Atul Butte's presentation to the Association of Medical School Pediatric Department Chairs #AMSPDC on March 3, 2018.
Some pre-publication data slides have been removed from this deck.
Atul Butte's presentation to the Association of Medical School Pediatric Department Chairs #AMSPDC on March 3, 2018.
Some pre-publication data slides have been removed from this deck.
The Uneven Future of Evidence-Based MedicineIda Sim
An Apple ResearchKit study enrolled 22,000 people in five days. A
study claims that Twitter can be used to identify depressed patients. A computer program crunches genomic data, the published literature, and electronic health record data to guide cancer treatment. The pace, the data sources, and the methods for generating medical evidence are changing radically. What will — what should — evidence-based medicine look like in a faster, personalized, data-dense tomorrow?
- Presented as the 3rd Annual Cochrane Lecture, October 2015 in Vienna, Austria.
The Uneven Future of Evidence-Based MedicineIda Sim
An Apple ResearchKit study enrolled 22,000 people in five days. A
study claims that Twitter can be used to identify depressed patients. A computer program crunches genomic data, the published literature, and electronic health record data to guide cancer treatment. The pace, the data sources, and the methods for generating medical evidence are changing radically. What will — what should — evidence-based medicine look like in a faster, personalized, data-dense tomorrow?
- Presented as the 3rd Annual Cochrane Lecture, October 2015 in Vienna, Austria.
"How Scientific Wellness will Drive The Future of Health" - Nathan Price (Pro...Hyper Wellbeing
"How Scientific Wellness will Drive The Future of Health" - Nathan Price (Professor, Institute of Systems Biology)
Delivered at the inaugural Hyper Wellbeing Summit, 14th November 2016, Mountain View, California.
For more information including details of subsequent events, please visit http://hyperwellbeing.com
The summit was created to foster a community around an emerging industry - Wellness as a Service (WaaS). Consumer technologies, in particular wearables and mobile, are powering a consumer revolution. A revolution to turn health and wellness into platform delivered services. A revolution enabling consumer data-driven disease risk reduction. A revolution extending health care past sick care towards consumer-led lifelong health, wellness and lifestyle optimization.
WaaS newsletter sign-up http://eepurl.com/b71fdr
@hyperwellbeing
Published Research, Flawed, Misleading, Nefarious - Use of Reporting Guidelin...John Hoey
Much published health sciences literature is misleading and biased
Efforts to correct this include use of reporting guidelines- criteria for doing science and reporting the results properly
Also discussion of conflicts of interest - how to report them.
Morphologomics - Challenges for Surgical Pathology in the Genomic Age by Dr. ...Cirdan
This presentation introduces and discussesthe concept of ‘morphologomics’ that is omics approaches critically reimagined and reappraised from the viewpoint of classic morphology.
It was delivered by Dr. Anthony Gill at the Pathology Horizons 2017 conference in Cairns, Australia.
introduce and discuss the concept of ‘morphologomics’ that is omics approaches critically reimagined and reappraised from the viewpoint of classic morphology.
NAPCRG Pearls: What Is New? The top nine research studies that will impact clinical practice for family physicians as presented by Drs. David Kaplan and David White at Family Medicine Forum in Quebec City, QC Nov 2014
In this talk, we present our work on developing large-scale text mining and machine learning tools as well as their uses in real-world applications in PubMed search, biocuration and healthcare (medical image analysis).
Dr. Swamy Venuturupalli talks about the latest developments in lupus at the 2015 Latest on Lupus Patient Conference held by Lupus LA on Saturday October 17th at UCLA Medical Center.
Bladder Cancer Diagnostic-Initial Team ProjectSagar Desai
A mini-project to find biomarkers for bladder cancer diagnosis. We narrowed down our list of viable candidates down to three that could be used in combination to provide sensitivity and specificity values greater than 94%. Furthermore, we calculated long-term monitoring and payor costs as well as potential profit.
5 years of “Rare” Progress Research: Cheryl Rockman-Greenberg, Max Rady College of Medicine, University of Manitoba
Rare Disease Day Conference 2020 March 9-10
Similar to Atul Butte's presentation for the FDA 5th Annual Scientific Computing Days (20)
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
NVBDCP.pptx Nation vector borne disease control program
Atul Butte's presentation for the FDA 5th Annual Scientific Computing Days
1. Translating a Trillion Points of Data into
Diagnostics, Therapies and New Insights
in Health and Disease
atul.butte@ucsf.edu
@atulbutte
Atul Butte, MD, PhD
Director, Institute for Computational
Health Sciences
University of California, San Francisco
12. 227 million substances x
1.3 million assays
More than a billion measurements
within a grid of 300 trillion cells
71 million meet Lipinski 5
1.2 million active substances
16. Preeclampsia: large cause of maternal and fetal death
• Incidence
• 5-8% of all pregnancies in the U.S. and worldwide
• 4.1 million births in the U.S. in 2009
• Up to 300K cases of preeclampsia annually in the U.S.
• Mortality
• Responsible for 18% of all maternal deaths in the U.S.
• Maternal death in 56 out of every 100,000 live births in US
• Neonatal death in 71 out of every 100,000 live births in US
• Cost
• $20 billion in direct costs in the U.S annually
• Average hospital stay of 3.5 days
Linda Liu
Bruce Ling
Matt Cooper
17.
18.
19.
20. New blood markers for preeclampsia
Linda Liu
Bruce Ling
Matt Cooper
@MarchofDimes
bit.ly/preeclamp
21. Need a
diagnostic for
preeclampsia
Public big data
available
March of Dimes
Center for
Prematurity
Research
Data analyzed,
diagnostic
designed
SPARK grant
($50k)
Life Science
Angels, other
seed investors
($2 million)
@CarmentaBio
progenity.com
bit.ly/carm_prog
24. Credit: Russ Altman and team
Human genome sequence can be used to predict drug adverse events
25. • Study published in 2008 in
Inflammatory Bowel Disease
• Crohn’s Disease and Ulcerative
Colitis
• Investigated 9 loci in 700 Finnish
IBD patients
• We record 100+ items
– GWAS, non-GWAS papers
– Disease, Phenotype
– Population, Gender
– Alleles and Genotypes
– p-value (and confidence)
– Odds ratio (and confidence)
– Technology, Study design
– Genetic model
• Mapped to UMLS concepts
Rong Chen
Optra Systems
26. • Study published in 2008 in
Inflammatory Bowel Disease
• Crohn’s Disease and Ulcerative
Colitis
• Investigated 9 loci in 700 Finnish
IBD patients
• We record 100+ items
– GWAS, non-GWAS papers
– Disease, Phenotype
– Population, Gender
– Alleles and Genotypes
– p-value (and confidence)
– Odds ratio (and confidence)
– Technology, Study design
– Genetic model
• Mapped to UMLS concepts
27. • Study published in 2009
in Rheumatology
• Ankylosing spondylitis
• Investigated 8 SNPs in
IL23R in 2000 UK case-
control patients
• Tables can be rotated
• NLP is hard
28. • Study published in 2009
in Rheumatology
• Ankylosing spondylitis
• Investigated 8 SNPs in
IL23R in 2000 UK case-
control patients
• Tables can be rotated
• NLP is hard
29. • Study published in 2009
in Rheumatology
• Ankylosing spondylitis
• Investigated 8 SNPs in
IL23R in 2000 UK case-
control patients
• Tables can be rotated
• NLP is hard
32. Alleles for rs1004819 are C and T
~11% of records reported genotypes in the negative strand
33. Credit: Rong Chen, Optra Systems, and Personalis, Inc.
Important genome differences “locked up” in publications
34. Credit: Rong Chen, Optra Systems, and Personalis, Inc.
Collect the “big data” of findings across publications to
analyze the “big data” of the genome
37. Number of
papers curated
Number of
records
Distinct SNPs Diseases and
phenotypes
~19,000 ~1.6 million ~473,000 ~7,400
Rong Chen
Optra Systems
Personalis
VARIMED: Variants Informing Medicine
Chen R, Davydov EV, Sirota M, Butte AJ.
PLoS One.
2010 October: 5(10): e13574.
44. Need to use
genomes to
predict
disease
Publications
available for
curation
Stanford
donor
funding
Science
curated,
methods
designed
Company
launched,
Stanford
license
MDV,
Lightspeed,
Abingworth
($20 million)
Same 3 plus
Wellington
Shields ($22
million)
Series C ($33
million)
51. Cancer Discovery 2013, 3:1.
Psychiatric Drug Imipramine Shows Significant Activity
Against Small Cell Lung Cancer
Vehicle control Imipramine
p53/Rb/p130
triple knockout
model of SCLC
Mice dosed after
tumor formation
Joel Dudley
Nadine Jahchan
Julien Sage
Alejandro Sweet-Cordero
Joel Neal
@NuMedii
52. Bin Chen
Wei Wei
Li Ma
Bin Yang
Mei-Sze Chua
Samuel So
Gastroenterology, 2017
53. Need more drugs
for more diseases
Public big data
available
NIH funding
Data analyzed,
method designed
Company launched,
ARRA, StartX,
Stanford license,
first deal
Claremont Creek,
Lightspeed ($3.5
million)
@NuMedii
54. The next big open data: clinical trials
Download 100+ studies today
Drug repositioning, new patient subsets,
digital comparative effectiveness, more!
immport.org
Sanchita Bhattacharya
Jeff Wiser
55. Reanalyzing RAVE
• Rituximab in ANCA-Associated Vasculitis (RAVE) trial of new approach to
the induction of remission
– randomized
– double-blind
– double-dummy
– active-controlled
– non-inferiority
56.
57.
58. Reproduce CD19+ B-cell depletion
using publicly released clinical trials data
Nasrallah M, …, Butte AJ. Arthritis Research & Therapy (2015) 17:262.
59. RAVE re-analysis
• 63 of the 99 patients in the rituximab group (64%) reached the
primary end point, as compared with 52 of 98 in the control group
(53%).
• The treatment difference of 11% points between the groups met the
criterion for non-inferiority (P<0.001).
In retrospect, do any measured factors
predict response?
Mazen Nasrallah
Nasrallah M, …, Butte AJ. Arthritis Research & Therapy (2015) 17:262.
60. Nasrallah M, …, Butte AJ. Arthritis Research & Therapy (2015) 17:262.
Granularity index higher in rituximab-treated
subjects with remission
SSC
1 2
Granulocyte Subpopulations and Treatment Outcomes
Panel A: representative bi-dimensional dot-plot of granulocyte sub-
populations identified by ImmPortFLOCK on the basis of FSC and SSC.
A1: Hypogranular granulocytes with an SSC of low or positive (2 or 3).
A2: Hyper granular granulocytes with an SSC of high (4).
Panel B: granularity index at day 0 among patients receiving rituximab or
cyclophosphamide, stratified by treatment outcome (failure: red,
success: blue). Data distribution is shown as a boxplot, with mean ±
SEM represented by dots and small error bars. CYC: cyclophosphamide,
RTX: rituximab. A Welch two-sided t-test was used to calculate
significance.
61. Nasrallah M, …, Butte AJ. Arthritis Research & Therapy (2015) 17:262.
ANCA-
associated
Vasculitis
Profiled
Therapy
~ 54% of patients
Non-profiled
Therapy
~46% of patients
Treat with
Rituximab
~ 30% of patients
Remission Rate ~ 83%
Treat with
Cyclophosphamide
~24% of patients
Remission Rate ~ 66%
Do not treat with
Cyclophosphamide
Failure rate ~ 67%
Do not treat with
Rituximab
Failure rate ~ 70%
GI ≤ -9.25%
OR
GI ≥ 47.6%
GI ≤ -9.25% GI ≥ 47.6%
Treat with either Rituximab or
Cyclophosphamide
according to best clinical judgement
Average Remission Rate ~ 60%
Non-profiled
Therapy
100% of patients
NO
Proposed
Method
Current
Method
Measure the Granularity Index
(GI)
YES
Mazen Nasrallah
62.
63. • Founded 2015
• 38 affiliated faculty members from UCSF’s four
top-ranked schools
– 5 in National Academy of Medicine
– 1 in National Academy of Science
– 2 in the American Society for Clinical Investigation
– 3 NIH Director’s Awards
– 2 Sloan Foundation fellows
– 1 HHMI faculty scholar
– 1 MacArthur Foundation fellow
– 1 Chan/Zuckerberg faculty fellow
64. Build the strongest team in the world in
biomedical computation and health data analytics
• Academic affinity home for faculty and staff
• Research and development (and spin out technologies)
• Develop new educational plans
• Bring the best new computational and informatics faculty members
to UCSF
• Organize infrastructure and operations
• Build and use our new data assets for precision medicine
66. Combining healthcare data from across the
six University of California medical schools and systems
Clinical Data Warehouse
A Big UC Healthcare Data Analytics Platform
67.
68.
69. What could we do with clinical data?
• Clinical researcher at UCLA could run a genome wide association study across UC Health
• Mobile health researcher at UCSD can enable patients to contribute data for research
• Community activist and researcher UC Merced can study environmental factors
contributing to health and disease
• Transplant patient at UC Irvine can download all their data across UC Health
• Data scientist at UC Santa Barbara can model development of Alzheimer's disease and build
a multi-modal predictor
• App designer at UC Riverside can show patients their choices with chronic disease
• CMO at UCSF can build predictive models for readmission, test, share across UC Health
• AI researcher at UC Berkeley can build deep-learning models for image-based diagnostics
• Health services researcher at UC Davis can build predictive models for drug efficacy, and
maybe enable pay-for-performance
• Cancer genomics researcher at UCSC can study all our clinical cancer genomes
70.
71. Take home points:
• Plenty of high-quality data already available:
some public, some private
• Don’t wait for perfection; data always
getting better
• Use and intersect data to ask new questions,
to innovative new diagnostics and drugs
• Academia and industry are compatible: the science
can and will continue in industry
72. UC Clinical Data Warehouse Team
Executive Team
• Atul Butte
• Joe Bengfort
• Michael Pfeffer
• Tom Andriola
• Chris Longhurst
Steering Committee
• Irfan Chaudhry
• Mohammed Mahbouba
• Lisa Dahm
• David Dobbs
• Kent Andersen
• Ralph James
• Jennifer Holland
• Eugene Lee
ETL Team
• Albert Dugan
• Tony Choe
• Michael Sweeney
• Timothy Satterwhite
• Ayan Patel
• Niranjan Wagle
• Ralph James
• Joseph Dalton
Data Harmonization
• Dana Ludwig
• Daniella Meeker
Data Quality
• Momeena Ali
• Jodie Nygaard
Epic
• Kevin Ames
• Ben Jenkins
• Steve Gesualdo
Business Analyst
• Ankeeta Shukla
Hardware
• Sandeep Chandra
• Jeff Love
• Scott Bailey
• Kwong Law
• Pallav Saxena
Support
• Jack Stobo
• Michael Blum
• Sam Hawgood
73. Collaborators
• Jeff Wiser, Patrick Dunn, Mike Atassi /
Northrop Grumman
• Ashley Xia and Quan Chen / NIAID
• Takashi Kadowaki, Momoko Horikoshi, Kazuo
Hara, Hiroshi Ohtsu / U Tokyo
• Kyoko Toda, Satoru Yamada, Junichiro Irie /
Kitasato Univ and Hospital
• Shiro Maeda / RIKEN
• Jeff Olgin / Cardiology
• Alejandro Sweet-Cordero, Julien Sage /
Pediatric Oncology
• Mark Davis, C. Garrison Fathman /
Immunology
• Russ Altman, Steve Quake / Bioengineering
• Euan Ashley, Joseph Wu, Tom Quertermous /
Cardiology
• Mike Snyder, Carlos Bustamante, Anne Brunet
/ Genetics
• Jay Pasricha / Gastroenterology
• Rob Tibshirani, Brad Efron / Statistics
• Hannah Valantine, Kiran Khush/ Cardiology
• Ken Weinberg / Pediatric Stem Cell
Therapeutics
• Mark Musen, Nigam Shah / National Center for
Biomedical Ontology
• Minnie Sarwal / Nephrology
• David Miklos / Oncology
74. Support
Admin and Tech Staff
• Mary Lyall
• Mounira Kenaani
• Kevin Kaier
• Boris Oskotsky
• Mae Moredo
• Ada Chen
• University of California, San Francisco
• NIH: NIAID, NLM, NIGMS, NCI, NHLBI, OD; NIDDK, NHGRI, NIA, NCATS
• March of Dimes
• Juvenile Diabetes Research Foundation
• Hewlett Packard
• Howard Hughes Medical Institute
• California Institute for Regenerative Medicine
• Luke Evnin and Deann Wright (Scleroderma Research Foundation)
• Clayville Research Fund
• PhRMA Foundation
• Stanford Cancer Center, Bio-X, SPARK
• Tarangini Deshpande
• Kimayani Butte
• Sam Hawgood
• Keith Yamamoto
• Isaac Kohane