHETIC MODEL OFF A COW
AS YOU SEE ON THE PICTURE ON
YOUR RIGHT.
AND THEN ON YOUR LEFT, THEY PUT
THE COW THAT THEY CREATED
SYNTHETICALLY IN A LOT OF
DIFFERENT ENVIRONMENTS WITH
DIFFERENT LIGHTING SO WE HAVE A
HARDS, IT WAS THOUGHT BEFORE
HAVING THE STANDARD DATA WHERE
THE PICTURE WAS TAKEN WITH THE
SAME LIGHTING IN THE SAME WAY
WITH THE SAME ANGLE.
SO WHAT THEY WERE TRYING TO DO
IS JUST TO USE ALL OF THOSE
DIFFERENT BACK IMROWNDS TO
BETTER TRAIN THE MODEL TO
CAPTURE THE BEHAVIORS OF THOSE
ANIMALS.
SO THIS IS 1 OF THE THINGS THAT
ARE BEING DONE IN THE PAST FEW
YEARS TO IMPROVE OUR ABILITY TO
USE OR SHOW INTELLIGENCE.
THIS IS ACTUALLY A VIDEO BUT I
DON'T KNOW WHY IT'S NOT PLAYING.
SO I WILL DESCRIBE TO YOU WHAT
HAPPENED HERE.
THIS IS ANOTHER SYNTHETIC DATA
SO THIS COMPANY FROM CANADA
CALLED 1 CUP, THEY CREATED A
LAMENESS MODEL OF A COW, SO THIS
COW WILL ACTUALLY BE WALKING
LAME AND THEN THEY CREATED A
MODEL TO FIND FOCAL POINTS THAT
THEY WANTED, SO ALL THE LAGS,
ALL THE HEAD, AND THEN PUT
LANDMARKS AS YOU SAW ON THAT
SHEEP IMAGE AND THEN THEY COULD
MEASURE DIFFERENT ANGLES OFF
THAT ANIMAL WALKING AND THEY'RE
JUST TRAINING THEIR MODEL AND
THEY'RE GOING TO TRY TO USE THAT
IN REAL ANIMALS AND SEE IF
TRAINING THE MODEL WITH
SYNTHETIC DATA CAN ACTUALLY BE
APPLIED TO LIVE ANIMALS.
SO JUST TO GIVE YOU SOME
CONCLUSION, ARTIFICIAL
INTELIENCE AND MACHINE LEARNING
OFFERS THE POTENTIAL TO PROVIDE
OBJECTIFICATION OF MEASURES THAT
WERE PREVIOUSLY OBJECTIVE,
ESPECIALLY THOSE WITH EMOTIONS
AND FEELINGS WHERE WE'RE STILL
STRUGGLING WHEN WE GO PUBLISH
AND IT ALSO OFFERS US WITH THE 3
Rs THAT WE ARE ALSO ALWAYS
TALKED ABOUT WHEN WE TALK ABOUT
ANIMAL WELFARE.
SO HAVING THAT REPLACEMENT AND
REPLACEMENT OF THE ANIMALS WITH
SYNTHETIC DATA TO TRAIN OUR
MODELS AND BETTER USE ON LIVE
ANIMAL ANDS THEN ALSO THE
REDUCTION OF THE NUMBER OF
IMAGES WE NEED AND THEN
REFINEMENT OF OUR METHODS.
AND WE ARE IN THE TECHNOLOGY ERA
SO YOU ALL USE YOUR PHONES.
YOU KNOW THAT THERE'S A LOT OF
TECHNOLOGY INVOLVED IN THAT AND
DON'T THINK WE CAN RUN AWAY FROM
ARTIFICIAL INTELIENCE AND
MACHINE LEARNING IN ANY OF THE
FIELDS SO WE JUST NEED TO
EMBRACE THAT AND BE OPEN MIND TO
LEARN DIFFERENT TOOLS WE CAN USE
TO IMPROVE THE WAY WE COLLECT
DATA.
AND WITH THAT, I JUST WANT TO
SAY THANK YOU FOR HAVING ME
HERE.
[ APPLAUSE ]
NI WOULD LIKE TO INVITE OUR
PANEL SPEAKERS FROM THE MORNING
PANELS, SO JUST FROM A
HOUSEKEEPING PERSPECTIVE, WE
HAVE AMERICA ICs SET UP IN THE
CENTER AISLES AND IF YOU HAVE A
QUESTION, I INVITE TO YOU COME
UP TO THE MIC AND YOU CAN DIRECT
YOUR QUESTION SPECIFICALLY TO 1
OF OUR PANELISTS OR FOR THE
PANELISTS TO RESPOND AS A GROUP
EMPLOY SO WE'LL JUST GET SET UP
HERE FOR A MOMENT, GET NAMES UP
AND PROCEED WITH THE PANEL
DISCUSSION HERE.
SO IF HAVE YOU ANY QUESTIONS IF
YOU WOULD LIKE TO MAKE YOUR WAY
TO 1 OF THE MICROPHONES AND IF
THE SPEAKERS COULD REPEAT THE
QUESTION, THAT MIGHT BE HELPFUL
TOO, IN CASE SOMEBODY MISSES
THAT.
SO I HOPE UP TO THE FLOWER NOW
AND INVITE THE ATTENDEES PLEASE
TO ASK SOME QUESTIONS.
MSO I'M INTERESTED IN WHAT CAN
PRACTICALLY BE DONE THROUGH PAIN
INTELIENCE OR OTHER MEANS.
HAVE YOU THOUGHT ABOUT CLOSED
LOOP SYSTEMS I CAN THINK OF
MAYBE GIVING ANIMALS OPIOIDS OR
EVEN IF YOU HAD GENE CIRCUITS OF
SOME SORT COMBINED WITH AI TO
PROVIDE RELIEF.
HAVE YOU THOUGHT ABOUT
CONNECTING THE TOOLS IN THAT
WAY?
>> SO THE QUESTION IS HOW WE CAN
CONNECT WITH THE ARTIFICIAL
INTELLIGENCE WITH TOOLS THAT CAN
MAYBE PROVIDE SOME OPIOIDS OR
SOMETHING THAT COULD HELP WITH
THE PAIN?
I THINK THE FIRST THING THAT, AT
LEASTOT LARGE ANIMAL SIDE, THAT
WE'RE TRYING TO DO IS JUST MAYBE
COME UP WITH AN ALERT SYSTEM FOR
THE PURPOSE THAT IS TAKING CARE
OF THOSE ANIMALS BECAUSE AS I
SAID BEFORE AND FINDING WORKERS
FOR OUR LARGE ANIMALS.
AND AND WORKING WITH THESE
ANIMALS TO TAKE A CLOSER LOOK.
>> I CAN SPEAK TO SOME OF THE
EXPERIENCES IN HUMAN MEDICINE SO
FOR EXAMPLE, FROM A NURSES
CONTROL PANEL AND THERE'S KIND
OF I THINK WE'RE SORT OF IN THE
SPACE OF HOW TO USE MACHINE
LEARNING IN A CLINICAL
ENVIRONMENT AND 1 OF THE
INTERESTING THINGS WE'VE
LEARNED--AND AGAIN, THIS
REQUIRES LIKE A REALLY LARGE
MULTIDISCIPLINARY EFFORT FOR
THESE NTHANKS FOR THE
THOUGHT-PROVOKING PRESENTATIONS,
I THOUGHT THE COMMON THEME WAS
ALL ABOUT HOW DO WE MOVE
FORWARD, HOW DO WE IMPROVE WHAT
WE'RE DOING, GET BETTER AND FIND
OTHER MEASUREMENT TECHNIQUES SO
WHETHER YOU'RE TRYING TO FIGURE
OUT WHICH MICRORNAs RELATE TO
PAIN OR WHETHER YOU'RE TRYING TO
APPLY ARTIFICIAL INTELIENCE, CAN
YOU COMMENT ON WHETHER OR NOT
YOU WORRY ABOUT THE GROUND TRUTH
GOING INTO IT BECAUSE YOU MAKE
ASSUMPTIONS BASED ON OUR CURRENT
ABILITY, AND YET THEA THE SAME
TIME YOU ARE TRYING TO IMPROVURE
ABILITY, BUT ARGUABLILY, IF YOU
IF THE AIM IS TO GET AS GO AS WE
CURRENTLY ARE, THEN WE'RE
NEVER--IF WE'RE ONLY 80%
ACCURATE NOW, WE'RE NEVER GOING
TO BE MORE THAN 80% ACCURATE SO
THAT'S THE FIRST PART, IF YOU
COULD COMMENT ON GROUND TRUTH.
HOW DO WE DEFINE THAT PAIN STATE
OR GRADES OF PAIN AS WE DEVELOP
NEW TECHNIQUES AND THE SECOND
PART REALLY DON'T MAKE ANY
ASSUMPTIONS.
THIS IS FROM A VERY NAIVE
PERSPECTIVE, THROW THE DATA INTO
THE CO AM PUTTER AND ASK IT TO
CREATE CLUSTERS AND PAUSE THE
DATA OUT AND THEN LOOK AT AND
KETECT THEM IN PAIN.
IN, YEAH, WELL, IT'S A GREAT
QUESTION.
IT'S A TOUGH 1.
I MEAN KNOWING THE GROUND TRUTH
OBVIOUSLY HELPS WHEN YOU TRY TO
IDENTIFY A PREDICTOR OF
BIOMARKER OR SOMETHING.
SO PREAND POST PROCEDURE.
YOU KNOW THOSE SCENARIOS WHERE
YOU--CAN YOU MAYBE NOT
NECESSARILY HAVE TO USE A
VETERINARY RELEVANT ANALGESIC OR
ANESTHETIC APPROACH BUT CAN YOU
REMOVE THAT PAIN SO THAT WILL
GIVE CONFIDENCE ON WHETHER IT'S
A PAIN OR NO PAIN STATE WOULD
HELP.
I WILL THINK ABOUT IT A BIT
MORE.
NI EMBASSY IT IS THE BIGGEST
CHALLENGE, IF WE THINK ABOUT
INDUCED MODELS OF PAIN YOU CAN
HAVE BEFORE AND AFTER, BUT IF
YOU THINK IT RECURRING, THAT'S
THE TREATMENT OF IT AND THAT'S
FINE AND THEN ONCE YOU DETERMINE
WHETHER THE ANIMAL IS IN PAIN OR
NOT AND HOW WOULD YOU REDUCE
THAT ARE YOU SURE YOUR TREATMENT
OR ANALGESIC IS PERFECT OR IS IT
THAT YOU CAN REDUCE PAIN AND
WILL YOUR EITHER SCORING SYSTEM
OR ARTIFICIAL MODEL BE ABLE TO
FOLLOW THAT TRAIN AS WELL,
BECAUSE THAT'S A THE BIGGEST
CHALLENGE.
>> THE SECOND PART OF THE
QUESTION AS WELL, I WILL COME
BACK TO THAT.
THAT IS IN SOME WAYS A VERY
ROUGH WAY WITH THE DIFFERENTIAL
GENE EXPRESSION ANALYSIS
COMPONENT OF THOSE COMPLEMENT OF
ANALYSIS WAS ENABLING THE DATA
TO SPEAK FOR ITSELF IN THE SENSE
OF WHAT ARE THOSE MICRORNAs
TELLING US THAT MAYBE THE
BEHAVIORS ARIC PICKING UP SO WE
SAW THOSE CHANGES WITH
MELOXICAM, THAT WASN'T PRESENT
IN THE OTHER MEASURES WE HAD IN
THIS STUDY, SO THERE'S A PLACE
FOR THAT IS LETTING THE DAILY
BASIS AT SPEAK AS WELL AND TRY
TO FIND.
WITH THAT WE DIDN'T RUN OVER AND
TRY TO FIND REALLY COMPLEX
SIGNATURES THERE, BUT YEAH, DO
THE UNBIASED UNSUPERVISED, AND I
WILL LET THE EXPERS TALK ABOUT
THAT.
>> IN RELATION TO YOU KNOW TRUTH
DATA I HAVE A QUICK STORY
TELLERS TOW TELL AND THAT IS
WHEN I FIRST STARTED, SORT OF
GETTING INTO THIS SPACE, WE
STARTED A PROJECT ON ULTRASOUND
MACHINE LEARNING TO DETECT
FELINE ABDOMINAL DISORDERS SO WE
HAD THE SMALL INTESTINE IMAGES
AND WE WANTED TO BUILD A MODEL
THAT COULD PREDICT IBD FROM
LYMPHOMA SO WE GOT A WHOLE BUNCH
OF DATA, MULTIINTUITIONAL STUDY,
BLOOD, SERUM DATA AND GENERATED
A WHOLE BUNCH OF MODELS WHICH
WORKED PRETTY OKAY, BUT THEN
WHEN I STARTED TO TALKING TO MY
PATHOLOGIST COLLEAGUES I
EXPLAINING MY MODEL, SAYING IT
WASN'T CORRELATED WORKING ON
ULTIMATELY THAT WELL AND MY
PATHOLOGY COLLEAGUE WAS SAYING
WELL WE DON'T REALLY KNOW WHERE
TO DRAW THE LINE BETWEEN IERK BD
AND LYMPHOMA IN THE FIRST PLACE,
AS A SCIENTIST I'M GOING, GIVE
ME A LABEL, PLEASE, BUT THE
ISSUE REALLY IS THAT THERE'S A
SPECTRUM AND SO, WHAT DO WE DO
AS SCIENTISTS IN WE SAY, LET'S
SEE IF WE CAN THROW MACHINE
LEARNING AT THE DIGITAL
HISTOPATHOLOGY ANALYSIS AND
MAYBE WE CAN IMPROVE THE
RELIABILITY OF THAT PROCESS AS
WELL, SO I THINK THERE'S TRUTH
DISCOVERY THAT'S HAPPENING HERE
AS WE GO DOWN THIS PATH OF
MACHINE LEARNING.
THE QUESTION RELATED TO
UNSUPERVISED LEARNING, I THINK,
THERE'S A--IT CAN BE AN
INCREDIBLE TOOL BECAUSE WE'RE
LIVING IN A SPACE NOW WHERE BIG
DATA AND IT'S OVERWHELPING TO BE
ABLE TO UNDERSTAND AND TRY TO
FIGURE OUT HOW THINGS MIGHT BE
CONNECTED.
WE LOOK AT, YOU KNOW IF YOU
COLLECT GENOMICS DAILY BASIS
THEA OR PROTEOMICS ICS DATA, THE
ARE TREMENDOUSLY LARGE DATA SETS
SO WITH THESE ALGORITHMS IS THEY
HELP SIMPLIFY IT A LITTLE BIT
FOR US HUMANS SO THAT WE CAN
KIND OF MAKE SENSE FROM IT.
THERE'S A NEW BRANCH OF SCIENCE
CALLED SUPERVISED MACHINE
LEARNING WHERE IT STADDLES THAT
SPACE BETWEEN SUPERVISED AND
UNSUPERVISED LEARNING IN THE
CASE WHERE IS YOU MAY HAVE
TREMENDOUSLY LARGE NUMBERS OF
DATA SETS AND YOU KNOW THERE ARE
CERTAIN THINGS FEATURES THAT
IDENTIFY DIFFERENT CLASSES, BUT
YOU DON'T NEED TO GO THROUGH THE
ENTIRE DATA SET TO BE ABLE TO
PARSE IT, SO IF YOU JUST TRAIN A
SMALL BIT OF--OR IDENTIFY A
SMALL SECTION OF THAT, AND
CLASSIFY THAT AND YOU CAN LET AN
ALGOGHT RICK IMPEDIMENTS GO AND
SORT IT OUT FOR XU THIS CAN BE
VERY POWERFUL IN THE SPACES OF
LIKE FOR EXAMPLE, DIGITAL
HISTOPATHOLOGY ANALYSIS AND
THINGS ALONG THOSE LINES.
SO I SEE IT, WE WILL SLEEP APNEA
AND OBESITYY A LOT OF IN THAT
SPACE IS ALL.
IF YOU COULD INTRUS YOURSELF AND
YOUR ARK --AFFILIATION TO THE
FOLKS THROUGH THE MIC, THAT
WOULD BE HELPFUL NI'M MONICA
FROM THE FDA AND MY QUESTION IS
REGARDING FOOD ANIMALS AND IT
SEEMS LIKE THERE'S AN INCREASING
GAP BETWEEN THE EVIDENCE OF
SAFETY AND EFFECTIVENESS SUCH AS
THE STUDY THAT
DR. BARRATT PRESENTED AND THE
ACTUAL ON THE GROUND FDA
APPROVAL AND THE ABILITY FOR
FARMERS TO USE THESE DRUGS
BECAUSE THEY DON'T HAVE FDA
APPROVAL FOR THE USES THAT ARE
EXPLORED IN THESE STUDIES AND I
THINK PART OF THAT IS MAYBE DUE
TO THEY'RE ALREADY GENERICALLY
AVAILABLE SO THERE'S LESS OF AN
ECONOMIC INCENTIVE BUT I'M
WONDERING IF YOU CAN SPEAK TO
THE PATHWAY FROM THESE STUDIES
TO APPROVAL AND ACTUAL USAGE ON
THE GROUND AND PERHAPS HOW YOU
SEE NEXT STEPS IN TERMS OF WHO
MIGHT FUND THESE STUDIES AND THE
PRACTICALITYS OF GETTING THERE.
>> >> IT'S A BIG QUESTION.
I'M NOT REALLY QUALIFIED TO
ANSWER, I DON'T THINK
PARTICULARLY HERE IN THE U.S.
HOW THAT WOULD WORK EMPLOY I
MEAN, I CAN ONLY SPEAK FOR THE
PATH THAT'S ARK HEAD FOR THE
BIOMARKERS I'VE SPOKEN ABOUT SO
THERE'S A LOT OF VALIDATION WORK
THAT IS THERE FOR THE OTHER
ASPECTS OFIOURE QUESTION, I
REALLY DON'T HAVE THE INSIGHT ON
IT.
>> ALL RIGHT, KATHLEEN
UNIVERSITY OF IOWA, I HAD
QUESTIONS THAT MIGHT BE RELATE
INDEED SOME WAY.
FIRST OF ALL TALKING ABOUT
BIOMARKERS SO I GUESS THIS GOES
TO DR. BARRATT, BUT WE'RE
TALKING ABOUT BIOMARKERS AND
WHEN YOU TALK ABOUT BIOMARKERS,
YOU'RE TALKING VERY GENERAL BUT
WHAT I WOULD LIKE YOU TO KIND OF
ADDRESS AND I'M NOT QUITE SURE
WHERE YOU ARE, ARE WE TALKING
ABOUT DIAGNOSTIC BIOMARKERS,
RESPONSE BIOMARKERS, PREDICTIVE
BIOMARKERS AND IN THE 2 PART
SERIES IS CAN WE DO SOME KIND OF
MACHINE LEARNING TYPE METHODS TO
NOT ONLY TAKE OUR BIOMARKERS BUT
MAYBE EXPAND OUR DEFINITION OF
BIOMARKERS AND INCLUDE THINGS
LIKE THE IMRIM AS SCALE OR THE
GAIT ASSESSMENT TO ENHANCE OUR
SENSITIVITY AND SPECIFICITY SO
WE MIGHT BE MORE ACCURATE.
DOES THAT MAKE SENSE?
>> YEAH.
>> SO THE FIRST PART OF THAT
QUESTION, FOR THESE CONTEXT OF
USE, WE'RE TALKING ABOUT, WE'RE
TRYING TO GET CLOSE TO A
SURROGATE BY O MARKER, WE MAY
NOT GET THERE.
IT'S REALLY TO SUPPORT ALONGSIDE
OF ALL THE OTHER ASSESSMENTS
THAT HAVE BEEN MADE IN THESE
TRIALS OF NEW ANALGESICS TO TRY
AND BUILD THAT LEVEL OF EVIDENCE
THAT ADDS ABJECTIVE MARKERS TO
THAT TO GIVE SUPPORT THAT THESE
ARE PRODUCING ANNAL GEESIA,
WE'RE NOT EASING THEM TO
PREDICT, WE ARE WANTING TO USE
THEM TO PROVIDE SUPPORTIVE
EVIDENCE THAT ANNAL GEESIA WAS
OCCURRING AND THESE--THE SECOND
PART, QUICKLY PROMPT ME AGAIN IN
NCOMBINING SOME OF THE
NONBIOMARKER, I LIKE THINK OF
THEM AS OTHER BIOMARKERS BUT
COMBINING THEM TOGETHER TO
IMPROVE OUR SENSITIVITY AND
SPECIFICITY AND THEN MAYBE WE
CAN IMPROVE OUTCOMES, NOT ONLY
IDENTIFICATION BUT OUTCOMES.
NMEASURES, I THINK IT'S WORTH
TRYING AS WELL THROUGH THAT
PROCESS, SEE IF YOU CAN ACTUALLY
IDENTIFY DIFFERENT DIMENSIONS OF
PAIN PERHAPS THOSE DIFFERENT
TOOLS ARE PULLING OUT AS WELL.
SAYING ABSOLUTELY I THINK THAT'S
WHERE WE NEED TO HEAD.
WITHIN THE SAMPLE SIZE HERE IT'S
HARD TO GET TOO COMPLEX IN
COMBINING MULTIPLE MARKERS
WHETHER THAT'S A BIOMARKER OR
ANY OTHER MEASURES BUT I THINK
THAT'S A WAY FORWARD, AND I
THINK THERE SPEAKER WILL BE
COVERING THAT AS WELL.
SO IT WILL BE INTERESTING TO SEE
WHAT THEY HAVE TO SAY.
>> HI, MARK WISE KANSAS STATE
UNIVERSITY.
I HAVE A QUESTION ABOUT THE
MACHINE LEARNING COMPONENT.
SO IN YOUR STUDY, WE TALKED
ABOUT BOTH DEEP LEARNING METHODS
WHICH ARE BLACK BOX METHODS BUT
YOU ALSO PRESENTED SUPPORT
VECTOR MACHINE METHODS WHICH ARE
PARSABLE, WEIGHT BOX METHODS AND
GETTING TO THE QUESTION ABOUT
UNSUPERVISED LEARNING WHICH
AIMEAN ALLOWS US TO TRY AND
UNDERSTAND DIMENSIONALLY WHAT'S
GOING ON.
THE PURSUIT OF POWER IN THESE
METHODS MOVES US TO THE DEEP
LEARNING AND BLACK BOX METHODS
WHICH WILL OBSCURE OUR APPROACH
TO UNDERSTANDING THE PATHWAY TO
UNDERSTAND THE PAIN DIMENSIONS.
SO WE'RE REALLY CHALLENGED
BECAUSE WE PURSUE UNDERSTANDING
AND PERFECTION AND MOST
REVEALING PREDICTIVE POWER
THROUGH THE BLACK BOX METHOD
WHICH IS GET US IN THE WAY OF
TRYING TO UNDERSTANDS WHAT WE
WISH TO UNDERSTAND.
SO I JUST WISH THE PANEL TO
WEIGH IN ON IT VALUABLE TO
PURSUE THE PERFECTION OF BLACK
BOX METHODS WHEN WHITE BOX
METHODS MIGHT BE MORE
REVOWELLING OF THE BIOLOGICAL
UNDERPINNINGS.
THANK YOU.
NI THINK THEY USER BIT DOESN'T
TAKE AWAY WHAT WE ARE DOING IN
THE BACKGROUND.
I DON'T THINK WE CAN USE 1
TECHNOLOGY ALONE LIKE ITSELFS.
I THINK WE NEED TO USE ALL THOSE
MEASURES TOGETHER TO GET TO A
BETTER UNDERSTANDING AND WE'RE
GOING TO BE STILL SEARCHING TO
UNDERSTAND WHAT'S GOING ON.
I DON'T THINK THAT WILL GO AWAY
WITH AI, I THINK THAT WILL GO
AWAY, I THINK WE NEED TO DO
RESEARCH ON WHAT'S GOING ON AND
FOCUS ON THE JUST RELY JUST ON
ARTIFICIAL INTELLIGENCE.
I THINK THAT IS JUST NOT--NOT
WHAT I WANT TO GO WITH IT AT
LEAST.
>> YEAH, I LOVE THAT QUESTION
AND LIKE COMPUTING SCIENTISTS CO
THEY COME UP WITH AI, WHICH IS
EXPLAINABLE AI, WHERE IN THIS
CASE, WHAT RESEARCHERS ARE DOING
ARE TRYING TO BREAK APART THE
PLAQUE BOX, RIGHT IN I HAVE THIS
PICTURE I OFTEN USE, IT'S LIKE A
MEAT GRAINEDDER AND WE DON'T
KNOW WHAT'S INDEED THE MEAT
GRINDER UNLESS WE TAKE IT ALL
APART AND IT'S NOT AN EASY THING
TO DO.
THIS IS THE SAME TECHNOLOGY
TRANSFER WITH THESE BLACK BOX,
VERY CONVOLUTIONAL NETWORK, IT'S
VERY DIFFICULT TO UNDERSTAND
WHAT'S GOING ON BUT THERE ARE
APPROACHES THAT PEOPLE CAN USE
TO HELP YOU UNDERSTAND WHAT IS
GOING INTO THE DECISION MAKING
PROCESS FOR THESE VERY
COMPLICATED MODELS.
SO 1 EXAMPLE, IS, WITH COVID
DETECTION AND X-RAY SCANS, SO,
THESE, WE FOUND THAT THESE DEEP
LEARNING MODELS ARE OUT
PERFORMING THESE FEATURE MODELS
YOU'RE TALKING ABOUT, YOU CAN
EXTRACT THAT FEATURE AND I KNOW
WHAT IT IS AND I CAN MODEL IT AS
OPPOSE TO DEEP LEARNING BLACK
BOX, DOES A BRILLIANT JOB.
AND WHAT PEOPLE HAVE BEEN ABLE
TO DO IS GENERATE HEAT MAPS
BASIC LYE WHERE IS THE ALGORITHM
PAYING ATTENTION IN THE IMAGE TO
COME UP WITH THAT PREDICTION.
AND THAT HELPS, THAT'S 2 THINGS.
IT HELPS US UNDERSTAND WHAT'S
GOING INTO THE ALGORITHM WHEN IT
AM CANS TO THAT DECISION MAKING
WHICH CAN BE VALUABLE BUT I WANT
TO ADD ANOTHER REALLY IMPORTANT
CAVEAT TO ALL OF THIS AND THAT
IS THAT IF YOU THROW IN THESE
HEAT MAPS INTO THIS IMAGE, AND A
RADIOLOGIST LOOKS AT THIS FOR
EXAMPLE, WHAT YOU'VE DONE IS YOU
HAVE--YOU BEING HAVE POTENTIALLY
BIASED THE PERSON LOOKING AT THE
IMAGE, AND SO NOW YOU'RE IN A
SITUATION WHERE, THE HEAT MAP
TOLD ME THIS AND I LOOK AT IT
AND IT SAYS, OH YEAH, THAT'S
RIGHT.
I SEE SOMETHING WEIRD HERE.
SO WE'VE NOW--WE'VE GOT
OURSELVES INTO A SITUATION WHERE
WE MIGHT HAVE BIASED SOMETHING.
SO MY TAKE ON THIS IS THAT, YOU
KNOW THE 1 THING THAT PROVES,
THAT IS EVIDENT OF SOMETHING
WORKS ARE THINGS LIKE RANDOMIZED
CLINICAL TRIALS.
YOU KNOW?
SO WE HAVE TO HAVE THAT
CONVERSATION ABOUT AI AND
RANDOMIZED CLINICAL TRIALS.
THAT'S ANOTHER QUESTION, YOU
KNOW A RABBIT HOLE, BUT THIS
WHOLE EXPLAINABLE AI IS AN
EMERGING FIELD AND I'M
HOPEFULFUL IT WILL HELP US OUT A
BIT NMARCH HUTCHISON UNIVERSITY
OF ADELAIDE, A CONVERSATION AT
COFFEE GOT ME THINKING ARE WE
TRYING TO FIGURE OUT THE PAIN OR
SHOULD WE ASK THE QUESTION OF
THERAPEUTIC EFFICACY AND IS THAT
SOMETHING WHERE WE ASK START
PREDICTING BEFORE WE TART
TREATMENT, WHICH TREATMENTS,
PHARMAICOLOGICAL OR
NONPHARMAICOLOGICAL MIGHT BE
APPROPRIATE FOR THE PATIENT IN
FRONT OF US, COMMENTS?
>> SHOULD WREE RE14 FROM SO THE
GUESS THIS WILL HELP US A LITTLE
BIT TO UNDERSTAND MORE ON THE
UNDERLYING MECHANISMS IF WE GO
INTO SENSORY TESTING, IF WE GO
TO GAIT ANALYSIS, CAN YOU KNOW
THE SENSORY PROFILE OF THAT
PATIENTS OR IF YOU USE A PAIN
SCORING SYSTEM THAT CAN GIVE YOU
MORE INFORMATION ABOUT THAT
STATE ISSUES NOT ONLY FUNCTIONAL
BUT THE EMOTIONAL STATE BEHIND
IT.
I GUESS THAT BRINGS A LOT MORE
INFORMATION TO THE TABLE TO
CHOOSE THE PROPER THERAPEUTICS.
SO I STILL BELIEVE THAT IT'S--IT
IS IMPORTANT TO HAVE THIS BASIS
AND GOOD RECOGNITION OF PAIN.
NHELLO, I AM UPON VLADIMIR,
SUBJECTS THAT ARE PRESENTING OR
NOT IN OUR WORK, TO USE
ARTIFICIAL INTELLIGENCE TO
ACTUALLY MAKE A KIND OF CATALOG
OF THE YOURS AND DISEASES AND
SEE HOW MUCH INTENSITY AND
DURATION AND EVOLUTION OF PAIN
IS.
SO FOR INSTANCE LET'S SAY
DIARRHEA OR A CASTRATION OR
BROKEN BONE OR SOMETHING LIKE
THAT.
AND IT'S INTERESTING THAT IN THE
WAY THAT WE THEN HARVEST THE
LANGUAGE MODELS FOR THIS TASK IS
THROUGH ASKING TO JUSTIFY TO THE
LANGUAGE MODELS SAY, BASED ON
EVOLUTIONARY PHYSIOLOGICAL
BEHAVIORIAL SOURCES AND ALL OF
THAT, HOW WOULD YOU JUSTIFY THIS
LEVEL OF PAIN OR THIS 1 OR THIS
1, YOU KNOW IN AND THE TIME?
SO I WOULD LIKE TO TAKE
ADVANTAGE OF MAYBE YOU
[INDISCERNIBLE] IF YOU CAN GIVE
YOUR FEEDBACK ON WHAT WOULD BE
THE LIMITATIONS OF ON DOING
THAT.
THE RESULT WE'VE BEEN HAVING ARE
SURPRISING BECAUSE IT CAN MAKE A
HUGE LITERATURE REVIEW FOR YOU,
YOU KNOW AND JUSTIFY THIS
DIFFERENT LEVELS OF PAIN AND SO
ON.
SO WE'VE BEEN VERY OPTIMISTIC
ABOUT THAT, OF COURSE IT DOESN'T
REPLACE HUMANS DOING IT BUT IT
HELPS A LOT.
SMRKS --
>> SO THE QUESTION WAS THE
POTENTIAL VALUE OF CLASSIFYING
DIFFERENT PROGRESSIONS OF
FEATURES FROM COMPUTER VERSION
TO APPROACHES OF ANIMALS AND
THAT MIGHT BE EXPRESSING PANE
AND I GUESS MY GENERAL COMMENT
IS THAT I THINK IT'S A--IT'S A
REALLY CLEVER IDEA, I THINK THIS
WHOLE IDEA OF BEING ABLE TO, YOU
KNOW IT'S NOT--THINGS ARE NEVER
BINARY IN THIS CASE, THERE'S A
SMOOTH PROBABLY A VERY--THERE'S
TRANSITIONS BETWEEN DIFFERENT
STATES, SO THE MORE DATA WE CAN
GET TO FILL IN THAT SPACE, THE
MORE WE UNDERSTAND WHAT MIGHT BE
HAPPENING IF THERE'S SORT OF
SHARP CHANGES IN THAT SPACE, AND
HOW IT DEPENDS ON TIME, THESE
ARE ALL SOMETHING I MENTIONED
EARLIER, YOU KNOW LIKE THE TIME
DEPENDENCE, I THINK ABOUT
IMETTING THAT RESOLUTION IS
SOMETHING CERTAINLY OF VALUE.
THIS, WE WILL FINISH OFF WITH
THE 2 QUESTIONS WE CURRENTLY
HAVE, SO GO AHEAD.
>> SO DORIS [INDISCERNIBLE],
WORKING IN PRACTICE AS A
VETERINARIAN, AND I WAS
LISTENING TO YOU AND I THINKING
ABOUT I CAN LOOK BACK ON TWEBT
YEARS IN PRACTICE WHEN I THINK
ABOUT THE STUDENTS NOW HO HAVE
TO DEAL WITH HAVING THESE NEW
TOOLS AND RELIGHT'RE LYING ON
THOSE--RELYING ON THOSE TOOLS
AND NOT GETTING MUCH PRACTICE,
SO I WAS WONDERING EVEN THOUGH
THEY ALREADY HAVE A HARD TIME TO
MAKE DECISION, IF IT'S GETTING
WORSE WHEN THEY ARE RELYING ON
THOSE TOOLS AND NOT RELYING ON
THEIR OWN EXPERIENCE THAT THEY
GET WHILE THEY'RE WORK NOTHING
CLINICAL PRACTICE, SO AND I WAS
WONDERING HOW TO IMPLEMENT THIS
IN THE CURRICULUM SO THAT THEY
ARE ABLE TO DEAL WITH THOSE
THINGS IS NOT JUST LIKE SHOW ME
THE PICTURES OR SHOW ME THE MRI
BEFORE THEY HAVE A LOOK AT THE
PATIENTS.
AND MAYBE 1 DAY IF EVERYTHING
PERFECT AND THEN WE WILL BE ABLE
TO DO THIS BUT IN THE MEAN
WHILE, I THINK LIKE THEY MAY BE
GET LACK OF PRACTICALIS, LIKE
CHANGING THEIR OWN BRAINS?
THANK YOU.
>> SO AS YOU HEARD BEFORE, I
GRADUATED FROM BRAZIL.
THE AMOUNT OF THINGS YOU GUYS
HAVE IN THE U.S. FOR DIAGNOSTICS
IS COMPLETELY DIFFERENT OF WHAT
I EXPERIENCED IN MY VET SCHOOL,
WE DIDN'T HAVE A LOT OF TOOLS
LIKE MRIs AND IT WAS JUST VERY
HARD FOR US TO MOVE ANIMALS TO
THE CAPITOLS TO ACTUALLY USE
THOSE TYPE OF TOOLS.
I THINK WHEN WE'RE TEACHING, WE
NEED TO START WITH THE BASICS
AND IN THE CLINIC AND THAT IS
WHERE YOU START AND TO USE THOSE
TOOLS IN LIKE VETERINARY
DIAGNOSTICS FOR EXAMPLE, YOU
NEED TO HAVE A CLINICAL,
WAYOU'RE SUSPECTING, WHAT YOU
THINK THAT ANIMAL HAS AND THAT
COMES FROM USING THE CLINIC OF
THAT ANIMAL AND I THINK THIS IS
A PLUS OF WHAT YOU'VE DONE ON
LOOKING AT THE ANIMAL AND
DECIDING WHAT THE CLINIC WAS
SHOWING TO YOU.
SO I THINK THERE'S POTENTIAL TO
USE BOTH TOGETHER INSTEAD OF
JUST USING THE TECHNOLOGY AND I
THINK THE MAIN GOAL AT LEAST ON
MY Ph.D. WORK WHERE WE LOOK AT
THE HUMAN OR WHETHER THE HUMAN
IS PRESENT AT ALL, WE WILL TREAT
BASED ON THE AI, USING THAT AS A
TOOL TO GO LOOK AT THE ANIMAL
MORE CLOSELY JUST BECAUSE
SPECIALLY WITH OUR SPECIES, IF
WE'RE PRESENT THEIR BEHAVIOR CAN
BE COMPLETELY DIFFERENT OR WHEN
YOU SAWOT DR. BROWN TALK
EARLIER, THE ACTIVITIES AND
PROJECTS MALIN THE VETERINARY
SETTINGS WAS COMLITELY DIFFERENT
THAN AT HOME SO I THINK THAT
WILL JUST GIVE US A TOOL TO LOOK
OVER ALL AT THE ANIMAL BUT THAT
DOESN'T TAKE AWAY FROM THE PART
OF DOING THE ACTUAL CLINIC
EVALUATION OF THE ANIMAL.
>> AND I MAY COMPLEMENT ON THAT,
I ALSO AGREE THAT THIS KIND OF
SIMULATION AS YOU SHOWED US CAN
REALLY HELP AS AN EDUCATIONAL
TOOL.
LET'S SEE HOW MANY LAME COWS
WOULD YOU SEE BACK THERE IN VET
SCHOOL?
HOW MANY STAGES OF THAT LAMENESS
WOULD YOU BE ABLE TO EVALUATE IN
SO IF YOU HAVE THESE TOOLS TO
HELP TRAINING ALSO THE STUDENTS,
THE CLINICIAN, WHEN THEY GET TO
THE FIELD, THEY CAN ALSO DETECT
THESE CHANGES MORE RAPIDLY, I
WOULD SAY.
MI JUST HAVE THIS 1 QUICK
COMMENT AND THAT IS A BILLIANT
QUOTE AND I FORGET THE NAME OF
THE AUTHOR AND IT WAS A PAPER IN
RADIOLOGY THAT SAID, YOU KNOW
WITH THE ISSUES OF RADIOLOGY AND
DEEP LEARNING AND SO FORTH, THE
STATEMENT WAS, AI WILL NOT
REPLACE RADIOLOGISTS, IT WILL
REPLACE RADIOLOGISTS THAT DON'T
KNOW AI, SO I THINK YOU JUST
REPLACED RADIOLOGISTS WITH
VETERINARIANS AND THAT'S THE
SPACE WE NEED TO WORK TOWARDS.
>> LAST QUESTION FOR THE MORNING
SESSION?
>> I JUST WANT TO SAY THANKS FOR
PUTTING THIS TOGETHER, SUPER
FASCINATING MY QUESTION FOR THE
PANEL IS HOW DID AI TECHNOLOGY
HANDLE DIFFERENTIAL RESPONSES
BETWEEN INDIVIDUALS LET'S SAY
WITH RESPECT TO SENSITIVITY TO
PAIN.
SO THE PAPER IN SCIENCE JUST
CAME OUT RECENTLY ABOUT
DIFFERENT SENSITIVITY TO PAIN IN
DOG BREEDS, CAN YOU REDUCE THAT
FURTHER TO SAY WITHIN A BREED,
YOU GD HAVE A DOG THAT'S HYPER
TOLERANT OF PAIN, VERSUS 1
THAT'S HIGHLY SENSITIVE.
I'M NOT A COMPUTER SCIENTISTS SO
I DON'T KNOW IF THE MODELING
TAKES CARE OF ALL OF THAT, BUT
IS THAT WRITTEN INTO THE MODEL
AND HOW WOULD THAT AFFECT IF WE
WERE TO IMPLEMENT AI IN A
CLINICAL SETTING HOW WOULD THAT
IMPLEMENT TREATMENT DECISIONS
FOR AN INDIVIDUAL VERSUS A
GROUP?
>> REALLY GREAT QUESTION.
I THINK ON EVERYTHING WE DO WE
HAVE A LOT OF VARIABILITY.
EVEN WHEN WE TALK ABOUT CORES,
OR INDIVIDUAL VARIABILITY
BETWEEN OUR ANIMALS AND THE
AMOUNT, I THINK THE WAY WE TRAIN
THE MODEL IS HAVING THE MOST
AMOUNT OF DATA WE CAN TO ACCOUNT
FOR THAT VARIABILITY.
I WOULD NOT BE THE PERSON TO
TELL YOU EXACTLY IF THAT WILL
WORK WHEN YOU'RE USING CLINICAL
SETTINGS BUT I THINK THE GOAL OF
TRAINING WITH A LOT OF DATA, IT
IS TO ACCOUNT FOR THE
VARIABILITY YOU MIGHT HAVE IN
BETWEEN ANIMALS.
>> YEAH, I HUNDRED PERCENT AGREE
BUT I THINK THERE'S A QUESTION
ABOUT USE CASE ALWAYS WHEN WE
DEVELOP AI, LIKE WHAT'S THE REAL
INTENTION OF THIS?
I MEAN IT'S QUITE--WE SEE
SITUATIONS WHERE IN
MULTIINSTITUTIONAL AI MODELS
THEY GENERALLY MIGHT PERFORM
VERY POORLY BECAUSE, IT'S KNOT
TOO MUCH AVERAGING GOING ON
BETWEEN THE DIFFERENT
INSTITUTIONS THAT ARE NOT
REFLECTING LOCAL POPULATIONS.
SO WE MAY BE SEEING SIMILAR, YOU
MIGHT SEE SIMILAR KINDS OF
BEHAVIOR HERE WITH DIFFERENT
KINDS OF BREEDS OF DOGS WHERE
YOU'RE SEEING AN AMALGAMATION OF
EFFECTS WHEN THERE'S ACTUALLY
DIFFERENT EFFECTS THAT CAN YOU
TEASE OUT BETWEEN BREEDS.
SO THESE ARE REALLY GREAT
QUESTIONS AND WE CAN CERTAINLY
EXPLORE IT, YOU KNOW USING
MACHINE LEARNING SO WE CAN ASK
THESE QUESTIONS AND HYPOTHESIS.
>> THANK YOU VERY MUCH.
>> WE WOULD LIKE TO THANK OUR
PANELISTS FOR AN OUTSTANDING
MORNING SESSION.
[ APPLAUSE ]
WE HAVE FORESHADOWING OF
CONVERSATIONS TO FOLLOW O.
SO WE MOVE THE FIRST SESSION
FROM TWIN STUDIES ELF 15:00 TO
12:30 TO GET YOUR TIME TO GO TO
THE EXPLURCH LEARNS SO THE NEXT
LUNCH AND LEARN SESSION WITH
DR. WEBB WILL START AT 12:30 AND
NOT 12:15.
SO THANK YOU VERY MUCH FOR
COMING AND LOOK FORWARD TO THE
AFTERNOON SESSION.
GOOD AFTERNOON.
THANK YOU EVERYONE FOR COMING
BACK FROM LUNCH TO APPRECIATE
ALL THE TALKS THAT WE HAVE IN
THIS AFTERNOON SESSION.
BEFORE I INTRODUCE THE SESSION,
I WANTED TO--OUR NEXT SPEAKER
WHO WILL BE DUNCAN LASCELLES,
WHO IS THE WITH THE NCITATE
UNIVERSITY, I WANT TO SAY A
LITTLE BIT ABOUT THE PAIN AND
ANIMAL WORKSHOP MEETING THAT'S
BEEN GOING ON NOW SINCE 2015 AND
ABOUT MICHELLE SHARKY WHO WE
HAVE THE INAUGURAL LECTURE HERE
IN HER NAME.
THE FIRST TIME I HAD YOU KNOW
HEARD ABOUT THIS IDEA OF
BRINGING SCIENTISTS TOGETHER TO
SPEAK ABOUT PAIN IN ANIMALS, IS
WHEN MICHELLE REACHED OUT TO ME
AND SAID SHE WOULD LIKE TO DO
COLLABORATION BETWEEN THE NIH
AND THE NDA TO SUPPORT RESEARCH
IN ANIMALS AND NO, SPECIFICALLY
TAPPING INTO THE EXPERTISE OF
VETERINARY COMMUNITYINARRIANS
AND IN PARTICULAR, SHE KNEW IT
WAS THE RIGHT PERSON TO, YOU
KNOW, REPRESENT THE RESEARCH
FIELD TO REPRESENT THE ACADEMICS
IN THAT AREA AND THAT WAS DUNCAN
LASCEWELL, LES, SO DUNCAN AND
MICHELLE SAID REACHED OUT AND
SAID TO ME WOULD NIH WANT TO
PARTNER IN DISCUSSING PAIN IN
ANIMALS AND UNDERSTANDING HOW
THEY CAN BE USED IN A
TRANSLATIONAL ASPECT IN ORDER TO
OVERCOME THE HURDLE,S THAT WE'VE
SEEN IN DEVELOPING THERAPEUTICS
FOR HUMANS IN PAIN.
THAT WE CAN ABSOLUTELY DO AND I
BROUGHT THAT TO SENIOR
LEADERSHIP AT NIH AND THEY GAVE
ME VETERINARIANS, YOU SURE, I
SAID WELL, LOOK AT IT FROM THIS
PERSPECTIVE, RIGHT IN WHAT
PERCENTAGE OF NIH'S DOLLARS GO
TO SUPPORTING RESEARCH IN
ANIMALS WITH THE OVERALL GOAL OF
UNDERSTANDING PATHOLOGICAL
CONDITIONS IN HUMANS, BUT WHAT
PERCENTAGE, AND THAT JUST ENDED
THE ARGUMENT RIGHT THERE.
YEP, THAT'S WHO WE SHOULD BE
TAPPING INTO IS THE EXPERTISE OF
VETERINARIANS.
SO THE NEXT I DID ON MY OWN AND
ASKING HOW MANY OF THOSE
VETERINARIANS ARE ASKING FOR NIH
TO SUPPORT THEIR RESEARCH BY
APPLYING AND THAT WAS A DISMALLY
SMALL NUMBER THAT IT WOULD SAY.
SO AS I INTRODUCE THIS SESSION,
I WANT TO MAKE A PITCH OVER HERE
FOR YOU TO KNOW THAT NIH IS
INTERESTED IN YOUR RESEARCH
PROPOSALS.
WE ARE INTERESTED IN RESEARCH
THAT YOU ARE DOING IN LARGE
ANIMALS, IN FARM ANIMALS, ET
CETERA.
THE PROCESS FOR APPLYING FOR NIH
GRANTS AND THE FRAMING OF THE
RESEARCH QUESTION MAY BE
SOMETHING THAT YOU COULD LEARN
FROM THE PROGRAM DIRECTORS THAT
MANAGE THOSE PORTFOLIOS IN
RESEARCH.
SO MY PITCH IS EITHER REACH OUT
TO MYSELF OR OTHER PROGRAM
DIRECTORS AND SEE IF YOUR IDEA
CAN FIT INTO NIH'S RESEARCH.
SO BACK TO THE PROGRAM AT-HAND
SO DR. LASCELLES WILL BE
PRESENTING OF THE OVERRUE OF THE
DOMAINS IMPACTED BY PAIN.
DR. LASCELLES?
>> [ APPLAUSE ]
NTHANK YOU VERY MUCH FOR THAT
INTRODUCTION AND WELCOME BACK
THIS AFTERNOON WHERE WE WILL
TALK ABOUT THE DOMAINS OR
DIMENSIONS IMPACTED BY PAIN AND
THE IDEA OF THIS AFTERNOON'S
SESSION IS TO REALLY BROADEN
EVERYONE'S OUTLOOK ON THE
MUTTITUDE OF WAYS THAT
PAIN--MIEWLTITUDE OF WAYS THAT
MAIN AFFECTS BODIES AND WITH THE
IDEA IS THERE SOMETHING ELSE WE
CAN MEASURE AND IS THAT THING
WE'RE GOING TO MEASURE GOING TO
BE RELEVANT, AND I LEAD UP THE
COMPARATIVE PAIN AND RESEARCH
CENTER, SO WHY KISS CUSS--WHY
DISCUSS IT TOPIC IN WELL IN
HUMANS PAIN IS USUALLY MEASURE
AM IS BASED ON SELF-REPORT AND
IN ANIMALS AS YET THEY DON'T
SELF-REPORT SO WHAT WE NEED TO
DO IS WE NEED TO ESTIMATE PAIN
BY MEASURING THE IMPACT OF PAIN
ON DOMAINS, DIMENSIONS, AND SO
THAT'S--THAT'S WHY WE NEED TO
HAVE THIS DISCUSSION BECAUSE I
THINK OFTEN, CERTAINLY IN MY
WORK, IN MY WORLD, I'VE BECOME
NAGHTER NARROW MINDED, NARROW
FOCUSED, I CAN MEASURE THIS, I
HAVE THE TOOL FOR MEASURING THE
OTHER THING, THAT'S WHAT WE DO
AND TO ADVANCE WE NEED TO
BROADEN OUT THAT CONVERSATION
AND HENCE THIS AFTERNOON'S
PROGRAM, WE WILL TOUCH ON THE
BIOPSYCHOSOCIAL MODEL OF PAIN.
WE WILL EXPLORE DOMAINS IMPACTED
BY ACUTE PAIN, BY CHRONIC PAIN.
SO JUST AS AN OVERRUE HERE, WHAT
IS IMPACTED?
WELL, VARIOUS DIAGRAMS, LIKE
THIS COME UP AND I GRAB THIS
FROM [INDISCERNIBLE] THESIS AND
SHE ADAPTED IT FROM MA GUYER
PUBLICATION IN 1992 YOU CAN SEE
PAIN IS AT THE TRUSTEES AND PAIN
AFFECTS VARIOUS THINGS CALLED
DOMAINS OR DIMENSIONS.
ONE THING I HOPE IS THAT SOMEOE
THIS AFTERNOON CAN SHED LIGHT ON
THE CORRECT TERM IS, IS IT
DOMAIN, DIMENSIONS OR MAYBE JUST
THINGS.
AND OF COURSE THESE DIAGRAMS
VARY BECAUSE HERE'S MY
ADAPTATION IN A PUBLICATION AND
THEY VARY BASED ON KIND OF
INTERESTS SO MY CURRENT RESEARCH
INTEREST IS OSTEOARTHRITIS PAIN,
MUSK LO SKELETAL PAIN.
I HAVE CHRONIC PAIN AT THE
TRUSTEES, I THINK IT'S FAIR TO
SAY THERE ISN'T A GOLD STANDARD
DEFINITION OF THE DOMAINS THAT
ARE IMPACTED BY ACUTE OR
PERSISTENT CHRONIC PAIN.
I THINK THE LABELS VARY
DEPENDING ON THE INTEREST OF THE
INDIVIDUAL AND THE DOMAINS VARY,
THE DOMAINS ARE DESCRIBED, VARY
WITH THE CONDITION AND CONTEXT
WITH WHICH THEY ARE BEING
DISCUSSED AND IN THIS FURTHER
VARIATION DEPENDING ON WHETHER
THE IMPACT THAT YOU'RE TALKING
ABOUT IS ON HEALTH OR WELL BEING
OR WHETHER THE DOMAINS ARE BEING
VIEWED FROM THE PERSPECTIVE OF
WHAT MEASUREMENT TOOLS ARE
AVAILABLE.
I MEAN QUITE FRANKLY IF YOU HAVE
CERTAIN MEASUREMENT TOOLS WHEN
YOU WRITE A PUBLICATION, THE
DOMAINS REFLEBT YOUR MEASUREMENT
TOOLS AND YOUR ABILITY.
SO I THINK THERE'S SOME
VARIATION THERE.
SO IN ANIMALS WE ESTIMATE PAIN
BY MEASURING THE IMPACT OF PAIN
ON DIFFERENT DIMENSIONS BUT WE
ALSO HAVE TO REMEMBER THE
BI-DIRECTIONAL RELATIONSHIP.
THIS IS IMPORTANT, SO YOU KNOW
FROM MY PERSPECTIVE, I'M ALWAYS
INTERESTED IN HOW PAIN AFFECTS
SOMETHING, PAIN AFFECTS SAY, THE
AFFECTITATE OR COGNITIVE FUNK
BUT WE HAVE TO REMEMBER THAT
THOSE DOMAINS HAVE AN EFFECT ON
THE PERCEPTION OF PAIN, SO THERE
IS THIS BI-DIRECTIONAL
RELATIONSHIP TO BE THINKING
ABOUT.
FOR EXAMPLE, WE MEASURE AFFECT
AND THE PAIN OF AFFECT, BUT WE
ALSO NEED TO UNDERSTAND THE
EFFECT OF AFFECT ON PAIN IF YOU
FOLLOWED THAT.
AND HERE'S A GREAT EXAMPLE OF
THAT.
SO IN DOGS WITH A PAIN STATE
SHOWED GREATER NOISE SENSITIVITY
BUT YOU COULD FLIP THAT AROUND
AND SAY WELL, THE NOISE
SENSITIVITY IS AN EXAMPLE OF
ANAN XIETY STATE IS VERY
IMPORTANT.
SO ANOTHER THING TO REMEMBER
HERE AS WE THINK ABOUT LABEL
ANDS DOMAIN, WITHIN EACH DOMAIN
ARE VARYING AS SPECTS OR
COMPONENTS LIKE WITHIN THE
DOMAIN BUT THE RELATIVE PURPOSES
OF EEP OF THESE ASPECTS.
SO FOR EXAMPLE, GO BACK TO THE
DIAGRAM I TOOK FROM MARGARET
BRUINS THESIS AND LET'S PULL OUT
COGNITIVE FUNCTION.
THE REALITY IS THERE'S NO 1
MEASURE OF COGNITIVE FUNCTION
AND IF YOU'RE MEASURING
COGNITIVE FUNCTION, YOU ACTUALLY
NEED TO MEASURE A WHOLE VARIETY
OF DIFFERENT THINGS, YOU KNOW
HOW MEANING OF PAIN IS
INTERPRETED, COPING MECHANISMS,
ATTENTIONAL DEMAND, EXECUTIVE
FUNCTION AND SO THE LIST GOES
ON.
AND SO, AS WE GO THROUGH THE
AFTERNOON, WE THINK ABOUT THE
DOMAINS WE NEED TO THINK ABOUT
THE COMPONENTS OF THOSE DOMAINS
BECAUSE THOSE ARE THE THINGS WE
ARE GOING TO BE MEASURING AND I
TRY TO COME UP WITH ANALOGIES
AND THIS NOT MAYBE THE BEST 1
BUT IT'S KIND OF LIKE WEATHER,
SO THERE'S 1 MEASURE OF WEATHER,
IS THERE?
YOU CAPTAIN --CAN'T PUT A NUMBER
ON WEATHER?
WHAT WE DO IS MEASURE THE
COMPONENTS, THE AMOUNT OF
PRECIPITATION, THE TYPE OF
PRECIPITATION, THE TEMPERATURE,
WIND, DIRECTION THE WIND IS
COMING FROM SO THESE ARE ALL
COMOPPOSITE BEHAVIORIAL
PHENOTYPENTS THAT WE MEASURE
THAT MAKE UP WEATHER.
I THINK THE ANALOGY I COULD TAKE
FURTHER BY SAYING THAT AS AN
INDIVIDUAL, THERE ARE COMPONENTS
OF WHETHER THERE ARE MORE OR
LESS FORTUNATE EACH INDIVIDUAL.
I THINK THE SAME THING IS TRUE
WHEN WE TALK ABOUT THE
COMPONENTS VEN THE ASSPEBTS THAT
FIT UNDER A DOMAIN THAT'S
AFFECTED BY PAIN, SO THERE MAY
BE CERTAIN COMPONENTS THAT HAVE
MORE MEANING TO AN INDIVIDUAL
WHEN THEY'RE PERTURBED VERSUS
OTHER COMPONENTS AND THAT IS A
CHALLENGE TO UNDERSTAND THE
MEANING THERE.
AND THEN JUST TO ADD A BIT MORE
COMPLEXITY OF THIS IN A POSITIVE
WAY, THIS IS GOOD COMPLEXITY,
THE COMPONENTS OF A DOMAIN THAT
ARE AFFECTED AND THEREFORE
MEASURABLE, VARY WITH THE PAIN
PHENOTYPE, THEREFORE FOR
EXAMPLE, WE COULD THINK ABOUT
CANINE ARTHRITIS AND THE
VARIABILITY OF MOVEMENT AND
PEOPLE OFTEN GRAVITATE TO FORCE
PLACED AND MEASURE GRAVITY AND
FORCES AND THAT'S IERK DELATWAL
WHEN YOU'RE TALKING ABOUT A DOG
WITH A SINGLE LIMB LAMENESS, IF
YOU HAVE A LAMENESS YOU CAN
ACCURATELY MEASURE THAT
LAMENESSITATE BY MEASURING
GROUND REACTION FORCES BY HOW
THE FLOOR IS PUSHING UP ON THE
LIMB BUT THEN AS YOU MOVE TO
ANOTHER DOG WITH OSTEOARTHRITIS,
SAY A DOG THAT HAS MULTIPLE
YOINTS AFFECTED, THE UTILITY OF
MEASURING GRAND REACTION FORCES,
DIMINISHES AND BECOMES MUCH
LESS, AND IN THAT CASE, THIS IS
TILL A DOG WITH OSTEOARTHRITIS
PAIN, IN THAT CASE, THEY'RE NOT
THAT USEFUL BECAUSE YOU KNOW YOU
CAN IMAGINE AITATE WHERE ALL
LIMBS ARE EQUALLY AFFECTED AND
SO THERE'S GOING TO BE NO CHANGE
IN GRAND REACTION FORCES SO YOU
MOVE TO MEASURING THINGS LIKE
OVERALL ACTIVITY OR SMOOTHNESS
OR QUALITY OF MOTION, POWER OF
MOVEMENT, SPEED OF MOVEMENT, SO
I THINK THERE ARE A NUMBER OF
LEVELS HERE.
WE NEED TO THINK ABOUT THE
DOMAINS THAT ARE IMPACTED, THE
COMPONENTS OF THOSE DOMAINS,
THINK ABOUT THAT BI-DIRECTIONAL
EFFECT THAT'S GOING ON BETWEEN
PAIN AND WHAT WE'RE MEASURING
AND ALSO THE VALUE OF THE
COMPONENTS IN THE INDIVIDUAL
DOMAINS TO THE INDIVIDUAL BUT I
DO THINK A COMPREHENSIVE
UNDERSTANDING OF THEIR DOMAINS
AND A WIDE COMPREHENSIVE
UNDERSTANDING OF THE DOMAINS AND
THE COMPONENTS THAT ARE IMPACTED
BY DIFFERENT PAIN STATES WILL
LEAD TO THE DEVELOPMENT OF NEW
MEASUREMENT APPROACHES AND TOOLS
AND THAT'S WHAT WE NEED.
WE NEED THAT MORE COMPREHENSIVE
MEASUREMENT OF PAIN.
WE NEED TO UNDERSTAND THE
BI-DIRECTIONAL NATURE AND A
CHALLENGE IS GOING TO BE TO
UNDERSTAND THE VARYING WAYS THAT
PAIN IMPACTS DIFFERENT
INDIVIDUALS EVEN WITHIN A PAIN
CONDITION EMPLOY THE IMPORTANCE
OF THIS IMPACT AND WHAT A
MEANINGFUL CHANGE IS AND I DO
THINK THAT MAYBE, I'LL JUST
THROW THIS OUT HERE TMIGHT SOUND
CRAZY BUT THE FUTURE OF CLINICAL
TRIALS WILL BE A COMPREHENSIVE
OF MEASUREMENT OF MULTIPLE
DOMAINS AND COMPONENTS WITH
SUCCESS DEFINED AS A MEANINGFUL
POSITIVE CHANGE IN 1 OR MORE
COMPONENT THAT WAS NEGATIVELY
IMPACTED BOO I PAIN.
ALMOST LIKE AN INDIVIDUALIZED
APPROACH TO PAIN ASSESSMENT,
PAIN EVALUATION JUST AS
PERSONALIZED MEDICINE IS BEING
TALKED ABOUT, AND ACTUALLY, I
JUST FINISHED BY SAYING, WE'RE
NO STRANGER TO THIS, SO
SOMETHING CALLED CLIENT SPECIFIC
OUTCOME MEASURES WHICH THOSE
EVEN INVOLVED IN SMALL
ANIMAL:ICAL PANE RESEARCH WILL
BE VERY FAMILIAR WITH, THEY ARE
INDIVIDUALIZED.
THAT'S NOT A COOKIE CUTTER SET
OF QUESTIONS, THE QUESTION, THE
TOPICS THE ITEMS ARE DECIDED
UPON BY THE INDIVIDUAL OWNER,
OWNER PET DIAD AND THE DOMAINS,
THE COMPONENTS OF DOMAINS THAT
ARE IMPORTANT ARE SELECTED BY
THAT OWNER AND FOLLOWED OVER
TIME.
WITH THAT I WILL TOP AND WE'LL
MOVE TO THE BIOPSYCHOSOCIAL
MEASUREMENT OF PAIN. .
[ APPLAUSE ]
OUR NEXT SPEAKER WILL BE MARK
HUTCHINSON, HE IS FROM THE
SCHOOL OF MEDICINE AT THE
UNIVERSITY OF ADELAIDE.
>> COLLEAGUES, THANK YOU FOR THE
OPPORTUNITY TO COME UP NORTH
AFTER AMERICA, AFTER COVID AND
LONG TIME BETWEEN VISITS AND
TELL YOU ABOUT THE JOURNEY WE'VE
BEEN ON IN TRYING TO
CONCEPTUALIZE BY O PSYCHOSOCIAL
PAIN AND THANK YOU DUNCAN FOR
GOING DOWN THE PATH OF
DIMENSIONS OR DOMAINS, I THINK
IT WILL BE BOTH AND I WILL
PROBABLY UNPACK A LITTLE BIT OF
THAT DURING THE TALK SO AS WE DO
IN AUSTRALIA, WE START BY
ACKNOWLEDGINGLY COUNTRY, SO IN
AUSTRALIA THE INDIGENOUS PEOPLE
OF HAVE BEEN THEIR FOR 65,000
YEAR ANDS WE ACKNOWLEDGE COUNTRY
IN ALL OF ITS MEANS BOTH 3
DIMENSIONAL AND THE FOURTH
DIMENSION OF TIME.
I CONTINUE TO LEARN MORE AND
MORE ABOUT INDIGENOUS KNOWLEDGE
AND INDIGENOUS PRACTICES AND I
HAVE TO ADMIT IT WAS ONLY A
COUPLE OF YEARS AGO THAT I
REALIZED WHEN WE SAY WE ARE
ACKNOWLEDGING COUNTRY, IT'S NOT
JUST THIS PLACE, IT'S THIS PLACE
IN THE TIME SPACE THAT WE ARE
AND HOW WE ARE INDELIBLY
CONNECTED TO THE PAST AND SO I
PAY RESPECT TO MY ELDERS PAST
AND PRESENT AND ACKNOWLEDGE ANY
INDIGENOUS PEOPLE HERE TO GIVE
CONNECTION TO YOUR HOME
COUNTRIES.
TO GIVE YOU AN IDEA OF HOW BIG
AUSTRALIA WE ARE DEALING WITH A
LARGE COUNTRY.
I HAVE SEVERAL CONFLICTS OF
ABOUT, I WILL TALK ABOUT
NONREGISTERED USES FOR
PHARMACEUTICAL TOOLS AND
THERAPIES, I HAVE A RANGE OF
CLINICAL ADVISITINGRY ROLES, BUT
I'M NOT WILL ISING YOU ANYTHING
OTHER THAN SCIENCE TODAY.
SO I'M CONFLICTED AND
INTERESTING, I HOPE.
IN THE WAY OF BEING CONFLICTED
AND INTEREST, I WOULD LIKE TO
ACKNOWLEDGE THE FUNDING SOURCES
AND WHAT YOU WILL NOTICE HERE
FOR THE WORK I'M PRESENTING
TODAY, IT COVERS EVERYTHING FROM
BIOPHOTONNICS TO SLEEP AND
LIVESTOCK.
I WANT TO TALK ABOUT WHO
CAREYOUR WORK, SPECIFICALLY
ABOUT THOSE FOR PAIN IN ANIMALS
AND NOW WE CAN TART COMING
TOGETHER IN LARGE SETS OF TEAMS
TO ACTUALLY ASK THESE CRITICAL
QUESTIONS.
I ALSO WANT TO ACKNOWLEDGE THE
PEOPLE THAT DO THIS WORK.
SO AS THE DIRECTOR OF THE CENTER
FOR NANOSCALE BIOPHOTONNICS, I
AM RESPONSIBLE FOR SCIENTISTS
ALL OFFER THE COUNTRY WHO TAKE
BRILLIANT WORK IN QUANTUM
PHYSICS ISSUES RIGHT IT TO
APPLIED WORK AND THEN TAKE IT TO
THE SCHOOL, AND UNIVERSITY AND
DAN WHO ARE THE BRAINS BEHIND A
LOT OF ANALYTICAL APPROACHES
THAT WE ARE UNDERTAKING TO START
PICKING APART THESE COMPLEX CHAL
ENKS.
BUT THE MAINLIOR WHY THAT
STARTED ME ON THIS YOWRNY,
TARTED ME IN ASKING THESE
QUESTIONS WAS THIS 2 DIMENSIONAL
GRAPH.
SO THIS IS THE YEARS LIVED WITH
DISABILITY.
THIS IS NOT, THINGS THAT KILL
YOU.
THIS IS THE--THESE ARE THE DECS
THAT WE ARE BURDENED WITH AS
SOCIETY LIFE LONG, SO YOU'LL
NOTICE THERE THAT DEFINED
PAINITATES ARE QUITE PREVALENT,
BUT WHAT'S CRITICAL IS TO
ACTUALLY ASK THE QUESTION, WHICH
OF THESE DISEASES ARE LIVED IN
PAIN?
AND THAT IS MORE THAN 3-QUARTERS
OF THE YEARS LIVED WITH
DISABILITY, ARE LIVED ASSOCIATED
WITH OR DIRECTLY CAUSED BY THAT
PAIN STATE.
AND SOME OF THIS IS ACUTE AND
SOME OF IT IS CHRONIC.
SO WE'RE BEING MOTIVATED BY THIS
PAIN, WE DON'T JUST SIMPLY RUN
ARK ROUND LIKE A HEADLESS
[INDISCERNIBLE] OR A BULL IN A
CHINA SHOP.
WE TRY TO TAKE A KEY PATH
THROUGH THE PROGRAM ROOM, TO
IDENTIFY TYPES OF MEASURE XMENT
THAT INCLUDES ANALYTICAL
APPROACHES TO UNDERSTAND WHAT'S
HAPPENING AND THEN TO HAVE AN
INTERVENTION IN MIEBD THAT WILL
THEN LEAD TO AN IMPROVEMENT IN
PERFORMANCE.
NOW THAT MEANS THAT WE START
LOOKING AT NOVEL BIOPHOTONNICS
TECH MEEKS, WE GO INTO THE
FUNDAMENT AMILLIO SCIENCE, WE
ARE LOOKING AT THE METASUITICALS
APPROACH, SO NOT JUST DRUGS
ABOUT YOU ALSO DEVICES, FOCUSED
ON PHOTONS, A BURCH OF THINGS
THAT COME TOGETHER TO IMPROVE AN
OUTCOME AND THAT THAT OUTCOME IS
FOR HEALTHY, HAVES, ILL
INDIVIDUALS AND ANIMALS.
SO IN THE NEXT 46 MINUTES BASED
ON MY TIMER, I WILL COVER 3 KEY
TOPICS, FIRSTLY TO UNPACK FOR
YOU WHAT WE ARE THINKING ABOUT
IN TERMS OF PAIN AS A COMPLEX
BIOPSYCHOSOCIAL PUZZLE.
I WANT TO THEN TAKE THAT AND
PLACE THAT THROUGH THE LENS OF
PSYCHONEUROIMMUNOLOGY AND THE
OPPORTUNITIES THAT VIEWING PAIN
THROUGH A PSYCHOLOGICAL LENS TO
UNDERSTAND BIOPSYCHOSOCIALITATE
AND THE OPPORTUNITY THAT PROVIDS
WHEN WE THEN TART THINKING ABOUT
MAKING MEASUREMENTS AND THESE
ARE COMPLEX METAMEASUREMENTS
THAT ALLOW US TO UNPACK PAIN
STATES.
AND I'VE PROMISED BEFORE, I WILL
TALK ABOUT SUBMARINE ANDS THIS
WILL BE AN IMPORTANT THING.
SO WHAT WE DO MEAN WHEN WE SAY
BIOPSYCHOSOCIAL EMPLOY IT'S A
WONDERFUL WORD THAT COVERS MANY,
MANY SCENES BUT IT CRITICAL TO
UNPACK WHAT WE TRULY MEAN WHEN
WE SAY PAIN IS BY O
PSYCHOSOCIAL.
IT MEANS WE ARE TALKING ABOUT
EVENTS AT THE ATOMIC SCALE.
THOSE ARE MOLECULAR INTERACTIONS
THAT ARE OCCURRING ON A NANO
SECOND KALE WITH MOLECULAR
ENTERACTIONS, THIS THEN SCALES
TO SYSTEMS OF NEURONAL NETWORKS
ACROSS SEBT METER KALE WHICH
THEN SCALES SOCIAL LEVEL AND
BIOLOGICAL LEVEL TO EVENTS THAT
ARE OCCURRINGA THE METERS SCALE.
THERE IS THOUGH PHYSICIST IN THE
WORLD IN THIS ROOM WHO WOULD
EVER SAY THAT MY TECHNOLOGY CAN
MEASURE FROM NANOMETERS THROUGH
TO METERS.
LET ALONE BEING ABLE TO THEN
MEASURE FROM THE NANO SECONDS OF
AN ACTION POTENTIAL THROUGH TO
THE YEARS OF ACCUMULATED
BIOLOGICAL BURDEN THAT THEN
CREATES THE RESILIENCE OR LACK
THEREOF FOR THE PRESENTATION OF
PAIN.
SO WHEN WE TART THINKING ABOUT
PAIN, IN BIOPSYCHOSOCIAL LENS,
WE'RE THINKING ABOUT PAIN IN
MULTIPLE DIMENSIONS, ON 2 AXIS,
IN THE FIRST INSTANCE, THAT OF A
TIME KALE --SCALE AND THAT OF A
LENGTH SCALE, BUT THEY'RE
CONNECTING THESE TOGETHER
BECAUSE IT'S NOT MAMGIC, IT'S
ACTUALLY ALL OF THESE SYSTEMS
COMING TOGETHER, SO THE UNIQUE
THING ABOUT OUR PHYSIOLOGY IS
THAT WE HAVE ANATOMICAL
COMPARTMENTS, WE'RE NOT JUST A
BIG BAG OF WATER, LIKE THE
PHYSICISTS LIKE TO MODEL US, WE
HAVE COMPARTMENTS ARE THESE
THINGS OPERATE IN ISOLATION SO
WE'RE ACTUALLY DEALING WITH A
MULTIDIMENSIONAL PARALLEL SYSTEM
OF OPERATION WITHIN OUR
PHYSIOLOGY.
AND THESE THINGS CHANGE WITH
TIME SO OUR EVENTS AT THE EARLY
LIFE ARE DIFFERENT TO AGED.
SO THIS IS MEANT IN THE SPACE OF
BIOPSYCHOSOCIAL RESEARCH THERE'S
BEEN A HEAD LONG BALGT BETWEEN
THE MIND BODY THEORIES OF
[INDISCERNIBLE], AND THE MORE
BODY IS A GARDEN APPROACH OF
EASTERN MEDICINE AND YET WHAT WE
ARE NOW SEEING IS THAT THERE ARE
LESSONS THAT WE CAN LEARN FROM
BOTH TO TART ACTUALLY
INTEGRATING A KNOWLEDGE OF
SOMETHING TO MOVE FORWARD WITH,
OF THE BODY CAN BE CONSIDERED A
MACHINE SOMETIMES, AND THERE ARE
ELEMENTS OF THIS COMPLEX
MULTIDIMENSIONAL SPACE OF A
GARDEN IMANNUALRY THAT ACTUALLY
HELPS US MOVE FORWARD.
BUT I DON'T WANT YOU TO THINK
THAT I'M ANYTHING SOFT ON YOU,
IT ALL COMES DOWN TO THE COMPLEX
INTERPLAY OF MOLECULE ANDS
CELLULAR SYSTEMS COMING
TOGETHER.
WHAT WE ABSOLUTELY DO NOT HAVE
YET, IS A TRUE UNDERSTANDING OF
WHAT THIS COMPLEX MAP ACTUALLY
MEANS.
BUT WHAT WE DO HAVE IS GOOD
PLACES TO START AND WE CAN START
USING THE CENTRAL NERVOUS SYSTEM
TISSUE TO START UNPACKING WHAT
IS ACTUALLY HAPPENING WITHIN THE
NEUROBIOLOGICAL SUBTRAITS THAT
UNDERPIN CERTAIN TYPES OF
BIOPSYCHOSOCIAL PAIN AND WE CAN
START USING STANDARD IMAGING OR
MUCH MORE ADVANCE SINGLE CELL
TRANSCRIPTOMICS TO TEASE APART
WHAT IS HAPPENING IN THIS
BIOPSYCHOSOCIAL PAIN.
BUT I NOW WANT TO JUMP QUICKLY
INTO VIEWING BIOPSYCHOSOCIAL
THROUGH AN NEUROLOGICAL AND
PSYCHONEUROLOGICAL LENDS GIVES
US HOOKS TO USE IN THIS SPACE.
AND IT'S FORTUNATE TAKEN--THEY
WE JUST CAME THRU THE PANDEMIC,
I CAN ASK YOU THE QUESTION HOW
DO YOU ACTUALLY KNOW YOU ARE
SICK?
BECAUSE 20, 30, YEARS AGO, THAT
QUESTION WAS NOT AN EASY 1 TO
ACTUAL LYE ANSWER.
BECAUSE THE VIEW WAS THE BRAIN
OF IMMUNO PRIVILEGED AND COULD
NOT RECEIVE THIS INFORMATION AND
THE REASON WHY WE FELT TIRED
WHEN WE WERE SICK IS BECAUSE OUR
IMMUNE SYSTEMS DREAN OUR ENERGY
AND HOW COULD THEY?
COULD THEY FUNCTION WITH AN
ACTIVE IMMUNE SYSTEM, CLEARLY
THAT'S NOT THE CASE, WE NOW
UNDERSTAND THAT NEUROSCIENCE
ISN'T ALL JUST ABOUT FLYING
THROUGH SPACE IN A LOVELY
ELECTRICAL OR IONIC PULSES VIA
NEWSONS IT'S MUCH INTENTIONALLY
COMPLICATED WITH THAT, WE'RE
DEALING WITH AN IMAWN COMPETENT
BRAIN WITH MULTIPLE IMMUNE CELL
TYPES WITHIN THE CENTRAL NERVOUS
SYSTEM THAT ARE RESIDENT THERE
BUT ALSO THIS CONCEPT THAT THAT
ARE IMMUNE CELLS HAPLY
TRAFFICKING INTO A FORMAL BRAIN.
AND BI-DIRECTIONAL
COMMUNICATION.
THANK YOU DUNCAN, PERFECT LAW UP
THERE, MASS PARALLEL
COMMUNICATION, IMMUNE TO BRAIN,
BRAIN TO MIEWN, ENVIRONMENT TO
IMMUNE, BRAIN TO UNICATION, ALL
ILDELATWALLIBLELY CONNECT INTOED
WHAT IS OUR CURRENT STATE.
NOW WE KNOW ABOUT SOME OF THE
PATHWAYS VIA WHICH THIS IMMUNE
COMMUNICATION FROM IMMUNE TO
BRAIN IS OCCURRING.
CLASSIC LOAMACYY THERE ARE 4
TYPES BUT MANY OTHER SUBTYPES.
ABOUT YOU WE CAN THINK OF THIS
AS THE CLASSICAL HUMOR ROOT,
POTENTIALLY LEAKY OR STICKY
PARTS OF THE PRAIN, THE
CLASSICAL ASCENDING PROJECTIONS
OF NEURONAL ACTIVATION LIKE THE
VAGUS, WE HAVE THE CELL TO CELL
CONTACT AND TETHERING OF CELLS
AT THE BLOOD BRAIN BARRIER TO
SIGNATURES 95 DIRECTLY ACROSS
THE BLOOD BRAIN BARRIER AND THE
MOVEMENT OF CELLS INTO THE
CENTRAL NERVOUS SYSTEM IN A
NONNEUROINFLAMED BRAIN.
NOW THERE'S KEY LANGUAGE IF YEAR
TRULY USING THE TERM
INNERFLAMMATION CORRECTLY, IT'S
ACTUALLY AFFAIRS TEAM
LEADERRERRED IMMUNE SIGNALING OF
THE CENTRAL NERVOUS SYSTEM, IT'S
SUBPYROGENIC, NOT TO THE GROSS
STATE OF ACTUAL EDEMA CHANGING
OR PATHOLOGICAL CHANGING TO THE
MACROSTRUCTURE.
NOW THIS BIOPSYCHOSOCIALITATE OF
PAIN AND THE WAY OUR BODY IS
INDELIBLY CONNECTED BETWEEN MIND
AND BRAIN, BODY AND BRAIN, MEANS
THAT THERE ARE GOOD ANDLE ANDENT
EVIDENCE NOW TO SUGGIEST THAT
OUR IMMUNE SYSTEM CAN CHANGE THE
WAY THAT WE ACTUALLY THINK.
SO THESE ARE GREAT STUDIES FROM
PREPANDEMIC BUT I'M SURE YOU'VE
ALL EXPERIENCED ABOUT HOW
TERRIBLE THE VACCINATION THEY
GOT WAS VERSUS YOU THAT WERE
REWRILIENT OF COURSE, AND YOU
DIDN'T COMPLAIN ABOUT THE
VACCINE OR ANY SIDE CENTER FOR
EXCELLENCE ON AGINGS THEREOF,
CRITICAL HERE IS THE REALIZE
THAT YOUR IMMUNOLOGY IS
RESPONDING TO IN A
PROINFLAMMATORY FASHION TO THAT
VACCINATION AND COMMUNICATING TO
THE BRAIN IN SPECIFIC PATHWAY
ANDS THIS PARTICULAR STUDY IN
2009 FROM HARRISON LOOKED AT
CONFUSION AND FATIGUE SCORES
MEASURED RESULLING FROM A
VACCINATION AND AND THE FMRI
SCANS AND THE BRAIN REGIONS
WHERE THE FATIGUE AND COB FUSION
IN THE CHAIMPLES IN THE REGION
WERE PROPOSITIONAL TO THE
CONFUSION AND FATIGUE CAUSED BY
THAT VACCINATION EMPLOY BUT
SIMILARLY THE WAY THAT YOU ARE
THINKING NOW CAN CHANGE YOUR
IMMUNE SYSTEM, SO THE SUDDEN
EXPERIENCE OF SADNESS OF RECALL
OF THE DEATH OF A LOVED 1 ARE
NOT ONLY CALLED THE DISCREET
BRAIN REGIONS BUT THE ACTIVATION
OF THESE REGIONS RESULTED IN A
CHANGE IN THE IMMUNE RESPONSE
WITHIN THE PERIPHERY WITHIN 20
MINUTES.
SO WE'RE NOT DEALING WITH 1
DIRECTIONAL OR 2 DIRECTIONAL
COMMUNICATION, WE'RE DEALING
WITH AN INDELIBLE CYCLE OF
INFORMATION NO AROUND AND AROUND
THIS CYCLE EMPLOY NOW THIS MEANS
THAT WHERE DOES PLACEBO FALL
INTO THIS AND WHAT I LIKE TO
THINK OF IS MORE OF A
CONDITIONED RESPONSE.
YES, PLACEBO EXISTS BUT IT'S
PLACEBO BECAUSE WE HAVEN'T
HARNESSED IT YET, BUT WHAT IF WE
GAVE IT A NAME EMPLOY SO GREAT
WORK OUT OF THE LEARNED
IMMUNOSUPPRESSION EXPERIMENTS
FROM GERMANY WHERE THEY'VE BEEN
ACTUALLY PAIRING, STRANGE
TASTING SOLUTION MILK WITH AN
IMMUNO SUPPRESS ANT IN ORGAN
TRANSPLANT PATIENTS AND THEN
REPEATEDLY DOING THAT LIKE PAF
LOVE'S DOG AND JUST REMOVING THE
IMMUNO SUPPRESSANTS IN THIS
CASE, PSYCHOSPORIN AND THEY
ACHIEVED THE SAME LEVEL OF
IMMUNOSUPPRESSION IN THE ABSENCE
OF CYCLOSPORIN JUST BY USING THE
STRANGE TASTING MILK SOLUTION
EMPLOY SO WE CAN CONTROL THIS
IMMUNE RESPONSE BUT SO I HOPE
YOU'RE THINKING, IF WE THINK OUR
IMMUNE SYSTEM WELL, DID THAT
MEAN OUR IMMUNE SYSTEM CAN
CHANGE OUR PHYSIOLOGY?
MAYBE IF WE CAN RUN THOSE LARGE
SCALE TRIALS.
OTHER EXAMPLES OF THIS MED TEAGZ
INDUCED CONTROL AND BREATHING
INDUCED CONTROL OF ANGIO TOXIN
RESPONSES, THE KEY OUTCOME HERE
IS THAT IF YOU GO THROUGH THE
BREATHING EXERCISE AND
MINDFULNESS PRACTICE, TRAINING
AND THEN GET AN EXPERIMENTAL
SEPTICEMIA USING INTRAVENOUS
ENDOTOXIN.
YOU HAVE COLVOLUNTARY CONTROL OF
YOUR AUTONOMIC SYSTEM AND
INTERLEUKIN AND RESPONSE TO THE
ENDOTOXIN AND BUT 1 FLY IN THE
OINTMENT IF THE HUMAN EXPECTED
TO GET A BEP FITOT OF THAT
TREATMENT THEY RESPONDED BETTER,
SUDDENLY THE ISHT ACTION BETWEEN
THE CLINICIAN AND PATIENT BECOME
SUPER IMPORTANT NOW I DON'T KNOW
HOW WE DO THAT IN AN ANIMAL
SETTING BUT APPROXIMATE WE CAN,
THESE ARE POWERFUL PLACEBO
CONDITIONED RESPONSES TO
HARNESS, NOT TO TRY AND
NECESSARILY DIMINISH, THESE
STRESS RESPONSES BUT THEN WE CAN
TRIGGER START TO GET REALLY
COMPLICATE INDEED TERMS OF THAT
MULTICOMPARTMENT COMPONENT OF
THE BIOPSYCHOSOCIALITATE.
SO WE'RE NOW SEEING THAT THERE
IMMUNE CELLS UNDER A
PSYCHOLOGICAL STRESS CONDITION
THAT ARE SELECTIVELY RECRUITING
INTO THE DEFINED REGIONS AND THE
RESULTING BEHAVIORIAL CONQUENCE
IN THOSE ANIMALS IS DEPENDENT
UPON THOSE EMUNE CELLS WITHIN
THOSE BRAIN REGIONS.
SO AGAIN THIS PERIPHERAL CENTRAL
COMMUNICATION IS CRUCIAL, BUT
JUST TO CLARIFY THIS, IT IS NOT
NEUROINFLAMMATION, IT IS LOW
GRADE IMMUNE SIGNALING WITHIN
THESE CENTRAL NERVOUS SYSTEM
COMPARTMENTS THAT IS THEN
ALTERING THE HOMEOSTATICITATE
THAT IS LEADING TO NEURONAL
CONSEQUENCES AND WE NOW
UNDERSTAND, THERE'S ACTUALLY A
MOLECULAR IMMUNOLOGICAL SIGNAL
DRIVEN FROM WE THINK MAYBE
METABOLICALLY STRESSED CELLS, TO
RELEASE THESE DANGEROUS
ASSOCIATED MOLECULAR PATENTS
THAT RECRUIT THIS BY THE INNATE
IMMUNE SIGNALING TO ENABLE THOSE
RESIDENTS IMMUNE CELLS,
MICROTBLIA AND ASTRO CITES AND
PERHAPS EVEN T-CELLS TO MODULATE
NEURONAL FUNCTION.
AND SO THIS IS LED TO, A LARGE
EXPLOSION OF WORK IN THE
MOLECULAR SIGNALS THAT UNDERPIN
BIOPSYCHOSOCIALITATE.
NOW MANY OF THESE ARE FALLING
INTO THE ASSOCIATED IN MOLECULAR
PANELS, AND SOME ARE THE
CLASSICAL 1S, ENDOTOXIN, LPS,
PATHOGEN ASSOCIATED BUT THE
MICROBIOMES SAY WE'RE REALLY
GOOD AND WE NEED THESE, SO NOW
WE HAVE MAPS, DAN MENTIONED THE
DANGER ASSOCIATE WIDE THE
MOLECULAR PATENTS AND THE
ENDOGENOUS FACTORS, THERE ARE
SMALL MOLECULE DRUGS LIKE
MORPHINE AND SOME OTHERS THAT
ARE DRUGS OF DEPENDENT WHICH
ACTIVATE SYSTEMS AND WE'RE
CALLING THEM, BUT THEN THERE IS
ALSO THIS CRUCIAL COGNITIVE AND
BEHAVIORIAL MOLECULAR PATENTS
THAT ARE DERIVED BECAUSE OF THE
EXPERIENCE, THE CONSCIOUS
EXPERIENCE OF THOSE EVENTS THAT
IS THEN TRIGGERING THE SIGNALING
VIA THE MOLECULAR SIGNALS
PRESENCE PALLY, THE TOLL-LIKE
RECEPTORS IN THE FIRST INITANCE.
NOW THESE ARE ALL WORKING IN
FEED FORWARD, FEEDBACK LOOPS AND
THE GOOD 1 HERE IS THE ALPHA
TINNIC COAL O 7 ARC THAT IS
RESULNOTHING CONTROL BETWEEN
BRAIN TO SPLENIC OUTPUT AND THE
CONTROL OF IMMUNE FUNCTION BUT
THERE ARE MANY NOW OCCURRING IN
THESE CONTINUE FEED FORWARD AND
FEEDBACK LOOPS.
IT'S CRUCIAL THEREFORE THAT
PERHAPS WHEN DUNCAN IS TALKING
ABOUT BI-DIRECTIONAL, A TO B,
THEY MIGHT LIKE TO GO FROM
NEW YORK TO SYDNEY TO LA RATHER
THAN JUST EAST-WEST.
SO WE NEED TO START THINKING
ABOUT HOW ARE THEE ACTUALLY
FORMING UP INTO MUCH MORE
COMPLEX 3 DIMENSIONAL SPACES.
SO WHEN WE TART THINKING ABOUT
THE PHYSIOLOGICAL STATE IN PAIN,
WE TEDE TO BE THINKING ABOUT THE
FACT THAT THE WHOLE SYSTEM KNOWS
IT IS IN PAIN.
AT A MOLECULAR LEVEL, SO WHEN WE
START INTERNATIONAL
CLASSIFICATION DPRAITING THE
BIOSOCIALITATE OF THIS, WE'RE
ACKNOWLEDGING THAT ALMOST EVERY
SINGLE COMPONENT THAT HAS THE
RECEPTOR LIGAND POTENTIAL
INTERACTION HAS THE CAPACITY TO
KNOW THAT OUR PHYSIOLOGY IS
EXPERIENCING WHATEVER THAT PAIN
MEANS.
AND OF COURSE, THIS OCCURS IN
DEFINED ANATOMICAL COMPART AMS
AND AN EXPERIENCE OF KNOWING A
MOLECULAR LEVEL MAY BE VERY
DEPINEDYY DEPENDENTOT PART.
NOW THIS IS CRUCIAL WHEN WE
START TO THINK ABOUT THE
CREATION OF BIOPSYCHOSOCIAL
RELEVANT EXPERIMENTAL PAIN
MODELS AND SO THE--DURING A VERY
LONG BOAT HERE, MY PAIN MODEL IS
HURTING PEOPLE INTENTIONAL WITH
BOTH EXPERIMENTAL SEPTICEMIA AND
[INDISCERNIBLE].
WHEN I'M TALKING ABOUT DOSES
THAT ARE ALLOWED TO BE IN A
STANDARD STERILE SALINE IN
HOSPITALS, AND THEN INTERDERMAL
CAP SIGNIFIA SIN, YOU CAN SEE
THAT THE DOTTED LINE FOR THE CAP
ASSIGNEDIN ALOACH, AND THE HYPER
ANNAL GEEZIA AND FLARE AND WHEN
THESE INDIVIDUALS IN A DOUBLE
BLIND PLACEBO CONTROL CROSS OVER
TRIAL RECEIVED ENDOTOXIN WE GET
A SINNER GESTIC INTERACTION TO
CREATE FUNDAMENTAL PAIN.
NOW WHAT'S INTERESTING ABOUT
THESE STUDIES ARE THE PENTINE
REGIMENINOIDS GABBA AND
PREPENTA, THEY WORK ALONE TO
DEMON TRAIT THEIR WORK.
I WOULD ARGUE THEY'RE OPERATING
ON IA SING ILLEGALS
DIMENSIONALITY, NOT TAKING INTO
ACCOUNT THE NEURAL IMMUNE STATE
AND THERE'S NO COMPONENT OF THAT
COMPLEXITY OF TIME EMPLOY SO
WHAT THIS MEANS IS WHEN WE TART
THINKING ABOUT THE PROBLEM OF
PAIN IN HUMANS AND THE PROBLEM
OF PAIN IN ANIMALS.
IT TRULY IS A MULTIDIAL
CHALLENGE.
WE HAVE BIO, PSYCHOLOGICAL AND
SOCIAL ELEMENTS CONTRIBUTING TO
AN UNDERPINNING DEVELOPMENT OF
THE EXISTING UNDERPINNING OF
WHAT IT MEANS TO HAVE
SENSITIZATION FOR EXAMPLE, WE
NEED TO HIT THE WHOLE RANGE OF
DIALS TO DO THE OLD AUDIO
CONTROL SYSTEM TO THEN GET THE
PERFECT PITCH OF NO PAIN OUT.
WOP DIAL WILL NOT HIT IT.
THE PAIN IS COMPLICATED BUT I
WILL ARGUE THAT THAT IS A GOOD
THING BECAUSE IF WE HAD A SIMPLE
PAINITATE AND WE WERE STILL NOT
ABLE TO DEAL WITH THE 77% OF THE
BURDEN OF DISEASE, THAT IS AN
ABSENCE OF HOPE AND ACTUALLY I
THINK THE FACT THAT WE'RE
ACKNOWLEDGING IT'S COMPLICATED
IS ON A PATH FORWARD.
SO WHAT DID THIS PATH FORWARD
MEAN IF WE START THEN THINKING
ABOUT MEASUREMENT WINDOWS INTO
THE BIOPSYCHOSOCIAL PAIN STATE.
SO THE STATE-OF-THE-ART, IN THE
ROYAL ADELAIDE HOSPITAL,
400-METERS DOWN THE ROAD FROM US
IN THE NEUROFORMACOLOGY LAB IS
YOU WERE ASKED ON A SCALE OF
1-10 HOW MUCH PAIN YOU'RE IN.
SAME AS BEFORE.
YOU THINK THAT'S FANTASTIC, WE
HAVE DIFFERENT GRADING THERE,
THERE'S A LOT OF INFORMATION.
NO, THIS IN AUSTRALIA LEADS TO A
FINEARY DECISION, IF YOU'RE LESS
THAN 4, YOU GET GET
NONSTEROIDAL, IF WE'RE GREATER
THAN 4, YOU MAY GET 3 DAYS OF
OPIOID TREATMENT.
THE OTHER PROBLEM WE HAVE HERE
IN THE NIH FUNDED OTHERS THANK
YOU PAIN MODELS, WE ARE DEALING
WITH MOST OF THE TIME, VISUAL
ANALOGUE SCALE 10 EQUIVALENT OF
MEASURES OF PAIN IN OUR ANIMALS.
SO IF YOU GO BACK TO THE OLD CCI
MODEL AND THE BENNETT, THEY HAD
ALL THE OTHER BITS IN BETWEEN
BUT IT WAS STATISTICALLY MOST
ROBUST, BECAUSE THEY HAD A
MASSIVE CEILING EFFECT BECAUSE
THEY COULDN'T GET ANYMORE ALOE
DENNIA WITH THE MEASURE AMS.
SO THE OTHER KEY PART IS NOW
WE'RE FUNDED MALE, FEMALE NIH
GRANS, THANK YOU BYOU WHEN WE'RE
DEALING WITH PRODUCTION SYSTEMS,
WE'RE DEALING WITH AN EASTERN
DOMINANT TESTOSTERONE DEPLETED
POP EULOGY.
WE HAVE NO DATA ON TESTOSTERONE
DEPLETED NEUROBIOLOGICAL STATES.
WE HAVE VERY MINIMAL DATA ON HOW
THESE DRUGS ACTUALLY WORK IN A
CYCLES FEMALE.
SO PAIN IS COMPLICATED.
WHAT IF WE TRY TO TAKE IT APART
AND JUST LOOK AT THE
BIOPSYCHOSOCIAL COMPONENT OF NO
SUSCEPTION.
AND WO,ING WITH PHYSICISTS IS A
PLESESSING SOMETIMES AND THEY
ASK YOU REALLY PROFOUND QUESTION
ANDS THEY MAKE YOU TOP AND
THINK.
SO JUST ON A QUICK SURVEY, WHO
THINKS PAIN IS ANALOGUE, AND WHO
THINKS PAIN IS DIGITAL.
ONE, 2, 3, GO.
ANALOGUE?
DIGITAL?
THOSE WHO RESPONDED ABOUT 80%
NONRESPONSE RATE, THAT'S VOTING
IN THE U.S., OKAY.
THIS IS CRUCIAL TO UNDERSTAND.
WHEN WE TART THINK BEING WHAT
WE'RE ACTUALLY TRYING TO MEASURE
IN PAIN IF WE ARE TO GET TO A
CELLULAR MEASURE, SO LET'S JUST
QUICKLY UNPACK THE ANALOGUE
STATE, IN ANALOGUE THE
INFORMATION IS CONTAINED WITHIN
THE DOSE, ALL OF THE CELLS
RESPOND PROPORTIONAL TO THE
AMOUNT OF PAIN SIGNAL.
BUT IN THE DIGITAL STATE, THAT
WILL HAPPEN, NOW THOSEITAL
SIGNALS MAY BE REALLY DIFFICULT
TO GET TO IF THEY'RE IN
AN ANATOMICAL COMPARTMENT.
BUT THE OTHER THING TO LOOK AT
DOWN THERE IS IF YOU RUN THIS
OFF A WESTERN BLOT TISSUE O
EALIZA OFF THE TOP, YOU WILL GET
THE SAME MEASURE WHETHER IT IS
KIJITTAL OR ANALOGUE.
SO WHAT THAT SAYS IS MOST OF OUR
MEASURE WANTS TO DATE UNLESS
THEY'RE SPATIALLY ORYEBTED HAVE
NO WAY OF DETERMINING WHETHER
WE'RE DEALING WITH AN AN LOG OR
DIGITAL SIGNAL.
SO THIS THEN ALSO ASKS THE
QUESTION, ARE WE ACTUALLY
SETTING UP OUR TRIALS TO EVEN
ASK THIS QUESTION OF WHETHER IT
IS ANALOGUE OR DIGITAL IN
BECAUSE WHERE WE TART LOOKINGA
THE THAT CHALLENGE OF EXTREMES
OF PAIN, NO PAIN VERSUS ALL
PAIN, ACTUALLY WE'RE NOT ABLE TO
ASK THIS QUESTION OF THE DEGREES
IN BETWEEN.
SO WE'RE REALLY SETTING
OURSELVES UP TO ONLY ASK THE
QUESTION, DO HAVE YOU PAIN?
OR DO YOU NOT?
ARE YOU AT 0 OR ARE YOU A 10 IN
CLENICALLY IN HUMANS MOST OF
THOSE HUMANS PRESENT BETWEEN 3
AND 7.
IN THE ANIMAL WORLD I'M ASSUMING
THAT WILL ALSO BE THE CASE.
SO WE STARTED EXPLORING THIS,
PETER GRACE A GREAT GRADUATE
STUDENT WHO IS NOW AT M. D.
ANDERSON, HE CREATED THE ALOE
DENNIA MODEL, WHERE WE MODEL
CITIZEN'RE MODIFY THE NERVES.
SO WE ASK WHICH YEENS CHANGE
THEIR TRANSCRIPTION PROPORTIONAL
TO THE AMOUNT OF PAIN BEHAVIORS,
ALOE DENNIA, YEAH IT'S 1
DIMENSIONAL, ALL WOE HAD AT THE
TIME, FORGIVE ME FOR THAT.
BUT WE ASKED THE QUESTIONS HOW
MANY YEENS CHANGED THERE
TRANSCRIPTION PORTION COMPARED
TO THE AMOUNT OF PAIN.
AND WE FOUND THERE WERE 600
YEENS THAT FELL INTO THE TAIL OF
EXPWRIEWKS.
THAT 600 MOLECULAR SWITCHES THAT
CHANGED THEIR EXPRESSION WITHIN
THE PENAL CORD OF THESE ANIMALS
PROPORTIONAL TO THE AMOUNT THE
ANIMALS ARE IN EMPLOY NOW THIS
IS A MASSIVE NUMBER OF TARGETS
THAT POINTS NEEDS TO HAVE A
COMPLEX ANSWER TO A COMPLEX
SOLUTION.
WITHIN THE CENTER FOR THE
BIOTONNICS WE'VE BEEN ABLE TO
IMPACT THIS MORE USING ADVANCED
REALTIME IMAGING IN THIS
PARTICULAR CASE THIS WAS GREAT
COLLABORATIONS WITH THE HOST
INSTITUTE IN CHINA WHERE WE HAD
AN OPTICAL WINDOW INTO THE
DORSAL HORN OF MICE THAT HAD
CHRONIC INJURY OF
[INDISCERNIBLE] NERVE INTEGRATED
FASHION AND WE'RE ABLE TO
MEASURE THESE REACTIVITY MARKERS
IN GFP EXPRESSING MICROGLIA OVER
TIME.
AND WE FOUND THAT THE DENSITY,
FORM AND VELOCITY OF THESE CELLS
ALL CHANGE PROPORTIONAL TO THE
MECHANICAL ALOE DENNIA THAT
THESE MICE ARE REPORTING.
SO WE'RE STARTING TO SEE IT'S
NOT JUST THE EFFECTORS THAT ARE
BEING RELEASED BUT THE
BIOMECHANICAL MOVEMENT OF THESE
CELLS.
SO THIS ALL STARTED TO GET
EXCITED ABOUT, IF WE'RE DEALING
WITH A CONNECTED SYSTEM OF MIND
AND BODY, BODY AND MIND, COULDY
TART ASKING QUESTIONS OF THE
MIND AND BODY JUST FROM THE
CIRCULATORY SYSTEM, JUST FROM
THE BLOOD.
SO DAN BRIEFLY SHOWED YOU THESE
DATA.
THIS IS AN ACCUMULATED DATA SET,
LOW PAIN, SCIATICA,
ENDOMETRIOSIS, POLYCYSTIC
FIBROID INDROAM, WHERE WE TAKE
THE INNATE STIMULATED RESPONSE
OF THE CELLS EXVIVO AND
DELINEATE A DIFFERENCE BETWEEN A
PAIN POPULATION AND A NO PAIN
POPULATION.
NOW CRUCIAL HERE THERE IS
DIFFERENCE THAT A SCIENTIFIC
TERM IN AUSTRALIA AT
NONSTIMMULATEDITATE.
WE DON'T SEE AN UNSTIMMULATED
DIFFERENCE BETWEEN THESE CELL
POPULATIONS.
WE MEDE TO WORK THEM.
WE NEED TO EXERCISE THEM IN THE
DISH.
MOW THIS DISCOVERY MANY MOONS
AGO HAS STIMULATED A RANGE OF
EXPLORATION INTO THIS SPACE.
SO WE HAVE 2 QUESTIONS THAT WERE
BEFORE, WHAT ARE WE ACTUALLY
MEASURING IN THE PAIN CELL TEST.
DO YOU HAVE PAIN OR NOT IN THE
PAIN SEQUENCING AND THE PAIN
SPECTRAL, HOW MUCH PAIN ARE YOU
IN?
MAGNITUDE.
AND 1 WE'RE REALLY EXCITED FOR
IN THE LIVESTOCK INDUSTRY, IS
SITTING IN THE [INDISCERNIBLE]
AND LOOKING AT THE LEVELS OF
THIS SPEED, WHAT IS THE PAIN
EXPERIENCE ACROSS YOUR LIFE, ALL
FROM IN LECULAR MEASURES FROM
WITHIN THE SPINAL CORD.
NOW WE'VE BEEN TALKING ABOUT
THIS FOR A LONG TIME AND THE
DEPARTMENT OF DEFENSE GOT
INTERESTED AND THEY ASKED US, DO
YOU THINK WE COULD START ASKING
THINGS ABOUT COGNITIVE
BIOLOGICAL COGNITIVE SUBTRAITS
AND PERFORMANCE IN REALLY ELITE
ATHLETE ANDS JUST AS AN EXAMPLE
OF 1 STUDY WE'VE DONE IN THE
ADELAIDE FOOTBALLERS WE'VE BEEN
LOOKING AT NEAR REALTIME
PREDICTION OF THEIR VIGILANT
ATTENTION ASSAY, O
PSYCHOVIGILANT ATTENTION ASSAY,
1 SUBTRAIT OF COGNITION, AS THEY
ISSUE MEASURE SOMETHING WE CAN
DEFINE TO A BRAIN REGION AND WE
HAVE EXCELLENT MEASURES FROM THE
BLOOD PREDICTING THEIR CURRENT
COGNITIVEITATE AND WE'VE GOT
NEAR TERM PREDICTION WORK AS
WELL.
I CAN TALK TO YOU ABOUT
AFTERWARDS.
SO WE'VE DONE ALL THIS IN
HUMANS, WE'VE DONE IT ALL IN
RODENTS, WHAT ABOUT A POPULATION
THAT ACTUALLY WE CAN IMPACT ON,
WITHIN MY LIFETIME, THAT BEING
LIFE STOCK.
SO WE STARTED WORKING WITH THE
LIVESTOCK TEAM AT THE ROSE
WORTHY FARM, WITH THE DAVIES
LIVESTOCK RESEARCH TRUSTEES TO
EXPLORE WHAT CAN WE TRANSLATE
RAPIDLY FROM THE LESSONS WE'VE
LEARNED FROM RODENTS AND HUMANS
TO THEN RAPIDLY GO INTO SHEEP
AND BEEF CATTLE.
AND AS AN EXAMPLE OF 1 OF THE
DOMAINS WE RAPIDLY JUMPED INTO
BY JUST HANGING OUT AT THE
[INDISCERNIBLE] AND CATCHING
HEADS ON THE LINE.
WE LOOKED AT WEANING PROBLEM AND
LOOKING AT DEVELOPMENT OF LIMBIC
STRUCTURES JUST IN THE BRAIN IN
THE HYPOCAMPUS OF THESE ANIMALS
LOOKING AT TOTAL DENSITY AND
NEUROLOGICAL, AND CELLULAR
RESERVE, WITHIN THE DENTATEIARUS
OF THE HYPOCAMPUS.
JUST BECAUSE THESE ANIMALS WENT
THROUGH MATERNAL SEPARATION OR
AN AUGMENTED WEANING PROGRAM
WHICH REALLY IS SOCIALIZATION
AND EXPOSURE TO ENVIRONMENT.
DAN MENTIONED SOME OF THE SHEEP
STUDIES THAT WE PULLED OUT AND 1
THING THAT BECAME VERY APPARENT
WAS THE DISKONTY TECH WE SEE
BETWEEN OUR CORES AND THE VIDEOS
AND THE TEST XG THE ENHANCING
DERMA TELOMERE EMPLOY SO WITHIN
4 HOURS, OUR LAMBS WERE UP AND
WALKING, THEY HAD NO ANNAL
GEESIA WHATSOEVER, AND THESE ARE
THE GIRLS WITH SIMPLICITY, WITH
THE RING DOCTORAL STUDENT, BUT
IF WE LOOK THE AT TESTING WE
COULD SEE SENSITIZATION ON THESE
MEASURES LONG-TERM.
LEALLY UNDERPIPING THAT LOOKING
IS 1 ELEMENT BUT TESTING AND
KNOWING AT THE CELLULAR
MOLECULAR IS CRUCIAL.
SO I WANT TO COVER ON A PATH
FORWARD, AND THIS IS WHERE IT'S
COMING.
A PATH FORWARD WHERE WE ACTUALLY
HAVE THE VIEW OF WHERE WE WANT
TO END UP AT A PRODUCTION
SETTING AND FROM A RESEARCH
PERSPECTIVE AND A REGULATORY
FRAMEWORK PERSPECTIVE AND DO NOT
CONFLATE THOSE BECAUSE THEY'RE
GOING TO BE FAST FAILED MEASURES
WE HAVE TO IMPLEMENT IF WE'RE
GOING TO ACHIEVE ANYTHING IN THE
NEXT 10 YEARS.
NOW THE REASON WHY I TAKE THIS
APPROACH IS BECAUSE IT DOES
WORK, IT'S WHAT HOLLYWOOD DOES,
SOMEONE WRITES A SCRIPT AND THEY
DON'T JUST PUT IT ON THE SHELF,
PUBLISHING OR PERISHING, YOU
PUBLISH IT TO ACTUALLY CREATE
THE MOVIE SO WHY DON'T WE IN THE
PAIN COMMUNITY ACTUALLY SET UP
THE SYSTEM TO EXPECT IT TO
SUCCEED.
I. E. THE BRILLIANT
CONVERSATIONS WE ALL HAVE HERE.
SO THE TARGET FOR US, WE'VE DONE
A LOT OF WORK WITH CONSUMERS,
WITH END USERS, THE
ACCEPTABILITY OF UPTAKE IF WE'RE
TO EVER HAVE A DEPLOYED FARM
DEPLOYED TOOL, IT HAS TO BE FAST
READING WITHIN SECONDS, IT HAS
TO BE REALLY, REALLY CHEAP,
SUBDOLLAR, AUSTRAILIAN DOLLAR,
WHAT ABOUT TWO-CENTS FOR YOU
GUYS, THESE 3 RUGGED SENSITIVE,
SPECIFIC AND HAS TO GIVE
ACTIONABLE INFORMATION.
IT DOESN'T WANT TO BE A 22.3 ON
THE SCORE, ITS GREEN LIGHT, RED
LIGHT, THIS DRUG VERSUS THAT
DRUG, IT SAYS CALL THE VET.
THOSE ARE THE THINGS THAT IT
WANTS.
NOT YOU HAVE 22.3 WITH A
RESCISSION MARGIN, BLAH, PLAW,
BLAH.
THE REGULATORY 1S DO WANT THAT.
SO THERE IS A JOURNEY HERE,
LET'S NOT THROW THE KID OUT WITH
THE BATH PARTY, WE DO WANT TO
HAVE BRILLIANT METAMEASURE UPONS
THAT ARE SUPER EXPENSIVE THAT
HELP US ENHANCE OUR
UNDERSTANDING.
BUT THAT ENHANCEMENT OF
UNDERSTANDING CAN'T BE THE END
GOAL.
SO WE SHOULDN'T TRY AND MAKE OUR
REALLY, REALLY EXPENSIVE THINGS
CHEAPER BECAUSE THERE'S PROBABLY
A FASTER, CHEAPER WAY TO DO THAT
FROM THE PRINCIPLE COMPONENTS
PERSPECTIVE.
THAT'S WHY WE THEED TO MOLECULAR
OMICS APPROACHES AT THE CELLULAR
LEVEL, THAT'S WHY WE NEED THE
IMAGES AND TECHNOLOGY TRANSFERS
LIKE THAT.
WE NEED THE AI COMPLEX
BEHAVIORIAL MODELS BUT WE'VE
TAKEN A LOT OF TIME TO MAKE IN
DECISIONS AROUND FOR US, WHAT
MIGHT BE A SUPER FAST SUPER
CHEAP WAY TO GANNA A HELLUVA LOT
OF DATA AND THE WAY WE'VE TAKEN
THE PATH FORWARD TO MEASURE THE
BIOPSYCHOSOCIAL SETTING IS TO
USE BIOLOGICAL COLOR.
NOW THE BEAUTY ABOUT COLOR WHEN
YOU WORK WITH PHYSICISTS THEY
SAY HOW MANY COLORS DO YOU WANT,
HOW MANY WINDOWS DO YOU WANT FOR
EVERY SINGLE PIXEL SO WHAT WE
HAVE ARE LASERS THAT SHINE LIGHT
ON TO UNTAINED TISSUES, SO YOU
KNOW IF YOU HAVE DONE THAT
HISTOLOGY AND YOU'RE ALWAYS
TRYING TO GET YOUR FLUORESCENT
SIGNAL ABOVE THAT OLD ANNOYING
AUTONEURESTIMATE THAD ENSEL, IS
NAIGED, WE ONLY CARE ABOUT THE
MOISE IN THESE IS ITS BECAUSE WE
CAN THEN DO IS CREATE THESE
IN-DIMENSIONAL DATA CUBES WHERE
EVERY SINGLE PIXEL HAS ITS OWN
SPECTRA AND WE CAN PUMP THAT
INTO MACHINE LEARNING AND
ACTUALLY BACK EXTRACT TO FIND
KNOWN FLORA FORS IN A SUPERVISED
WAY LIKE WE TALKED ABOUT THIS
MORNING OR WE CAN GO UNGUARDED.
WE CAN JUST SAY, TELL US WHETHER
THERE ARE THINGS SO WE MIGHT BE
INTERESTED, PLEASE AND DELINEATE
DIFFERENCES.
SO WHEN WE GENERATED THESE
IMAGES, MY CELL CULTURE,
COLLEAGUES NEARLY DAYS, THEY'RE
ALL SECELLS, WE MEASURED THEM ON
MASS, 10,000 CELLS IN THE BOTTOM
OF A DISH.
NO, THEY ARE NOT ALL THE SAME.
THEY'RE ALL SLIGHTLY DIFFERENT
SPATIAL ARRANGEMENTS ISSUES
LIGHTLY DIFFERENT CELL STATES,
ALL OPERATING INDIVIDUALLY.
SO WE'VE TAKEN THIS APPROACH AND
WE'VE DONE IT BOTH IN GUIDED AND
UNGUIDED AND I WILL SHOW YOU THE
SEMIGOIDED RESULTS AND THIS IS
CREATING A GRADED NEUROPATHY AND
THE SPECTRAL IMAGING AND WHAT WE
EXTRACTED OUT HERE WAS, TELL US
WHICH PIXELS ARE CHANGING YOUR
COLOR, PROPORTIONAL TO THE PAIN
BEHAVIORS, 1 DIMENSIONAL, I KNOW
SORRY, [INDISCERNIBLE] TEST,
PROPORTIONAL TO THE PAIN THAT
THESE ANIMALS ARE EXPERIENCING
AND THIS IS THE DORSAL HORN OF
THE PINEAL CORD.
BUT A PIXEL IN ISOLATION BEARS
NO BIOLOGICAL RESEMBLANCE.
WE WANT TO LOOK FOR THINGS IN
UOF THE KLF-TWOERS, IN BLOBS AS
MY PHYSICIST FRIENDS SAY THAT
MIGHT BE CELLULAR STRUCTURES
THAT MIGHT BE MOVING TOGETHER.
AND SO WE ENDED UP WITH THE
B-PANEL THERE, THE PAIN MASKS.
THESE BLOBS WERE THINGS THAT
CHANGE THEIR COLOR, PROPORTIONAL
TO THE PAIN BEHAVIORS OUR
ANIMALS WERE EXPERIENCING.
AND THEN WE LAYERED ON TO THAT,
THE CELL STAIN TO DETERMINE
WHO'S THERE.
THE BRICKS AND MORTAR AND
PROPORTION TO THE PAIN DEHAD A
FEWS THAT WE WERE SEEING.
SO YES, IT'S CELLULAR, THE
BIOPSYCHOSOCIAL STATE ALSO HAS
TO DO WITH THIS MOLECULAR, THE
EXTRA CELLULAR MATRIX.
NOW WE CAN ALSO DO THIS IN THE
BLOOD AND THIS IS JUST A QUICK
EXAMPLE IN A MIGRAINE PROGRAM
WHERE WE RAN A BUNCH OF VERY,
VERY SICK INDIVIDUALS THROUGH
AND JUST USED THE SIGNATURE FROM
THEIR BLOOD TO DELINEATE.
SO WE HAVE HERE PEOPLE WHO ARE
MIGRAINE FREE, IS IT WE WERE
ABLE TO USE THE CELLS WITHIN THE
TO DELINEATE IN A CATAGORICAL
SENSE, WITH THE CHRONIC MIGRAINE
EMPLOY AND MEASURE TO THE
SEVERITY OF THEIR DISEASEITATE
AND 1 OF THE DIMENSIONAL
COMPONENTS THAT WE'RE ABLE TO
PULL OUT WAS YES AND AND THE
SIGNATURE FROM THE BLOOD, THAT
ACTUAL NUMBER OF MIGRAINES THAT
THEY SHOULD EXPERIENCE THIS IS
SUPER IMPORTANT FOR THIS DRUG
COMPANY FOR THE TRIAL, BECAUSE
THIS THERAPY WAS GOING TO COST
$27,000 A YEAR TO ADMINISTER,
AND IF EVERYBODY WHO CLAIMED TO
HAVE MIGRAINE IN AUSTRALIA TOOK
IT, SEE YOU LATER AUSTRALIA'S
ECONOMY, IT WOULD ALL GO TO
NOVARTIS, WE COULD ONLY PREKRIEB
TO INDIVIDUAL WHO IS ARE
CONSIDERED CHRONIC MIGRAINE.
SO IN THE LAST 2 MINUTES, I WANT
TO TALK ABOUT SUBMARINES.
HOW DO WE ACTUALLY GET THIS
ADVANCED FORD AND WHAT'S
SPECTACULAR ABOUT PEOPLE ALREADY
TOUCHING ON TECHNOLOGY TRANSFERS
THAT I HAD MY MY SLIDES THAT I
DIDN'T NEED TO ALTER.
HOW DO WE ADVANCE THIS, WE NEED
TO EMBODY THE CONVERGENT
APPROACH, WE NEED TO BRING
BRILLIANT PEOPLE TOGETHER WHO
UNDERSTAND HOW TO PARTNER, WORK
TOGETHER AND HAVE TRAINEES THERE
WITH FUNDING TO UNDERPIN THIS TO
ALLOW US TO WORK AS COMPLEX
TEAMS SO WE NEED TO EMBODY THE
BIG BANG THEORY, THOU I'VE
EXPERIENCED WORKING BIG BANG
THEORY BECAUSE I WORKED WITH THE
BRILLIANT PHYSICIST WHO HAVE NO
QUOTIENT WHATSOEVER, SO YOU HAVE
TO BRING THEM ALONG SEPARATELY
AND ASK A QUESTION APPROPRIATELY
BUT WHEN YOU HAVE THE QUESTION
ASK, ALL TOOLS ARE ON THE TABLE
ON DAY 1 AND THE KNOWLEDGE THAT
CAN ACTUALLY ACTION THIS.
AND THIS BRINGS ME TO SUBMARINES
FROM THE U.S. TO BUY 400 BILLION
DOLLARS WORTH OF SUBMARINES BUT
IT'S NOT ALL ABOUT SUBMARINES.
THIS IS A TRI LATERAL
ARAINCHLMENT BETWEEN THE UK,
U.S. AND AUSTRALIA WITH PILLAR
2, ALL BEING ABOUT INNOVATION
AND KNOWLEDGE SHARING, IT'S
GOING TO BE WORKING ABOUT A
TRILLION DOLLAR, THIS IS
SOMETHING WE CAN ACTUALLY ALL
THE THINGS THEY CARE ABOUT AND
THEY WANT THINGS FAST SO THEY
WANT MULTIPURPLE OSTEOSARCOMA
TECHNOLOGIES AND SOLUTIONS FOR
WORK.
SO ALL WE DO HERE IS FLIP OUT
THE LOGOS AND WE ARE TALKING
ABOUT THE DEPARTMENT'S DEFENSE
BECAUSE IT'S THE SAME TECHNOLOGY
TRANSFER THAT THEY WANT FOR THE
FIRST RESPONDERS AND THE WAR
FIGHTERS.
SO WE'RE NOW RUNNING THE PROGRAM
USING BIOPSYCHOSOCIAL PAIN
PRINCIPALS IN THE NO PROGRAM TO
CREATE A MULTIDIMENSIONAL STAND
UP OPERATOR, AND LOOKING AT
HUMAN PERFORMANCE AND EXPLOSION.
SUBITUTE LITERALLY FIND AND
REPLACE THE HUMAN IN THERE AND
WE HAVE THE BLISS, THE BEEF AND
LIVESTOCK INTEGRATED SYSTEM TO
LOOK AT A FULLY INTEGRATED MODEL
OF ANIMAL WELL BEING INCLUDING
INFECTION, IMMUNITY, PAIN AND
ETHICS ALL IN THERE BECAUSE IF
WE GET A SECURITY THREAT WE WANT
RESILIENT PSYCHOLOGICALLY
SOUNDING ANIMALS.
WHY IS THIS IMPORTANT TO DO THIS
NOW?
WE'RE GOING TO MARS IN THE NEXT
DECADE.
NOW NIH IS REALLY WELL FUNDED,
BUT AS SOON AS THE POLITICIANS
REALIZE THAT GOING TO MARS IS
REALLY, REALLY COOL AND WILL GET
VOTES, WE NEED TO MAKE OUR
RESEARCH IN ANIMAL PAIN AS COOL
AS GOING TO MARS.
SO WE NEEDED TO CREATE A PLAN
FOR TREATING ANIMALS IN PAIN AND
PREDICKING ANIMALS IN PAIN AND
INTERVENING ANIMALS IN PAIN,
LITERALLY PAIR WITH NASA BECAUSE
I WOULD LOVE NASA BUMET JUST FOR
PAIN, YES, IT'S GOOD SO MY CHAL
TOARVELG US OUT OF THIS MEETING
IS I WILL BE A PAIN IN THE
ASS AND ASK CAN WE WRITE WHITE
PAPERS POSITIONING THIS WORKSHOP
AS THE ARE WE STILL GOING TO
DEAL WITH PAN OR WE HAVE A PLAN
TO SET OUT SO THAT WHEN WE ARE
ON MARS, HOW ARE WE TREATING
HUMANS ON MARS TREATING THEIR
POTENTIAL PAIN.
THANK YOU COLLEAGUES.
PLEASURE TO MEET YOU. .
[ APPLAUSE ]
NTHATCHING YOU TO DUNCAN AND
MARK FOR INSPIRING TALKS WE WILL
HAVE A BREAK UNTIL 3:20 P.M. WE
WILL COME BACK FOR 2 MORE
EXCELLENT TALKS.
THANK YOU FOR
COMING BACK FROM THE BREAK.
OUR NEXT SPEAKER IS
KATHLEEN SLUKA
ADIG TO THIS RESEARCHER IS ALSO
A CLINICIAN IN PHYSICAL THERAPY
SO SHE BRINGS A VERY BEING AND
INFORMED DIMENSION TO HER
RESEARCH FROM HER YEARS AS A
CLINICIAN.
THANK YOU VERY MUCH.
OKAY, JUSTIN, WE WILL COME BACK
TO YOU.
>> ALL RIGHT, WE'RE GOING TO
SWITCH GEARS AND TALK ABOUT
CHRONIC PAIN NOW AND WE'RE GOING
TO TALK ABOUT THE CLINICAL
ASPECT OF CHRONIC PAIN.
SO I DO--I AM A PHYSICAL
THERAPIST, I ALSO DO CLINICAL
TRIALS, AND HAVE DONE ANIMAL
RESEARCH, STILL DO, BUT WE'RE
GOING TO TALK ABOUT THE CLINICAL
ASSESSMENT OF PAIN IN HUMANS
ITED AND I WILL TRY TO TRANSLATE
SOME OF THAT TO SOME ANIMALS
REALLY BRIEFLY EMPLOY BEFORE WE
GET THERE, I WANT TO START WITH
THE DEFINITION OF PAIP, SO THIS
IS THE DEFINITION OF PAIN BY THE
INTERNATIONAL ASSOCIATION FOR
THE STUDY OF PAIN.
IT WAS UPDATED JUST A COUPLE OF
YEARS AGO AND IT IS AN
UNPLEASANT SENSORY AND EMOTIONAL
EXPERIENCE, ASSOCIATED WITH OR
RESEMBLING THAT ASSOCIATED WITH
ACTUAL OR POTENTIAL DAMAGE.
SO THERE'S A LOT IN THAT
DEFINITION.
RIGHT, THERE'S EMOTIONAL
COMPONENT, A SENSORY COMPONENT,
IT HAS TO BE UNPLEASANT, AND
THERE'S SOME ASSOCIATION WITH
WHAT MIGHT BE TISSUE DAMAGE.
AT THE SAME TIME THIS HAPPENED,
THIS COMMITTEE WHICH I WAS A
PART OF AND IT WAS QUITE A FUN
EXPERIENCE, TOOK YEARS TO GET IT
REVAMPED AND 1 OF THE THINGS
THAT THEY DID IS THEY HAVE A
BUNCH OF ACCOMPANYING NOTES AND
I WILL NOT SHARE WITH YOU ALL OF
THEIR NOTES BUT I SUGGEST YOU GO
READ THEM, I WANT TO SHARE A
COUPLE OF THEIR NOTES BECAUSE I
THINK THEY'RE DIRECTLY RELEVANT
TO WHAT WE'RE TALKING ABOUT
HERE.
FIRST OF ALL, PAIN IS ALWAYS A
PERSONAL EXPERIENCE THAT IS
INFLUENCED TO VARYING DEGREES BY
BIOLOGICAL AND PSYCHOLOGICAL AND
SOCIAL FACTORS AND THAT IS THE
BY O PSYCHOSOCIAL MODEL AND YOU
HEARD DR. HUTCHISON TALK ABOUT
THAT JUST BRIEFLY, BEFORE AND
THERE'S LOTS OF DIFFERENT WAYS
TO THINK ABOUT THE BY O
PSYCHOSOCIAL MODEL BUT IT'S
VERYIABLE BETWEEN PEOPLE AND
WITHIN THE SAME CONDITION AND
BETWEEN CONDITIONS.
THE SECOND PART OF THE NOTE
SECTION THAT WE TOOK A LOT OF
EFFORTS ON WAS THIS 1: VERBAL
DESCRIPTION IS ONLY 1 OF SEVERAL
BEHAVIORS TO EXPRESS PAIN.
THE INABILITY TO COMMUNICATE
DOES NOT NEUROECTODERMAL GATE
THE POSSIBILITY THAT A HUMAN OR
A NONHUMAN ANIMAL EXPERIENCES
PAIN.
AND THIS WAS VERY INTENTIONALLY
PUT IN THERE PARTICULARLY THE
NONHUMAN ANIMAL PART BECAUSE FOR
YEARS WEs SAID OH IF YOU
CAN'T--THE ONLY WAY TO ARK
ASSESSES PAIN IS BY ASKING
SOMEBODY MUCH BUT WE RECOGNIZE
CHILDREN PREVERBAL EXPERIENCE
PAIN, AND COGNITIVE INDIVIDUALS
WHO ARE IMPAIRED EXPERIENCE
PAIN, SO WHY WOULDN'T WHO'S SEEN
AN ANIMAL KNOW THEY ARE
EXPERIENCING PAIN.
SO AT THE COMMITTEE LEVEL WE
KEICIDED WE THEED TO PUT THAT UP
THERE AND IT'S UP TO INDIVIDUALS
WHO ARE TESTING ANIMALS TO COME
UP WITH WAYS TO MEASURE THAT
PAIN ADEQUATELY.
OH, I WEPT THE WRONG WAY, SORRY
ABOUT THAT, SO WE THINK ABOUT
DOMAINS AND WE THINK ABOUT THOSE
THINGS BECAUSE A LOT OF THESE
PREDICT OUTCOME OF REPONS TO
TREATMENT AND CHRONIC PAIN, AND
THEY'LL PREDICT THE TRANSITION
FROM AN ACUTE TO A CHRONIC PAIN
STATE AND SO, I'VE KIND OF
LABELED THEM HERE HERE AND TO
FOREAND WE WILL GO OVER THESE
BUT PAIN IS 1 OF THE DOMAINS
THAT WE ASSESS, PSYCHOLOGICAL
FACTOR, SOCIAL FACTORS AND
FUNCTION, THESE ARE THE TOP 4 I
THINK ABOUT WHEN I THINK ABOUT
DOMAINS.
PAIN FUNCTION, PSYCHOLOGICAL
FACTOR, SOCIAL, THE OTHER 2 THAT
COME UP A LOT ARE THINGS RELATED
TO DISABILITY AND QUALITY OF
LIFE.
IN THE HUMAN CONDITION THAT'S A
BIG DEAL, GET A DRUG THROUGH AD
A TREATMENT THROUGH, WE NOT ONLY
WANT IT TO REDUCE PAIN, WE WANT
IT TO REDUCE DISABILITY, WE WANT
IT TO DO MORE THAN JUST REDUCE
PAIN.
THERE'S THIS CONCEPT OF
RESILIENCE THAT WE THINK,
INCREASING 3 THINK MORE ABOUT IN
THE CLINICAL WORLD.
SO WE'RE GOING TO GO THROUGH
EACH 1 OF THESE.
BEFORE WE DO THAT, I WANT TO
HIGHLIGHT THAT IN ADDITION TO
PAIN THERE ARE A WHOLE SLEW OF
OTHER SYMPTOMS THAT MAINLY
RESULT IN THE SAME BEHAVIORS
THAT YOU'RE SEEING, RIGHT IN O
THERE'S FATIGUE, THAT OCCURS IN
80 TO A HUNDRED% OF PEOPLE WITH
CHRONIC PAIN.
IT DEPENDS ON WHAT STUDY YOU
READ BUT IT'S HIGH.
AND TALK TO ANYBODY WITH CHRONIC
PAIN AND JUST ASK THEM, ARE YOU
FATIGUED?
THEY ALL SAY YES.
MULTIPLE PAIN AREAS, IT TURNS
OUT THAT ALMOST NOBODY HAS PAIN
IN A SINGLE SPOT WHEN YOU
INTERVIEW THEM, ONLY ABOUT 20%
OF PEOPLE DO, THERE'S BEEN LARGE
KALE STUDIES THAT HAVE ASKED
THIS AND THE MORE SPOTS YOU
HAVE, THE WORSE YOUR FUNCTION
IS, THE WORSE YOUR MOOD, THE
WORSE YOUR DISABILITY IS AND SO
IT MATTERS, THE NUMBER OF PAIN
AREAS.
QUITE COMMON.
FUNCTIONAL DEFICITS.
PAIN IMPACTS EVERY ASPECT OF
THEIR LIFE WHETHER IT'S
FUNCTION, COGNITIVE, OR SLEEP,
IT IMPACT FUNCTION.
ANXIETY AND DEPRESSION AS
CO-MORBIDITIES ARE MORE COMMON
IN THE GENERAL PUBLIC BUT LESS
COMMON THAN THINGS LIKE FATIGUE
AND FUNCTION.
COGNITIVE DEFICITS ARE MORE
IMPORTANT BUT REPORTED AND MORE
ALONG THE LINES OF PAIN AND
DEPRESSION, BUT ALONG THE LEANS
OF DISABILITY, TRUE DISABILITY
AS WE MEASURE IT ARE RELATIVELY
LOW AND WE WILL TALK ABOUT WHAT
THIS IS AND WHY THAT IS IN A
LITTLE BIT.
SO 50 OF ALL PAIN, I'VE HEARD
PEOPLE TALK AND SHOW THE VISUAL
ANALOGUE SCALE HERE TODAY, WE DO
A WHOLE LOT MORE THAN THAT WHEN
WE ASSESS PAIN IN AN INDIVIDUAL
OR IN A CLINICAL TODAY OR IN THE
CLINIC THEMSELVES WHEN THEY COME
IN TO SEE YOU, SO WE ASK WHAT IS
YOUR PAIN RIGHT NOW, WHAT IS
YOUR RESTING PAIN, BUT WE DO
THINGS LIKE, ASK ABOUT WHAT YOUR
CURRENT PAIN IS, WHAT YOUR
AVERAGE PAIN IT, WHAT YOUR WORSE
PAIN IS.
ONE OF THE MOST IMPORTANT
CONSTRUCTS OF PAIN INTENSITY IS
MOVEMENT EVOKED PAIN.
SO IT'S THE MOVEMENT EVOKED PAIN
THAT OCCURS PARTICULARLY IN
PEOPLE WITH MUSK LO SKELETAL
PAIN THAT INTERFERES WITH THEIR
FUNCTION, RIGHT.
IF IT HURTS WHEN I WALK, WILL I
WALK?
EVERY TIME I WALK ON THE
TREADMILL TO GET EXERCISE AND
AFTER A MINUTE I HAVE TO DO IT
WITH PAIN BUT AFTER 30 MINUTES
THAT'S TOUGH, SO WE LOOK AT
THOSE CONTRUCTS SO YOU LOOK AT
MOVEMENT AND DURING A PRESCRIBED
ACTIVITY TEST, LIKE HOW MANY
TIMES YOU SIT UP AND DOWN, HOW
MUCH ASK IT HURT WHEN I GO UP A
FLIGHT OF TEARS, I WOULD HAVE
THEM CO THAT TASK ASK RATE THEIR
PAIN AND IT WOULD BE DISEASE
SPECIFIC.
WE LOOK AT WIDE SPREAD PAIN
LOCATION, WHERE IS IT?
THAT'S USUALLY DONE WITH A BODY
DIAGRAM, PATIENTS FILL IT OUT,
THEY CAN SEE WHERE IT IS, IN
AN ANIMAL YOU CAN LOOK AT
PRESSURE, SENSITIVITY AND
TENDERNESS IN MULTIPLE SITES.
ONE OF THE THINGS THAT WE KNOW
IS THAT PAIN IS QUITE VARIABLE
AND ANYBODY WHO TREATS PAIN
KNOWS ITS VARIABLE AND THERE'S
GOOD DAYS AND BAD DAYS, THIS IS
TRUE FOR ANIMALS, THIS IS TRUE
FOR THE PEOPLE.
RIGHT IN THIS IS NOT NOVEL TO
PEOPLE, SO, GETTING A SINGLE
WINDOW OF DAY OF TIME MAY NOT BE
AS ACCURATE AS TAKING A WEEK OR
A MONTH LONG TRAJECTORY.
WE ALSO KNOW THAT THE
TRANSLATIONAL RESEARCH YECTRY OF
RESPONSE, SO IF YOU'RE GOING TO
TREAT THE PAIN, AND THAT
TRAJECTORY OF THE RESPONSE FROM
THE BEGINNING OF THE TREATMENT
TO AFTER THE TREATMENT PREDICTS
YOUR OUTCOME.
SO IF HAVE YOU A BETTER
TRAJECTORY YOU MIGHT LAKELY BE
ABLE TO RESPOND TO TREATMENT
THAN IF YOU DEPARTMENT.
SO THAT CAN BE DONE WITH DAILY
LOGS, DONE WITH QUESTIONNAIRES,
AND ANIMALS WE WILL OFTEN TEST
MULTIPLE DAYS.
THE SAME MEASURE.
ANOTHER BIG CONSTRUCT IS PAIN
INTERFERENCE, AND THE OTHER 1 IS
QUANTITATIVE SENSORY TESTING.
SO PAIN ISHT FER ENSEL IS HELP
HOW PANE INTERFERES WITH THE
INDIVIDUAL AND I WILL SHOW YOU A
QUESTIONNAIRE ON THAT AND THAT
WOULD BE HOW IT INTERFERES AND
YOU HEARD A LITTLE BIT ABOUT
THIS EARLIER TODAY, WITH THE K9
BRIEF PAIN INVENTORY BUT
ACTUALLY LOOKSA THE THAT IN
DOGS, BUT IN PEOPLE, THAT'S
WHERE IT CAME FROM, THE BRIEF
PAIN INVENTOR EXPE CONNECTICUT
SEPTORS OF THAT IS PAIN
INTERFERENCE.
WE LOSE A LOT OF QUAWPTITATIVE
SENSORY TESTING TO REALLY GET AT
MECHANISMS BUT IT'S NOT REALLY
DONE CLINICALLY, WE DO IT IN
CLINICAL TRIALS EMPLOY SO WE
LOOK AT CONDITION PAIN
MODULATION TO GET A CENTRAL
SENSITIVITY.
MAINLY CENTRAL INHIBITION FOR
THAT 1 AND TEMPORAL ENHANCED
SEPSATIVITY AND THEN WE LOOK AT
PAIN THRESHOLDS, SO AS YOU CAN
SEE PAIN IS REALLY COMPLEX
EMPLOY WE ALSO LOOK AT
MECHANISMS, SO A PERSON WITH
PAIN YOU KNOW WHEN AN ANIMAL
MODEL, WE INYECT THEM, WE INJURY
THE MUSCLE, WE KNOW WHAT KIND OF
PAIN THEY GOT, WE KNOW THAT
INJURY, BUT IN A PERSON, WE HAVE
THE NOCICEPTIVE, WHERE
NOCIPLASTIC IS DUE TO CENTRAL
CHANGES IN THE CENTRAL NEUROUS
SYSTEM AND NEUROPATHIC IS DUE O
THE SENSORY AND IDENTIFY THOSE
WAYS.
SO THIS IS JUST A PICTURE OF THE
BODY DIAGRAM LIKE I WOULD HAVE,
YOU HAND IT OFF TO I PERSON, YOU
HAVE THEM FILL IT OUT.
THIS IS THE INTERFERENCE
COMPONENT OF THE BRIEF PAIN
INVENTORY AND CAN YOU SEE IT IS,
HOW MUCH DOES PAIN INTERFERE
WITH THE GENERAL ACTIVITY, WITH
YOUR MOOD, WALKING ABILITY, AND
THAT IS REALLY USEFUL BECAUSE IT
REALLY GETS AT THE IMPACT OF
PAIN ON THE PERSON.
THESE ARE KINDS OF QUANTITATIVE
TESTING YOU MIGHT DO.
YOU MIGHT ELECTRIC AT PAIN
THRESHOLDS, YOU MIGHT LOOK AT
THEM AT THE SITE AND YOU MIGHT
LOOK AT THEM PRETTY FAR AWAY
FROM THE SITE OF THE INJURY.
AND THOSE AT THE SITE MIGHT BE
INDICATIVE OF HYPER ALGEESIA AND
THOSE AT THE SITE.
THOSE AWAY MAY BE MORE
INDICATIVE OF CHANGES IN THE
SEBTERAL NERVOUS SYSTEM, OR
SYSTEMIC.
BUT IT GERONTOLOGYSTSS MORE
COMPLICATED BECAUSE IT LOOKS AT
HEAT, MECHANICAL, SKIN, DEEP
TISSUE AND TURNS OUT SOME OF THE
MOST PREDICTIVE 1S HAPPEN TO BE
THE PRESSURES OF THE DEEP
TISSUE, LIKE PRESSURE PAIN
THRESHOLDS ON THE DEEP TISSUE.
THOSE ARE MORE PREDICTIVE THAN
SOME OF THE OTHERS, OF THE SKIN.
YOU CAN ALSO DO TEMPORAL
SUMMATION AND THIS IS REPEATED
SIMULATION WITH THE SAME
STIMULATION ONCE EVERY SECOND
AND YOU ASK PEOPLE TO RATE THEIR
PAIN DURING THAT TIME AND IT
GOES UP AND IT'S A MEASURE OF
THE EXCITABILITY OF THE NERVOUS
SYSTEM.
AND PEOPLE WITH HIGHER LEVELS OF
PAIN HAVE LOWER TEMPORALS OF
SUMMATION THAN THOSE WITH LOWER
LEVELS OF PAIN.
AGAIN, CAN YOU DO THAT WITH WITH
HEAT, CHEMICAL STIMULI WITH THE
PEN IN THE UPPER CORNER OVER
HERE, WISH I COULD GET OVER
HERE, LIKE THIS 1 RVEG ISSUE AND
JUST REPEAT IT OR YOU CAN DO IT
WITH THE DEEP PRESSURE STIMULUS
WHICH WE'VE DEVELOPED A METHOD
TO DO THAT WITH DEEP PRESSURE
AND THEY'RE ALL PROBABLY TELLING
YOU SOMETHING DIFFERENT AND THEN
CAN YOU MEASURE CENTRAL
INHIBITION.
AND THAT'S A TEST CALLED
CONDITIONED PAIN MODULATION, YOU
PUT A HAND IN A VERY COLD BATH
OR A FOOT OR A HOT BATH OR YOU
GIVE ASCHEMIC PRESSURE OF VERY
PAINFUL CONDITION AND YOU
MEASURE PAIN THRESHOLDS OUTSIDE
THAT AREA AND THOSE PAIN THRESH
HOLES GO UP AND IN INDIVIDUALS
WITH CHRONIC PAIN, THEY TEND TO
GO DOWN BUT NOT IN EVERYBODY.
SO THE PROBLEM WITH QUANTITATIVE
TESTING IS WE DON'T HAVE NORMS.
WE DON'T KNOW WHAT'S ABNORMAL
AND WE DON'T KNOW WHAT'S NORMAL.
AND THEN PAIN MECHANISMS, I'M
SORRY MY COMPUTER DIED BEFORE I
FIX THAT THING ON THE SIDE LAST
NIGHT AND I FORGOT MY CHARGER AT
HOME.
ONE OF THE WAYS WE DO THAT IS SO
SIMPLE WITH NOCIKEPTIVE PAIN
IT'S EASY, DO THEY HAVE
LOCALIZATION, PAIN DUE TO
DAMAGE, HAVE SOMETHING THAT
BEING LOAMACYS LIKE PERIPHERAL
DAMAGE.
EITHER A CENTRAL LESION OR A
NEURAL LESION, AND NOCICEPTIVE
IS HAVE THAT, 1 TECHNOLOGY
TRANSFER THAT DAN PROPOSE SYSTEM
TO USE THE FIBROMYALGIA
CRITERIA, AND WE CAN GET A
SCORE, IT'S RARELY ON HOW YOU
SPEND ON THE SCORE, HOW MUCH
SENSITIVITY YOU HAVE AND THAT
SLEEP DISTURBANCE IS A CENTRAL
CONCEPT CAN COGNITIVE
DYSFUNCTION IS.
AND SO YOU PUT THOSE ALTOGETHER
AND YOU GET AN ALGORITHM AND AN
ASSESSMENT AND THAT'S PRETTY
MUCH HOW WE DO IT SO IT'S A BIT
HARDER, THERE'S NO GREAT
PRESSURE YET.
THIS IS THE CRITERIA AND SO WE
WILL SKIP THAT.
THAT'S PAIN AND THAT WAS A LOT.
THAT'S JUST PAIN.
SO FUNCTION I'M ONLY GOING TO
TALK BRIEFLY AND IT CAN BE
DIVIDED INTO MULTIPLE CONCEPTS,
WE WILL TALK ABOUT PHYSICAL
FUNCTION BECAUSE PEOPLE TALK
ABOUT THAT THE MOST WHEN THEY
TALK ABOUT FUNCTION AND THEY CAN
BE ASSESSED IN PEOPLE WITH A
SURVEY AND WE CALL THAT
PERCEIVED FUNCTION, HOW DO THEY
PERCEIVE WHAT THEY'RE DOING, YOU
CAN DO PERFORMANCE BASED TEST
AND HOW FAST--HOW FAR CAN YOU
WALK IN 6 MINUTES, HOW LONG DOES
IT TAKE YOU TO STAND UP AND DOWN
FROM A CHAIR 5 TIMES.
THOSE ARE PERFORMANCE BASED
TASKS.
YOU MIGHT DO GAIT MEASURE AMS OR
WEIGHT BEARING MEASUREMENTS.
YOU MIGHT DO ACTIVITY MONITORING
AND YOU KNOW YOU TALKED ABOUT
THIS LAST TIME AND YOU MIGHT DO
PHYSICAL ACTIVITY LEVELS BY
SELF-REPORT AS OPPOSE TO ACCEL
ROMETRY.
AND ALL OF THESE ARE DIFFERENT.
THIS IS THE PROBLEM, SO IF I IF
I WERE TO TAKE PEOPLE AND THIS
IS A STUDY THAT A GRADUATE
OPPORTUNITY DID IN MY LABORATORY
AND WE HAD 300 INDIVIDUALS
BEFORE AND AFTER SURGERY WE
ASKED THISEM TO RATE THEIR
FUNCTION ON SELF-REPORT DID A
PERFORMANCE BASED FUNCTION, AND
AND FROM PREOP, IT GOT BETTER,
SO ON THE SLIDE IS OUR CONTROLS,
OUR AGE AND SEX MATCHED
CONTROLS.
THEY PRETTY MUCH GOT TO AGE AND
PERFOR THE PURPOSANCE CONTROLS.
THE PAIN GOT BETTER BY 6 MONTHS
ABOUT YOU OUR ACTIVITY
MONITORING WENT TO PREOP LEVELS
AND IT WAS SUBSTANTIALLY LOWER
THAN CONTROLS.
SO THEY'RE ALL DIFFERENT
CONSTRUCKS AND THEY'RE ALL
MEASURING SOMETHING DIFFERENT IN
ADDITION TO THAT WE HAVE THE
PHYSICAL FATIGUE WHICH AGAIN YOU
CAN MEASURE AS PERCEIVED
FATIGUE, PERFORMANCE BASED AND
FATIGUE.
AND IF YOU MEASURE PERCEIVED
FATIGUE, YOU MIGHT GET QUITE A
DIFFERENCE OF PEOPLE WITH
FIBROMYALGIA THAN HEALTHY
CONTROLS DURING A FATIGUE TEST.
SO WOE GAVE THEM A FATIGUE TEST,
THEY HAD TO DO MORE TASKS BUT
THEY DID EQUALLY WELL
PERFORMANCE BASED.
SO THERE'S FATIGUE AND
PERFORMANCE CAN YOU CAN'T--THIS
WAS A PHYSICAL FUNCTION TASK, WE
HAD THE SAME THING WITH A
PERCEIVED FATIGUE COGNITIVE
FATIGUE, SO THEY'RE ALL
DIFFERENT AND THEY'RE ALL
MEASURES SOMETHING DIFFERENT AND
I THINK ABOUT THIS A LOT BECAUSE
IN OUR ANIMALS WE'RE ALWAYS
DOING THE TASK.
AND ASSUMING THAT THAT IS WHAT
THE PERSON IS PERCEIVING AND IT
MAY NOT BE.
SO COGNITIVE FUNCTION AND
FATIGUE IS VERY SIMILAR EMPLOY
CAN YOU LOOK AT PERFORMANCE OR
TASK BASED TASKS.
YOU CAN LOOK AT PERCEIVED
FATIGUE, CAN YOU LOOK AT
PERFORMANCE BASED FATIGUE, DO
THEY ACTUALLY FATIGUE WITH THE
TASK, PHYSICALLY OR COGNITIVELY.
THERE'S A WHOLE LOT OF
QUESTIONNAIRES AND THE
QUESTIONNAIRES BETWEEN COGNITIVE
FATIGUE AND FUNCTION ARE VERY
SIMILAR.
SO I SUGGEST YOU LOOK AT THESE
IF YOU'RE TRYING TO DEVELOP AN
ASSAY.
AND THEN HERE, WE GET REALLY
SUBSTANTIAL INCREASE WITH
FATIGUE WITH THE COGNITIVE
MYALGIA BUT THEY DO APPROXIMATE
WELL ON THE COGNITIVE TASK
EMPLOY SO KEEP THAT IN MIND WHEN
WE TRANSLATE THIS BACK TO
ANIMALS.
ANOTHER THING IS SLEEP.
AGAIN, WE ASK PEOPLE A LOT ABOUT
THEIR SLEEP, WE HAVE THEM FILL
OUT SURVEYS BUT WE HAVE DIRECT
MEASURE AM ANDS WE'VE GOT DATA
ON THIS, TOO, I WILL NOT SHOW IT
TO YOU BECAUSE IT'S GOING TO BE
EXACTLY THE SAME, WHERE YOU GET
DIFFERENCES BETWEEN PERCEIVED
SLEEP IMPAIRMENTS AND ACTUAL
TELEMETRY BASED OR POLYSIM
NOGRAPHY AND OTHER CASES ASK
CONDITIONS PEOPLE MATCH.
BUT, THESE ARE REALLY IMPORTANT
CONSTRUCKS AND WE DON'T THINK
ABOUT SLEEP A LOT.
BUT IF YOU CAN IMAGINE, IF YOU
HAVE CHRONIC PAIN AND YOU CAN'T
SLEEP BECAUSE THE PAIN IS TOO
GREAT.
SO THE OTHER DOMAIN THEY REALLY
WANT TO--THERE'S ONLY A COUPLE
MORE DOMAINS I WANT TO TALK
ABOUT BUT 1 IS PSYCHOLOGICAL
FACTORS AND WE TALK A LOT ABOUT
THESE, DEPRESSION AND ANXIETY
ARE CLEAR PREDICTERS, THERE'S
INCREASED INDENSE RATES, AND SO
THEY'RE PRETTY IMPORTANT.
THESE ARE BEST MEASURED IN
HUMANS BY SELF-REPORT.
WE CERTAINLY DON'T DO ANY TASK
BASED MEASUREMENTS.
ANOTHER CONSTRUCT IS PAYING
KACCT TAFT RAIFIESING OR KIND OF
WORRYING ABOUT YOUR PAIN ALL THE
TIME.
ANOTHER 1 IS FEAR OF MOVEMENT,
SO THERE'S FEAR THAT MOVEMENT
WILL MAKE THE PAIN WORSE, AND
THE LAST 1 IS SOMETHING CALLED
SELF-EFFICACY.
AND THIS IS THAT I CAN DO MY
TASK DESPITE THE PAIN.
ALL RIGHT, SO THESE ARE PRETTY
HUMAN BASED COP SEPTORSS WE HAVE
AN ANIMAL, SOME TESTS WE DO FOR
DEPRESSION AND ANXIETY AND WE
WILL TALK ABOUT THEM IN A MINUTE
BUT I DON'T KNOW HOW THEY RELATE
TO DEPRESSION AND ANXIETY WHEN I
LOOK AT SOME OF THESE QUESTIONS
THAT YOU'RE ASKING, RIGHT?
SO JUST KEEP THAT IN MIND, THESE
ARE DEFINITELY HUMAN BASED,
QUESTIONNAIRE BASED, I CAN'T
COME UP WITH OBLIGATIONS YECTIVE
MEASURE OF THESE, IN HUMANS.
SAME THING WITH THE SOCIAL
DOMAIN.
WE'RE TALKING ABOUT SATISFACTION
WITH YOUR SOCIAL DOMAIN SOME OF
THESE THINGS YOU MIGHT BE ABLE
TO FIGURE OUT IN AN ANIMAL AND
SOME YOU MAY NOT BE AND THESE
ARE IMPORTANT CONSTRUCKS TOO,
STUDIED IN THE CLINICAL WORLD
AND PARTICULARLY IN THE ANIMAL
LIFTER, AND ANIMAL AND PAIN.
ALL RIGHT, DISABILITY AS A
CONCEPT, SO, I'M BRING
THANKSGIVING UP BECAUSE I'VE
HEARD MY COLLEAGUES TALK ABOUT
DISABILITY IN THEIR ANIMALS AND
I HAVE A HARTIME WITH THAT AND
YOU CAN TELL ME I'M WRONG BUT I
HAVE A HARD TIME WITH IT BECAUSE
DISABILITY TO ME IS A HIGHER
ORDER CONTRUCT.
IF SOMEBODY IMETS TO THE POINT
WHERE THEY HAVE A TRUE
DISABILITY ASK IT INVOLVES
MULTIPLE CONSTRUCT ANDS THIS IS
FROM THE CDC, IT'S A CONDITION
OF THE BODY OR MIND THAT MAKE
ITS MORE DIFFICULT FOR THE
PERSON WITH THE CONDITION TO DO
ACTIVITIES AND INTERACT WITH THE
WORLD AROUND THEM AND TO GET TO
THE POINT WHERE YOU HAVE SOCIAL
SECURITY BASED DISABILITY, IT'S
HIGHER BAR.
SO THEY HAVE TO HAVE AN
IMPAIRMENT AND THEY HAVE TO HAVE
ACTIVITY LIMITATION OF
SIGNIFICANT AMOUNT AND IT HAS TO
HAVE PARTICIPATION RESTRICTIONS,
LIKE THEY'RE NOT DOING THEIR
NORMAL DAILY ACTIVITIES.
AND SOMEHOW WE ARE TO PUT THAT
ALTASD TOGETHER, TO CAPTURE THAT
THERE ARE CERTAINLY ANDLINGS
LIKE THE [INDISCERNIBLE] OR THE
OSWESTRY DISABILITY INDEX, SO
THAT'S JUST A CONTRUCT THAT WE
USE, WE LIKE BECAUSE IF WOE CAN
IMPROVE DISABILITY, WE THINK
WE'RE DOING SOMETHING GOOD FOR
OUR PATIENTS.
AND THEN QUALITY OF LIFE.
AUTOALSO A HIGH DIMENSIONAL
CONSTRUCT LIKE DISABILITY IS
THAT IS METABOLICALLY TO CAPTURE
THE WELL BEING OF AN INDIVIDUAL
BOTH THE PHYSICAL AND MENTAL
LEVEL EMPLOY AND THIS IS A
PROMISE, GLOBAL QUALITY OF LIFE
INKECKS THAT I CRUST PUT UP
HERE, MOST OF ALL OF THESE
CONSTRUCKS THE PROMISE WHICH WAS
DEVELOPED BY THE NIH OF COURSE
HAS SOME FORM OF THIS SO CAN YOU
GET A HANDLE ON WHAT THEY LOOK
LIKE WHEN THINKING ABOUT THAT AS
A MEASURE.
ALL RIGHT, AND THEN RESILIENCE
IS THE ABILITY TO ADAPT TO
ADVERSE SITUATIONS.
AND BRAZILIANS IS ACTUALLY
PERTECTIVE AGAINST CHRONIC PAIN
AND PREDIBS PEOPLE WILL NOT GET
BETTER OR NOT TRANSITION AND SO
THERE ARE A COUPLE OF RESILIENCE
SCALES OUT THERE, THIS IS JUST 1
AS AN EXAMPLE, AND THE MORE
RERELYING ZENS YOU HAVE, THE
BETTER OFF YOU DO IN RESPONSE TO
AN INSULT.
SO LASTLY, ALL PAIN IS NOT THE
SAME.
SO, OSTEOARTHRITIS PAIN IS NOT
FIBROMYALGIC PAIN SO WE CAN'T
HAVE 1 SINGLE MEASURE FOR PAIN
AND IT CAN BE THE SAME MEASURE
FOR ALL CONDITIONS.
FOR INSTANCE IT'S HARD FOR
PEOPLE WITH NEOOSTEOARTHRITIS TO
WALK UP STAIRS, NOT SUCH A BIG
PROBLEM FOR PEOPLE WITH
NEUROPATHIC PAIN USUALLY SO THEY
HAVE A LOT MORE MOVEMENT PAIN,
NEUROPATHIC PAIN HAS SPONTANEOUS
PAIN, SHOOTING PAINS DOESN'T
HAPPEN AS MUCH IN
OSTEOARTHRITIS, THEY HAVE
DIFFERENT CONSTRUCTS AND WITHIN
THE SAME INDIVIDUAL, ARE THE
SAME CONDITION, YOU MIGHT HAVE A
BIG VARIABILITY, SOME MIGHT HAVE
STRONGER SOCIAL CONSTRUCTS,
MIGHT HAVE STRONGER EFFECTS ON
THE AFFECTIVE DOMAIN OR THE
PSYCHOLOGICAL DOMAIN AND OTHERS
MIGHT HAVE STRONGER EFFECTS IN
THE FUNCTIONAL DOMAIN SO WE HAVE
TO INDIVIDUALIZE IT AND YOU
HEARD ABOUT THE
INDIVIDUALIZATION WITH THE
SPECIFIC FUNCTIONAL SCALES.
AND THOSE ARE OUT THERE.
WE USE THEM IN CLINICAL TRIALS
CALLED THE PATIENT SPECIFIC
FUNCTIONAL SCALE, IT'S NICE
BECAUSE PEOPLE PICK WHAT
BROTHERS THISEM AND THEN YOU CAN
SEE IF THAT GERONTOLOGYSTSS
BETTER.
IT'S A LITTLE HARDER TO DO
BECAUSE YOU BRING THE SAME 1
BACK EVERY TIME FOR THAT
INDIVIDUAL PERSON BUT IT'S
DOABLE.
OKAY, THIS IS MY LAST SLIDE.
SO TRANSLATION TO ANIMALS.
HA WE DO IN ANIMALS IS
SELF-REPORT MEASURE, WE DO THE
BEST WE CAN TO ASSESS THAT AND
THAT'S OKAY BUT WE NEED TO KEEP
IN MIND THAT STILL OUR GOLD
STANDARDS FOR PAIN, FATIGUE,
DISABILITY, QUALITY OF LIFE AND
PSYCHOLOGICAL FACTORS ARE ALWAYS
GOING TO BE SELF-REPORT.
SO WHEN WE GET TO OUR ANIMALS,
BUT THESE ARE NOT ALWAYS THE
SAME CONSTRUCT AND AS I SHOWED
YOU, THERE WILL BE DIFFERENCES
BETWEEN THE PERFORMANCE AND THE
SELF-REPORT AND WHAT MATTERS TO
THE PATIENT, I HATE TO TELL YOU
IS ALL THE SELF-REPORT.
IF THEY THINK THEY'RE BETTER,
THEY'RE HAPPY AS A CLAM DESPITE
THEY'RE DOING THE SAME EXACT
ACTIVITY PRESURGERY.
AND THEN, ANIMAL MEASURES THAT
WE DO FOR ALL OF THESE THINGS,
ALWAYS TEND TO INVOLVE A MOTOR
TASK OF SOME SORT.
NOW JUST TO PUT IT OUT HERE IS
THAT MOTOR TASK INVOLVES THE
MOTOR SYSTEM AND THEREFORE IF I
HAVE A DEFICIT IN THE MOTOR
SYSTEM, I HAVE MUSCLE, PHYSICAL
FATIGUE.
AM I REALLY MEASURING PAIN OR AM
I MEASURING FATIGUE AS A
CONSTRUCT?
COMPREHEND AND I CAN TELL YOU
I'VE USED THE SAME MEASURES IN
ANIMAL MODELS OF PANE --PAIN THT
I USE INDEED ANIMAL MODELS OF
FATIGUE EMPLOY SO I HAVE TO
FIGURE OUT WAYS TO VALENTINED
DIADIC THAT SO THAT I AM
MEASURING WHAT I AM SUPPOSED TO
BE MEASURING AND IT DOES LEAD TO
A LOT OF DIFFICULTY WITH INTEP
RETATION.
AND LAST TECHNOLOGY TRANSFER I
WILL THROW OUT THERE IS ASSESS
DISABILITY AND SOCIAL FUNCTION
AND SOME PSYCHOLOGICAL NURVEGZ
ANIMALS PROBABLY NOT DOABLE,
WELL, I LIED THERE WAS 1 MORE
AND THESE ARE THE ASSESS WANTS
WE DO IN ANIMALS I'M MOSTLY A
RODENT RESEARCHER, I DON'T DO
LARGE ANIMAL RESEARCH, I DON'T
EVEN OWN PETS BUT SO THIS IS
WHAT I'VE GOT FOR YOU BUT YOU
KNOW REMEMBER, THE GRIMACE SCALE
IS REALLY A GREAT MEASURE OF
ACUTE PAIN, IT'S SO GOOD FOR
CHRONIC PAIN.
--IN THE OUTCOME MEASURES WE USE
TO,A ASSESSES THE SAME
CONSTRUCTS.
AND SOA I'M TELLING SURVEYS WE
NEED TO BE THOUGHTFUL AND
CAREFUL WHEN WE PAIK
INTERPRETATIONS.
IN OUR ANIMALS, ABOUT WHETHER
THAT'S PAIN OR IS IT SOMETHING
ELSE ASK JUST AN OPEN MIND TO
ALL THE FACTORS THAT COULD BE
CONTRIBUTING TO THAT.
THAT I WILL SAY, THANK YOU AND
HOPEFULLY WE CAN GET JUSTIN BACK
ON EMPLOY.
>> THANK YOU SO MUCH DR. SLUKA
FOR AN INPIERING TALK EMPLOY SO
WE ARE GOING TO TRY TO BRING UP
AGAIN JUSTIN BERG, FIFTH YEAR
Ph.D. CANDIDATE AT COLUMBIA
UNIVERSITY, HE ALSO DID
UNDERGRADUATE TRAINING IN WU'S
LAB AND HE IS CURRENTLY IN THE
LAB OF DR. ISHMAIL DUS-SABOOR.
HELLO I'M JUSTIN
BERG, Ph.D. CANDIDATE FROM THE
LAB AT COLUMBIA UNIVERSITY, I'M
OF COURSE NOT ISHMAIL, HE WISHES
HE COULD BE HERE TODAY BUT
INFORTUNATELY HE IS INCREDIBLY
SICK.
TODAY I WILL GIVE A TALK ON THE
ACUTE DIMENSION OF PAIN.
SPECIFICALLY ABOUT OUR LAB'S
WORK TO AUTOMATE BOTH THE
ANALYSIS AND STIMULUS FOR EVOKED
MECHANICAL PAIN ASSAYS.
NOW LET'S START WITH THE SIMPLE
QUESTION OF HOW DO YOU KNOW IF A
HUMAN OR MAY MOUSE IS IN PAIN.
WELL, FOR HUMANS WE HAVE A LOT
OF DIFFERENT TOOLS, WITH THE
MOST FEMALE ANDSOUS 1 BEING THE
SELF-REPORT ASSAY OF 0 TO 10
PAIN SCALE WHICH CAN BE DONE FOR
BOTH MAX, MEDIAL, MODERATE PAIN
OR WHATEVER YOU'RE LOOKING FOR
IN A PARTICULAR QUESTIONNAIRE.
IT'S INCREDIBLY USEFUL
ESPECIALLY SINCE A PATIENT'S
FEELING OF PAIN IS PROBABLY
WHAT'S MOST IMPORTANT TO THEM
BUT UNFORT HATELY THIS REALLY
DOESN'T--ISN'T FEASIBLE IN MICE,
YOU CAN'T ASK THEM WHAT THEIR
PAIN RATING IS SO WHAT WE
INSTEAD RELY UPON IS BEHAVIOR.
SO LET'S ZOOM IN ON A SPECIFIC
TYPE OF PAIN BEHAVIOR AND THAT'S
ACUTE MECHANICAL PAIN.
NOW, 1 OF THE MOST COMMONLY USED
ASSAYS FOR MEASURING ACUTE
MECHANICAL TOUCH AND PAIN IS THE
[INDISCERNIBLE] ASSAY, WHERE WE
TAKE A FILAMENT, AND APPLY IT TO
THE MOUSE'S PAW.
WE THEN MEASURE DID THE MOUSE
RESPOND TO THIS FILAMENT OR NOT
AND LOOK AT IT AND MEASURE IT IN
TERMS OF WITHDRAWAL RESPONSE
PERCENTAGE.
NOW, YOU CAN DO THIS IN MANY
DIFFERENT WAYS, WITH MANY
DIFFERENT VARIATIONS OF THESE
FIBERS AND WHAT YOU WILL FIND IS
BOTH THAT ACROSS DIFFERENT LABS
YOU WILL GET MASSIVELY VARYING
WITHDRAWAL PERCENTAGES FOR THIS
EXACT SAME FIBER, AND ALSO GET
VERY DIFFERENT INTERPRETATIONS
OF THE THIS DATA WITH SOME
ARGUING THIS IS A PAIN ASSAY,
AND SOME ARGUING THAT SOME
FILAMENTS ARE TOUCH RELATED,
SOME ARE INTERMEDIATE, SOME ARE
NOXIOUS AND SOME ARGUING THAT
THIS ONLY MEASURES MECHANICAL
TOUCH OR SENSITIVITY.
FEIGNALLY AS HAS BEEN KNOWN OVER
IN DETAIL DEAD, PAIN IS VERY
MULTIDIMENSIONAL AND THIS
PARTICULAR ASSAY ONLY LOOKS AT
PAIN IN THAT SING WILL DIMENSION
OF WITHDRAWAL PERCENTAGE.
SO HOW CAN WE DO BETTER IN MY
LAB'S ANSWER COMES IN THE FORM
OF VIDEOGRAPHY, THEY'RE
RESPONDING TO THE PIN PRICKING
INTO THE PAW AND HOW THAT
STIMULATES THEM.
LET'S TART ABOUT 60 SPS, ABOUT
WHAT YOU COULD SEE WITH THE
NAKED EYE. .
YOU CAN CLEARLY SEE THAT IT'S
MARKED BY THE STIMULUS AND
BEYOND THAT YOU CAPTAIN SEE MUCH
MORE.
NOW LET'S SLOW IT DOWN.
AT 2000 FRAMES PER SECTION, YOU
CAN MEASURE THE MAX HEIGHT THE
MOUSE WENT TO AS WELL AS SEE
THAT THE MOUSE GUARDED WITH ITS
PAW AND SHOOK IT AROUND BOTH
ASPECTS THAT INDICATE BOTH THE
MOUSE WAS TRYING TO ALLEVIATE
PAIN BUT ALSO TRYING TO PROTECT
ITS PAW FROM FURTHER
STIMULATION.
SO WE TOOK THESE HIGH SPEED
VIDEOS AND WITHIN THEM WE
MEASURED ASPECTS OF THE PAW
MOVEMENT, WHETHER THE MOUSE
GUARDED WITH OUR PAW, WHETHER
THEY SHOOK THE PAW, WHETHER THEY
GRIMACED, AND WHETHER THEY
JUMPED WITH THEIR WHOLE BODY.
WE THEN MEASURED THESE
INDIVIDUAL FEATURES MANUALLY AND
COMBINED THEM INTO A PAIN SCALE
WHICH RATED THE MOUSES REACTION
ON A SCALE FROM MOST TOUCH LIKE
TO MOST PAIN LIKE.
THIS WAS OUR INITIAL WORK WITH
HIGH SPEED VIDEOGRAPHY, BUT IT
ISN'T WHERE WE FINISHED OUR
DEVELOPMENT OF THIS TECHNIQUE.
THE NEXT STEP IN DEVELOPING IS
AUTOMATING THE ANALYSIS OF THESE
STIMULI.
SO WE USED SOFTWARE, FIRST
PROANALYSTS AND NOW SOFTWARE
CALLED SLEEP TO TRACK THE MOTION
OF THE MOUSES PAW IN RESPONSE TO
A STIMULI.
THIS GAVE US INCREDIBLY DETAILED
INFORMATION ABOUT HOW THE MOUSE
WAS RESPONDING AND ALLOWED US TO
DO FAR MORE IN TERMS OF ANALYSIS
THAN WAS EVER POSSIBLE WITH
MANUAL ANALYSIS.
LET'S START WITH JUST LOOKING AT
THE TRAJECTORY OF THESE
RESPONSES.
HERE YOU CAN SEE RESPONSES TO
CONSWAB, DYNAMIC BRUSH, LIGHT
PIN PRICK, HEAVY PIN PRICK,
ACROSS A VARIETY OF MOUSE
PHENOTYPES, C56 BLACK J, 1 OF
THE MOST COMMON TO 1S SUCH AS
BALB CAND AY, NOW WHAT I WOULD
LIKE YOU TO FOCUS ON THOSE IS
HOW THERE ARE SIMILARITIES
ACROSS ALL THESE MOUSE LINES
WHEN YOU LOOK AT BRUSH BEHAVIOR,
YOU WILL SEE CROSS ALL OF THESE
RESPONSES A SORT OF HILL LIKE
PATTERN EMERGES, A SIMPLE
UPDOWN, WHEREAS WHEN YOU LOOK AT
THE LIGHT PIN PRICK AND HEAVY
PIN PRICK RESPONSES YOU SEE FAR
GREATER VARIETY AND FAR MORE
INTENSE REACS EVEN IN MANY CASES
SHOWING A SORT OF FIGURE THE 8
PATTERN.
SO, CLEARLY FROM JUST LOOKING AT
THESE TRAJECTORIES WE CAN SEE
VARIATION BUT HOW CAN WE BETTER
ANALYZE THIS TRACKING DATA.
OUR ANSWER TO THIS IS THE PAWS
SOFTWARE WE DEVELOPED IN-HOUSE,
WHAT THIS SOFTWARE DID IS IT
TAKES THAT TRACKING DATA THAT WE
HAVE AND IT PULLS OUT SPECIFIC
FEATURES SUCH AS THE MAX
HEIGHTH, THE PAW GOES TO, THE
MAX VELOCITY, THE MEMBER OF
TIMES IT SHAKES ITS PAW, THE
AMOUNT OF TIME IT SPENDS
GUARDING AND TOTAL DISTANCE
TRAVELED.
WE'VE GONE PRACTICES THAT SINGLE
DIMENSION OF DID THE MOUSE
WITHDRAW ITS PAW OR NOT, TO A
MULTIDIMENSIONAL LOOK AT THE
SINGLE SWRAWL RESPONSE WHICH CAN
GIVE US FAR MORE INFORMATION
THIS HAS ENDED UP WITH THE WORK
FLOW WHERE WE TAKE A LOOK AT THE
MOUSE'S RESPONSE TO A TIMULOUS
AT HIGH SPEED, TRACK IT WITH A
PROGRAM SUCH AS DLC OR SLEEP,
RUN THIS TRACKING DATA THROUGH
OUR PAWS ARK MALSIS SOFTWARE,
AND THEN IF WE WISH, WE CAN THEN
BRING IT DOWN AGAIN TO A SINGLE
PAIN SCALE TO RATE IT ON A
MEASURE PRACTICES MOST PAIN LIKE
TO LEAST PAIN LIKE.
THOUGH WE HAVE FOUND RECENTLY HA
KEEPING THESE FEATURES AS IS AND
LOOKINGA THE THIS BEHAVIOR IN A
MULTIDIMENSIONAL SENSE MIGHT BE
FAR MORE USEFUL FOR MANY PAIN
MODELS.
I WOULD LIKE TO PAUSE AT THIS
MOMENT TO RECOGNIZE THE WORK OF
JESSICA JONES AND WILL FOSTER
WHOSE HARD WORK WAS TRIEWMENTAL
-INSTRUMENTAL IN THE
DEVELOPMENT OF THIS TECHNIQUE.
ON ANOTHER NOTE, I WILL ALSO
LIKE TO RECOGNIZE THE WORK OF
ANDRE TUSSAINT IN OUR LAB WHO
APLOYED THIS TECHNIQUE ALSO TO
RATS FINDING THAT THE SAME
PRINCIPLES WERE EFFECTIVE IN
MEASURING PAIN IN RATS.
SO WHERE DO WE GO FROM HERE IN
WELL WE HAVE SEVERAL PRONL
ECTOMYOSINS THAT HAVE TAKEN THIS
TECHNIQUE AND MOVED FORWARD IN
OUR LAB WITH IT.
ONE OF THEM IS WORK THAT'S
FUNDED PIE THE NIH HEAL INITTIA
ITIVE AND IT'S LOOKING AT
GENETIC VARIATION IN PAIN.
GENETIC VARIATION IN PAIN IS OF
COURSE INCREDIBLY IMPORTANT TO
STUDY AS INCREASED SENSITIVITY
TO BASE LINE PAIN DUE TO GENETIC
FACTORS IN HUMANS, IS A LEADING
RISK FACTOR FOR THE DEVELOPMENT
OF CHRONIC PAIN AND POTENTIAL
FOR OPIOID MISUSE.
SO HOW CAN WE STUDY IT IN MICE
IN WELL, THE STRATEGY WE'VE USED
IS LOOKING AT AS YOU'VE SEEN
PREVIOUSLY IN THIS SLIDE SHOW,
MULTIPLE INBRED MOUSE LINE ANDS
LOOKING TO SEE, DO WE SEE ANY
VARIATION IN BASE LINE OR
ONGOING PAN BEHAVIOR.
IN THIS PARTICULAR CASE, WE HAVE
A MOUSE LINE CALLED SJL, THAT
SHOWS INCREASED PAIN BEHAVIOR IN
RESPONSE TO BOTH CONSWAB AND
HEAVY PIN PRICK, SO BOTH
HYPOALOE GENERATEDDIA, ACROSS
THE GRAPHS HERE, WE SEE
GUARDING, SHAKING AND GRIMACING
BUT ALSO WE SEE IT IN WHAT WE
ARGUE ARE MORE REFLEXIVE ASSPECS
SUCH AS THE MAX PAW HEIGHT ISSUE
THE PAW GOES TO IN RESPONSE TO
THESE STIMULI.
WE INTEND TO MOVE FORWARD WITH
THIS PROJECT BY LOOKING AT HOW
THESE MICE SIZE UP TO THE C57
MICE WHEN WE ELECTRIC AT HEIGHT
AND PAINITATESSAs WELL AS
LOOKING AT THE MECHANISMS THAT
MIGHT BE BEHIND THIS DIFFERENCE
IN BASE LINE PAIN AND ROOT
BEHAVIOR.
FROM HERE, I WILL LOOK AT HOW
OUR MODEL HAS FUNCTIONED WHEN WE
LOOK AT DIFFERENT TYPES OF
HEIGHTENED PAINITATES.
THIS WORK WAS CONDUCTED IN
PARTNERSHIP WITH THE CABRERA LAB
AND THE SMITH LAB.
SO WE'RE GOING TO BE LOOKING
TODAY AT 2 DIFFERENT PAIN
MODELS.
THE CORAGINAN MODEL WHICH IS
COMMONLY USED TO ELECTRIC AT
INFLAMMATION BASED PAIN IN THE
PAW WHERE YOU INJECT IT INTO THE
PAW AND THEN LOOK AT IT, ACROSS
THE 4 HOUR AND 24 HOUR TIME
POINT LOOKING AT HOW THE
INFLAMMATION PROMPTED BY THE
CARRAGEENAN MODEL.
THE SECOND MODEL IS WHERE WE
TAKE AN ENYEKS IN THE KNEE AND
PROMPTS SIMULATION THAT IS LIKE
OSTEOARTHRITIS IN THE MOUSE.
WHEN YOU LOOK AT THIS AT BASE
LINE AT THE DAY 3 AND 10 TIME
POINTS.
SO HOW DOES THIS LOOK WHEN WE
AMRI OUR HIGH SPEED IMANNUALING
MODEL TO THESE MICE.
SO LET'S START WITH THE
CARRAGEENAN MODEL.
WHAT WE FOUND WAS INTERESTING,
WHEN LOOKING AT SHAKING BEHAVIOR
AS SEEN IN FIGURE B, WE FOUND
ONLY ALOE DENNIA AT THE 4
HOURIME POINT WITH APPARENTLY
THAT ALOE DENNIA HAVING SUBSIDED
BY THE 24 HOUR TIME POINT AND NO
HYPER ALGEEZIA BY SHAKING.
ON THE OTHER HAND WHEN YOU LOOK
AT GUARDING, WE FOUND ALODENNIA
IS NOT AN THE 24 HOUR TIME POINT
BUT WE FOUND INCREASED GUARDING
FOR FOR PIN PRICK AT THE 24 HOUR
TIMELINE.
BY LOOKING AT THIS BEHAVIOR IN A
MULTIDIMENSIONAL WAY, WE'RE ABLE
TO DETECT INCREASED PAIN STATE
THAT WOULD NOT BE POSSIBLE TO
DETECT IF WE WERE ONLY LOOKING
AT IT USING TOUCH STIMULI OR IF
WE WERE ONLY MEASURING 1 OF
THESE ASPECTS OF PAIN.
NEXT FOR THE OSTEOARTHRITIS
MODEL WE FOUND NO HYPER ALGEEZIA
BUT WE FOUND ALODENNIA AT THE
DAY TIME POINT BY GUARDING.
ONCE AGAIN SHOWING THAT BY
KEEPING THESE FEATURES SEPARATED
AND NOT LOOKING AT IT IN A
MONODISCIPLINARY MENINGAL MEARP,
WE CAN DETECT FEATURES THAT WERE
NOT POSSIBLE BEFORE.
THIS COULDN'T BE REALLY
DETERMINED BY JUST LOOKING AT
WITHDRAWAL RESPONSE BUT INSTEAD
BY SLOWING THINGS DOWN AND
LOOKING AT THIS FEATURE OF
GUARDING.
SO LET'S ZOOM BACK OUT FOR THE
ORIGINAL ASSAYS THAT I SHOWED
YOU EARLIER BECAUSE WE TALKED
ABOUT IMLIMITTATIONS WITH THE
CURRENT WAYS OF ANALYZING THOSE
ARK SAYS ABOUT YOU WE DIDN'T
REALLY TALK ABOUT WHAT ARE SOME
OF THE MORE FUNDAMENTAL ISSUES
WITH HOW WE DO THESE ASSAYS IN
WELL, ON A LOGISTICAL LEVEL,
THEY REQUIRE AN INCREDIBLY
SKILLED INDIVIDUAL IN ORDER TO
APPLY THESE VON FREY HAIRS,
OFTEN IT IS SEEN AS SOMEONE WHO
IS NOT WELL TRAINED AND ABLE TO
GENERATE DATA UNTIL AFTER 3-6
MONTHS OF TREANING AND PRACTICE.
AND IT IS COMMON PRACTICE NOT TO
COMPARE THESE 2, AS 1 WAY THEY
WILL APPLY THIS IS DIFFERENT
THAN ANOTHER WAY A RESEARCHER
MAY.
AND I WOULD GO FARTHER TO ARGUE
THAT DATA FOR A SINGLE
RESEARCHER SHOULDN'T REALLY BE
COMPARED BETWEEN YEARS BECAUSE
YOU WILL EVOLVE IN HOW YOU
STIMULATE THESE MICE OVERTIME AS
IT PASSES.
IT OF COURSE REQUIRES AN ABLE
BODIED RESEARCHER WHICH LIMITS
ACCESSIBILITY TO THIS RESEARCH.
IT'S A WORKPLACE HAZARD BUT MOST
IMPORTANTLY FOR SOME OF SUBJECTS
THAT WE'RE TALKING ABOUT TODAY,
IT HAS INCONSISTENCIES WITH HOW
YOU DELIVER THE STIMULUS FROM
TRIAL TO TRIAL, CREATING ISSUES
FOR ANALYZING OUR DATA, BUT
ALSO, INTRODUCES THE PROBLEM OF
STRESS.
THE VERY PROBLEM FOR THE
RESEARCHER LOOMING OVER THE
MICE, THE BODY ODOR, THE PICTURE
OF THEM THERE LOOMING OVER THE
MICE WILL STRESS THEM OUT
MASSIVELY SO WE'RE DRIEWSING
THIS ADDITIONAL FACTOR WHEN WE
PERFORM THESE ARK SAYS THAT WE
ARE TRYING TO MEASURE AND THAT
COULD BE MESSING WITH OUR DATA.
SO HOW CAN WE IMPROVE UPON THIS
IN OUR LABS ANSWER THIS
QUESTION, IS THE AUTOMATED
REPRODUCIBLE MECHANO STIMULATOR
OTHERWISE KNOWN AS THE ARM.
THIS DEVICE IS USED TO APPLY A
CONSISTENT STIMULUS TO THE
MOUSE, SO WE CAN CHANGE IT EVERY
WAY WE WISH SO EVERY SINGLE
MOUSE WILL RECEIVE THE EXACT
SAME STIMULUS, IN THIS CASE, YOU
SLEEP APNEA AND OBESITYY IT
RECEIVING A COTTON SWAB.
THIS DEVICE ALLOWS FOR FAR MORE
ACCURATE STIMULATION OF THE
MICE.
ONE FACT ISSUE WITH TRADITIONAL
MA CHANICAL STIMULI THAT I
DIDN'T MENTION EARLIER IS THAT
OFTEN YOU NEED TO REPEAT
MEASURES WITH MECHANICAL STIMULI
BECAUSE YOU MISS THE PAW,
BECAUSE YOU HIT IT IN THE WRONG
SPOT, YOU GLANCE OFF IT AND HIT
THE BELLY.
ALL THESE FACTORS MEAN THAT THE
SECOND TIME YOU STIMULATE, WON'T
BE THE SAME AS THE FIRST TIME
YOU COULD HAVE STIMULATED IT.
SO FAR BETTER ACCURACY WILL LEAD
TO FAR BETTER RESULTS.
IN THIS CASE, OUR DATA HAS SHOWN
THERE'S A 92% INKRES IN ACRAZZY
WHEN USING THE ARM FOR ACTUALLY
STIMULATING THE TARGET YOU WISH
TO TARGET EMPLOY BUT WHAT CAN WE
SAY ABOUT THE STIMULUS ITSELF.
THEY'VE SAID QUITE A LOT ABOUT
DIFFERENT RESEARCHERS BUT HOW
DOES THAT ACTUALLY COMPARE WITH
THE ARM.
WELL, LET'S JUST TART WITH 1
RESEARCHER.
SO WE TOOK A FORCE GAUGE AND
HOOKED IT UP TO THE ARM AND
APPLY A 1 APPLYING VAN FREY HAIR
TO THE FIRST CAGE.
WHAT WE FOUND WAS THERE WAS SOME
INCONSISTENCY THAT APPEARED TO
BE BASED ON THE PACT THAT THE
FIRST CAGE HAS A MINIMUM
RESOLUTION OF 0.05-GRAM FORCE.
AND THE VARIATION WE SAW WITH
THE ARM STIMULUS APPEARED TO BE
MOSTLY RELATED TO THAT REZONING
AND SO THIS WAS A VERY GOOD
RESULT, BUT NOW LET'S TRY
APPLYING THAT SAME GRAIM FORCE
BY HUMAN HANDS.
WHAT WE FOUND WAS MASSIVELY MORE
VARIATION, EVEN WHEN THE
RESEARCHER WAS ATTEMPTING TO
LINE UP THE TIME FRAME EXACTLY
BETWEEN STIMULI, THEY WERE
UNABLE TO MATCH THE ACCURACY OF
THE ARM AS WELL AS THE VARIATION
IN WHAT FORCE THEY WERE ACTUALLY
APPLYING OVERTIME WAS EXTREME.
THIS WAS CONSISTENT WHEN LOOKING
AT 2-GRAM AND THEN 6-GRAM
VON FREY HAIRS WITH THE INCREASE
IN VARIATION AS WE INCREASED THE
FORCE BEING APPLIED, LEAKILY IN
PART BEING BOTH DUE TO THE
DIFFERENCES IN THESE VON FREY
HAIRS BUT ALSO BECAUSE THE
LIMITATION OF THIS TEST BEING
THE 0.05-GRAM FORCE RESOLUTION
NOT BEING AS MUCH OF A PROBLEM
ONCE WE MOVED ON TO 2 BRAHMA AND
6-GRAM.
AS CAN YOU SEE, THE ARM BECAME
MORE ACCURATE AS WE INCREASED
FORCE WHILE HUMANS BECAME LESS
ACCURATE.
SO WE'VE SHOWN THAT THE ARM IS
FAR MORE ACCURATE, BUT IS THERE
ANY WAY TO MEASURE NEW THINGS BY
USING THE ARM.
BY MESSING AROUND WITH THE ARM
AND CONNECTING IT UP WITH OUR
HIGH SPEED CAMERA, WE WERE ABLE
TO MEASURE AND WITHDRAWAL THE
STIMULUS FOR BOTH COTTON SWAB
AND PIN PRICK BEHAVIOR.
WE FOUND THAT USING THIS MEASURE
ALONE WE WERE ABLE TO SEPARATE
HOW MALE AND FEMALE MICE BETWEEN
A COTTON SWAB RESPONSE AND A PIN
PRICK RESPONSE ALLOWING FOR YET
ANOTHER BEHAVIOR THAT WE CAN ADD
TO OUR MULTIKIMENTIONAL VIEW OF
A WITHDRAWAL RESPONSE.
THIS THESE MEASURES ARE BEING
MADE MANUELLY BUT WE INCORPORATE
IT INTO OUR PAWS SOFTWARE.
MOVES FORWARD WE WANT TO ASK A
SIMPLE QUESTION, SO WE'VE
DECREASED VARIATION IN STIMULUS
BUT WHAT EFFECT HAS THAT HAD ON
VARIATION IN MOUSE PAIN
BEHAVIOR.
WE LOOKED AT LIGHT AND HEAVY PIN
PRICK BEHAVIOR ACROSS MALE AND
FEMALE MICE.
AND TREATING THESE 4 DPROWPS
EACH AS A DATA SET.
WE THEN PRESSURE, CALCULATED
SOMETHING CALLED CO EFFICIENT OF
VARIATION WHICH IS THE STANDARD
DEVIATION OF A DATA SET
NORMALIZED BY THE ME.
WHAT THAT MEANS IS WE CAN
COMPARE THE VARIATION IN A
SINGLE DATA SET ACROSS SAY,
MANUAL VERSUS ARM DATA.
WHAT WOE FOUND WAS INTERESTING.
WE FOUND THAT CROSS MAX HEIGHT,
MAX WIDE VELOCITY AND DISTANCE
TRAVELED TREATING THEM AS A
GROUP, A HIGHLY SIGNIFICANT
DECREASE IN THE VARIATION IN
MOUSE PAIN BEHAVIOR WHEN LOOKING
ACROSS THESE DATA SETS.
AND LOOKING MASS TRAVELED
DISTANCE, WE FOUND DID YOU
CREASE IN VARIATION, THIS WAS
ABOUT 26%.
WHAT DOES THAT MEAN FOR RESEARCH
IN WELL THAT MEANS THAT EVEN IF
YOU ARE DOING IT IN A BLIND
MANNER, HAVE YOU NO CLUE WHICH
GROUPS OF MICE YOU'RE TESTING.
YOU WILL STILL INTRODUCE
VARIABILITY INTO YOUR DATA BY
HOW YOU'RE STIMULATING THESE
MICE THAT COULD LEAD TO YOU
ACCIDENTALLY SEEING A
SIGNIFICANT DIFFERENCE IN
BEHAVIOR, THAT ISN'T THERE OR
HIDING 1 THAT IS.
FINALLY, WE HAVE DONE SOME
INCREDIBLE WORK WITH THE HELP OF
SUMMER MENTEES LEAH AND NOAH
WHERE WE HAVE ALLOWED FOR THE
REMOTE CONTROL OF THE ARM, WHERE
A RESEARCHER CAN CONTROL THE ARM
FROM THE DESK, FROM ANOTHER
FLOOR IN THE BUILDING OR EVEN
CALIFORNIA.
THOUGH AT FESTER THIS MIGHT SEEM
LIKE SORT OF A STRENUOUS THING,
IT NOW MEANS THAT YOU NO LONGER
HAVE TO HAVE A RESEARCHER IN THE
ROOM.
WE CAN NOW ELIMINATE THE TRESES
INTRODUCED BY THAT RESEARCHER,
AND BETTER MEASURE THE ACTUAL
PAIN BEHAVIOR THAT WE WISH TO
MEASURE INCLUDING SAY, ASPECTS
OF THAT PAIN BEHAVIOR INCLUDING
THE STRESS CAUSED BY THAT PAIN
BUT NOT BY THE RESEARCHER.
SO TO SORT OF GIVE FINAL
REMARKS, WE FOUND THAT BY THE
DEVELOPMENT OF THIS DEVICE, WE
CAN ALLOW FOR THE FAR MORE
CONSIEVENT STIMULI AND THAT WE
CAN LOOK AT FURTHER DIMENSIONS
OF PAIN BEHAVIOR WHILE REDUCING
THE VARIABILITY IN THE PAIN
BEHOUSTON AND RICE FOOTBALLIAL
DATA WE ARE PRODUCING.
WE HOPE THAT THIS DEVICE CAN NOW
BE USED TO BETTER LOOK AT HOW
MOUSE PAIN BEHAVIOR CHANGES IN
DIFFERENT STATES WITHOUT THE
ISSUES THAT ARE BROUGHT ON BY
THE PREVIOUS METHODS OF
INVESTIGATING THIS BEHAVIOR.
I'D LIKE TO THANK AWE THE
MEMBERS OF THE SABCORRELATED
ORPAYS LAB, ESPECIALLY MEMBERS
OF THE ARM, PAWS AND SJL TEAMS
AND I DON'T KNOW, ARE WE DOING
QUESTIONS?
>> THANK YOU VERY MUCH JUSTIN,
WE'RE GOING TO DO A PANEL NOW,
SO PLEASE STAY ON AND THE OTHER
SPEAKERS CUM UP, DUNCAN, MARK
AND KATHLEEN, PLEASE.
>> ONCE AGAIN I WOULD LAKE TO
THANK ALL THE SPEAKERS FOR THIS
PARTICULAR--NCAN YOU STOP
SHARING YOUR SLIDES PLEASE YOUNG
MAN.
>> I WILL START OFF WITH A
QUESTION OR 2 AND THEN WE WILL
LIKE TO TAKE QUESTIONS FROM THE
CROWD ALSO SO PLEASE COME TO THE
MICROPHONES OR LINE UP AT THE
MICROPHONES.
ALL RIGHT, SO, START OFF WITH A
COMBINED QUESTION AND I'M
LOOKING FOR BOTH KATHLEEN AND
DUNCAN TO ANSWER THIS 1.
SO IN THE CONTEXT OF THE DOMAINS
OF PAIN AND INTERPRETING WHETHER
OR NOT THE ANIMALS BEHAVIOR IS
ANXIETY OR SOME OTHER DOMAIN IN
ITS REACTION, PSYCHOLOGICALLY TO
THE STIMULUS THAT THAT'S
PRESENTED HOW ARE THE OWNER OF
THE ANIMAL AND THE OWNER
ASSESSMENT TOOL, OR IN THE
ASSESSMENT TOOL WHERE WE'RE
LOOKING OBJECTIVELY IN THE VIDEO
NOW, JUSTIN YOU CAN CONTRIBUTE
TO THIS, HOW DO WE,A ASSESSES
WHETHER OR NOT THE ANIMALS
REALLY EXPERIENCING PAIN AND NOT
SOME OTHER PSYCHOLOGICAL
EXPERIENCE?
>> SO, JUST BY LOOKING AT THEM
ALONE IS PROBABLY NOT THE ONLY
METHOD.
WHAT WE OFTEN DO IN SAY A LAB
SETTING IS YOU WOULD THEN
CONFIRM IT BY GIVING THEM
SOMETHING THAT WOULD BE
ANALGESIC THAT WOULD REDUCE THE
PAIN ACUTELY AND SEE IF THAT
PAIN CHANGES.
THAT COULD BE SOMETHING AS
SIMPLE AS ICE, WHICH WOULD STOP
THE PAIN OR IT COULD BE A DRUG
LIKE AN NSAID OR MORPHINE OR AN
OPIOID, AND THEN I SUPPOSE, IT
GETS HARDER TO DETERMINE WHETHER
OR NOT IT'S ANXIETY OR
DEPRESSION BECAUSE YOU KNOW THE
ANTIDEPRESSANTS ALSO HAVE
EFFECTS ON PAIN.
SO THAT MAKE ITS A LITTLE BIT
HARDER BUT MY THOUGHTS ARE, YOU
HAVE--IT HAS TO BE KIND OF A
SINGLE MEASURE ISN'T GOING TO DO
IT USING MULTIPLE MEASURES AND
THINK BEING IT FROM MULTIPLE
PERSPECTIVES, ALL PUT TOGETHER
AND THEN SEEING AND LOOKING FOR
RESPONSE TREATMENTS IS PROBABLY
WHAT'S GOING TO TAKE IT.
IT'S LIKE ANYTHING WE DO EVEN IN
A PERSON, APART FROM ASKING THE
PAIN, WE HAVE TO PUT IT TOGETHER
IN A BIGGER PICTURE.
NYEAH, COMLITELY AGREE, I THINK
THE KEY THERE IS MULTIPLE
MEASURES WITH AND WITHOUT,
BEFORE AND AFTER TREATMENTS THAT
ARE REPORTED TO ALTER THOSE
STATES AND MULTIPLE MEASURES OF
THESE DIFFERENT STATES
ESSENTIALLY CREATE A THEN,
DIAGRAM OF CONFIDENCE OVERLAP
ABOUT WHAT YOU'RE ACTUALLY
MEASURING IN THAT PARTICULAR
INSTANCE.
NI GOET IT THAT MAKES A LOT OF
SENSE.
JUSTIN DO YOU WANT TO WEIGH IN
HERE IN.
>> SURE.
I COMPLETELY AGREE, WITH 1 OF
THE THINGS WE FOUND WITH
VALIDATING OUR DIFFERENT
TECHNIQUES FOR LOOKING AT PAIN
IN MICE, IS THAT WHEN WE LOOK AT
THESE DIFFERENT HEIGHTENED PAIN
STATES WE CAN SEE VERY DIFFERENT
CHANGES BASED ON HOW THE
INCREASED PAIN IS OCCURRING, AND
I BELIEVE IT WAS BROUGHT UP IN A
TALK EARLIER, THAT THERE CAN BE
ISSUES WITH HOW DO WE KNOW WE'RE
MEASURING PAIN VERSUS
DIFFERENCES IN MOBILITY OR
SOMETHING AND IN THAT WE HAVE
FOUND THAT LOOKING AT FEATURES
SUCH AS GUARDING AND SHAKING, WE
FIND FAR MORE CONSISTENT CHANGES
THAT CAN SORT OF BE LINKED TO
DIFFERENCES IN PAIN A LONE.
>> EXCELLENT.
THANKS.
WE ARE A QUESTION FROM THE
AUDIENCE?
>> MARK EPSTEIN, TOTAL
HOSPITALS IN THE CHARLOTTE NORTH
CAROLINA AREA EMPLOY I'M
FASCINATED BY THIS DISCUSSION
PARTICULARLY IN THE DOMAIN OF
CLINICAL DEPRESSION OR MAJOR
DEPRESSIVE DISORDER AND THESE
METRICSICATIONS YOU MENINGED THE
SSRIs WILL TREAT BOTH
APPROXIMATE SHOULD BE NO
SURPRISE, I GUESS BUT WHEN WE
SEE THESE OLDER DOG ANDS CATS IN
MY WORLD, CLINICALLY I CAN'T
HELP BUT HAVE THAT SUSPICION
THAT THE CO-MORBIDITY EXISTS SO
MY DUAL QUESTION WAS DPIFORT OF
ALL WHAT WAS THE MODEL THAT GOT
THOSE DRUGS TESTED AND LABELED
PRECLAINICALLY FOR DEPRESSION,
NUMBER 1, AND NUMBER 2 AND THE
BY O PSYCHOSOCIAL WORLD,
DR. HUTCHINSON, WHAT WOULD
THEORETICALLY BE A MODEL WE
COULD ESTABLISH THAT SAME TYPE
OF THING CLINICALLY IN DOGS AND
CATS OR ANY OTHER ANIMAL FOR
THAT MATTER.
NTHERE'S A COUPLE OF MODELS THAT
ARE USED FOR DEPRESSION AND
ANXIETY.
ONE IS THEY HANG A MOUSE FROM
ITS TAIL UPSIDE DOWN
UNTIL--MEASURE THE TIME IT TAKES
FOR HIM IT JUST STOP DOING THAT,
KIND OF A LEARNED HELPLESSNESS
AT ALL.
>> I DON'T LOVE THAT AT ALL.
>> OKAY, THE OTHER IS HAVING
THEM SWIM UNTIL HE DOESN'T WANT
TO SWIM ANYMORE FOR A FORCED
SWIM TEST THOSE ARE THE 2 MOST
COMMON 1S FOR DEPRESSION, YOU
CAN SEE HOW THEY ARE VERY MOTOR
DRIVEN TASKS AND IF YOU HAD
FATIGUE, YOU WOULD ALSO GET A
RESPONSE, THE ANXIETY 1S IS THEY
PUT THEM ON THESE MAZES AND PART
OF THE MAZE HAS CLOSED ARMS SO
THAT THEY FEEL COMFORTABLE
WALKING AROUND ON THE OUTSIDE
AND PART OF IT IS OPEN, SO IF
THEY'RE ANXIOUS THEY DON'T GO
OUT INTO THE PLACE WHERE THERE
ARE NO WALLS ON THE SIDE AND
MIGHT FALL OFF AND GO TO THE
GROUND, SO THEY HAVE THESE IN
SWEARS, IN CIRCLES, AND SO THEY
JUST MEASURE HOW MUCH TIME THEY
SPEND IN THESE ARMS.
AND THOSE ARE THE ANXIETY
MEASURES.
SO THEY'RE PRETTY BASIC AND SO
WHEN I SAY YES THEY'VE DONE THEM
AND THEY'VE IMPROVED THEM AND
THEN THEY MOVE THEM UP THE SCALE
AND GET THEM INTO HUMANS THOSE
ARE THE MEASURES WE USE SO THERE
ARE APPROXIMATIONS, JUST LIKE
OUR PAIN MEASURES ARE, IN
ANIMALS, BUT YOU COULD SEE HOW
IF YOU HAD PAIN OR YOU HAD
FATIGUE OR MOTEAR DEFINITE, YOU
ALSO MIGHT NOT DO THOSE TASKS.
SO, IT'S A GOOD QUESTION.
WHAT WAS THE SECOND PART OF YOUR
QUESTION.
>> SO WHAT WOULD BE
HYPOTHETICALLY A MODEL TO TEST
FOR DEPRESSIVE DISORDERS IN
HIGHER ORDER ANIMALS YOU MIGHT
SAY, DOGS, CATS, HORSES,
LIVESTOCK AND SO ON EMPLOY.
>> I'M GOING TO LEAVE THAT TO
YOU EMPLOY.
>> SO, YEAH.
IT'S 2 PARTS TO THIS.
WHEN I'VE SAT WITH INDIGENOUS
KNOWLEDGE HOLDERS IN AUSTRALIA
AND ASKED THIS QUESTION, THEY
ALWAYS COME BACK AND SAY, WHY DO
YOU COLONIALISTS LOVE NAMES
THINGS WHEN IT'S ALL THE SAME
THING.
AND SO WHAT THEY TALK TO IS WE
HAVE 1 DIMENSION HERE, 1
DIMENSION HERE AND WE ALWAYS
WANT TO PUT IT ON THAT SINGLE I
MENTION, WE'RE OPERATING IN THE
SPACE IN THE MIDDLE SO WE CALL
IT DEPRESSION, ANXIETY, PAIN,
THEY WOULD JUST OPERATE IN THIS
LITTLE SPACE OUT HERE, NOW
THAT'S NOT THAT HELPFUL FROM A
REGULATORY FRAMEWORK SAYING YOU
CAN HAVE THIS DRUG VERSUS THAT
DRUG, BUT I THINK IT'S HELPFUL
TO REALIZE THESE ARE COLONIAL
POST MODERNISM CONSTRUCTS THAT
WE HAVE CREATED AS NAMES, THAT
WE NEED TO UNSHACKLE OURSELVES
FROM WHEN WE TART TRYING TO
CONTEMPLATE THIS TRUE
INTERNATIONAL CLASSIFICATION
IMRAIGZ AND TRUE CONVERGENCE OF
KNOWLEDGE.
HOW DO WE THEN ARK ASSESSES THE
SINGLE DISCIPLINARY MENING IN
THE KALGT, WE'RE USING A 2
CHOICE LICK TEST OUT IN THE
FIELD WHERE WE HAVE A SWEET
TASTING LICK AND A LESS SWEET
TASTING LICK AND THE MORE TIME
THE RFID TAG ON THAT KALGT IS
WITH THE SWEET TASTING LICK, THE
GREATER HEDONIC PLEASURE WE KNOW
THE ANIMAL WILL THEN EXPERIENCE
AND THAT CHANGE IN 1 DIMENSION
HAS BEEN ASSOCIATE WIDE ANAHID
OWNIA AND HEDONIC LIKEITATE AND
DEPRESSIVE LIKEITATE ANDS THAT'S
AS GO AS IT GETS.
I THINK THE CONVERSATION AROUND
NOCIACCEPTION, THAN IT IS TO
UNDERSTAND WHAT PAIN IS BECAUSE
I THINK THE NOCICEPGZ WE MIGHT
END UP WITH MEASURES OF
NOCICEPTION, BUT THE LEVEL OF
PAIN WITH THE ALL THE PULT PEL
INPUT OF PAIN AND PLEASURES THAT
WE HAVE IN THAT SPACE BECOME
SUPER, SUPER COMPLICATED.
>> THANK YOU.
NI'LL JUST ADD VERY BRIEFLY,
MAYBE A QUICK QUESTION, ANY
BEHAVIORORRISTS OUT THERE, SEE
THAT'S WHAT WE NEED IN THE ROOM,
BECAUSE THE--YOU KNOW VARIOUS
COMPONENTS OF THE AFFECTIVEITATE
ARE BEING MEASURED IN, CERTAINLY
IN CATS AND DOGS, THEY'VE DONE A
LOT OF WORK IN CATTLE, OTHER
FOLK HAVE WORKED IN OTHER
SPECIES, SO, YOU KNOW THIS IS AN
IMPORTANT TO ADDRESS, THE
MEASUREMENT TECHNIQUES ARE BEING
DEVELOPED.
EVERYONE PUTS A LABEL ON THEM
AND THERE MAY BE A CROSS OVER
WITH OTHER DOMAINS THAT
INFLUENCING THE RESULTS BUT IT
IS AN IMPORTANT AREA FOR US TO
TALK ABOUT AS WE TRY AND
UNDERSTAND THE IMPACT OF PAIN
AND THE INFLUENCE ON PAIN OF
AREAS OF VARIOUS OTHER FACTORS.
THE NEXT QUESTION ON THE LEFT?
NREALLY EXCITING AND INTERESTING
STUFF.
FOR SOMEONE THAT'S NOT FAMILIAR
WITH ALL OF THIS RESEARCH, 1
THINK THIS THAT I'VE SEEN
THROUGH MANY OF THESE
PRESENTATIONS ARE ILLUSTRATIONS
OF DIFFERENT TIME SCALES AND
DIFFERENT PHYSICAL DIMENSIONS
AND HOW YOU CAN ABOUT MEASURING
OR QUANTIFYING THESE MEASURES OF
PAIN IN SOME WAY OR FORM.
SO MY QUESTION IS, MORE SORT OF
A--IS THE GENERALIZABILITY OF
THOSE WAYS THAT YOU ARE ARK
ASSESSING PAIN, GIVEN THE FACT
THAT WITHIN HUMANS THERE'S
ACTUALLY A VERY NARROW RANGE OF
THINGS LIKE MASS, VOLUME AND
SIZE, WHEREAS WITH ANIMALS WE
HAVE AN INCREDIBLY TREMENDOUS
RANGE AND SO MY QUESTION IS, IS
IT WITH ALL THESE THINGS WE'RE
DEPRIVATIONING, HOW CAN WE BE
ASSURED THAT THEY'RE GOING TO BE
GENERALIZABLE FOR ALL THESE
POTENTIAL SWAYINGS THAT THEY
COULD BE APPLIED.
>> GO AHEAD MARK?
>> SO, THAT SO THAT CONSTANT
ARRIVE OF TIME OR DISTANCE THAT
WILL USE AS A GLORIFIED FUDGE
FACTOR TO TRI TO WORK THROUGH
THOSE KALES OF ANATOMICAL SCALES
OF SYSTEMS IS AN EXTRAORDINARY
THING WE HAVE OVERLOOKED EMPLOY
BECAUSE IF I LOOK AT THE DORSAL
HORN OF A MOUSE, I HAVE ROUGHLY
A 2-3-MILLIMETER DISTANCE AND
DIFFUSION I NEED TO ARK CHIEF TO
GET LATERALIZATION OF THE CHEMO
TACTIC FACTORS OR SENSITIZING
FACTORS FROM 1 SIDE TO THE
OTHER.
IN A SHEEP, I'VE GOT A
CENTIMETER.
AND I'M DIFFUSING IN 3
DISCIPLINARY MENINGS SO THAT IS
PROFOUNDLY A MUCH MORE DIFFICULT
MOTION TO GET ACROSS THAT SAME
ANATOMICAL COMPARTMENT, LET
ALONE WHEN WE THEN START TALKING
[INDISCERNIBLE] SCENARIO.
SO I THINK WHERE WE ARE NOW
HEADING WITH OUR DIGITAL
TWINNING COMPONENT IS TO
ACTUALLY EXPLORE AS CLOSE AS WE
CAN FROM SMALL TO LARGER MODEL,
AND THEN ASKING WHAT THAT
CONSTANT ACTUALLY IS AND WHAT IT
ISN'T SO WE CAN ACTUALLY TART
CREATING THAT TRUE DIGITAL TWIN
OF THEORETICAL BIT BETWEEN,
BECAUSE I THINK IT'S GOING TO BE
THOSE BITS IN BETWEEN IN THAT
KINETIC AND THAT WILL CRACK OPEN
A HUGE RANGE OF REALLY EXCITING
DISCOVERIES, WHERE WE CAN THEN
START TO LOOK AT THAT FLOW,
SYSTEM AND JUST CASE IN POINT,
THE WORK BY JOHNNY KIPNIS, ON
THE GLYMPHATICS FOR EXAMPLE,
SUDDENLY OPENS UP DRAINAGE OF
THE CENTRAL NERVOUS SYSTEM, THAT
ARE INTERESTING AT A HUMAN LARGE
ANIMAL SCALE THEY ARE JUST
FASCINATING.
>> EXCELLENT QUESTION, THANK
YOU.
>> MIKE FROM NIH, I WOULD LIKE
TO SAY DR. HUTCHINSON, I GREATLY
APPRECIATE AND KATHLEEN AS WELL
AND DUNCAN, THE COMPLEXITY OF
PAIN YOU ARTICULATED BUT I'M
KIND OF A PERIPHERALLIST SO I
THINK IT CAN BE SIMPLIFIED AND
IT'S QUITE EVIDENT THAT IF YOU
SHUT OFF WHAT WE CALL THE
PERIPHERAL GEPERATOR, ALL OF THE
PAIN GOES AWAY INTAN TAINIOUSLY,
YES, YES, YES, YES.
ALL RIGHT, SO, AND THEY SAY I'M
PAIN FREE, I'M PAIN FREE, SO WE
RECEIPTLY TREATED SOMEONE WITH
30 YEARS OF PHANTOM LIMB PAN BY
ENYECTING THE L3, L4, L34 AND 5
LUMBAR GANGLIA AND WITH LIAISON
DO CAIN AND WITHIN SECONDS, THE
PAIN WAS GONE, SO HOW DO
YOU--EXCUSE ME, HOW DO YOU
EXPLAIN THAT?
AND I KNOW THAT EVERYTHING'S
STILL THERE, IN BRAIN, IT'S ALL
THERE, IT HASN'T BEEN SHUT OFF,
ALSO SO THERE'S NO AUTONOMOUS
GENERATOR FOR PAIN THAT'S
FLOATING AROUND, SOME ENGRAM, IN
YOUR CORTEX THAT SAYS, PAIN,
PAIN, PAIN, IT JUST SHUTS OFF.
>> SO I FUNDAMENTALLY DISAGREE
AND THE REASON IS THAT THE
CURRENT ISP OF DEFINITION OF
PAIN SAYS YOU DO NOT NEED TO
HAVE PRIMARY AFFERENT ACTIVATION
IN ORDER TO EXPERIENCE PAIN.
AND THE DIFFERENTIATION MAKE
HERE I WOULD MAKE IS PRIMARY
ACTIVATION IS NO SUSCEPTION
LEADING TO A PAINFUL EXPERIENCE.
THE EMOTIONAL TRIGGERS THAT THEN
ACTIVATE, LET'S NOT CALL AN
ENGRAM BUT BROADER CENTRAL
CENTERS THAT ARE ASSOCIATED WITH
THE PAIN EXPERIENCE, IS STILL
CLASSIFIED AS PAIN YOU SHOULD
THE ISP DEFINITION BECAUSE YOU
DON'T HAVE TO HAVE THE PRIMARY
ACTIVATION.
AND IN THAT SENSE, THIS IS AN
INCORRECT CONCEPTUALIZATION
BECAUSE IF YOU SHUT IT OFF, AND
THE PERSON TELLS YOU, I DON'T
FEEL PAIN, THEN, YOU KNOW, YOU
HAVE TO ACCEPT THEIR
EXPLANATION.
NSO MIKE, I AGREE WITH YOU IN
SOME INDIVIDUALS IF YOU GIVE
LIDOCAINE OR PERIPHERALS WHERE
YOU SHUT IT OFF RIGHT AWAY AND
THERE ARE A PORTION OF
INDIVIDUAL WHERE IS IT DOESN'T
AND EACH IF YOU LOOK AT THE
PHANTOM LIMB LITERATURE IT WILL
REDUCE PANE BY 50%.
FIFTY% OF IT STILL REMAINS AND
THE PHANTOM LIMB LITERATURE
MEANS PHANTOM LIMB PAIN IS
SEBTERAL.
IF YOU DO THE SAME TECHNOLOGY
TRANSFER IN ANOTHER CONDITION
LIKE OA AND YOU IMIF LIDOCAINE
IN GREAT PROPORTION THE PAIN
WILL GO AWAY AND SOME OF THEM IT
WILL NOT AND THERE WILL BE
LINGERING PAIN THAT DIDN'T GO
AWAY OR THERE WILL BE A
PROPORTION WHERE IT DIDN'T AND
THEY WILL SEE, OH THAT MEANS
PAIN'S ALL PERIPHERAL BUT THERE
ARE A UNIQUE POPULATION A FEW OF
THEM WHERE PAIN DOESN'T GO AWAY.
THE GREAT MAIORITY THERE IS A
PERIPHERAL GENERATOR I WOULD
AGREEN CELLS WITH YOU AND MOST
PEOPLE DO HAVE IT.
BUT THERE ARE A PROPORTION THAT
DON'T.
THERE'S ALSO THESE WHOLE SLEW OF
STUDIES WHICH I FIND FASCINATING
WHERE THEY INDUCE PERFECT PEOPLE
WITH NO PERIPHERAL ANYTHING, NO
PAIN AND THEY GIVE VERY
STRESSFUL EVENTS, THEY DO STRESS
MENTAL TRESES TESTS THEY MAKE
THEM DO MENTAL MATH FOR SOME
PEOPLE THAT'S STRESSFUL BUT FOR
SOME PEOPLE IT'S FUN AND BUT
THEY HAVE THEM DO THIS AND THEY
CAN INDUCE PAIN IN THESE PEOPLE
IN LUSK LO SKELETAL SYSTEM JUST
AS IF THEY WERE HAVING PAIN
OTHERWISE SO YOU KNOW YOU CAN
ADDRESS IT CAN THERE CAN BE SOME
INSTANCES IN WHICH IT IS, BUT I
AGREE THAT THERE--MOST OF THE
TIME THERE'S A PERIPHERAL
GENERATOR BUT THERE ARE
CONDITIONS WHERE THERE ISN'T AND
WE HAVE TO ACKNOWLEDGE WHAT
THOSE ARE AND DECIPHERING THEM.
WE ALSO KNOW THAT THE SAME TIME
WHEN YOU DO THOSE STRESS TESTS,
PEOPLE PUT EMGs INTO THE
MUSCLES AND THEY CAN GET
INCREASE PERIPHERAL ACTIVITY OF
THE MUSCLE AND INCREASED
TENDERNESS OF THE MUSCLE,
DESPITE THE FACT THAT IT WASN'T
THERE BEFORE.
SO THERE ARE WAYS YOU CAN DEDUCE
THEM, DO THEM THAT ARE
INDEPENDENT SO JUST UNKNOWING
THAT MEANS WE HAVE TO KEEP AN
OPEN MIND TO ALL POSSIBILITIES
N2 THINGS I'M PERFECTLY WILLING
TO ACCEPT THE BROADER DEFINITION
OF PAIN AS A SPOUSE BY ISP.
THE OTHER ASPECT IS THAT YES,
AND I'M ALSO WILLING TO EMBRACE
THE EXCEPTIONS THAT YOU IMAGINE,
BUT THERE ARE MANY--LIKE YOU
JUST SAID AND YOU DON'T HAVE TO
SAY IT, YOU SAID IT THAT THERE'S
MANY, MANY PAIN PROBLEMS THAT OF
LONG DURATION, THAT ARE
SUSCEPTIBLE TO PERIPHERAL INPUT,
AND I MIGHT ALSO ARGUE THAT THE
PEOPLE THAT DON'T RESPOND TO
LET'S SAY, AN INTERVENTION,
PROBABLY IT'S NOT THE PAIN
THAT'S THE PROBLEM, IT'S THE
ISHT VENTION THAT WAS A PROBLEM
AND IT WASN'T 100%.
SO IF YOU HAD A 100% EEIVETTIVE
INTERVENTION, PROBABLY MANY OF
YOUR XEPGS WOULD DISAPPEAR NWE
DO HAVE POST STROKE PAIN.
WE HAVE LESIONS IN THE BRAIN.
>> THAT'S 1 OF THE EXCEPTIONS
THAT I'M NOT GOING TO COMMENT ON
BECAUSE YOU KNOW, BUT EVEN THAT
CAN BE.
>> BUT THERE'S ALSO MS LESIONS
THAT LEAD TO PAIN NSPINAL CORD
PAIN NYEAH, THOSE ARE NOT
PERIPHERAL.
CLEARLY MICHAEL THOSE ARE NOT
PERIPHERAL GENERATORS.
SNZ AS LONG AS WE REALIZE THERE
ARE AREAS IN THE BRAIN WHERE CAN
YOU HAVE A LESION AND PATIENTS
HAVE PAIN.
>> RIGHT.
QUESTION TO DR. BERG, I GUESS,
WAS IT IN SO, QUITE A WHILE AGO
WE DID HIGH SPEED VIDEOGRAPHY IS
1 THING THAT STRUCK ME IS THAT
THE ANIMAL ORIENTS HIS HEAD IN
THE SAME TIME FRAME AS THE PAW
DRAW, SO I'M WONDERING IF YOU
CAN COMMENT ARE THEY DOING
THREAD ASSESS AM, A MEMORY
COMPONENT, EXACTLY WHAT OR WHY
DO THEY NEED TO EVOLVE THEIR
EYES IN THAT WHOLE NEED TO
WITHDRAW FROM PAIN RESPONSE?
>> SO THIS IS SOMETHING WE'VE
LOOKED AT A GREAT DEAL OVER THE
YORES WITH LOOKING AT BOTH THE
HEAD MOVEMENT AND THE WITHDRAWAL
RESPONSE, WE OFTEN FIEBD THAT
FOR SAY A PIN PRICK, YOU ARE
GOING TO SEE THE WITHDRAWAL
RESPONSE AND THEN A HEAD
RESPONSE WHEREAS WE SAY COTTON
SWAB, YOU WILL SEE OFTEN
THAT--HEAD RESPONSE FIRST AND
THEN THE MOUSE MITOCHONDRIAL
MOVE ITS PAW EMPLOY OUR
INTERPRETATION OF THIS BEHAVIOR
IS THAT MOUSE HAS NO CLUE WHAT'S
JUST HAPPENED.
IT FELT MANAGE ON ITS PAW AND
IT'S ORIENTS ITS HEAD TO TRY TO
FIGURE OUT HAS IT STEPPED ON
SOMETHING, HAS SOMETHING ABOUT
THE GROUND CHANGED AND SO
HONESTLY I DO THINK IT IS
INVESTIGATION.
AND THE FACT THAT IT WILL OCCUR
OFTEN FIRST BEFORE WITHDRAWAL,
AND TESTING STIMULUS, VERSUS
AFTER WITHDRAWAL AND A PAIN
STIMULUS WHERE THE PRIORITY IS
PROTECT THE PAW, GET IT OUT OF
THERE, PROTECT THE PAW AND
FIGURE OUT WHAT HAPPENED BACKS
UP THIS INTERPRETATION MY
THOUGHTS NRIGHT NOKAY, THANK
YOU.
NTHANKS EVERYBODY.
SO FOR THE FINAL QUESTION--IS
THERE ANOTHER 1?
>> PLEASE.
>> THANK YOU IT'S DORIS
AGAIN,IME STILL STRUGGLING A
LITTLE BIT WITH THE PAIN AND
STRESS SO TALKING ABOUT THE
LIMBIC SYSTEM THAT IS HAS AND
ALSO THINK BEING LIKE IF YOU CAN
AM FROM A DIFFERENT ACEROUSAL AT
THAT TIMEUS, THE REACTION MIGHT
BE FASTER, AND MIGHT EVEN MORE
ECK OUT, LIKE IN PRACTICE, LIKE
BEING A STRESSED VETERINARIAN
WITH A STRESSED TECHNICIAN, THEN
HAVE YOU A STRESSED ANIMAL AND
THEN IT MIGHT BE DIFFICULT TO
ARK ASSESSES PAIN, AND SO, I'M
COMING BACK TO QUALITY OF LIFE
THINKING ABOUT THE VIDEO THAT WE
SAW IN THE BEGENERATEDDING WITH
THE DOG WAS VERY IMPRESSIVE BUT
I WAS WONDERING WHAT HAPPENS THE
REST 23 HOURS AND 45 MINUTES.
IS THE DOG HAPPY IN KIND OF
DEPENDING ON THE BEHAVIOR?
AND KIND OF PART OF SECOND
QUESTION WHEN I REFER TO PEOPLE,
WHERE WE KNOW ABOUT THE
POLYVITAL THEORY WHERE THEY SAY
LIKE THEY GO TO THE FREEZE
RESPONSE WHEN LIKE LEARN TO
HELPLESSNESS, AND IF I LOOK AT
THE BEHAVIOR AND THE ANIMALS
DON'T EVEN ESCAPE ANYMORE FROM A
STRONG STIMULUS, SO WHERE'S THE
CUT OFF, WHERE I SAID LIKE, THIS
IS NOT A NORMAL PAIN REACTION
ANYMORE.
IT'S A KIND OF BEHAVIORIAL THING
THAT WE HAVE TO LEARN
HELPLESSNESS.
THANK YOU.
NKATHLEEN DO HAVE YOU THAT
QUESTION IN.
>> SO IF YOU WANT TO SUMMARIZE
THAT AS A QUESTION, I HEAR
THERE'S A LOT OF COMMENTS THERE.
EXACTLY WHAT'S THE QUESTION?
YOU WANT TO ADDRESS ANXIETY IN
THE CONTEXT OF PAIN, CAN YOU
REALLY SEPARATE THE 2 SOME.
>> YEAH, WHEN YOU APPROACH THE
PAIN, HOW DO YOU THINK ABOUT THE
AROUSAL STATUS OF THE ANIMAL
NTHE AROUSAL STATUS OF THE
ANIMAL NSO I THINK INDEED THE
STRESS CERTAINLY AFFECTS THE
PAIN CONDITION, RIGHT.
SO IN A HIGHLY STRESS ANIMAL
WHICH WE TRY TO AVOID, BUT IS
MUCH PROBABLY HARDER IN
VETERINARY PRACTICE THAN IT IS
IN OUR ANIMAL STUDIES AND I WILL
HIGHLY STRESSED ENVIRONMENT OUR
MODEL YES IT'S GOING TO AFFECT
YOUR PAIN.
HAVE YOU A VERY DIFFICULT TIME
SEPARATING THEM OR FIGURING THAT
OUT.
AND SO, I LOVE THE IDEA OF
SELF-REPORT BY USING CARE TAKERS
OR THE OWNERS OR WHOEVER THE
PEOPLE ARE, BECAUSE THEY
UNDERSTAND THAT.
IT'S THE SAME TAKE THAT 1 USES
FOR SOMEONE WHO'S COGNITIVELY
IMPAIRED, SOME CHILD BEHAVIOR IS
YOU ASK THE PARENTS OR
CAREGIVERS BECAUSE THEY HAVE A
BETTER IDEA OF WHAT THE BIGGER
PICTURE IS, THE OTHER 23 HOURS
OF THE DAY THAT THEY'RE NOT IN
YOUR OFFICE, RIGHT?
SO I LOVE THAT IDEA, AND HAVING
SOME MEASURES WRAPPED AROUND
THAT.
ONE OF THE REASONS I'VE LIKED
WHEN WE SAW THE CANINE BRIEF
PAIN INVENTORY IS THAT IT DOES
THAT.
IT ASKS ABOUT THE ANIMAL OUTSIDE
OF THE DAY-TO-DAY, WHERE THEY
ARE RIGHT THERE IN A WAY SO I
THINK YOU HAVE TO RELY ON SOME
OF THOSE OTHER MEASURES BECAUSE,
ACTUALLY GOING TO TO THE VET OR
ANYTHING TO SEE SOMEBODY IS
STRESSFUL FOR SOME ANIMALS AND
THEY DON'T LIKE IT.
THEY DON'T LIKE THE TRANSPORT IN
THE CAR, OTHERS LOVE IT, BUT YOU
HAVE TO SEPARATE IT AND MAYBE
THE WAY AROUND THAT IS TO LOOK
FOR THOSE OTHER SELF-REPORT
MEASURES CAN YOU USE.
>> BRIEFLY THE 1 DIMENSION WE'VE
HAVEN'T POKEN ABOUT IS PREDATOR
TO PREY SCENARIO, SO TAKEN--THEY
DIMENSIONALITY IN A PREDATOR
PRESENTS DIFFERENTLY TO THEM, IN
A PREY SPECIES SO I THINK THAT'S
A FASCINATING SPACE WHERE WE'RE
USING RODENTS TO EXPLAIN
MULTIPLE SPECIES BEHAVIORS
INCLUDING OURS AND YEAH, I DON'T
FREEZE AS MUCH AS I SHOULD BE
APPARENTLY.
SO IN YOUR MODEL WHERE YOU
STIMULATE THE ANIMAL WITHOUT A
USER IN THE ROOM AND LOOK AT THE
HIGH SPEED ANALYSIS AND ADD
SOMETHING LIKE FOX URINE IS THAT
SOMETHING YOUR GROUP AS LOOKED
AT IN.
>> SO WE HAVEN'T GONE AS FAR AS
FOX URINE YET BUT WE HAVE BEEN
INVESTIGATING WHAT IS THE EFFECT
OF EVEN THE PRESENCE OF A
RESEARCHER IN THE ROOM.
AND SOMETHING THAT'S INTERESTING
IS THIS AFFECT APPEARS TO BE
INCONSISTENT WITH--FOR SAY TOUCH
STIMULI IT CAN OFTEN LEAD TO THE
MOUSE BEING LESS REACTIVE
WHEREAS FOR PAIN STIMULI FOR
CERTAIN MICE, IT SEEMS TO CAUSE
THEM TO BE MORE REACTIVE, THIS
RESEARCH IS ONGOING SO I WON'T
SHARE TOO MANY SPECIFICS BUT
ANOTHER ASPECT THAT HAS COME UP
IS THAT AN ANXIETY MODEL ALONE
APPLIED TO A MOUSE APPEAR TOTION
CAUSE DIFFERENCES IN MECHANICAL
SENSITIVITY AND LOOKING AT THE
RESEARCH AS A WHOLE, LOOKING AT
STRESS AS A FACTOR IN PAIN, THE
RESEARCH HAS BEEN SOMEWHAT
INCONSISTENT WITH WHAT ITS FOUND
WITH WHETHER IT LEADS TO
INCREASES IN PANE BEHAVIOR OR
DECREASES BASED ON HOW YOU'RE
MEASURING THAT BEHAVIOR WHICH IS
SOMETHING THAT WE'VE ONLY FOUND
MORE SO WHEN WE LOOK AT HIGH
SPEED AND LOOK COMPARING THESE
DIFFERENT SCENARIOS.
EVEN LOOKING AT SOMETHING LIKE
SAY A DOG, I HAVE A DOG MYSELF,
AS WELL AS HAVE BEEN AROUND MANY
DOGS OVER THE YEARS INCLUDING
THOSE WHO HAVE BEEN IN PAIN AND
FOUND THAT 1 DOG WHO'S IN PAIN,
WILL START BITING PEOPLE WHEREAS
ANOTHER DOG WHO'S IN PAIN WILL
JUST BECOME FAR MORE WITHDRAWN.
AND I DON'T THINK WE SHOULD
EXPECT THAT EVEN WITH THE SAME
EXACT ASSAY, SAME EXACT
EXPERIMENTAL CONDITION IN ALL OF
THAT, THAT EVERY SINGLE ANIMAL,
EVEN OF THE SAME SPECIES IS
GOING TO SHOW THE EXACT SAME
RESPONSE TO THE PAIN AND SAME
INTERACTION BETWEEN THAT AND
ANXIETY.
>> GREAT POINT.
THANK YOU SO MUCH.
GO ARK HEAD KATHLEEN NSO THE
RPGHT THING I WANT YOU TO THINK
ABOUT AND MAYBE SOMEBODY CAN
COME UP WITH MEASURES FOR THIS,
BUT IN THE CHILDREN, PEDIATRIC
LITERATURE, IF A PARENT HAS HIGH
PAIN CATASTROPHIZING, IT
INFLUENCES THE CHILD AND
PRODUCES NEGATIVE OUTCOMES.
SO I IMAGINE IT WILL BE EXACTLY
THE SAME YOU HAVE TOUGH ON THAT
BECAUSE YOU NEED TO THINK ABOUT
MAYBE THE OTHER PEOPLE IN THE
PICTURE MAYBE NOT JUST THE
ANIMAL.
>> MAYBE A TEASE FOR A COUPLE
YEARS TIME, DR. MARGARET AND HER
TEAM ARE WORKING ON THAT AT THIS
MOMENT.
IN FACT I HAD A PROJECT MEETING
ON THAT TODAY.
>> VERY GOOD.
>> EXCELLENT.
SO I WANT TO THANK ALL THE
MEMBERRINGS OF THE PANEL, ALL
THE MEMBERS OF THE AUDIENCE,
PARTICIPATION, EXCELLENT
QUESTIONS AND AND PLEASE ENJOY
THE RECEPTION AND PARTAKE IN THE
POSTERS WHICH WILL BE FROM
4:45 P.M. UNTIL 7:00 P.M. THIS
EVENING.
THANK YOU.
[ APPLAUSE ]