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GOOD AFTERNOON.

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I'M DR. SHILPY DIXIT, PROGRAM

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DIRECTOR AT THE NATIONAL CENTER

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ON SLEEP DISORDERS RESEARCH, AND

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I WANT TO THANK YOU FOR JOINING

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US AT THE ANNUAL SLEEP

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101 SYMPOSIUM.

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THE SLEEP 101 SYMPOSIUM IS A

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JOINT EFFORT OF THE AMERICAN

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ACADEMY OF SLEEP MEDICINE.

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THE SLEEP RESEARCH SOCIETY, AND

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THE NATIONAL HEART, LUNG AND

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BLOOD INSTITUTE AT THE NATIONAL

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INSTITUTES OF HEALTH.

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THIS SYMPOSIUM IS DEDICATED TO

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HIGHLIGHTING THE LATEST ADVANCES

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AND EMERGING OPPORTUNITIES IN

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SLEEP AND SIR Q AND CIRCADIAN SS

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WELL AS FEDERAL RESEARCH FUNDING

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REPRESENTATIVES TO ENGAGE IN

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CUTTING EDGE RESEARCH AND

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INNOVATIVE APPLICATIONS.

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TODAY, WE WILL HEAR FROM EXPERTS

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ON CIRCADIAN BIOLOGY, CIRCADIAN

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MEDICINE, AND CHRONOMEDICINE,

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WHO WILL ADDRESS THE SIGNIFICANT

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GAP WITH IT BETWEEN ADVANCING --

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AND ITS CURRENT APPLICATION IN

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CLINICAL SETTINGS.

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ALTHOUGH RESEARCH HAS

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ILLUMINATED THE CRITICAL ROLE OF

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CIRCADIAN RHODE ISLAND  RHYTHMSD

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DISEASE, THIS KNOWLEDGE HAS YET

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TO BE FULLY HARNESSED TO ENHANCE

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PATIENT CARE AND PUBLIC HEALTH.

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ATTENDEES WILL GAIN VALUABLE

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INSIGHTS INTO HOW THESE

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ADVANCEMENTS ARE RESHAPING BOTH

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RESEARCH AND CLINICAL PRACTICE,

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OFFERING NEW AVENUES TO IMPROVE

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OUTCOMES THROUGH THE INTEGRATION

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OF CIRCADIAN PRINCIPLES.

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THIS WEBINAR AIMS TO BRIDGE THE

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GAP BETWEEN WHAT IS KNOWN AND

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WHAT CAN BE ACHIEVED BY

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EXPLORING THE LATEST RESEARCH IN

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IDENTIFYING NEW OPPORTUNITIES,

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AND ENCOURAGES RESEARCHERS AND

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CLINICIANS TO INCORPORATE

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CIRCADIAN PRINCIPLES INTO THEIR

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WORK TO OPTIMIZE HEALTH

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OUTCOMES.

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NOW BEFORE I INTRODUCE THE

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SPEAKERS, I'D LIKE TO REMIND YOU

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THAT YOUR AUDIO IS MUTED, AND

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YOUR VIDEO IS TURNED OFF TO

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MINIMIZE INTERRUPTIONS.

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WE ENCOURAGE YOU TO INCLUDE ANY

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QUESTIONS ON THIS TOPIC FOR ANY

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OF OUR PANELISTS IN THE Q &
A ON

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THE ZOOM PLATFORM.

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WE WILL HAVE DEVOTED Q & A

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DURING THE LAST HALF-HOUR OF THE

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SYMPOSIUM, AND LOOK FORWARD TO

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YOUR THOUGHTFUL QUESTIONS.

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NOW ALLOW ME TO INTRODUCE OUR

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SPEAKERS TODAY.

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DR. MATTHEW BUTLER IS AN

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ASSOCIATE PROFESSOR AT THE

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OREGON INSTITUTE OF OCCUPATIONAL

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HEALTH SCIENCES AND THE

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DEPARTMENT OF BEHAVIORAL

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NEUROSCIENCE AT OREGON HEALTH

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AND SCIENCE UNIVERSITY.

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HIS RESEARCH EXPLORES THE ROLE

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OF CIRCADIAN RHYTHMS IN HEALTH

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AND DISEASE.

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FOCUSING ON THE CUES THAT

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SYNCHRONIZE BIOLOGICAL CLOCKS

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AND THEIR RELEVANCE TO TREATMENT

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STRATEGIES.

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HIS WORK SPANS ANIMAL MODELS AND

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COLLABORATIVE HUMAN STUDIES,

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EMPHASIZING THE EFFECTS OF

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ENVIRONMENTAL, NUTRITIONAL, AND

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BEHAVIORAL CUES ON

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CARDIOMETABOLIC HEALTH.

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DR. SABRA ABBOTT IS ASSOCIATE

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PROFESSOR OF NEUROLOGY AT THE

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NOWRT WESNORTHWESTERN UNIVERSITG

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SCHOOL OF MEDICINE, PROGRAM

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DIRECTOR FOR THE SLEEP MEDICINE

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FELLOWSHIP AND DIRECTOR OF THE

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NORTHWESTERN CIRCADIAN MEDICINE

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CLINIC.

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HER RESEARCH AND CLINICAL

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INTERESTS FOCUS ON THE

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PATHOPHYSIOLOGY AND TREATMENT OF

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CIRCADIAN RHYTHM SLEEP-WAKE

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DISORDERS.

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DR. NOUR MAKAREM IS AN ASSISTANT

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PROFESSOR OF EPIDEMIOLOGY AT

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COLUMBIA UNIVERSITY'S SCHOOL OF

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PUBLIC HEALTH.

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HER RESEARCH FOCUSES ON THE

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CARDIOVASCULAR DISEASE

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PREVENTION AND PROMOTING HEALTH

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EQUITY.

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PARTICULARLY THE ROLE OF SLEEP

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AND CIRCADIAN HEALTH.

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SHE CONDUCTS POPULATION-BASED

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STUDIES AND CLINICAL TRIALS

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FUNDED BY THE NIH AND THE

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AMERICAN HEART ASSOCIATION AIMED

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AT IMPROVING CARDIOVASCULAR

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HEALTH THROUGH MULTILEVEL

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INTERVENTIONS.

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WE'LL KICK OFF OUR PRESENTATIONS

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WITH AN OVERVIEW ON CIRCADIAN

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BIOLOGY BY DR. BUTLER.

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>> OKAY.

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THANK YOU VERY MUCH FOR THAT

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INTRODUCTION.

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IT'S MY GREAT PLEASURE TO

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INTRODUCE THIS SYMPOSIUM WITH A

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BASIC BACKGROUND ON CIRCADIAN

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CLOCKS TO HELP US BASICALLY

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UNDERSTAND THE INTERACTION OF

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CLOCKS WITH HEALTH AND DISEASE

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AT A NUMBER OF DIFFERENT LEVELS.

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I DO NOT HAVE ANY CONFLICTS OF

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INTEREST TO DISCLOSE.

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AND IN TERMS OF LEARNING

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OBJECTIVES, THIS FIRST ONE IS

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THE MOST IMPORTANT.

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I WANT TO SORT OF GO OVER SOME

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OF THE FUNDAMENTAL PROPERTIES OF

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CLOCKS IN TERMS OF THEIR PERIOD

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AND PHASE, AND I'LL HIGHLIGHT

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THAT BECAUSE I THINK THAT SOME

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OF THE MAJOR FUTURE

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OPPORTUNITIES STILL REVOLVE

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AROUND THESE AND UNDERSTANDING

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HOW THESE WORK IN THE CONTEXT OF

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A NETWORK OF CLOCKS THAT ARE

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WORKING.

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I'LL BRIEFLY TALK ABOUT THE

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DIFFERENCE BETWEEN ENDOGENOUS

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RHYTHMS AND THOSE THAT ARE

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DRIVEN.

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DESCRIBE HOW CLOCKS ARE

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DISTRIBUTED THROUGHOUT THE BODY,

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NOT JUST IN THE BRAIN.

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I'LL TOUCH ON EATING TIME AS A

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REALLY IMPORTANT MODULATOR OF

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HEALTH.

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AND THEN FINALLY, I JUST WANT

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EVERYBODY TO HAVE AN

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APPRECIATION OF THE FACT THAT

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BIOLOGICAL RHYTHMS ARE REALLY

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DIVERSE.

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THEY ARE PHYLOGENETICALLY

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DIVERSE, PHYSIOLOGICALLY DIVERSE

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AND MOLECULARLY DIVERSE, LEADING

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TO, I THINK, A LOT OF

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COMPLICATION BUT A LOT OF

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INTEREST.

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SO I'LL START WITH THE

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PHYLOGENY.

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CLOCKS HAVE EVOLVED MULTIPLE

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TIMES, STRONGLY SUGGESTING THE

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CRITICAL ROLE IN FITNESS.

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WHAT'S INTERESTING ABOUT IT IS

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THAT DIFFERENT BRANCHES OF LIFE,

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HOWEVER, HAVE EVOLVED DIFFERENT

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CLOCK MECHANISMS.

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THE ONE THAT WE HAVE IN OUR

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BODIES IS BASED ON THE PER

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OSCILLATOR, AND IT'S CONSERVED

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BETWEEN INSECTS AND MAMMALS.

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WHEN WE TALK ABOUT RHYTHMS, THIS

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IS A NICE CARTOON TO GET US

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GOING.

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WE HAVE AN INDIVIDUAL WHO'S

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SLEEPING, HE WAKES UP, HE GOES

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TO WORK DURING THE DAY, HE GOES

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TO SLEEP AT NIGHT.

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AND IN THE BACKGROUND OF THIS,

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THERE ARE A WHOLE SET OF

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PHYSIOLOGICAL RHYTHMS THAT ARE

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ONGOING.

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THERE'S A RHYTHM OF GROWTH

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HORMONE THAT PEAKS WHEN THE

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PERSON IS ASLEEP.

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TEMPERATURE IS HIGH DURING THE

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DAY AND LOW DURING THE NIGHT.

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PLASMA CORTISOL PEAKS DURING THE

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WAKEUP TIME.

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AND WHAT'S IMPORTANT TO NOTE

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HERE IS THAT ALMOST ANYTHING YOU

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CAN MEASURE IN THE HUMAN BODY

202
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EXHIBITS SOME TYPE OF DAILY

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RHYTHM, BUT THEY DON'T ALL HAVE

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PEAKS AT THE SAME TIME.

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SO WE HAVE DIFFERENT RHYTHMS

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THAT HAVE DIFFERENT NAIZ PHASES,

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THEIR PEAK TIME, THAT ARE

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DISTRIBUTED ACROSS THE DAY.

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UNFORTUNATELY, THIS LITTLE

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CARTOON VERSION OF CIRCADIAN

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RHYTHMS IS PROBABLY NOT VERY

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WELL REPRESENTATIVE OF REALITY,

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AND OUR OWN EXPERIENCE IS MUCH

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MORE LIKE THIS.

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SO CLOCKS ARE DISRUPTED BY A

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MULTITUDE OF DIFFERENT

217
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ENVIRONMENTAL FACTORS.

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THEY CAN INCLUDE SHIFT WORK AND

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JET LAG, MORE RECENTLY WE'RE

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RECOGNIZING THE IMPORTANCE OF

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SOCIAL JET LAG, WHICH IS THE

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DIFFERENCE IN SLEEP TIME BETWEEN

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WEEKENDS AND WEEKDAYS, BUT

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NIGHTTIME EATING CAN DISRUPT

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CLOCK, EVENINGITE WHEN EVENING E

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ALL AT OUR SCREENS CAN

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PATHOLOGICALLY PUSH CLOCKS ONE

228
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WAY OR ANOTHER.

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AND CLOCK DISRUPTION IN SHIFT

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WORK HAVE BEEN ASSOCIATED WITH

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INCREASED RISK FOR A WHOLE HOST

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OF DIFFERENT CHRONIC CONDITIONS.

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THAT'S NOT AN EXHAUSTIVE LIST ON

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THE RIGHT, BUT OBESITY,

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DIABETES, HEART DISEASE, CANCER,

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INFERTILITY I INCLUDE HERE

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BECAUSE I'LL BE TOUCHING ON THAT

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IN A LITTLE BIT.

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SO CLOCKS ARE OFTEN MEASURED BY

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LOOKING AT SOMETHING THAT WE CAN

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OBJECTIVELY MEASURE IN THE

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LABORATORY.

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IN THIS PARTICULAR CASE, THIS

244
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DIAGRAM ON THE LEFT IS JUST

245
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SHOWING A SCHEMATIC OF A MOUSE'S

246
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ACTIVITY PATTERNS.

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SO THE MOUSE IS INACTIVE DURING

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THE DAY TIME BECAUSE IT'S

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NOCTURNAL, AND THIS BLACK BAR

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SHOWS THAT THE ANIMAL IS ACTIVE

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DURING THE NIGHT.

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AND IN A LIGHT-DARK CYCLE, THIS

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ANIMAL IS STRICTLY NOCTURNAL.

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IT ALWAYS BEGINS RUNNING AT THE

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SAME TIME EVERY DAY, IT STOPS

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RUNNING AT THE SAME TIME EVERY

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DAY, AND WE CALL THIS ENTRAINED

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00:08:24,506 --> 00:08:27,042
OR SYNCHRONIZED.

259
00:08:27,042 --> 00:08:27,709
TO DETERMINE WHETHER OR NOT THIS

260
00:08:27,709 --> 00:08:29,544
IS ACTUALLY A TRUE RHYTHM, WE

261
00:08:29,544 --> 00:08:32,814
RELEASE THE ANIMALS INTO

262
00:08:32,814 --> 00:08:33,548
CONSTANT CONDITIONS.

263
00:08:33,548 --> 00:08:35,217
SO IN CONSTANT DARKNESS, YOU CAN

264
00:08:35,217 --> 00:08:39,621
ACTUALLY SEE THIS RHYTHM REMAINS

265
00:08:39,621 --> 00:08:40,255
ROBUST.

266
00:08:40,255 --> 00:08:41,256
HOWEVER, IT'S NO LONGER

267
00:08:41,256 --> 00:08:42,524
SYNCHRONIZED TO THE LIGHT-DARK

268
00:08:42,524 --> 00:08:43,124
CYCLE.

269
00:08:43,124 --> 00:08:45,193
INSTEAD, THIS ANIMAL IS WAKING

270
00:08:45,193 --> 00:08:46,595
UP AND RUNNING IN HIS WHEEL

271
00:08:46,595 --> 00:08:47,495
ABOUT 30 MINUTES EARLIER EACH

272
00:08:47,495 --> 00:08:48,463
DAY.

273
00:08:48,463 --> 00:08:51,199
SO THIS IS A FREE-RUNNING

274
00:08:51,199 --> 00:08:51,433
RHYTHM.

275
00:08:51,433 --> 00:08:53,268
SO IT'S NOT SYNCHRONIZED TO

276
00:08:53,268 --> 00:08:53,535
ANYTHING.

277
00:08:53,535 --> 00:08:55,136
IT'S NOT EXACTLY 24 HOURS.

278
00:08:55,136 --> 00:08:57,105
THEY'RE USUALLY CLOSE TO BUT NOT

279
00:08:57,105 --> 00:08:59,407
EXACTLY 24.

280
00:08:59,407 --> 00:09:01,743
SO THE TWO FUNDAMENTAL FEATURES

281
00:09:01,743 --> 00:09:03,245
OF CLOCKS, THERE ARE A COUPLE OF

282
00:09:03,245 --> 00:09:04,713
OTHERS THAT ARE IMPORTANT, BUT

283
00:09:04,713 --> 00:09:06,281
FIRST IS THAT THEY ARE

284
00:09:06,281 --> 00:09:08,149
AUTONOMOUS, MEANING THAT THEY

285
00:09:08,149 --> 00:09:09,451
FREE-RUN IN CONSTANT CONDITIONS,

286
00:09:09,451 --> 00:09:11,319
AND WE CAN MEASURE THE PERIOD OF

287
00:09:11,319 --> 00:09:12,754
THAT RHYTHM.

288
00:09:12,754 --> 00:09:14,589
THE NEXT IS THAT THEY ARE

289
00:09:14,589 --> 00:09:16,591
ENTRAINABLE, THAT THEY

290
00:09:16,591 --> 00:09:17,325
SYNCHRONIZE TO PERIODIC CUES.

291
00:09:17,325 --> 00:09:18,760
IN THIS PARTICULAR CASE, THE CUE

292
00:09:18,760 --> 00:09:21,162
IS A LIGHT-DARK CYCLE, AND WE

293
00:09:21,162 --> 00:09:22,597
CAN DEFINE A PHASE OF THE

294
00:09:22,597 --> 00:09:23,698
RHYTHM, IN THIS CASE, THE PHASE

295
00:09:23,698 --> 00:09:25,700
COULD BE ACTIVITY ONSET WHEN WE

296
00:09:25,700 --> 00:09:27,736
SAY THE PHASE OF ACTIVITY ONSET

297
00:09:27,736 --> 00:09:30,005
IS AT THE LIGHT-DARK TRANSITION.

298
00:09:30,005 --> 00:09:31,773
SO AUTONOMOUS CLOCKS THAT ARE

299
00:09:31,773 --> 00:09:32,774
ENTRAINABLE, THIS IS THE KEY --

300
00:09:32,774 --> 00:09:35,944
THESE ARE THE KEY FEATURES OF

301
00:09:35,944 --> 00:09:40,215
ENDOGENOUS BIOLOGICAL CLOCKS

302
00:09:40,215 --> 00:09:41,283
SO I'VE MENTIONED BEFORE THAT

303
00:09:41,283 --> 00:09:42,050
ALMOST EVERYTHING YOU CAN

304
00:09:42,050 --> 00:09:44,052
MEASURE IS INDEED RHYTHMIC, BUT

305
00:09:44,052 --> 00:09:45,720
THERE ARE TONS OF RHYTHMS THAT

306
00:09:45,720 --> 00:09:50,025
ARE NOT ENDOGENOUS AND THAT ARE

307
00:09:50,025 --> 00:09:50,392
INSTEAD DRIVEN.

308
00:09:50,392 --> 00:09:52,127
THIS IS AN EXAMPLE OF AIR

309
00:09:52,127 --> 00:09:53,261
TRAFFIC, AND IT'S A LITTLE BIT

310
00:09:53,261 --> 00:09:54,963
DIFFICULT TO SEE, BUT THIS

311
00:09:54,963 --> 00:09:56,398
PORTION HERE THAT'S IN SHADOW IS

312
00:09:56,398 --> 00:09:57,165
THE NIGHTTIME.

313
00:09:57,165 --> 00:09:59,200
THIS IS THE DAY TIME OVER HERE.

314
00:09:59,200 --> 00:10:00,669
IF YOU LOOK AT EUROPE, THERE'S

315
00:10:00,669 --> 00:10:02,771
NOT A LOT OF YELLOW DOTS.

316
00:10:02,771 --> 00:10:03,505
THESE ARE ALL THE PLANES THAT

317
00:10:03,505 --> 00:10:04,205
ARE IN THE AIR.

318
00:10:04,205 --> 00:10:05,473
WHEN I START THE VIDEO, YOU'RE

319
00:10:05,473 --> 00:10:08,076
GOING TO SEE DAWN MOVING THIS

320
00:10:08,076 --> 00:10:08,643
DIRECTION, AND YOU'LL START

321
00:10:08,643 --> 00:10:10,378
SEEING A WHOLE BUNCH OF PLANES

322
00:10:10,378 --> 00:10:10,712
TAKE OFF.

323
00:10:10,712 --> 00:10:11,913
IN FACT, HERE YOU CAN ALREADY

324
00:10:11,913 --> 00:10:13,014
SEE THIS LINE OF PLANES THAT

325
00:10:13,014 --> 00:10:14,382
HAVE TAKEN OFF IN THE EVENING

326
00:10:14,382 --> 00:10:16,418
THAT ARE HEADED TOWARDS EUROPE.

327
00:10:16,418 --> 00:10:19,354
SO LET'S DO THIS.

328
00:10:19,354 --> 00:10:20,689
I NEED TO TAKE OFF THE LASER

329
00:10:20,689 --> 00:10:22,857
POINTER.

330
00:10:22,857 --> 00:10:25,360
SO YOU CAN SEE AS DAWN MOVES

331
00:10:25,360 --> 00:10:27,128
ACROSS, YOU CAN SEE A DRAMATIC

332
00:10:27,128 --> 00:10:28,396
CHANGE IN THE NUMBER OF PLANES

333
00:10:28,396 --> 00:10:29,965
THAT ARE FLYING.

334
00:10:29,965 --> 00:10:31,833
NOT VERY MANY DURING THE NIGHT,

335
00:10:31,833 --> 00:10:33,234
PLENTY DURING THE DAY.

336
00:10:33,234 --> 00:10:34,769
BUT A PLANE CLEARLY DOES NOT

337
00:10:34,769 --> 00:10:36,838
HAVE AN ENDOGENOUS CLOCK ON

338
00:10:36,838 --> 00:10:37,405
BOARD.

339
00:10:37,405 --> 00:10:39,474
THIS IS CLEARLY JUST A DRIVEN

340
00:10:39,474 --> 00:10:40,008
RHYTHM.

341
00:10:40,008 --> 00:10:42,777
THIS IS REFLECTING OUR OWN WANTS

342
00:10:42,777 --> 00:10:46,147
AND NEEDS, AND SO WE WOULDN'T

343
00:10:46,147 --> 00:10:47,782
CALL IT A BIOLOGICAL RHYTHM EVEN

344
00:10:47,782 --> 00:10:50,518
THOUGH IT'S AN IMPORTANT RHYTHM.

345
00:10:50,518 --> 00:10:53,688
IN TERMS OF ANIMALS, AND IN

346
00:10:53,688 --> 00:10:55,557
TERMS OF BIOLOGICAL RHYTHMS THAT

347
00:10:55,557 --> 00:10:58,393
WE CAN MEASURE IN THE

348
00:10:58,393 --> 00:10:59,060
LABORATORY, WE TALK ABOUT

349
00:10:59,060 --> 00:11:00,795
SOMETHING CALLED MASKING.

350
00:11:00,795 --> 00:11:02,464
SO IN THAT LAST ONE, THAT WAS

351
00:11:02,464 --> 00:11:05,100
SORT OF MASKING BY LIGHT ON THE

352
00:11:05,100 --> 00:11:06,267
FLIGHTS OF PLANES.

353
00:11:06,267 --> 00:11:08,269
WE CAN ALSO SEE THAT IN ANIMALS

354
00:11:08,269 --> 00:11:09,437
AS WELL.

355
00:11:09,437 --> 00:11:12,173
SO THIS IS A CRY 1 KNOCKOUT

356
00:11:12,173 --> 00:11:16,778
MOUSE, SO THE DASH DASH MEANS IT

357
00:11:16,778 --> 00:11:21,349
BEEN KNOCKED OUT, 1 AND 2.

358
00:11:21,349 --> 00:11:23,551
SO I HAVE THE BOTTOM PANELS

359
00:11:23,551 --> 00:11:24,586
COVERED UP, BUT IF YOU JUST LOOK

360
00:11:24,586 --> 00:11:25,854
AT THE TOP, YOU CAN SEE THAT

361
00:11:25,854 --> 00:11:28,823
THIS ANIMAL'S ACTIVITY, THESE

362
00:11:28,823 --> 00:11:30,358
LITTLE BLACK HASH MARKS ARE WHEN

363
00:11:30,358 --> 00:11:31,659
THE ANIMAL IS RUNNING IN THE

364
00:11:31,659 --> 00:11:33,194
WHEEL, YOU CAN SEE THEY ALL LOOK

365
00:11:33,194 --> 00:11:35,263
ROUGHLY SIMILAR WITH THE

366
00:11:35,263 --> 00:11:36,031
ACTIVITY RESTRICTED TO THE

367
00:11:36,031 --> 00:11:36,664
NIGHTTIME.

368
00:11:36,664 --> 00:11:38,400
SO THEY ALL LOOK ROBUSTLY

369
00:11:38,400 --> 00:11:39,801
RHYTHMIC.

370
00:11:39,801 --> 00:11:41,703
IF WE LOOK AT THE WILD TYPE

371
00:11:41,703 --> 00:11:43,138
MOUSE, THIS IS JUST A REGULAR

372
00:11:43,138 --> 00:11:44,773
OLD MOUSE, YOU CAN SEE THAT THIS

373
00:11:44,773 --> 00:11:46,508
RHYTHM REMAINS IN CONSTANT

374
00:11:46,508 --> 00:11:46,808
CONDITIONS.

375
00:11:46,808 --> 00:11:48,943
IT'S DRIFTING VERY SLIGHTLY TO

376
00:11:48,943 --> 00:11:51,446
THE LEFT, SO THE ANIMAL IS

377
00:11:51,446 --> 00:11:52,647
WAKING UP SLIGHTLY EARLIER EACH

378
00:11:52,647 --> 00:11:54,082
DAY, SO THE PERIOD IS SLIGHTLY

379
00:11:54,082 --> 00:11:56,818
LESS THAN 24 HOURS.

380
00:11:56,818 --> 00:12:00,755
THE KNOCKOUT OF THIS CLOCK GENE,

381
00:12:00,755 --> 00:12:03,024
SO IF YOU LOSE THE CRY 1 GENE,

382
00:12:03,024 --> 00:12:05,326
YOU ACTUALLY HAVE A FASTER

383
00:12:05,326 --> 00:12:06,428
CLOCK, MOVING MORE TO THE LEFT,

384
00:12:06,428 --> 00:12:08,063
AND THE CRY 2 KNOCKOUT HAS A

385
00:12:08,063 --> 00:12:09,097
SLOWER CLOCK SO IT'S MOVING MORE

386
00:12:09,097 --> 00:12:10,498
TO THE RIGHT, SO THIS PERIOD IS

387
00:12:10,498 --> 00:12:11,466
LONGER THAN 24 HOURS.

388
00:12:11,466 --> 00:12:12,634
THIS PERIOD IS LESS THAN 24

389
00:12:12,634 --> 00:12:14,102
HOURS.

390
00:12:14,102 --> 00:12:15,403
BUT THEY'RE STILL RHYTHMIC IN

391
00:12:15,403 --> 00:12:16,604
CONSTANT CONDITIONS.

392
00:12:16,604 --> 00:12:20,642
IN CONTRAST, THE CRY 1/CRY

393
00:12:20,642 --> 00:12:21,843
2 DOUBLE KNOCKOUT, SO IF YOU

394
00:12:21,843 --> 00:12:23,611
REMOVE BOTH COPIES OF THIS GENE,

395
00:12:23,611 --> 00:12:25,914
THE CLOCK IS COMPLETELY

396
00:12:25,914 --> 00:12:27,348
ABOLISHED, THIS ANIMAL IS

397
00:12:27,348 --> 00:12:28,850
COMPLETELY ARRHYTHMIC AND IT'S

398
00:12:28,850 --> 00:12:30,618
GONE FROM WHAT LOOKS LIKE A NICE

399
00:12:30,618 --> 00:12:31,686
RHYTHMIC BEHAVIOR IN A

400
00:12:31,686 --> 00:12:34,122
LIGHT-DARK CYCLE TO ONE THAT IS

401
00:12:34,122 --> 00:12:34,689
COMPLETELY ARRHYTHMIC.

402
00:12:34,689 --> 00:12:36,858
SO THIS IS AN EXAMPLE OF A

403
00:12:36,858 --> 00:12:37,959
MASKED RHYTHM, AND THIS IS

404
00:12:37,959 --> 00:12:39,260
IMPORTANT BECAUSE THERE ARE MANY

405
00:12:39,260 --> 00:12:41,329
TIMES WHERE WE'RE MEASURING

406
00:12:41,329 --> 00:12:46,468
SOMETHING THAT IS PERIODIC IN

407
00:12:46,468 --> 00:12:48,203
PHYSIOLOGY OR MOLECULAR

408
00:12:48,203 --> 00:12:49,537
EXPRESSION, IT MAY INDEED BE

409
00:12:49,537 --> 00:12:51,239
DRIVEN BY AN ENDOGENOUS CLOCK OR

410
00:12:51,239 --> 00:12:52,507
IT MAY BE DRIVEN BY SOMETHING

411
00:12:52,507 --> 00:12:53,575
ELSE.

412
00:12:53,575 --> 00:12:54,843
IN THIS PARTICULAR CASE, THIS IS

413
00:12:54,843 --> 00:12:55,777
PROBABLY DRIVEN BY THE

414
00:12:55,777 --> 00:12:56,211
LIGHT-DARK CYCLE.

415
00:12:56,211 --> 00:12:57,178
IT COULD BE SECONDARY TO

416
00:12:57,178 --> 00:12:58,813
SOMETHING ELSE, MOTIVATION TO

417
00:12:58,813 --> 00:12:59,848
RUN, MAYBE MOTIVATION TO EAT, ET

418
00:12:59,848 --> 00:13:01,015
CETERA.

419
00:13:01,015 --> 00:13:07,589
WE'RE NOT SURE.

420
00:13:07,589 --> 00:13:09,424
THEN JUST TO FORESHADOW, ARE

421
00:13:09,424 --> 00:13:10,625
THESE HEALTHY ANIMALS?

422
00:13:10,625 --> 00:13:11,860
I'LL COME BACK TO THAT, AND THE

423
00:13:11,860 --> 00:13:13,261
ANSWER IS PROBABLY NOT EXACTLY,

424
00:13:13,261 --> 00:13:14,796
EVEN THOUGH THEY SEEM TO HAVE

425
00:13:14,796 --> 00:13:16,664
INTACT CLOCKS AND SEEM TO

426
00:13:16,664 --> 00:13:20,935
SYNCHRONIZE PERFECTLY.

427
00:13:20,935 --> 00:13:23,004
SO WHERE DO RHYTHMS EMERGE FROM?

428
00:13:23,004 --> 00:13:24,739
WE HAVE A STRUCTURE IN THE BRAIN

429
00:13:24,739 --> 00:13:28,076
CALLED THE SUPRACHIASMATIC

430
00:13:28,076 --> 00:13:28,676
NUCLEUS.

431
00:13:28,676 --> 00:13:33,948
IT SITS RIGHT ABOVE THE CHIASM,

432
00:13:33,948 --> 00:13:35,150
THIS IS A STAJ TALL SECTION

433
00:13:35,150 --> 00:13:38,419
THR -- THESAGITTAL SECTION THROE

434
00:13:38,419 --> 00:13:39,053
BRAIN.

435
00:13:39,053 --> 00:13:41,890
THIS LITTLE AREA IS THE OPTIC

436
00:13:41,890 --> 00:13:43,825
CHIAS, WHERE THE OPTIC NERVE

437
00:13:43,825 --> 00:13:44,626
COMES INTO THE BRAIN AND BEFORE

438
00:13:44,626 --> 00:13:45,927
THEY'VE GONE UP TO THE VISUAL

439
00:13:45,927 --> 00:13:46,361
CENTERS.

440
00:13:46,361 --> 00:13:49,097
RIGHT ABOVE THAT CHIASM OUTLINED

441
00:13:49,097 --> 00:13:50,632
HERE IN WHITE IS A SMALL REGION

442
00:13:50,632 --> 00:13:55,003
THAT IS THE SUPRACHIASMATIC

443
00:13:55,003 --> 00:13:58,840
NUCLEUS AND THIS IS THE AREA

444
00:13:58,840 --> 00:13:59,574
THAT HOUSES THE ENDOGENOUS

445
00:13:59,574 --> 00:13:59,908
CLOCK.

446
00:13:59,908 --> 00:14:02,210
WE CAN TAKE IT OUT AND PUT IT IN

447
00:14:02,210 --> 00:14:04,078
A DISH, THANKFULLY THIS IS FROM

448
00:14:04,078 --> 00:14:07,782
A MOUSE, NOT A HUMAN, AND YOU

449
00:14:07,782 --> 00:14:09,751
CAN SEE ROBUST RHYTHM,

450
00:14:09,751 --> 00:14:12,153
EXPRESSION OF THE PERIOD 2 GENE,

451
00:14:12,153 --> 00:14:13,588
ANOTHER CORE CLOCK GENE, AND

452
00:14:13,588 --> 00:14:15,123
IT'S BEEN FUSED TO LUCIFERASE,

453
00:14:15,123 --> 00:14:17,625
WHICH IS SIMPLY THE ENZYME THAT

454
00:14:17,625 --> 00:14:18,760
MAKES LIGHT IN A FIREFLY.

455
00:14:18,760 --> 00:14:22,997
SO WE CAN WATCH THE ENDOGENOUS

456
00:14:22,997 --> 00:14:29,904
RIRHYTHMICITY EACH DAY.

457
00:14:29,904 --> 00:14:30,872
IT WORKS IN A DISH.

458
00:14:30,872 --> 00:14:35,243
ALSO IMPORTANTLY, IF WE LESION

459
00:14:35,243 --> 00:14:37,312
THE SCN, THIS ANIMAL IS A

460
00:14:37,312 --> 00:14:38,746
CHIPMUNK IN THIS PARTICULAR CASE

461
00:14:38,746 --> 00:14:39,847
THIS, IS DOUBLE PLOTTED SO IT'S

462
00:14:39,847 --> 00:14:42,150
ON A 48-HOUR TIME SCALE, JUST

463
00:14:42,150 --> 00:14:47,422
TOESE TOEASE THE VISUALIZATION.

464
00:14:47,422 --> 00:14:50,558
AS SOON AS THIS SCN HAN

465
00:14:50,558 --> 00:14:52,427
LESIONED, THE ANIMAL BECOMES

466
00:14:52,427 --> 00:14:54,696
ARRHYTHMIC, THERE'S NEVER ANY

467
00:14:54,696 --> 00:15:05,907
REKOREKOPF RREKORECOVERY OF RHY.

468
00:15:06,774 --> 00:15:09,177
IN THE BACKGROUND, THERE WAS

469
00:15:09,177 --> 00:15:10,845
THIS SORT OF AN ACKNOWLEDGMENT

470
00:15:10,845 --> 00:15:12,113
THAT THIS WAS NOT THE ENTIRE

471
00:15:12,113 --> 00:15:13,181
STORY.

472
00:15:13,181 --> 00:15:16,484
AND IT EMERGED REALLY FROM

473
00:15:16,484 --> 00:15:18,653
EATING BEHAVIOR, AND FOOD

474
00:15:18,653 --> 00:15:20,321
ANTICIPATORY ACTIVITY.

475
00:15:20,321 --> 00:15:22,056
SO FOOD ANTICIPATORY ACTIVITY IS

476
00:15:22,056 --> 00:15:23,224
WHAT YOU LOVE TO SEE WHEN YOU GO

477
00:15:23,224 --> 00:15:24,359
TO THE ZOO.

478
00:15:24,359 --> 00:15:25,560
RIGHT BEFORE FEEDING TIME, THE

479
00:15:25,560 --> 00:15:26,661
ANIMALS ARE RUNNING AROUND,

480
00:15:26,661 --> 00:15:28,930
THEY'RE ANTICIPATING THAT

481
00:15:28,930 --> 00:15:29,297
PERIODIC MEAL.

482
00:15:29,297 --> 00:15:30,932
WE CAN STUDY THAT IN THE LAB,

483
00:15:30,932 --> 00:15:32,567
AND IMPORTANTLY, IT CAN BE

484
00:15:32,567 --> 00:15:35,637
STUDIED IN ANIMALS THAT ARE

485
00:15:35,637 --> 00:15:36,204
ALREADY ARRHYTHMIC.

486
00:15:36,204 --> 00:15:40,575
SO THIS IS AN SCN LESIONED RAT.

487
00:15:40,575 --> 00:15:42,076
IF YOU LOOK AT JUST THIS TOP

488
00:15:42,076 --> 00:15:43,544
PORTION, THERE'S NO CONSOLIDATED

489
00:15:43,544 --> 00:15:43,945
ACTIVITY.

490
00:15:43,945 --> 00:15:46,247
THIS ANIMAL IS ARRHYTHMIC.

491
00:15:46,247 --> 00:15:48,883
BUT AS SOON AS FOOD IS

492
00:15:48,883 --> 00:15:50,518
PRESENTED, TWO HOURS PER DAY,

493
00:15:50,518 --> 00:15:53,788
AND THAT'S SHOWN HERE IN THESE

494
00:15:53,788 --> 00:15:55,223
HATCHED MARK, WE SEE THIS LARGE

495
00:15:55,223 --> 00:15:56,424
BOLUS OF ACTIVITY THAT PRECEDES

496
00:15:56,424 --> 00:15:56,891
IT.

497
00:15:56,891 --> 00:15:58,726
SO THIS IS THAT FOOD

498
00:15:58,726 --> 00:15:59,494
ANTICIPATORY ACTIVITY.

499
00:15:59,494 --> 00:16:01,362
WHAT'S VERY IMPRESSIVE, THOUGH,

500
00:16:01,362 --> 00:16:02,230
IS THAT WHEN THE FOOD IS

501
00:16:02,230 --> 00:16:04,198
PRESENTED ON A 23-HOUR SCHEDULE,

502
00:16:04,198 --> 00:16:06,034
IT'S NOT THE CASE THAT THEY CAN

503
00:16:06,034 --> 00:16:09,003
LEARN TO ANTICIPATE 23 HOURS.

504
00:16:09,003 --> 00:16:11,272
AND WHAT HAD BEEN CONSOLIDATED

505
00:16:11,272 --> 00:16:12,707
NOW BEGINS TO FREE-RUN, SO THIS

506
00:16:12,707 --> 00:16:14,676
IS ACTUALLY GOING BACK TO THAT

507
00:16:14,676 --> 00:16:15,576
FUNDAMENTAL PROPERTY OF CLOCKS.

508
00:16:15,576 --> 00:16:19,180
THIS IS A FREE-RUNNING RHYTHM

509
00:16:19,180 --> 00:16:21,149
THAT PERPETUATES EVEN THOUGH WE

510
00:16:21,149 --> 00:16:25,086
HAVE THIS POTENTIAL

511
00:16:25,086 --> 00:16:26,721
SYNCHRONIZING CUE THAT'S A

512
00:16:26,721 --> 00:16:29,557
LITTLE BIT TOO SHORT, IT LOOKS

513
00:16:29,557 --> 00:16:30,024
LIKE.

514
00:16:30,024 --> 00:16:31,759
ONCE THE FOOD SCHEDULE IS

515
00:16:31,759 --> 00:16:34,062
RESTORED TO 24 HOURS, THEN THE

516
00:16:34,062 --> 00:16:36,130
ANIMAL IS REENTRAINED TO IT AND

517
00:16:36,130 --> 00:16:36,497
RESYNCHRONIZED.

518
00:16:36,497 --> 00:16:37,865
SO THIS IS SHOWING US THAT EVEN

519
00:16:37,865 --> 00:16:39,834
IN THE ABSENCE OF AN SCN CLOCK

520
00:16:39,834 --> 00:16:41,803
IN THE BRAIN, THERE IS THE

521
00:16:41,803 --> 00:16:44,972
ABILITY FOR CLOCKS ELSEWHERE TO

522
00:16:44,972 --> 00:16:49,711
SUPPORT A CIRCADIAN RHYTHM.

523
00:16:49,711 --> 00:16:51,779
MOLECULARLY, THESE RHYTHMS ARE

524
00:16:51,779 --> 00:16:53,848
BASED ON A NETWORK OF GENES.

525
00:16:53,848 --> 00:16:56,684
THIS IS JUST THE VERY BAREST

526
00:16:56,684 --> 00:16:57,251
MINIMUM.

527
00:16:57,251 --> 00:17:01,723
WE HAVE TWO POSITIVE REGULATORS,

528
00:17:01,723 --> 00:17:02,290
BMAL1 AND CLOCK.

529
00:17:02,290 --> 00:17:03,925
THEY BIND TO E-BOXES THAT ARE IN

530
00:17:03,925 --> 00:17:05,426
THE DNA AND THEY DRIVE THE

531
00:17:05,426 --> 00:17:07,028
TRANSCRIPTION OF THE PER AND THE

532
00:17:07,028 --> 00:17:08,930
CRY GENES, SO THIS IS THAT

533
00:17:08,930 --> 00:17:10,898
CRYPTO CHROME FROM EARLIER, THIS

534
00:17:10,898 --> 00:17:12,100
IS THAT PERIOD GENE FROM

535
00:17:12,100 --> 00:17:12,567
EARLIER.

536
00:17:12,567 --> 00:17:14,302
THEY BECOME PROTEINS, THEY

537
00:17:14,302 --> 00:17:15,937
DIMERIZE AND THEY INHIBIT THEIR

538
00:17:15,937 --> 00:17:16,604
OWN TRANSCRIPTION.

539
00:17:16,604 --> 00:17:17,972
AND THIS LOOP TAKES ABOUT 24

540
00:17:17,972 --> 00:17:19,006
HOURS.

541
00:17:19,006 --> 00:17:20,341
THERE ARE A HOST OF OTHER

542
00:17:20,341 --> 00:17:22,210
MOLECULAR PLAYERS THAT I DON'T

543
00:17:22,210 --> 00:17:24,379
WANT TO GO INTO.

544
00:17:24,379 --> 00:17:26,781
WE ARE STARTING TO LEARN A LOT

545
00:17:26,781 --> 00:17:28,082
ABOUT HOW THOSE WORK

546
00:17:28,082 --> 00:17:29,517
BIOCHEMICALLY, BUT WE HAVE A LOT

547
00:17:29,517 --> 00:17:35,323
IN THE FUTURE TO FIGURE OUT.

548
00:17:35,323 --> 00:17:37,592
SO BECAUSE THOSE CLOCK GENES ARE

549
00:17:37,592 --> 00:17:38,860
OSCILLATING, WE CAN ACTUALLY

550
00:17:38,860 --> 00:17:40,595
LOOK AT ALL DIFFERENT TISSUES,

551
00:17:40,595 --> 00:17:42,330
AND WHEN WE DO THAT, WE ACTUALLY

552
00:17:42,330 --> 00:17:44,165
FIND THAT MOST TISSUES ACTUALLY

553
00:17:44,165 --> 00:17:45,600
HAVE FUNCTIONAL CLOCKS.

554
00:17:45,600 --> 00:17:49,670
HERE'S EXAMPLE OF THYROID GLAND,

555
00:17:49,670 --> 00:17:52,373
SKELETAL MUSCLE, ET CETERA.

556
00:17:52,373 --> 00:17:54,242
IN EACH CASE, WE CAN REMOVE THIS

557
00:17:54,242 --> 00:17:55,576
TISSUE, WE CAN PUT IT IN A DISH

558
00:17:55,576 --> 00:17:59,847
AND WE CAN SEE MULTIPLE CYCLES

559
00:17:59,847 --> 00:18:03,317
OF RHYTHMICITY AND THIS REMAINS

560
00:18:03,317 --> 00:18:04,852
CLOSE TO 24 HOURS EVEN IN THE

561
00:18:04,852 --> 00:18:05,052
DISH.

562
00:18:05,052 --> 00:18:06,487
THIS HAS LED NOW TO A MODEL

563
00:18:06,487 --> 00:18:08,790
WHERE WE HAVE AN SCN, WHICH IS

564
00:18:08,790 --> 00:18:11,826
STILL A MAIN COORDINATOR OF

565
00:18:11,826 --> 00:18:12,059
CLOCKS.

566
00:18:12,059 --> 00:18:14,462
IT'S STILL SENSITIVE TO LIGHT.

567
00:18:14,462 --> 00:18:16,998
BUT IT'S SPEAKING AND

568
00:18:16,998 --> 00:18:17,632
SYNCHRONIZING POTENTIALLY

569
00:18:17,632 --> 00:18:19,167
RHYTHMS OF CLOCKS IN MANY, MANY

570
00:18:19,167 --> 00:18:23,204
DIFFERENT TISSUES.

571
00:18:23,204 --> 00:18:23,871
IMPORTANTLY, THOUGH, NOT EVERY

572
00:18:23,871 --> 00:18:25,373
CLOCK IS SENSITIVE TO THE SAME

573
00:18:25,373 --> 00:18:27,275
CUES, AND EXERCISE MAY AFFECT

574
00:18:27,275 --> 00:18:28,609
THINGS, FEEDING MAY AFFECT

575
00:18:28,609 --> 00:18:30,244
THINGS, PATHOGENS, ET CETERA,

576
00:18:30,244 --> 00:18:31,312
TEMPERATURE IS A STRONG

577
00:18:31,312 --> 00:18:32,880
RESETTING CUE, AND DIFFERENT

578
00:18:32,880 --> 00:18:34,382
CLOCKS MAY BE SENSITIVE TO

579
00:18:34,382 --> 00:18:36,250
DIFFERENT CUES.

580
00:18:36,250 --> 00:18:37,952
HERE'S A BEAUTIFUL EXAMPLE OF

581
00:18:37,952 --> 00:18:38,519
THIS.

582
00:18:38,519 --> 00:18:39,754
THIS HAS LED TO A LOT OF

583
00:18:39,754 --> 00:18:41,956
INTEREST IN WHAT FOOD TIMING IS

584
00:18:41,956 --> 00:18:42,490
DOING.

585
00:18:42,490 --> 00:18:44,792
THESE WERE MICE THAT WERE SIMPLY

586
00:18:44,792 --> 00:18:45,626
FED EXCLUSIVELY DURING THE

587
00:18:45,626 --> 00:18:46,661
NIGHT, SO 12 HOURS OF FOOD IN

588
00:18:46,661 --> 00:18:48,396
THE NIGHT OR 12 HOURS OF FOOD

589
00:18:48,396 --> 00:18:49,730
DURING THE DAY.

590
00:18:49,730 --> 00:18:52,567
AND THESE PICTURES ARE OF THE

591
00:18:52,567 --> 00:18:54,335
BRAIN AT THE LEVEL OF SCN AND

592
00:18:54,335 --> 00:18:55,503
THESE LITTLE BLACK DOTS ARE THE

593
00:18:55,503 --> 00:18:56,838
EXPRESSION OF PERIOD 2, AND YOU

594
00:18:56,838 --> 00:18:58,139
CAN JUST SEE THAT BETWEEN THE

595
00:18:58,139 --> 00:19:00,875
TOP AND BOTTOM, THERE'S ONLY

596
00:19:00,875 --> 00:19:02,310
EXPRESSION HERE TOWARDS THE END

597
00:19:02,310 --> 00:19:05,246
OF THE LIGHT PHASE.

598
00:19:05,246 --> 00:19:06,681
BUT IF WE LOOK AT THE SAME GENE

599
00:19:06,681 --> 00:19:09,851
IN THE LIVER, NOW WE HAVE A

600
00:19:09,851 --> 00:19:11,185
12-HOUR PHASE SHIFT BASED ON

601
00:19:11,185 --> 00:19:12,019
THIS FEEDING.

602
00:19:12,019 --> 00:19:14,088
SO THERE'S HYPER 2 EXPRESSION IN

603
00:19:14,088 --> 00:19:15,656
THE NIGHT FED ANIMALS DURING THE

604
00:19:15,656 --> 00:19:17,925
NIGHT AND HIGH PER 2 EXPRESSION

605
00:19:17,925 --> 00:19:19,026
DURING THE DAY IN THE DAY-FED

606
00:19:19,026 --> 00:19:19,494
ANIMALS.

607
00:19:19,494 --> 00:19:20,895
SO THIS IS A CASE WHERE ONE

608
00:19:20,895 --> 00:19:25,399
CLOCK IN THE BODY IS INSENSITIVE

609
00:19:25,399 --> 00:19:27,401
TO THE FEEDING PHASE AND ONE IS

610
00:19:27,401 --> 00:19:28,569
SENSITIVE TO THE FEEDING PHASE,

611
00:19:28,569 --> 00:19:32,507
SO WE HAVE A MISALIGNMENT OR

612
00:19:32,507 --> 00:19:34,175
UNCOUPLING OF THE CLOCKS IN THE

613
00:19:34,175 --> 00:19:36,010
BODY INDUCED BY FOOD TIME.

614
00:19:36,010 --> 00:19:39,514
I'LL ALSO PRESENT THIS, I DON'T

615
00:19:39,514 --> 00:19:42,250
WANT TO GO INTO IT, BUT THESE

616
00:19:42,250 --> 00:19:43,551
CLOCKS, THESE CORE CLOCK GENES

617
00:19:43,551 --> 00:19:44,752
THAT ARE IN THE BODY IN THESE

618
00:19:44,752 --> 00:19:47,955
DIFFERENT TISSUES ARE ACTUALLY

619
00:19:47,955 --> 00:19:50,791
COORDINATING A VAST RHYTHMIC

620
00:19:50,791 --> 00:19:51,459
TRANSCRIPTOME.

621
00:19:51,459 --> 00:19:52,894
SO IF WE LOOK AT THE ENTIRE --

622
00:19:52,894 --> 00:19:54,629
SORT OF THE ENTIRE TRANSCRIPTOME

623
00:19:54,629 --> 00:19:55,730
AND LOOK AT ALL THE PROTEIN

624
00:19:55,730 --> 00:19:56,664
CODING GENES, THE ESTIMATE IS

625
00:19:56,664 --> 00:19:59,333
THAT UP TO 40% OF THOSE ARE

626
00:19:59,333 --> 00:20:00,434
RHYTHMICALLY EXPRESSED IN AT

627
00:20:00,434 --> 00:20:01,536
LEAST ONE TISSUE.

628
00:20:01,536 --> 00:20:03,704
IF WE LOOK SPECIFICALLY AT THE

629
00:20:03,704 --> 00:20:05,139
LIVER, 16% OF ALL THE PROTEIN

630
00:20:05,139 --> 00:20:06,774
CODING GENES ARE RHYTHMIC.

631
00:20:06,774 --> 00:20:09,443
LESS SO IN THE BRAIN, BUT I'LL

632
00:20:09,443 --> 00:20:12,446
POINT OUT THE BRAIN IS ALSO

633
00:20:12,446 --> 00:20:13,548
HIGHLY RETROGENIUS AND THERE

634
00:20:13,548 --> 00:20:14,849
COULD BE VERY DIFFERENT PATTERNS

635
00:20:14,849 --> 00:20:16,017
OF EXPRESSION, DEPENDING WHERE

636
00:20:16,017 --> 00:20:16,651
YOU ARE.

637
00:20:16,651 --> 00:20:21,355
THIS IS ALL WORK DONE BY THE

638
00:20:21,355 --> 00:20:22,323
HOGANICH LAB.

639
00:20:22,323 --> 00:20:23,190
VERY BEAUTIFUL.

640
00:20:23,190 --> 00:20:26,427
SO I WANT TO PIVOT TO JUST

641
00:20:26,427 --> 00:20:28,362
SHOWING A QUICK SNAPSHOT OF THE

642
00:20:28,362 --> 00:20:30,197
ONGOING WORK THAT'S IN MY

643
00:20:30,197 --> 00:20:30,498
LABORATORY.

644
00:20:30,498 --> 00:20:31,966
WE'RE INTERESTED IN PHYSIOLOGY

645
00:20:31,966 --> 00:20:34,168
AND HOW CLOCKS ARE RELATED TO

646
00:20:34,168 --> 00:20:36,337
THAT, AND SPECIFICALLY HOW FOOD

647
00:20:36,337 --> 00:20:38,105
TIMING AND LIGHT-DARK CYCLE

648
00:20:38,105 --> 00:20:39,640
TIMING ARE BEING INTEGRATED BUT

649
00:20:39,640 --> 00:20:43,144
THE ANIMAL, LEADING TO A HEALTH

650
00:20:43,144 --> 00:20:43,444
OUTCOME.

651
00:20:43,444 --> 00:20:44,545
WE'RE INTERESTED IN SHIFT WORK

652
00:20:44,545 --> 00:20:46,314
BECAUSE IT'S BEEN ASSOCIATED

653
00:20:46,314 --> 00:20:49,717
WITH A HOST OF DIFFERENT

654
00:20:49,717 --> 00:20:53,654
REPRODUCTIVE HEALTH

655
00:20:53,654 --> 00:20:55,189
DIFFICULTIES, REG MENSTRUAL

656
00:20:55,189 --> 00:20:57,058
CYCLES, LOW BIRTH WEIGHT,

657
00:20:57,058 --> 00:20:58,259
INFERTILITY, AND WE HAVE A LOT

658
00:20:58,259 --> 00:21:00,461
OF PEOPLE IN THIS COUNTRY ON

659
00:21:00,461 --> 00:21:01,429
NON-STANDARD WORK SHIFTS,

660
00:21:01,429 --> 00:21:02,430
ESPECIALLY IN THAT AGE GROUP

661
00:21:02,430 --> 00:21:03,931
THAT IS TRANSITIONING TO

662
00:21:03,931 --> 00:21:04,932
PARENTHOOD, THERE'S A HIGH

663
00:21:04,932 --> 00:21:07,134
PREVALENCE OF SHIFT WORK.

664
00:21:07,134 --> 00:21:08,235
OVERALL, U.S. INFERTILITY IS

665
00:21:08,235 --> 00:21:11,839
VERY HIGH, ESPECIALLY FOR FIRST

666
00:21:11,839 --> 00:21:12,740
BIRTHS, AND THERE'S INCREASING

667
00:21:12,740 --> 00:21:14,709
NEED FOR FERTILITY TREATMENTS IN

668
00:21:14,709 --> 00:21:18,613
NIGHT SHIFT WORKERS, AND A

669
00:21:18,613 --> 00:21:21,582
GRADUAL RECOGNITION THAT SHIFT

670
00:21:21,582 --> 00:21:24,218
WORK IS A DIFFICULT CHALLENGE

671
00:21:24,218 --> 00:21:25,620
FOR PEOPLE TRYING TO BECOME

672
00:21:25,620 --> 00:21:27,254
PREGNANT.

673
00:21:27,254 --> 00:21:28,456
ALSO IMPORTANTLY, I JUST SHOWED

674
00:21:28,456 --> 00:21:29,991
YOU THE VERY STRONG EFFECTS OF

675
00:21:29,991 --> 00:21:34,362
FOOD TIMING ON CLOCKS, AND SHIFT

676
00:21:34,362 --> 00:21:36,564
WORK IS A VERY POTENT EFFECTOR

677
00:21:36,564 --> 00:21:37,898
OF WHEN YOU EAT.

678
00:21:37,898 --> 00:21:39,734
SO WE WERE INTERESTED IN TRYING

679
00:21:39,734 --> 00:21:41,836
TO MODEL THIS.

680
00:21:41,836 --> 00:21:43,471
IN MY LABORATORY, WE STUDY

681
00:21:43,471 --> 00:21:45,539
PRIMARILY MICE, IN SORT OF THE

682
00:21:45,539 --> 00:21:48,175
BASIC PORTION OF THE LAB.

683
00:21:48,175 --> 00:21:49,343
AND WE'RE INTERESTED IN

684
00:21:49,343 --> 00:21:50,244
INDIVIDUALS AND THEIR RESPONSE

685
00:21:50,244 --> 00:21:51,846
TO FOOD TIMING, WE'RE INTERESTED

686
00:21:51,846 --> 00:21:53,214
IN HOW THEY INTERACT WITH EACH

687
00:21:53,214 --> 00:21:54,582
OTHER, WE'RE INTERESTED IN

688
00:21:54,582 --> 00:21:55,950
PREGNANCY HEALTH, AND FINALLY

689
00:21:55,950 --> 00:22:00,421
PREGNANCY SUCCESS.

690
00:22:00,421 --> 00:22:02,056
SO OUR FIRST EXPERIMENT, WE

691
00:22:02,056 --> 00:22:03,724
ACTUALLY JUST PAIRED ANIMALS, SO

692
00:22:03,724 --> 00:22:06,460
WE'VE HAD DARK-FED MALES AND

693
00:22:06,460 --> 00:22:09,196
DARK-FED FEMALES, WE PAIRED THEM

694
00:22:09,196 --> 00:22:10,731
TOGETHER, AND WE SIMPLY WATCHED

695
00:22:10,731 --> 00:22:12,033
THEM TO SEE WHEN THEY GAVE

696
00:22:12,033 --> 00:22:14,769
BIRTH.

697
00:22:14,769 --> 00:22:16,504
SO WE PAIRED THEM AT WEEK ZERO.

698
00:22:16,504 --> 00:22:18,639
MICE HAVE A GESTATION TIME OF

699
00:22:18,639 --> 00:22:19,807
THREE WEEKS SO YOU DON'T EXPECT

700
00:22:19,807 --> 00:22:21,575
ANY LITTERS UNTIL HERE, AND LO

701
00:22:21,575 --> 00:22:23,844
AND BEHOLD, AT WEEK FOUR, WE

702
00:22:23,844 --> 00:22:25,179
START SEEING LITTERS BORN TO

703
00:22:25,179 --> 00:22:25,946
BOTH GROUPS.

704
00:22:25,946 --> 00:22:27,248
HOWEVER, THE ANIMALS THAT ARE

705
00:22:27,248 --> 00:22:28,282
FED IN THEIR ACTIVE PHASE, SO

706
00:22:28,282 --> 00:22:29,350
THESE ARE THE ONES FED DURING

707
00:22:29,350 --> 00:22:31,419
THE DARK, BECAUSE THEY'RE

708
00:22:31,419 --> 00:22:33,254
NOCTURNAL, YOU CAN SEE THAT BY

709
00:22:33,254 --> 00:22:34,622
SIX WEEKS, HALF OF THEM HAVE

710
00:22:34,622 --> 00:22:37,692
GIVEN BIRTH, AND BY 13 WEEKS,

711
00:22:37,692 --> 00:22:39,160
ALL 100% OF THE PAIRS HAD GIVEN

712
00:22:39,160 --> 00:22:39,794
BIRTH.

713
00:22:39,794 --> 00:22:41,328
IN CONTRAST, THE ANIMALS THAT

714
00:22:41,328 --> 00:22:42,863
WERE FED DURING THE DAY TIME OR

715
00:22:42,863 --> 00:22:45,166
DURING THEIR LIGHT PHASE, THEY

716
00:22:45,166 --> 00:22:47,468
ARE SLOWER TO THEIR FIRST BIRTH,

717
00:22:47,468 --> 00:22:53,407
THEY DON'T HIT 50% UNTIL ABOUT Y

718
00:22:53,407 --> 00:22:56,143
PLATEAU AT 75%, SO 25% OF THESE

719
00:22:56,143 --> 00:22:57,545
MICE ARE SIMPLY NOT GIVING BIRTH

720
00:22:57,545 --> 00:22:59,280
AT ALL.

721
00:22:59,280 --> 00:23:00,948
THESE ARE OTHERWISE COMPLETELY

722
00:23:00,948 --> 00:23:02,149
HEALTHY MICE.

723
00:23:02,149 --> 00:23:03,918
THIS IS A VERY DRAMATIC EFFECT,

724
00:23:03,918 --> 00:23:08,589
AND IN FACT, IN SUBSEQUENT

725
00:23:08,589 --> 00:23:10,057
REPLICATIONS, WE KEEP SAYING THE

726
00:23:10,057 --> 00:23:12,326
SAME EFFECT AND, IN FACT, IT'S

727
00:23:12,326 --> 00:23:13,561
PROBABLY WORSE THAN THIS.

728
00:23:13,561 --> 00:23:15,629
IT'S ACTUALLY CAUSED A LOT OF

729
00:23:15,629 --> 00:23:17,164
PROBLEMS TO TRY AND GENERATE

730
00:23:17,164 --> 00:23:19,233
PUPS IF YOU'RE INTERESTED IN THE

731
00:23:19,233 --> 00:23:22,203
STUDY OF THE OFFSPRING.

732
00:23:22,203 --> 00:23:23,871
SO TO TRY AND UNDERSTAND THE

733
00:23:23,871 --> 00:23:25,272
BIOLOGICAL BASIS FOR WHY THIS

734
00:23:25,272 --> 00:23:28,008
INFERTILITY MIGHT BE OCCURRING,

735
00:23:28,008 --> 00:23:29,143
WE'VE GONE DOWN SEVERAL

736
00:23:29,143 --> 00:23:29,877
DIFFERENT AVENUES.

737
00:23:29,877 --> 00:23:30,878
I'M JUST GOING TO SHOW ONE,

738
00:23:30,878 --> 00:23:31,946
WHICH IS LOOKING AT THE TIMING

739
00:23:31,946 --> 00:23:33,814
OF OVULATION.

740
00:23:33,814 --> 00:23:35,583
CIRCADIAN RHYTHMS AND MATING

741
00:23:35,583 --> 00:23:37,551
BEHAVIOR HAVE A LONG HISTORY OF

742
00:23:37,551 --> 00:23:39,520
BEING TIED TOGETHER, PARTLY

743
00:23:39,520 --> 00:23:41,922
BECAUSE THE TRIGGER FOR

744
00:23:41,922 --> 00:23:44,325
OVULATION IN FEMALES IS THIS

745
00:23:44,325 --> 00:23:45,092
LUTEINIZING HORMONE SURGE.

746
00:23:45,092 --> 00:23:48,596
IT OCCURS EVERY FOUR DAYS IN A

747
00:23:48,596 --> 00:23:50,030
MOUSE ESTRUS CYCLE OR A RAT

748
00:23:50,030 --> 00:23:51,565
ESTRUS CYCLE, AND IMPORTANTLY,

749
00:23:51,565 --> 00:23:53,200
IT OCCURS AT THE SAME TIME OF

750
00:23:53,200 --> 00:23:53,501
DAY.

751
00:23:53,501 --> 00:23:55,936
IT VERY PREDICTABLE, AND OCCURS

752
00:23:55,936 --> 00:23:58,005
AT THE LIGHT TO DARK TRANSITION.

753
00:23:58,005 --> 00:24:00,541
AND SO WE CAN STUDY THE

754
00:24:00,541 --> 00:24:03,177
LUTEINIZING HORMONE SURGE TIMING

755
00:24:03,177 --> 00:24:04,445
IN OUR MICE TO TRY MCDADE A

756
00:24:04,445 --> 00:24:08,849
SAND GET ASENSE OF TIMING OF OVN

757
00:24:08,849 --> 00:24:10,284
MIGHT GET DISRUPTED BY THE FOOD

758
00:24:10,284 --> 00:24:10,518
TIMING.

759
00:24:10,518 --> 00:24:12,720
SO HERE WE HAVE A 24-HOUR CLOCK.

760
00:24:12,720 --> 00:24:14,054
NOON IS AT THE TOP.

761
00:24:14,054 --> 00:24:15,756
LIGHTS OFF IS AT 6:00 P.M.,

762
00:24:15,756 --> 00:24:18,192
LIGHTS ON IS AT 6:00 A.M., AND

763
00:24:18,192 --> 00:24:21,162
WE EXPECT ALL OF OUR LH SURGES

764
00:24:21,162 --> 00:24:23,030
TO OCCUR HERE IN THIS WINDOW.

765
00:24:23,030 --> 00:24:24,031
WE WERE BLEEDING EVERY TWO

766
00:24:24,031 --> 00:24:25,533
HOURS, SO YOU'LL SEE PEAKS EVERY

767
00:24:25,533 --> 00:24:29,170
TWO HOURS POTENTIALLY.

768
00:24:29,170 --> 00:24:31,272
SO FOR OUR CONTROLS, WE HAD TWO

769
00:24:31,272 --> 00:24:33,541
AT 6:00 P.M., WE HAD FOUR AT

770
00:24:33,541 --> 00:24:34,441
8:00 P.M., ABOUT WHEN YOU'D

771
00:24:34,441 --> 00:24:35,843
EXPECT THEM TO BE.

772
00:24:35,843 --> 00:24:37,611
FOR THE ANIMALS FED IN THEIR

773
00:24:37,611 --> 00:24:40,781
ACTIVE PHASE, WE FOUND ALL SIX

774
00:24:40,781 --> 00:24:44,385
OF THEM AT 8:00 P.M.

775
00:24:44,385 --> 00:24:45,419
THE ONES IN THE REST PHASE,

776
00:24:45,419 --> 00:24:46,487
HOWEVER, WERE DISTRIBUTED AROUND

777
00:24:46,487 --> 00:24:48,856
THE CLOCK.

778
00:24:48,856 --> 00:24:50,424
IN A VERY UNPREDICTABLE WAY.

779
00:24:50,424 --> 00:24:51,425
THEY'RE NOT HERE AS YOU WOULD

780
00:24:51,425 --> 00:24:51,859
EXPECT.

781
00:24:51,859 --> 00:24:54,495
THEY'RE ALSO NOT HERE, WHERE YOU

782
00:24:54,495 --> 00:24:57,331
MIGHT EXPECT IF IT WAS ENTRAINED

783
00:24:57,331 --> 00:24:59,333
BY THE FOOD TIMING.

784
00:24:59,333 --> 00:25:00,868
INSTEAD, THE LIGHT CYCLE TIMING

785
00:25:00,868 --> 00:25:03,037
AND THE FOOD CYCLE TIMING HAVE

786
00:25:03,037 --> 00:25:05,906
SOMEHOW HAD SOME KIND OF

787
00:25:05,906 --> 00:25:06,540
DESTRUCTIVE INTERFERENCE LEADING

788
00:25:06,540 --> 00:25:12,880
TO THIS DISORGANIZED PHYSIOLOGY.

789
00:25:12,880 --> 00:25:14,448
I ALSO WANT TO POINT OUT THAT

790
00:25:14,448 --> 00:25:16,851
IT'S NOT JUST TIMING OF CUES, SO

791
00:25:16,851 --> 00:25:19,820
REMEMBER, WE TALKED ABOUT

792
00:25:19,820 --> 00:25:21,255
PERIODICITY AND WE TALKED ABOUT

793
00:25:21,255 --> 00:25:22,656
SYNCHRONIZATION, AND THE PERIOD

794
00:25:22,656 --> 00:25:25,626
ALSO IS VERY IMPORTANT.

795
00:25:25,626 --> 00:25:27,928
SO I SAID I WAS FORESHADOWING

796
00:25:27,928 --> 00:25:30,331
FOR THESE CRYPTO CHROME

797
00:25:30,331 --> 00:25:31,432
KNOCKOUTS, THIS IS THIS SLIDE

798
00:25:31,432 --> 00:25:31,632
HERE.

799
00:25:31,632 --> 00:25:32,633
THIS WAS A VERY INTERESTING

800
00:25:32,633 --> 00:25:33,767
STUDY WHERE THEY WERE JUST

801
00:25:33,767 --> 00:25:34,835
LOOKING AT THE PREGNANCY RATE IN

802
00:25:34,835 --> 00:25:36,704
MIDDLE AGED TO OLDER MICE.

803
00:25:36,704 --> 00:25:38,239
YOU KNOW, 8 TO 12 MONTHS IS

804
00:25:38,239 --> 00:25:40,641
STARTING TO BE WHERE YOU EXPECT

805
00:25:40,641 --> 00:25:42,176
PREGNANCY RATES TO START TO GO

806
00:25:42,176 --> 00:25:44,378
DOWN.

807
00:25:44,378 --> 00:25:46,447
SO IF WE LOOK AT THE WILD TYPE

808
00:25:46,447 --> 00:25:47,882
MICE, 75% OF THESE ANIMALS ARE

809
00:25:47,882 --> 00:25:51,185
SUCCESSFULLY HAVING LITTERS.

810
00:25:51,185 --> 00:25:54,355
IN THE CRY 1 KNOCKOUTS AND THE

811
00:25:54,355 --> 00:25:55,456
CRYPTOCHROME 2 KNOCKOUTS,

812
00:25:55,456 --> 00:25:57,191
REMEMBER THIS HAD THE FASTER AND

813
00:25:57,191 --> 00:25:58,292
SLOWER CLOCK SPEED, YOU CAN SEE

814
00:25:58,292 --> 00:25:59,860
THAT THE SUCCESSFUL PREGNANCY

815
00:25:59,860 --> 00:26:00,928
RATE IS VERY LOW.

816
00:26:00,928 --> 00:26:03,130
IT'S DOWN AT ABOUT 10% NOW.

817
00:26:03,130 --> 00:26:05,432
SO THESE ANIMALS APPEAR TO HAVE

818
00:26:05,432 --> 00:26:08,168
MAYBE ADVANCED REPRODUCTIVE

819
00:26:08,168 --> 00:26:08,502
AGING.

820
00:26:08,502 --> 00:26:09,904
MAYBE THEY'VE ALREADY GONE

821
00:26:09,904 --> 00:26:13,941
THROUGH THEIR PRODUCTIVE PERIOD.

822
00:26:13,941 --> 00:26:19,880
HOWEVER, WHAT  THEY SIMPLY HOUSD

823
00:26:19,880 --> 00:26:21,515
THESE WILL ANIMALS IN A

824
00:26:21,515 --> 00:26:22,750
LIGHT-DARK CYCLE THAT MATCHED UP

825
00:26:22,750 --> 00:26:24,885
WITH THEIR ENDOGENOUS CLOCK

826
00:26:24,885 --> 00:26:25,252
SPEED.

827
00:26:25,252 --> 00:26:28,789
SO THE CRY 1 KNOCKOUTS WITH THE

828
00:26:28,789 --> 00:26:31,125
FASTER CLOCK, HE HOUSED THEM IN

829
00:26:31,125 --> 00:26:32,826
11 AND A QUARTER HOURS OF LIGHT,

830
00:26:32,826 --> 00:26:34,128
11 AND A QUARTER HOURS OF DARK.

831
00:26:34,128 --> 00:26:35,696
FOR THE CRY 2 ANIMALS, IT WAS A

832
00:26:35,696 --> 00:26:38,299
LONGER THAN 24-HOUR LIGHT-DARK

833
00:26:38,299 --> 00:26:40,501
CYCLE, AND HE RESCUED THE

834
00:26:40,501 --> 00:26:42,169
FERTILITY RATE IN THESE ANIMALS.

835
00:26:42,169 --> 00:26:44,338
THIS IS THIS IDEA OF CIRCADIAN

836
00:26:44,338 --> 00:26:46,073
RESONANCE, THAT THERE'S

837
00:26:46,073 --> 00:26:46,840
SOMETHING IMPORTANT ABOUT THE

838
00:26:46,840 --> 00:26:49,043
CIRCADIAN PERIOD OF THE CLOCK

839
00:26:49,043 --> 00:26:50,044
MATCHING THE DRIVING

840
00:26:50,044 --> 00:26:52,880
ENVIRONMENTAL CYCLE, LEADING TO

841
00:26:52,880 --> 00:26:55,282
OPTIMAL PHYSIOLOGY AND IN THIS

842
00:26:55,282 --> 00:26:57,184
PARTICULAR CASE, INCREASED

843
00:26:57,184 --> 00:27:03,190
FERTILITY.

844
00:27:03,190 --> 00:27:05,392
SO WHEN I THINK ABOUT THE GAPS

845
00:27:05,392 --> 00:27:06,794
IN OPPORTUNITIES AS THIS FIELD

846
00:27:06,794 --> 00:27:07,995
MOVES FORWARD, I REALLY THINK IT

847
00:27:07,995 --> 00:27:09,229
IS STILL ABOUT THE FUNDAMENTALS

848
00:27:09,229 --> 00:27:09,997
OF CLOCKS.

849
00:27:09,997 --> 00:27:11,598
IT'S ABOUT PHASE, IT'S ABOUT

850
00:27:11,598 --> 00:27:13,367
PERIOD, AND IT'S HOW THEY

851
00:27:13,367 --> 00:27:13,767
INTERACT.

852
00:27:13,767 --> 00:27:16,070
BUT INSTEAD OF SIMPLY DESCRIBING

853
00:27:16,070 --> 00:27:17,604
THESE, WE NEED TO REALLY

854
00:27:17,604 --> 00:27:20,140
UNDERSTAND THEIR MECHANISMS IN A

855
00:27:20,140 --> 00:27:22,109
DISTRIBUTED CLOCK NETWORK.

856
00:27:22,109 --> 00:27:25,713
THIS IS A NICE DIAGRAM FROM JEN

857
00:27:25,713 --> 00:27:26,914
MOHAWK FROM ABOUT 10 YEARS AGO

858
00:27:26,914 --> 00:27:30,884
NOW SHOWING SCN AS THIS TOP-DOWN

859
00:27:30,884 --> 00:27:31,418
COORDINATOR OF CLOCKS.

860
00:27:31,418 --> 00:27:33,487
WE CAN USE THE LIVER AS AN

861
00:27:33,487 --> 00:27:33,954
EXAMPLE.

862
00:27:33,954 --> 00:27:35,522
AND THERE ARE A LOT OF DIFFERENT

863
00:27:35,522 --> 00:27:37,124
WAYS THAT TIMING INFORMATION

864
00:27:37,124 --> 00:27:40,861
GETS TO THE LIVER.

865
00:27:40,861 --> 00:27:42,863
GLUCOCORTICOIDS, BODY

866
00:27:42,863 --> 00:27:43,497
TEMPERATURE, AUTONOMIC

867
00:27:43,497 --> 00:27:43,831
INNERVATION.

868
00:27:43,831 --> 00:27:46,900
FEEDING TIME IS ALSO BASICALLY

869
00:27:46,900 --> 00:27:47,935
ADDING TO THIS COMPLEXITY.

870
00:27:47,935 --> 00:27:49,803
THE LIGHT-DARK CYCLE IS

871
00:27:49,803 --> 00:27:50,904
IMPINGING ON BOTH BEHAVIORS AS

872
00:27:50,904 --> 00:27:53,407
WELL AS THE SCN DIRECTLY.

873
00:27:53,407 --> 00:27:54,842
WE HAVE A STRONG INTEREST THESE

874
00:27:54,842 --> 00:27:57,678
DAYS IN UNDERSTANDING MEDICATION

875
00:27:57,678 --> 00:27:58,012
TIMING.

876
00:27:58,012 --> 00:27:59,646
IS THAT AFFECTING THE CLOCK?

877
00:27:59,646 --> 00:28:03,050
DOES ITS EFFECT DEPEND ON THE

878
00:28:03,050 --> 00:28:04,051
PHASE OF THIS CLOCK?

879
00:28:04,051 --> 00:28:06,787
AND DOES ITS EFFECT DEPEND ONLY

880
00:28:06,787 --> 00:28:08,022
ON THE PHASE OF THIS CLOCK BUT

881
00:28:08,022 --> 00:28:09,656
ALSO ON THE PHASE OF THIS CLOCK?

882
00:28:09,656 --> 00:28:11,625
OR OTHER CLOCKS IN THE BODY?

883
00:28:11,625 --> 00:28:14,461
SO WE CAN TALK ABOUT CIRCADIAN

884
00:28:14,461 --> 00:28:14,795
MISALIGNMENT.

885
00:28:14,795 --> 00:28:16,797
WHAT DOES IT MEAN WHEN CLOCKS

886
00:28:16,797 --> 00:28:18,732
ARE UNCOUPLED FROM THE BODY AND

887
00:28:18,732 --> 00:28:19,233
THE ENVIRONMENT?

888
00:28:19,233 --> 00:28:21,535
LIKE IN SHIFT WORK?

889
00:28:21,535 --> 00:28:24,071
WHAT ABOUT INTERNAL MISALIGNMENT

890
00:28:24,071 --> 00:28:25,839
AMONG THE INTERNAL CLOCKS?

891
00:28:25,839 --> 00:28:27,608
THIS CAN BE BOTH PHASE AND

892
00:28:27,608 --> 00:28:27,941
PERIOD.

893
00:28:27,941 --> 00:28:30,010
IN TERMS OF BASIC SCIENCE, I'M

894
00:28:30,010 --> 00:28:32,112
VERY INTERESTED, OF COURSE, IN

895
00:28:32,112 --> 00:28:33,080
SPECIES DIFFERENCES.

896
00:28:33,080 --> 00:28:35,516
ARE THESE MECHANISMS CO CONSERVD

897
00:28:35,516 --> 00:28:38,152
ACROSS ALL SPECIES, ACROSS ALL

898
00:28:38,152 --> 00:28:39,920
BODY SIZES OF SPECIES, BUT ALSO

899
00:28:39,920 --> 00:28:41,488
ACROSS TISSUES, IF WE SEE THAT

900
00:28:41,488 --> 00:28:42,823
CLOCKS ARE IN EACH TISSUE AND WE

901
00:28:42,823 --> 00:28:44,091
KNOW THE TRANSCRIPTOMES THAT

902
00:28:44,091 --> 00:28:45,526
THEY ARE COORDINATING ARE

903
00:28:45,526 --> 00:28:47,161
DIFFERENT, WHAT DOES THAT MEAN

904
00:28:47,161 --> 00:28:49,463
FOR HOW THE CIRCADIAN MOLECULAR

905
00:28:49,463 --> 00:28:50,798
NETWORK IS AFFECTING THE

906
00:28:50,798 --> 00:28:52,199
FUNCTION OF DIFFERENT CELLS IN

907
00:28:52,199 --> 00:28:53,267
DIFFERENT TISSUES?

908
00:28:53,267 --> 00:28:55,302
I THINK THESE ARE ALL REALLY

909
00:28:55,302 --> 00:28:56,503
TIMELY AND IMPORTANT QUESTIONS

910
00:28:56,503 --> 00:28:59,473
TO ANSWER AS WE MOVE FORWARD.

911
00:28:59,473 --> 00:29:02,409
AND FINALLY, ONE OF THE

912
00:29:02,409 --> 00:29:04,611
FUNDAMENTAL DIFFICULTIES IS,

913
00:29:04,611 --> 00:29:08,449
OFTEN, HOW DO YOU MEASURE TIME?

914
00:29:08,449 --> 00:29:11,752
DO WE RELY ON CLOCK GENES, DO WE

915
00:29:11,752 --> 00:29:14,354
RELY ON THE CLOCK GENE

916
00:29:14,354 --> 00:29:15,355
DOWNSTREAM EFFECTORS, AND HOW DO

917
00:29:15,355 --> 00:29:15,923
WE MEASURE THEM?

918
00:29:15,923 --> 00:29:17,791
HOW DO WE MEASURE THEM IN HUMANS

919
00:29:17,791 --> 00:29:20,961
WHERE WE CAN'T DO INVASIVE

920
00:29:20,961 --> 00:29:23,097
TESTING, WHAT KINDS OF POTENTIAL

921
00:29:23,097 --> 00:29:24,031
BIOMARKERS ARE THERE THAT ARE

922
00:29:24,031 --> 00:29:25,265
OUT THERE THAT CAN HELP US MOVE

923
00:29:25,265 --> 00:29:27,267
FORWARD TO UNDERSTANDING THESE

924
00:29:27,267 --> 00:29:28,669
INTERACTIONS.

925
00:29:28,669 --> 00:29:30,270
WITH THAT, I'D JUST LIKE TO SAY

926
00:29:30,270 --> 00:29:31,638
THANK YOU TO THE PEOPLE IN MY

927
00:29:31,638 --> 00:29:33,173
LAB THAT HAVE CONTRIBUTED TO

928
00:29:33,173 --> 00:29:33,373
THIS.

929
00:29:33,373 --> 00:29:35,843
ALSO TO THE FACULTY MEMBERS WHO

930
00:29:35,843 --> 00:29:37,077
HAVE BEEN IMPORTANT MENTORS FOR

931
00:29:37,077 --> 00:29:39,613
ME AS I MOVE THROUGH AS A JUNIOR

932
00:29:39,613 --> 00:29:40,481
FACULTY MEMBER.

933
00:29:40,481 --> 00:29:42,883
MY COLLABORATORS ELSEWHERE,

934
00:29:42,883 --> 00:29:44,251
FUNDING FROM NIH, THE AMERICAN

935
00:29:44,251 --> 00:29:45,986
SLEEP MEDICINE FOUNDATION, AND

936
00:29:45,986 --> 00:29:48,355
THE STATE OF OREGON.

937
00:29:48,355 --> 00:29:49,923
AND I'LL JUST LEAVE YOU WITH

938
00:29:49,923 --> 00:29:51,091
THIS, THAT WHEN WE THINK ABOUT

939
00:29:51,091 --> 00:29:53,427
THE THREE PILLARS OF HEALTH, OF

940
00:29:53,427 --> 00:29:56,063
DIET, SLEEP AND EXERCISE, WE

941
00:29:56,063 --> 00:29:57,030
REALLY UNDERSTAND THAT THE

942
00:29:57,030 --> 00:29:58,732
TIMING OF ALL OF THESE MATTERS.

943
00:29:58,732 --> 00:30:00,134
IT'S NOT JUST WHAT YOU EAT, IT'S

944
00:30:00,134 --> 00:30:01,668
WHEN YOU EAT.

945
00:30:01,668 --> 00:30:02,569
IT'S NOT JUST HOW MUCH YOU

946
00:30:02,569 --> 00:30:04,438
SLEEP, IT'S WHEN YOU SLEEP.

947
00:30:04,438 --> 00:30:05,739
SAME FOR EXERCISE.

948
00:30:05,739 --> 00:30:07,608
AND SO MOVING FORWARD, I THINK

949
00:30:07,608 --> 00:30:10,077
WE HAVE A GREAT OPPORTUNITY TO

950
00:30:10,077 --> 00:30:11,845
UNDERSTAND HOW THE CIRCADIAN

951
00:30:11,845 --> 00:30:14,081
CLOCK IS INTERACTING WITH THE

952
00:30:14,081 --> 00:30:15,883
ENVIRONMENT IN COORDINATING AND

953
00:30:15,883 --> 00:30:16,416
ORGANIZING THESE.

954
00:30:16,416 --> 00:30:23,891
THANK YOU VERY MUCH.

955
00:30:23,891 --> 00:30:25,726
>> THANK YOU SO MUCH,

956
00:30:25,726 --> 00:30:26,160
DR. BUTLER.

957
00:30:26,160 --> 00:30:29,429
NEXT UP, DR. SABRA ABBOTT WILL

958
00:30:29,429 --> 00:30:31,632
GIVE US A PRESENTATION ON

959
00:30:31,632 --> 00:30:41,975
CIRCADIAN MEDICINE.

960
00:30:49,783 --> 00:30:51,885
>> ALL RIGHT.

961
00:30:51,885 --> 00:30:54,087
SO THANK YOU SO MUCH TO THE

962
00:30:54,087 --> 00:30:55,289
ORGANIZERS FOR INVITING ME TO

963
00:30:55,289 --> 00:30:56,490
SPEAK IN THIS SYMPOSIUM.

964
00:30:56,490 --> 00:30:58,025
AND I HAVE TO SAY, I'M

965
00:30:58,025 --> 00:30:59,026
ABSOLUTELY THRILLED TO SEE HOW

966
00:30:59,026 --> 00:30:59,993
MANY PEOPLE ARE INTERESTED IN

967
00:30:59,993 --> 00:31:01,228
THIS TOPIC.

968
00:31:01,228 --> 00:31:03,830
AND I THREW THIS SLIDE IN AT THE

969
00:31:03,830 --> 00:31:06,066
VERY -- RIGHT BEFORE WE STARTED

970
00:31:06,066 --> 00:31:07,234
TODAY BECAUSE I THINK IT

971
00:31:07,234 --> 00:31:08,435
HIGHLIGHTS JUST HOW FAR WE'VE

972
00:31:08,435 --> 00:31:09,069
COME AS A FIELD.

973
00:31:09,069 --> 00:31:11,305
WHEN I WAS GETTING STARTED IN

974
00:31:11,305 --> 00:31:13,273
THIS FIELD, THIS IS A PIECE OF

975
00:31:13,273 --> 00:31:14,141
MAIL THAT I GOT.

976
00:31:14,141 --> 00:31:16,877
IT WAS A TRANSCRIPTION FROM A

977
00:31:16,877 --> 00:31:18,178
MEDICAL RECORDS DEPARTMENT AND

978
00:31:18,178 --> 00:31:20,280
WE WERE TELLING THEM THE ADDRESS

979
00:31:20,280 --> 00:31:22,683
WAS THE CIRCADIAN RHYTHM SLEEP

980
00:31:22,683 --> 00:31:23,850
LAB AND YOU CAN SEE THEY DID

981
00:31:23,850 --> 00:31:25,452
THEIR BEST TO TRY TO FIGURE OUT

982
00:31:25,452 --> 00:31:26,653
WHAT ON EARTH THESE WORDS WERE

983
00:31:26,653 --> 00:31:29,389
THAT I WAS EVEN SAYING AND THEY

984
00:31:29,389 --> 00:31:33,327
CAME UP WITH SIRCAD.

985
00:31:33,327 --> 00:31:34,228
IAN RIBBON SO

986
00:31:34,228 --> 00:31:35,862
I THINK WE'RE LUCKY WE'VE COME

987
00:31:35,862 --> 00:31:38,599
TO THE POINT WHERE MOST PEOPLE

988
00:31:38,599 --> 00:31:39,800
REALIZE CIRCADIAN RHYTHMS EXIST

989
00:31:39,800 --> 00:31:41,568
AND WE'RE MOVING IT INTO THE

990
00:31:41,568 --> 00:31:42,669
FIELD OF MEDICINE.

991
00:31:42,669 --> 00:31:43,971
I DON'T HAVE ANY RELEVANT

992
00:31:43,971 --> 00:31:44,838
CONFLICTS OF INTEREST.

993
00:31:44,838 --> 00:31:46,173
TO GO THROUGH OUR LEARNING

994
00:31:46,173 --> 00:31:46,974
OBJECTIVES, I'M GOING TO TAKE

995
00:31:46,974 --> 00:31:48,308
THIS SESSION INTO THE DIRECTION

996
00:31:48,308 --> 00:31:49,509
OF THE CLINIC AND TALK ABOUT

997
00:31:49,509 --> 00:31:51,111
SOME OF THE WORK THAT I DO WITH

998
00:31:51,111 --> 00:31:53,180
PATIENTS WITH PRIMARY CIRCADIAN

999
00:31:53,180 --> 00:31:53,747
RHYTHM DISORDERS.

1000
00:31:53,747 --> 00:31:55,949
SO WE'RE GOING TO TALK ABOUT

1001
00:31:55,949 --> 00:31:56,617
SPECIFICALLY TWO OF THE

1002
00:31:56,617 --> 00:31:58,252
DISORDERS I SEE MOST OFTEN,

1003
00:31:58,252 --> 00:31:59,686
DELAYED SLEEP-WAKE PHASE

1004
00:31:59,686 --> 00:32:02,422
DISORDER AND NON-24-HOUR

1005
00:32:02,422 --> 00:32:03,557
SLEEP-WAKE RHYTHM DISORDER.

1006
00:32:03,557 --> 00:32:05,058
WE'RE GOING TO TALK ABOUT HOW

1007
00:32:05,058 --> 00:32:07,361
THESE DISORDERS HAVE UNIQUE

1008
00:32:07,361 --> 00:32:08,795
CAUSES, EVEN WITHIN A SINGLE

1009
00:32:08,795 --> 00:32:10,197
DISORDER, AND WE NEED TO START

1010
00:32:10,197 --> 00:32:11,431
THINKING ABOUT INDIVIDUALIZED

1011
00:32:11,431 --> 00:32:13,267
TREATMENT STRATEGIES FOR THESE

1012
00:32:13,267 --> 00:32:13,533
PATIENTS.

1013
00:32:13,533 --> 00:32:15,002
AND THEN LASTLY, I'M GOING TO

1014
00:32:15,002 --> 00:32:16,770
GET ON MY OWN LITTLE PERSONAL

1015
00:32:16,770 --> 00:32:17,938
SOAP BOX AND TALK A LITTLE BIT

1016
00:32:17,938 --> 00:32:23,143
ABOUT THE ROLE FOR ACTIDRAPHY

1017
00:32:23,143 --> 00:32:24,578
AND MELATONIN TESTING IN THE

1018
00:32:24,578 --> 00:32:26,346
DIAGNOSIS OF CIRCADIAN RHYTHM

1019
00:32:26,346 --> 00:32:26,913
SLEEP-WAKE DISORDERS.

1020
00:32:26,913 --> 00:32:28,515
SO JUST TO KIND OF SET THE STAGE

1021
00:32:28,515 --> 00:32:31,051
HERE, HOW DID I EVEN GET INTO

1022
00:32:31,051 --> 00:32:31,485
THIS SPACE?

1023
00:32:31,485 --> 00:32:36,156
I ACTUALLY GOT MY START IN THIS

1024
00:32:36,156 --> 00:32:38,025
FIELD TWEFN YEARS AGO NOW

1025
00:32:38,025 --> 00:32:40,327
WORKING AS A GRAD STUDENT AND

1026
00:32:40,327 --> 00:32:41,662
SPENDING A LOT OF TIME SITTING

1027
00:32:41,662 --> 00:32:43,163
IN A DARK BASEMENT HANGING OUT

1028
00:32:43,163 --> 00:32:46,733
WITH THESE GUYS, SO THIS IS A

1029
00:32:46,733 --> 00:32:48,769
C57 BLACK 6 MOUSE AND SPENDING A

1030
00:32:48,769 --> 00:32:50,437
LOT OF TIME WATCHING THEM RUN ON

1031
00:32:50,437 --> 00:32:51,071
RUNNING WHEELS.

1032
00:32:51,071 --> 00:32:53,974
SO YOU'LL NOW BE FAMILIAR WITH

1033
00:32:53,974 --> 00:32:55,375
WHAT THIS MOUSE RUNNING WHEEL

1034
00:32:55,375 --> 00:32:57,678
DATA LOOKS LIKE AFTER THE LAST

1035
00:32:57,678 --> 00:32:59,212
PRESENTATION, BUT JUST GIVING

1036
00:32:59,212 --> 00:33:00,414
YOU A SENSE OF WHAT THEY LOOK

1037
00:33:00,414 --> 00:33:01,715
LIKE WHEN THEY'RE ENTRAINED AND

1038
00:33:01,715 --> 00:33:02,949
WHEN THEY'RE IN FREE-RUNNING

1039
00:33:02,949 --> 00:33:03,383
CONDITIONS.

1040
00:33:03,383 --> 00:33:04,918
AND AS I WAS WRAPPING UP MY

1041
00:33:04,918 --> 00:33:05,852
GRADUATE SCHOOL TRAINING,

1042
00:33:05,852 --> 00:33:07,321
THERE'S ALWAYS THE QUESTION OF

1043
00:33:07,321 --> 00:33:09,423
WHAT DO YOU WANT TO DO FROM A

1044
00:33:09,423 --> 00:33:11,391
MEDICAL PERSPECTIVE.

1045
00:33:11,391 --> 00:33:13,794
AND MY SORT OF PIE IN THE SKY

1046
00:33:13,794 --> 00:33:15,329
DREAM AT THAT POINT WAS TO

1047
00:33:15,329 --> 00:33:16,797
REALLY FIGURE OUT A WAY TO TAKE

1048
00:33:16,797 --> 00:33:19,199
THIS PHENOMENAL BASIC CIRCADIAN

1049
00:33:19,199 --> 00:33:20,734
SCIENCE THAT EXISTED AT THE TIME

1050
00:33:20,734 --> 00:33:21,868
AND FIGURE OUT WAYS THAT WE CAN

1051
00:33:21,868 --> 00:33:25,038
ACTUALLY APPLY THAT WITHIN THE

1052
00:33:25,038 --> 00:33:26,707
CLINICAL SPACE, SO I COMPLETED A

1053
00:33:26,707 --> 00:33:28,975
NEUROLOGY RESIDENCY, SLEEP

1054
00:33:28,975 --> 00:33:32,245
MEDICINE FELLOWSHIP AND ENDED UP

1055
00:33:32,245 --> 00:33:33,347
AT NORTHWESTERN WHERE THEY WERE

1056
00:33:33,347 --> 00:33:35,015
JUST IN THE PROCESS OF STARTING

1057
00:33:35,015 --> 00:33:36,116
A CIRCADIAN MEDICINE CLINIC.

1058
00:33:36,116 --> 00:33:37,150
SO THIS WAS ACTUALLY -- I'M

1059
00:33:37,150 --> 00:33:38,552
GOING TO WALK YOU THROUGH SOME

1060
00:33:38,552 --> 00:33:39,986
OF THE LESSONS AND QUESTIONS

1061
00:33:39,986 --> 00:33:41,722
THAT I LEARNED FROM WORKING WITH

1062
00:33:41,722 --> 00:33:44,257
SOME OF THESE PATIENTS.

1063
00:33:44,257 --> 00:33:47,794
AND IT WAS PROBABLY ON MY FIRST

1064
00:33:47,794 --> 00:33:52,032
MONTH AS A BRAND NEW ATTENDING,

1065
00:33:52,032 --> 00:33:52,933
THIS PATIENT WALKED THROUGH MY

1066
00:33:52,933 --> 00:33:56,470
DOOR AND WE ENDED UP GETTING

1067
00:33:56,470 --> 00:33:58,205
ACTIGRAPHY ON HIM AND JUST TO

1068
00:33:58,205 --> 00:33:59,840
ORIENT YOU, EACH OF THESE LINES

1069
00:33:59,840 --> 00:34:00,774
REPRESENTS 24 HOURS, AND YOU CAN

1070
00:34:00,774 --> 00:34:02,709
SEE THAT THIS PARTICULAR

1071
00:34:02,709 --> 00:34:05,379
PATIENT, EVERY SINGLE DAY, HE

1072
00:34:05,379 --> 00:34:06,613
WAKES UP A LITTLE BIT LATER AND

1073
00:34:06,613 --> 00:34:08,014
A LITTLE BIT LATER AND A LITTLE

1074
00:34:08,014 --> 00:34:08,782
BIT LATER.

1075
00:34:08,782 --> 00:34:10,650
SO AS SOMEBODY WHO KIND OF CUT

1076
00:34:10,650 --> 00:34:12,452
THEIR TEETH LOOKING AT

1077
00:34:12,452 --> 00:34:13,820
FREE-RUNNING MICE, I FELT RIGHT

1078
00:34:13,820 --> 00:34:15,288
AT HOME WITH THIS PATIENT

1079
00:34:15,288 --> 00:34:16,890
BECAUSE IT FELT LIKE I WAS BACK

1080
00:34:16,890 --> 00:34:19,926
IN THAT CIRCADIAN LAB AGAIN.

1081
00:34:19,926 --> 00:34:22,329
BUT THE ADDED BENEFIT WAS THAT

1082
00:34:22,329 --> 00:34:23,864
NOW UNLIKE THE MICE, THESE

1083
00:34:23,864 --> 00:34:24,965
PATIENTS CAN TALK TO ME.

1084
00:34:24,965 --> 00:34:26,733
THEY CAN TELL ME ABOUT THEIR

1085
00:34:26,733 --> 00:34:29,269
EXPERIENCE, THEY CAN TELL ME

1086
00:34:29,269 --> 00:34:30,670
WHAT IT FEELS LIKE WHEN THEY GET

1087
00:34:30,670 --> 00:34:32,339
PUSHED INTO THESE RHYTHMS, WHEN

1088
00:34:32,339 --> 00:34:33,774
I GIVE THEM INTERVENTIONS, HOW

1089
00:34:33,774 --> 00:34:35,208
DO THEY RESPOND, DO THEY FEEL

1090
00:34:35,208 --> 00:34:36,977
LIKE THEY ACTUALLY ARE ADJUSTING

1091
00:34:36,977 --> 00:34:38,612
AND ADAPTING AND DID THEY FEEL

1092
00:34:38,612 --> 00:34:40,147
GOOD OR DID THEY FEEL LIKE

1093
00:34:40,147 --> 00:34:42,416
THEY'RE ONLY GETTING THERE

1094
00:34:42,416 --> 00:34:44,084
THROUGH SHEER WILLPOWER FORCING

1095
00:34:44,084 --> 00:34:45,952
THEMSELVES TO BE ON THIS

1096
00:34:45,952 --> 00:34:48,688
SCHEDULE BUT WE'RE NOT ACTUALLY

1097
00:34:48,688 --> 00:34:49,756
REALLY ACHIEVING THEIR GOALS.

1098
00:34:49,756 --> 00:34:51,825
SO I FEEL LIKE I HAVE -- IT'S AN

1099
00:34:51,825 --> 00:34:53,160
IMMENSE HONOR TO BE ABLE TO TALK

1100
00:34:53,160 --> 00:34:54,694
TO THESE PATIENTS AND WORK WITH

1101
00:34:54,694 --> 00:34:58,965
THEM AND LEARN FROM THEM SO

1102
00:34:58,965 --> 00:35:00,200
WE'RE GOING TALK THROUGH SOME OF

1103
00:35:00,200 --> 00:35:01,735
THE QUESTIONS MY PATIENTS HAVE

1104
00:35:01,735 --> 00:35:03,804
CHALLENGED ME WITH AND HOW THESE

1105
00:35:03,804 --> 00:35:04,571
HAVE SORT OF TURNED INTO

1106
00:35:04,571 --> 00:35:05,338
RESEARCH QUESTIONS.

1107
00:35:05,338 --> 00:35:07,407
SO THIS PARTICULAR PATIENT HAD

1108
00:35:07,407 --> 00:35:09,509
SOMETHING CALLED NON-24-HOUR

1109
00:35:09,509 --> 00:35:10,510
SLEEP-WAKE RHYTHM DISORDER.

1110
00:35:10,510 --> 00:35:14,748
AS YOU CAN IMAGINE, HE HAS A

1111
00:35:14,748 --> 00:35:15,649
CONSOLIDATED TIME OF REST AND

1112
00:35:15,649 --> 00:35:17,217
TIME OF ACTIVITY THAT SHIFTS

1113
00:35:17,217 --> 00:35:21,021
EVERY SINGLE DAY.

1114
00:35:21,021 --> 00:35:23,123
SO SOMETIMES HE'S ASLEEP AT

1115
00:35:23,123 --> 00:35:24,324
NIGHT, SOMETIMES DURING THE DAY.

1116
00:35:24,324 --> 00:35:24,991
SOMETIMES THESE PATIENTS HAVE A

1117
00:35:24,991 --> 00:35:26,526
CLEAR SENSE OF WHAT'S GOING ON,

1118
00:35:26,526 --> 00:35:27,727
SOMETIMES THEY JUST COME IN WITH

1119
00:35:27,727 --> 00:35:28,962
THIS DISORGANIZED HISTORY THAT

1120
00:35:28,962 --> 00:35:31,164
THEY CAN'T REALLY TELL YOU WHEN

1121
00:35:31,164 --> 00:35:32,132
THEY PREFER TO SLEEP.

1122
00:35:32,132 --> 00:35:33,366
THEY KNOW THAT SOMETIMES THEY

1123
00:35:33,366 --> 00:35:34,668
CAN'T SLEEP, SOMETIMES THEY

1124
00:35:34,668 --> 00:35:36,236
CAN'T WAKE UP WHEN THEY WANT TO

1125
00:35:36,236 --> 00:35:39,706
AND THEN SOMETIMES THINGS ARE

1126
00:35:39,706 --> 00:35:40,273
OKAY.

1127
00:35:40,273 --> 00:35:42,776
I'VE INCLUDED HERE, THESE ARE

1128
00:35:42,776 --> 00:35:43,743
THE INTERNATIONAL CLASSIFICATION

1129
00:35:43,743 --> 00:35:45,145
OF SLEEP DISORDERS CRITERIA,

1130
00:35:45,145 --> 00:35:46,279
THAT THESE SHOULD BE PRESENT FOR

1131
00:35:46,279 --> 00:35:47,848
THREE MONTHS, AND THEN I WANT TO

1132
00:35:47,848 --> 00:35:48,982
HIGHLIGHT THAT REALLY TO

1133
00:35:48,982 --> 00:35:50,317
RECOGNIZE THIS, YOU DO WANT TO

1134
00:35:50,317 --> 00:35:53,153
GET SLEEP LOGS AND PREFERABLY

1135
00:35:53,153 --> 00:35:54,821
ACTIGRAPHY MONITORING TO REALLY

1136
00:35:54,821 --> 00:35:55,822
DEMONSTRATE WHAT'S GOING ON.

1137
00:35:55,822 --> 00:35:59,192
AND THEN OBVIOUSLY IT'S NOT

1138
00:35:59,192 --> 00:36:00,760
BETTER EXPLAINED BY ANOTHER

1139
00:36:00,760 --> 00:36:01,628
SLEEP DISORDERS.

1140
00:36:01,628 --> 00:36:04,264
WHAT'S REALLY INTERESTING ABOUT

1141
00:36:04,264 --> 00:36:05,699
THAT PATIENT I STARTED WITH, WE

1142
00:36:05,699 --> 00:36:08,668
OFTEN THINK OF NON-24 HOUR

1143
00:36:08,668 --> 00:36:10,103
SLEEP-WAKE DISORDER AS BEING A

1144
00:36:10,103 --> 00:36:10,971
DISORDER OF PEOPLE WHO ARE

1145
00:36:10,971 --> 00:36:11,304
BLIND.

1146
00:36:11,304 --> 00:36:12,839
WE KNOW WE RESPOND TO

1147
00:36:12,839 --> 00:36:13,974
ENVIRONMENTAL LIGHT, AND SO IF

1148
00:36:13,974 --> 00:36:16,042
YOU DO HAVE RETINAL PATHOLOGY SO

1149
00:36:16,042 --> 00:36:18,044
YOU DON'T GET THAT LIGHT INPUT,

1150
00:36:18,044 --> 00:36:19,846
IT'S UNDERSTANDABLE THAT YOU MAY

1151
00:36:19,846 --> 00:36:22,215
FOLLOW YOUR ENDOGENOUS RHYTHM,

1152
00:36:22,215 --> 00:36:23,517
YOUR ENDOGENOUS PERIOD, BUT

1153
00:36:23,517 --> 00:36:24,751
THERE'S ACTUALLY A WHOLE

1154
00:36:24,751 --> 00:36:27,320
COLLECTION OF PATIENTS INCLUDING

1155
00:36:27,320 --> 00:36:29,256
THIS ONE THAT THEY HAVE NORMAL

1156
00:36:29,256 --> 00:36:30,557
IMAGE-FORMING VISION, SO THEY BY

1157
00:36:30,557 --> 00:36:34,761
ALL OF OUR DESCRIPTORS CAN SEE,

1158
00:36:34,761 --> 00:36:38,265
BUT THEY STILL EXHIBIT THESE

1159
00:36:38,265 --> 00:36:39,132
CIRCADIAN BEHAVIORS AS THOUGH

1160
00:36:39,132 --> 00:36:40,500
THEY'RE NOT RESPONDING TO LIGHT.

1161
00:36:40,500 --> 00:36:41,368
THE OTHER THING THAT'S VERY

1162
00:36:41,368 --> 00:36:42,068
INTERESTING ABOUT THESE

1163
00:36:42,068 --> 00:36:43,136
PATIENTS, THESE ARE JUST SOME

1164
00:36:43,136 --> 00:36:45,906
EXAMPLES OF VARIOUS ACTIGRAPHY

1165
00:36:45,906 --> 00:36:46,706
FROM DIFFERENT PATIENTS HERE,

1166
00:36:46,706 --> 00:36:48,074
YOU CAN SEE THAT MANY OF THEM,

1167
00:36:48,074 --> 00:36:50,710
INSTEAD OF FOLLOWING THIS

1168
00:36:50,710 --> 00:36:51,978
PREDICTIVE EVERY SINGLE DAY IS A

1169
00:36:51,978 --> 00:36:53,213
LITTLE BIT LATER COMPARED TO THE

1170
00:36:53,213 --> 00:36:55,682
DAY BEFORE, THEY WILL GO THROUGH

1171
00:36:55,682 --> 00:36:56,516
THESE TIME PERIODS OF WHAT HE

1172
00:36:56,516 --> 00:36:58,451
WITH CALL RELATIVE ENTRAINMENT,

1173
00:36:58,451 --> 00:37:00,120
SO THEY MAY END UP BEING DELAYED

1174
00:37:00,120 --> 00:37:03,523
FOR A WHILE, THINGS JUST GET SO

1175
00:37:03,523 --> 00:37:05,158
BAD, THEY BECOME NON-24, THEN

1176
00:37:05,158 --> 00:37:06,459
THEY'RE DELAYED FOR A WHILE.

1177
00:37:06,459 --> 00:37:08,662
SO THERE'S OFTEN AN OVERLAP

1178
00:37:08,662 --> 00:37:10,130
BETWEEN PATIENTS WITH DELAYED

1179
00:37:10,130 --> 00:37:12,632
SLEEP WAKE-PHASE DISORDER AND

1180
00:37:12,632 --> 00:37:15,835
SIGHTED NON-24.

1181
00:37:15,835 --> 00:37:19,573
SO WHAT IS DELAYED SLEEK

1182
00:37:19,573 --> 00:37:20,407
WAKE-PHASE DISORDER?

1183
00:37:20,407 --> 00:37:21,308
IN THIS CASE THESE ARE PEOPLE

1184
00:37:21,308 --> 00:37:23,276
WHO HAVE A REGULAR PATTERN OF

1185
00:37:23,276 --> 00:37:24,377
FALLING ASLEEP AND WAKING UP

1186
00:37:24,377 --> 00:37:25,946
THAT IS MUCH LATER THAN

1187
00:37:25,946 --> 00:37:27,347
CONVENTIONAL TIMES, AND IT'S

1188
00:37:27,347 --> 00:37:28,982
ALSO MUCH LATER THAN THEY WOULD

1189
00:37:28,982 --> 00:37:30,450
DESIRE TO BE, SO THEY WANT TO GO

1190
00:37:30,450 --> 00:37:31,751
TO BED EARLIER AND WAKE UP

1191
00:37:31,751 --> 00:37:33,086
EARLIER OR THEY NEED TO BECAUSE

1192
00:37:33,086 --> 00:37:34,754
OF WORK REQUIREMENTS, AND THEY

1193
00:37:34,754 --> 00:37:36,623
JUST ARE UNABLE TO.

1194
00:37:36,623 --> 00:37:38,625
THE OTHER DIAGNOSTIC CRITERIA

1195
00:37:38,625 --> 00:37:41,895
ARE THE SAME AS FOR NON-24.

1196
00:37:41,895 --> 00:37:44,230
AND I THINK ONE OF THE FIRST

1197
00:37:44,230 --> 00:37:45,298
QUESTIONS THAT'S SPARKED BY

1198
00:37:45,298 --> 00:37:46,600
THIS, HAVING TALKED TO MANY OF

1199
00:37:46,600 --> 00:37:48,969
THESE PATIENTS AND REALLY

1200
00:37:48,969 --> 00:37:51,237
GETTING A SENSE THAT THIS IS A

1201
00:37:51,237 --> 00:37:52,005
FRUSTRATING PHENOMENON WHERE

1202
00:37:52,005 --> 00:37:54,040
THEY ARE TRYING, THEY'RE GETTING

1203
00:37:54,040 --> 00:37:55,275
INTO BED, THEY'RE FOLLOWING ALL

1204
00:37:55,275 --> 00:37:57,744
OF THE RIGHT SLEEP HYGIENE

1205
00:37:57,744 --> 00:37:58,745
RECOMMENDATIONS, THEY'RE SETTING

1206
00:37:58,745 --> 00:38:00,313
MILLIONS OF ALARMS AND THEY

1207
00:38:00,313 --> 00:38:02,048
CANNOT FALL ASLEEP AND WAKE UP

1208
00:38:02,048 --> 00:38:03,717
WHEN SOCIETY WANT THEM TO.

1209
00:38:03,717 --> 00:38:05,485
AND SO IT REALLY SUGGESTS

1210
00:38:05,485 --> 00:38:07,821
THERE'S SOME SORT OF STRONG

1211
00:38:07,821 --> 00:38:10,423
UNDERLYING BIOLOGICAL FACTOR

1212
00:38:10,423 --> 00:38:11,691
THAT'S DRIVING THIS, SO WHAT ARE

1213
00:38:11,691 --> 00:38:12,993
SOME OF THE POTENTIAL CAUSES FOR

1214
00:38:12,993 --> 00:38:13,426
THAT?

1215
00:38:13,426 --> 00:38:16,196
SO OVER HERE ON THE LEFT, I JUST

1216
00:38:16,196 --> 00:38:18,298
HAVE A CARTOON ILLUSTRATING SORT

1217
00:38:18,298 --> 00:38:20,066
OF THE BASICS OF HOW IT IS THAT

1218
00:38:20,066 --> 00:38:23,870
MOST OF US ARE ASLEEP AT NIGHT

1219
00:38:23,870 --> 00:38:24,804
AND AWAKE DURING THE DAY TIME.

1220
00:38:24,804 --> 00:38:27,073
SO MOST OF US HAVE AN ENDOGENOUS

1221
00:38:27,073 --> 00:38:29,275
PERIOD A LITTLE BIT LONGER THAN

1222
00:38:29,275 --> 00:38:30,744
24 HOURS, SO IF I PUT YOU IN A

1223
00:38:30,744 --> 00:38:32,045
CAVE EVERY SINGLE DAY, YOU WOULD

1224
00:38:32,045 --> 00:38:33,713
GET A LITTLE BIT LATER AND A

1225
00:38:33,713 --> 00:38:35,148
LITTLE BIT LATER, BUT IT'S THAT

1226
00:38:35,148 --> 00:38:36,883
DAILY EXPOSURE TO LIGHT DURING

1227
00:38:36,883 --> 00:38:39,853
THE DAY THAT PROVIDES A PHASE

1228
00:38:39,853 --> 00:38:41,321
ADVANCING SIGNAL THAT SHIFT YOU

1229
00:38:41,321 --> 00:38:44,891
EARLIER, AND SO THE ULTIMATE

1230
00:38:44,891 --> 00:38:47,227
EFFECT IS THAT YOU END UP BEING

1231
00:38:47,227 --> 00:38:49,229
ALIGNED SO YOU FALL ASLEEP WHEN

1232
00:38:49,229 --> 00:38:51,665
IT'S DARK AND AWAKE WHEN IT'S

1233
00:38:51,665 --> 00:38:52,098
LIGHT.

1234
00:38:52,098 --> 00:38:53,967
ONE POTENTIAL WAY YOU CAN

1235
00:38:53,967 --> 00:38:55,268
DEVELOP THIS IS BECAUSE MAYBE

1236
00:38:55,268 --> 00:38:57,737
THESE ARE PEOPLE WHO TEND TO BE

1237
00:38:57,737 --> 00:38:58,705
STAYING UP LATER, THEY'RE

1238
00:38:58,705 --> 00:39:00,240
GETTING LATER LIGHT EXPOSURE AT

1239
00:39:00,240 --> 00:39:01,608
NIGHT SO MAYBE THEY'RE GETTING

1240
00:39:01,608 --> 00:39:05,311
TOO MUCH LIGHT AT NIGHT THAT'S

1241
00:39:05,311 --> 00:39:07,514
GIVING THEM A GREATER PUSH IN

1242
00:39:07,514 --> 00:39:08,481
THEIR OWN DIRECTION AND MAYBE

1243
00:39:08,481 --> 00:39:09,416
THEY'RE NOT GETTING ENOUGH LIGHT

1244
00:39:09,416 --> 00:39:10,950
IN THE MORNING, THE NEXT DAY, SO

1245
00:39:10,950 --> 00:39:12,686
THEY'RE NOT GETTING ENOUGH OF

1246
00:39:12,686 --> 00:39:14,254
THAT SIGNAL TO PUSH THEM

1247
00:39:14,254 --> 00:39:16,456
EARLIER, SO THEN THAT BALANCE IS

1248
00:39:16,456 --> 00:39:18,091
THAT THEIR SLEEP-WAKE WINDOW IS

1249
00:39:18,091 --> 00:39:19,292
SKEWED A LITTLE BIT IN THE LATER

1250
00:39:19,292 --> 00:39:19,793
DIRECTION.

1251
00:39:19,793 --> 00:39:21,227
SO WE HAVE A LITTLE BIT OF DATA

1252
00:39:21,227 --> 00:39:23,630
LOOKING INTO THAT.

1253
00:39:23,630 --> 00:39:25,699
THIS IS TAKING TWO GROUPS OF

1254
00:39:25,699 --> 00:39:27,267
INDIVIDUALS EITHER CONTROLLED

1255
00:39:27,267 --> 00:39:29,035
WHO FOLLOW A CONVENTIONAL

1256
00:39:29,035 --> 00:39:31,971
SLEEP-WAKE TIME VERSUS A GROUP

1257
00:39:31,971 --> 00:39:33,206
OF PEOPLE WHO ARE DELAYED BUT

1258
00:39:33,206 --> 00:39:36,309
ABLE TO FOLLOW THEIR HABITUAL

1259
00:39:36,309 --> 00:39:37,744
SLEEP-WAKE KEL.

1260
00:39:37,744 --> 00:39:39,913
WHAT YOU CAN SEE IS IF YOU LOOK

1261
00:39:39,913 --> 00:39:41,748
AT THEIR DAILY LIGHT EXPOSURE

1262
00:39:41,748 --> 00:39:42,849
PATTERNS AND MAP THOSE BASED ON

1263
00:39:42,849 --> 00:39:44,250
CLOCK TIME, YOU CAN SEE THAT THE

1264
00:39:44,250 --> 00:39:45,185
INDIVIDUALS WHO ARE DELAYED TEND

1265
00:39:45,185 --> 00:39:46,286
TO GET MUCH MORE LIGHT BETWEEN

1266
00:39:46,286 --> 00:39:51,191
THE HOURS OF 10:00 P.M. AND 4:0S

1267
00:39:51,191 --> 00:39:52,892
TEND TO GET MUCH MORE LIGHT THAN

1268
00:39:52,892 --> 00:39:53,893
THE DELAYED INDIVIDUALS BETWEEN

1269
00:39:53,893 --> 00:39:56,596
ABOUT 6:00 A.M. AND NOON.

1270
00:39:56,596 --> 00:39:59,833
BUT WHAT WE KNOW ABOUT CIRCADIAN

1271
00:39:59,833 --> 00:40:01,468
RESETTING IS THAT IT'S NOT BASED

1272
00:40:01,468 --> 00:40:04,104
ON EXTERNAL CLOCK TIME, IT'S

1273
00:40:04,104 --> 00:40:06,439
ACTUALLY BASED ON YOUR INTERNAL

1274
00:40:06,439 --> 00:40:06,806
CIRCADIAN TIME.

1275
00:40:06,806 --> 00:40:10,143
AND SO IF WE LOOK AT THE PROFILE

1276
00:40:10,143 --> 00:40:13,847
OF MEL TOE  MELATONIN PRODUCTIOF

1277
00:40:13,847 --> 00:40:15,548
THE MARKERS WE HAVE OF CIRCADIAN

1278
00:40:15,548 --> 00:40:16,683
PHASE AND THEN LOOK AT THAT

1279
00:40:16,683 --> 00:40:18,418
LIGHT EXPOSURE RELATIVE TO THAT,

1280
00:40:18,418 --> 00:40:19,819
IT TURNS OUT THAT THIS WINDOW

1281
00:40:19,819 --> 00:40:21,354
OUT HERE, WHERE WE WOULD EXPECT

1282
00:40:21,354 --> 00:40:23,256
THAT TOO MUCH LIGHT MIGHT PUSH

1283
00:40:23,256 --> 00:40:25,425
THEM TOO LATE IN THE WRONG

1284
00:40:25,425 --> 00:40:26,226
DIRECTION, THEY AREN'T ACTUALLY

1285
00:40:26,226 --> 00:40:27,293
GETTING THAT MUCH MORE LIGHT

1286
00:40:27,293 --> 00:40:28,895
WITHIN THAT WINDOW BASED ON

1287
00:40:28,895 --> 00:40:30,897
THEIR BIOLOGICAL TIME.

1288
00:40:30,897 --> 00:40:32,165
THERE'S JUST A LITTLE BIT OF A

1289
00:40:32,165 --> 00:40:34,567
DIFFERENCE SORT OF OUT HERE,

1290
00:40:34,567 --> 00:40:36,870
SORT OF LATE IN THE

1291
00:40:36,870 --> 00:40:37,504
MORNING/EARLY AFTERNOON, WHERE

1292
00:40:37,504 --> 00:40:39,472
THEY MAY BE GETTING JUST A

1293
00:40:39,472 --> 00:40:40,974
LITTLE BIT LESS OF THAT MORNING

1294
00:40:40,974 --> 00:40:44,811
ADVANCING LIGHT LIGHT SIGNAL.

1295
00:40:44,811 --> 00:40:46,546
SO THIS MAY NOT BE THE PRIMARY

1296
00:40:46,546 --> 00:40:46,880
EXPLANATION.

1297
00:40:46,880 --> 00:40:48,915
SO THEN THE OTHER POSSIBILITY IS

1298
00:40:48,915 --> 00:40:52,418
PERHAPS THESE INDIVIDUALS HAVE A

1299
00:40:52,418 --> 00:40:53,186
PHYSIOLOGIC DIFFERENCE IN TERMS

1300
00:40:53,186 --> 00:40:55,455
OF HOW SENSITIVE THEY ARE TO

1301
00:40:55,455 --> 00:40:55,889
LIGHT.

1302
00:40:55,889 --> 00:40:56,990
SO MAYBE THEY'RE GETTING THE

1303
00:40:56,990 --> 00:40:58,057
SAME AMOUNT OF LIGHT AT NIGHT,

1304
00:40:58,057 --> 00:40:59,893
BUT IT HAS A STRONGER EFFECT, SO

1305
00:40:59,893 --> 00:41:01,761
IT PUSHES THEM LATER.

1306
00:41:01,761 --> 00:41:03,129
OR THEY'RE GETTING THE SAME

1307
00:41:03,129 --> 00:41:05,098
AMOUNT OF LIGHT IN THE MORNING

1308
00:41:05,098 --> 00:41:07,634
BUT THEY'RE NOT AT RESPONSIVE TO

1309
00:41:07,634 --> 00:41:09,169
IT, THEIR EYES JUST DON'T

1310
00:41:09,169 --> 00:41:10,603
PERCEIVE IT IN THE SAME WAY, SO

1311
00:41:10,603 --> 00:41:11,905
THEY DON'T RESPOND TO IT.

1312
00:41:11,905 --> 00:41:14,240
AND SOME OF THE HINTS FOR THIS

1313
00:41:14,240 --> 00:41:15,341
ACTUALLY COME FROM THE PATIENTS,

1314
00:41:15,341 --> 00:41:18,311
AND SO ESPECIALLY IN THESE

1315
00:41:18,311 --> 00:41:21,414
PATIENTS WITH EXTREME DELAYED

1316
00:41:21,414 --> 00:41:22,849
SLEEP-WAKE PHASE DISORDER OR

1317
00:41:22,849 --> 00:41:24,584
SIGHTED NON-24, I OFTEN GET THIS

1318
00:41:24,584 --> 00:41:26,019
RESPONSE OF I HATE LIGHT AND IT

1319
00:41:26,019 --> 00:41:27,821
DOESN'T WORK.

1320
00:41:27,821 --> 00:41:29,556
AND WE TRY EVERYTHING WE CAN

1321
00:41:29,556 --> 00:41:30,990
WITH MAKING SURE THAT IT'S BEING

1322
00:41:30,990 --> 00:41:33,293
GIVEN AT THE RIGHT TIME, AND IT

1323
00:41:33,293 --> 00:41:34,727
JUST DOESN'T HAVE THE EFFECT

1324
00:41:34,727 --> 00:41:36,162
THAT WE WOULD EXPECT, AND THEY

1325
00:41:36,162 --> 00:41:38,331
OFTEN TEND TO FIND IT MUCH MORE

1326
00:41:38,331 --> 00:41:39,566
IRRITATING AND, IN FACT, ONE OF

1327
00:41:39,566 --> 00:41:41,134
THE WAYS I'VE STARTED TO TEASE

1328
00:41:41,134 --> 00:41:42,902
SOME OF THESE PATIENTS APART IS

1329
00:41:42,902 --> 00:41:45,171
ACTUALLY ASKING THEM, IF YOU

1330
00:41:45,171 --> 00:41:47,240
COULD CHANGE THE LIGHT INTENSITY

1331
00:41:47,240 --> 00:41:48,541
IN THIS ROOM, IF YOU COULD MAKE

1332
00:41:48,541 --> 00:41:50,577
IT BRIGHTER OR YOU COULD MAKE IT

1333
00:41:50,577 --> 00:41:54,914
DIMMER, WHAT WOULD B YOU PREFER?

1334
00:41:54,914 --> 00:41:56,316
THERE'S A NUMBER OF PATIENTS

1335
00:41:56,316 --> 00:41:57,851
THAT WOULD PREFER TO BE IN THAT

1336
00:41:57,851 --> 00:41:58,685
DIMMER ENVIRONMENT, SO ALL OF

1337
00:41:58,685 --> 00:42:00,320
THIS SUGGESTS MAYBE THERE IS

1338
00:42:00,320 --> 00:42:01,187
SOMETHING DIFFERENT ABOUT HOW

1339
00:42:01,187 --> 00:42:02,755
THESE INDIVIDUALS ARE PERCEIVING

1340
00:42:02,755 --> 00:42:05,558
LIGHT PHYSIOLOGICALLY.

1341
00:42:05,558 --> 00:42:07,594
SO WE'VE ALREADY TALKED A LITTLE

1342
00:42:07,594 --> 00:42:11,431
BIT ABOUT THE SUPRACHIASMATIC

1343
00:42:11,431 --> 00:42:12,966
NUCLEUS, THE PRIMARY PACEMAKER

1344
00:42:12,966 --> 00:42:14,467
WITHIN THE BRAIN, AND THE WAY

1345
00:42:14,467 --> 00:42:17,070
THAT WE GET LIGHT TO THE SCN, IF

1346
00:42:17,070 --> 00:42:18,738
WE LOOK OVER HERE ON THE LEFT,

1347
00:42:18,738 --> 00:42:20,506
THIS IS AN ENLARGED

1348
00:42:20,506 --> 00:42:21,808
CROSS-SECTION OF THE RETINA, OF

1349
00:42:21,808 --> 00:42:22,375
YOUR EYE.

1350
00:42:22,375 --> 00:42:24,811
WE HAVE OUR TRADITIONAL ROD AND

1351
00:42:24,811 --> 00:42:26,145
CONE PHOTO RECEPTORS HERE.

1352
00:42:26,145 --> 00:42:28,114
BUT THEN THE CIRCADIAN LIGHT

1353
00:42:28,114 --> 00:42:30,516
SIGNAL IS ACTUALLY TRANSMITTED

1354
00:42:30,516 --> 00:42:33,953
THROUGH THESE INKRIN SICKLY

1355
00:42:33,953 --> 00:42:35,588
FOCUSED RETINAL GANGLION CELLS.

1356
00:42:35,588 --> 00:42:39,259
THEY SEND PR PROJECTIONS TO THES

1357
00:42:39,259 --> 00:42:40,360
CN BUT PREVIOUSLY FOR US THEY

1358
00:42:40,360 --> 00:42:42,195
ALSO SEND PROJECTIONS TO YOUR

1359
00:42:42,195 --> 00:42:44,297
BRAINSTEM, WHERE THEY SIN APPS

1360
00:42:44,297 --> 00:42:48,334
WITH THE PRETACTILE NUCLEUS AND

1361
00:42:48,334 --> 00:42:49,602
THAT GOES BACK TO YOUR PUPIL.

1362
00:42:49,602 --> 00:42:51,704
SO WE CAN ACTUALLY USE MEASURES

1363
00:42:51,704 --> 00:42:54,140
OF HOW YOUR PUPIL RESPONDS TO

1364
00:42:54,140 --> 00:42:55,575
LIGHT AS A SURROGATE MARKER FOR

1365
00:42:55,575 --> 00:42:56,843
HOW WELL THESE CELLS ARE

1366
00:42:56,843 --> 00:42:58,845
WORKING.

1367
00:42:58,845 --> 00:43:01,414
AND SO WE UNDERTOOK A PROJECT

1368
00:43:01,414 --> 00:43:02,282
ACTUALLY LOOKING AT LIGHT

1369
00:43:02,282 --> 00:43:03,650
SENSITIVITY IN THESE PATIENTS,

1370
00:43:03,650 --> 00:43:05,485
AND SO WE TOOK THREE GROUPS,

1371
00:43:05,485 --> 00:43:07,120
EITHER CONTROLS, WHO SORT OF

1372
00:43:07,120 --> 00:43:09,522
FOLLOWED CONVENTIONAL SLEEP-WAKE

1373
00:43:09,522 --> 00:43:10,890
TIMING, INDIVIDUALS WHO HAD

1374
00:43:10,890 --> 00:43:13,092
DELAYED SLEEP-WAKE PHASE

1375
00:43:13,092 --> 00:43:14,527
DISORDER BUT HAD NEVER GOTTEN TO

1376
00:43:14,527 --> 00:43:16,162
THE POINT WHERE THEY ACTUALLY

1377
00:43:16,162 --> 00:43:17,964
WENT AROUND THE CLOCK AND GOT

1378
00:43:17,964 --> 00:43:19,499
LATER AND LATER EACH DAY.

1379
00:43:19,499 --> 00:43:20,934
THEN A THIRD GROUP OF

1380
00:43:20,934 --> 00:43:22,468
INDIVIDUALS WHO SORT OF TOWED

1381
00:43:22,468 --> 00:43:25,238
THAT LINE BETWEEN BEING DELAYED

1382
00:43:25,238 --> 00:43:27,740
ADD NON-24 ALL WITHIN THAT

1383
00:43:27,740 --> 00:43:29,075
SIGHTED NON-24 CATEGORY.

1384
00:43:29,075 --> 00:43:32,245
AND ESSENTIALLY WHAT WE FOUND IN

1385
00:43:32,245 --> 00:43:35,815
THIS CASE, A LARGER PIPR MEANS

1386
00:43:35,815 --> 00:43:37,917
THOSE CELLS ARE WORKING BETTER.

1387
00:43:37,917 --> 00:43:39,719
SMALLER PIPR MEANS THEY'RE NOT

1388
00:43:39,719 --> 00:43:41,621
WORKING AS WELL, SO THE NON-24

1389
00:43:41,621 --> 00:43:45,858
PATIENTS HAVE A SIGNIFICANT

1390
00:43:45,858 --> 00:43:47,393
DECREASE IN THE FUNCTION OF

1391
00:43:47,393 --> 00:43:50,096
THESE CELLS AND A SIGNIFICANTLY

1392
00:43:50,096 --> 00:43:51,931
SMALLER PIPR.

1393
00:43:51,931 --> 00:43:52,832
FURTHERMORE, IF YOU LOOK AT THEM

1394
00:43:52,832 --> 00:43:54,200
WHEN ALL OF THESE PATIENTS ARE

1395
00:43:54,200 --> 00:43:55,802
IN A STATE OF RELATIVE

1396
00:43:55,802 --> 00:43:57,370
ENTRAINMENT AND YOU LOOK AT THE

1397
00:43:57,370 --> 00:43:58,771
MIDPOINT OF THEIR SLEEP, SO WHEN

1398
00:43:58,771 --> 00:44:00,640
THEY GET TO SLEEP ON THEIR

1399
00:44:00,640 --> 00:44:02,208
PREFERRED SCHEDULE, HOW LATE IS

1400
00:44:02,208 --> 00:44:04,610
THAT TIME, AND THE LATER YOUR

1401
00:44:04,610 --> 00:44:07,847
BODY WANTS TO SLEEP, THE SMALLER

1402
00:44:07,847 --> 00:44:10,350
THAT PIPR IS, SUGGESTING, GOING

1403
00:44:10,350 --> 00:44:11,784
BACK TO OUR CARTOON HERE, THAT

1404
00:44:11,784 --> 00:44:13,386
WE FOUND A POPULATION OF

1405
00:44:13,386 --> 00:44:15,121
INDIVIDUALS WHO MAY HAVE A

1406
00:44:15,121 --> 00:44:18,424
DECREASE IN LIGHT SENSITIVITY

1407
00:44:18,424 --> 00:44:20,660
EVEN THOUGH THEY HAVE NORMAL

1408
00:44:20,660 --> 00:44:21,160
IMAGE-FORMING VISION.

1409
00:44:21,160 --> 00:44:22,362
NOW WHAT'S REALLY INTERESTING

1410
00:44:22,362 --> 00:44:24,097
ABOUT THIS IS THAT AT THE SAME

1411
00:44:24,097 --> 00:44:25,498
TIME THAT WE WERE DOING THIS

1412
00:44:25,498 --> 00:44:29,268
WORK, AND I FORGOT TO HIGHLIGHT

1413
00:44:29,268 --> 00:44:33,473
HERE, A SHOUT OUT TO THE

1414
00:44:33,473 --> 00:44:35,208
AMERICAN SLEEP FOUNDATION, BUT

1415
00:44:35,208 --> 00:44:37,110
AS WE WERE DOING THIS WORK, AT

1416
00:44:37,110 --> 00:44:38,678
THE SAME TIME THERE WAS A GROUP

1417
00:44:38,678 --> 00:44:39,879
IN AUSTRALIA ASKING SOME OF THE

1418
00:44:39,879 --> 00:44:40,980
SAME QUESTIONS SO THEY ACTUALLY

1419
00:44:40,980 --> 00:44:41,881
FOUND A POPULATION OF

1420
00:44:41,881 --> 00:44:44,751
INDIVIDUALS WITH DELAYED

1421
00:44:44,751 --> 00:44:46,052
SLEEP-WAKE PHASE DISORDER BUT IN

1422
00:44:46,052 --> 00:44:47,487
THEIR CASE, THEY ACTUALLY FOUND

1423
00:44:47,487 --> 00:44:49,188
THEY HAD GREATER LIGHT

1424
00:44:49,188 --> 00:44:51,524
SENSITIVITY, AND SO THEY SHOWED

1425
00:44:51,524 --> 00:44:52,725
GREATER PHASE SHIFTS TO EVENING

1426
00:44:52,725 --> 00:44:54,894
LIGHT, AND GREATER MELATONIN

1427
00:44:54,894 --> 00:44:55,461
SUPPRESSION.

1428
00:44:55,461 --> 00:44:58,564
SO IT LOOKS LIKE SOME PEOPLE

1429
00:44:58,564 --> 00:45:01,401
WITH DSPD CAN FALL ON ONE END OF

1430
00:45:01,401 --> 00:45:02,635
THE SPECTRUM WHERE THEY HAVE

1431
00:45:02,635 --> 00:45:03,603
INCREASED LIGHT SENSITIVITY AND

1432
00:45:03,603 --> 00:45:04,871
OTHERS CAN FALL ON THE OTHER END

1433
00:45:04,871 --> 00:45:06,973
OF THE SPECTRUM WHERE THEY HAVE

1434
00:45:06,973 --> 00:45:07,940
DECREASED LIGHT SENSITIVITY.

1435
00:45:07,940 --> 00:45:09,542
NOW, WHAT I LOVE ABOUT THIS

1436
00:45:09,542 --> 00:45:11,177
PROJECT IS, IT ACTUALLY HAS LED

1437
00:45:11,177 --> 00:45:13,479
TO A COLLABORATION BETWEEN OUR

1438
00:45:13,479 --> 00:45:15,515
GROUP AND THE AUSTRALIAN GROUP,

1439
00:45:15,515 --> 00:45:18,151
AND TRYING TO FIGURE OUT WHY OR

1440
00:45:18,151 --> 00:45:19,652
HOW THESE DIFFERENT PHENOTYPES

1441
00:45:19,652 --> 00:45:20,853
EXIST AND WHAT WE CAN DO FOR

1442
00:45:20,853 --> 00:45:22,055
THEM.

1443
00:45:22,055 --> 00:45:24,323
SO THIS IS A MODEL THAT ANDREW

1444
00:45:24,323 --> 00:45:25,425
PHILLIPS PUT TOGETHER TRYING TO

1445
00:45:25,425 --> 00:45:27,326
EXPLAIN THIS, BECAUSE ONE OF THE

1446
00:45:27,326 --> 00:45:28,461
MOST INTERESTING THINGS BETWEEN

1447
00:45:28,461 --> 00:45:32,031
OUR TWO POPULATIONS WAS THAT OUR

1448
00:45:32,031 --> 00:45:33,766
LOW LIGHT SENSITIVITY

1449
00:45:33,766 --> 00:45:36,269
INDIVIDUALS TENDED TO HAVE MUCH

1450
00:45:36,269 --> 00:45:38,438
LATER HABITUAL SLEEP TIMES THAN

1451
00:45:38,438 --> 00:45:39,639
THEIR HIGHLIGHT SENSITIVITY

1452
00:45:39,639 --> 00:45:40,173
INDIVIDUALS.

1453
00:45:40,173 --> 00:45:41,741
SO WHAT HE'S PUT TOGETHER HERE,

1454
00:45:41,741 --> 00:45:44,110
JUST TO WALK YOU THROUGH THIS,

1455
00:45:44,110 --> 00:45:45,645
IS A GRAPH LOOKING AT HOW

1456
00:45:45,645 --> 00:45:47,613
SENSITIVE YOU ARE TO LIGHT, SO

1457
00:45:47,613 --> 00:45:49,449
HIGHER AND LOWER, AND THEN WHAT

1458
00:45:49,449 --> 00:45:52,251
YOUR INTRINSIC CIRCADIAN PERIOD

1459
00:45:52,251 --> 00:45:52,418
IS.

1460
00:45:52,418 --> 00:45:53,920
SO MOST OF US ARE RELATIVELY

1461
00:45:53,920 --> 00:45:57,824
CLOSE TO 24 HOURS HERE, BUT SOME

1462
00:45:57,824 --> 00:45:59,125
INDIVIDUALS WITH THE CIRCADIAN

1463
00:45:59,125 --> 00:46:00,860
DISORDERS TEND TO HAVE LONGER

1464
00:46:00,860 --> 00:46:01,227
PERIODS.

1465
00:46:01,227 --> 00:46:02,862
SO IF YOU'RE OUT HERE WHERE

1466
00:46:02,862 --> 00:46:04,864
YOU'VE GOT A RELATIVELY NORMAL

1467
00:46:04,864 --> 00:46:05,898
PERIOD AND IT DOESN'T REALLY

1468
00:46:05,898 --> 00:46:07,600
SEEM TO MATTER WHAT YOUR LIGHT

1469
00:46:07,600 --> 00:46:09,135
SENSITIVITY IS, BUT AS YOU GET

1470
00:46:09,135 --> 00:46:12,305
TO A POINT WHERE YOUR PERIOD IS

1471
00:46:12,305 --> 00:46:14,474
LONGER, IF YOU HAVE EITHER HIGH

1472
00:46:14,474 --> 00:46:16,442
OR LOW LIGHT SENSITIVITY, YOU

1473
00:46:16,442 --> 00:46:20,680
COULD HAVE DEVELOPED A SLEEP

1474
00:46:20,680 --> 00:46:22,448
WAKE PHASE -- YOU COULD EVEN

1475
00:46:22,448 --> 00:46:23,850
HAVE NORMAL LIGHT SENSITIVITY

1476
00:46:23,850 --> 00:46:26,352
AND STILL DEVELOP DSPD, AND THEN

1477
00:46:26,352 --> 00:46:28,855
IF YOU'RE UNFORTUNATE ENOUGH TO

1478
00:46:28,855 --> 00:46:32,325
HAVE BOTH A LONG PERIOD AND LOW

1479
00:46:32,325 --> 00:46:34,594
LIGHT SENSITIVITY THEN YOU MAY

1480
00:46:34,594 --> 00:46:38,297
FALL INTO THE NON-24 CATEGORY.

1481
00:46:38,297 --> 00:46:43,236
STHIS IDEA THAT WE HAVE DIFFERET

1482
00:46:43,236 --> 00:46:45,471
PATHWAYS TO DSPD AND DIFFERENT

1483
00:46:45,471 --> 00:46:47,206
PHENOTYPES IS NOT NEW.

1484
00:46:47,206 --> 00:46:49,208
SO THIS IS A PAPER THAT WAS

1485
00:46:49,208 --> 00:46:50,576
PUBLISHED IN 2017 THAT WAS

1486
00:46:50,576 --> 00:46:52,645
TRYING TO RECRUIT PATIENTS WITH

1487
00:46:52,645 --> 00:46:53,079
DSPD.

1488
00:46:53,079 --> 00:46:54,714
AND BASED ON CLINICAL INTERVIEW,

1489
00:46:54,714 --> 00:46:56,749
THEY ALL MET THE CRITERIA THAT I

1490
00:46:56,749 --> 00:46:58,084
OUTLINED FROM THE ICSD AND THEY

1491
00:46:58,084 --> 00:47:00,987
ALL MET THE CRITERIA FOR DSPD.

1492
00:47:00,987 --> 00:47:03,189
THEY THEN TOOK A MEASURE OF

1493
00:47:03,189 --> 00:47:04,524
MELATONIN, WHICH IS ONE OF THE

1494
00:47:04,524 --> 00:47:06,626
MARKERS THAT CAN HELP INDICATE

1495
00:47:06,626 --> 00:47:09,695
CIRCADIAN TIMING, AND THEY FOUND

1496
00:47:09,695 --> 00:47:16,135
THAT ABOUT 60% OF THEM HAD A

1497
00:47:16,135 --> 00:47:18,504
DOWN LOW OCCURRING BEFORE

1498
00:47:18,504 --> 00:47:21,240
BEDTIME WHEREAS ABOUT 40% DO

1499
00:47:21,240 --> 00:47:21,674
NOT.

1500
00:47:21,674 --> 00:47:23,543
WE CAN GO THROUGH SORT OF AN

1501
00:47:23,543 --> 00:47:23,976
EXAMPLE HERE.

1502
00:47:23,976 --> 00:47:27,013
IF WE HAVE OUR CONTROL KIND OF

1503
00:47:27,013 --> 00:47:28,214
OUR CONVENTIONAL SLEEP-WAKE

1504
00:47:28,214 --> 00:47:30,516
TIMING HERE, UNDER NORMAL

1505
00:47:30,516 --> 00:47:32,218
CONDITIONS, YOUR MELATONIN ONSET

1506
00:47:32,218 --> 00:47:34,086
SHOULD BE ABOUT TWO HOURS BEFORE

1507
00:47:34,086 --> 00:47:35,955
YOUR H HABITUAL BEDTIME, SO

1508
00:47:35,955 --> 00:47:37,456
SOMEBODY WHO'S SLEEPING FROM

1509
00:47:37,456 --> 00:47:39,325
10:00 P.M. TO 6:00 A.M., WE

1510
00:47:39,325 --> 00:47:42,728
WOULD EXPECT THEIR DLMO TO OCCUR

1511
00:47:42,728 --> 00:47:43,229
ABOUT HERE.

1512
00:47:43,229 --> 00:47:45,298
WE HAVE TWO DIFFERENT PEOPLE

1513
00:47:45,298 --> 00:47:48,267
HERE WITH DSPD, BOTH ARE FALLING

1514
00:47:48,267 --> 00:47:50,269
ASLEEP AT 2 AND WAKING UP AT 10

1515
00:47:50,269 --> 00:47:52,138
BUT YOU CAN IMAGINE BOTH OF THEM

1516
00:47:52,138 --> 00:47:54,240
MAY WANT TO GO TO BED AT 10 AND

1517
00:47:54,240 --> 00:47:56,242
WAKE UP AT SIX.

1518
00:47:56,242 --> 00:48:00,313
THE QUOTE-UNQUOTE CIRCADIAN

1519
00:48:00,313 --> 00:48:03,916
DSWPD INDIVIDUAL, THEIR DLMO IS

1520
00:48:03,916 --> 00:48:09,155
OCCURRING PAST THEIR -- THIS

1521
00:48:09,155 --> 00:48:10,423
OTHER GROUP IS REALLY

1522
00:48:10,423 --> 00:48:12,091
INTERESTING, SO THE

1523
00:48:12,091 --> 00:48:15,528
NON-CIRCADIAN DSPD, THEIR DLMO

1524
00:48:15,528 --> 00:48:16,295
IS OCCURRING AT THE SAME TIME AS

1525
00:48:16,295 --> 00:48:18,698
SOMEBODY WHO CAN FALL ASLEEP AT

1526
00:48:18,698 --> 00:48:20,800
10:00 BUT THEY'RE NOT ABLE TO

1527
00:48:20,800 --> 00:48:22,368
FALL ASLEEP UNTIL 2:00 A.M.

1528
00:48:22,368 --> 00:48:23,703
NOW WHAT'S REALLY INTERESTING

1529
00:48:23,703 --> 00:48:25,004
ABOUT THIS POPULATION IS THAT

1530
00:48:25,004 --> 00:48:26,272
THEY'RE PRESUMABLY ABLE TO DO

1531
00:48:26,272 --> 00:48:28,040
THIS NIGHT AFTER NIGHT, AND SO

1532
00:48:28,040 --> 00:48:29,775
THERE SEEMS TO BE A DESYNCHRONY

1533
00:48:29,775 --> 00:48:34,880
OR A MISMATCH BETWEEN THAT MEL

1534
00:48:34,880 --> 00:48:37,383
TOE NEN SAIR CADEIAN MARKER AND

1535
00:48:37,383 --> 00:48:38,484
THAT MARKER OF SLEEP THAT

1536
00:48:38,484 --> 00:48:39,352
PERSISTS.

1537
00:48:39,352 --> 00:48:40,219
SO THIS INDIVIDUAL, I DON'T

1538
00:48:40,219 --> 00:48:42,188
THINK IS THE SAME AS THIS

1539
00:48:42,188 --> 00:48:43,723
INDIVIDUAL, BUT I'M NOT SURE

1540
00:48:43,723 --> 00:48:45,291
THAT THEY DON'T HAVE A CIRCADIAN

1541
00:48:45,291 --> 00:48:45,558
PROBLEM.

1542
00:48:45,558 --> 00:48:47,827
I THINK IT MAY JUST BE A

1543
00:48:47,827 --> 00:48:51,998
DIFFERENT CIRCADIAN PROBLEM THAN

1544
00:48:51,998 --> 00:48:52,632
OUR MIDDLE INDIVIDUAL.

1545
00:48:52,632 --> 00:48:54,400
BECAUSE OF THAT, WE SUGGESTED

1546
00:48:54,400 --> 00:48:55,668
MORE NEUTRAL TERMINOLOGY UNTIL

1547
00:48:55,668 --> 00:48:57,169
WE BETTER FIGURE OUT THE

1548
00:48:57,169 --> 00:48:59,071
PATHOLOGY, SO PACEICALLY JUST

1549
00:48:59,071 --> 00:49:02,108
TAKING THAT CIRCADIAN GROUP AND

1550
00:49:02,108 --> 00:49:08,547
CALLING THEM DSPD TYPE 1 AND

1551
00:49:08,547 --> 00:49:10,182
TYPE 2 UNTIL WE CAN BETTER

1552
00:49:10,182 --> 00:49:11,784
UNDERSTAND WHY THESE TWO

1553
00:49:11,784 --> 00:49:12,218
PHENOTYPES EXIST.

1554
00:49:12,218 --> 00:49:13,986
AND WHY IS THAT IMPORTANT?

1555
00:49:13,986 --> 00:49:18,024
AND FOR THAT, I WANT TO CIRCLE

1556
00:49:18,024 --> 00:49:19,825
BACK TO SOME OF THE QUESTIONS

1557
00:49:19,825 --> 00:49:22,028
THAT MY PATIENTS HAVE POSE THE.

1558
00:49:22,028 --> 00:49:25,431
WHAT I HAVE HERE IS THE 2007

1559
00:49:25,431 --> 00:49:27,466
PRACTICE PARAMETERS FOR CLINICAL

1560
00:49:27,466 --> 00:49:28,701
EVALUATION AND TREAT M OF

1561
00:49:28,701 --> 00:49:29,568
CIRCADIAN RHYTHM SLEEP

1562
00:49:29,568 --> 00:49:29,902
DISORDERS.

1563
00:49:29,902 --> 00:49:31,404
THAT PATIENT I SHOWED YOU AT THE

1564
00:49:31,404 --> 00:49:32,705
BEGINNING ON HIS VERY FIRST

1565
00:49:32,705 --> 00:49:33,773
APPOINTMENT, HE WALKED IN WITH

1566
00:49:33,773 --> 00:49:36,409
THIS PAPER IN HAND, AND HE SAID,

1567
00:49:36,409 --> 00:49:38,444
THESE WERE PUBLISHED IN 2007.

1568
00:49:38,444 --> 00:49:39,979
AT THAT TIME, THE ONLY

1569
00:49:39,979 --> 00:49:41,414
RECOMMENDATIONS WERE TO USE

1570
00:49:41,414 --> 00:49:43,049
LIGHT AND MELATONIN.

1571
00:49:43,049 --> 00:49:44,550
IT'S NOW 2013.

1572
00:49:44,550 --> 00:49:49,021
WHAT ELSE IS AVAILABLE?

1573
00:49:49,021 --> 00:49:50,790
AND THAT REALLY STRUCK ME AT THE

1574
00:49:50,790 --> 00:49:52,958
TIME, ESPECIALLY WHEN OUR 2015

1575
00:49:52,958 --> 00:49:54,260
GUIDELINES CAME OUT AND WE

1576
00:49:54,260 --> 00:49:56,128
ACTUALLY ENDED UP WITH EVEN LESS

1577
00:49:56,128 --> 00:49:57,530
TO OFFER HIM AT THAT POINT.

1578
00:49:57,530 --> 00:49:59,832
SO IF YOU LOOK AT THE 2015

1579
00:49:59,832 --> 00:50:04,070
TREATMENT GUIDELINES, THE

1580
00:50:04,070 --> 00:50:05,037
QUESTION IS WHAT HAPPENED TO

1581
00:50:05,037 --> 00:50:06,138
LIGHT AT THAT POINT?

1582
00:50:06,138 --> 00:50:08,441
AND IT'S NOT THAT LIGHT WAS

1583
00:50:08,441 --> 00:50:11,577
DEMONSTRATED TO BE HARMFUL AT

1584
00:50:11,577 --> 00:50:13,446
ALL IN THIS POPULATION.

1585
00:50:13,446 --> 00:50:15,414
IT'S JUST THERE WAS INSUFFICIENT

1586
00:50:15,414 --> 00:50:16,882
EVIDENCE TO SUPPORT EFFICACY OF

1587
00:50:16,882 --> 00:50:18,117
LIGHT THERAPY USING THEIR OUT

1588
00:50:18,117 --> 00:50:19,518
COME MEASURES, SO THEY WEREN'T

1589
00:50:19,518 --> 00:50:24,090
ABLE TO MAKE A RECOMMENDATION.

1590
00:50:24,090 --> 00:50:25,725
I THINK PART OF THAT, AND THIS

1591
00:50:25,725 --> 00:50:27,526
IS ME THEORIZING, COMES FROM THE

1592
00:50:27,526 --> 00:50:29,495
FACT THAT THEY HAVE THIS SORT OF

1593
00:50:29,495 --> 00:50:30,830
MUDDY POPULATION WHERE WE'RE PUT

1594
00:50:30,830 --> 00:50:32,465
AGO CLINICAL PHENOTYPE TOGETHER

1595
00:50:32,465 --> 00:50:34,734
WHEN THEY MAY HAVE DIFFERENT

1596
00:50:34,734 --> 00:50:36,001
UNDERLYING PATHOPHYSIOLOGY.

1597
00:50:36,001 --> 00:50:38,671
JUST TO ILLUSTRATE THAT, ONE OF

1598
00:50:38,671 --> 00:50:43,376
THE PAPERS THAT WAS CITED TO SEE

1599
00:50:43,376 --> 00:50:45,111
IF WE COULD RECOMMEND LIGHT IS

1600
00:50:45,111 --> 00:50:47,079
THIS ONE HERE, THESE -- A BRIGHT

1601
00:50:47,079 --> 00:50:49,315
WHITE LIGHT MASK OR PLACEBO,

1602
00:50:49,315 --> 00:50:51,951
THEY GIVE THEM LIGHT FOR FOUR

1603
00:50:51,951 --> 00:50:53,719
HOURS ON AWAKENING, AND THEY

1604
00:50:53,719 --> 00:50:55,254
FOUND THAT OVERALL, THE RESULTS

1605
00:50:55,254 --> 00:50:56,956
WERE NOT SIGNIFICANT, BUT IF

1606
00:50:56,956 --> 00:50:58,724
THEY DID A SUBGROUP ANALYSIS

1607
00:50:58,724 --> 00:51:00,359
LOOKING AT THOSE INDIVIDUALS WHO

1608
00:51:00,359 --> 00:51:03,929
HAD LATER MELATONIN ACROPHASES,

1609
00:51:03,929 --> 00:51:05,030
THEY ACTUALLY DID RESPOND

1610
00:51:05,030 --> 00:51:05,998
COMPARED TO THE REST OF THE

1611
00:51:05,998 --> 00:51:06,332
GROUP.

1612
00:51:06,332 --> 00:51:08,434
AND SO YOU CAN THEORIZE THAT

1613
00:51:08,434 --> 00:51:13,038
MAYBE THEY HAD THEM -- THOSE WHO

1614
00:51:13,038 --> 00:51:15,841
HAD A LATER AND MORE CONCORDANT

1615
00:51:15,841 --> 00:51:17,476
DLMO WERE THE ONES WHO ACTUALLY

1616
00:51:17,476 --> 00:51:19,211
RESPONDED TO LIGHT AND IT MAYING

1617
00:51:19,211 --> 00:51:22,815
THAT THIS POPULATION DOESN'T

1618
00:51:22,815 --> 00:51:24,550
RESPOND AS WELL TO LIGHT AND WE

1619
00:51:24,550 --> 00:51:27,920
NEED TO START BETTER PHENOTYPING

1620
00:51:27,920 --> 00:51:29,021
TO FIND BETTER TREATMENTS.

1621
00:51:29,021 --> 00:51:31,724
SO THIS IS KIND OF LAYING OUT

1622
00:51:31,724 --> 00:51:34,894
WHAT THAT MIGHT LOOK LIKE.

1623
00:51:34,894 --> 00:51:38,597
IF YOU HAVE SOMEBODY WHO IS DS

1624
00:51:38,597 --> 00:51:41,634
PD-1 WITH HIGH IS THE LIGHT

1625
00:51:41,634 --> 00:51:42,735
SENSITIVITY, AVOID EVENING

1626
00:51:42,735 --> 00:51:43,302
LIGHT, SEEK MORNING LIGHT.

1627
00:51:43,302 --> 00:51:46,105
IF YOU HAVE DS PD-1 WITH LOW

1628
00:51:46,105 --> 00:51:48,207
LIGHT SENSITIVITY, YOU CAN

1629
00:51:48,207 --> 00:51:58,117
OPTIMIZE NON-PHOTI, ZEITGEBERS,

1630
00:51:58,117 --> 00:51:59,752
ANYTHING LIGHT-BASED THAT HELPS

1631
00:51:59,752 --> 00:52:02,254
YOUR BODY KNOW WHAT TIME IT IS,

1632
00:52:02,254 --> 00:52:03,656
AND PHARMACOLOGICALLY WE'RE

1633
00:52:03,656 --> 00:52:08,160
LOOKING AT ARE THERE -- CAN WE

1634
00:52:08,160 --> 00:52:11,330
RESCUE THE CIRCADIAN LIGHT

1635
00:52:11,330 --> 00:52:12,198
RESPONSE.

1636
00:52:12,198 --> 00:52:14,033
IS THIS SOMEBODY THAT MAY HAVE

1637
00:52:14,033 --> 00:52:17,069
THE CIRCADIAN STATE, BUT THEY --

1638
00:52:17,069 --> 00:52:19,371
THAT HELPS THEM TO FALL ASLEEP

1639
00:52:19,371 --> 00:52:23,309
THEN, AND ARE THERE -- CAN WE

1640
00:52:23,309 --> 00:52:25,344
PULL FROM THINGS WE DO IN

1641
00:52:25,344 --> 00:52:26,779
INSOMNIA AND ELSEWHERE TO TRY TO

1642
00:52:26,779 --> 00:52:27,847
HELP THIS PARTICULAR POPULATION

1643
00:52:27,847 --> 00:52:31,884
AN WHY IS IT THAT THEY HAVE THAT

1644
00:52:31,884 --> 00:52:32,551
INTERNAL DESYNCHRONY.

1645
00:52:32,551 --> 00:52:34,186
SO WE WERE ASKED TO KIND OF

1646
00:52:34,186 --> 00:52:37,890
HIGHLIGHT GAPS IN AND AREAS OF

1647
00:52:37,890 --> 00:52:38,557
REAR SEARCH.

1648
00:52:38,557 --> 00:52:42,862
WE DO NEED TO TAKE INTO ACCOUNT

1649
00:52:42,862 --> 00:52:44,230
THESE DIFFERENT -- I THINK IT

1650
00:52:44,230 --> 00:52:46,966
WILL HELP US COME UP WITH

1651
00:52:46,966 --> 00:52:47,833
BETTER, MORE TARGETED

1652
00:52:47,833 --> 00:52:48,434
TREATMENTS.

1653
00:52:48,434 --> 00:52:52,004
ALSO, AS WE'RE TALKING ABOUT

1654
00:52:52,004 --> 00:52:52,972
TREATMENTS, AGAIN GOING BACK TO

1655
00:52:52,972 --> 00:52:54,039
THAT PATIENT AFTER I STARTED

1656
00:52:54,039 --> 00:52:56,675
SEEING HIM, THIS STUDY WAS

1657
00:52:56,675 --> 00:53:01,146
RELEASED LOOKING AT TASIMELTEON

1658
00:53:01,146 --> 00:53:02,982
FOR NON-24 HOUR SLEEP-WAKE

1659
00:53:02,982 --> 00:53:03,249
DISORDER.

1660
00:53:03,249 --> 00:53:04,416
IN THIS PARTICULAR TRIAL, THEY

1661
00:53:04,416 --> 00:53:05,918
DID FIND THAT ABOUT 20% OF THE

1662
00:53:05,918 --> 00:53:09,755
PATIENTS WHO ARE ENROLLED DID

1663
00:53:09,755 --> 00:53:10,256
ENTRAIN WITHIN ONE MONTH

1664
00:53:10,256 --> 00:53:12,157
COMPARED TO ABOUT 3% IN THE

1665
00:53:12,157 --> 00:53:12,858
PLACEBO GROUP.

1666
00:53:12,858 --> 00:53:16,629
AND I PUT HERE THE ACTUAL

1667
00:53:16,629 --> 00:53:20,366
VERBIAGE FROM THE FDA ABOUT THE

1668
00:53:20,366 --> 00:53:21,767
APPROVAL OF THIS MEDICATION FOR

1669
00:53:21,767 --> 00:53:22,968
USE IN NON-24.

1670
00:53:22,968 --> 00:53:26,805
YOU CAN SEE INDICATIONS AND

1671
00:53:26,805 --> 00:53:29,708
USAGE, BUT AS A CLINICIAN, IT

1672
00:53:29,708 --> 00:53:33,612
HAS BEEN PARTICULARLY CHALLENGES

1673
00:53:33,612 --> 00:53:34,346
BECAUSE IF THE INSURANCE

1674
00:53:34,346 --> 00:53:36,181
COMPANIES IF BACK TO THE PRIMARY

1675
00:53:36,181 --> 00:53:37,716
DATA, THEY SAY THIS MEDICATION

1676
00:53:37,716 --> 00:53:40,219
WAS ONLY STUDIED IN BLIND

1677
00:53:40,219 --> 00:53:41,520
INDIVIDUALSMENT AND SO THEY

1678
00:53:41,520 --> 00:53:47,993
OFTEN DENY IT FOR MY CITED

1679
00:53:47,993 --> 00:53:50,563
PATIENTS EVEN THOUGH THE FDA

1680
00:53:50,563 --> 00:53:54,733
SPECIFICATIONS DON'T SPECIFY.

1681
00:53:54,733 --> 00:53:56,468
SO MY AREA OF RESEARCH NEED,

1682
00:53:56,468 --> 00:53:58,103
NUMBER TWO, IS TO MAKE SURE

1683
00:53:58,103 --> 00:53:58,737
YOU'RE CONSIDERING THE FACT THAT

1684
00:53:58,737 --> 00:54:00,306
BOTH SIGHTED AND BLIND

1685
00:54:00,306 --> 00:54:03,809
INDIVIDUALS MAY HAVE NON-24,

1686
00:54:03,809 --> 00:54:07,746
THEY MAY -- RIGHT NOW WE HAVE

1687
00:54:07,746 --> 00:54:08,581
ALMOST NOTHING TO RECOMMEND FOR

1688
00:54:08,581 --> 00:54:09,148
THEM.

1689
00:54:09,148 --> 00:54:11,984
IT'S ALL SORT OF EXPERIMENTAL.

1690
00:54:11,984 --> 00:54:14,720
AND THEN LASTLY, JUST TO BRIEFLY

1691
00:54:14,720 --> 00:54:20,192
GET ON MY CLINICIAN SOAP BOX, I

1692
00:54:20,192 --> 00:54:23,662
HIGHLIGHTED THE ICSD DIAGNOSTIC

1693
00:54:23,662 --> 00:54:26,966
CRITERIA FOR DSPD, AND JUST TO

1694
00:54:26,966 --> 00:54:31,470
POINT OUT HERE, ONE OF THE TOOLS

1695
00:54:31,470 --> 00:54:33,305
WE USE TO DIAGNOSE IS A

1696
00:54:33,305 --> 00:54:34,640
RECOMMENDATION FOR ACTIGRAPHY

1697
00:54:34,640 --> 00:54:35,374
MONITORING.

1698
00:54:35,374 --> 00:54:37,576
NOW, AS A FIELD, I THINK ANYBODY

1699
00:54:37,576 --> 00:54:40,312
WHO PRACTICES SLEEP OR SAADE

1700
00:54:40,312 --> 00:54:48,921
MEDICIRCADIANRESEARCH, THIS STUS

1701
00:54:48,921 --> 00:54:50,889
PUBLISHED SEVERAL YEARS AGO

1702
00:54:50,889 --> 00:54:54,393
SHOWING ALL THE SPACES

1703
00:54:54,393 --> 00:54:58,764
ACTIGRAPHY CAN BE HELPFUL FOR

1704
00:54:58,764 --> 00:54:59,632
OUR PATIENTS.

1705
00:54:59,632 --> 00:55:02,568
ANY TIME YOU ACTUALLY TRY TO USE

1706
00:55:02,568 --> 00:55:05,838
ACTIGRAPHY IN THIS CASE AND TRY

1707
00:55:05,838 --> 00:55:07,039
TO GET IT -- AGAIN, WE'RE BACK

1708
00:55:07,039 --> 00:55:12,244
TO BEING DENIED BY -- TRYING TO

1709
00:55:12,244 --> 00:55:13,812
FIGURE OUT WHAT IS THE RATIONALE

1710
00:55:13,812 --> 00:55:14,980
WHEN AS A FIELD, WE'RE SAYING WE

1711
00:55:14,980 --> 00:55:16,315
NEED THIS AND THE INSURANCE

1712
00:55:16,315 --> 00:55:18,083
COMPANIES ARE PUSHING BACK AND

1713
00:55:18,083 --> 00:55:20,486
SAYING NO, AND SO GOING INTO THE

1714
00:55:20,486 --> 00:55:21,654
COVERAGE GUIDELINES AND ACTUALLY

1715
00:55:21,654 --> 00:55:22,988
READING AND TRYING TO GET A

1716
00:55:22,988 --> 00:55:24,056
PERSPECTIVE OF WHERE THEY'RE

1717
00:55:24,056 --> 00:55:27,660
COMING FROM, THIS IS WHERE THAT

1718
00:55:27,660 --> 00:55:29,728
DENIAL IS COMING FROM, WHICH IS

1719
00:55:29,728 --> 00:55:33,232
BASICALLY THAT ACTIGRAPHY IS

1720
00:55:33,232 --> 00:55:34,633
CONSIDERED EXPERIMENTAL,

1721
00:55:34,633 --> 00:55:37,302
INVESTIGATIONAL AND/OR UNPROVEN,

1722
00:55:37,302 --> 00:55:38,604
AND IT'S REALLY THAT THEY'VE SET

1723
00:55:38,604 --> 00:55:40,005
THE BAR FOR WHETHER OR NOT

1724
00:55:40,005 --> 00:55:41,206
ACTIGRAPHY IS BENEFICIAL RIGHT

1725
00:55:41,206 --> 00:55:42,274
HERE.

1726
00:55:42,274 --> 00:55:46,211
WHICH SAYS, DOES THE USE OF ACT

1727
00:55:46,211 --> 00:55:48,080
GA FEE IN THE USE OF SLEEP

1728
00:55:48,080 --> 00:55:50,616
DISORDERS IMPROVE THE NET HEALTH

1729
00:55:50,616 --> 00:55:51,150
OUTCOME?

1730
00:55:51,150 --> 00:55:55,187
WHICH IS KIND OF A HARD BAR TO

1731
00:55:55,187 --> 00:55:56,588
HIT.

1732
00:55:56,588 --> 00:55:57,823
COMPARING ACTIGRAPHY TO THINGS

1733
00:55:57,823 --> 00:56:00,092
LIKE GSP AND SLEEP DIARIES AND

1734
00:56:00,092 --> 00:56:01,193
ESSENTIALLY WHAT THEY CAME DOWN

1735
00:56:01,193 --> 00:56:02,628
TO BOTH FOR ADULTS AND FOR

1736
00:56:02,628 --> 00:56:04,797
CHILDREN WAS THAT THE EVIDENCE

1737
00:56:04,797 --> 00:56:05,698
IS INSUFFICIENT TO DETERMINE

1738
00:56:05,698 --> 00:56:09,301
THAT THE TECHNOLOGY RESULTS IN

1739
00:56:09,301 --> 00:56:12,771
AN IMPROVEMENT IN THE NET HEALTH

1740
00:56:12,771 --> 00:56:16,408
OUTCOMES.

1741
00:56:16,408 --> 00:56:17,376
OUTCOME.

1742
00:56:17,376 --> 00:56:19,144
MY FINAL CHARGE IS FOR YOU TO

1743
00:56:19,144 --> 00:56:21,747
MAKE USE OF THESE CON DER FULL

1744
00:56:21,747 --> 00:56:23,282
TOOLS WE HAVE IN THE CLINIC.

1745
00:56:23,282 --> 00:56:24,583
ONE OF THE BIGGEST BARRIERS WE

1746
00:56:24,583 --> 00:56:25,984
HAVE RIGHT NOW IS MAKING SURE

1747
00:56:25,984 --> 00:56:27,519
THAT OUR PATIENTS ARE ABLE TO

1748
00:56:27,519 --> 00:56:30,556
GET THESE DIAGNOSTIC TOOLS PAID

1749
00:56:30,556 --> 00:56:30,723
FOR.

1750
00:56:30,723 --> 00:56:32,124
SO IF WE'RE GOING TO PLAY THE

1751
00:56:32,124 --> 00:56:34,293
INSURANCE GAME, WE NEED MORE

1752
00:56:34,293 --> 00:56:36,261
TRIALS TO DEMONSTRATE THE

1753
00:56:36,261 --> 00:56:38,530
BENEFIT OF INCLUDING ACTIGRAPHY

1754
00:56:38,530 --> 00:56:42,267
AND ALSO MELATONIN TESTING, FOR

1755
00:56:42,267 --> 00:56:43,469
THE CLINICAL OUTCOMES OF THESE

1756
00:56:43,469 --> 00:56:44,036
POPULATIONS.

1757
00:56:44,036 --> 00:56:45,637
AND SO WITH THAT, I WOULD JUST

1758
00:56:45,637 --> 00:56:47,506
LIKE TO WRAP UP BY ACKNOWLEDGING

1759
00:56:47,506 --> 00:56:49,708
BOTH PHYLLIS AND KATHY, WHO

1760
00:56:49,708 --> 00:56:52,010
REALLY HELPED ME WITH GETTING

1761
00:56:52,010 --> 00:56:53,445
THE CIRCADIAN CLINIC GOING, AS

1762
00:56:53,445 --> 00:56:54,613
WELL AS TRANSITIONING FROM

1763
00:56:54,613 --> 00:56:57,249
ANIMAL TO HUMAN RESEARCH, OUR

1764
00:56:57,249 --> 00:57:05,324
COLLABORATORS IN YOU -- AS WELLS

1765
00:57:05,324 --> 00:57:06,925
OUR STAFF WHO COLLECTED MUCH OF

1766
00:57:06,925 --> 00:57:08,393
THE DATA I SHOWED AS WELL AS THE

1767
00:57:08,393 --> 00:57:09,495
FUNDING AND LAST BUT CERTAINLY

1768
00:57:09,495 --> 00:57:11,764
NOT LEAST, ALL OF THE PATIENTS

1769
00:57:11,764 --> 00:57:18,470
WHO ALCOHOL E CHALLENGED ME ANDE

1770
00:57:18,470 --> 00:57:19,638
ABOUT THIS DISEASE.

1771
00:57:19,638 --> 00:57:20,873
THE PHRASE THAT IS CONSTANTLY IN

1772
00:57:20,873 --> 00:57:22,474
THE BACK OF MY MIND, WHICH IS,

1773
00:57:22,474 --> 00:57:23,776
IT'S 2024, WHAT ELSE DO WE HAVE

1774
00:57:23,776 --> 00:57:24,476
NOW?

1775
00:57:24,476 --> 00:57:26,445
I HAVE TO SAY, MY PATIENT IS

1776
00:57:26,445 --> 00:57:26,979
VERY KIND.

1777
00:57:26,979 --> 00:57:28,514
HE DOES NOT COME TO EVERY SINGLE

1778
00:57:28,514 --> 00:57:29,948
APPOINTMENT AND SAY THAT OVER

1779
00:57:29,948 --> 00:57:31,150
AND OVER, BUT IN THE BACK OF MY

1780
00:57:31,150 --> 00:57:33,252
HEAD, EVERY TIME I TURN THE

1781
00:57:33,252 --> 00:57:34,119
CALENDAR, THAT'S THE PHRASE

1782
00:57:34,119 --> 00:57:36,522
THAT'S OUT THERE AND I THINK

1783
00:57:36,522 --> 00:57:37,523
REMEMBERING THAT WE HAVE

1784
00:57:37,523 --> 00:57:39,057
PATIENTS SITTING IN CLINIC RIGHT

1785
00:57:39,057 --> 00:57:40,058
NOW LOOKING FOR THESE ANSWERS

1786
00:57:40,058 --> 00:57:40,793
FOR US.

1787
00:57:40,793 --> 00:57:42,227
SO WITH THAT, I WOULD BE HAPPY

1788
00:57:42,227 --> 00:57:49,368
TO WRAP UP.

1789
00:57:49,368 --> 00:57:53,138
>> THANK YOU SO MUCH.

1790
00:57:53,138 --> 00:57:53,806
AND DEFINITELY SOMETHING TO

1791
00:57:53,806 --> 00:57:54,072
REMEMBER.

1792
00:57:54,072 --> 00:57:54,973
WE HAVE SOME EXCELLENT QUESTIONS

1793
00:57:54,973 --> 00:57:56,208
IN THE CHAT.

1794
00:57:56,208 --> 00:57:58,977
I JUST WANTED A QUICK REMINDER,

1795
00:57:58,977 --> 00:58:00,646
KEEP PUTTING YOUR -- OR IN THE Q

1796
00:58:00,646 --> 00:58:01,280
& A BOX.

1797
00:58:01,280 --> 00:58:02,447
KEEP PUTTING YOUR QUESTIONS IN

1798
00:58:02,447 --> 00:58:03,949
THE Q & A BOX FOR THE
DESIGNATED

1799
00:58:03,949 --> 00:58:05,317
Q & A SESSION FOLLOWING THE
NEXT

1800
00:58:05,317 --> 00:58:05,717
TALK.

1801
00:58:05,717 --> 00:58:08,587
AND NOW I'D LIKE TO INTRODUCE

1802
00:58:08,587 --> 00:58:10,522
DR. NOUR MAKAREM FOR A

1803
00:58:10,522 --> 00:58:21,066
PRESENTATION ON CHRONOMEDICINE.

1804
00:58:23,502 --> 00:58:25,637
>> GOOD AFTERNOON,
EVERYONE.

1805
00:58:25,637 --> 00:58:28,574
AND THANK YOU SO MUCH TO THE

1806
00:58:28,574 --> 00:58:29,708
ORGANIZERS FOR INVITING ME TO

1807
00:58:29,708 --> 00:58:30,542
PRESENT.

1808
00:58:30,542 --> 00:58:33,145
MY PRESENTATION WILL ADDRESS

1809
00:58:33,145 --> 00:58:34,680
ADVANCES AND OPPORTUNITIES IN

1810
00:58:34,680 --> 00:58:35,547
CHRONOMEDICINE FOR HEALTH

1811
00:58:35,547 --> 00:58:36,748
PRESERVATION AND CHRONIC DISEASE

1812
00:58:36,748 --> 00:58:39,384
PREVENTION.

1813
00:58:39,384 --> 00:58:41,019
I HAVE NO CONFLICTS OF INTEREST

1814
00:58:41,019 --> 00:58:42,554
TO DISCLOSE.

1815
00:58:42,554 --> 00:58:44,089
IN TERMS OF THE LEARNING

1816
00:58:44,089 --> 00:58:45,624
OBJECTIVES FOR MY TALK, BY THE

1817
00:58:45,624 --> 00:58:48,894
END OF THIS PRESENTATION,

1818
00:58:48,894 --> 00:58:51,063
ATTENDEES SHOULD BE ABLE TO

1819
00:58:51,063 --> 00:58:52,397
DEFINE CHRONOMEDICINE AND

1820
00:58:52,397 --> 00:58:53,899
UNDERSTAND ITS POTENTIAL ROLE IN

1821
00:58:53,899 --> 00:58:56,435
HEALTH PRESERVATION AND CHRONIC

1822
00:58:56,435 --> 00:59:00,372
DISEASE AND TREATMENT, TO

1823
00:59:00,372 --> 00:59:01,773
DESCRIBE -- FOCUSING ON

1824
00:59:01,773 --> 00:59:03,442
CARDIOMETABOLIC OUTCOMES AND

1825
00:59:03,442 --> 00:59:04,743
CARDIOVASCULAR DISEASE, AND ALSO

1826
00:59:04,743 --> 00:59:09,581
TO DESCRIBE HOW OPTIMIZING IF --

1827
00:59:09,581 --> 00:59:10,883
COULD ENHANCE PREVENTION AND

1828
00:59:10,883 --> 00:59:12,985
TREATMENT APPROACHES.

1829
00:59:12,985 --> 00:59:14,519
I'LL END BY OUTLOONING

1830
00:59:14,519 --> 00:59:16,488
CHALLENGES TO ADVANCING

1831
00:59:16,488 --> 00:59:18,023
CHRONOMEDICINE RESEARCH AND ALSO

1832
00:59:18,023 --> 00:59:18,557
HIGHLIGHTING KEY RESEARCH

1833
00:59:18,557 --> 00:59:20,893
PRIORITIES TO ADVANCE THIS FIELD

1834
00:59:20,893 --> 00:59:21,526
AND LEVERAGE CHRONOMEDICINE

1835
00:59:21,526 --> 00:59:22,861
APPROACHES FOR EXTENDING

1836
00:59:22,861 --> 00:59:23,729
HEALTHSPAN AND PREVENTING

1837
00:59:23,729 --> 00:59:26,498
CHRONIC DISEASE.

1838
00:59:26,498 --> 00:59:29,001
SO I'LL START WITH BASICS WITH

1839
00:59:29,001 --> 00:59:30,769
THE DEFINITION OF CHRONOMEDICINE

1840
00:59:30,769 --> 00:59:31,603
WHICH ESSENTIALLY TELLS US THAT

1841
00:59:31,603 --> 00:59:33,138
TIMING MATTERS.

1842
00:59:33,138 --> 00:59:35,073
CHRONOMEDICINE IS AN INNOVATIVE

1843
00:59:35,073 --> 00:59:35,908
SUBDISCIPLINE OF MEDICINE THAT

1844
00:59:35,908 --> 00:59:37,743
IS FOCUSED ON THE ROLE OF TIME

1845
00:59:37,743 --> 00:59:40,879
IN PHYSIOLOGY, ENDOCRINOLOGY,

1846
00:59:40,879 --> 00:59:42,848
METABOLISM AND BEHAVIOR AT

1847
00:59:42,848 --> 00:59:44,383
MULTIPLE ORGANIZATIONAL LEVELS

1848
00:59:44,383 --> 00:59:45,617
TO PRESERVE HEALTH AND TO

1849
00:59:45,617 --> 00:59:46,351
PREVENT, DIAGNOSE AND TREAT

1850
00:59:46,351 --> 00:59:48,086
DISEASE.

1851
00:59:48,086 --> 00:59:50,989
NOW CHRONOMEDICINE HAS MANY

1852
00:59:50,989 --> 00:59:51,623
APPLICATIONS AT THE INDIVIDUAL

1853
00:59:51,623 --> 00:59:53,458
AND THE POPULATION LEVEL THAT

1854
00:59:53,458 --> 00:59:55,861
ARE PHARMACOLOGIC OR

1855
00:59:55,861 --> 00:59:56,395
NON-PHARMACOLOGIC.

1856
00:59:56,395 --> 01:00:04,870
FORM ENCLOSE JIK APPLICATIONSPHE

1857
01:00:04,870 --> 01:00:06,271
TOXICITY AND SIDE EFFECTS.

1858
01:00:06,271 --> 01:00:08,040
SO REALLY GOOD EXAMPLES OF THIS

1859
01:00:08,040 --> 01:00:09,207
WOULD INCLUDE PAYING ATTENTION

1860
01:00:09,207 --> 01:00:11,410
TO THE TIMING OF CHEMOTHERAPY

1861
01:00:11,410 --> 01:00:15,847
AMONG CANCER PATIENTS, OR

1862
01:00:15,847 --> 01:00:17,749
BEDTIME DOSING MEDICATION TO

1863
01:00:17,749 --> 01:00:18,750
IMPROVE THE BLOOD PRESSURE

1864
01:00:18,750 --> 01:00:20,052
PATTERN DURING SLEEP AND

1865
01:00:20,052 --> 01:00:21,153
ATTENUATE THE MORNING SURGE.

1866
01:00:21,153 --> 01:00:22,788
BUT IN MY TALK TODAY, I'M GOING

1867
01:00:22,788 --> 01:00:25,524
TO FOCUS MORE ON THE

1868
01:00:25,524 --> 01:00:27,259
NON-PHARMACOLOGIC APPLICATIONS,

1869
01:00:27,259 --> 01:00:28,360
SPECIFICALLY ADDRESSING THE

1870
01:00:28,360 --> 01:00:30,429
TIMING OF ENVIRONMENTAL CUES AND

1871
01:00:30,429 --> 01:00:31,797
BEHAVIORAL FACTORS TO OPTIMIZE

1872
01:00:31,797 --> 01:00:34,733
CIRCADIAN RHYTHMS AND TO PROMOTE

1873
01:00:34,733 --> 01:00:35,300
HEALTH, MAXIMIZE DISEASE

1874
01:00:35,300 --> 01:00:41,907
PREVENTION AND DIESEL B DECELERE

1875
01:00:41,907 --> 01:00:42,307
BIOLOGICAL AGING.

1876
01:00:42,307 --> 01:00:43,675
SO AS THE PRIOR SPEAKERS HAVE

1877
01:00:43,675 --> 01:00:45,744
ALREADY INDICATED, OUR CIRCADIAN

1878
01:00:45,744 --> 01:00:48,714
RHYTHMS ARE CLOALED BY A MASTER

1879
01:00:48,714 --> 01:00:51,249
CLOCK THAT IS ENTRAINED BY

1880
01:00:51,249 --> 01:00:52,551
LIGHT.

1881
01:00:52,551 --> 01:00:55,153
BUT OUR OUR BEGANS, INVOLVED IN

1882
01:00:55,153 --> 01:00:57,689
METABOLIC PROCESSES, ALSO HAVE

1883
01:00:57,689 --> 01:00:58,623
THEIR OWN CLOCKS THAT REGULATE

1884
01:00:58,623 --> 01:00:59,558
THEIR FUNCTION AND THESE CLOCKS

1885
01:00:59,558 --> 01:01:01,493
ARE ALSO ENTRAINED BY OUR

1886
01:01:01,493 --> 01:01:02,694
EATING, SLEEP AND ACTIVITY

1887
01:01:02,694 --> 01:01:04,563
PATTERNS.

1888
01:01:04,563 --> 01:01:05,998
SO WHEN EATING, SLEEP AND

1889
01:01:05,998 --> 01:01:08,600
ACTIVITY PATTERNS OCCUR AT

1890
01:01:08,600 --> 01:01:09,901
UNCONVENTIONAL CIRCADIAN TIMES

1891
01:01:09,901 --> 01:01:13,605
OR ARE IRREGULAR, THESE PRIF RAM

1892
01:01:13,605 --> 01:01:14,906
CLOCKS BECOME MISS ALIGNED WITH

1893
01:01:14,906 --> 01:01:17,209
THE MASTER CLOCK IN THE BRAIT

1894
01:01:17,209 --> 01:01:22,147
CREATING A CASE OF CIRCADIAN

1895
01:01:22,147 --> 01:01:24,983
MISALIGNMENT WHICH LEADS TO

1896
01:01:24,983 --> 01:01:27,619
OBESITY, TYPE 2 DIABETES,

1897
01:01:27,619 --> 01:01:30,022
HYPERTENSION, HEART DISEASE, AS

1898
01:01:30,022 --> 01:01:31,957
WELL AS OTHER THINGS LIKE CANCER

1899
01:01:31,957 --> 01:01:33,525
AND OTHER PSYCHIATRIC DISORDERS.

1900
01:01:33,525 --> 01:01:36,294
IN MY NEXT SET OF SLIGHTS, I'M

1901
01:01:36,294 --> 01:01:38,463
GOING TO PROVIDE A HIGH LEVEL

1902
01:01:38,463 --> 01:01:42,601
SUM REAL OF WHAT IF WE KNOW

1903
01:01:42,601 --> 01:01:43,168
ABOUT THIS.

1904
01:01:43,168 --> 01:01:45,937
AND I'LL START WITH

1905
01:01:45,937 --> 01:01:47,105
CHRONONUTRITION WHICH REALLY

1906
01:01:47,105 --> 01:01:48,206
FOCUSES ON THE TIMING AND

1907
01:01:48,206 --> 01:01:49,875
REGULARITY OF EATING PATTERNS IN

1908
01:01:49,875 --> 01:01:51,309
THE 24-HOUR DAY AND ACROSS DAYS,

1909
01:01:51,309 --> 01:01:52,944
WHICH MAY BE AN IMPORTANT TARGET

1910
01:01:52,944 --> 01:01:55,480
FOR PROMOTING OUR CIRCADIAN

1911
01:01:55,480 --> 01:01:57,549
HEALTH.

1912
01:01:57,549 --> 01:02:00,252
SO ASPECT OF CHRONONUTRITION,

1913
01:02:00,252 --> 01:02:01,153
LIKELY CONTRIBUTES SUBSTANTIALLY

1914
01:02:01,153 --> 01:02:02,354
TO THE CHRONIC DISEASE BURDEN

1915
01:02:02,354 --> 01:02:04,089
THAT WE OBSERVE AT THE

1916
01:02:04,089 --> 01:02:05,190
POPULATION LEVEL, PARTICULARLY

1917
01:02:05,190 --> 01:02:06,525
THAT AMERICANS HAVE A TENDENCY

1918
01:02:06,525 --> 01:02:08,593
FOR LATER EATING TIMING,

1919
01:02:08,593 --> 01:02:12,697
SIGNIFICANT NIGHTTIME EATING AND

1920
01:02:12,697 --> 01:02:15,100
ERRATIC -- SHOWS THAT U.S.

1921
01:02:15,100 --> 01:02:17,069
ADULTS ESSENTIALLY EAT AROUND

1922
01:02:17,069 --> 01:02:18,870
THE CLOCK AND THERE'S A

1923
01:02:18,870 --> 01:02:22,441
FIVE-HOUR WINDOW BETWEEN 1 AND

1924
01:02:22,441 --> 01:02:26,711
6A.M. DURING WHICH -- MOST OF

1925
01:02:26,711 --> 01:02:28,814
THE CLORK INTAKE TENDS TO OCCUR

1926
01:02:28,814 --> 01:02:30,582
LATER IN THE DAY, AND THERE

1927
01:02:30,582 --> 01:02:32,884
SEEMS TO BE SUBSTANTIAL DAY TO

1928
01:02:32,884 --> 01:02:34,753
DAY VARIABILITY IN EATING TIMING

1929
01:02:34,753 --> 01:02:36,388
PATTERNS, WHICH BECOMES MOST

1930
01:02:36,388 --> 01:02:37,823
PRONOUNCED WHEN WE COMPARE

1931
01:02:37,823 --> 01:02:44,830
WEEKDAYS TO WEEKENDS.

1932
01:02:44,830 --> 01:02:46,932
NOW THESE METRICS HAVE BEEN MOST

1933
01:02:46,932 --> 01:02:48,667
EXTENSIVELY STUDIED IN RELATION

1934
01:02:48,667 --> 01:02:49,301
TO OBESITY RISK.

1935
01:02:49,301 --> 01:02:54,573
HERE ON MY SLIDE, I A COUPLE OF

1936
01:02:54,573 --> 01:02:56,641
LANDMARK FIGURES.

1937
01:02:56,641 --> 01:02:59,811
THESE ARE FINDINGS FROM A LARGE

1938
01:02:59,811 --> 01:03:00,612
PROSPECTIVE OBSERVATIONAL STUDY

1939
01:03:00,612 --> 01:03:02,781
OF U.S. AND CANADIAN ADULTS

1940
01:03:02,781 --> 01:03:06,084
RECRUITED FROM SEVENTH DAY

1941
01:03:06,084 --> 01:03:07,752
CHURCHES AND THEY EVALUATED THE

1942
01:03:07,752 --> 01:03:09,254
TIMING OF THE LARGEST MEAL IN

1943
01:03:09,254 --> 01:03:10,989
RELATION TO BMI AND THEY FOUND

1944
01:03:10,989 --> 01:03:16,595
THAT RELATIVE TO THOSE -- HAD A

1945
01:03:16,595 --> 01:03:22,934
SIGNIFICANT DECREASE I DURING TE

1946
01:03:22,934 --> 01:03:24,469
SEVEN-YEAR FOLLOW-UP PERIOD.

1947
01:03:24,469 --> 01:03:25,570
THE FIGURE ON THE RIGHT SIDE OF

1948
01:03:25,570 --> 01:03:26,972
MY SLIDE ARE FINDINGS FROM A

1949
01:03:26,972 --> 01:03:31,910
MEMETA-ANALYSIS OF RCTs AND THE

1950
01:03:31,910 --> 01:03:34,880
RESULTS CLEARLY SHOW EARLIER

1951
01:03:34,880 --> 01:03:36,348
EATING IMPROVES WEIGHT LOSS BY

1952
01:03:36,348 --> 01:03:38,483
23% WHICH IS A REALLY CLINICALLY

1953
01:03:38,483 --> 01:03:39,551
MEANINGFUL RESULT.

1954
01:03:39,551 --> 01:03:41,453
NOW ALTHOUGH EATING TIMING HAS

1955
01:03:41,453 --> 01:03:43,088
BEEN MOSTLY STUDIED TO OBESITY

1956
01:03:43,088 --> 01:03:46,925
RISK, IT'S ALSO BEEN RELATED TO

1957
01:03:46,925 --> 01:03:48,994
A -- THE FINDINGS GENERALLY TEND

1958
01:03:48,994 --> 01:03:50,662
TO SHOW THAT EARLIER EATING

1959
01:03:50,662 --> 01:03:52,597
TIMING IS RELATING TO LOWER

1960
01:03:52,597 --> 01:03:57,736
LEVELS OF LDL CHOLESTEROL,

1961
01:03:57,736 --> 01:03:59,404
BETTER FLY SEE MIBG REGULATION

1962
01:03:59,404 --> 01:04:10,615
 -- BETTER GLYCEMIC -- NOWANOTHF

1963
01:04:10,615 --> 01:04:12,350
CARDIOMETABOLIC OUTCOMES IS THE

1964
01:04:12,350 --> 01:04:13,351
VARIABILITY IN EATING TIMING

1965
01:04:13,351 --> 01:04:13,785
PATTERNS.

1966
01:04:13,785 --> 01:04:15,620
AND HERE I'M PRESENTING FINDINGS

1967
01:04:15,620 --> 01:04:18,490
FROM A COUPLE OF PAPERS THAT WE

1968
01:04:18,490 --> 01:04:20,792
PUBLISHED IN MY RESEARCH GROUP

1969
01:04:20,792 --> 01:04:22,827
WHICH EVALUATED DAY TO DAY

1970
01:04:22,827 --> 01:04:24,029
VARIABILITY IN EATING TIMING AS

1971
01:04:24,029 --> 01:04:25,730
WELL AS EATING JET LAG IN

1972
01:04:25,730 --> 01:04:27,265
RELATION TO CARDIOMETABOLIC

1973
01:04:27,265 --> 01:04:28,800
OUTCOMES, SO WHAT WE DID IN THIS

1974
01:04:28,800 --> 01:04:32,070
STUDY IS THAT WE USED THE MIH'S

1975
01:04:32,070 --> 01:04:36,808
SAS24 TO OBTAIN ELECTRONIC FOOD

1976
01:04:36,808 --> 01:04:38,143
RECORDS, AND THESE DATA WERE

1977
01:04:38,143 --> 01:04:39,544
USED TO EX-PRAK THE TIMING OF

1978
01:04:39,544 --> 01:04:43,949
THE FIRST AND THE LAST EATING --

1979
01:04:43,949 --> 01:04:45,483
AND WE USED THE STANDARD

1980
01:04:45,483 --> 01:04:47,452
DEVIATION OF THESE VARIABLES AS

1981
01:04:47,452 --> 01:04:49,087
A MEASURE OF DAY TO DAY

1982
01:04:49,087 --> 01:04:51,356
VARIABILITY IN EATING TIMING

1983
01:04:51,356 --> 01:04:53,158
PATTERNS AND WEEKDAY/WEEKEND

1984
01:04:53,158 --> 01:04:54,459
DIFFERENCES AS A MEASURE OF WHAT

1985
01:04:54,459 --> 01:04:56,094
WE CALLED EATING JET LAG.

1986
01:04:56,094 --> 01:04:58,263
WHAT WE FOUND IS GREATER DAY TO

1987
01:04:58,263 --> 01:05:02,267
DAY VARIABILITY IN EATING TIMING

1988
01:05:02,267 --> 01:05:05,103
WAS ASSOCIATED WITH

1989
01:05:05,103 --> 01:05:08,073
SIGNIFICANTLY HIGHER BMI, HIGHER

1990
01:05:08,073 --> 01:05:09,507
WASTE CIRCUMFERENCE, HIGHER

1991
01:05:09,507 --> 01:05:11,243
BLOOD PRESSURE, AND HIGHER

1992
01:05:11,243 --> 01:05:15,447
LEVELS OF CRP AS A MARKER OF

1993
01:05:15,447 --> 01:05:18,316
SYSTEMIC INFLAMMATION.

1994
01:05:18,316 --> 01:05:19,951
NOW TIGHTLY INTERTWINED WITH THE

1995
01:05:19,951 --> 01:05:21,219
TIMING AND REGULARITY OF OUR

1996
01:05:21,219 --> 01:05:22,287
EATING PATTERNS IS, OF COURSE,

1997
01:05:22,287 --> 01:05:25,357
THE TIMING AND REGULARITY OF OUR

1998
01:05:25,357 --> 01:05:26,491
SLEEP-WAKE PATTERNS, WHICH IS

1999
01:05:26,491 --> 01:05:28,226
ALSO AN IMPORTANT TARGET FOR

2000
01:05:28,226 --> 01:05:29,194
PROMOTING CIRCADIAN HEALTH.

2001
01:05:29,194 --> 01:05:31,196
IT IS WELL ESTABLISHED THAT

2002
01:05:31,196 --> 01:05:33,298
LATER SLEEP TIMING, WHICH WE

2003
01:05:33,298 --> 01:05:35,500
TYPICALLY OBSERVE IN EVENING

2004
01:05:35,500 --> 01:05:40,472
OROTATING SHIFT WORK AND IN --

2005
01:05:40,472 --> 01:05:42,607
AS WELL AS SLEEP DURATION AND

2006
01:05:42,607 --> 01:05:46,011
SLEEP TIMING ARE BOTH RINKED --

2007
01:05:46,011 --> 01:05:47,779
METABOLIC SYNDROME, DIABETES,

2008
01:05:47,779 --> 01:05:51,816
HYPERTENSION, AND ALSO TO HIGHER

2009
01:05:51,816 --> 01:05:54,786
ODDS OF HAVING POOR

2010
01:05:54,786 --> 01:05:56,454
CARDIOVASCULAR HEALTH AS DEFINED

2011
01:05:56,454 --> 01:05:57,355
BY THE AMERICAN HEART

2012
01:05:57,355 --> 01:05:57,889
ASSOCIATION FRAME WORKS.

2013
01:05:57,889 --> 01:05:59,991
BUT BEYOND JUST LOOKING AT SLEEP

2014
01:05:59,991 --> 01:06:02,794
TIMING AND REGULARITY, WE CAN

2015
01:06:02,794 --> 01:06:05,530
INTEGRATE INFORMATION ON SLEEP

2016
01:06:05,530 --> 01:06:12,237
AND ACTIVITY FROM MULTIPLE DAYS

2017
01:06:12,237 --> 01:06:13,438
TO -- THESE REPRESENTING SENT

2018
01:06:13,438 --> 01:06:15,740
THE MAGNITUDE TIMING -- IN THE

2019
01:06:15,740 --> 01:06:17,309
24-HOUR DAY AND ACROSS DAYS AND

2020
01:06:17,309 --> 01:06:20,045
CAN SERVE AS A MEASURE OF

2021
01:06:20,045 --> 01:06:22,981
CIRCADIAN RHYTHMICITY IN A

2022
01:06:22,981 --> 01:06:23,648
FREE-WORLD SETTING.

2023
01:06:23,648 --> 01:06:26,184
NOW BEFORE I JUMP INTO SOME

2024
01:06:26,184 --> 01:06:27,519
FINDINGS ABOUT REST ACTIVITY

2025
01:06:27,519 --> 01:06:28,820
RHYTHMS IN RELATION TO CHRONIC

2026
01:06:28,820 --> 01:06:30,255
DISEASE, I JUST WANTED TO

2027
01:06:30,255 --> 01:06:31,790
MENTION THAT WE CAN USE

2028
01:06:31,790 --> 01:06:33,224
PARAMETRIC AND NON-PARAMETRIC

2029
01:06:33,224 --> 01:06:34,526
APPROACHES TO MEASURE REST

2030
01:06:34,526 --> 01:06:35,994
ACTIVITY RHYTHMS.

2031
01:06:35,994 --> 01:06:37,495
IN MY SLIDES I'M GOING TO FOCUS

2032
01:06:37,495 --> 01:06:39,998
MORE ON THE NON-PARAMETRIC REST

2033
01:06:39,998 --> 01:06:41,333
ACTIVITY RHYTHM VARIABLES

2034
01:06:41,333 --> 01:06:42,434
BECAUSE THEY ARE -- I FEEL THAT

2035
01:06:42,434 --> 01:06:45,403
THEY ARE EASIER TO INTERPRET AND

2036
01:06:45,403 --> 01:06:48,239
MORE EASILY TRANSLATED INTO

2037
01:06:48,239 --> 01:06:50,675
PUBLIC HEALTH GUIDELINES.

2038
01:06:50,675 --> 01:06:53,611
SO THE FIRST METRIC IS ENTER

2039
01:06:53,611 --> 01:06:55,680
DAILY STABILITY, WHICH IS A

2040
01:06:55,680 --> 01:06:57,248
MEASURE OF INVARIABILITY BETWEEN

2041
01:06:57,248 --> 01:06:58,783
DAYS AND SYNCHRONIZATION TO

2042
01:06:58,783 --> 01:07:00,518
LIGHT AND DARK CYCLES WHEREBY

2043
01:07:00,518 --> 01:07:03,722
HIGHER VALUES INDICATE GREATER

2044
01:07:03,722 --> 01:07:05,156
STABILITY.

2045
01:07:05,156 --> 01:07:11,796
THE SECOND METRIC IS INTERDAILY

2046
01:07:11,796 --> 01:07:13,231
VARIABILITY, WHEREBY HIGHER

2047
01:07:13,231 --> 01:07:14,366
VALUES INDICATE A MORE

2048
01:07:14,366 --> 01:07:15,533
FRAGMENTED RHYTHM AND

2049
01:07:15,533 --> 01:07:16,868
INEFFICIENT SLEEP.

2050
01:07:16,868 --> 01:07:19,371
WE ALSO EXTRACT THE COUNTS AND

2051
01:07:19,371 --> 01:07:22,474
THE MIDPOINT OF THE MOST ACTIVE

2052
01:07:22,474 --> 01:07:24,008
10-HOUR PERIOD AND THE LEAST

2053
01:07:24,008 --> 01:07:26,878
ACTIVE FIVE-HOUR PERIOD.

2054
01:07:26,878 --> 01:07:29,514
FOR THE MOST -- AND A HIGHER

2055
01:07:29,514 --> 01:07:31,383
MIDPOINT WOULD REPRESENT BEING

2056
01:07:31,383 --> 01:07:32,784
ACTIVE LATER ON IN THE DAY.

2057
01:07:32,784 --> 01:07:35,253
FOR THE LEAST ACTIVE FIVE HAD

2058
01:07:35,253 --> 01:07:38,156
BEEN HOUR PERIOD, HIGHER COUNTS

2059
01:07:38,156 --> 01:07:41,292
WOULD INDICATELESS RESTFUL SLEEP

2060
01:07:41,292 --> 01:07:45,063
AND A LIGHTER -- AND FINALLY WE

2061
01:07:45,063 --> 01:07:49,000
USE THESE MEASURES TO COMPUTE

2062
01:07:49,000 --> 01:07:50,668
RELATIVE AMPLITUDE WHICH WE CAN

2063
01:07:50,668 --> 01:07:52,337
THINK OF AS A SUMMARY RE SURE OF

2064
01:07:52,337 --> 01:07:54,472
THE ROBUSTNESS OF THE OVERALL

2065
01:07:54,472 --> 01:07:55,774
ACTIVITY RHYTHM WHERE HIGHER

2066
01:07:55,774 --> 01:07:58,309
VALUES REPRESENT A GREATER

2067
01:07:58,309 --> 01:08:01,279
OVERALL CIRCADIAN RHYTHMICITY.

2068
01:08:01,279 --> 01:08:03,148
SO JUST TO SHOW YOU WHAT THIS

2069
01:08:03,148 --> 01:08:09,287
TYPICALLY LOOKS LIKE, THE

2070
01:08:09,287 --> 01:08:09,954
ACTIGRAPHY DATA LOOKS LIKE WHAT

2071
01:08:09,954 --> 01:08:11,389
YOU SEE HERE IN THE TOP FIGURE

2072
01:08:11,389 --> 01:08:12,290
ON MY SLIDE.

2073
01:08:12,290 --> 01:08:14,592
YOU SEE A VERY CLEAR REST

2074
01:08:14,592 --> 01:08:15,660
ACTIVITY PATTERN WITH HIGH

2075
01:08:15,660 --> 01:08:17,262
LEVELS OF ACTIVITY DURING WAKE

2076
01:08:17,262 --> 01:08:18,930
TIME, AND CONSOLIDATED SLEEP

2077
01:08:18,930 --> 01:08:23,301
PERIODS AT NIGHT.

2078
01:08:23,301 --> 01:08:24,602
WHEREAS SOMEONE -- HERE CAN YOU

2079
01:08:24,602 --> 01:08:27,038
SEE FROM THEIR ACTIGRAPHY, THAT

2080
01:08:27,038 --> 01:08:28,740
THEIR RHYTHM IS REALLY SPORADIC

2081
01:08:28,740 --> 01:08:32,310
AND THERE IS NO CLEERM PATTERN.

2082
01:08:32,310 --> 01:08:34,546
SO THESE ARE GENERALLY OBSERVED

2083
01:08:34,546 --> 01:08:36,781
IN A NUMBER OF NEURODEGENERATIVE

2084
01:08:36,781 --> 01:08:39,417
DISEASES AND PRE-CLINICAL

2085
01:08:39,417 --> 01:08:40,418
ALZHEIMER'S DISEASE AND CANCER

2086
01:08:40,418 --> 01:08:42,954
PATIENTS AND PSYCHIATRIC

2087
01:08:42,954 --> 01:08:45,123
DISORDERS, PARTICULARLY AMONG

2088
01:08:45,123 --> 01:08:48,393
INDIVIDUALS WITH DEPRESSION,

2089
01:08:48,393 --> 01:08:53,231
AND -- HIGHER RISK FOR POOR COG

2090
01:08:53,231 --> 01:08:54,766
NICKS, ACCELERATE BID BIOLOGICAL

2091
01:08:54,766 --> 01:08:57,302
AGING AND ALSO TO ANNUM BER OF

2092
01:08:57,302 --> 01:08:58,503
CARDIOMETABOLIC DISEASES AS I

2093
01:08:58,503 --> 01:08:59,304
WILL SHOW IN THE NEXT COUPLE OF

2094
01:08:59,304 --> 01:09:03,041
SLIDES.

2095
01:09:03,041 --> 01:09:04,042
SO HERE I'LL GIVE AN EXAMPLE

2096
01:09:04,042 --> 01:09:05,643
FROM A STUDY THAT WE PUBLISHED

2097
01:09:05,643 --> 01:09:07,846
ON REST-ACTIVITY RHYTHMS IN

2098
01:09:07,846 --> 01:09:08,980
RELATION TO CARDIOVASCULAR

2099
01:09:08,980 --> 01:09:10,615
DISEASE, HYPERTENSION, OBESITY

2100
01:09:10,615 --> 01:09:12,417
AND CENTRAL ADIPOSITY IN A

2101
01:09:12,417 --> 01:09:13,284
NATIONALLY REPRESENTATIVE SAMPLE

2102
01:09:13,284 --> 01:09:15,153
OF U.S. ADULTS.

2103
01:09:15,153 --> 01:09:17,889
AND IN THAT STUDY, WE SHOW THAT

2104
01:09:17,889 --> 01:09:19,858
GREATER DAY TO DAY STABILITY IN

2105
01:09:19,858 --> 01:09:22,060
SLEEP WAKE AND REST ACTIVITY

2106
01:09:22,060 --> 01:09:23,361
PATTERNS, A MORE ACTIVE WAKE

2107
01:09:23,361 --> 01:09:25,563
PERIOD AND MORE ROBUST OVERALL

2108
01:09:25,563 --> 01:09:28,199
RHYTHM ARE ASSOCIATED WITH UP TO

2109
01:09:28,199 --> 01:09:30,702
72% LOWER ODDS OF PREVALENT

2110
01:09:30,702 --> 01:09:34,005
CARDIOVASCULAR DISEASE, WHEREAS

2111
01:09:34,005 --> 01:09:36,841
HAVING A MORE FRAGMENTED RHYTHM

2112
01:09:36,841 --> 01:09:39,143
AND LESS RESTFUL SLEEP WERE

2113
01:09:39,143 --> 01:09:43,214
ASSOCIATED WITH UP TO THREE

2114
01:09:43,214 --> 01:09:44,816
HOLDS -- NOW WHEN WE EVALUATED

2115
01:09:44,816 --> 01:09:46,484
THE ASSOCIATIONS OF THESE REST

2116
01:09:46,484 --> 01:09:49,254
ACTIVITY WITHIN VARIABLES WITH

2117
01:09:49,254 --> 01:09:51,856
OTHER CARDIOMETABOLIC OUTCOMES,

2118
01:09:51,856 --> 01:09:52,957
SPECIFICALLY HYPERTENSION,

2119
01:09:52,957 --> 01:09:54,259
OBESITY AND CENTRAL ADIPOSITY,

2120
01:09:54,259 --> 01:09:57,161
AGAIN WE OBSERVED SIMILAR

2121
01:09:57,161 --> 01:09:57,929
ASSOCIATIONS, PARTICULARLY FOR

2122
01:09:57,929 --> 01:09:59,330
OBESITY, THE ASSOCIATIONS

2123
01:09:59,330 --> 01:10:01,199
EXACTLY MIRRORED WHAT WE

2124
01:10:01,199 --> 01:10:03,535
OBSERVED FOR CARDIOVASCULAR

2125
01:10:03,535 --> 01:10:05,837
DISEASE, WITH YOU ONE THING ON

2126
01:10:05,837 --> 01:10:09,340
REST ACTIVITY RHYTHMS IN

2127
01:10:09,340 --> 01:10:12,343
RELATION TO DPSH EMERGES AS A

2128
01:10:12,343 --> 01:10:13,978
VERY STRONG PREDICTOR.

2129
01:10:13,978 --> 01:10:16,481
SO THIS REALLY UNDERSCORES THE

2130
01:10:16,481 --> 01:10:19,851
IMPORTANCE OF CIRCADIAN

2131
01:10:19,851 --> 01:10:21,219
RHYTHMICITY FOR PREVENTING

2132
01:10:21,219 --> 01:10:22,120
DISEASE AT THE CHRONIC

2133
01:10:22,120 --> 01:10:23,521
POPULATION LEVEL.

2134
01:10:23,521 --> 01:10:24,923
NOW IN THE PREVIOUS STUDY THAT I

2135
01:10:24,923 --> 01:10:27,191
SHOWED YOU, WE DID NOT LOOK AT

2136
01:10:27,191 --> 01:10:30,161
TYPE 2 DIABETES AS AN OUTCOME,

2137
01:10:30,161 --> 01:10:31,896
BUT I DID WANT TO SHARE THESE

2138
01:10:31,896 --> 01:10:33,131
FINDINGS FROM ANOTHER ANALYSIS

2139
01:10:33,131 --> 01:10:36,067
IN A DIFFERENT COHORT,

2140
01:10:36,067 --> 01:10:37,735
SPECIFICALLY THE -- JUST TO SHOW

2141
01:10:37,735 --> 01:10:39,837
THAT THE ASSOCIATIONS

2142
01:10:39,837 --> 01:10:41,372
ESSENTIALLY MIRRORED WHAT WE SAW

2143
01:10:41,372 --> 01:10:42,974
FOR KRARD YOE VASCULAR DISEASE,

2144
01:10:42,974 --> 01:10:44,642
AND THIS IS VERY NICELY

2145
01:10:44,642 --> 01:10:46,644
ILLUSTRATED IN THIS FIGURE HERE,

2146
01:10:46,644 --> 01:10:49,380
WHERE WE PREIVET THE PREVALENCE

2147
01:10:49,380 --> 01:10:50,815
OF -- AND YOU CAN SEE VERY

2148
01:10:50,815 --> 01:10:52,116
CLEARLY THAT THOSE WHO ARE IN

2149
01:10:52,116 --> 01:10:55,186
THE HIGHEST QUINTILE OF RELATIVE

2150
01:10:55,186 --> 01:10:58,590
AM BLI TEUD, HAD THE LOWEST

2151
01:10:58,590 --> 01:11:01,025
PREVALENCE OF TYPE 2 DIABETES AT

2152
01:11:01,025 --> 01:11:01,926
13% COMPARED TO THOSE IN THE

2153
01:11:01,926 --> 01:11:02,961
LOWEST QUINTILE OR THOSE WHO

2154
01:11:02,961 --> 01:11:08,099
HAVE THE LOWEST RHYTHMICITY THE

2155
01:11:08,099 --> 01:11:09,534
PREVALENCE WAS MUCH HIGHER AT

2156
01:11:09,534 --> 01:11:11,936
32%.

2157
01:11:11,936 --> 01:11:15,239
OH ?T PREVIN THE PREVIOUS SLIDEI

2158
01:11:15,239 --> 01:11:17,208
PROVIDED A SUMMARY OF THE

2159
01:11:17,208 --> 01:11:19,177
ASSOCIATION BETWEEN BEHAVIORAL

2160
01:11:19,177 --> 01:11:21,212
RHYTHMS AND A NUMBER OF

2161
01:11:21,212 --> 01:11:21,846
TRADITIONAL CARDIOMETABOLIC

2162
01:11:21,846 --> 01:11:23,281
OUTCOMES THAT ARE TYPICALLY

2163
01:11:23,281 --> 01:11:24,382
CAPTURED IN A CLINICAL SETTING

2164
01:11:24,382 --> 01:11:27,285
OR A PUBLIC HEALTH SETTING.

2165
01:11:27,285 --> 01:11:28,052
BUT ONE IMPORTANT THING TO

2166
01:11:28,052 --> 01:11:31,756
REMEMBER IS THAT THESE CLINICAL

2167
01:11:31,756 --> 01:11:33,224
INDICATORS OR THESE

2168
01:11:33,224 --> 01:11:35,994
CARDIOMETABOLIC RISK FACTORS

2169
01:11:35,994 --> 01:11:38,062
THEMSELVES HAVE RHYTHMS THAT MAY

2170
01:11:38,062 --> 01:11:39,797
BE INFLUENCED BY BEHAVIORAL

2171
01:11:39,797 --> 01:11:42,333
RHYTHMS AND THAT MAY OFFER

2172
01:11:42,333 --> 01:11:43,334
PROGNOSTIC SIGNIFICANCE BEYOND

2173
01:11:43,334 --> 01:11:45,069
WHAT IS TYPICALLY CAPTURED IN A

2174
01:11:45,069 --> 01:11:46,170
CLINICAL AND PUBLIC HEALTH

2175
01:11:46,170 --> 01:11:46,838
SETTING.

2176
01:11:46,838 --> 01:11:48,539
AND A REALLY GOOD EXAMPLE OF

2177
01:11:48,539 --> 01:11:50,274
THIS IS BLOOD PRESSURE.

2178
01:11:50,274 --> 01:11:52,443
SO OUR BLOOD PRESSURE FOLLOWS A

2179
01:11:52,443 --> 01:11:54,545
DIURNAL PATTERN THAT COULD BE

2180
01:11:54,545 --> 01:11:56,180
MEASURED BY AMBULATORY BLOOD

2181
01:11:56,180 --> 01:12:01,019
PRESSURE MONITORING, SO AN

2182
01:12:01,019 --> 01:12:04,522
INDIVIDUAL WEARS TH THE MONITORR

2183
01:12:04,522 --> 01:12:05,523
A 24 HOUR PERIOD AND GOES ABOUT

2184
01:12:05,523 --> 01:12:09,694
THEIR DAILY ACTIVITIES, AND IT'S

2185
01:12:09,694 --> 01:12:12,930
MONITORED TO MONITOR SAY EVERY

2186
01:12:12,930 --> 01:12:13,231
30 MINUTES.

2187
01:12:13,231 --> 01:12:14,966
THIS ALLOWS US TO EXTRACT

2188
01:12:14,966 --> 01:12:19,003
MEASURES LIKE MEAN 24-HOUR BLOOD

2189
01:12:19,003 --> 01:12:21,873
PRESSURE, NOW IN HEALTHY

2190
01:12:21,873 --> 01:12:22,874
INDIVIDUALS, THE BLOOD PRESSURE

2191
01:12:22,874 --> 01:12:25,510
VARIATION PATTERN OVER 24 HOURS

2192
01:12:25,510 --> 01:12:27,278
TYPICALLY IS SUCH THAT BLOOD

2193
01:12:27,278 --> 01:12:28,379
PRESSURE IS HIGHER DURING

2194
01:12:28,379 --> 01:12:30,782
WAKEFULNESS AND LOWER DURING

2195
01:12:30,782 --> 01:12:31,315
SLEEP.

2196
01:12:31,315 --> 01:12:36,154
AND IN FACT THE IN A HEALTHY

2197
01:12:36,154 --> 01:12:40,958
INDIVIDUAL SHOULD DIP10 TO 20%

2198
01:12:40,958 --> 01:12:41,626
DURING THE SLEEP PERIOD.

2199
01:12:41,626 --> 01:12:43,828
THIS IS NOT NECESSARILY THE

2200
01:12:43,828 --> 01:12:45,697
PHENOTYPE, THERE ARE MANY OTHER

2201
01:12:45,697 --> 01:12:47,665
PHENOTYPES.

2202
01:12:47,665 --> 01:12:52,370
SOME HAVE -- OTHERS ARE EXTREME

2203
01:12:52,370 --> 01:12:53,805
DIPPERS MEANING IT DIPS TOO MUCH

2204
01:12:53,805 --> 01:12:55,273
AND OTHERS HAVE A RISER PATTERN

2205
01:12:55,273 --> 01:12:56,541
WHICH MEANS PRESSURE GOES UP

2206
01:12:56,541 --> 01:12:57,141
DURING THEIR SLEEP.

2207
01:12:57,141 --> 01:12:58,443
OF COURSE THE EXTENT OF THE

2208
01:12:58,443 --> 01:13:00,545
MORNING SURGE CAN ALSO VARY.

2209
01:13:00,545 --> 01:13:02,513
FROM PERSON TO PERSON.

2210
01:13:02,513 --> 01:13:03,815
AND THESE DIFFERENT PHENOTYPES

2211
01:13:03,815 --> 01:13:06,451
HAVE DIFFERENTIAL ASSOCIATIONS

2212
01:13:06,451 --> 01:13:10,121
WITH CHRONIC DISEASE RISK.

2213
01:13:10,121 --> 01:13:12,090
INDEED STUDIES ARE INCREASINGLY

2214
01:13:12,090 --> 01:13:13,357
SHOWING THAT LOSS OR DISRUPTION

2215
01:13:13,357 --> 01:13:16,094
OF THE CIRCADIAN RHYTHM --

2216
01:13:16,094 --> 01:13:17,762
SORRY, LOSS OR DISRUPTION OF

2217
01:13:17,762 --> 01:13:20,665
BLOOD PRESSURE CIRCADIAN RHYTHM

2218
01:13:20,665 --> 01:13:24,168
IS LINKED TO A NUMBER OF ADVERSE

2219
01:13:24,168 --> 01:13:26,838
OUTCOMES INCLUDING DEMENTIA,

2220
01:13:26,838 --> 01:13:30,007
CHRONIC KID KNEES DEED.

2221
01:13:30,007 --> 01:13:33,077
YOU CAN CLEARLY SEE THAT

2222
01:13:33,077 --> 01:13:34,212
INDIVIDUALS WHO HAD HIGHER

2223
01:13:34,212 --> 01:13:35,446
NIGHTTIME BLOOD PRESSURE AND A

2224
01:13:35,446 --> 01:13:37,281
HIGHER NIGHT TO DAY RATIO AND

2225
01:13:37,281 --> 01:13:38,116
NON-DIPPING PATTERN IN ADDITION

2226
01:13:38,116 --> 01:13:40,418
TO A HIGHER DAY TIME BLOOD

2227
01:13:40,418 --> 01:13:41,586
PRESSURE HAVE SIGNIFICANTLY

2228
01:13:41,586 --> 01:13:43,087
HIGHER RISK OF CARDIOVASCULAR

2229
01:13:43,087 --> 01:13:45,523
DISEASE AND A SIGNIFICANTLY

2230
01:13:45,523 --> 01:13:46,324
HIGHER RISK OF MORTALITY AND

2231
01:13:46,324 --> 01:13:47,825
THESE ASSOCIATIONS ARE NOT JUST

2232
01:13:47,825 --> 01:13:50,194
OBSERVED IN INDIVIDUALS WITH

2233
01:13:50,194 --> 01:13:51,529
HYPERTENSION, THEY'RE ALSO

2234
01:13:51,529 --> 01:13:52,230
OBSERVED IN THE GENERAL

2235
01:13:52,230 --> 01:13:55,166
POPULATION.

2236
01:13:55,166 --> 01:13:56,367
IN ADDITION THERE IS EMERGING

2237
01:13:56,367 --> 01:13:58,269
EVIDENCE THAT NIGHTTIME BLOOD

2238
01:13:58,269 --> 01:14:01,005
PRESSURE MAY BE A STRONGER

2239
01:14:01,005 --> 01:14:02,406
PREDICTOR OF DISEASE RISK THAN

2240
01:14:02,406 --> 01:14:03,741
DAY TIME BLOOD PRESSURE, AND

2241
01:14:03,741 --> 01:14:05,877
THAT HAVING A HIGH NIGHTTIME

2242
01:14:05,877 --> 01:14:07,178
BLOOD PRESSURE IN ADDITION TO A

2243
01:14:07,178 --> 01:14:09,280
RISER OR A NON-DIPPER PATTERN

2244
01:14:09,280 --> 01:14:10,481
CAN BE ASSOCIATED WITH HIGHER

2245
01:14:10,481 --> 01:14:14,352
RISK OF OVERALL CARDIOVASCULAR

2246
01:14:14,352 --> 01:14:15,119
DISEASE, ATHEROSCLEROSIS AND

2247
01:14:15,119 --> 01:14:15,753
HEART FAILURE.

2248
01:14:15,753 --> 01:14:17,955
NOW DESPITE THIS EMERGING

2249
01:14:17,955 --> 01:14:19,390
LITERATURE, WE ACTUALLY KNOW

2250
01:14:19,390 --> 01:14:22,026
VERY LITTLE ABOUT HOW BEHAVIORAL

2251
01:14:22,026 --> 01:14:23,327
RHYTHMS INFLUENCE DIURNAL

2252
01:14:23,327 --> 01:14:24,328
PATTERN OF BLOOD PRESSURE IN

2253
01:14:24,328 --> 01:14:26,164
REALTIME AND CURRENT DIAGNOSTIC

2254
01:14:26,164 --> 01:14:27,832
AND THERAPEUTIC APPROACHES LACK

2255
01:14:27,832 --> 01:14:29,867
SUFFICIENT ATTENTION TO BLOOD

2256
01:14:29,867 --> 01:14:36,140
PRESSURE CIRCADIAN RHYTHMICITY.

2257
01:14:36,140 --> 01:14:37,775
ANOTHER REALLY GOOD EXAMPLE IS

2258
01:14:37,775 --> 01:14:39,010
BLOOD GLUCOSE WHICH ALSO FOLLOWS

2259
01:14:39,010 --> 01:14:41,045
A DIURNAL PATTERN THAT IS

2260
01:14:41,045 --> 01:14:41,979
DISTINCT IN INDIVIDUALS WHO ARE

2261
01:14:41,979 --> 01:14:42,780
HEALTHY COMPARED TO INDIVIDUALS

2262
01:14:42,780 --> 01:14:44,382
WHO HAVE TYPE 2 DIABETES.

2263
01:14:44,382 --> 01:14:46,484
IN HEALTHY INDIVIDUALS, GLUCOSE

2264
01:14:46,484 --> 01:14:47,718
TOLERANCE AND INSULIN

2265
01:14:47,718 --> 01:14:48,586
SENSITIVITY ARE LOWER IN THE

2266
01:14:48,586 --> 01:14:50,555
EVENING COMPARED TO THE MORNING.

2267
01:14:50,555 --> 01:14:54,425
AND NOW WL TH WITH THE INTRODUCN

2268
01:14:54,425 --> 01:14:55,827
OF CONTINUOUS GLUCOSE MONITORING

2269
01:14:55,827 --> 01:14:57,461
WE'RE ABLE TO USE IT NOT JUST

2270
01:14:57,461 --> 01:14:58,930
AMONG TYPE 2 DIABETES PATIENTS

2271
01:14:58,930 --> 01:15:00,164
BUT ALSO IN RESEARCH SETTING

2272
01:15:00,164 --> 01:15:01,499
AMONG HEALTHY INDIVIDUALS AND

2273
01:15:01,499 --> 01:15:03,534
INDIVIDUALS WITH PREDIABETES TO

2274
01:15:03,534 --> 01:15:06,637
EXTRACT ADDITIONAL MARKERS OF

2275
01:15:06,637 --> 01:15:11,008
DIURNAL GLUCOSE VARIATION.

2276
01:15:11,008 --> 01:15:16,480
SPECIFICALLY RELATED TO INTERAND

2277
01:15:16,480 --> 01:15:25,690
INTRADAILY GLYCEMIC VARIABILITY.

2278
01:15:25,690 --> 01:15:26,691
HERE I JUST WANTED TO GIVE AN

2279
01:15:26,691 --> 01:15:27,859
EXAMPLE OF THIS STUDY WHICH I

2280
01:15:27,859 --> 01:15:29,126
THINK ILLUSTRATES THIS REALLY

2281
01:15:29,126 --> 01:15:29,360
NICELY.

2282
01:15:29,360 --> 01:15:31,229
THIS WAS A STUDY IN PARTICIPANTS

2283
01:15:31,229 --> 01:15:34,365
WHO DON'T HAVE TYPE 2 DIABETES.

2284
01:15:34,365 --> 01:15:36,033
AND DATA FROM CONTINUOUS GLUCOSE

2285
01:15:36,033 --> 01:15:38,369
MONITORING WAS USED TO EXTRACT

2286
01:15:38,369 --> 01:15:43,174
THE MEAN AMPLITUDE OF GLYCEMIC

2287
01:15:43,174 --> 01:15:45,176
EXCURSION OR MAGE, WHICH ALSO

2288
01:15:45,176 --> 01:15:48,446
SERVES AS AN INDEX OF GLYCEMIC

2289
01:15:48,446 --> 01:15:48,746
VARIABILITY.

2290
01:15:48,746 --> 01:15:51,349
YOU CAN SEE VERY CLEARLY THE

2291
01:15:51,349 --> 01:15:52,750
CARDIOVASCULAR DISEASE EVENT

2292
01:15:52,750 --> 01:15:54,418
RATE WAS SUBSTANTIALLY HIGHER IN

2293
01:15:54,418 --> 01:15:59,156
THOSE WITH HIGH MAGE COMPARED TO

2294
01:15:59,156 --> 01:16:03,094
LOW, AND INDIVIDUALS WITH HIGHER

2295
01:16:03,094 --> 01:16:05,730
MAGE OR GLYCEMIC VARIABILITY HAD

2296
01:16:05,730 --> 01:16:06,964
A 5.6 FOLD INCREASE IN

2297
01:16:06,964 --> 01:16:07,932
CARDIOVASCULAR DISEASE RISK,

2298
01:16:07,932 --> 01:16:12,970
WHICH IS A REALLY PROFOUND

2299
01:16:12,970 --> 01:16:13,371
ASSOCIATION.

2300
01:16:13,371 --> 01:16:14,405
BUT JUST LIKE BLOOD PRESSURE,

2301
01:16:14,405 --> 01:16:15,973
AGAIN, WE DON'T HAVE VERY MUCH

2302
01:16:15,973 --> 01:16:17,808
STUDIES ON HOW BEHAVIORAL

2303
01:16:17,808 --> 01:16:19,343
RHYTHMS INFLUENCE THIS DIURNAL

2304
01:16:19,343 --> 01:16:22,146
PATTERN IN REALTIME, AND THE

2305
01:16:22,146 --> 01:16:23,848
DIURNAL PATTERN OF GLUCOSE IS

2306
01:16:23,848 --> 01:16:25,650
NOT NECESSARILY INCORPORATED

2307
01:16:25,650 --> 01:16:27,285
INTO CURRENT PREVENTION AND

2308
01:16:27,285 --> 01:16:32,156
THERAPEUTIC APPROACHES.

2309
01:16:32,156 --> 01:16:33,591
SO THIS BRINGS ME TO THE LAST

2310
01:16:33,591 --> 01:16:35,126
PORTION OF MY TALK, WHICH IS ON

2311
01:16:35,126 --> 01:16:36,894
CHALLENGES AND OPPORTUNITIES.

2312
01:16:36,894 --> 01:16:38,729
AND AGAIN FOCUSING ON CHALLENGES

2313
01:16:38,729 --> 01:16:41,132
AND OPPORTUNITIES FOR

2314
01:16:41,132 --> 01:16:42,633
POPULATION-BASED AND COMMUNITY

2315
01:16:42,633 --> 01:16:45,269
ENGAGED RESEARCH.

2316
01:16:45,269 --> 01:16:48,139
SO THE FIRST CHALLENGE IS THAT

2317
01:16:48,139 --> 01:16:49,407
MOST POPULATION AND

2318
01:16:49,407 --> 01:16:52,209
COMMUNITY-BASED COHORT STUDIES

2319
01:16:52,209 --> 01:16:54,412
LACK TIME STAMPED DATA ON

2320
01:16:54,412 --> 01:16:55,046
LIFESTYLE BEHAVIORS.

2321
01:16:55,046 --> 01:16:58,049
THIS IS PARTICULARLY PRONOUNCED

2322
01:16:58,049 --> 01:16:58,683
FOR DIET.

2323
01:16:58,683 --> 01:17:00,985
MOST COHORT STUDIES USE FOOD

2324
01:17:00,985 --> 01:17:02,186
FREQUENCY QUESTIONNAIRES TO

2325
01:17:02,186 --> 01:17:03,220
MEASURE DIET WHICH HAVE NO

2326
01:17:03,220 --> 01:17:05,523
INFORMATION ON CHRONONUTRITION

2327
01:17:05,523 --> 01:17:06,958
METRICS.

2328
01:17:06,958 --> 01:17:08,793
ANOTHER CHALLENGE IS THAT IN

2329
01:17:08,793 --> 01:17:11,362
MOST COHORT STUDIES WE DON'T

2330
01:17:11,362 --> 01:17:12,129
ROUTINELY COLLECT INFORMATION ON

2331
01:17:12,129 --> 01:17:15,199
THE DIURNAL PATTERN OF A NUMBER

2332
01:17:15,199 --> 01:17:17,301
OF BIOMARKERS AND

2333
01:17:17,301 --> 01:17:17,969
CARDIOMETABOLIC RISK FACTORS.

2334
01:17:17,969 --> 01:17:20,037
I KNOW THERE ARE NOW SOME

2335
01:17:20,037 --> 01:17:21,405
ANCILLARY STUDIES IN SOME

2336
01:17:21,405 --> 01:17:24,809
COHORTS THAT INCLUDE ABPM AND

2337
01:17:24,809 --> 01:17:26,544
CGM BUT UNFORTUNATELY THIS TENDS

2338
01:17:26,544 --> 01:17:28,079
TO BE A CROSS-SECTIONAL

2339
01:17:28,079 --> 01:17:29,647
ASSESSMENT AND THAT IS NOT

2340
01:17:29,647 --> 01:17:30,314
CONCURRENT WITH THE ASSESSMENT

2341
01:17:30,314 --> 01:17:31,615
OF LIFESTYLE.

2342
01:17:31,615 --> 01:17:32,550
SO THE OPPORTUNITY HERE IS THAT

2343
01:17:32,550 --> 01:17:35,419
WE NEED TO COLLECT MORE

2344
01:17:35,419 --> 01:17:36,721
TIME-STAMPED LIFESTYLE DATA THAT

2345
01:17:36,721 --> 01:17:38,723
IS CONCURRENT WITH CLINICAL

2346
01:17:38,723 --> 01:17:39,590
INDICATOR DATA TO UNDERSTAND

2347
01:17:39,590 --> 01:17:42,126
BETTER HOW THE TIMING OF

2348
01:17:42,126 --> 01:17:43,894
LIFESTYLE BEHAVIORS INFLUENCES

2349
01:17:43,894 --> 01:17:45,029
MULTIPLE CHRONIC DISEASE

2350
01:17:45,029 --> 01:17:46,497
OUTCOMES IN EEK LOGIC SETTINGS

2351
01:17:46,497 --> 01:17:48,966
AT THE POPULATION LEVEL USING A

2352
01:17:48,966 --> 01:17:50,868
LIFECOURSE APPROACH.

2353
01:17:50,868 --> 01:17:53,504
NOW A SECOND CHALLENGE OR

2354
01:17:53,504 --> 01:17:55,473
RESEARCH GAP IS THAT MUCH OF THE

2355
01:17:55,473 --> 01:17:56,874
EXISTING LITERATURE FOCUSES ON

2356
01:17:56,874 --> 01:17:58,909
THE TIMING OF LIFESTYLE

2357
01:17:58,909 --> 01:18:02,279
BEHAVIORS RELATIVE TO CLOCK TIME

2358
01:18:02,279 --> 01:18:03,948
AND NOT NECESSARILY RELATIVE TO

2359
01:18:03,948 --> 01:18:05,316
BIOLOGICAL TIME.

2360
01:18:05,316 --> 01:18:07,785
NOW DIM LIGHT MELATONIN ONSET OF

2361
01:18:07,785 --> 01:18:08,786
COURSE IS CURRENTLY THE GOLD

2362
01:18:08,786 --> 01:18:10,021
STANDARD APPROACH FOR

2363
01:18:10,021 --> 01:18:11,922
DETERMINING BIOLOGICAL TIME AND

2364
01:18:11,922 --> 01:18:13,991
IT REALLY IMPORTANT TO LOOK AT

2365
01:18:13,991 --> 01:18:14,625
BECAUSE A GOOD EXAMPLE OF THIS

2366
01:18:14,625 --> 01:18:17,194
FROM THE FIELD OF

2367
01:18:17,194 --> 01:18:19,063
CHRONONUTRITION IS WHAT IS

2368
01:18:19,063 --> 01:18:20,598
CONSIDERED LATE NIGHT EATING FOR

2369
01:18:20,598 --> 01:18:23,234
SOMEONE WHO HAS DIM LIGHT

2370
01:18:23,234 --> 01:18:24,902
MELATONIN ONSET AT 7:00 OR

2371
01:18:24,902 --> 01:18:26,337
8:00 P.M. IS DIFFERENT FROM

2372
01:18:26,337 --> 01:18:27,671
SOMEONE WHOSE DIM LIGHT

2373
01:18:27,671 --> 01:18:29,240
MELATONIN ONSET OCCURS LATER,

2374
01:18:29,240 --> 01:18:31,075
BUT WE HAVEN'T REALLY

2375
01:18:31,075 --> 01:18:31,776
DISENTANGLED THESE ASSOCIATIONS

2376
01:18:31,776 --> 01:18:33,511
YET.

2377
01:18:33,511 --> 01:18:35,046
MAINLY BECAUSE IT'S REALLY

2378
01:18:35,046 --> 01:18:36,947
COSTLY AND TEDIOUS TO DO DIM

2379
01:18:36,947 --> 01:18:39,016
LIGHT MELATONIN ONSET MEASURES

2380
01:18:39,016 --> 01:18:40,518
IN PUBLIC HEALTH SETTINGS AND IN

2381
01:18:40,518 --> 01:18:43,120
POPULATION STUDIES.

2382
01:18:43,120 --> 01:18:44,121
SO THE OPPORTUNITY HERE IS THAT

2383
01:18:44,121 --> 01:18:45,623
WE NEED TO DEVELOP MORE

2384
01:18:45,623 --> 01:18:49,060
INNOVATIVE RELIABLE APPROACHES

2385
01:18:49,060 --> 01:18:50,327
TO ASSESS BIOLOGICAL TIMING AND

2386
01:18:50,327 --> 01:18:52,563
WE NEED TO DEVELOP MARKERS OF

2387
01:18:52,563 --> 01:18:53,564
CIRCADIAN BIOLOGY THAT CAN BE

2388
01:18:53,564 --> 01:18:55,332
MORE EASILY INTEGRATED INTO

2389
01:18:55,332 --> 01:18:56,767
CLINICAL AND EPIDEMIOLOGIC

2390
01:18:56,767 --> 01:18:57,201
RESEARCH.

2391
01:18:57,201 --> 01:18:59,303
BUT IN THE MEANTIME, WE DO NEED

2392
01:18:59,303 --> 01:19:00,771
TO CONDUCT MORE STUDIES THAT

2393
01:19:00,771 --> 01:19:02,740
EVALUATE THE TIMING OF BEHAVIORS

2394
01:19:02,740 --> 01:19:04,175
IN RELATION TO BIOLOGICAL TIME

2395
01:19:04,175 --> 01:19:06,944
BY USING SOME SUITABLE PROXIES

2396
01:19:06,944 --> 01:19:08,579
FOR BIOLOGICAL TIME LIKE SLEEP

2397
01:19:08,579 --> 01:19:12,083
TIMING.

2398
01:19:12,083 --> 01:19:13,317
A THIRD GAP THAT I WANTED TO

2399
01:19:13,317 --> 01:19:14,852
HIGHLIGHT IS THAT WE KNOW VERY

2400
01:19:14,852 --> 01:19:17,721
LITTLE ABOUT THE MECHANISMS

2401
01:19:17,721 --> 01:19:21,158
UNDERLYING CIRCADIAN

2402
01:19:21,158 --> 01:19:22,460
RHYTHM-MEDIATED CLINICAL RISK

2403
01:19:22,460 --> 01:19:24,428
FACTOR REGULATION OR THE DIURNAL

2404
01:19:24,428 --> 01:19:26,363
PATTERNS OF SOME OF THESE

2405
01:19:26,363 --> 01:19:26,964
CARDIOMETABOLIC RISK FACTORS

2406
01:19:26,964 --> 01:19:27,665
THAT I MENTIONED.

2407
01:19:27,665 --> 01:19:29,633
FOR EXAMPLE, WE KNOW DIE URGE

2408
01:19:29,633 --> 01:19:32,403
GLUCOSE AND BLOOD PRESSURE

2409
01:19:32,403 --> 01:19:33,370
RHYTHMICITY PARAMETERS ARE

2410
01:19:33,370 --> 01:19:35,239
DRIVEN IN PART BY ENDOGENOUS

2411
01:19:35,239 --> 01:19:36,440
RHYTHMS AND DRIVEN IN PART BY

2412
01:19:36,440 --> 01:19:37,942
ENVIRONMENTAL AND BEHAVIORAL

2413
01:19:37,942 --> 01:19:38,909
RHYTHMS BUT THESE ASSOCIATIONS

2414
01:19:38,909 --> 01:19:40,010
ARE UNDERSTUDIED.

2415
01:19:40,010 --> 01:19:41,879
IT'S ALSO UNCLEAR WHAT THE

2416
01:19:41,879 --> 01:19:43,180
BENEFITS OF THERAPIES AND

2417
01:19:43,180 --> 01:19:44,215
PREVENTION APPROACHES THAT

2418
01:19:44,215 --> 01:19:46,083
CONSIDER THESE DIURNAL PATTERNS

2419
01:19:46,083 --> 01:19:47,318
OF BLOOD PRESSURE GLUCOSE AND

2420
01:19:47,318 --> 01:19:49,320
OTHER INDICATORS, IF THEY'RE

2421
01:19:49,320 --> 01:19:50,521
ACTUALLY BENEFICIAL.

2422
01:19:50,521 --> 01:19:52,389
THE BENEFIT ARE UNKNOWN.

2423
01:19:52,389 --> 01:19:54,024
SO THE OPPORTUNITY HERE IS THAT

2424
01:19:54,024 --> 01:19:55,593
WE NEED MORE STUDIES TO

2425
01:19:55,593 --> 01:19:57,661
UNDERSTAND HOW EPIGENETIC,

2426
01:19:57,661 --> 01:19:58,863
ENVIRONMENTAL, PSYCHOSOCIAL AND

2427
01:19:58,863 --> 01:20:00,364
BEHAVIORAL FACTORS INFLUENCE THE

2428
01:20:00,364 --> 01:20:02,099
DIURNAL PATTERNS OF THESE

2429
01:20:02,099 --> 01:20:03,400
CARDIOMETABOLIC RISK FACTORS,

2430
01:20:03,400 --> 01:20:05,002
AND TO DETERMINE WHETHER HIGH

2431
01:20:05,002 --> 01:20:06,437
RISK PHENOTYPES CAN BE REVERSED

2432
01:20:06,437 --> 01:20:09,607
OR MODIFIED TO DEVELOP MORE

2433
01:20:09,607 --> 01:20:11,642
INNOVATIVE INTERVENTIONS.

2434
01:20:11,642 --> 01:20:13,644
SO A REALLY GOOD EXAMPLE OF THIS

2435
01:20:13,644 --> 01:20:15,179
IS, FOR EXAMPLE, WE'RE NOW

2436
01:20:15,179 --> 01:20:16,614
SEEING THAT GLYCEMIC VARIABILITY

2437
01:20:16,614 --> 01:20:18,182
MAY BE A RISK FACTOR, BUT WE

2438
01:20:18,182 --> 01:20:21,051
DON'T KNOW IF THIS COULD BE --

2439
01:20:21,051 --> 01:20:22,653
IF THIS CAN BE AND TO WHAT

2440
01:20:22,653 --> 01:20:25,022
EXTENT IT CAN BE IMPROVED OR

2441
01:20:25,022 --> 01:20:27,958
REVERSED BY MODIFYING BEHAVIORAL

2442
01:20:27,958 --> 01:20:30,661
RISK FACTORS, FOR EXAMPLE.

2443
01:20:30,661 --> 01:20:32,997
AND LAST BUT CERTAINLY NOT

2444
01:20:32,997 --> 01:20:35,266
LEAST, I THINK THE ROLE OF

2445
01:20:35,266 --> 01:20:36,467
CHRONOMEDICINE IN ADDRESSING

2446
01:20:36,467 --> 01:20:39,904
HEALTH INEQUITIES IS VERY

2447
01:20:39,904 --> 01:20:40,571
UNDERSTUDIED.

2448
01:20:40,571 --> 01:20:41,572
THERE IS A DERTH OF EVIDENCE

2449
01:20:41,572 --> 01:20:43,641
FROM RACIALLY AND ETHNICALLY

2450
01:20:43,641 --> 01:20:46,443
DIVERSE COHORTS, AND MINORITIZED

2451
01:20:46,443 --> 01:20:48,412
POPULATIONS BROADLY SPEAKING.

2452
01:20:48,412 --> 01:20:50,581
SO THE OPPORTUNITY HERE IS THAT

2453
01:20:50,581 --> 01:20:52,082
WE NEED MORE SUFFICIENTLY

2454
01:20:52,082 --> 01:20:53,918
POWERED POPULATION STUDIES TO

2455
01:20:53,918 --> 01:20:55,452
UNDERSTAND DIFFERENCES BY SEX,

2456
01:20:55,452 --> 01:20:57,288
RACE, ETHNICITY, AND TO QUANTIFY

2457
01:20:57,288 --> 01:20:58,923
THE CONTRIBUTION OF CIRCADIAN

2458
01:20:58,923 --> 01:21:02,326
HEALTH INEQUITIES TO THE BROADER

2459
01:21:02,326 --> 01:21:05,529
HEALTH INEQUITIES THAT WE

2460
01:21:05,529 --> 01:21:07,064
OBSERVE AT THE POPULATION LEVEL.

2461
01:21:07,064 --> 01:21:13,504
I TH -- IN REAL WORLD SETTINGS.

2462
01:21:13,504 --> 01:21:17,408
SO I THINK UPON ADDRESSING THESE

2463
01:21:17,408 --> 01:21:18,909
RESEARCH GAPS, WE CAN TRULY

2464
01:21:18,909 --> 01:21:20,444
UNLOCK THE POTENTIAL OF

2465
01:21:20,444 --> 01:21:22,379
CHRONOMEDICINE TO PRESERVE AND

2466
01:21:22,379 --> 01:21:23,013
RESTORE CIRCADIAN HEALTH.

2467
01:21:23,013 --> 01:21:25,449
SOME REALLY IMPORTANT FUTURE

2468
01:21:25,449 --> 01:21:27,618
APPLICATIONS COULD BE ENHANCING

2469
01:21:27,618 --> 01:21:29,453
DISEASE RISK PREDICTION

2470
01:21:29,453 --> 01:21:30,321
ALGORITHMS, FINALLY

2471
01:21:30,321 --> 01:21:32,289
INCORPORATING THE CONCEPT OF

2472
01:21:32,289 --> 01:21:33,924
TIME INTO GUIDELINES,

2473
01:21:33,924 --> 01:21:35,226
SPECIFICALLY LIFESTYLE

2474
01:21:35,226 --> 01:21:36,961
GUIDELINES, AND DEVELOPING

2475
01:21:36,961 --> 01:21:37,962
CONTEXTUAL BEHAVIORAL

2476
01:21:37,962 --> 01:21:39,029
INTERVENTIONS THAT WORK NOT JUST

2477
01:21:39,029 --> 01:21:41,298
IN A LAB BUT ALSO IN A REAL

2478
01:21:41,298 --> 01:21:43,367
WORLD SETTING TO ADDRESS HEALTH

2479
01:21:43,367 --> 01:21:44,235
INEQUITIES, EXTEND HEALTHSPAN

2480
01:21:44,235 --> 01:21:46,537
AND LIFESPAN, AND OPTIMIZE

2481
01:21:46,537 --> 01:21:47,705
CHRONIC DISEASE PREVENTION AND

2482
01:21:47,705 --> 01:21:49,673
MANAGEMENT.

2483
01:21:49,673 --> 01:21:52,843
SO THE TAKE-HOME MESSAGE FROM MY

2484
01:21:52,843 --> 01:21:54,144
PRESENTATION TODAY, I HOPE, IS

2485
01:21:54,144 --> 01:21:58,515
THAT ENHANCE BEING THE

2486
01:21:58,515 --> 01:22:00,150
RHYTHMICITY OF HEALTH BEHAVIORS

2487
01:22:00,150 --> 01:22:02,620
AND OPTIMIZING DIE URGE PATTERNS

2488
01:22:02,620 --> 01:22:03,821
OF PHYSIOLOGICAL RISK FACTORS

2489
01:22:03,821 --> 01:22:04,922
MAY REPRESENT AN IMPORTANT

2490
01:22:04,922 --> 01:22:06,223
APPROACH TO EXTENDED HEALTHSPAN

2491
01:22:06,223 --> 01:22:09,026
AND LIFESPAN BUT THERE'S A LOT

2492
01:22:09,026 --> 01:22:10,094
MORE RESEARCH GAPS THAT NEED TO

2493
01:22:10,094 --> 01:22:13,197
BE ADDRESSED.

2494
01:22:13,197 --> 01:22:15,633
IT HAS NOT BEEN FULLY HARNESSED

2495
01:22:15,633 --> 01:22:16,433
FOR IMPROVING HUMAN HEALTH.

2496
01:22:16,433 --> 01:22:18,302
THANK YOU ALL FOR YOUR ATTENTION

2497
01:22:18,302 --> 01:22:19,503
THIS AFTERNOON.

2498
01:22:19,503 --> 01:22:23,173
AND I JUST WANT TO ACKNOWLEDGE

2499
01:22:23,173 --> 01:22:25,342
THE NIH, THE AHA FOR FUNDING MY

2500
01:22:25,342 --> 01:22:27,211
WORK, AND ALL THE RESEARCH

2501
01:22:27,211 --> 01:22:28,379
PARTICIPANTS, RESEARCH STAFF AND

2502
01:22:28,379 --> 01:22:29,480
COLLABORATORS THAT CONTRIBUTED

2503
01:22:29,480 --> 01:22:30,481
GREATLY TO A LOT OF THE WORK

2504
01:22:30,481 --> 01:22:31,915
THAT I SHOWED YOU TODAY.

2505
01:22:31,915 --> 01:22:40,991
THANK YOU.

2506
01:22:40,991 --> 01:22:43,560
>> THANK YOU ALL SO MUCH!

2507
01:22:43,560 --> 01:22:48,265
WE HAD THREE VERY AMAZING

2508
01:22:48,265 --> 01:22:49,466
PRESENTATIONS.

2509
01:22:49,466 --> 01:22:50,567
AND WE HAVE SOME EXCELLENT

2510
01:22:50,567 --> 01:22:54,038
QUESTIONS IN THE CHAT.

2511
01:22:54,038 --> 01:22:55,572
SO AGAIN, IF YOU HAVE QUESTIONS,

2512
01:22:55,572 --> 01:23:01,178
PLEASE PUT THEM IN THE Q &
A.

2513
01:23:01,178 --> 01:23:03,113
THE Q & A BOX IS LOCATED ON
THE

2514
01:23:03,113 --> 01:23:04,315
MENU BAR LOCATED AT THE BOTTOM

2515
01:23:04,315 --> 01:23:09,019
OF YOUR SCREEN.

2516
01:23:09,019 --> 01:23:09,987
PLEASE PUT YOUR QUESTIONS IN THE

2517
01:23:09,987 --> 01:23:10,220
CHAT.

2518
01:23:10,220 --> 01:23:11,955
WE WILL NOT BE BRINGING

2519
01:23:11,955 --> 01:23:12,489
PARTICIPANTS OFF MUTE.

2520
01:23:12,489 --> 01:23:14,558
THANK YOU.

2521
01:23:14,558 --> 01:23:20,030
SO ONE QUESTION THAT I DID WANT

2522
01:23:20,030 --> 01:23:21,532
TO HIGHLIGHT FROM THE Q & A
BOX

2523
01:23:21,532 --> 01:23:24,468
WAS BROUGHT UP BY A PARTICIPANT,

2524
01:23:24,468 --> 01:23:26,670
AN ATTENDANT, BARBARA PERI.

2525
01:23:26,670 --> 01:23:28,872
CAN YOU PLEASE ADDRESS -- THIS

2526
01:23:28,872 --> 01:23:29,673
IS TO EVERYBODY.

2527
01:23:29,673 --> 01:23:32,710
SO IF WE CAN SPOTLIGHT EVERYBODY

2528
01:23:32,710 --> 01:23:33,977
ON THE PANEL TODAY.

2529
01:23:33,977 --> 01:23:36,914
CAN YOU PLEASE ADDRESS SEX AND

2530
01:23:36,914 --> 01:23:37,915
AGE EFFECTS?

2531
01:23:37,915 --> 01:23:42,920
SO THIS IS DEFINITELY A RESEARCH

2532
01:23:42,920 --> 01:23:43,787
PRIORITY ACROSS NIH AND FOR

2533
01:23:43,787 --> 01:23:45,823
THOSE OF YOU WHO MAY OR MAY NOT

2534
01:23:45,823 --> 01:23:47,157
KNOW, THE NATIONAL CENTER ON

2535
01:23:47,157 --> 01:23:48,892
SLEEP DISORDERS RESEARCH, WHILE

2536
01:23:48,892 --> 01:23:50,327
HOUSED AT THE NATIONAL HEART,

2537
01:23:50,327 --> 01:23:51,595
LUNG AND BLOOD INSTITUTE,

2538
01:23:51,595 --> 01:23:52,896
ACTUALLY DOES COORDINATE SLEEP

2539
01:23:52,896 --> 01:23:53,897
AND CIRCADIAN RESEARCH ACROSS

2540
01:23:53,897 --> 01:23:56,834
THE NIH.

2541
01:23:56,834 --> 01:24:00,871
AND SO WHEN WE CONSIDER THESE

2542
01:24:00,871 --> 01:24:02,506
BIG QUESTIONS ABOUT SLEEP AND

2543
01:24:02,506 --> 01:24:03,574
CIRCADIAN RESEARCH, WE LOOK AT

2544
01:24:03,574 --> 01:24:04,441
PRIORITIES ACROSS THE NIH AS

2545
01:24:04,441 --> 01:24:05,542
WELL.

2546
01:24:05,542 --> 01:24:11,582
AND SO THIS QUESTION ABOUT SLEEP

2547
01:24:11,582 --> 01:24:12,916
AND CIRCADIAN CLINICAL RELEVANCE

2548
01:24:12,916 --> 01:24:14,985
ACROSS THE LIFESPAN, AND OF

2549
01:24:14,985 --> 01:24:16,487
COURSE WITH -- THROUGH THE LENS

2550
01:24:16,487 --> 01:24:18,555
OF SEX AND GENDER DO COME UP IN

2551
01:24:18,555 --> 01:24:20,657
OUR RESEARCH PRIORITIES, AND OUR

2552
01:24:20,657 --> 01:24:21,191
RESEARCH QUESTIONS.

2553
01:24:21,191 --> 01:24:25,863
SO TO THE PANELISTS, WHAT SORT

2554
01:24:25,863 --> 01:24:30,667
OF CRITICAL QUESTIONS ARE

2555
01:24:30,667 --> 01:24:32,403
CONSIDERED WITH CIRCADIAN

2556
01:24:32,403 --> 01:24:33,470
BIOLOGY, WITH CIRCADIAN

2557
01:24:33,470 --> 01:24:36,373
MEDICINE, WITH CHRONOMEDICINE

2558
01:24:36,373 --> 01:24:37,841
WITH REGARD TO SEX AND ACROSS

2559
01:24:37,841 --> 01:24:41,145
THE LIFESPAN?

2560
01:24:41,145 --> 01:24:42,746
I KNOW THAT'S A VERY BROAD

2561
01:24:42,746 --> 01:24:43,147
QUESTION.

2562
01:24:43,147 --> 01:24:45,182
TELL US ALL THE THINGS ABOUT

2563
01:24:45,182 --> 01:24:48,986
ACROSS THE LIFESPAN.

2564
01:24:48,986 --> 01:24:50,421
HOW DOES CIRCADIAN BIOLOGY

2565
01:24:50,421 --> 01:24:54,992
CHANGE AS WE AGE?

2566
01:24:54,992 --> 01:24:57,494
>> I'LL JUST START AND
JUMP IN

2567
01:24:57,494 --> 01:25:01,198
BY SAYING THAT WITHIN THE ANIMAL

2568
01:25:01,198 --> 01:25:02,599
LITERATURE, IT VERY WELL

2569
01:25:02,599 --> 01:25:04,868
ESTABLISHED THAT AS YOU -- AS

2570
01:25:04,868 --> 01:25:06,904
THE ANIMALS GET OLDER, THEIR

2571
01:25:06,904 --> 01:25:09,273
CIRCADIAN RHYTHMS DO START TO

2572
01:25:09,273 --> 01:25:09,540
FRAGMENT.

2573
01:25:09,540 --> 01:25:12,309
YOU SEE SOMETHING LIKE WHAT NOUR

2574
01:25:12,309 --> 01:25:15,846
WAS SHOWING IN TERMS OF THIS

2575
01:25:15,846 --> 01:25:17,981
AMPLITUDE OF -- THE AMPLITUDE OF

2576
01:25:17,981 --> 01:25:20,684
THE RHYTHMICITY IS DREE

2577
01:25:20,684 --> 01:25:21,018
CREASING.

2578
01:25:21,018 --> 01:25:25,122
AN --DECREASING.

2579
01:25:25,122 --> 01:25:26,023
IN TERMS OF HOW THAT'S

2580
01:25:26,023 --> 01:25:27,090
ASSOCIATED WITH THE ANIMAL'S

2581
01:25:27,090 --> 01:25:28,759
HEALTH, I DON'T KNOW.

2582
01:25:28,759 --> 01:25:32,663
THERE'S ALSO, OF COURSE, STRONG

2583
01:25:32,663 --> 01:25:35,966
DIFFERENCES BETWEEN THE SEXES.

2584
01:25:35,966 --> 01:25:37,701
SO FEMALES HAVE A VERY

2585
01:25:37,701 --> 01:25:40,103
INTERESTING PATTERN, IT'S

2586
01:25:40,103 --> 01:25:41,605
SOMETIMES CALLED SCALLOPING,

2587
01:25:41,605 --> 01:25:45,342
WHERE THERE'S A CHANGE IN THEIR

2588
01:25:45,342 --> 01:25:47,611
RHYTHM PHASE EVERY FOUR DAYS IN

2589
01:25:47,611 --> 01:25:50,247
CONCERT WITH THEIR ESTRADIOL

2590
01:25:50,247 --> 01:25:52,649
LEVELS AND THEIR ESTRUS CYCLE.

2591
01:25:52,649 --> 01:25:54,718
AND THAT WAS USED, OF COURSE,

2592
01:25:54,718 --> 01:25:57,120
FOR DECADES TO SAY THAT LET'S

2593
01:25:57,120 --> 01:26:00,257
NOT STUDY THEM BECAUSE IT'S TOO

2594
01:26:00,257 --> 01:26:00,924
COMPLICATED.

2595
01:26:00,924 --> 01:26:04,094
IT TURNS OUT, THOUGH, THAT

2596
01:26:04,094 --> 01:26:06,663
EXCEPT FOR THAT SCALLOPING, THE

2597
01:26:06,663 --> 01:26:08,866
ACTUAL CIRCADIAN PATTERN OF

2598
01:26:08,866 --> 01:26:09,867
RUNNING WHEEL ACTIVITY IN

2599
01:26:09,867 --> 01:26:11,168
FEMALES IS MUCH MORE STABLE

2600
01:26:11,168 --> 01:26:15,172
ACTUALLY THAN IN MALES.

2601
01:26:15,172 --> 01:26:16,840
SO THERE'S A HORMONAL EFFECT ON

2602
01:26:16,840 --> 01:26:19,776
THE RHYTHMS ITSELF, BUT CLEARLY

2603
01:26:19,776 --> 01:26:22,412
A SEX DIFFERENCE AS WELL IN HOW

2604
01:26:22,412 --> 01:26:26,683
THOSE RHYTHMS ARE ORGANIZED.

2605
01:26:26,683 --> 01:26:28,185
>> HOW DOES THAT TRANSLATE
TO

2606
01:26:28,185 --> 01:26:31,755
HUMAN STUDIES AND CLINICAL

2607
01:26:31,755 --> 01:26:32,289
IMPLEMENTATION, CLINICAL

2608
01:26:32,289 --> 01:26:35,292
QUESTIONS?

2609
01:26:35,292 --> 01:26:37,461
>> I CAN TAKE THE NEXT
STAGE UP

2610
01:26:37,461 --> 01:26:40,030
MAYBE, AND I THINK FROM A

2611
01:26:40,030 --> 01:26:40,797
CLINICAL STANDPOINT, THERE ARE A

2612
01:26:40,797 --> 01:26:43,433
COUPLE OF THINGS TO KEEP IN

2613
01:26:43,433 --> 01:26:43,867
MIND.

2614
01:26:43,867 --> 01:26:45,936
FROM AN AGING PERSPECTIVE IN A

2615
01:26:45,936 --> 01:26:47,037
HUMAN POPULATION, IT'S BEEN WELL

2616
01:26:47,037 --> 01:26:49,106
DESCRIBED THAT WE KNOW THAT

2617
01:26:49,106 --> 01:26:51,475
EVERYBODY, NO MATTER WHAT YOUR

2618
01:26:51,475 --> 01:26:53,010
UNDERLYING CHRONOTYPE IS, TENDS

2619
01:26:53,010 --> 01:26:54,745
TO GET LATER WHEN THEY GO

2620
01:26:54,745 --> 01:26:57,281
THROUGH ADOLESCENCE, AND THEN AS

2621
01:26:57,281 --> 01:27:00,450
THEY GET OLDER, THEY TEND TO GET

2622
01:27:00,450 --> 01:27:00,984
EARLIER.

2623
01:27:00,984 --> 01:27:02,085
SO JUST FROM A RECOGNITION

2624
01:27:02,085 --> 01:27:03,086
STANDPOINT, I THINK IT'S REALLY

2625
01:27:03,086 --> 01:27:04,788
IMPORTANT TO REALIZE THAT OUR

2626
01:27:04,788 --> 01:27:06,423
PATIENTS WITH THESE CIRCADIAN

2627
01:27:06,423 --> 01:27:07,858
DISORDERS ARE GOING TO START

2628
01:27:07,858 --> 01:27:09,860
PRESENTING IN THAT ADOLESCENT

2629
01:27:09,860 --> 01:27:10,027
AGE.

2630
01:27:10,027 --> 01:27:10,694
THAT'S WHEN THEY'RE REALLY GOING

2631
01:27:10,694 --> 01:27:12,963
TO START STRUGGLING, AND I THINK

2632
01:27:12,963 --> 01:27:14,598
KEEPING IN MIND THAT IT ISN'T

2633
01:27:14,598 --> 01:27:16,333
NECESSARILY JUST THAT THEY'RE AN

2634
01:27:16,333 --> 01:27:17,868
ADOLESCENT WHO DOESN'T WANT TO

2635
01:27:17,868 --> 01:27:18,969
PUT DOWN THEIR DEVICE AND GO TO

2636
01:27:18,969 --> 01:27:20,604
BED AND DOESN'T WANT TO GET UP

2637
01:27:20,604 --> 01:27:21,038
FOR SCHOOL.

2638
01:27:21,038 --> 01:27:22,673
THERE MAY BE AN UNDERLYING

2639
01:27:22,673 --> 01:27:23,774
DISORDER, SO KEEPING THAT LEVEL

2640
01:27:23,774 --> 01:27:28,612
OF AWING IN MI -- OF AGING IN MK

2641
01:27:28,612 --> 01:27:29,446
IS REALLY IMPORTANT.

2642
01:27:29,446 --> 01:27:30,881
THE QUESTION OF SEX AND GENDER

2643
01:27:30,881 --> 01:27:32,516
IS A REALLY INTERESTING ONE

2644
01:27:32,516 --> 01:27:33,784
BECAUSE IF YOU LOOK AT

2645
01:27:33,784 --> 01:27:35,419
ALL-COMERS FOR MOST OF THE

2646
01:27:35,419 --> 01:27:37,521
DELAYED SLEEP-WAKE PHASE

2647
01:27:37,521 --> 01:27:39,022
DISORDER STUDIES, IF YOU JUST

2648
01:27:39,022 --> 01:27:40,223
SORT OF PUT A GENERAL POLL OUT

2649
01:27:40,223 --> 01:27:42,092
THERE AND SAY WE'RE LOOKING FOR

2650
01:27:42,092 --> 01:27:44,995
PEOPLE WITH DSPD, ALMOST ALWAYS

2651
01:27:44,995 --> 01:27:46,196
UNLIKE MOST OTHER RESEARCH

2652
01:27:46,196 --> 01:27:48,198
STUDY, YOU TEND TO GET MORE MEN

2653
01:27:48,198 --> 01:27:49,533
ENROLLING THAN YOU DO WOMEN.

2654
01:27:49,533 --> 01:27:52,135
NOW, DO WE KNOW THAT THE

2655
01:27:52,135 --> 01:27:54,438
PREVALENCE OF DSPD IS HIGHER IN

2656
01:27:54,438 --> 01:27:54,972
MEN?

2657
01:27:54,972 --> 01:27:56,840
I'M NOT SURE, AND WE'RE

2658
01:27:56,840 --> 01:27:58,108
CONDUCTING A STUDY RIGHT NOW

2659
01:27:58,108 --> 01:28:00,978
TRYING TO BETTER PHENOTYPE THESE

2660
01:28:00,978 --> 01:28:02,279
INDIVIDUALS BUT I THINK IT WILL

2661
01:28:02,279 --> 01:28:03,046
BE VERY INTERESTING TO LOOK INTO

2662
01:28:03,046 --> 01:28:03,914
WHAT THOSE DIFFERENCES ARE AND

2663
01:28:03,914 --> 01:28:06,116
WHY IS IT WE'RE TENDING TO SEE

2664
01:28:06,116 --> 01:28:07,317
THAT MORE OFTEN THAN IF WE'RE

2665
01:28:07,317 --> 01:28:08,619
JUST PUTTING GENERAL CALLS OUT

2666
01:28:08,619 --> 01:28:14,891
THERE FOR PEOPLE WITH DSPD.

2667
01:28:14,891 --> 01:28:16,493
>> I'LL JUST JUMP IN AND I
GUESS

2668
01:28:16,493 --> 01:28:17,327
TALK ABOUT THE POPULATION

2669
01:28:17,327 --> 01:28:17,594
RESEARCH.

2670
01:28:17,594 --> 01:28:20,530
IN TERMS OF THE RESEARCH ON REST

2671
01:28:20,530 --> 01:28:24,635
ACTIVITY RHYTHMS, THESE

2672
01:28:24,635 --> 01:28:25,602
DEFINITELY TEND TO CHANGE WITH

2673
01:28:25,602 --> 01:28:25,769
AGE.

2674
01:28:25,769 --> 01:28:27,804
A LOT OF THE RESEARCH ON REST

2675
01:28:27,804 --> 01:28:29,139
ACTIVITY RHYTHMS IN RELATION TO

2676
01:28:29,139 --> 01:28:30,407
HEALTH OUTCOMES IN POPULATION

2677
01:28:30,407 --> 01:28:31,708
STUDIES IS CROSS-SECTIONAL, BUT

2678
01:28:31,708 --> 01:28:33,477
IN GENERAL, WE'RE MORE LIKELY TO

2679
01:28:33,477 --> 01:28:35,212
SEE DISRUPTED REST ACTIVITY

2680
01:28:35,212 --> 01:28:37,481
RHYTHMS IN OLDER INDIVIDUALS.

2681
01:28:37,481 --> 01:28:39,683
WE KNOW THAT CIRCADIAN RHYTHMS

2682
01:28:39,683 --> 01:28:41,618
CAN ALSO DAMPEN WITH AGING AND

2683
01:28:41,618 --> 01:28:43,854
THIS IS REFLECTED ALSO WITH REST

2684
01:28:43,854 --> 01:28:45,022
ACTIVITY RHYTHMS, AND THIS IS

2685
01:28:45,022 --> 01:28:47,190
WHY WE SEE ALL THESE STRONG

2686
01:28:47,190 --> 01:28:48,992
ASSOCIATIONS WITH AGE-RELATED

2687
01:28:48,992 --> 01:28:50,227
DISEASE AND AGING-RELATED

2688
01:28:50,227 --> 01:28:50,494
OUTCOMES.

2689
01:28:50,494 --> 01:28:51,662
IN FACT, I THINK THERE'S

2690
01:28:51,662 --> 01:28:53,497
PROBABLY MORE WORK ON REST

2691
01:28:53,497 --> 01:28:55,232
ACTIVITY RHYTHMS IN AGING THAN

2692
01:28:55,232 --> 01:28:57,200
THERE IS ON SOME OF THE

2693
01:28:57,200 --> 01:28:58,101
CARDIOMETABOLIC OUTCOMES THAT I

2694
01:28:58,101 --> 01:29:02,239
WORK ON AND PRESENTED ON TODAY.

2695
01:29:02,239 --> 01:29:03,974
IN TERMS OF SEX DIFFERENCES,

2696
01:29:03,974 --> 01:29:09,146
THOUGH, I WILL SAY THAT WHEN WE

2697
01:29:09,146 --> 01:29:10,881
STRATIFY BY SEX IN THIS WORK,

2698
01:29:10,881 --> 01:29:12,516
FROM AT LEAST IN THE WORK THAT I

2699
01:29:12,516 --> 01:29:14,751
DO ON REST ACTIVITY RHYTHMS AND

2700
01:29:14,751 --> 01:29:15,686
CARDIOMETABOLIC OUTCOMES, THE

2701
01:29:15,686 --> 01:29:17,254
ASSOCIATIONS TEND TO BE THE SAME

2702
01:29:17,254 --> 01:29:21,058
INTENTINAND TEND TO PERSIST IN H

2703
01:29:21,058 --> 01:29:21,591
SEXES.

2704
01:29:21,591 --> 01:29:25,095
SIMILARLY WITH THE WORK ON

2705
01:29:25,095 --> 01:29:25,729
CHRONONUTRITION, ONE THING THAT

2706
01:29:25,729 --> 01:29:27,731
I WILL HIGHLIGHT AS I WAS

2707
01:29:27,731 --> 01:29:30,667
PREPPING FOR THIS PRESENTATION

2708
01:29:30,667 --> 01:29:33,503
IS THAT WHEN WE THINK ABOUT THE

2709
01:29:33,503 --> 01:29:35,372
DIURNAL MARKERS OF

2710
01:29:35,372 --> 01:29:36,807
CARDIOMETABOLIC RISK FACTORS,

2711
01:29:36,807 --> 01:29:37,674
THERE'S DEFINITELY MUCH LESS

2712
01:29:37,674 --> 01:29:40,177
WORK IN FEMALE POPULATIONS AND I

2713
01:29:40,177 --> 01:29:40,811
BELIEVE THIS WAS SOMETHING THAT

2714
01:29:40,811 --> 01:29:42,913
WAS HIGHLIGHTED IN THE NHLBI

2715
01:29:42,913 --> 01:29:44,848
WORKSHOP ON CHRONOTHERAPY AND

2716
01:29:44,848 --> 01:29:45,215
BLOOD PRESSURE.

2717
01:29:45,215 --> 01:29:46,616
I THINK THERE IS MUCH LESS

2718
01:29:46,616 --> 01:29:47,918
EVIDENCE IN FEMALES COMPARED TO

2719
01:29:47,918 --> 01:29:53,423
MALES.

2720
01:29:53,423 --> 01:29:56,026
>> THANK YOU FOR
HIGHLIGHTING

2721
01:29:56,026 --> 01:29:56,993
THAT.

2722
01:29:56,993 --> 01:29:57,527
ACTUALLY THERE WAS ANOTHER

2723
01:29:57,527 --> 01:29:58,762
QUESTION, AND I DID WANT TO

2724
01:29:58,762 --> 01:30:02,265
JUST -- IT SORT OF PIGGY BACKS

2725
01:30:02,265 --> 01:30:05,535
OFF OF THIS, BUT IT IS VERY

2726
01:30:05,535 --> 01:30:08,705
SPECIFIC TO YOUR TALK,

2727
01:30:08,705 --> 01:30:09,005
DR. MAKAREM.

2728
01:30:09,005 --> 01:30:10,574
CAN YOU SPEAK TO THE

2729
01:30:10,574 --> 01:30:12,442
RELATIONSHIP BETWEEN BEHAVIORAL

2730
01:30:12,442 --> 01:30:13,610
AND CIRCADIAN RHYTHMS?

2731
01:30:13,610 --> 01:30:15,045
THIS IS COMING FROM STEVEN

2732
01:30:15,045 --> 01:30:16,747
CARLSON, WHO'S IN ATTENDANCE

2733
01:30:16,747 --> 01:30:17,013
TODAY.

2734
01:30:17,013 --> 01:30:18,949
HE SAYS, I COULD IMAGINE IF

2735
01:30:18,949 --> 01:30:20,917
THESE ARE BIDIRECTIONAL, BUT IS

2736
01:30:20,917 --> 01:30:24,554
THERE ANY EVIDENCE THAT THERE IS

2737
01:30:24,554 --> 01:30:26,723
A STRONGER RELATIONSHIP IN ANY

2738
01:30:26,723 --> 01:30:27,190
PARTICULAR DIRECTION?

2739
01:30:27,190 --> 01:30:27,924
AND I'M SURE ALL OF YOU CAN

2740
01:30:27,924 --> 01:30:31,428
SPEAK TO THIS RELATIONSHIP

2741
01:30:31,428 --> 01:30:32,496
BETWEEN VIECIALT TALL OR

2742
01:30:32,496 --> 01:30:34,698
BEHAVIORAL CUES AS WELL AS

2743
01:30:34,698 --> 01:30:41,171
CIRCADIAN CUES.

2744
01:30:41,171 --> 01:30:44,007
DO YOU THINK -- IN YOUR

2745
01:30:44,007 --> 01:30:45,442
OPINIONS, I GUESS, IS CIRCADIAN

2746
01:30:45,442 --> 01:30:49,346
STRONGER THAN EXTERNAL CUES, OR

2747
01:30:49,346 --> 01:30:51,114
IS THERE CONTEXT OR NUANCE TO BE

2748
01:30:51,114 --> 01:30:56,686
CONSIDERED IN THESE CASES?

2749
01:30:56,686 --> 01:30:57,888
>> I KNOW THIS QUESTION
WAS

2750
01:30:57,888 --> 01:30:59,723
DIRECTED TO ME, BUT I FEEL LIKE

2751
01:30:59,723 --> 01:31:01,057
MY COLLEAGUES MIGHT ANSWER THIS

2752
01:31:01,057 --> 01:31:03,660
BETTER BECAUSE IN POPULATION

2753
01:31:03,660 --> 01:31:05,095
RESEARCH, LIKE I MENTIONED,

2754
01:31:05,095 --> 01:31:08,932
BECAUSE A LOT OF THIS,

2755
01:31:08,932 --> 01:31:12,569
ESPECIALLY THESE ACTGRAPHYSTUDIO

2756
01:31:12,569 --> 01:31:13,770
BE CROSS-SECTIONAL.

2757
01:31:13,770 --> 01:31:16,273
BUT OF COURSE THERE IS A

2758
01:31:16,273 --> 01:31:17,340
BIDIRECTIONAL RELATIONSHIP, I

2759
01:31:17,340 --> 01:31:22,078
WOULD IMAGINE, BETWEEN I MAIJ

2760
01:31:22,078 --> 01:31:22,846
CIRCADIAN RHYTHMS AND BEHAVIORAL

2761
01:31:22,846 --> 01:31:23,280
RHYTHMS.

2762
01:31:23,280 --> 01:31:26,116
IN TERMS OF DIE URGE PATTERNS OF

2763
01:31:26,116 --> 01:31:26,750
BIOMARKERS, THAT WAS ONE OF THE

2764
01:31:26,750 --> 01:31:30,287
AREAS I HIGHLIGHTED AS A GAP

2765
01:31:30,287 --> 01:31:33,557
BECAUSE LIKE I SAID, OFTENTIMES

2766
01:31:33,557 --> 01:31:34,558
THE EVALUATION OF THE BEHAVIORAL

2767
01:31:34,558 --> 01:31:36,326
RHYTHMS IS NOT CONCURRENT WITH

2768
01:31:36,326 --> 01:31:38,495
THE EVALUATION OF THE DIURNAL

2769
01:31:38,495 --> 01:31:40,564
PATTERNS OF THE BEHAVIORAL RISK

2770
01:31:40,564 --> 01:31:41,765
FACTOR, SO IT'S BEEN REALLY HARD

2771
01:31:41,765 --> 01:31:42,766
TO TEASE OUT WHAT THOSE

2772
01:31:42,766 --> 01:31:43,967
ASSOCIATIONS LOOK LIKE IN

2773
01:31:43,967 --> 01:31:45,502
REALTIME.

2774
01:31:45,502 --> 01:31:48,572
I DON'T KNOW IF THE OTHER

2775
01:31:48,572 --> 01:31:49,773
PRESENTERS HAVE MORE INSIGHT

2776
01:31:49,773 --> 01:31:51,775
FROM CLINICAL WORK AND BASIC

2777
01:31:51,775 --> 01:31:54,311
SCIENCE.

2778
01:31:54,311 --> 01:31:56,580
>> I HAVE LOTS OF THOUGHTS
ON

2779
01:31:56,580 --> 01:32:00,183
THIS.

2780
01:32:00,183 --> 01:32:02,352
SO I THINK WHAT IT BOILS DOWN TO

2781
01:32:02,352 --> 01:32:04,120
IS WHETHER OR NOT THERE'S SOME

2782
01:32:04,120 --> 01:32:06,089
OPTIMAL TIME OF THE CIRCADIAN

2783
01:32:06,089 --> 01:32:07,624
CYCLE IN WHICH THESE BEHAVIORS

2784
01:32:07,624 --> 01:32:10,894
NEED TO OCCUR, OR WHETHER YOU

2785
01:32:10,894 --> 01:32:11,995
CAN SOLVE EVERYTHING BY SIMPLY

2786
01:32:11,995 --> 01:32:15,332
HAVING ALL THE BEHAVIORS AT THE

2787
01:32:15,332 --> 01:32:16,700
SAME TIME, AND SORT OF IGNORE

2788
01:32:16,700 --> 01:32:17,234
THE CIRCADIAN CLOCK.

2789
01:32:17,234 --> 01:32:18,635
AND I THINK THERE'S EVIDENCE FOR

2790
01:32:18,635 --> 01:32:23,573
BOTH OF THOSE.

2791
01:32:23,573 --> 01:32:28,044
SO WHETHER  THERE WAS A NICE STM

2792
01:32:28,044 --> 01:32:29,779
THE ESCOBAR LABORATORY ABOUT 10

2793
01:32:29,779 --> 01:32:32,115
OR 15 YEARS AGO, AND I THINK

2794
01:32:32,115 --> 01:32:33,750
THEY HAD RATS EATING A HIGH FAT

2795
01:32:33,750 --> 01:32:35,418
DIET DURING THE DAY TIME, SO IN

2796
01:32:35,418 --> 01:32:36,953
THEIR INACTIVE PHASE AND THOSE

2797
01:32:36,953 --> 01:32:38,455
ANIMALS GOT FAT, AS YOU MIGHT

2798
01:32:38,455 --> 01:32:39,122
EXPECT.

2799
01:32:39,122 --> 01:32:40,156
AND THEN THEY SIMPLY ALLOWED

2800
01:32:40,156 --> 01:32:41,424
THOSE ANIMALS TO -- THEY PUT

2801
01:32:41,424 --> 01:32:43,093
THEM IN A WHEEL THAT WAS MOVING

2802
01:32:43,093 --> 01:32:46,830
TO KEEP THEM AWAKE AND MOVING

2803
01:32:46,830 --> 01:32:47,998
DURING THAT DAY TIME WHEN THEY

2804
01:32:47,998 --> 01:32:48,999
HAD THE FOOD.

2805
01:32:48,999 --> 01:32:50,967
SO NOW THEY'RE PAIRING HIGHER

2806
01:32:50,967 --> 01:32:52,402
ACTIVITY WITH THE TIME OF

2807
01:32:52,402 --> 01:32:55,138
EATING, AND IT COMPLETELY SOLVED

2808
01:32:55,138 --> 01:32:56,106
EVERYTHING.

2809
01:32:56,106 --> 01:32:58,174
EVEN THOUGH THEIR CIRCADIAN

2810
01:32:58,174 --> 01:33:00,844
CLOCK IN THEIR BRAIN, IN THEIR

2811
01:33:00,844 --> 01:33:02,545
SCN WOULD STILL BE ENTRAINED TO

2812
01:33:02,545 --> 01:33:04,514
THE LIGHT-DARK CYCLE NORMALLY.

2813
01:33:04,514 --> 01:33:05,882
SO THAT WOULD ARGUE FOR THE FACT

2814
01:33:05,882 --> 01:33:06,716
THAT AS LONG AS YOU HAVE ALL

2815
01:33:06,716 --> 01:33:08,084
THESE BEHAVIORS PAIRED TOGETHER

2816
01:33:08,084 --> 01:33:09,119
AT THE SAME TIME, THAT WOULD BE

2817
01:33:09,119 --> 01:33:10,520
IMPORTANT.

2818
01:33:10,520 --> 01:33:12,389
IF WE THINK ABOUT THAT FOR

2819
01:33:12,389 --> 01:33:14,257
HUMANS, THEN YOU COULD SAY OKAY,

2820
01:33:14,257 --> 01:33:15,892
MAYBE IT DOESN'T MATTER IF

2821
01:33:15,892 --> 01:33:17,928
THEY'RE SHIFT WORKERS, AS LONG

2822
01:33:17,928 --> 01:33:19,629
AS THEY'RE EXERCISING AND EATING

2823
01:33:19,629 --> 01:33:20,997
AND DOING ALL THOSE THINGS AT

2824
01:33:20,997 --> 01:33:22,565
THE SAME TIME OF DAY, AND TRYING

2825
01:33:22,565 --> 01:33:24,134
TO KEEP THEM STABLE.

2826
01:33:24,134 --> 01:33:26,002
WE ALL KNOW ONE OF THE BIG

2827
01:33:26,002 --> 01:33:27,304
CHALLENGES FOR SHIFT WORKERS IS

2828
01:33:27,304 --> 01:33:29,039
THAT THEY HAVE ONE PARTICULAR

2829
01:33:29,039 --> 01:33:31,007
WORK SCHEDULE BUT THEN THEY HAVE

2830
01:33:31,007 --> 01:33:32,642
FAMILY DEMANDS, THEY HAVE KIDS

2831
01:33:32,642 --> 01:33:34,077
SOCCER GAMES TO GO TO ON THE

2832
01:33:34,077 --> 01:33:37,047
WEEKENDS, ET CETERA.

2833
01:33:37,047 --> 01:33:38,882
HOWEVER, I'LL ALSO SAY THAT

2834
01:33:38,882 --> 01:33:40,317
THERE'S BEEN A LOT OF INTEREST

2835
01:33:40,317 --> 01:33:42,852
IN TIME RESTRICTED EATING, AND

2836
01:33:42,852 --> 01:33:46,890
HOW THAT COULD BE A

2837
01:33:46,890 --> 01:33:47,257
CHRONONUTRITION,

2838
01:33:47,257 --> 01:33:48,124
CHRONOTHERAPEUTIC FOR CHRONIC

2839
01:33:48,124 --> 01:33:49,759
CONDITIONS, AND THE EVIDENCE

2840
01:33:49,759 --> 01:33:54,030
REALLY SUGGESTS THAT EARLY TIME

2841
01:33:54,030 --> 01:33:55,432
RESTRICTED EATING MAY BE BETTER

2842
01:33:55,432 --> 01:33:56,933
THAN LATER TIME RESTRICTED

2843
01:33:56,933 --> 01:33:57,200
EATING.

2844
01:33:57,200 --> 01:33:59,669
SO THAT THERE IS SOME BENEFIT

2845
01:33:59,669 --> 01:34:01,571
ACTUALLY TO HAVING THE CALORIES

2846
01:34:01,571 --> 01:34:04,841
MATCHED UP TO THE CIRCADIAN

2847
01:34:04,841 --> 01:34:06,276
CYCLE.

2848
01:34:06,276 --> 01:34:07,344
I THINK THAT THIS IS AN AREA

2849
01:34:07,344 --> 01:34:12,816
THAT IS REALLY RIPE FOR FURTHER

2850
01:34:12,816 --> 01:34:14,150
RESEARCH, BECAUSE THE KINDS OF

2851
01:34:14,150 --> 01:34:15,552
FOOD THAT PEOPLE MIGHT BE

2852
01:34:15,552 --> 01:34:17,420
SELECTING IF THEY'RE EARLY

2853
01:34:17,420 --> 01:34:19,689
EATERS VERSUS LATE EATERS MIGHT

2854
01:34:19,689 --> 01:34:20,256
BE DIFFERENT.

2855
01:34:20,256 --> 01:34:21,458
I WOULD BE SHOCKED IF THE

2856
01:34:21,458 --> 01:34:22,359
CIRCADIAN SYSTEM IS NOT

2857
01:34:22,359 --> 01:34:26,129
IMPORTANT IN THIS, HOW FAR

2858
01:34:26,129 --> 01:34:28,698
ITS TENDRILS EXTEND INTO THE

2859
01:34:28,698 --> 01:34:29,733
PHYSIOLOGY.

2860
01:34:29,733 --> 01:34:33,003
BUT I'LL LEAVE ITBU AT THAT.

2861
01:34:33,003 --> 01:34:34,838
>> AND I'LL JUST CHIME IN
FROM

2862
01:34:34,838 --> 01:34:35,372
MY STANDPOINT.

2863
01:34:35,372 --> 01:34:37,140
I THINK THIS KIND OF GETS AT THE

2864
01:34:37,140 --> 01:34:39,876
HEART OF WHAT I THINK

2865
01:34:39,876 --> 01:34:43,480
MYCO-SPEAKERS ALSO TOU TOUCHED ,

2866
01:34:43,480 --> 01:34:44,581
WHICH IS THAT ONE OF THE

2867
01:34:44,581 --> 01:34:48,651
CHALLENGES WE HAVE WITH

2868
01:34:48,651 --> 01:34:49,719
CIRCADIAN TIMING OVERALL IN THE

2869
01:34:49,719 --> 01:34:50,820
CONTEXT OF PATIENTS WITH

2870
01:34:50,820 --> 01:34:53,156
CIRCADIAN DISORDERS IS, WHAT

2871
01:34:53,156 --> 01:34:54,791
IS OUR ULTIMATE GOAL IF WE'RE

2872
01:34:54,791 --> 01:34:56,192
TRYING TO OPTIMIZE THEIR HEALTH?

2873
01:34:56,192 --> 01:34:59,829
IS IT THAT WE ADJUST THEIR

2874
01:34:59,829 --> 01:35:00,930
ENVIRONMENT SO THAT THEY'RE ABLE

2875
01:35:00,930 --> 01:35:03,466
TO FOLLOW THERREL BIOLOGICALLY

2876
01:35:03,466 --> 01:35:04,200
PREFERRED SCHEDULE?

2877
01:35:04,200 --> 01:35:05,535
IT JUST DOESN'T MATCH UP WITH

2878
01:35:05,535 --> 01:35:07,070
EVERYBODY ELSE?

2879
01:35:07,070 --> 01:35:09,406
AND IT'S MISALIGNED WITH THE

2880
01:35:09,406 --> 01:35:10,573
ENVIRONMENTAL LIGHT-DARK BUT

2881
01:35:10,573 --> 01:35:12,208
THEY'RE AT LEAST NOT GETTING

2882
01:35:12,208 --> 01:35:14,344
SLEEP RESTRICTED, THEY GO TO BED

2883
01:35:14,344 --> 01:35:15,879
AT THE SAME TIME,AM WE'VE GIVEN

2884
01:35:15,879 --> 01:35:17,080
THEM THAT REGULARITY BY

2885
01:35:17,080 --> 01:35:18,748
ADJUSTING THEIR SCHOOL START

2886
01:35:18,748 --> 01:35:21,751
TIMES, WORK SCHEDULES AND THOSE

2887
01:35:21,751 --> 01:35:23,853
TYPES OF THINGS, OR IS IT MORE

2888
01:35:23,853 --> 01:35:25,188
IMPORTANTLY THAT WE SHIFT THEIR

2889
01:35:25,188 --> 01:35:26,489
RHYTHM AND PUSH THEM SO THAT

2890
01:35:26,489 --> 01:35:27,791
THEY'RE SLEEPING AT NIGHT LIKE

2891
01:35:27,791 --> 01:35:29,893
EVERYBODY ELSE IS, AND WHAT IS

2892
01:35:29,893 --> 01:35:31,428
THE WORST DRIEMP THERE?

2893
01:35:31,428 --> 01:35:39,836
IS IT THE APPROPRI THE INAPPROPT

2894
01:35:39,836 --> 01:35:40,937
EXPOSURE D AS WE TRY TO FIGURE

2895
01:35:40,937 --> 01:35:42,572
OUT HOW DO WE OPTIMIZE THE

2896
01:35:42,572 --> 01:35:44,240
HEALTH BECAUSE WE HAVE

2897
01:35:44,240 --> 01:35:44,908
POPULATION-BASED DATA SHOWING

2898
01:35:44,908 --> 01:35:47,644
THAT THEY DO HAVE WORSE HEALTH

2899
01:35:47,644 --> 01:35:53,116
OUTCOMES BUT WHAT COMPONENT OF

2900
01:35:53,116 --> 01:35:55,351
THAT IS IT THAT'S CONTRIBUTING

2901
01:35:55,351 --> 01:35:56,519
TO THAT IN THAT POPULATION.

2902
01:35:56,519 --> 01:35:58,621
AND THAT TIES TOGETHER BOTH

2903
01:35:58,621 --> 01:36:05,728
THEIR BEHAVIORS OF WHEN THEY'RE

2904
01:36:05,728 --> 01:36:08,031
DOING THINGS AND THOSE THAT ARE

2905
01:36:08,031 --> 01:36:08,998
MISALIGNED WITH THE EXTERNAL

2906
01:36:08,998 --> 01:36:09,332
ENVIRONMENT.

2907
01:36:09,332 --> 01:36:12,735
>> SO THERE IS SOME

2908
01:36:12,735 --> 01:36:13,369
POPULATION-BASED EVIDENCE AND

2909
01:36:13,369 --> 01:36:16,239
THERE IS SOME CLINICAL-BASED

2910
01:36:16,239 --> 01:36:17,107
EVIDENCE TO SUGGEST THAT

2911
01:36:17,107 --> 01:36:18,641
SHIFTING THE TIMING OF, SAY,

2912
01:36:18,641 --> 01:36:22,378
REST ACTIVITY, CALORIC INTAKE,

2913
01:36:22,378 --> 01:36:24,013
THINGS LIKE THAT, CAN MODIFY

2914
01:36:24,013 --> 01:36:27,517
HEALTH BUT WE HAVE THIS OTHER

2915
01:36:27,517 --> 01:36:28,818
VARIABLE OF BEHAVIOR THAT ALSO

2916
01:36:28,818 --> 01:36:31,888
NEEDS TO BE CONSIDERED AND

2917
01:36:31,888 --> 01:36:34,224
REALLY THE HUMAN CONDITION.

2918
01:36:34,224 --> 01:36:34,657
OKAY.

2919
01:36:34,657 --> 01:36:35,058
EXCELLENT.

2920
01:36:35,058 --> 01:36:38,828
I WOULD LIKE TO JUMP OFF OF

2921
01:36:38,828 --> 01:36:40,130
DR. ABBOTT, YOUR -- THERE WERE

2922
01:36:40,130 --> 01:36:42,132
SEVERAL QUESTIONS WITH REGARD TO

2923
01:36:42,132 --> 01:36:44,968
THE DESIGN OF YOUR EXPERIMENTS

2924
01:36:44,968 --> 01:36:49,038
IN SOME OF THESE -- I WAS REALLY

2925
01:36:49,038 --> 01:36:50,673
LOOKING FOR A WAY TO BRIDGE INTO

2926
01:36:50,673 --> 01:36:52,342
LIKE THE NITTY GRITTY OF SOME OF

2927
01:36:52,342 --> 01:36:55,278
THESE QUESTIONS, BUT YOU CREATED

2928
01:36:55,278 --> 01:37:00,216
THE BRIDGE FOR US.

2929
01:37:00,216 --> 01:37:01,651
SO REGARDING THE DIFFERENT

2930
01:37:01,651 --> 01:37:03,086
FINDINGS, THIS IS FROM REBECCA

2931
01:37:03,086 --> 01:37:04,687
COX, WHO'S AN ATTENDANT,

2932
01:37:04,687 --> 01:37:06,022
REGARDING THE DIFFERENT FINDINGS

2933
01:37:06,022 --> 01:37:11,161
OBSERVED FROM PIPR IN DELAYED

2934
01:37:11,161 --> 01:37:12,562
SLEEP-WAKE, IS IT POSSIBLE THAT

2935
01:37:12,562 --> 01:37:13,496
THESE DIFFERENCES COULD BE DUE

2936
01:37:13,496 --> 01:37:16,032
IN PART TO WHEN PIPR WAS

2937
01:37:16,032 --> 01:37:17,534
ASSESSED RELATIVE TO CIRCADIAN

2938
01:37:17,534 --> 01:37:20,236
TIMING?

2939
01:37:20,236 --> 01:37:21,871
>> HI, REBECCA.

2940
01:37:21,871 --> 01:37:23,373
THAT IS A GREAT QUESTION, AND I

2941
01:37:23,373 --> 01:37:24,707
DIDN'T GET INTO ALL OF THE

2942
01:37:24,707 --> 01:37:25,942
DETAILS OF IT BUT YOU'RE

2943
01:37:25,942 --> 01:37:29,412
ABSOLUTELY RIGHT.

2944
01:37:29,412 --> 01:37:31,147
SO THE PIPR DOES CHANGE WITH

2945
01:37:31,147 --> 01:37:33,683
TIME OF DAY BUT IT TENDS TO BE

2946
01:37:33,683 --> 01:37:35,218
MOST SENSITIVE TO THOSE CHANGES

2947
01:37:35,218 --> 01:37:37,287
RIGHT AROUND THE TIME OF DLMO,

2948
01:37:37,287 --> 01:37:39,055
SO SHORTLY BEFORE SLEEP ONSET.

2949
01:37:39,055 --> 01:37:41,324
IN OUR INITIAL PILOT STUDY, WE

2950
01:37:41,324 --> 01:37:43,660
WEREN'T ABLE TO PRECISELY

2951
01:37:43,660 --> 01:37:45,295
CONTROL FOR TIME SINCE WAKE FOR

2952
01:37:45,295 --> 01:37:48,698
EVERY SINGLE PIPR ASSESSMENT

2953
01:37:48,698 --> 01:37:50,233
BECAUSE SOMETIMES WE WERE JUST

2954
01:37:50,233 --> 01:37:51,568
PULLING THEM FROM CLINIC AND

2955
01:37:51,568 --> 01:37:53,636
BRINGING THEM OVER, BUT THAT

2956
01:37:53,636 --> 01:37:56,673
BEING SAID, THE FINAL WAS ABOUT

2957
01:37:56,673 --> 01:37:58,341
ONE TO SIX HOURS, I THINK, SO

2958
01:37:58,341 --> 01:38:01,978
THEY ALL STAYED OUTSIDE OF THAT

2959
01:38:01,978 --> 01:38:03,713
KNOWN WINDOW, THE PIPR DOES

2960
01:38:03,713 --> 01:38:04,147
CHANGE.

2961
01:38:04,147 --> 01:38:06,783
WE DID AN ANALYSIS WHERE WE

2962
01:38:06,783 --> 01:38:08,718
ADJUSTED FOR TIME SINCE WEIGHT

2963
01:38:08,718 --> 01:38:10,053
IN THE WHOLE ANALYSIS AS WELL

2964
01:38:10,053 --> 01:38:11,254
AND IT DIDN'T SEEM TO PLAY A

2965
01:38:11,254 --> 01:38:11,921
ROLE IN IT.

2966
01:38:11,921 --> 01:38:13,289
SO DEFINITELY A GREAT QUESTION,

2967
01:38:13,289 --> 01:38:14,123
SOMETHING WE THOUGHT ABOUT, AND

2968
01:38:14,123 --> 01:38:15,758
AS WE'RE DOING A MORE DETAILED

2969
01:38:15,758 --> 01:38:17,060
DIVE INTO THIS POPULATION, WE'RE

2970
01:38:17,060 --> 01:38:18,661
GOING TO MORE STRICTLY CONTROL

2971
01:38:18,661 --> 01:38:21,798
WHEN EXACTLY THAT PIPR

2972
01:38:21,798 --> 01:38:23,366
ASSESSMENT IS DONE.

2973
01:38:23,366 --> 01:38:27,003
>> DOES MELATONIN OFFSET
HAVE

2974
01:38:27,003 --> 01:38:29,339
ANY ROLE IN PREDICTINGRE OUTCOMS

2975
01:38:29,339 --> 01:38:30,240
OF CIRCADIAN DISORDERS?

2976
01:38:30,240 --> 01:38:40,583
THIS IS FOR ANYBODY.

2977
01:38:41,884 --> 01:38:43,386
EVERYBODY IS GIVING ME THE NO

2978
01:38:43,386 --> 01:38:43,586
FACE.

2979
01:38:43,586 --> 01:38:45,121
>> I THINK THAT THE ANSWER
TO

2980
01:38:45,121 --> 01:38:49,058
THAT WOULD BE YES.

2981
01:38:49,058 --> 01:38:53,997
I WOULD DEFER TO MY COLLEAGUE

2982
01:38:53,997 --> 01:38:57,267
HERE, ANDREW MACHILL WHO'S

2983
01:38:57,267 --> 01:38:58,901
STUDIED THIS IN THE INTENSIVE

2984
01:38:58,901 --> 01:39:00,136
PHYSIOLOGY IN LAB EXPERIMENTS,

2985
01:39:00,136 --> 01:39:00,770
BECAUSE WHEN WE LOOK AT THE

2986
01:39:00,770 --> 01:39:04,307
PEOPLE THAT HAVE LATER DLMOs,

2987
01:39:04,307 --> 01:39:05,975
OFTEN A LOT OF THEM DO TEND TO

2988
01:39:05,975 --> 01:39:10,413
HAVE A LATER OFFSET, AND IT

2989
01:39:10,413 --> 01:39:11,714
MEANS PEOPLE ARE AWAKENING,

2990
01:39:11,714 --> 01:39:13,716
THEY'RE HAVING THEIR FIRST MEAL

2991
01:39:13,716 --> 01:39:17,453
POTENTIALLY AT A TIME WHERE

2992
01:39:17,453 --> 01:39:20,156
MELATONIN IS EITHER STILL HIGH

2993
01:39:20,156 --> 01:39:21,591
OR BECAUSE OF BRIGHT LIGHT, IT'S

2994
01:39:21,591 --> 01:39:23,059
BEEN CURTAILED ARTIFICIALLY, SO

2995
01:39:23,059 --> 01:39:24,894
THEY'VE HAD KIND OF A REDUCED

2996
01:39:24,894 --> 01:39:31,501
TOTAL MELATONIN DURATION.

2997
01:39:31,501 --> 01:39:32,402
BUT UNFORTUNATELY APOLOGIES TO

2998
01:39:32,402 --> 01:39:33,603
ANDREW, I DON'T REMEMBER THE

2999
01:39:33,603 --> 01:39:35,138
EXACT RESULTS OFF THE TOP OF MY

3000
01:39:35,138 --> 01:39:41,511
HEAD.

3001
01:39:41,511 --> 01:39:43,179
>> WITH REGARD TO LIGHT,
AND

3002
01:39:43,179 --> 01:39:46,649
LIGHT BEING ONE OF THE STRONGEST

3003
01:39:46,649 --> 01:39:52,322
CUES, IS THERE A SIGNIFICANT

3004
01:39:52,322 --> 01:39:53,656
DIFFERENCE BETWEEN EXPERIMENTAL

3005
01:39:53,656 --> 01:39:55,558
LIGHT, LET'S SAY, FOR EXAMPLE,

3006
01:39:55,558 --> 01:39:59,896
THE INDOOR LIGHT INTENSITY THAT

3007
01:39:59,896 --> 01:40:01,531
WE USE FOR EXPERIMENTS LIKE,

3008
01:40:01,531 --> 01:40:04,834
LET'S SAY, 3,000, RIGHT, THAT

3009
01:40:04,834 --> 01:40:07,804
WAS NOTED IN DR. ABBOTT'S

3010
01:40:07,804 --> 01:40:10,473
SLIDES, VERSUS OUTDOOR, AS FAR

3011
01:40:10,473 --> 01:40:14,477
AS IT BEING A RELEVANT CUE, AND

3012
01:40:14,477 --> 01:40:19,515
DOES LIGHT SENSITIVITY CHANGE

3013
01:40:19,515 --> 01:40:24,454
ACROSS THE DAY TYPICALLY, AND

3014
01:40:24,454 --> 01:40:26,856
HOW DOES THAT NEED TO BE

3015
01:40:26,856 --> 01:40:28,358
CONSIDERED IN A CLINICAL

3016
01:40:28,358 --> 01:40:33,029
ENVIRONMENT OR CLINICAL TESTING?

3017
01:40:33,029 --> 01:40:35,198
>> I'LL START WITH THAT
ONE IF

3018
01:40:35,198 --> 01:40:37,233
ANYONE ELSE WANTS TO CHIME IN AS

3019
01:40:37,233 --> 01:40:37,433
WELL.

3020
01:40:37,433 --> 01:40:38,301
IT'S A GREAT QUESTION AND I

3021
01:40:38,301 --> 01:40:40,269
THINK IT GETS AT ONE OF MY

3022
01:40:40,269 --> 01:40:41,270
PERSONAL PET PEEVES WHEN IT

3023
01:40:41,270 --> 01:40:43,940
COMES TO LIGHT STUDY, WHICH IS

3024
01:40:43,940 --> 01:40:47,844
THAT I THINK WE'VE REACHED A

3025
01:40:47,844 --> 01:40:50,146
POINT WHERE AS GENERAL

3026
01:40:50,146 --> 01:40:51,347
POPULATION, WE HAVE STARTED TO

3027
01:40:51,347 --> 01:40:54,217
VIEW LIGHT AT NIGHT AS BAD.

3028
01:40:54,217 --> 01:40:57,620
AND THERE'S ALL OF THIS WORK TO

3029
01:40:57,620 --> 01:40:59,155
SORT OF AVOID LIGHT AND BLUE

3030
01:40:59,155 --> 01:41:00,990
LIGHT BLOCKING GLASSES AND

3031
01:41:00,990 --> 01:41:01,891
EVERYTHING ELSE, BUT IT TURNS

3032
01:41:01,891 --> 01:41:04,193
OUT THAT REALLY, IT'S YOUR SUM

3033
01:41:04,193 --> 01:41:05,428
LIGHT EXPOSURE THAT MAKES A

3034
01:41:05,428 --> 01:41:06,596
DIFFERENCE.

3035
01:41:06,596 --> 01:41:08,464
AND SO IT'S NOT SO MUCH, FOR

3036
01:41:08,464 --> 01:41:09,732
EXAMPLE, THAT THE MOST IMPORTANT

3037
01:41:09,732 --> 01:41:11,868
THING YOU NEED TO DO IS AVOID

3038
01:41:11,868 --> 01:41:13,669
LIGHT BEFORE BEDTIME.

3039
01:41:13,669 --> 01:41:15,405
BUT IT'S ACTUALLY THE MORE LIGHT

3040
01:41:15,405 --> 01:41:19,575
YOU GET DURING THE DAY, THE MORE

3041
01:41:19,575 --> 01:41:20,676
PROTECTIVE IT IS AT NIGHTTIME.

3042
01:41:20,676 --> 01:41:23,546
SO IF YOU'RE IN A STRONG

3043
01:41:23,546 --> 01:41:24,514
AMPLITUDE HIGHLY LIT ENVIRONMENT

3044
01:41:24,514 --> 01:41:25,882
ALL DAY LONG, YOU'RE ACTUALLY

3045
01:41:25,882 --> 01:41:28,050
GOING TO BE LESS SENSITIVE IN

3046
01:41:28,050 --> 01:41:32,088
MOST CASES TO THAT EVENING LIGHT

3047
01:41:32,088 --> 01:41:32,488
EXPOSURE.

3048
01:41:32,488 --> 01:41:33,623
SO I THINK IT'S REALLY IMPORTANT

3049
01:41:33,623 --> 01:41:37,126
TO THINK ABOUT LIGHT IN SORT OF

3050
01:41:37,126 --> 01:41:39,328
YOUR OVERALL CUMULATIVE EXPOSURE

3051
01:41:39,328 --> 01:41:42,598
AND NOT JUST SINGLE INTENSITY

3052
01:41:42,598 --> 01:41:43,833
HERE OR THERE.

3053
01:41:43,833 --> 01:41:44,734
ALSO I THINK THE OTHER THING

3054
01:41:44,734 --> 01:41:46,135
THAT WE'RE REALLY MOVING AWAY

3055
01:41:46,135 --> 01:41:48,204
FROM IS IT'S NOT JUST THE

3056
01:41:48,204 --> 01:41:51,274
INTENSITY IN TERMS OF LUX BUT

3057
01:41:51,274 --> 01:41:52,074
IT'S REALLY THE SPECTRUM OF

3058
01:41:52,074 --> 01:41:52,708
LIGHT.

3059
01:41:52,708 --> 01:41:56,679
SO THE MELANOPIC EXPOSURE YOU'RE

3060
01:41:56,679 --> 01:41:57,980
GETTING AS OPPOSED TO HOW

3061
01:41:57,980 --> 01:41:59,081
INTENSE IT IS, SO ARE YOU

3062
01:41:59,081 --> 01:42:01,717
ACTUALLY ACTIVATING THOSE

3063
01:42:01,717 --> 01:42:03,119
IPRGCs VERSUS GETTING OTHER

3064
01:42:03,119 --> 01:42:04,420
LIGHT EXPOSURE.

3065
01:42:04,420 --> 01:42:06,422
SO ALL OF THESE THINGS PLAY INTO

3066
01:42:06,422 --> 01:42:08,191
IT SO LIGHT CONTINUES TO BE MORE

3067
01:42:08,191 --> 01:42:09,592
AND MORE COMPLEX TO ACTUALLY

3068
01:42:09,592 --> 01:42:11,227
STUDY BECAUSE YOU HAVE TO TAKE

3069
01:42:11,227 --> 01:42:13,329
INTO ACCOUNT THE WAVELENGTH, THE

3070
01:42:13,329 --> 01:42:14,897
FREQUENCY, THE TIME AND YOUR

3071
01:42:14,897 --> 01:42:16,299
LIGHT HISTORY WHEN YOU'RE

3072
01:42:16,299 --> 01:42:18,067
ANALYZING IT.

3073
01:42:18,067 --> 01:42:18,701
>> ALL RIGHT.

3074
01:42:18,701 --> 01:42:21,037
VERY COOL.

3075
01:42:21,037 --> 01:42:23,906
WE HAVE A QUESTION FROM THE

3076
01:42:23,906 --> 01:42:25,842
CHAT -- OR FROM THE Q & A
BOX

3077
01:42:25,842 --> 01:42:28,644
FROM AN ATTENDANT, OLIVIA WALSH.

3078
01:42:28,644 --> 01:42:38,721
WHAT ARE YOUR THOUGHTS ON SUR ON

3079
01:42:38,721 --> 01:42:39,255
CIRCADIAN AMPLITUDE?

3080
01:42:39,255 --> 01:42:41,791
WHAT DOES IT MEAN TO YOU AND

3081
01:42:41,791 --> 01:42:43,759
WHAT DO YOU THINK OF IT AS A

3082
01:42:43,759 --> 01:42:46,128
TARGET FOR INTERVENTION?

3083
01:42:46,128 --> 01:42:48,164
>> I'M HAPPY TO START WITH
THIS

3084
01:42:48,164 --> 01:42:48,598
ONE.

3085
01:42:48,598 --> 01:42:49,799
I DON'T WANT TO HOG THE

3086
01:42:49,799 --> 01:42:51,801
CONVERSATION, BUT I AM A BIG FAN

3087
01:42:51,801 --> 01:42:52,435
OF AMPLITUDE.

3088
01:42:52,435 --> 01:42:55,805
AND I WILL ACTUALLY SAY THAT

3089
01:42:55,805 --> 01:42:58,374
THIS IS ONE OF THE AREAS I HAD

3090
01:42:58,374 --> 01:43:00,076
MENTIONED PARTICULARLY THAT

3091
01:43:00,076 --> 01:43:01,377
NON-24 PATIENTS, IT'S VERY, VERY

3092
01:43:01,377 --> 01:43:02,678
HARD TO FIND APPROPRIATE

3093
01:43:02,678 --> 01:43:07,083
TREATMENTS FOR THEM.

3094
01:43:07,083 --> 01:43:10,353
AND RATHER THAN A LOT OF WHAT WE

3095
01:43:10,353 --> 01:43:13,089
DO A VERY SPECIFIC CIRCADIAN

3096
01:43:13,089 --> 01:43:16,592
TIME INTERVENTIONS WE'VE BEEN

3097
01:43:16,592 --> 01:43:18,628
FOCUSING ON AMPLITUDES -- HAVING

3098
01:43:18,628 --> 01:43:21,230
A HIGH EXPOSURE DURING THE DAY,

3099
01:43:21,230 --> 01:43:24,400
AND SET LIGHT WINDOWS OF TIME

3100
01:43:24,400 --> 01:43:27,503
FOR THEM -- SO THEY GET THE

3101
01:43:27,503 --> 01:43:29,138
AMPLITUDE.

3102
01:43:29,138 --> 01:43:30,873
I'VE HAD SOME, IF THEY VIN

3103
01:43:30,873 --> 01:43:32,275
CREASED ACTIVITY AMPLITUDE OVER

3104
01:43:32,275 --> 01:43:35,945
THE DAY, SO THEIR OVERALL

3105
01:43:35,945 --> 01:43:37,246
ACTIVITY IMPROVES, WE ALSO SEE

3106
01:43:37,246 --> 01:43:38,514
IMPROVEMENTS THERE, SO ANS

3107
01:43:38,514 --> 01:43:40,483
LUTELY I THINK AMPLITUDE IS THE

3108
01:43:40,483 --> 01:43:41,584
FUTURE IN TERMS OF REALLY

3109
01:43:41,584 --> 01:43:43,185
PROVIDING THOSE CONTRASTS AS

3110
01:43:43,185 --> 01:43:45,855
OPPOSED TO THINKING OF CIRCADIAN

3111
01:43:45,855 --> 01:43:47,290
RHYTHMS AS KIND OF A SINGLE

3112
01:43:47,290 --> 01:43:57,633
TIMED INTERVENTION.

3113
01:43:58,634 --> 01:44:05,241
>> I HAVE NOTHING TO ADD.

3114
01:44:05,241 --> 01:44:06,576
BUT I AGREE WITH DR. ABBOTT

3115
01:44:06,576 --> 01:44:08,878
ABOUT ESSENTIALLY ADDRESSING

3116
01:44:08,878 --> 01:44:10,546
BEHAVIORS AND CUES ACROSS THE

3117
01:44:10,546 --> 01:44:13,149
24-HOUR CYCLE.

3118
01:44:13,149 --> 01:44:14,150
AS OPPOSED TO A SPECIFIC TIME OF

3119
01:44:14,150 --> 01:44:14,383
DAY.

3120
01:44:14,383 --> 01:44:15,618
>> OKAY.

3121
01:44:15,618 --> 01:44:17,353
SO BASICALLY ALL IN FAVOR.

3122
01:44:17,353 --> 01:44:18,020
>> YEAH.

3123
01:44:18,020 --> 01:44:19,221
THE ONLY THING I WOULD ADD TO

3124
01:44:19,221 --> 01:44:24,760
THAT IS THAT IN SOME OF THE

3125
01:44:24,760 --> 01:44:26,162
ASSOCIATION STUDIES, LOW

3126
01:44:26,162 --> 01:44:29,432
AMPLITUDE RHYTHMS IN, SAY,

3127
01:44:29,432 --> 01:44:30,900
ACTIGRAPHY, IT'S HARD TO

3128
01:44:30,900 --> 01:44:32,234
DIFFERENTIATE A CIRCADIAN

3129
01:44:32,234 --> 01:44:35,304
COMPONENT TO THAT VERSUS, SAY,

3130
01:44:35,304 --> 01:44:39,875
LIKE THE SICK COMPONENT OR

3131
01:44:39,875 --> 01:44:41,510
PEOPLE ARE STRESSED, ANXIOUS OR

3132
01:44:41,510 --> 01:44:41,811
DEPRESSED.

3133
01:44:41,811 --> 01:44:43,512
THERE ARE A LOT OF DIFFERENT

3134
01:44:43,512 --> 01:44:45,548
BEHAVIORAL REASONS FOR WHY THOSE

3135
01:44:45,548 --> 01:44:46,716
AMPLITUDES CHANGE, SO

3136
01:44:46,716 --> 01:44:47,950
UNDERSTANDING THE MECHANISMS

3137
01:44:47,950 --> 01:44:49,852
BEHIND THE AMPLITUDE DIFFERENCES

3138
01:44:49,852 --> 01:44:53,856
IS REALLY A CRITICAL FEATURE.

3139
01:44:53,856 --> 01:44:55,358
>> ALL RIGHT, GOOD TO
KNOW.

3140
01:44:55,358 --> 01:44:55,658
GOOD POINT.

3141
01:44:55,658 --> 01:44:56,993
ALL RIGHT.

3142
01:44:56,993 --> 01:44:59,829
SO PIVOTING TO PATIENT CARE AND

3143
01:44:59,829 --> 01:45:03,299
CLINICAL SETTINGS.

3144
01:45:03,299 --> 01:45:06,469
HOW WELL ARE PHENOTYPES FOR

3145
01:45:06,469 --> 01:45:10,439
HUMAN SIR CADE CIRCADIAN RHYTHMS

3146
01:45:10,439 --> 01:45:12,942
CHARACTERIZED, AND WILL THIS BE

3147
01:45:12,942 --> 01:45:14,677
PART OF -- WILL THIS BE PART OF

3148
01:45:14,677 --> 01:45:18,547
OUR WORKUP AT PHYSICAL AND --

3149
01:45:18,547 --> 01:45:19,448
LIKE WILL THIS BECOME PART OF

3150
01:45:19,448 --> 01:45:21,183
OUR PHYSICAL, LIKE PART OF OUR

3151
01:45:21,183 --> 01:45:24,553
CLINICAL WORK WORKUP AND OUR GUE

3152
01:45:24,553 --> 01:45:27,690
ON MAINTAINING GOOD HEALTH?

3153
01:45:27,690 --> 01:45:33,729
AND DO YOU THINK IT SHOULD BE?

3154
01:45:33,729 --> 01:45:36,666
>> ABSOLUTELY --

3155
01:45:36,666 --> 01:45:38,701
>> DOES THIS BECOME A
VITAL SIGN

3156
01:45:38,701 --> 01:45:39,669
IS BASICALLY THE QUESTION.

3157
01:45:39,669 --> 01:45:40,569
>> ABSOLUTELY.

3158
01:45:40,569 --> 01:45:42,972
I DON'T THINK I HAVE ANY

3159
01:45:42,972 --> 01:45:44,173
DISAGREEMENT FROM MY FELLOW

3160
01:45:44,173 --> 01:45:45,307
PANELISTS WITH THAT.

3161
01:45:45,307 --> 01:45:47,109
AND I THINK THERE ARE KIND OF

3162
01:45:47,109 --> 01:45:47,610
TWO COMPONENTS TO THAT.

3163
01:45:47,610 --> 01:45:52,782
SO I THINK THERE'S THE IDEA OF

3164
01:45:52,782 --> 01:45:54,650
ACROSS ANY GENERAL PCP

3165
01:45:54,650 --> 01:45:55,785
POPULATION AS THEY'RE SEEING

3166
01:45:55,785 --> 01:45:57,186
PATIENTS, I THINK THEY SHOULD BE

3167
01:45:57,186 --> 01:45:58,387
ASSESSING SOME OF THESE THINGS.

3168
01:45:58,387 --> 01:45:59,488
IT'S CHALLENGING BECAUSE THEY'VE

3169
01:45:59,488 --> 01:46:01,057
GOT A VERY SHORT, LIMITED TIME

3170
01:46:01,057 --> 01:46:03,793
VISIT, SO I THINK IT'S SORT OF

3171
01:46:03,793 --> 01:46:05,294
THE BURDEN IS ON US TO COME UP

3172
01:46:05,294 --> 01:46:08,164
WITH EASY, QUICK ASSESSMENTS

3173
01:46:08,164 --> 01:46:09,632
THAT THEY CAN BUILD INTO THEIR

3174
01:46:09,632 --> 01:46:10,933
CLINIC THAT CAN HELP WITH

3175
01:46:10,933 --> 01:46:13,636
GETTING SOME OF THAT INFORMATION

3176
01:46:13,636 --> 01:46:14,904
SO THAT WE CAN PROVIDE THAT

3177
01:46:14,904 --> 01:46:15,337
DATA.

3178
01:46:15,337 --> 01:46:18,174
IN TERMS OF WHAT ASSESSMENTS WE

3179
01:46:18,174 --> 01:46:20,042
SHOULD BE DOING IN THE CIRCADIAN

3180
01:46:20,042 --> 01:46:23,846
CLINIC, CAN I GO  I CAN GO INTOE

3181
01:46:23,846 --> 01:46:25,448
OF THAT IF WE NEED TO BUT I WANT

3182
01:46:25,448 --> 01:46:26,849
OTHER PANELISTS TO WEIGH ON WHAT

3183
01:46:26,849 --> 01:46:28,784
WE SHOULD BE DOING TO ASSESS

3184
01:46:28,784 --> 01:46:33,956
THIS IN THE GENERAL POPULATION.

3185
01:46:33,956 --> 01:46:36,492
>> I AGREE, OF COURSE,
WITH WHAT

3186
01:46:36,492 --> 01:46:38,994
DR. ABBOTT SAID.

3187
01:46:38,994 --> 01:46:41,664
I THINK I REALLY AGREE WITH THE

3188
01:46:41,664 --> 01:46:46,335
POINT YOU MADE ABOUT THAT

3189
01:46:46,335 --> 01:46:46,902
UNFORTUNATELY, THESE THINGS

3190
01:46:46,902 --> 01:46:47,803
WOULD BE VERY TEDIOUS TO ASSESS

3191
01:46:47,803 --> 01:46:49,638
IN A CLINICAL SETTING, WHICH IS

3192
01:46:49,638 --> 01:46:54,243
WHY THEY'RE NOT FEES  FEASIBLE A

3193
01:46:54,243 --> 01:46:55,244
POPULATION OR HEALTH SETTING.

3194
01:46:55,244 --> 01:46:56,879
I THINK P T

3195
01:46:56,879 --> 01:46:58,047
ASSESSING -- I'M TALKING IN A

3196
01:46:58,047 --> 01:47:00,616
PUBLIC HEALTH SETTING, PROXIES

3197
01:47:00,616 --> 01:47:04,720
FOR ASSESSING THOSE THINGS COULD

3198
01:47:04,720 --> 01:47:06,756
BE EVALUATING PEOPLE'S

3199
01:47:06,756 --> 01:47:11,660
CHRONOTYPE OR, AGAIN, LOOKING AT

3200
01:47:11,660 --> 01:47:13,729
SLEEP TIMING, SO USING SOME

3201
01:47:13,729 --> 01:47:18,701
PROXIES OF BIOLOGICAL TIMING AND

3202
01:47:18,701 --> 01:47:21,771
SEEING INTERVENTIONS -- CONSIDER

3203
01:47:21,771 --> 01:47:23,339
THOSE THINGS WOULD WORK AND

3204
01:47:23,339 --> 01:47:24,473
WOULD OPTIMIZE CURRENT

3205
01:47:24,473 --> 01:47:27,376
BEHAVIORAL APPROACHES.

3206
01:47:27,376 --> 01:47:30,646
I THINK WE ALREADY HAVE IN

3207
01:47:30,646 --> 01:47:32,214
CERTAIN WAYS EVIDENCE THAT

3208
01:47:32,214 --> 01:47:34,283
PAYING ATTENTION TO TIMING AND

3209
01:47:34,283 --> 01:47:35,785
REGULARITY DOES OPTIMIZE

3210
01:47:35,785 --> 01:47:36,552
BEHAVIORAL INTERVENTIONS.

3211
01:47:36,552 --> 01:47:37,953
WE KNOW THIS FROM SOME OF THE

3212
01:47:37,953 --> 01:47:41,991
TRIALS ON SLEEP, WHICH HAVING

3213
01:47:41,991 --> 01:47:44,460
REGULAR SLEEP SCHEDULES CAN

3214
01:47:44,460 --> 01:47:46,095
REALLY IMPROVE CARDIOMETABOLIC

3215
01:47:46,095 --> 01:47:48,030
RISK FACTORS AND TRIALS, WE KNOW

3216
01:47:48,030 --> 01:47:49,865
FOR SOME OF THE CHRONONUTRITION

3217
01:47:49,865 --> 01:47:53,035
STUDIES ALSO THAT EATING TIMING

3218
01:47:53,035 --> 01:47:54,370
MATTERS, AND THERE'S SOME

3219
01:47:54,370 --> 01:47:55,371
CONFLICTING EVIDENCE ON THIS,

3220
01:47:55,371 --> 01:47:57,673
BUT OFTEN THAT EVEN WITH

3221
01:47:57,673 --> 01:47:59,375
TIME-RESTRICTED FEEDING, THAT

3222
01:47:59,375 --> 01:48:00,576
EARLIER TIME-RESTRICTED FEEDING

3223
01:48:00,576 --> 01:48:05,714
IS WHAT IS MOST HELPFUL TO

3224
01:48:05,714 --> 01:48:07,483
IMPROVE CARDIOMETABOLIC HEALTH.

3225
01:48:07,483 --> 01:48:09,485
BUT THAT WAS, I THINK, FROM A

3226
01:48:09,485 --> 01:48:12,221
POPULATION STANDPOINT WHY IN THE

3227
01:48:12,221 --> 01:48:13,556
OPPORTUNITIES SECTION OF MY

3228
01:48:13,556 --> 01:48:16,492
TALK, I MENTIONED THAT WE NEED

3229
01:48:16,492 --> 01:48:18,861
MORE METHODOLOGICAL ADVANCEMENT

3230
01:48:18,861 --> 01:48:20,062
FOR FINDING MARKERS THAT CAN BE

3231
01:48:20,062 --> 01:48:23,632
MORE INTEGRATED INTO DEEM

3232
01:48:23,632 --> 01:48:26,268
LOGIC RESRS AND INTO COMMIT CAL

3233
01:48:26,268 --> 01:48:27,970
SETTING, WE CAN'T REALLY MAKE

3234
01:48:27,970 --> 01:48:30,973
ANY PRESCRIPTIONS, I THINK.

3235
01:48:30,973 --> 01:48:33,475
IN A PUBLIC HEALTH SETTING OR A

3236
01:48:33,475 --> 01:48:34,677
CLINICAL SETTING.

3237
01:48:34,677 --> 01:48:36,579
SO YES, IT'S IMPORTANT, BUT MORE

3238
01:48:36,579 --> 01:48:37,513
RESEARCH IS NEEDED BEFORE IT

3239
01:48:37,513 --> 01:48:39,515
ACTUALLY HAPPENS, I THINK IS

3240
01:48:39,515 --> 01:48:45,354
THE -- IS THE SHORT SUMMARY.

3241
01:48:45,354 --> 01:48:51,460
>> FOR THE PANEL -- DR.
BUTLER,

3242
01:48:51,460 --> 01:48:52,595
DO YOU HAVE ANYTHING TO ADHERE?

3243
01:48:52,595 --> 01:48:53,162
GO AHEAD.

3244
01:48:53,162 --> 01:48:54,563
>> I DON'T HAVE ANYTHING

3245
01:48:54,563 --> 01:48:55,865
SIGNIFICANT TO ADD TO THAT, NO.

3246
01:48:55,865 --> 01:48:56,332
THAT WAS PER FORECAST.

3247
01:48:56,332 --> 01:49:01,070
>> WEPERFECT.>> THEN
I WOULD LIW

3248
01:49:01,070 --> 01:49:02,538
UP WITH, DO YOU THINK THERE WILL

3249
01:49:02,538 --> 01:49:05,507
EVER BE A SIMPLE TEST OF

3250
01:49:05,507 --> 01:49:07,409
BIOMARKERS, SOMETHING FOR

3251
01:49:07,409 --> 01:49:10,579
DIAGNOSING OR IDENTIFYING

3252
01:49:10,579 --> 01:49:13,315
CIRCADIAN PHENOTYPES THAT COULD

3253
01:49:13,315 --> 01:49:15,818
BE DEPLOYABLE AT THE CLINIC

3254
01:49:15,818 --> 01:49:19,355
LEVEL OR AT THE POPULATIONUL

3255
01:49:19,355 --> 01:49:21,991
LEVEL, AND WHAT IS THE BARRIER,

3256
01:49:21,991 --> 01:49:24,393
WHAT IS STANDING IN THE WAY, I

3257
01:49:24,393 --> 01:49:27,229
MEAN, YOU CURRENTLY TOUCHED ON

3258
01:49:27,229 --> 01:49:28,864
IT, DR. MAKAREM, SO I DON'T WANT

3259
01:49:28,864 --> 01:49:31,066
YOU TO GO OVER IT AGAIN, BULL

3260
01:49:31,066 --> 01:49:33,936
WHAT IS THE BIGGEST THING THAT

3261
01:49:33,936 --> 01:49:38,007
IS STANDING STANDING IN THE WAYF

3262
01:49:38,007 --> 01:49:39,308
VALIDATED BIOMARKERS FOR

3263
01:49:39,308 --> 01:49:41,810
CIRCADIAN BIOLOGY, OR FOR SLEEP

3264
01:49:41,810 --> 01:49:46,382
RESEARCH AS WELL?

3265
01:49:46,382 --> 01:49:49,551
>> I THINK FOR VALIDATED

3266
01:49:49,551 --> 01:49:51,086
MARKERS, I THINK MAYBE THAT'S

3267
01:49:51,086 --> 01:49:52,688
MORE A QUESTION FOR THE OTHER

3268
01:49:52,688 --> 01:49:54,456
PRESENTERS, BUT IN TERMS OF SOME

3269
01:49:54,456 --> 01:49:56,392
OF THE THINGS I TALKED ABOUT, IF

3270
01:49:56,392 --> 01:49:58,961
WE TAKE BLOOD PRESSURE AS AN

3271
01:49:58,961 --> 01:49:59,962
EXAMPLE, AMBULATORY BLOOD

3272
01:49:59,962 --> 01:50:00,930
PRESSURE MONITORING, EVEN THOUGH

3273
01:50:00,930 --> 01:50:03,365
IT IS A GOLD STANDARD APPROACH

3274
01:50:03,365 --> 01:50:05,501
TO EVALUATE BLOOD PRESSURE, IT'S

3275
01:50:05,501 --> 01:50:07,569
NOT NECESSARILY ALL AWLS

3276
01:50:07,569 --> 01:50:12,608
REIMBURSABLREIMBURSABLE AND SOME

3277
01:50:12,608 --> 01:50:14,443
IT AS HIGHLY BURDENSOME AND

3278
01:50:14,443 --> 01:50:15,544
DON'T WANT TO DO IT.

3279
01:50:15,544 --> 01:50:16,645
PARTICULARLY WHEN WE'RE DOING A

3280
01:50:16,645 --> 01:50:18,113
STUDY ON SLEEP AND IF THEY'RE

3281
01:50:18,113 --> 01:50:20,649
SAYING IT'S DISRUPTING MY SLEEP,

3282
01:50:20,649 --> 01:50:22,484
THIS DOESN'T MAKE ANY SENSE.

3283
01:50:22,484 --> 01:50:24,653
AND SIMILARLY FOR CGM, I THINK

3284
01:50:24,653 --> 01:50:27,923
THE USE SO FAR HAS BEEN IN TYPE

3285
01:50:27,923 --> 01:50:29,425
2 DIABETES PATIENTS FOR

3286
01:50:29,425 --> 01:50:31,060
MONITORING GLYCEMIC CONTROL.

3287
01:50:31,060 --> 01:50:34,229
WEAR USING A LITTLE MORE IN

3288
01:50:34,229 --> 01:50:36,732
RESEARCH SETTINGS NOW BUT IT'S

3289
01:50:36,732 --> 01:50:39,768
NOT SOMETHING WE ROUTINELY USE

3290
01:50:39,768 --> 01:50:44,006
TO ASSESS SOMEONE'S USE.

3291
01:50:44,006 --> 01:50:45,741
FROM A BARRIER POPULATION

3292
01:50:45,741 --> 01:50:46,408
STANDPOINT, WE NEED MORE

3293
01:50:46,408 --> 01:50:50,012
EVIDENCE REALLY ON HOW MUCH

3294
01:50:50,012 --> 01:50:52,448
THOSE INDICATORS THAT WE EXTRACT

3295
01:50:52,448 --> 01:50:54,984
FROM CG M&A BPM PREDICT
FUTURE

3296
01:50:54,984 --> 01:50:56,552
DISEASE RISK AND HOW AND IF THEY

3297
01:50:56,552 --> 01:50:59,621
COULD BE MODIFIED BY BEHAVIORAL

3298
01:50:59,621 --> 01:51:01,924
RHYTHMS.

3299
01:51:01,924 --> 01:51:03,325
SO THAT'S FROM THE RESEARCH

3300
01:51:03,325 --> 01:51:05,627
POPULATION STANDPOINT.

3301
01:51:05,627 --> 01:51:09,732
BUT I DON'T KNOW IF MY

3302
01:51:09,732 --> 01:51:11,934
COLLEAGUES HAVE ANYTHING TO ADD

3303
01:51:11,934 --> 01:51:15,104
ABOUT BIOLOGY INDICATOR OR

3304
01:51:15,104 --> 01:51:15,371
BIOMARKER.

3305
01:51:15,371 --> 01:51:18,907
>> I'LL JUST SAID, I THINK

3306
01:51:18,907 --> 01:51:21,744
PROBABLY THE CIRCADIAN MEDICINE

3307
01:51:21,744 --> 01:51:23,379
TO ANY OTHER FIELD OF MEDICINE,

3308
01:51:23,379 --> 01:51:25,280
IS WHAT IS THE MARKER YOU'RE

3309
01:51:25,280 --> 01:51:26,181
ACTUALLY INTERESTED IN?

3310
01:51:26,181 --> 01:51:27,716
ARE YOU INTERESTED IN PHASE, ARE

3311
01:51:27,716 --> 01:51:29,451
YOU INTERESTED IN AMPLITUDE, ARE

3312
01:51:29,451 --> 01:51:33,222
YOU INTERESTED NR INTERNAL

3313
01:51:33,222 --> 01:51:33,956
MISALIGNMENT AND EACH OF THOSE

3314
01:51:33,956 --> 01:51:35,057
HAS A DIFFERENT MARKER.

3315
01:51:35,057 --> 01:51:36,658
I'M NOT GOING TO SAY THAT

3316
01:51:36,658 --> 01:51:39,061
DIABETES IS EASY, BUT THEY HAVE

3317
01:51:39,061 --> 01:51:41,030
AN A1C THAT TELLS THEM HOW HIGH

3318
01:51:41,030 --> 01:51:42,131
THEIR GLUCOSE LEVELS ARE AND

3319
01:51:42,131 --> 01:51:43,599
THAT CAN KIND OF TELL THEM

3320
01:51:43,599 --> 01:51:45,367
GENERALLY WHAT THE

3321
01:51:45,367 --> 01:51:46,468
PATHOPHYSIOLOGY IS.

3322
01:51:46,468 --> 01:51:49,538
BUT I THINK IT'S THE CHALLENGES,

3323
01:51:49,538 --> 01:51:50,773
WHAT ARE YOU -- SO I THINK WE'VE

3324
01:51:50,773 --> 01:51:52,408
GOT SOME PRETTY GOOD TARGETS OUT

3325
01:51:52,408 --> 01:51:53,375
THERE RIGHT NOW IN TERMS OF

3326
01:51:53,375 --> 01:51:56,278
BLOOD TESTING THAT MAY TELL YOU

3327
01:51:56,278 --> 01:51:57,613
WHAT YOUR CIRCADIAN PHASE IS,

3328
01:51:57,613 --> 01:51:58,914
BUT TAKING THAT INTO THE

3329
01:51:58,914 --> 01:52:00,616
POPULATION, IS THAT THE MARKER

3330
01:52:00,616 --> 01:52:02,818
WE CARE ABOUT, OR IS IT THAT WE

3331
01:52:02,818 --> 01:52:05,421
WANT TO FIGURE OUT SOMEBODY THAT

3332
01:52:05,421 --> 01:52:16,832
FIGURE SOMETHING THAT'SA GOOD I,

3333
01:52:16,832 --> 01:52:18,434
THAT'S WHERE IT BECOMES MUCH

3334
01:52:18,434 --> 01:52:19,535
MORE CHALLENGING ON A POPULATION

3335
01:52:19,535 --> 01:52:20,602
LEVEL, AND THEN TAKING IT INTO

3336
01:52:20,602 --> 01:52:23,539
KIND OF THE MORE ESOTERIC

3337
01:52:23,539 --> 01:52:24,840
CIRCADIAN CLINIC LEVEL, I OFTEN

3338
01:52:24,840 --> 01:52:27,676
DO GET THIS QUESTION OF CAN'T

3339
01:52:27,676 --> 01:52:30,612
YOU JUST COME UP WITH A SIMPLE

3340
01:52:30,612 --> 01:52:32,181
BIOMARKER, CAN'T YOU JUST MAKE

3341
01:52:32,181 --> 01:52:34,550
IT MUCH EASIER TO DIAGNOSE THESE

3342
01:52:34,550 --> 01:52:34,817
PATIENTS?

3343
01:52:34,817 --> 01:52:36,218
THE PROBLEM IS IT'S NOT JUST A

3344
01:52:36,218 --> 01:52:42,524
MATTER OF SAYING YOUR MELATONIN

3345
01:52:42,524 --> 01:52:44,860
ONSET - -- WHEN IS YOUR PREFERRD

3346
01:52:44,860 --> 01:52:46,228
CIRCADIAN TIME, WHEN ARE YOU

3347
01:52:46,228 --> 01:52:47,196
ACTUALLY FALLING ASLEEP, DOES

3348
01:52:47,196 --> 01:52:48,530
THAT OR DOES THAT NOT INTERFERE

3349
01:52:48,530 --> 01:52:49,698
WITH WHAT YOU'RE DOING?

3350
01:52:49,698 --> 01:52:52,835
BECAUSE YOU MAY BE A SECOND OR

3351
01:52:52,835 --> 01:52:54,036
THIRD SHIFT WORKER AND IT

3352
01:52:54,036 --> 01:52:55,237
ACTUALLY WORKS JUST FINE FOR YOU

3353
01:52:55,237 --> 01:52:57,973
TO HAVE A DELAYED CIRCADIAN

3354
01:52:57,973 --> 01:53:00,476
PHASE, OR MAYBE YOU ARE VERY

3355
01:53:00,476 --> 01:53:01,677
ADVANCED AND YOU HAVE TO BE AT

3356
01:53:01,677 --> 01:53:07,716
WORK AT 6:00 A.M. SO IT'S HARD

3357
01:53:07,716 --> 01:53:09,685
TO SIMPLIFY IT DOWN TO A SINGLE

3358
01:53:09,685 --> 01:53:10,586
VALUE THAT TELLS US IS THERE A

3359
01:53:10,586 --> 01:53:11,453
PROBLEM OR IS THERE NOT A

3360
01:53:11,453 --> 01:53:14,389
PROBLEM.

3361
01:53:14,389 --> 01:53:15,791
GLI WANT TO ADD TWO THINGS.

3362
01:53:15,791 --> 01:53:18,060
I THINK ONE OF THE CHALLENGES

3363
01:53:18,060 --> 01:53:20,229
THAT WE CERTAINLY SEE IS THE

3364
01:53:20,229 --> 01:53:23,265
FACT THAT WE DON'T KNOW WHAT THE

3365
01:53:23,265 --> 01:53:24,700
CIRCADIAN PHASE IS OF INDIVIDUAL

3366
01:53:24,700 --> 01:53:27,536
ORGANS THAT MAY BE OF INTEREST.

3367
01:53:27,536 --> 01:53:31,640
AND SO TRYING TO UNDERSTAND HOW

3368
01:53:31,640 --> 01:53:33,509
TO NOT JUST FIND BIOMARKERS OF

3369
01:53:33,509 --> 01:53:34,810
PHASE, BECAUSE THERE HAVE BEEN

3370
01:53:34,810 --> 01:53:41,550
SOME VERY NICE STUDIES TA TAKINA

3371
01:53:41,550 --> 01:53:42,951
LOOK AT THIS NUMBER OF PROTEINS,

3372
01:53:42,951 --> 01:53:44,286
THIS NUMBER OF GENES AND YOU CAN

3373
01:53:44,286 --> 01:53:49,158
GET PHASE, PHASE AS DEFINED BY

3374
01:53:49,158 --> 01:53:50,392
SLMO ESSENTIALLY, THEY'RE TRYING

3375
01:53:50,392 --> 01:53:53,095
TO SAY WHEN SLMO WOULD BE OR

3376
01:53:53,095 --> 01:53:54,062
WHEN CORE BODY TEMPERATURE WOULD

3377
01:53:54,062 --> 01:53:55,264
BE MINIMUM.

3378
01:53:55,264 --> 01:53:57,866
BUT TRYING TO -- BLOOD, OF

3379
01:53:57,866 --> 01:54:00,269
COURSE, IS SORT OF A HOMOGENIZED

3380
01:54:00,269 --> 01:54:01,136
OUTPUT OF A WHOLE LOT OF

3381
01:54:01,136 --> 01:54:07,643
DIFFERENT THINGS, SO TRYING TO

3382
01:54:07,643 --> 01:54:09,178
FIGURE OUT WHAT KIND OF ORGAN

3383
01:54:09,178 --> 01:54:10,579
SPECIFIC BIOMARKERS MIGHT BE

3384
01:54:10,579 --> 01:54:12,748
AVAILABLE IN BLOOD, URINE,

3385
01:54:12,748 --> 01:54:14,149
SALIVA, I THINK THAT'S A BIG

3386
01:54:14,149 --> 01:54:14,716
CHALLENGE.

3387
01:54:14,716 --> 01:54:16,318
THE OTHER THING I WOULD SAY,

3388
01:54:16,318 --> 01:54:18,053
THOUGH, IS MAYBE WE DON'T NEED

3389
01:54:18,053 --> 01:54:21,223
TO ACTUALLY FIND A BIOMARKER FOR

3390
01:54:21,223 --> 01:54:22,457
ALL THOSE PHASES.

3391
01:54:22,457 --> 01:54:24,860
ONE OF THE THINGS THAT HAS COME

3392
01:54:24,860 --> 01:54:27,162
UP IS THIS IDEA OF REGULARITY

3393
01:54:27,162 --> 01:54:33,835
OF CHANGES IN ACTIVITY PATTERNS.

3394
01:54:33,835 --> 01:54:34,970
SABRA SHOWED THAT KIND OF

3395
01:54:34,970 --> 01:54:36,705
RELATIVE COORDINATION OR

3396
01:54:36,705 --> 01:54:37,639
ENTRAINMENT WHERE PEOPLE ARE

3397
01:54:37,639 --> 01:54:38,540
GOING THROUGH PERIODS WHERE

3398
01:54:38,540 --> 01:54:39,741
THEY'RE SHIFTING AND

3399
01:54:39,741 --> 01:54:41,243
NON-SHIFTING OR JUST DAY TO DAY

3400
01:54:41,243 --> 01:54:43,111
OR WEEKEND TO WEEKDAY.

3401
01:54:43,111 --> 01:54:45,314
IT MIGHT BE THAT WITH WEARABLES

3402
01:54:45,314 --> 01:54:47,616
AND WITH HAVING A LONGER

3403
01:54:47,616 --> 01:54:49,952
LONGITUDAL TIME SPAN OF DATA, WE

3404
01:54:49,952 --> 01:54:51,920
MIGHT ACTUALLY END UP BEING ABLE

3405
01:54:51,920 --> 01:54:53,789
TO INFER CLOCK FUNCTION FROM

3406
01:54:53,789 --> 01:54:55,190
THINGS THAT ARE HAPPENING IN

3407
01:54:55,190 --> 01:54:56,925
THEIR DAY TO DAY.

3408
01:54:56,925 --> 01:55:00,462
SO IF WE -- IF THEY HAVE SORT OF

3409
01:55:00,462 --> 01:55:01,430
DEFINED WORK SCHEDULES AND WE

3410
01:55:01,430 --> 01:55:03,332
CAN SEE HOW THEIR ACTIVITY IS

3411
01:55:03,332 --> 01:55:05,200
SHIFTING RELATIVE TO THOSE, WE

3412
01:55:05,200 --> 01:55:08,604
MIGHT ACTUALLY BE ABLE TO DANCE

3413
01:55:08,604 --> 01:55:12,207
AROUND THE IDEA OF EXTRACTING

3414
01:55:12,207 --> 01:55:15,010
PHASE SPECIFICALLY AND DEFINE IT

3415
01:55:15,010 --> 01:55:16,211
BASED ON CHANGES THAT ARE

3416
01:55:16,211 --> 01:55:20,415
OCCURRING IN OTHER PARAMETERS.

3417
01:55:20,415 --> 01:55:24,653
>> VERY INTERESTING.

3418
01:55:24,653 --> 01:55:25,654
SO IT IS DIFFICULT BECAUSE

3419
01:55:25,654 --> 01:55:27,756
CONTEXT MATTERS AND IT IS VERY

3420
01:55:27,756 --> 01:55:28,991
PERSONAL, IT IS VERY

3421
01:55:28,991 --> 01:55:32,160
INDIVIDUALIZED.

3422
01:55:32,160 --> 01:55:33,629
ONE QUESTION FROM THE CHAT BUT

3423
01:55:33,629 --> 01:55:35,631
ALSO SOMETHING THAT I'M CURIOUS

3424
01:55:35,631 --> 01:55:39,334
ABOUT, IS THERE ANY RECORDED

3425
01:55:39,334 --> 01:55:40,636
EPIGENETIC MODIFICATION TO

3426
01:55:40,636 --> 01:55:43,338
CIRCADIAN RHYTHMS OR LIKE TO THE

3427
01:55:43,338 --> 01:55:46,508
CORE CLOCK GENES THAT ARE

3428
01:55:46,508 --> 01:55:48,477
INFLUENCED BY ENVIRONMENTAL

3429
01:55:48,477 --> 01:55:54,416
CUES, BEHAVIORAL CUES?

3430
01:55:54,416 --> 01:55:59,354
>> SO IN TERMS OF E
EPIGENETIC

3431
01:55:59,354 --> 01:56:00,455
MODIFICATIONS ON THE CORE CLOCK

3432
01:56:00,455 --> 01:56:01,757
GENES, I DON'T -- I CAN'T

3433
01:56:01,757 --> 01:56:04,359
REMEMBER OFF THE TOP OF MY HEAD.

3434
01:56:04,359 --> 01:56:06,228
BUT IT'S CERTAINLY THE CASE THAT

3435
01:56:06,228 --> 01:56:09,064
IF YOU LOOK AT, FOR EXAMPLE,

3436
01:56:09,064 --> 01:56:10,666
HISTONE MARKERS THAT ARE

3437
01:56:10,666 --> 01:56:12,734
INSTRUMENTAL IN CONTROLLING

3438
01:56:12,734 --> 01:56:13,735
TRANSCRIPTION OF DIFFERENT

3439
01:56:13,735 --> 01:56:16,138
GENES, THERE IS A VERY DEFINED

3440
01:56:16,138 --> 01:56:18,807
TIME COURSE OF HISTONE MARKERS

3441
01:56:18,807 --> 01:56:20,342
THAT ARE SORT OF GETTING PUT IN

3442
01:56:20,342 --> 01:56:21,677
AND OUT OF THE HISTONES THAT

3443
01:56:21,677 --> 01:56:24,479
SEEMS TO PLAY A ROLE IN

3444
01:56:24,479 --> 01:56:26,882
ORGANIZING THE TEMPORAL

3445
01:56:26,882 --> 01:56:28,750
STRUCTURE OF THE TRANSCRIPTOME.

3446
01:56:28,750 --> 01:56:30,719
THAT WAS WORK THAT CAME OUT OF

3447
01:56:30,719 --> 01:56:36,091
JOE TACK  TAKAHASHI'S LAB ABOUT0

3448
01:56:36,091 --> 01:56:36,458
YEARS AGO.

3449
01:56:36,458 --> 01:56:38,460
THEY SHOWED ALSO  THAT PAPER

3450
01:56:38,460 --> 01:56:40,696
THAT THIS CORE CLOCK GENE IN

3451
01:56:40,696 --> 01:56:42,097
ADDITION TO SIMPLY INTERACTING

3452
01:56:42,097 --> 01:56:43,498
WITH EACH OTHER, THEY ARE ALSO

3453
01:56:43,498 --> 01:56:45,334
BINDING TO THOUSANDS OF

3454
01:56:45,334 --> 01:56:49,471
LOCATIONS IN THE GENOME, SO THAT

3455
01:56:49,471 --> 01:56:51,006
THEIR EFFECTS COULD BE VERY

3456
01:56:51,006 --> 01:56:52,140
WIDESPREAD, AND PART OF THAT

3457
01:56:52,140 --> 01:56:58,413
COULD BE PURELY CLOCK AND --

3458
01:56:58,413 --> 01:57:00,282
PLEIOTROPIC EFFECTS WITH MANY OF

3459
01:57:00,282 --> 01:57:01,750
THESE GENES THAT COULD BE

3460
01:57:01,750 --> 01:57:03,852
MODIFIED THROUGH EPIGENETIC

3461
01:57:03,852 --> 01:57:05,187
MECHANISMS AS WELL.

3462
01:57:05,187 --> 01:57:07,155
>> AND WHAT SORT OF
CLINICAL

3463
01:57:07,155 --> 01:57:09,291
IMPLICATIONS WOULD THOSE HAVE

3464
01:57:09,291 --> 01:57:13,995
OVER TIME?

3465
01:57:13,995 --> 01:57:16,064
FOR OUR OTHER PANELISTS IF YOU

3466
01:57:16,064 --> 01:57:16,798
WANTED TO SPECULATE?

3467
01:57:16,798 --> 01:57:19,534
>> WELL, I PUT IN THAT
THERE'S

3468
01:57:19,534 --> 01:57:24,906
THIS VERY INTERESTING IDEA OF

3469
01:57:24,906 --> 01:57:25,774
REPETITIVE INSULTS IN THE

3470
01:57:25,774 --> 01:57:27,309
ENVIRONMENT THAT YOU CAN KIND OF

3471
01:57:27,309 --> 01:57:29,978
ALMOST GET A CRYSTALLIZATION OF

3472
01:57:29,978 --> 01:57:34,149
EP GENETIC CONTROL LI LIKE YOU N

3473
01:57:34,149 --> 01:57:36,885
GET A WHOLE BUNCH OF

3474
01:57:36,885 --> 01:57:41,123
METHYLATIONS ON THE GENOME, AND

3475
01:57:41,123 --> 01:57:44,292
WE'RE VERY INTERESTED TO

3476
01:57:44,292 --> 01:57:46,595
UNDERSTAND WHETHER OR NOT SHIFT

3477
01:57:46,595 --> 01:57:49,965
WORK COULD, OVER MANY YEARS,

3478
01:57:49,965 --> 01:57:51,967
EVENTUALLY HAVE A RESIDUAL

3479
01:57:51,967 --> 01:57:54,970
EFFECT IN TERMS OF THE GENOMIC

3480
01:57:54,970 --> 01:57:55,637
CONTROL.

3481
01:57:55,637 --> 01:57:56,938
WE'D DONE A STUDY A NUMBER OF

3482
01:57:56,938 --> 01:57:59,007
YEARS AGO JUST LOOKING AT

3483
01:57:59,007 --> 01:58:00,976
TRANSIENT PHASE SHIFTING IN

3484
01:58:00,976 --> 01:58:05,147
MICE, AND FOUND THAT THE -- JUST

3485
01:58:05,147 --> 01:58:06,448
THE CIRCADIAN PATTERN OF A

3486
01:58:06,448 --> 01:58:08,049
SINGLE HISTONE METHYLATION

3487
01:58:08,049 --> 01:58:10,585
MARKER WAS REALLY DYSREGULATED

3488
01:58:10,585 --> 01:58:11,620
AFTER THOSE EIGHT WEEKS.

3489
01:58:11,620 --> 01:58:13,989
WE HAD THE EIGHT WEEKS, LET THEM

3490
01:58:13,989 --> 01:58:15,190
REENTRAIN, AND YET THINGS WERE

3491
01:58:15,190 --> 01:58:16,591
STILL KIND OF ALL OVER THE PLACE

3492
01:58:16,591 --> 01:58:20,662
IN TERMS OF THE TIMING OF THOSE

3493
01:58:20,662 --> 01:58:23,965
METHYLATION MARKS ACROSS GENES.

3494
01:58:23,965 --> 01:58:25,267
>> WOW, THAT'S ACTUALLY
KIND OF

3495
01:58:25,267 --> 01:58:28,537
WHAT I WAS GETTING AT, IS THAT

3496
01:58:28,537 --> 01:58:30,272
LONG TERM, HOW WOULD THIS

3497
01:58:30,272 --> 01:58:33,341
IMPACT, HEALTH OUTCOMES, PER

3498
01:58:33,341 --> 01:58:33,642
POPULATION.

3499
01:58:33,642 --> 01:58:35,510
WITH THAT, I THINK WE'RE OUT OF

3500
01:58:35,510 --> 01:58:36,178
TIME.

3501
01:58:36,178 --> 01:58:36,945
THAT VERY INTERESTING NOTE.

3502
01:58:36,945 --> 01:58:43,084
SO I WOULD LIKE TO THANK YOU,

3503
01:58:43,084 --> 01:58:48,790
DR. BUTLER, DR. ABBOTT, DR. MA

3504
01:58:48,790 --> 01:58:49,090
DR. MAKAREM.

3505
01:58:49,090 --> 01:58:51,560
THANK YOU FOR JOINING US FOR THE

3506
01:58:51,560 --> 01:58:53,595
ANNUAL SLEEP 101 SYMPOSIUM.

3507
01:58:53,595 --> 01:58:55,363
YOUR ENGAGEMENT IS VITAL TO

3508
01:58:55,363 --> 01:58:56,331
ADVANCING THE CONVERSATION

3509
01:58:56,331 --> 01:58:58,166
AROUND CIRCADIAN SCIENCE AND ITS

3510
01:58:58,166 --> 01:58:59,067
APPLICATION TO RESEARCH,

3511
01:58:59,067 --> 01:59:00,469
CLINICAL PRACTICE AND POPULATION

3512
01:59:00,469 --> 01:59:01,036
HEALTH.

3513
01:59:01,036 --> 01:59:03,004
AS WE MOVE FORWARD, WE ENCOURAGE

3514
01:59:03,004 --> 01:59:07,108
YOU TO CONTINUE TO EXPLORE THE

3515
01:59:07,108 --> 01:59:08,310
INNOVATIVE APPROACHES WE

3516
01:59:08,310 --> 01:59:11,680
DISCUSSED TODAY, AND TO CONSIDER

3517
01:59:11,680 --> 01:59:13,982
HOW TO -- HOW CAN YOU INFORM

3518
01:59:13,982 --> 01:59:14,983
YOUR WORK AND IMPROVE PATIENT

3519
01:59:14,983 --> 01:59:16,918
OUTCOMES AND PUBLIC HEALTH.

3520
01:59:16,918 --> 01:59:18,687
SO WE HOPE THIS SYMPOSIUM HAS

3521
01:59:18,687 --> 01:59:22,157
SPARKED NEW IDEAS, AND

3522
01:59:22,157 --> 01:59:23,158
COLLABORATIONS, AND THAT YOU

3523
01:59:23,158 --> 01:59:24,459
WILL TAKE THESE CONVERSATIONS

3524
01:59:24,459 --> 01:59:25,994
FURTHER IN YOUR RESEARCH AND IN

3525
01:59:25,994 --> 01:59:26,962
YOUR PRACTICE.

3526
01:59:26,962 --> 01:59:29,431
SO ON BEHALF OFF  THE AMERICAN

3527
01:59:29,431 --> 01:59:31,066
ACADEMY OF SLEEP MEDICINE, THE

3528
01:59:31,066 --> 01:59:32,901
SLEEP RESEARCH SOCIETY AND THE

3529
01:59:32,901 --> 01:59:34,870
NATIONAL CENTER ON SLEEP

3530
01:59:34,870 --> 01:59:35,637
DISORDERS RESEARCH AT THE

3531
01:59:35,637 --> 01:59:37,372
NATIONAL HEART, LUNG AND BLOOD

3532
01:59:37,372 --> 01:59:38,473
INSTITUTE, WE LOOK FORWARD TO

3533
01:59:38,473 --> 01:59:40,942
SEEING YOU IN THE FUTURE.

3534
01:59:40,942 --> 01:59:42,410
A RECORDING OF THIS PRESENTATION

3535
01:59:42,410 --> 01:59:46,781
WILL BE AVAILABLE AT

3536
01:59:46,781 --> 01:59:47,983
VIDEOCAST.NIH.GOV IN THE COMING

3537
01:59:47,983 --> 01:59:48,517
DAYS.

3538
01:59:48,517 --> 01:59:50,252
THANK YOU AGAIN FOR YOUR

3539
01:59:50,252 --> 01:59:51,319
PARTICIPATION.

3540
01:59:51,319 --> 01:59:53,355
GOODBYE, EVERYBODY.

3541
01:59:53,355 --> 01:59:54,389
>> THANK YOU.

3542
01:59:54,389 --> 02:00:04,389
BYE.