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IN THIS ISSUE Letter From the Editor................................ 4 Director’s Message.................................... 5 News at a Glance...................................... 6 Twitter Feature........................................... 7 Feature Infographic.................................... 8 Feature: Sleep.......................................... 10 Special BMC Feature............................... 26 Faculty Spotlight...................................... 28 Student Spotlight..................................... 30 IMS Scientific Day................................... 32 Special TRP Feature................................. 34 Viewpoint................................................. 36 Past Events............................................... 39 Book Review............................................ 40 Diversions................................................ 41
FEATUREINFOGRAPHIC GRAPHIC FEATURE
P14 P8 CANADIAN CHRONIC PAIN STATISTICS Created by Sam Holmes
Copyright © 2016 by Institute of Medical Science, University of Toronto. All rights reserved. Reproduction without permission is prohibited. The IMS Magazine is a student-run initiative. Any opinions expressed by the author(s) are in no way affiliated with the Institute of Medical Science or the University of Toronto.
MAGAZINE STAFF EDITOR-IN-CHIEF
Kasey Hemington Rebecca Ruddy Katherine Schwenger
JOURNALISTS & EDITORS
Alexandra Mogadam Anna Badner Adam Betel Arunima Kapoor Ayda Ghahremani Chelsea Lowther Danielle Cha Ekaterina An Gaayathiri Jegatheeswaran Jabir Mohamed Jessie Lim Jonathon Chio Joshua Lipszyc Meital Yerushalmi Melissa Galati Mirkamal Tolend Muhtashim Mian Rachel Dragas Sarah Peters Shokoufeh Yaseri Petri Takkala Usman Saeed Vanessa Rojas Luengas Yekta Dowlati
Sam Holmes Sarah Kim Melissa Phachanhla Sonia Seto Kelly Speck
SOCIAL MEDIA EXECUTIVES
Beatrice Ballarin Fadl Nabbouh Tahani Baakdhah
Antigona Ulndreaj Carina Freitas
Chung Ho Leung Elizaveta Semechko Meital Yerushalmi Pratiek Matkar Tahani Baakdhah
Cover design by Kelly Speck “This cover was inspired by the article about central nervous system stimulant caffeine. The illustration depicts caffeine molecules binding to A2A receptors in the cell membrane. Molecular structures are based on data from the Protein Data Bank.”
IMS MAGAZINE SUMMER 2016 SLEEP | 3
LETTER FROM THE EDITOR
LETTER FROM THE
EDITOR A s I lay in bed tossing and turning, pondering over the first lines of this column, the irony of the situation became clear. After months of discussing and compiling a whole issue–including a graduate student survey– focused on sleep, here I was, losing sleep over it. This vignette is not uncommon in the modern era of increased work-related stress, sedentary lifestyles, and sleep deprivation. Some 40% of graduate students we surveyed reported poor sleep quality and 50% reported trouble falling asleep most nights. I don’t want to give it all away here, so for more sleep statistics and the results to our Graduate Student Sleep Survey, I strongly urge you to take a look at our ‘Feature Infographic’ on Sleep. Furthering our discussion on sleep, we bring you cutting-edge research from sleep experts Dr. Richard Horner, Dr. Colin Shapiro, Dr. Andrew Lim, Dr. Indra Narang, and Dr. Gillian Einstein. We discuss everything from sex differences in sleep, to sleep-related disorders in children, and even the genetic determinants of early wakefulness (yes, there is such a thing!). I hope that our feature will stimulate conversations and engaging questions in sleep and beyond.
ANNETTE YE Editor-in-Chief, IMS Magazine
I encourage you to have a look at our ‘Spotlight’ articles as we get up close and personal with Dr. Andreas Laupacis and Biomedical Communications Masters student, Judy Rubin. Also of interest is our expanded ‘Diversions’ section containing reviews on the popular documentary, ‘My Beautiful Broken Brain’, as well as Meg Jay’s TED talk on why 30 is not the new 20.
Annette is a fourth year PhD candidate at the Institute of Medical Science. She is currently conducting research on biomarker discovery in neurodevelopmental disease at the Hospital for Sick Children.
It is with a heavy heart that I announce my departure from the IMS Magazine. It has truly been a privilege to work with such incredibly talented colleagues, physicians, and scientists in this venture. Words cannot describe how inspired I am by my fellow graduate students whom volunteer their time to be a part of the IMS Magazine. To the content committee, photographers, sponsorship executives, our social media team, and the design team: thank you. The magazine would not be half of what it is without your creativity and enthusiasm. I would also like to thank Dr. Mingyao Liu and the IMS department for their ongoing support, and congratulate the design team on another stunning production of this magazine. To you, our readers and supporters, stay curious, ask questions, and join our discussions via our website, twitter, or directly at email@example.com.
Annette Ye, Editor-in-Chief, IMS Magazine
4 | IMS MAGAZINE SUMMER 2016 SLEEP
Photo by Meital Yerushalmi
elcome to another issue of the IMS Magazine, focused on the intriguing topic of sleep. This issue highlights content from an esteemed panel of sleep experts within our department, featuring Dr. Indra Narang, Dr. Andrew Lim, Dr. Gillian Einstein, Dr. Richard Horner, and Dr. Colin Shapiro. Our students also ran a ‘Graduate Student Sleep Survey’, asking their peers to rate their sleep habits and quality of sleep. I hope that people will be interested in this interesting topic.
Photo by Tahani Baakdhah
It has been a busy summer at the IMS. On May 20, 2016, we held our annual Scientific Day at the St. Andrew’s Club and Conference Centre. It was an inspiring event being able to celebrate the scientific and academic achievements of our department through poster presentations, data blitz talks, and award celebrations. Dr. Victor Dzau, our keynote speaker from the National Academy of Medicine shared compelling results from his work in regenerative cardiovascular therapy. He also reminded students to chase their passions and to love what they are doing, every day.
DR. MINGYAO LIU Director, Institute of Medical Science Professor, Department of Surgery Senior Scientist Toronto General Research Institute, University Health Network
In June, we welcomed a new cohort of undergraduate students from across Canada and internationally into our Summer Undergraduate Research Program. The IMS Student Alumni Faculty Engagement committee, in partnership with our student association, IMSSA, hosted a public “UofT Talks” featuring “Baby Boomer and Millennials: Writing the next Chapter”. Congratulations to IMSSA and the committee for hosting a successful event. Congratulations to Annette Ye and her team for their continued dedication and collective creative energies in producing this publication. The IMS Magazine has been a tremendous success and is just one of the many wonderful, student-led initiatives that make the IMS a very special institute. I fully support the ongoing publication and look forward to reading and learning about the outstanding research that is being conducted by our faculty and trainees in IMS. On behalf of everyone at the IMS, I wish you a terrific summer ahead. Mingyao Liu, MD, MSc Director, Institute of Medical Science IMS MAGAZINE SUMMER 2016 SLEEP | 5
NEWS AT A GLANCE
IMPORTANT DATES JUN
June Convocation information and dates are posted at www.convocation.utoronto.ca
Final date to drop May-to-August session Y section courses without academic penalty
Final date to enrol in July coursework-only programs
Canada Day holiday (University closed)
Final date to enrol in July-to-August courses
Coursework must be completed and grades submitted for May-to-June F section courses
Final date to drop July-to-August S section courses without academic penalty
Grades for May-to-June F section courses available for viewing by students on Student Web Services (ROSI/ACORN)
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Indra Narang, MD, FRCPCH Director of Sleep Medicine and Staff Respirologist, Department of Respiratory Medicine, The Hospital for Sick Children Associate Scientist, Department of Physiology and Experimental Medicine,The Hospital for Sick Children Research Institute Associate Professor, Department of Paediatrics, University of Toronto Associate Member, Institute of Medical Science
RECOGNIZING AND TREATING PAEDIATRIC SLEEP DISORDERS A New Wake-Up Call An interview with Dr. Indra Narang By Rachel Dragas
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r. Indra Narang is a paediatric respirologist and the Director of Sleep Medicine at the Hospital for Sick Children. She is also an associate professor in the Department of Paediatrics and an associate graduate faculty member in the Institute of Medical Science at the University of Toronto. Dr. Narang’s research examines the cardiovascular, metabolic, and neurocognitive consequences of childhood sleep disorders like obstructive sleep apnea, and how they may be amplified by factors such as obesity. Aside from her work, she is also a tireless advocate for increasing awareness about paediatric sleep disorders and resource availability in Canada. I sat down with Dr. Narang to hear more about her successful
career and the progress that’s been made in diagnosing and providing early treatment for children with sleep disorders, particularly obstructive sleep apnea. Can you tell us a bit about your education, background, and training? I’m originally from London, England where I completed medical school, my doctoral research degree, and postgraduate training in paediatrics and respirology. As part of this training, I completed a one year fellowship in paediatric respirology at the Hospital for Sick Children. This was my first real introduction to paediatric sleep medicine. I undertook further training in sleep medicine at the Children’s
FEATURE Hospital of Philadelphia. Following this, I was offered a position at the Hospital for Sick Children in 2007. Can you give us some insight on sleep disorders in children and your research findings? Our research is mainly focused on the diagnosis and optimal management, as well as the cardiovascular, metabolic, and neurocognitive consequences of sleep disorders in children. Sleep disorders encompass a variety of conditions, ranging from teenagers who have chronic sleep deprivation to very young children and teenagers who have obstructive sleep apnea. Sleep disorders, whether it be sleep deprivation or sleep apnea, can affect most of the physiological systems of the body, and treatment can have a significant positive impact not only on the child’s physical health, but mental health and wellbeing. Obstructive sleep apnea is a common childhood disorder that arises from narrowing of the upper airway. It is characterized by loud snoring and pauses in breathing, ultimately resulting in low blood oxygen levels and sleep fragmentation with impairment of daytime functioning. Historically, paediatric obstructive sleep apnea, which occurs in approximately 3% of all healthy children, was not recognized as a significant morbidity, and as such, many children were not diagnosed nor treated. We now recognize that sleep apnea can result in significant fatigue during the day and is an independent risk factor for cardiovascular disease, systemic hypertension, and insulin resistance. This disorder is further complicated by obesity. Up to 60% of obese children have sleep apnea, which may magnify the underlying cardiovascular and metabolic burdens associated with obesity. What are the main impacts of your research? We have developed a large clinical and research team, and together we have heightened awareness and highlighted the impact of sleep disorders on both health and disease. For example, our research has shown that children with sickle cell disease, Down syndrome, and metabolic disorders, have a very high rate of obstructive sleep apnea (> 30%) and treatment improves daytime functioning.
Other research has shown that a significant number of teenagers are generally sleep deprived, resulting in an increase in both blood pressure and weight, both risk factors for health problems in adults. Moreover, as a result of our research, we now receive three times the number of referrals to our center compared to five years ago. This translates to more children getting the treatments they need in a timelier fashion. Furthermore, there has been an increasing interest, especially within the public, on the influence of sleep on health and disease. Should every child with sleep apnea be treated? What is the best timing for intervention? From a clinical perspective, if a child has a diagnosis of sleep apnea with daytime consequences (disruptive behavioural problems, hyperactivity, etc.), then the child should absolutely be treated. In children, the most common cause of obstructive sleep apnea is enlarged tonsils and adenoids in the upper airway, which block the nasal passages and make breathing through the nose difficult. The gold standard of care for a young, otherwise healthy child with obstructive sleep apnea, is an adeno-tonsillectomy. Timing of intervention is important because young children are often at a critical stage of brain development, and sleep apnea with related hypoxia can have detrimental effects on the developing brain. Timely intervention is crucial to prevent or limit any impact on learning, memory, and behaviour. What are some of the challenges and controversies in this field? Paediatric sleep medicine is a rapidly expanding field and it is hard to keep pace with all of the new and evolving research that ultimately determines our best models for clinical care. I think an enormous challenge for us right now is the obesity epidemic, as obese children and adolescents have a very high risk of developing obstructive sleep apnea. Conventional surgical treatments are not necessarily successful in these children and we are currently researching into the optimal treatment for these cases. However, the lack of resources in paediatric sleep medicine across Canada probably means a
significant number of obese children will not be diagnosed or treated for obstructive sleep apnea. This is probably the greatest challenge for paediatric sleep specialists across Canada. Was there a defining moment in your work as a scientist? Recently, we have established a large sleep network across Canada. Paediatric and adult researchers have come together and established the Canadian Sleep and Circadian Network (CSCN), involving 17 universities in total. We all share the same core goal which is looking at sleep disorders across the life span, and this includes collecting DNA samples from patients with sleep disorders. Having the paediatric and adult team finally come together is a really big venture and was validated by a $4 million grant from CIHR and research institutes across Canada allowing us to do this work. Not only is there increasing awareness and work being done on paediatric sleep disorders, but we’ve also integrated paediatric sleep into a national sleep network. What is the most rewarding part of your job? The Hospital for Sick Children has the largest and most comprehensive sleep program in all of Canada. We have increasing academic output, most of which has been achieved within the last five years. To me, that’s immensely rewarding. Our sleep program provides state-of-the-art clinical care, conducts unique and innovative research, and is taking the lead in training excellent paediatric sleep physicians. It’s pretty incredible to look back and see how far we’ve come in such a short time. What words of wisdom do you have for graduate students? You have to be really passionate about wanting to do research. Research is incredibly hard work involving the most amazing ‘highs’ which are sadly balanced by ‘lows’ on the way. Being in the right institution with the right mentorship is vitally important for success as long as you are passionate about your work and motivated to succeed. Ultimately research can reap huge rewards!
IMS MAGAZINE SUMMER 2016 SLEEP | 11
OF SEX AND SLEEP Gillian Einstein, PhD Associate Professor, Dalla Lana School of Public Health, University of Toronto Associate Professor, Department of Psychology, University of Toronto Director, Collaborative Graduate Program in Women’s Health, University of Toronto Adjunct Scientist, Women’s College Research Institute Member, IMS
By Ekaterina An
n 2009, Health Canada introduced the Sex and Gender-Based Analysis Policy that required numerous health research organizations, including the Canadian Institutes of Health Research (CIHR), to “develop, implement and evaluate research, programs and policies to address the different needs of women and men.”1 This mandate reflected the importance of understanding the health determinants of both sexes, and was followed by a 2010 CIHR and 2014 National Institutes 12 | IMS MAGAZINE SUMMER 2016 SLEEP
of Health requirement that applicants discuss whether their study included sex or gender. When it comes to sex and sleep, a number of studies have identified differences in sleep quality between men and women. For example, Zhang and Wing2 found that women were more likely to experience insomnia than men, a trend that remained consistent and progressive across age groups. Further research into sleep differences reported that women’s 24-hour circadian rhythms are markedly
different from men3 and that differences in sleep quality between sexes only become apparent following the onset of puberty.4 These results all point to a potential hormonal explanation for the differences in sleep quality between sexes, but there is a lack of consensus regarding the nature of this link: some studies were able to demonstrate an association between sleep quality and estradiol (an ovarian hormone), while others found no associations between the two.5
Photo by Tahani Baakdhah
EXPLORING SEX DIFFERENCES IN SLEEP HEALTH AND RESEARCH
FEATURE Dr. Gillian Einstein, an associate professor in the Department of Psychology and in the Dalla Lana School of Public Health, and the Director of the Collaborative Graduate Program in Women’s Health at the University of Toronto, is no stranger to this entanglement of sex and sleep differences. “Sleep is very complex,” she says, laughing. Dr. Einstein’s current research interests center around women’s health, and incorporating sex and gender into basic science and clinical research. But her interest in sleep was first piqued about 15 years ago when she heard Dr. Allan Hobson, a prominent sleep researcher, address some of her students on the importance of conducting sleep research. “At that time, sleep was under-researched, he [Dr. Hobson] thought, because people thought it was voyeuristic. You were studying people when they were vulnerable and unaware, but he said it was incredibly important for health because somebody could go to the doctor awake and not have any heart problems, and somebody could be sleeping and they would have tachycardia,” Dr. Einstein says. Given the murky picture of the interaction between sleep and sex and her interest in women’s health in particular, Dr. Einstein set out to explore the relationships within the triad of hormones, mood, and sleep in women. The latter two factors–mood and sleep–have been linked: disturbed sleep is a hallmark of many mood disorders.6 Similarly, hormones and mood are associated with one another, with women of reproductive age reporting mood variations that align with the menstrual cycle.7 However, there is a lack of consensus on the influence of hormones on sleep quality. Alongside her colleague, Dr. Sarah Romans, Dr. Einstein conducted the Sleep and Mood in Daily Life study in non-helpseeking, community-dwelling women.5,8 They collected data on mood, urinary estrogen and progesterone concentrations, and self-reported and objective measures of sleep quality from 19 women aged 18 – 43 years old.5 The study, published in Sleep Medicine, found that sleep quality generally did not correlate with hormone levels, but was strongly correlated with mood.5 Only objective measures of sleep were found to correlate slightly with ovarian hormone levels.5 Contrary to some reports in the literature on the relationship
between female hormones and sleep, Dr. Einstein and her team found that estrogen and progesterone played an insignificant role in daily sleep variation.5 “Women feel they’re getting not as much sleep as they should and it’s poor quality, but in the group we studied it’s not something that is related to the menstrual cycles or hormones by the objective measures we used,” says Dr. Einstein. While the link between sleep quality and ovarian hormones in healthy women was minimal, there was a strong correlation of sleep quality with perceived mood. Women who felt that they were “Feeling on Top of Things” reported higher sleep quality, while those who felt that they had “Difficulty Coping” reported poorer sleep.5 This finding is consistent with previous reports on the association between sleep quality and affect.6 Interestingly, mood and hormones did not correlate in this cohort of women. Thus, although sleep quality was highly contingent on mood, perceived mood was unaffected by the menstrual cycle9 or levels of ovarian hormones–a finding that surprised Dr. Einstein: “We came out of that study thinking that PMS [premenstrual syndrome whose symptoms include mood swings, fatigue, and irritability]10 was probably something that was more socially constructed.” One explanation for this lack of association between mood and hormones in this sample may be the fact that this cohort of women differed from the traditional study participant in that they were non-help-seeking (participants were recruited using random-digit dialing), a fact that may influence how women perceive their own sleep quality and mood. Additionally, Dr. Einstein believes that hiding the menstrual cycle focus of the study may have mitigated the risk of confirmation bias in participant responses. She also notes that while estrogen may have a direct effect on neurons, there are a multitude of brain regions and social factors that influence one’s mood, such that some neuronal responses might be negated by others that are unaffected by estrogens. The lack of correlation between sleep and hormones in Dr. Einstein’s study does not discourage her from pursuing further research in this field. She believes that estrogens do have a direct effect on neurons, and is interested in studying sleep
quality and sleep patterns in women who have had their ovaries removed prior to natural menopause. Currently working with this group of women, Dr. Einstein says, “Of course they talk about sleep problems, a lot. And it’s hard to know whether their sleep problems are because of estrogen withdrawal leading to hot flashes and such–or whether it’s actually that estrogen withdrawal affects the parts of the brain that are involved in sleep or might actually play a role in creating sleep apnea.” Although women continue to report poorer sleep quality than men, they have historically been under-represented in sleep research.11 As more differences between male and female sleep patterns are coming to light, it is clear that this field of research would benefit from further exploration of the sex and gender differences in sleep quality. Dr. Einstein encourages researchers from all disciplines to consider sex and gender effects in both pre-clinical and clinical studies. For those looking to learn more about the impact of gender and sex on health, Dr. Einstein’s course, Gender and Health (CHL5109H), examines the clinical and social implications of women’s health research and gender-based medicine.
References 1. Health Canada [Internet]. [Canada]: Government of Canada, 2009 [updated 2010 Mar 12; cited 2016 May 10]. Available from: http:// www.hc-sc.gc.ca/hl-vs/pubs/women-femmes/sgba-policy-politiqueags-eng.php 2. Zhang B, Wing Y. Sex differences in insomnia: a meta-analysis. Sleep 2006 Jan 1; 29(1):85. 3. Duffy JF, Cain SW, Chang AM, Phillips AJ, Münch MY, Gronfier C, Wyatt JK, Dijk DJ, Wright KP, Czeisler CA. Sex difference in the near-24-hour intrinsic period of the human circadian timing system. Proc. Natl. Acad. Sci. 2011 Sep 13; 108(Supplement 3):15602-8. 4. Krishnan V, Collop NA. Gender differences in sleep disorders. Curr. Opin. Pulm. Med. 2006 Nov 1;12(6):383-9. 5. Li DX, Romans S, De Souza MJ, Murray B, Einstein G. Actigraphic and self-reported sleep quality in women: associations with ovarian hormones and mood. Sleep Med. 2015 Oct 31;16(10):1217-24. 6. Benca RM, Okawa M, Uchiyama M, Ozaki S, Nakajima T, Shibui K, Obermeyer WH. Sleep and mood disorders. Sleep Med. Rev. 1997 Nov 30;1(1):45-56. 7. Rubinow DR, Roy-Byrne P, Hoban MC, Grover GN, Stambler N, Post RM. Premenstrual mood changes: characteristic patterns in women with and without premenstrual syndrome. J. Affect. Disord. 1986 Mar 1;10(2):85-90. 8. Romans SE, Kreindler D, Einstein G, Laredo S, Petrovic MJ, Stanley J. Sleep quality and the menstrual cycle. Sleep Med. 2015 Apr 30;16(4):489-95. 9. Schwarz S, Hassebrauck M. Self-perceived and observed variations in women’s attractiveness throughout the menstrual cycle—a diary study. Evol. Hum. Behav. 2008 Jul 31; 29(4):282-8. 10. Frequently asked questions. Gynecologic problems FAQ057. Premenstrual syndrome. [Internet] [Washington, DC]: American College of Obstetricians and Gynecologists, 2015 [cited 2016 May 10]. Available from: http://www.acog.org/Patients/FAQs/Premenstrual-Syndrome-PMS 11. Mong JA, Cusmano DM. Sex differences in sleep: impact of biological sex and sex steroids. Phil. Trans. R. Soc. B. 2016 Feb 19; 371(1688):20150110.
IMS MAGAZINE SUMMER 2016 SLEEP | 13
FACULTY SPOTLIGHT Photo crourtesy of Doug Nicholson/Sunnybrook
Andrew Lim, MD, FRCPC Scientist, Evaluative Clinical Sciences, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute Staff Neurologist, Department of Medicine, Sunnybrook Health Sciences Centre Assistant Professor, Department of Medicine, University of Toronto Associate Member, IMS
FACULTY SPOTLIGHT ON
Dr. Andrew Lim By Jabir Mohamed
r. Andrew Lim is perhaps best known for discovering a genotype associated with earlier wakefulness. The clinician-scientist at Sunnybrook Hospital is investigating the connection between genetics in sleep and circadian biology, using a combination of mathematical models and statistical genetic tools. The IMS Magazine sat down with Dr. Lim to learn how his interest in sleep medicine evolved, and the implications of his current work. Could you begin by talking a little about your personal background, where you grew up and your early education? I completed my undergrad at the University of British Columbia, where I
14 | IMS MAGAZINE SUMMER 2016 SLEEP
majored in microbiology and immunology. I then came to Toronto for medical school, and that was the beginning of my eventual affair with neuroscience. My interest in sleep medicine developed during my neurology residency, through the work I did with Drs. Brian Murray, Richard Wennberg, and Andres Lozano. Thereafter, I ended up at Harvard for more clinical and research training. What was your thesis on and how did you decide on it? The thesis evolved in an odd way. Clif [Saper], my supervisor, had an ongoing collaboration with some folks in Chicago who had postmortem brain tissue and actigraphy data from Alzheimerâ€™s
You can’t actually know where your career is going to go and it’s very difficult to plan. So it’s good to be in a place where you are surrounded by helpful people.
patients. Although the actigraphy data was being collected for other reasons—specifically, to measure physical activity—Cliff wondered if we could obtain some useful information about sleep architecture and its relationship to sleep circuitry. The original project centered on the ventrolateral preoptic nucleus, and, as you know in rodents, lesions of this region lead to a deficit in sleep continuity. However, it wasn’t clear what the best actigraphic correlate of sleep fragmentation was going to be in these patients; after all, we didn’t have any EEG data. With the help of some folks at the Rey Laboratory, we developed a mathematical model. In the end, the thesis ended up being three papers. There was a paper on the development of the mathematical technique, one on the correlation between the actigraphy and cell counts, and there was a paper correlating the actigraphy to cognitive outcomes. What was it like to work with Clif? Well, it was a wealth of opportunity. Clif runs a very productive lab, and he was an absolutely fantastic mentor, not just from a scientific perspective but also, from a career development and career advice perspective. His group is extremely well funded, so if ever something was needed, it was ordered. If you needed computing resources, you got it. If you needed mentorship in x, y, and z, you got it. People are very receptive to an email from Clif— it kind of solved your problems.
on statistical and human genetics. Third was meeting Philip De Jager, a neurologist who also happens to be an expert in statistical genetics. David Bennett, the person who runs the cohort in Chicago, started a collaboration with Phil to explore the genome of the Alzheimer’s cohort and the thought sort of came as to whether we could take the actigraphy data and look for genetic influences. So under David and Phil’s guidance, I developed an algorithm to extract information about circadian rhythmicity from the actigraphy and genotype data. Could you talk about the work your group does now? There are three main things we do. One of the projects we have funded asks the question, what are common gene variants associated with various sleep and circadian phenotypes? Our target is a recruitment of 4,000 middle-aged folks in Ontario, 1,000 folks in their 20’s and 30’s from De Jagger’s group, and a collection of elderly people from the Chicago group. The plan is to genotype all of them and get actigraphy data, with the hope of identifying genes associated with sleep and circadian biology. The other part is taking a look at circadian rhythms of gene expression and epigenomic modification, using mathematical modeling. We also have another project applying machine learning approaches to the analysis of human EEG data. The goal is to automate, to the greatest extent possible, the capacity to do large-scale analysis of human EEG data for research and clinical purposes.
What got you interested in circadian biology?
Where do you see the field going in the next few years?
It was very roundabout, but there are three things. The first thing was the seminar series on sleep biology and circadian biology I regularly attended as a graduate student. The other thing was the coursework—for various reasons, it was heavy
I think it’s difficult to talk about one direction that circadian biology is going. Certainly one thing is the idea of personalized, circadian biology-driven medicine—that through genetics, we could use information on individual
variations in sleep and circadian traits to inform decisions from a clinical and occupational health perspective. There are also benefits from a chronotherapeutic perspective; if you know that drug X targets channel Y, but that channel Y is expressed preferentially at certain times of the day, then it makes sense to administer drug X when channel Y is expressed rather than when it’s down-regulated. This is particularly important when you have medications with short half-lives. The other big thing is to understand how circadian biology influences risk for diseases. If you take a look at something like stroke risk, you’ll see a peak of stroke risk at a certain time, and a trough of stroke risk at another. If you were to take this profile of stroke risk and figure out what is causing this peak at a certain time and beat it down, so that the entire day you just had your baseline stroke risk, you could have a substantial impact on overall stroke risk. The change between peak and trough is by definition dynamic and temporary, so it may be a much better target for intervening then what causes the baseline level. Do you have any advice to share for newcomers in the field? Find out the great people who are doing exciting work in the field and who are going to teach you good techniques. You want good scientists who will teach you useful things, and to some degree, open doors for you from a mentorship perspective. These are all important things to look for when you’re making a decision on where to go. I think this is true for two reasons. You can’t actually know where your career is going to go and it’s very difficult to plan. So, it’s good to be in a place where you’re surrounded by helpful people; it makes random good things more likely to happen, and when the random good things happen, it makes it much easier to take advantage of them. IMS MAGAZINE SUMMER 2016 SLEEP | 15
ONE MORE REASON TO GET A GOOD NIGHT’S SLEEP
OF SLEEP & By Beatrice Ballarin
hy do we sleep anyways? Scientists don’t have a satisfying answer to this question. Sleep is a complex and mysterious phenomenon, or at least it is to many people. Assuming that we’ll be living a long and (hopefully) happy life until we are 90 years old, we will have spent a total of 32 years sleeping. Aristotle, the father of logic, was the first to attempt an answer to this question in his work, On Sleep and Sleeplessness, from 350 B.C.. He considered sleeping merely a passive state, defined as an unremarkable and unimportant period that lacked the ‘sense of perceptions,’ the lack of awareness into the world. Surprisingly, in this current time, our perception of sleep has not changed that much from Aristotle’s view. We seem to have forgotten the importance of a good night’s sleep. Is sleep overrated? When the hours of the day are not enough to conclude our work, staying up late seems to be a good solution; as a result, we deprive ourselves of adequate sleep. Why do we sleep, anyways? It seems like such an unproductive use of time. Couldn’t we just stay awake and do some work? 16 | IMS MAGAZINE SUMMER 2016 SLEEP
Nevertheless, some hours every night have to be dedicated to the act of sleeping. While our perception of sleep has not changed much since Aristotle’s time, our understanding of its functions has evolved. Sleep likely has multiple functions. An increasing area of interest in neuroscience is the link between sleep and memory, as anyone who has ever had a sleepless night knows it can ruin the capacity to retrieve information. From a synaptic point of view, sleep allows synaptic consolidation and strengthening of the connections among neurons, making it critical to plastic remodeling to occur within the neural circuits.1 If it is true that sleep results in the processing of information acquired while awake, then in theory it should be possible to detect some sort of neuronal firing during sleep. An intriguing study published in Science attempted to address this question by recording from single neurons in songbirds.2 Yes, songbirds. By recording neurons in the forebrain region that is involved in the production of the song, the group, led by Dr. Margoliash, was able to show that the timing and structure
of the firing pattern elicited by the playback of the song during sleep matched the activity during the daytime singing. It was as if the song-producing circuits were unconsciously and spontaneously rehearsing these patterns while sleeping. Historically, REM (rapid eye movement) sleep, the stage of sleep where we dream the most, has been linked to spatial and emotional memory consolidation. However, whether REM sleep plays a direct role in memory consolidation remains controversial. The influence of REM sleep on memory has been hard to study because of the transient nature of REM sleep and the devastating effect of sleep deprivation experiments. However, Richard Boyce and his colleagues at McGill University have recently taken a novel approach to establishing this link.3 Using optogenetics in mice, they were able to interrupt REM sleep by reducing theta wave oscillation in the cortex and hippocampus (the main memory structure in the brain) during REM sleep without disturbing sleeping behavior. When they looked into the animal’s spatial memory ability,
those with undisrupted REM sleep spent more time exploring an object moved to a novel location than an unmoved object, while mice with disrupted REM sleep seemed to not remember the objects’ earlier positions. And that’s not it. Surprisingly, the mice with disrupted REM sleep lose their natural preservation instinct, showing fewer signs of fear in a place where they had previously received electric shocks during a fear conditioning experiment. Interfering with theta waves during other stages of sleep didn’t cause the same memory dysfunction, conferring to REM sleep this unique role of memory consolidation. Magical things happen at night, especially during REM sleep. Another innovative concept that attempts to explain why we sleep is based on the “aggregation theory.”4 Let’s take a step back: it is known that one of the main pathologies that characterizes Alzheimer’s disease (AD), one of the most pervasive and debilitating forms of dementia, is the aggregation of amyloid-β (Aβ) in the extracellular space, predominantly in the cortex. It is also known that clinical
symptoms present 10 to 15 years later and by that time, there is already a consistent neuronal and synaptic loss. An interesting set of experiments conducted by Holtzman and his colleagues at Washington University have shown that in a mouse model of AD the sleep-wake cycle was disrupted once Aß plaques formed.⁵ They were able to rescue the normal sleep pattern by eliminating the plaques, suggesting that plaque formation was somewhat responsible for the sleep disturbances. Could this suggest that sleep disruption might be a risk factor for developing Aβ deposition and possibly AD? Can sleep disturbance be an early marker for brain changes? One thing is for sure: Aβ aggregation may cause sleep disturbances long before the clinically-detected AD symptoms.⁶ Early detection of these sleep disturbances could potentially delay the onset of the symptoms of dementia.⁶ This study builds on previous work regarding memory consolidation, leading toward a new understanding of why we sleep: to clear potentially toxic proteins from the brain.
Although these studies only address a few aspects of sleep, scientists have made tremendous strides in discovering what happens while we sleep and what mechanisms are involved. This is definitely not the end of this chapter, leaving space for generating new knowledge about this essential part of life that we spend silent, still, and dreaming. In Italy, we have a saying: “La notte porta consiglio” (“the night will carry advice”). So let’s sleep on this one. Sleep well.
References 1. Diekelmann, S. & Born, J. The memory function of sleep. Nat. Rev. Neurosci. 11, 114–126 (2010). 2. Dave, A. S. & Margoliash, D. Song replay during sleep and computational rules for sensorimotor vocal learning. Science 290, 812–816 (2000). 3. Boyce, R., Glasgow, S. D., Williams, S. & Adamantidis, A. Causal evidence for the role of REM sleep theta rhythm in contextual memory consolidation. Science 352, 812–816 (2016). 4. Lucey, B. P. & Holtzman, D. M. How amyloid, sleep and memory connect. Nat. Neurosci. 18, 933–934 (2015). 5. Kang, J.-E. et al. Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science 326, 1005–1007 (2009). 6. Mander, B. A. et al. β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nat. Neurosci. 18, 1051–1057 (2015).
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FEATURE Photo credit Sam Holmes
You had me at...
CAFFEINE By Meital Yerushalmi and Jonathon Chio
ethyltheobromine, otherwise known as caffeine,1 is a central nervous system stimulant and the world’s most popular drug. In its pure form, caffeine is a white, bitter-tasting powder,2 which lends its psychoactive properties to many popular foods and beverages. Naturally found in the leaves and seeds of various plants, caffeine sources include coffee beans, cocoa beans, kola nuts, tea leaves, yerba mate, and guarana.3 Caffeine is also added to some prescription and over-the-counter medications, including cough, cold, and pain remedies.2 While caffeine is a popular drug engrained in our culture, its use as a stimulant and a social drink is not unique to modern 18 | IMS MAGAZINE SUMMER 2016 SLEEP
times and dates centuries back. Yet, the abundancy of caffeine-containing plants around the world makes it challenging to pinpoint its origins.4 In Arabia, caffeine was discovered in the coffee bean (Coffea arabica), while in China, it was found in the tea leaf (Thea sinensis). In West Africa, caffeine was discovered in the kola nut (Cola nitida), and in Mexico, it was found in the cocoa bean (Theobroma cacao). Interestingly, the etymology of the word coffee originates from Arabia, where “qahwah” (coffee) translates to “a drink made from plants.”5, 6 A famous tale recounts the discovery of the stimulant properties of caffeine, dating back to 850 AD Egypt, where an Arabic goat herder named Khaldi shepherd his flock. One night, Khaldi’s goats didn’t return home and he found them dancing around a shrub of red berries, which were actually
coffee beans. When he consumed the beans himself, Khaldi also began to dance.6
The first cultivation of coffee beans and subsequent production of coffee are likely traced to 15th century Ethiopia.6, 7 Popularized for its stimulatory effects, coffee quickly spread to Yemen, Turkey, and Europe. By the 17th century, coffee was introduced to the Western world. In Yemen, coffee was used to facilitate all-nighters centuries ago, as its wakepromoting qualities were cleverly exploited for religious purposes. According to a local legend, the abbot of a Yemenite monastery prescribed coffee to facilitate his monks’ nighttime prayers.8 Remarkably, since coffee and caffeine have been introduced to the Western world, they have become an integral component
FEATURE of everyday culture and one of the most important commercial commodities. In fact, coffee is the world’s second most valuable traded commodity following petroleum,9 with an annual consumption of 120,000 tons of coffee worldwide.10 Americans consume 146 billion cups of coffee per year, making the United States the leading consumer of coffee worldwide,11 while Canadians follow with an annual consumption of 2.1 billion servings.12 Coffee represents 75% of all the caffeine consumed in the United States,11 and it is estimated that 85% of Americans consume at least 1 caffeinated beverage per day.13 Surely, America Runs on Dunkin.
How much caffeine is in your favorite drink? Hortons: medium 200 mg Tim coffee large brewed 180 mg McDonald’s: coffee Hortons: large ice 150 mg Tim cappuccino venti, mochaflavoured frappuccino 140 mg Starbucks: Horton’s: medium Earl 70 mg Tim Grey tea 70 mg Red Bull: can 15
The caffeine content of coffee depends on its method of preparation. Yet, regardless of technique, caffeine is broken down into more than 25 metabolites in humans.18 The metabolizing efficiency of caffeine is dependent on multiple individual factors, including genetic polymorphisms, weight, sex, and presence of hepatic diseases, as these factors affect the availability of caffeine-metabolizing enzymes and the concentration of caffeine receptors.13 But how does caffeine exert its effects? Three main theories have been proposed to explain the mechanism underlying the physiological effects of caffeine. First, the calcium mobility theory proposes that caffeine, an inotropic agent (compound capable of altering force and nature of muscle contractions), indirectly increases the influx of calcium into the cells. This causes an increase in the force of cardiac muscle contraction and cardiac output.10 Second, the phosphodiesterase inhibition theory proposes that caffeine inhibits phosphodiesterase, the enzyme
that degrades cyclic AMP (cAMP).19 Additionally, consumption of caffeine has been shown to raise plasma levels of catecolamines, which increase cAMP by activating adenylate cyclase.19 Subsequently, there is an increase in cAMP and cAMP-dependent protein kinases, which promote glycogenolysis and lipolysis.19, 20 However, it is now recognized that the concentrations of caffeine required for both these proposed mechanisms are very high and not likely reached in clinical or social doses. Subsequently, a third mechanism has been proposed whereby caffeine antagonizes adenosine receptors. Adenosine is an endogenous nucleoside and a neuromodulator derived from the breakdown of adenosine triphosphate (ATP), which mediates CNS depression and produces sedation.21 Caffeine is structurally similar to adenosine and competitively inhibits its binding to receptors, thereby blocking its effects.10 By this action, caffeine opposes the sleeppromoting effects of adenosine.22 In low to moderate doses (20-200 mg), caffeine produces subjective effects of increased sense of well-being, alertness, energy, concentration, self-confidence, motivation for work, and desire to talk to people.23 Peripherally, caffeine stimulates cardiac muscle, relaxes smooth muscle, and increases gastric secretions and diuresis.24 Yet, high doses of caffeine (800-1500 mg) may cause restlessness and nervousness, diuresis, gastrointestinal disturbance, hypertension, insomnia, cardiac arrhythmias, delusions, and psychosis.24, 25 In addition to its physiological properties, a discussion about caffeine is not complete without a consideration of its profound social and cultural roles. Social gatherings often involve coffee, giving rise to the many chains of coffee shops we are all familiar with. The combination of their pleasant background music, dim lighting, smell of freshly-ground coffee,26 and of course, the caffeinated beverage (and free Wi-Fi) make coffee shops the location of choice for many business meetings, study sessions, and even dates. Underlying its role as a social lubricant27 is caffeine’s aforementioned effect of increasing one’s desire to talk to people, an interesting tidbit you may recall when you next reconnect with a childhood friend over a cup of coffee.
References 1. Compound Summary for CID 2519: Caffeine. [Internet]. National Center for Biotechnology Information, U.S. National Library of Medicine. Available from: https://pubchem.ncbi.nlm.nih.gov/ compound/2519. 2. Caffeine. Toronto, ON: CAMH - Centre for Addiction and Mental Health; 2011 . Available from: http://www.camh.ca/en/hospital/health_information/a_z_mental_health_and_addiction_information/caffeine/Pages/default.aspx. 3. Food Sources of Caffeine. Toronto, ON: Dietitians of Canada 2014 [cited 2016]. Available from: http://www.dietitians.ca/Your-Health/ Nutrition-A-Z/Caffeine/Food-Sources-of-Caffeine.aspx. 4. Persad LA. Energy drinks and the neurophysiological impact of caffeine. Front Neurosci. 2011;5:116. 5. Cappelletti S, Piacentino D, Sani G, et al. Caffeine: cognitive and physical performance enhancer or psychoactive drug? Curr Neuropharmacol. 2015;13(1):71-88. 6. Fredholm BB. Notes on the history of caffeine use. Handb Exp Pharmacol. 2011(200):1-9. 7. Carman AJ, Dacks PA, Lane RF, et al. Current evidence for the use of coffee and caffeine to prevent age-related cognitive decline and Alzheimer’s disease. J Nutr Health Aging. 2014;18(4):383-92. 8. Nehlig A, Daval JL, Debry G. Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Brain Res Rev. 1992;17(2):139-70. 9. Coffee in the Global Economy. San Francisco, CA: Global Exchange; 2011 [cited 2016]. Available from: http://www.globalexchange.org/ fairtrade/coffee/faq. 10. Weinberg BA, Bealer BK. The world of caffeine : the science and culture of the world’s most popular drug. New York: Routledge; 2001. xxi, 394 p. p. 11. Coffee Statistics Report 2014 Edition. Vancouver, WA: Coffee Statistics 2014. Available from: http://www.coffee-statistics.com/ coffee-statistics-report.php. 12. Decline in Java Consumption Speaks to Shifting Habits of Canadians. Toronto, ON: The NPD Group, Inc.; 2015 [cited 2016]. Available from: https://www.npdgroup.ca/wps/portal/npd/ca/news/ press-releases/whats-in-your-coffee-mug/. 13. Clark I, Landolt HP. Coffee, caffeine, and sleep: A systematic review of epidemiological studies and randomized controlled trials. Sleep Med Rev. 2016. 14. Nutrition by the Cup: Starbucks Coffee Company; 2011. Available from: http://globalassets.starbucks.com/assets/7cd1d989cd0c4ddba75b22d53f7af8bc.pdf. 15. Tim Hortons - Caffeine Content. Oakville, ON: Tim Hortons Research and Development; 2015. Available from: https://www. timhortons.com/ca/en/pdf/CAFFEINE_CONTENT_-_Canada.pdf. 16. McCafe Coffee Caffeine Content: Exis; 2015. Available from: http:// www.caffeineinformer.com/mccafe-coffee-caffeine-content. 17. Caffeine Content of Food & Drugs Centre for Science in the Public Interest 2014. Available from: http://www.cspinet.org/new/cafchart. htm. 18. Echeverri D, Montes FR, Cabrera M, et al. Caffeine’s Vascular Mechanisms of Action. Int J Vasc Med. 2010;2010:834060. 19. The effect of caffeine ingestion on exercise performance. Department of Kinesiology and Health Education. Austin, TX: The University of Texas at Austin. 20. Metabolism of Caffeine. Newark, DE: University of Delaware 2011 [cited 2016]. Available from: http://udel.edu/~danikoll/metabolism. html. 21. Bryant B, Knights K. Pharmacology for Health Professionals, 3rd ed. . Chatswood, NSW: Elsevier; 2011. 22. Morin CM, Espie CA. The Oxford handbook of sleep and sleep disorders. Oxford: Oxford University Press; 2011. 23. Griffiths R, Juliano L, Chausmer A. Caffeine pharmacology and clinical effects. In: Graham AW, Schultz TK, Mayo-Smith M, editors. Principles of addiction medicine. 3rd ed. Chevy Chase, MD.: American Society of Addiction Medicine; 2003. p. 193–224. 24. Abou-Donia MB. Mammalian toxicology. Chichester, West Sussex: John Wiley & Sons; 2015. 25. Diagnostic and statistical manual of mental disorders DSM-5. Washington, D.C.: American Psychiatric Association; 2013. Available from: http://psy-gradaran.narod.ru/lib/clinical/DSM5.pdf. 26. Stewart L. Ask In Your Face. 2011 [cited 2016]. Available from: http://askinyourface.com/2011/02/05/is-our-culture-obsessed-withcoffee-and-its-social-aspects/. 27. Rashid S. Ezine Articles. 2008. Available from: http://ezinearticles com/?Wake-Up-And-Smell-The-Coffee&id=910418.
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Photo courtesy of iStock
How’s your Hypothalamus Doing? By Jonathon Chio and Fadl Nabbouh
oogle dictionary defines sleep as, “a condition of body and mind such as that which typically recurs for several hours every night, in which the nervous system is relatively inactive, the eyes closed, the postural muscles relaxed, and consciousness practically suspended.” While it is unknown why we sleep, sleep increases our cognition and well-being.1 Multiple theories have aspired to explain why we sleep; indicating that sleep 1) keeps organisms out of danger, 2) allows organisms to conserve energy, 3) allows the body to repair, and 4) permits the brain to consolidate neuronal networks. Despite the benefits of sleep, uncontrolled 20 | IMS MAGAZINE SUMMER 2016 SLEEP
occurrence of sleep is debilitating. An inability to regulate sleep and wakefulness is a layman description of narcolepsy, a neurological disorder with relatively unknown etiology that typically starts at age 15 to 25; affecting 1/2000 individuals and both genders equally.2,3 Narcolepsy affects regions of the brain that regulate sleep-wake cycles,4 and its symptoms decrease the patients’ quality of life (QOL). Two main symptoms are excessive daytime sleepiness and cataplexy; both of which are associated with occurrence of positive emotions. The former is described as sudden bouts of sleep that last between
a few seconds to several minutes, while the latter is a sudden loss of muscle control despite maintaining consciousness. Other indications are associated with abnormal occurrence of rapid-eye movement (REM) sleep; including hallucinations, microsleep, night-time wakefulness, and sleep paralysis. Although the severity of symptoms decreases over time, patients’ QOL suffer due to the associated complications in all facets of their lives. Increased frequency of sleep episodes and cataplexy, render patients susceptible to physical harm, obesity, and traffic accidents. The latter is of particular concern, as according to a study conducted by the University of Maryland,
FEATURE over 75% of patients report falling asleep behind the wheel and 56% report being almost involved in an accident.5 Furthermore, narcolepsy patients exhibit decreased cognitive function and greater depression. Establishing a cause-and-effect relationship between narcolepsy and these factors is challenging. Research on narcolepsy etiology has been centered on major neurotransmitters involved in sleep regulation, one of which is orexin (OX)/hypocretin (HCRT). Differences in nomenclature can be attributed to the same neurotransmitter having been discovered by two independent laboratories.6 While the terms are interchangeable, HCRT will be used for the rest of this article. HCRT is generated from enzymatic processing of prepro-HCRT to yield HCRT1 and HCRT2, of which the latter plays a dominant role in sleep regulation.6,7 HCRT-secreting neurons are found in the posterolateral hypothalamus and project to a variety of neuronal networks. These networks include cholinergic and gamma-aminobutyric acid (GABA)ergic networks, which then project to the cortex, thalamus, and brain stem.6,8 Generally, cholinergic systems promote wakefulness, while GABA-ergic systems favour sleep.6 Moreover, HCRT regulates other physiological functions, such as thermal regulation, metabolism, feeding, autonomic tone, pain sensation, and addiction.8,9 Pre-clinical animal models have been a valuable research tool to understand narcolepsy etiology and develop treatments. These models can naturally develop narcolepsy or be genetically modified to exhibit the narcoleptic phenotype.9 These data indicate that a deficient HCRT system leads to imbalance between cholinergic and GABA-ergic systems; thus, causing inappropriate transitions between wakefulness and sleep.6,7,10 However, clinical translation of these results are mediocre. Similar to pre-clinical models, narcoleptic patients exhibit a dysfunctional HCRT system by losing 90% of HCRT-secreting neurons and having very low levels of HCRT in their cerebrospinal fluid (CSF). However, unlike patients, most animal models are caused by deletion or mutation of genes for HCRT and its receptor (HCRTR).7
Although no distinct genetic mutations have been found in human narcolepsy to date, there is still a modest genetic component.9 While first degree relatives of narcoleptic patients have about a 1% chance of developing the disorder, there is a 0.1% chance in people without an affected first degree relative. Unique to humans is the relationship between autoimmunity and narcolepsy. Genome-wide association studies have linked narcolepsy to polymorphisms occurring in regions rich with immunologically relevant genes.7 Further, there is higher prevalence of narcolepsy after HIN1 vaccine administration. A protein present in the H1N1 vaccine has been identified to cross-react with the HCRTR antigen;11 potentially tricking immune cells to destroy host neurons containing HCRTR. However, since autoantibodies that are unique to narcoleptic patients have not been discovered, further research is warranted to explore the relationship.7,8 Similar to determining narcolepsy etiology, diagnosis of narcolepsy is also difficult. While excessive daytime sleepiness is a prominent symptom, it is also suggestive of various sleep disorders, depression, and epilepsy. Relative to other sleep disorders, cataplexy is unique to narcolepsy and is often recognized by the physician as the telltale sign of narcolepsy.4 Occurrence of cataplexy is often used as a reason to conduct additional testing, such as analysis of CSF hypocretin levels, as low levels may be indicative of narcolepsy. Other tests that can be conducted are nocturnal polysonogram and multiple sleep latency test (MSLT), which tests brain activity during sleep and amount of time it takes a patient to fall asleep respectively. For a narcoleptic patient, results of their polysonogram and MSLT will demonstrate that a patient enters REM sleep rapidly. Finally, doctors may also implement an Epworth Sleepiness Scale, where a high score may suggest narcolepsy in a patient.12 The majority of the clinically available treatments devised to date are stimulants with arousing effects.8 As these compounds combat against the symptoms of narcolepsy, they are arguably inefficient. However, preclinical data of treatments that target known causes of narcolepsy is promising. Given that HCRT system deficiencies can explain various aspects of
narcolepsy, HCRT replacement therapy is a viable option. Delivery of HCRT can be achieved by intranasal, intravenous, intracisternal, or intracerebroventricular modes of administration while more targeted and specific techniques include transplantation of hypocretin-secreting neurons developed from pluripotent stem cells and recombinant adeno-associated viral vector based delivery of HCRT gene.11 However, as HCRT controls multiple physiological functions, a critical pitfall of this therapy is the potential of adverse and unforeseen side effects. In summary, preclinical animal models and clinical studies have sparked a surge of research that has substantially improved our understanding of narcolepsy. Through identifying the importance of HCRT and exploring possible roles of genetics and autoimmunity in etiology, these discoveries have led to some success in diagnosis and treatment. However, our premature understanding of narcolepsy continues to hinder us from effectively treating the root cause(s). As HCRT plays key roles in sleep-wakefulness regulation and other physiological processes, stronger understanding of the HCRT system has twofold benefits. It can resolve existing barriers in narcolepsy research, and perhaps most importantly, expand our knowledge regarding the networks active in a healthy brain. References 1. Why Do We Sleep, Anyway? [Internet]. Healthysleep.med.harvard. edu. 2016 [cited 14 May 2016]. Available from: http://healthysleep. med.harvard.edu/healthy/matters/benefits-of-sleep/why-do-wesleep 2. Siegel J. Narcolepsy. Cell. 1999;98(4):409-412. 3. Chemelli R, Willie J, Sinton C et al. Narcolepsy in orexin Knockout Mice. Cell. 1999;98(4):437-451. 4. Nishino S, Okura M, Mignot E. Narcolepsy: genetic predisposition and neuropharmacological mechanisms: REVIEW ARTICLE. Sleep Medicine Reviews. 2000 Feb 29;4(1):57-99. 5. Narcolepsy [Internet]. umm.edu. 2012 [Cited 14 May 2016]. Available from: http://umm.edu/health/medical/reports/articles/ narcolepsy 6. Cao M and Chow M. The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress. Nature and Science of Sleep. 2016;:81. 7. Mahlios J, De la Herrรกn-Arita A, Mignot E. The autoimmune basis of narcolepsy. Current Opinion in Neurobiology. 2013;23(5):767773. 8. Burgess C and Scammell T. Narcolepsy: Neural Mechanisms of Sleepiness and Cataplexy. Journal of Neuroscience. 2012;32(36):12305-12311. 9. Bear M, Connors B, Paradiso M. Neuroscience. Philadelphia, PA: Lippincott Williams & Wilkins; 2007. 10. Black S, Yamanaka A, Kilduff T. Challenges in the development of therapeutics for narcolepsy. Progress in Neurobiology. 2015. 11. Elliott LSwick T. Treatment paradigms for cataplexy in narcolepsy: past, present, and future. Nature and Science of Sleep. 2015;:159. 12. Symptoms and Treatment of Narcolepsy [Internet]. helpguide.org. 2016 [Cited May 14 2016]. Available from: http://www.helpguide. org/articles/sleep/narcolepsy.htm
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Dr. Richard Horner By Melissa Galati
hen I sat down with Dr. Richard Horner, I was expecting to gain some muchneeded advice on a better night’s sleep. While much of our conversation revolved around his research—Dr. Horner is a Tier 1 Canada Research Chair and leading
scientist in sleep physiology—we also discussed the importance of knowledge translation in science, and common hurdles faced by graduate students. Dr. Horner obtained his Bachelor’s degree in physiology at the University
Richard Horner, PhD Professor, Department of Medicine, University of Toronto Professor, Department of Physiology, University of Toronto Canada Research Chair in Sleep and Respiratory Neurobiology Member, Institute of Medical Science, University of Toronto 22 | IMS MAGAZINE SUMMER 2016 SLEEP
of Sheffield in the United Kingdom. Following his passion for physiology, he accepted a PhD position at the University of London in one of the United Kingdom’s first sleep laboratories. In this setting, Dr. Horner not only gained research training, but also obtained many years of clinical experience in sleep physiology. He went on to complete two post-doctoral fellowships; first, at the University of Toronto (U of T) and then at the University of Pennsylvania, where he engaged in basic neuroscience research—the basis of his work today. He then returned to U of T to accept a faculty position in the Department of Medicine with an appointment in the Institute of Medical Science (IMS) and cross-appointment in the Department of Physiology. Having been a member of IMS for almost two decades, I wondered how Dr. Horner’s research had changed over the course of his career. He offered some advice to those striving for a career in academia. “The first thing you have to do when you start a faculty career is focus… You commit to what you can do and try to publish papers.” He concedes that the high competition and uncertainty that comes with research can sometimes stifle innovation. Much of Dr. Horner’s early research focused on more specific aspects of sleep and breathing, but with greater long-term support, he was able to take more risks and diversify his research. He now asks more fundamental questions regarding the generation of sleep, the mechanisms of anaesthesia, and the effects of sedating drugs and painkillers on brain and respiratory function. “[Research] is
Debunking the “Mystery” of Sleep like investments. If your portfolio is too focused, you’re vulnerable if something ever goes wrong. But if it’s too diverse, you’re not really going to gain anything. It’s a question of keeping your eye on what you perceive to be important and having the courage to invest your funds in the people and infrastructure to get it done.” As I asked Dr. Horner what he believed to be his most significant scientific contribution, his wry smile suggested I might be asking the wrong question. “I guess the easy answer is that when we started, there was a lot of clinical observation about breathing that becomes impaired during sleep. But there was no science that could explain what was going on in the brain that causes the change in physiology that ultimately predisposes to the problem… we have provided that knowledge.” Dr. Horner adds that much of his efforts are now also focused on knowledge translation. “In reality, all the work that we do is funded by the people surrounding us. I think it’s a duty to translate that knowledge in some way.” In fact, Dr. Horner has written a book on the evolution of sleep entitled, The Universal Pastime: Sleep and Rest Explained. “[My] motivation for the book was that I got so tired of hearing that sleep is a mystery. It’s nonsense to keep perpetuating this myth… We’re in a cloud of so much information... sometimes the hardest thing to do is to step back, look at the information, and [say] “it’s not that complicated.” Dr. Horner points out that, in research, while we are always striving to push the boundaries of knowledge, consolidating the information to make it accessible often takes more time than we are prepared to invest.
Dr. Horner’s book is primarily focused on the principles of evolution and answers questions such as “how is life organized?” and “why would twenty-four hours of circadian biology emerge?” The book looks at separating the real purpose of sleep from those activities that merely occur during sleep; for example, activities, such as growth and repair, are often cited as reasons for why sleep is important, but, in reality, sleep exists for the simple reason that it makes us better at being awake. We know that our genes are a way for biology to prime an organism to be fit in its environment, however, as we interact with the environment, the connectivity of the brain changes. This plasticity enables the brain to better interact with the environment. “That’s an incredibly powerful thing,” remarks Dr. Horner. “The only thing you need is for natural selection to select for the ability of the brain to change. And by doing so, you have an organism that can adapt…it can discover the things that help it survive…Sleep enables that process [of restructuring]. This is why organisms all over the planet have found this solution for life—because it boosts their ability to adapt and behave.” Looking toward the future of sleep research, Dr. Horner remarks that there is an increased awareness of the importance of sleep health—alongside nutrition and exercise—to human health more broadly. He specifically points to mechanisms of circadian biology and understanding the powerful influence of 24 hour rhythms on health as a major growth area in medical research, as well as understanding the role of sleep in optimizing and perhaps treating the growing burden of mental health problems.
In addition to engaging in outreach activities, Dr. Horner is incredibly committed to mentoring students, receiving numerous awards for excellence in teaching at both the graduate and undergraduate level. “I take the experience of graduate students very seriously and I think it’s the elephant in the room that obtaining a graduate degree is not always a great experience for trainees.” He cites several reasons for this. “I think a lot of trainees go into research without really knowing what it is or having a passion for it.” The perception in today’s world, he points out, is that in order to do well, you need to have a graduate degree and, for some, that is the main motivation rather than the research. “The second side of the equation is that not all supervisors are sufficiently caring [for] or mentoring their trainees.” On top of this, the many stresses that litter graduate careers are concerning from a mental health point of view. Dr. Horner reflects on a conversation with a colleague who noted that roughly 60% of graduate trainees at his institute have mental health concerns. “I think there are possibly similar numbers here. The people who are in the best position to help trainees… are their supervisors, peers, and graduate units.” His advice for students is to choose their mentors wisely. “They should be looking after your well-being as well as the research.” Second, he encourages students to make sure they enjoy what they do. And finally, he advises students to, “put sleep in its place.” We don’t necessarily need to create rigid schedules for ourselves, but finding sufficient time and placing value in sleep allows us to wake up “at the top of our game,” which, I think we can all agree, is a great feeling. IMS MAGAZINE SUMMER 2016 SLEEP | 23
The Diversity of Z
leep medicine is a rapidly evolving field. In the last half century sleep research has prized open many facets of sleep including why do we need good sleep quality and its connection to the functioning of other body systems. However, many intriguing questions remain and one anticipates a huge increase in the emphasis of sleep medicine in health care and in society in general.
Working in this field we are very enthusiastic about running new research projects to answer the questions about blank spots in sleep medicine.
By Colin Shapiro, PhD, FRCPC Senior Scientist, Krembil Research Institute Professor, Department of Psychiatry, University of Toronto Member, IMS
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We are currently in the midst of an exciting and unique research project in neurophysiology with linkages to senior researchers at St Michael’s Hospital (Toronto). This project “How sleep deprivation affects brain activity during driving in adolescents and young adults” involves a number of facets including participants mental state and sleep quality assessment, polysomnographic sleep evaluation, excessive daytime sleepiness measurement, the evaluation of driving function using a driving simulator, and the measurement of the brain activity by fMRI
while using the driving simulator installed in an fMRI. Sleep deprivation is a major cause of motor vehicle accidents, and can impair the human brain as much as alcohol. It has been estimated that between 16% and 60% of all motor vehicle accidents are caused by poor sleep (resulting in poor attention). Adolescents and young adults frequently have sleep complaints and this study is unique in this population. To give a sense of the range of clinical interest in sleep, another study that we are currently doing involves the sleep problems in patients who have recently had a concussion. This is a common problem and sleep sequelae are one of the key presenting features. In this program, the evaluation of circadian rhythms, which involves the objective measurement of melatonin, a rather bizarre test. One stays up in a dark room from 7 pm until 3 am and provides a saliva sample every hour, from which the melatonin level can be assayed. This allows one to establish if the curve of secretion is normal or not. It is a test that is particularly relevant in adolescents especially those who might be going
Sleep Research Z “
...my answer somewhat facetiously was that in the textbook for physiology that we studied, there was only one paragraph on the subject of sleep and I realized that if I was going to do a research project it would probably be easy to become an expert in sleep more so than in other areas.
to bed late and getting up late, to try and clarify whether the reason is a biological or a behavioral one.
As an indicator of the impact of sleep disorders most people will have heard of “sleep apnea,” where people repeatedly stop breathing in their sleep. Sleep apnea has been linked to many medical problems including myocardial infarction, stroke, glaucoma, diabetes, impotence, and cognitive decline. One project apparently underway is to look at the impact of early treatment of sleep apnea patients diagnosed with arrhythmia to evaluate whether this facilitates improvement in the arrhythmia. Another project underway concerns the best way to treat sleep apnea in patients with glaucoma.
At the start of the modern era of sleep research the field was dominated by psychiatrists who came from a background of an interest in sleep and dreams. The biological shift has seen an evolution in
which respiratory medicine has become a dominant force but there remains much to be learned about psychiatric conditions— almost every one of which will have a sleep consequence. The research here is as diverse as trying to evaluate if there are biological markers of depression in the sleep architecture with some recent successes in this area. There is an increased interest in the issue of suicidality being linked to circadian rhythm disruption and sleep difficulties and an increasing awareness that as with hypertension, if one does not treat a sleep problem in depression one is going to have a much more difficult task in managing the condition. These issues and the question of whether many children are mislabeled with ADHD, but really have a sleep problem, is also being studied.
I have often been asked what caused me to be interested in sleep research for over 45 years and my answer somewhat facetiously was that in the textbook for
physiology that we studied, there was only one paragraph on the subject of sleep and I realized that if I was going to do a research project it would probably be easy to become an expert in sleep more so than in other areas. I think the real reason was that I recognized that there was a huge chasm of unknown information that would probably be very important and it would be a challenging and exciting sojourn to study sleep. This certainly has been the case and I believe it will be in the future. I often comment that about 60-70 years ago, the only people who measured blood pressure were cardiologists and today every family physician will measure blood pressure. I believe the same will happen with sleep. There is currently a relatively small group of sleep specialists who are evaluating sleep in depth, but with the advance of technology this will become a front line activity in family medicine and those in the sleep field would need to “up their game” and deal with more difficult rather than front line issues.
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BIOMEDICAL COMMUNICATIONS MASTER OF SCIENCE IN
Biomedical communications bridges disciplines (art, science, medicine and communication) to develop visual material for health promotion, medical education, and as part of the process of scientific discovery.
Artwork by Diana Grossi, 1T6
26 | IMS MAGAZINE SUMMER 2016 SLEEP
This interactive, illustrated website aims to help primary care providers become more competent in caring for trans and gender-diverse clients. It is the product of a Masterâ€™s Research Project in collaboration with Rainbow Health Ontario, an organization that works to improve the health and well-being of LGBTQ people in Ontario. Project by Kelly Speck, MScBMC Candidate 2016
To learn more please visit www.rainbowhealthontario.ca/ trans-health-connection
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Dr. Andreas Laupacis Executive Director, Li Ka Shing Knowledge Institute, St. Michael’s Hospital Professor, Department of Medicine, Faculty of Medicine, University of Toronto Professor, Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto
here are a few things you need to know about Dr. Andreas Laupacis. The industrious professor of Health Policy and Management at the University of Toronto has a knack for timely publications. Consider these two articles:
We know that not everyone is helped by a drug or therapy—some get benefit, some are harmed, and others are unaffected. In the first publication, Andreas wondered if there was a better way to explain results of clinical trials to doctors and encourage them to base their treatments on good scientific evidence. Following discussions with two other clinical epidemiologists, he published his first principal work: the concept of “numbers needed to treat”, or for short, ‘NNT’.1 The NNT is a meaningful way of expressing the effectiveness of a specific intervention compared with a control. Despite turning 24 this year, this concept continues to be used by clinicians worldwide and has become a vital component in the clinical and research lexicon. The next publication came in an era where economic evaluations and cost effective analyses of health care services were just starting to be produced. Andreas and his colleagues proposed a classification system to evaluate the cost-effectiveness of new technologies based on their methodological rigour and clinical benefit.2 For this 28 | IMS MAGAZINE SUMMER 2016 SLEEP
work and contributions to health policy, Andreas has been recognized nationally and internationally; most notably, he received the 2010 Jill M. Sanders Award of Excellence in Health Technology Assessment, the 2011 Health Services Research Advancement Award, and the 2013 CIHR Barer-Flood Prize in Health Services and Policy Research. Andreas is also known to engage citizens in making decisions about their health and health care. In a Canadian first, he led a team of researchers to identify the most important unanswered questions (or uncertainties) about the management of kidney failure using the James Lind Alliance (JLA) method—an approach that involves patients, their caregivers, and clinicians in determining research priorities. He also founded Healthy Debate (healthydebate.ca), a novel online platform that provides unbiased information about Canada’s health care system to the public. Above all, Andreas is a well-respected general internist who currently practices palliative care at St. Michael’s Hospital. In 2015, he was included in the Medical Post’s “Power List” of the 30 most influential physicians in Canada. Here’s what the Medical Post had to say in September about Andreas: “It would be enough for any clinician with Laupacis’ research smarts to focus on building an ivory-tower career. An internist by training, he has
gone beyond the walls of academe to reach out to the government and the public at large to translate clinical trial results into useful knowledge.” And so, over two separate sessions— because one wasn’t enough—the IMS Magazine spoke with triple-threat physician Dr. Andreas Laupacis to learn more about his early research career, Healthy Debate, and general advice to students. You started as a generalist, and at some point you enrolled in a Masters; do you remember what your MSc was about? I did my Masters pretty early in my career. I took two years off during my residency to work with Calvin Stiller, a transplant nephrologist in London, Ontario. I had the opportunity to be involved in running a randomized trial of Cyclosporin in kidney transplantation, which turned out to be a terrific drug. That turned me on to doing clinical trials and to research actually, but I realized I needed some formal training in research methods and that’s why I went to McMaster at the end of my residency to complete a Masters [in clinical epidemiology]. Could you comment on the major trends in health service and policy research in the past decade? Are there any topics researchers have left behind or not approaching properly?
Photo credit Chung Leung
By Jabir Mohamed
FACULTY SPOTLIGHT Wow—that’s a whole essay on its own! The complexities of doing research about the impact of health system interventions was the topic of a Healthy Debate article – http://healthydebate.ca/2016/03/topic/ health-care-models-evaluation. Speaking of Healthy Debate, what led you to establish it? I was always struck during the time of provincial and federal elections that Canadians would say that one of the most important things driving their vote was their health care system, yet the level and intelligence of discourse about the issues around health care was often incredibly low. I didn’t see a place where non-experts could easily access articles, [specifically ones] that weren’t simplistic. So the goal at Healthy Debate was to provide a thoughtful description of important health care issues that wasn’t excessively oversimplified or too technical. Why the name Healthy Debate? How did you guys come up with that? Honestly, I’m not super good at finding titles but frankly, we did want a healthy debate and it was about health care. However, the tagline—unbiased facts, informed opinions—has its own story worth sharing. I was reading the obituary in the New Yorker of Daniel Patrick Moynihan, a highly respected American politician from New York. The quote if I remember correctly, is that he said, “Everyone is entitled to their own opinions but not their own facts.” And I loved that because the facts are kind of the facts; for example, people in Northern Ontario don’t live as long as people in Southern Ontario, and that’s a fact. What we do about that— the approach to increase longevity—is really informed by opinions, by where someone comes from, and what they think. Staff write the Articles but Opinions can be written by anyone. What should a prospective writer keep in mind if they would like to get published on Healthy Debate? What are the main reasons that an Opinion piece gets rejected? Gets accepted? Two main issues - the topic and the writing. For the topic, it should be one that is of broad interest to readers, including
those who don’t work in health care. An opinion piece about the details of how ophthalmologists are paid compared to how geriatricians are paid might be important to those two specialties, but isn’t a great topic for Healthy Debate. Folks thinking of writing an opinion piece can send us an email and tell us the topic they are thinking of writing about, and we can tell them if it would be of interest. Regarding writing, it’s important that the writing is crisp, clear and not too technical. We do sometimes provide considerable editing to a piece to make it suitable for publication, but sometimes the writing is just too bad for it to ever be publishable. You’ve recently introduced Faces of Health Care to Healthy Debate. What was the inspiration? My wife and I were at the Tenement Museum in NYC and we ended up in their bookstore where I saw the book, Humans of New York (http://humansofnewyork. com). I’m embarrassed to say, but I hadn’t heard of it before and I just loved it as soon as I saw it. I guess what I loved about it was the quality of the photographs, and Brandon Stanton, the author is very good interviewer as well. So, I basically looked at it and thought, “I’d love to do something like this for healthcare in Ontario,” and that was really the genesis of Faces of Healthcare (FOH). Most, if not all Faces featured are remarkable. How do you decide on whom to spotlight? So far, it’s been largely word of mouth. We strive for broad coverage of people and topics; we don’t want to only have faces limited to downtown Toronto, and we don’t want to only focus on specific health care experiences. That’s why we have done interviews in the Ottawa valley, Shawville Quebec and Kingston. Regarding the people we interview, we try to get people who are able to articulate their positive and negative experiences of the health care system. Are there particular faces/scenarios you feel are currently underrepresented and want to give a voice through your platform? We do sometimes look at the site and say whoa, you know, there are whole experiences
we’re missing. As an example, we don’t have a single story on the site that has a First Nation or Aboriginal perspective. So two weeks ago, one of the photographers and I spent two days in Marathon, Ontario, interviewing First Nations people. Similarly, there are very few people from Regent Park [represented on the site] and we’re going to do two interviews with people who have been raised or lived there within the next month. What’s next for Healthy Debate? The website has done us very well for the first four and half years, but I think it’s time for a refresh. It’s also time to integrate the Faces of Healthcare more into the site. We now have the new web site up that allows us to do that. I’d like to see us integrate the FOH into curricula in nursing schools and medical schools across the province. We’ve been supported recently by the Associated Medical Services, which is a group in Ontario that focuses on increasing humanities in medicine at the six medical schools across the province. We’re hoping to work with them to maybe introduce Faces into the curriculum. And finally, a lot of our readers are graduate students who may aspire to drive change in health care one day. Do you have any advice as to how they could get involved in health policy or health service initiatives? I am a clinician, and one of the things I think has made me at least quasi-credible is that I was a pretty decent clinician. This gave me credibility with my colleagues and policy folks, and also gave me all sorts of research ideas from the front lines that I never would have had otherwise. The opportunities to get involved in policy happened gradually and without a lot of planning—they just came up. If the graduate student is a clinician, my first piece of advice is to spend the time needed to become a really good doctor or nurse or physiotherapist—that’s harder to learn than the policy stuff. Not sure I have great advice for the non-clinicians because I am not one. References 1. Laupacis A, Sackett DL, Roberts RS. (1988) An assessment of clinically useful measures of the consequences of treatment. NEJM 318, 1728-33 2. Laupacis A, Feeny D, Detsky AS, Tugwell PX. (1992) How attractive does a new technology have to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations. Can Med Assoc 146(4), 473-81
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Student Spotlight on
JUDY RUBIN Msc Candidate in Biomedical Communications, Institute of Medical Science, University of Toronto
By Sarah Peters
n a field as diverse as science, it is unsurprising that coherent abstracts and unambiguous presentations are necessary to project ideas and results across the multitude of medical disciplines. While Institute of Medical Science faculty and students most often wield Microsoft Office in the pursuit of clear communication, students in the Biomedical Communications department hone their digital fine art skills to convey research in aesthetically pleasing ways. 30 | IMS MAGAZINE SUMMER 2016 SLEEP
Judy Rubin is a student in BMC at the University of Toronto, one of four such programs in North America. Despite being the largest BMC program on the continent, it is home to only 16 students—according to Judy, this is due to the incredibly specialized skillset required of successful applicants. Students in the two-year Masters program take courses in both arts and sciences, including media design and neuroanatomy; additionally, students are exposed to several digital design packages,
may be involved in medical procedure observerships, and eventually complete individual thesis projects. Judy happily explained that she has always been keenly interested in both science and art. Growing up as the daughter of a science-oriented mother, she spent her childhood peering into microscopes and bringing her observations to life not with paper and pencil, but instead with cell stain pigment. This hobby grew into an
Photo credit Meital Yerushalmi
Many Institute of Medical Science students may self-describe as ‘researchers;’ some may identify as ‘scientists,’ while others prefer ‘academic.’ For students in the University of Toronto’s Biomedical Communications (BMC) program, these terms must all be appended with ‘artist.’ Judy Rubin recently completed her first year of BMC and sat down with me to explain her program, pursuits, and inspirations.
STUDENT SPOTLIGHT association that has impacted her academic trajectory: “When you go to the lab, you get to do art.” As a young adult, Judy spent several years pursuing her interests separately. She first attained a biology degree from the University of Maryland Baltimore County and later underwent training at the Schuler School of Fine Arts. This metaphorical tug-of-war was primarily between the “intellectual satisfaction” of biology and the personal indulgence of illustration; when Judy learned about the biomedical communications field, it “perfectly matched [her] passions.”
Spending so many hours transcribing sulci and gyri from a picture prompts an inquiry that is all too familiar to Judy: “A question I get a lot of the time is, ‘Why can’t you just photograph it’?” One of Judy’s main goals is to edit concepts into graphics that are more easily understood than, for example, untouched photographs. As technology continues to advance, she believes more tools will continue to emerge for this type of unique, human-modified communication; specifically, she is interested in interactivity and 3D modeling. These techniques may be particularly salient in coming years as
tech companies roll out interactive virtual reality applications. Although most IMS students will not go on to pursue BMC, it is beneficial to be mindful of the way in which biomedical communicators bridge knowledge as we continue to share our discoveries. Students may find inspiration in a particularly helpful diagram, or perhaps will take the initiative to learn a new digital application to create a figure. As Judy advises, “Don’t be scared to try. If you have a passion, don’t be scared to go for it and follow it!”
Integrating science and art is a responsibility that Judy takes seriously as both student and educator. In her words, the goal of medical illustration is to transform information into visual formats that can be easily communicated to a wide audience. “People assume that you have to be a really good artist. That’s true, but you also [need] to have really good design sense and focus on layout, composition, design, and data visualization.”
Illustration by Judy Rubin
Judy’s insight may not come as a surprise, especially for those with experience designing their own research posters. Judy and her classmates likely have an advantage when it comes to this type of science communication, since they “come from a unique place where [they] can see information and integrate that into visual design.” Biomedical communicators are integral to the way in which scientists and students teach, learn, and share. From textbook images to medical school lessons, the language of science is predominantly visual; this process of translating knowledge into art is quite familiar to students in BMC. Judy begins a typical project as any IMS student would: with research. The type and amount of research varies with the project and could include anything from observing a series of surgical procedures to poring over anatomical details of the cerebellum. Next, artists begin their first drafts—Judy prefers to do this step by hand—and continue to refine images, eventually “cleaning up” the final product in a program like Adobe Illustrator. IMS MAGAZINE SUMMER 2016 SLEEP | 31
Photo credit IMS
IMS SCIENTIFIC DAY
Celebrating Excellence in Research By Melissa Galati
he Institute of Medical Science (IMS) is one of the largest graduate departments at the University of Toronto, fostering multidisciplinary translational research. As members of the department with such a diverse and collaborative research focus, it can be easy to be oblivious to the incredible and groundbreaking research of our peers. For this reason, the IMS annually hosts Scientific Day—the academic highlight of the year. Scientific Day 2016 was presented in collaboration with the Friends of CIHR, the Peter Munk Cardiac Centre, and the Heart & Stroke Richard Lewar Centres of Excellence in Cardiovascular Research. The quality of research presented and energy of both students and faculty were truly inspiring. Students arrived bright and early to set up their posters for the Alan Wu poster 32 | IMS MAGAZINE SUMMER 2016 SLEEP
competition. This year, approximately 90 students participated in the competition, presenting their diverse research to a panel of judges. The winners of the Alan Wu Poster Awards were Angela Brijmohan and Fatima Jessa, with honourable mentions awarded to Laura Best, Megan Hird, Maria Marano, Anuj Rastogi, Usman Saeed, Siraj Zahr, Liane Bailey, Moritz Kaths, Reena Yaman, Trisha Roy, and Andras Fecso.
and failures of regenerating heart tissue after damage. Following the keynote lecture, the six finalists of the Laidlaw Manuscript competition delivered oral presentations of their work. The two winners selected based on the quality of both their manuscript and oral talk were Robert D’Cruz and Vanessa Williams. Other finalists included Ashton Connor, Anna Badner, Mohamad Hussain, and Amy Hyemin Oh.
This year, Dr. Victor Dzau delivered the Bernard Langer Annual Lecture in Health Sciences—the keynote lecture of the event. Dr. Dzau is the President of the National Academy of Medicine (just one of the many positions and honours he holds) and one of the world’s preeminent health leaders. His talk entitled, “Healing and Regenerating Hearts: 21st Century Prometheus,” focused on the successes
A “Lunch & Learn” information session for aspiring IMS students took place where students learned about the exciting programs and research opportunities offered by the department. Finally, following the successful debut at last year’s Scientific Day, students and faculty members took part in three Data Blitz sessions. These breakout sessions occurred concurrently and highlighted
Photo credit IMS
IMS SCIENTIFIC DAY
research in Cardiovascular/Respiratory/ Musculoskeletal health, Population Health/Education, and Neuroscience/ Brain Health. The sessions kicked off with keynote addresses from Dr. Phyllis Billia, Dr. Cynthia Whitehead, and Dr. Richard Horner—all leading scientists in their respective fields—and these were followed by several five-minute presentations from students in each of the three research areas. The Data Blitz presentations provided a more intimate atmosphere to cultivate open conversation between students and faculty. The day concluded with the award presentations. The Whiteside and Siminovitch-Salter Awards are given to recent MSc and PhD graduates respectively, who have made outstanding scholarly contributions. This years winners were Roman Reznikov and
Ashleigh Tuite. The Roncari Book Prize was given to Annette Ye for her outstanding contributions to the academic experience of graduate students—particularly her role as the Editor-in-Chief of the IMS Magazine! Finally, Pratiek Matkar was awarded the Sara Al-Bader Memorial Award, which recognizes an international doctoral-stream student with great academic promise. In addition to recognizing excellence in its students, the IMS also acknowledged several faculty members for excellence in teaching. Dr. Gary Rodin won the Mel Silverman Mentorship Award. The IMS Graduate Course Director and IMS Graduate Course Lecturer Awards were presented to Dr. Jim Eubanks and Dr. SteffenSebastian Bolz, respectively. Finally, as a new addition to the award ceremony, the IMS module Director Award was presented to Dr. Simon Kitto for his
sustained contributions to the development of an IMS module. The success of Scientific Day is a reflection of each and every member of the IMS community. Congratulations to those recognized for their scholarly contributions as well as those recognized for improving the academic experiences of other students! The quality of research presented is a humbling reminder of the hard work and dedication of our peers and mentors each day. We hope that Scientific Day will remain as a day to celebrate and share excellence in research, both for current and aspiring students and faculty members.
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WHO IS A
“TRANSLATOR”? By Joseph Ferenbok, PhD
Joseph Ferenbok, PhD Director, Translational Research Program in Health Science, Institute of Medical Science Co-Director, Health Innovation Hub Assistant Professor, Department of Psychiatry, Faculty of Medicine, University of Toronto Although most people don’t know it, and many that do will deny it, we are in the midst of a revolution—a rethinking of how things are done, by whom they are done, and how people are rewarded. The system is currently broken—how our society (though this is generalizable beyond Canada) uses the niversity and research funding mechanism to drive innovation is increasingly being put under a microscope.
Photo credit: Kelly Speck
From a very high level, the university system and the Tri-Council funding mechanism, to a degree, is supposed to help support the kind of research that does not have the immediate economic benefits to society that other stakeholders may need to support that kind of discovery research. It’s not always the case, but industry generally tries to support R&D that has a high potential for generating revenue. Funding research that generates knowledge for knowledge’s sake is a luxury that most businesses cannot always support. Generating benefits to society in the long-term is really the business of universities and other publically funded research facilities—or at least that’s been established wisdom for some time. To generate new knowledge, governments fund research by various mechanisms that might not otherwise be funded. This machinery is supported by peer review and publications, and the best and the brightest investigators drive knowledge 34 | IMS MAGAZINE SUMMER 2016 SLEEP
production that feeds innovation— changes how we do things, what we do and even when we do it. The currency of this system is publications that are then the basis of more grants and (presumably) more discoveries. Investigators who do not publish, perish—they fail to advance, they fail to attract new students/talent, and they fail to maintain their labs. However, beyond publishing the new knowledge generated, there is often little incentive for researchers to explore ways of implementing the knowledge. Actually spending time to explore how discoveries may be applied takes time away from publication and research. Although some institutions are beginning to acknowledge other performance measures, like patents filed in their promotions, this metric is far from established. (At one institution, when researchers found out that patents were being considered for promotion decisions, there was suddenly a frenzy of frivolous patent filings.) Although there are those ‘super-human’ intellectuals, researchers and innovators who somehow manage to do amazing discovery science and somehow, in their off hours, commercialize ideas, implement policy, and run international corporations, they are few; they are the elite. Not all outstanding researchers, who are producing innovative and meaningful science, are also moguls of industry—or even wish to be. So, if there is this disincentive to step off the
Join us at:
www.TRP.utoronto.ca publication assembly-line, where many of the scientific discoveries published cannot be replicated, and knowledge is created disproportionately to efforts being made to apply it, who are the “translators”? Or, put another way, where do the translators fit in this system? This is where the revolution comes in. I think we are facing a revolution, the development of a new class of scientist, a new type of professional—the applied scientist, the scientific creative professional. This is a kind of person who is familiar with science, trained in the language of science, and a disciple of scientific methods. But this professional is not always found at the bench, conducting experiments, or writing papers. These scientists are different. They use science, they apply science, they spend their time looking at needs, problems, regulation, legal frameworks, and marketing. They are at home reading a journal and they are at home looking at users, customers, and patients. They are bridge builders who currently have no distinct role in our academies of higher learning. They are the entrepreneurs, the networkers, problem-solvers, and risk takers. They are the conduits of innovation, but they are also scientists—they love the science. But they are comfortable being the consumers rather than producers of knowledge. They are the translators. They are found amongst investigators who ‘see’ the big picture, who are somehow able
to understand the needs they are trying to address and the big-picture pathways for moving their discoveries into tangible benefits. These applied scientists are found in a growing class of professionals who apply science, who translate knowledge, who design solutions to existing problems. These are scientists who help communicate the science, not just for audiences of peers, but to physicians, clinicians, patients, and the public; who take knowledge and translate it for consumption by diverse audiences. These people help set policy and influence behaviour. Others still look at the implementation of research, the science of adoption, and effectiveness of new interventions. These are the people who try to learn how to do things better; how to understand the processes of successfully implementing the discoveries for benefit. Some of these people are chameleons, masquerading in labs as quasi-productive academics, but most give up and find ways to help apply science in government, industry, and research administration. What’s more, these translators are starting to build a body of knowledge around the process of translation. This new field of investigation, focused on understanding the scientific and operational principles, suggests that translational projects need not be conducted by trial and error, that perhaps there is a systematic methodology or best practices behind the translation of science, discoveries, and knowledge more generally. At the Translational Research
Program in the Faculty of Medicine at the University of Toronto, we refer to this as Translational Thinking, a systematic experiential approach of mobilizing research towards addressing the health and care needs of individuals and populations. The methodology is patient-centric and forms the underlying structure of the two year Master’s program; and the students in the program, who are themselves working on translational projects are also contributing to the development of the Science of Translation through reflection on and abstraction of their experiences building bridges between cells and society. It’s not likely that translational research will ever reach a point where every attempted project will succeed—just like not every experiment is successful—but through the development of operational practices and a community of highly qualified translators, this growing trend— a necessary one—may become a social imperative not only to fund discovery research, but also to establish ways to encourage and reward the translation of publicly funded research. Though they are not currently given the badges and accolades of those who make discoveries, the translators are the foot-soldiers of innovation, the worker bees whose absence in the current system has created artificial encumbrances to the current mechanism of innovation. They are the new revolutionaries, missionaries for the public good, to translate research into tangible benefits for people. IMS MAGAZINE SUMMER 2016 SLEEP | 35
better safe By Ekaterina An & Meital Yerushalmi
he path to becoming a physician is marked with many important milestones: the White Coat Ceremony, reciting the Hippocratic Oath at graduation, and commencing residency training. This process involves an extraordinary amount of hard work and determination. Yet, integral to the job is an issue that has sparked much controversy over the years: sleep deprivation among resident physicians. We have come a long way since the days resident physicians were, quite literally, residents. In 1889, with the inception of residency training in the United States, residents lived at the hospital and were expected not to marry. William Halsted was one of John Hopkins’ “Big Four” founding professors and became the first chief of surgery in the 1890s. He created the first surgical residency training program in the United States, which required residents to be on call 362 days of the year. However, it was later revealed that he maintained his arduous work schedule with the aid of cocaine. Work ethic aside, the debate continues surrounding the impact of the extensive work hours during residency on patients and physicians alike. The many sacrifices made by physicians to place patient care above all else have fueled their societal image of part martyr, part hero. It may, then, be ironic that at times the prevailing culture among residents of working themselves to the limit seemingly contradicts the cornerstone of medicine, 36 | IMS MAGAZINE SUMMER 2016 SLEEP
primum non nocere: above all, do no harm. Perhaps the most notable case which brought this issue to the headlines was that of Libby Zion. In 1984, the 18-year-old was admitted to the New York Hospital with a fever, agitation, and disorientation. She was evaluated by a resident and an intern, prescribed meperidine, a painkiller and a sedative, and subsequently haloperidol, an anti-psychotic. A few hours later, Zion’s fever became dangerously high and she died of a cardiac arrest.1 When Zion’s father, a columnist for The Daily Times, learned that his daughter’s doctors had been on duty for nearly 24 hours when they evaluated her, and that residents were routinely awake for over 36 hours, he sued the hospital and the doctors, and publicized the circumstances he believed led to her death.2 Subsequently, public awareness increased and reforms followed. In 1989, New York State limited resident work hours to 80 per week, a restriction later imposed by the Accreditation Council for Graduate Medical Education (ACGME) on all US training programs in 2003. The ACGME also prohibited direct patient care after 24 hours of duty, and mandated at least one day off per week.2 While reforms took place widely in the US, Canadian policies remained largely unchanged. The only exception was Quebec, where the Fédération des médecins résidents du Québec (FMRQ) successfully reduced on-call shift hours from 36 to 24 in 1984.3
In addition to sparking reforms to resident duty hours, the Libby Zion case highlighted the presumed dangers of sleepless 24-hour shifts. Her death has encouraged the formation of numerous expert committees, panels, and studies to examine the impact of sleep deprived and fatigued residents on patient safety and physician health. It has been long recognized that sleep plays a key restorative role in maintaining effective neurocognitive performance. Lack of sleep diminishes alertness and neurocognitive function: 24 hours of sleep deprivation led to an impairment of neurobehavioural performance on par with a blood alcohol level of 0.10%.4 Sleep deprivation can also result in a loss of situational awareness, fatigue amnesia, grogginess,4 higher risk of car accidents, hospital-related injuries or infections, and compromised mental health.5 Empirical evidence of the detrimental impact of fatigue and sleep deprivation on cognition supported the argument against extensive resident duty hours. Yet, specific evidence was still needed to demonstrate the impact of sleep deprivation on patient and resident outcomes. The Intern Sleep and Patient Safety Study6,7 set out to elucidate the consequences of sleep deprivation; the study compared the traditional 30-hour shift with a 16-hour maximum intervention shift schedule. The authors found that attentional failures (slow-rolling eye movements that occur at the transition from wakefulness to sleep) were more than doubled during night shifts on the traditional
than tired? schedule.6 Additionally, interns made 36% more serious medical errors (medication, procedural, and diagnostic errors that cause or have the potential to cause harm) during the traditional 30-hour shift.7 More recently, the Canadian National Steering Committee on Resident Duty Hours reported that continuous 24-hour shifts pose risks to the “physical, mental, and occupational health of residents.”8 The amassed empirical evidence seems to clearly indicate that the fatigue and sleep deprivation that accompany long shifts have serious, negative effects on physicians’ safety and cognition. It may come as a surprise, then, that the regulations to restrict resident duty hours have not resulted in the expected improvement in patient outcomes. A recent randomized trial of 117 general surgery residency programs in the United States examined the impact of duty-hour restrictions on both patient and resident outcomes.9 Participating programs were assigned to either the current ACGME standard duty hours (a maximum of 16 hours per shift in the first year of training, and 28 hours thereafter) or flexible duty hours that may exceed the aforementioned restrictions per shift. Participating programs in both groups were to limit their residents’ duty hours to 80 per week and on-call frequency to every third night; in addition to one day off per week. Interestingly, residents in programs assigned to flexible duty hours reported benefits with respect to continuity of care,
surgical training, and professionalism without an appreciable difference in resident safety, leading the authors to conclude that flexible hours result in non-inferior patient outcomes.9 Furthermore, a systematic review concluded that reduction in duty hours negatively affects patient care.10 Another matter that must be considered when assessing the impact of different policies is resident education. Achieving mastery in surgery requires extensive and immersive experience,11 as does the practice of medicine as a whole. Residents, serving the dual role of health care providers and learners, acquire the skills and knowledge of their specialty while practicing under the supervision of experienced staff physicians and through independent study. While some studies demonstrate that restricted duty hours result in improved examination scores12 and allow more time for independent study and knowledge acquisition,13 residents reported similar satisfaction rates with respect to their quality of education under restricted and flexible duty hours.9 Similarly, a systematic review found no evidence of improved educational or training experiences with 16-hour duty caps. In fact, a multitude of studies demonstrate a decline in performance on some certification exams following regulations to limit duty hours.14 As with most aspects of this debate, data and opinions are conflicted. So the question remains of whether duty hour restrictions improve patient and
resident outcomes. When blanket dutyhour restrictions were first implemented, there was little empirical support for the benefits of shorter shifts. However, with the widespread implementation of duty-hour regulations, we are starting to recognize additional factors that influence patient care and safety. One of the most common arguments against duty-hour restrictions is the resultant decrease in continuity of care. Shorter shifts mean that more doctors are responsible for the care of a single patient–as one doctor leaves, another one must take over. Patient handoff procedures are not standardized and create more opportunities for medical errors. In fact, patient handoffs are one of the most preventable causes of serious medical errors and patient harm.15 Additionally, most of the aforementioned studies were conducted in surgical residency programs, as this field has been impacted extensively by duty-hour restrictions, with residents being asked to leave the hospital mid-surgery or transfer patient care in the middle of an emergency situation because their shift was up.16 This example, whereby a resident leaves a case mid-surgery as a result of dutyhour restrictions, serves to illustrate the dissonance between residency training and general practice. Furthermore, in revisiting the case of Libby Zion, it is clear that multiple factors led to the circumstances of her death: intern fatigue, minimal supervision, and a lack of safeguards against a fatal drug interaction. Although fatigue IMS MAGAZINE SUMMER 2016 SLEEP | 37
(continued...) and sleep deprivation play a role in adverse patient outcomes, some experts suggest that other factors are at play which may exacerbate and compound the impact of sleep deprivation: inadequate supervision17 and limited experience of residents in complex cases.10 Undoubtedly, the debate surrounding resident duty hours is a complex and multifaceted one. While the physiological and mental effects of sleep deprivation were used to promote policies that restrict resident duty hours, several studies failed to show a consistent association with improvement in resident well-being and patient outcomes. Whether or not dutyhour restrictions are implemented, experts have suggested several ways to enhance patient outcomes and improve resident education that address other underlying issues. For example, medical errors and preventable adverse events decreased by 23% and 30%, respectively, with the implementation of a handoff-training intervention.18 In fact, an evidence-based standardized approach to improving handoff procedure has been developed.19 Another avenue that may be explored in enhancing training opportunities is simulations aimed at improving various interventional and surgical techniques. Though their impact on patient outcomes remains unknown, such simulations can be utilized in programs where duty-hour restrictions limit hands-on experience.10 Furthermore, technology can also be implemented to avoid the issue of drug interaction by implementing computerized 38 | IMS MAGAZINE SUMMER 2016 SLEEP
prescribing systems that automatically alert physicians to potential drug interactions.2 Further, some experts also recommend the implementation of strategies to deal with fatigue, such as strategic napping and alertness management,20 as well as screening and addressing resident burnout and improving scheduling practices to optimize sleep.10 In fact, another trial is currently comparing the effect of different scheduling practices on patient safety and trainee education.21 In line with the recommendations above, the Canadian Medical Association and the Canadian National Committee on Resident Duty Hours have shifted from strict, blanket reductions in resident duty hours to a more integrated and flexible approach.22 Whether or not these recommendations are implemented effectively in Canadian residency programs remains to be seen; surely, decision makers will need to sleep on it. References 1. Lerner, B. A case that shook medicine. The Washington Post [Internet]. 2006 Nov 28 [cited 2016 May 30]. Available from: http:// www.washingtonpost.com/wp-dyn/content/article/2006/11/24/ AR2006112400985.html 2. Sanghavi, D. The phantom menace of sleep-deprived doctors. The New York Times Magazine [Internet]. 2011 Aug 5 [cited on 2016 May 30]. Available from: http://www.nytimes.com/2011/08/07/magazine/the-phantom-menace-of-sleep-deprived-doctors.html?_r=5 3. Lajoie MR. End of 24-hour institutional on-call duty in Quebec A measure even practising physicians are calling for. Can Fam Physician. 2012 May 1;58(5):e296-7. 4. Cziesler, C. The Gordon WIlson Lecture: Work hours, Sleep, and Patient Safety in Residency Training Trans Am Clin Climatol Assoc. 2006 117:159-188. 5. Comondore VR, Wenner JB, Ayas NT. The impact of sleep deprivation in resident physicians on physician and patient safety: Is it time for a wake-up call?. BCMJ; 2008 50(10): 560-564. 6. Lockley SW, Cronin JW, Evan EE, Cade BE, Lee CJ, Landrigan, CP et al. Effect of reducing interns’ weekly work hours on sleep and attentional failures. N Engl J Med. 2004 Oct;351:1829-1837 doi:1056/NEJMoa041404 7. Landrigan CP, Rothschild JM, Cronin JW, Kaushal R, Burdick E,
Katz JT et al. Effect of reducing interns’ work hours on serious medical errors in intensive care units. N Engl J Med. 2004 Oct;351:18381848 doi: 10.1056/NEJMoa041406 8. National Steering Committee on Resident Duty Hours. Fatigue, Risk and Excellence: Towards a Pan-Canadian Consensus on Resident Duty Hours. Ottawa, Ontario: The Royal College of Physicians and Surgeons of Canada; 2013. 9. Bilimora KY, Chung JW, Hedges LV, Dahlke AR, Love R, Cohen M et al. National Cluster-randomized trial of duty-hour flexibility in surgical training. N Engl J Med. 2016 Feb; 647:713-727 doi:10.1056/ NEJMoa1515724 10. Ahmed N, Devitt KS, Keshet I, Imrie K, Feldman L, Cools-Lartique J et al. A systematic review of the effects of resident duty hour restrictions in surgery: impact on resident wellness, training, and patient outcomes. Ann Surg. 2014 Jun;259(6):1041-1053 doi: 10.1097/SLA.0000000000000595 11. American College of Surgeons Task Force. Position of the Americal College of Surgeons on restrictions on resident work hours. Bull Am Coll Surg. 2009 Jan;94(1): 11-18 12. Durkin ET, McDonald R, Munoz A, Mahvi D. The impact of work hour restrictions on surgical resident education. J Surg Educ. 2008 Jan; 65(1):54-60 doi:10.1016/j.jsurg.2007.08.008. 13. Accreditation Council for Graduate Medical Education: Duty Hours Subcommittee Report. Chicago: Accreditation Council for Graduate Medical Education; 2009. 14. Imrie K, Frank JR, Ahmed N, Gorman L, Harris KA. A new era for resident duty hours is surgery calls for greater emphasis on resident wellness. Can J Surg. 2013 Oct; 56(5):295-296 doi: 10.1503/ cjs.017713 15. American College of Surgeons. Reform to resident physicians’ work hours does not improve surgical patient safety. Chicago, IL: American College of Surgeons 16. Weissmann J. Years ago, we decided that young doctors need more sleep. The plan might have backfired. Slate [Internet]. 2015 Dec [cited on 2016 May 30]. Available from: http://www.slate.com/ blogs/the_drift/2015/12/02/young_doctors_needed_more_sleep_ but_the_plan_for_them_to_get_it_might_have.html 17. Bell BM. Supervision, not regulation of hours, is the key to improving the quality of patient care. JAMA. 1993 Jan 20;269(3):403-4. 18. Starmer AJ, Spector ND, Srivastava R, West DC, Rosenbluth G et al. Changes in medical errors after implementation of a handoff program. N Engl J Med. 2014 Nov;371:1803-1812 doi:10.1056/ NEJMsa1405556 19. I-PASS Handoff Study [Internet]. Boston: I-PASS Study Group/ Boston Children’s Hospital. 2014 [cited on 2016 May 30]. Available from: http://www.ipasshandoffstudy.com/about 20. Rosenbaum L, Lamas D. Residents’ Duty Hours - toward an empirical narrative. N Engl J Med. 2012 Nov; 367:2044-2049 doi:10.1056/ NEJMsr1210160 21. iCOMPARE Study Executive Summary [Internet]. Boston: Brighman and Woman’s Hospital/Harvard Medical School. 2014 Sep [cited on 2016 May 30]. Available from: http://www.jhcct.org/ icompare/docs/iCOMPARE%20-%20Design%20Summary%20 (20140908).pdf 22. Canadian Medical Association. Management of physician fatigue. Ottawa, Ontario: Canadian Medical Association; 2014. Available from:http://policybase.cma.ca/dbtw-wpd%5CPolicypdf%5CPD14-09.pdf
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Cognitive Impairment in Major Depressive Disorder Clinical Relevance, Biological Substrates and Treatment Opportunities
ognitive Impairment in Major Depressive Disorder: Clinical Relevance, Biological Substrates, and Treatment Opportunities is a comprehensive text written by leading researchers in the field of psychiatry across the globe. The text provides a cogent argument for the relevance of cognitive impairment among individuals affected by major depressive disorder (MDD), the topics discussed include but are not limited to, the implications of cognitive impairments among youth with MDD, the relevance of cognition in primary care of individuals with MDD, neurophysiological consequences of MDD on cognitive function, and novel treatment targets for cognitive impairment in mood disorders. This work is among the first of its kind as it provides access to leading-edge research while simultaneously informing its readers of 40 | IMS MAGAZINE SUMMER 2016 SLEEP
the importance of developing methods by which cognitive impairments can be recognized and treated in this vulnerable population. The data presented not only provide us with a wealth of information regarding the various domains of cognition (e.g., attention, memory, information processing, executive function) that are significantly affected by MDD, but also force us to recognize the complexity of this heterogeneous disorder and strategies for tackling this most highly prevalent mental illness in a targeted and meaningful way. For example, the authors of the disparate chapters in the text indicate that there are distinct differences in the manner by which individuals with MDD may report experiencing cognitive impairments subjectively as compared to objectively (i.e., a high functioning
Edited by Dr. Roger S. McIntyre (Associate Editor: Danielle S. Cha) Reviewed by Juhie Ahmed
professional with MDD reported experiencing significant cognitive impairments but performed exceptionally well on neuropsychological tests vs. a high functioning professional with MDD who reported experiencing no cognitive impairment but performed poorly on the neuropsychological tests). However, currently, no â€œgold-standardâ€? for the evaluation of cognitive function exists for this clinical population. Therefore, this text clearly aims to stimulate a broader discussion of cognition, the way in which it is defined, measured, understood, treated, and perhaps enhanced. Taken together, this textbook provides a comprehensive review of the scientific literature of cognition in MDD and successfully communicates the urgency of pursuing this line of research to improve the lives of those affected.
MY BEAUTIFUL BROKEN
BRAIN Review by Rebecca Ruddy
Rarely do we get the opportunity to witness real world examples of the diseases or injuries we study in basic science laboratories, but this glimpse into the real life of a stroke patient helps put the research we do into perspective.
young woman awakens to excruciating pain in her head, which marks the beginning of a challenging journey into a new phase of her life, a life post-stroke. My Beautiful Broken Brain, a 2014 documentary film directed by Lotje Sodderland and Sophie Robinson, takes the viewer through a complex and real journey of recovery from acquired brain injury. After a regular evening with friends, Lotje Sodderland found herself in the hospital the next day following a “severe medical emergency to her brain” that left her with a high probability of death. Throughout the documentary, the viewer is able to follow Lotje post-stroke through her own videos documenting her incredible journey and demonstrating the devastating effects of stroke. While Lotje is able to speak and comprehend, she clearly has challenges articulating her ideas and finding words. She is unable to read and write and has difficulty with even the simplest
of words, such as ‘the’. Her journey to recovery takes her (and the viewer) to an in-patient rehabilitation centre, as well as to experimental transcranial stimulation therapy. Overall, this documentary was a raw and eye-opening story of recovery. Lotje’s hopeful outlook and perseverance was truly inspiring. One particularly outstanding aspect of the documentary was the way it was filmed and conveyed to the audience. Much of the footage was shot by Lotje herself, providing her personal insight into her feelings and recovery; thus, the viewer is able to feel more immersed in her journey and follow her progress. Although her thoughts and words were not always easy for her to convey, her story was very clearly communicated to the audience. Since parts of the documentary were filmed from Lotje’s point of view, a view skewed by her altered vision, the viewer was able to experience colours and sound like never before, just as Lotje did. These
aspects of the film provided insight into Lotje’s new world post-stroke and allowed the viewer to become even more invested in her story and outcome. As a student in the field of neuroscience and in a lab that studies stroke models, this documentary was an enlightening look into the aftermath of stroke. Rarely do we get the opportunity to witness real world examples of the diseases or injuries we study in basic science laboratories, but this glimpse into the real life of a stroke patient helps put the research we do into perspective. I would highly recommend watching this documentary, as it gives an in depth look into the life and struggles after acquired brain injury. The documentary not only shares Lotje’s perspective, but also demonstrates how acquired brain injury affects those around her. It is rare to see such an up-close and detailed account of the ups and downs of brain injury, which is why this film has left such an impact. IMS MAGAZINE SUMMER 2016 SLEEP | 41
TED TALK REVIEW
TED Talk Review
Insights from Dr. Meg Jay By Alexandra Mogadam
IN SCIENCE, IS 30 NOW THE NEW 20? D
r. Meg Jay is a clinical psychologist who specializes in young adult development. Drawing from science and anecdotal snippets, Dr. Jay argues in her book and Ted Talk that one’s twenties are a defining decade of adulthood development, and warns about promoting them as a period of downtime and procrastination—as is often encouraged in our culture.
pause and exploring where the sensation of uncertainty stems from. Avoiding to ask these questions by simply doing more schooling, in an abstract way, falls into the mentality that Dr. Jay describes; by hanging on to what is safe, you delay your exploration and development of who you want to become. Right now, during your “developmental sweet spot”, as Dr. Jay puts it, is the best time to figure that out.
Initially, I did not feel personally connected to this topic. After all, pursuing a degree in medical science does not equate to the developmental stagnation she refers to. A lot of work and effort goes into obtaining a graduate degree, and the constant challenge of staying afloat promotes growth and development, which is exactly what she advocates.
In addition to identifying a potential challenge for many twenty-somethings today, Dr. Jay offers two pieces of advice that are relevant to this discussion. First, she suggests young adults gain “identity capital.” This involves exploring and doing things that add value to who you are. It does not just refer to the opportunities you seek out for your resume, but also your personal experiences. Second, she encourages nurturing and growing relationships with your “weak” ties, the people that exist in your periphery who may have different ideas and opportunities than those in your closest circles. I like these two points, and think they are good pieces of advice. As students of science we often get caught up in the details of our work, and forget to explore what exists beyond the lab door. Embracing a little creativity in thought and action can go a long way, both for our science, as well as our personal development. Therefore, dare to look into what interests you, and try and reach out to those connections that exist within your reach; fully take charge of your (scientific) development, and move forward deliberately.
However, when I thought about it more abstractly, I realized that there was something I could learn from her. Soon I will have to decide whether I want to pursue additional schooling after the completion of my MSc. The path forward in academia and/or medicine is fairly structured and straightforward. Of course the work required to get through all the different steps is challenging, but the logic behind the progression of degrees is evident; the roadmap is clear and there is precedent. This is not a criticism; in fact, for those that are certain they want to pursue a career in academia and/or medicine, this works very well. However, for those like me that are unsure, it can be a pitfall. The allure of continuing up the academic ladder is strong, as it feels safe and readily accessible. At this point in time, the alternative seems much scarier; taking 42 | IMS MAGAZINE SUMMER 2016 SLEEP
References 1. Jay M. The Defining Decade: Why Your Twenties Matter--And How to Make the Most of Them Now. Twelve; 2012 Apr 17. 2. Jay M. Why 30 is not the new 20 [Ted Talk]. Ted2013, 2013.
ACROSS 5 7 9 10 11 12
A theory that we sleep to reduce the accumulation of amyloid-beta in the extracellular space of the cortex The sleep stage with the most dreaming (3 words) A large sleep network across Canada with the goal of looking at sleep disorders across the lifespan (5 words) An explanation for the differences in sleep quality between the sexes The hospital with the most comprehensive sleep study program in Canada (5 words) A sudden loss of muscle control despite maintaining consciousness
DOWN 1 2 3 4 6 8
A brain region that produces deficits in sleep continuity when lesioned in rodents (3 words) A chemical name for caffeine A biological process oscillating over a 24 hour period (2 words) A childhood disorder that results from narrowing of the upper airway (4 words) A major neurotransmitter involved in sleep regulation An inability to regulate sleep and wakefulness
1 Ventrolateral preoptic nucleus 2 Methyltheobromine 3 Circadian rhythm 4 Paediatric obstructive sleep apnea 5 Aggregation theory 6 Hypocretin 7 Rapid eye movement 8 Narcolepsy 9 Canadian Sleep and Circadian Network 10 Hormones 11 The Hospital for Sick Children 12 Cataplexy
“Vacation relaxation?”, “Common Sleep Disorders in Academia," and“Dream On” by Jorge Cham, www.phdcomics.com
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