IMS Magazine Fall 2012

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SOCIAL INEPTITUDE Is our increasing reliance on technology hindering interpersonal growth?

IMS STRATEGIC PLAN Learn where the IMS is headed in the next five years



Learn about trauma management from leading experts in the field Student-Led Initiative


Cover photo taken by Paulina Rzeczkowska and modified by Design Editors; SURP photo courtesy of the IMS Office; Viewpoint photo courtesy of; ID#1575568.

IN THIS ISSUE... Commentary ....................................03 Letter from the Editor ......................06 News at a Glance ...........................07 Director’s Message .........................10 Strategic Plan ..................................11 Feature.............................................13 Spotlight ..........................................25 Book Reviews ..................................27 Viewpoint ........................................29 Close Up...........................................33 Future Directions .............................35 SURP Highlight.................................37 Ask the Experts................................40 Past Events ......................................41 Diversions .......................................42


Blunt and Penetrating Trauma

With the help of our world-renowned experts, we guide you through prevention, acute care, and post-traumatic injury management.

MAGAZINE STAFF Editor-in-Chief Natalie Venier Managing Editor Nina Bahl Assistant Managing Editors S. Amanda Ali Tetyana Pekar Brittany Rosenbloom Adam Santoro Departmental Advisors Marika Galadza Kamila Lear Design Editors Melissa Cory Laura Greenlee Michael Soong Inessa Stanishevskaya Andrea Zariwny Advertising Manager Laura Seohyun Park Magazine Committee Salvador Alcaire Rickvinder Besla Nancy Butcher Jill Cates Josephine D’Abbondanza Danielle DeSouza Melanie Guenette Aaron Kucyi Rosa Marticorena Benjamin Mora Karrie Wong Zeynep Yilmaz Photography Yekta Dowlati Brett Jones Laura Feldcamp Paulina Rzeczkowska


IMS SURP Highlight Read about this year’s Summer Undergraduate Research Program, including the numerous student accomplishments.


Copyright © 2011 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.

Viewpoint: Science Fact vs. Fiction Adam Santoro discusses his perspective regarding the communication of scientific information to the public.

Cover Art Cover design by the IMS Magazine Design Editors. The original photograph was taken by Paulina Rzeczkowska at Sunnybrook Health Sciences Centre--one of Canada’s largest trauma centres.



Big Fan with Small Ideas As a new graduate student with the IMS, I’m a big fan of the magazine! I think it’s absolutely amazing and a real pleasure to read. While looking through the most recent issue, I thought of an interesting new section or issue theme and wanted to share these ideas. One of the most attractive components of graduate school (based on what I have heard) is presenting at international or national conferences. Especially for a huge travel fanatic like myself, I think it would be really exciting to have graduate students share their conference travel experiences in a “Travel Bites” section. It would provide IMS students with a unique way to share their experiences while highlighting the opportunities available in research-focused degrees. If there is any further interest in these ideas, I would love to get involved. Keep up the great work! - Anna Badner Thanks for your input! Be sure to check out our new, reader-inspired Travel Bites section in the next issue of the magazine. If you have a conference experience you would like to highlight, please email us for more information at - IMS Magazine

RE: All ways of knowing are equal,

but some are more equal than others

(by Adam Santoro, Summer 2012)

“Thus, it is not a simple case of complementary systems of knowing that can live in harmony...” I understand the definitive necessity of methodological naturalism in science, but, “ways we cannot detect” aside, are there any theories that so-called “Christian scientists” have come up with that fully support methodological naturalism while simultaneously appreciating theological possibilities? Or is one always at the expense of the other? - RB Join in our online discussion of this article at



Commentary Dear Editor, I read with great interest your article titled “Double Doctors, Double Trouble” in the Spring 2012 issue of the IMS Magazine. In this commentary, I would like to clarify few issues raised in the article. Being a physician scientist is a privilege that allows one to be involved in both compassionate care and cutting edge research. Commitment to a dual career is made early on when students enroll in a combined MD/PhD program or when they obtain their PhD during residency. As described in your article, a physician scientist commits to both pursuits; however, the dynamic framework underlying this balance is not captured in your article. The majority of physician scientists operate under different work models. For example, some opt for a 50-50 split, i.e., 50% of their time is protected for clinical duties and the other 50% for research activities. Others may opt for an 80-20 split, or slightly different breakdowns. While physician scientists commit to both endeavours, your article paints a picture of an individual who is “spread too thin,” and struggles to spend every work day conducting experiments, teaching students, and operating on patients. This picture is inaccurate, as physician scientists have protected time, and they have research/clinical colleagues to help them prioritize particular activities while not compromising the quality of any particular endeavour. The University of Toronto has Canada’s oldest and largest MD/PhD program and it takes the responsibility of educating and mentoring future physician scientists quite seriously. Leadership from the Faculty of Medicine and MD/PhD program raise significant funds to provide financial support, offer formal and informal mentorship, and ensure that their trainees receive the finest medical education and research experience. Their success is evinced by the excellent publication record of MD/PhD trainees in top tier journals such as Cancer Cell, Cell Stem Cell, Science, etc.

MD/PhD students have received top awards for outstanding research, leadership, community service, and publishing that have garnered them national and international recognition. Thus, I am not convinced that, as stated by the article, MD/PhD trainees or graduates spend their time dispelling rumors of being inadequate clinicians and researchers. I read with curiosity about the characterization of MD/PhD graduates and the world they inhabit. The labeling of scientists as “skeptical” or of patients as “submissive” is intriguing and inaccurate. Scientists have developed a rigorous method of hypothesisdriven research and this drives their curiosity and the high standards to which they hold all scientific findings, and this is not due to any underlying skepticism. Furthermore, patients are empowered to be active participants in the care they receive. While this empowerment is embodied in the guiding principle of “autonomy,” physicians encounter situa-

COMMENTARY tions in which patients may not have all the information required to make an informed decision. In such cases, physicians (including MD/PhD graduates) are guided by principles of beneficence and non-malfeasance, and always provide patients with all required information and include them in every healthcare decision. They provide patients with material to make an informed decision. To characterize patients as “submissive” suggests a power imbalance that works in favour of a physician’s hidden agenda. Research and clinical work have their own timelines and moments of urgency, and it would be unfair to characterize research as lacking “hard deadlines” and clinical work as “fast-paced…reacting to emergency situations.” Finally, MD/PhD trainees and graduates, to my knowledge, are not living in a conflicting world ranging from “nerdiness” to “level-headedness” as you suggest is portrayed in popular television series. While the article points to a recent survey done at the University of Toronto, I would like to refer you to data stating that >60% of MD/PhD graduates from the University of Toronto have gone on to have academic careers, which is similar in number to recent statistics from US programs. It is improper to extrapolate one student’s comments (without the appropriate context) as being reflective of all students’ experience. While the article

raises questions about the level of preparedness for clinical contexts or ability to carry out research, it is important to point out that trainees and graduates take their responsibilities as researchers and physicians very seriously. All MD/PhD students receive a PhD that is approved by the School of Graduate Studies, and they all complete their medical education (including residency) with a license to practice from their relevant national residency/fellowship organization. This means that all MD/PhD graduates fulfill all the requirements as determined by relevant research and clinical organizations. All physicians, whether they are involved in research or not, commit to being life-long learners. This philosophy stems from the fact that 1) it is impossible to have an encyclopedic medical knowledge, 2) medical knowledge and research are constantly evolving towards approaches that ensure superior patient centered care, and 3) physician scientists operate in a broader context (i.e. an interprofessional healthcare team) and, hence, they can always consult with their colleagues. We are at a crucial time in building clinical knowledge and in developing therapeutic interventions for our patients. Being a physician scientist is a privilege and we recognize the impact of a short-term encounter while supporting a patient through a difficult medical diagnosis or a death of a family member. We also recognize the long-term impact of a scientific discovery on individuals we may never meet. If I had written the article, I would have entitled it “Double Doctors, Double Responsibility.”

Call for Articles The IMS Magazine is looking for scientific content to post on the IMS Magazine website. Whether you are a current blogger looking to cross-post your scientific musings, or are just looking to get your ideas out there on our platform, your submissions are welcome. Submissions are expected to be approximately 800 words in length (with considerable leeway) and priority will be given to individuals who comment and report on IMS specific issues (e.g. research in the department, conferences, general scientific issues that affect the IMS faculty and students, etc.) although viewpoints and commentaries are also welcome. Send an email to for more information.

Contact Us We encourage our readers to send their feedback -- comments, questions, corrections, and letters to the editor -- to theimsmagazine@ Please also visit us at and engage in our article-specific, online discussion.

By Sagar Dugani, MD, PhD University of Toronto 2012 Resident, Internal Medicine Brigham and Women’s Hospital-Affiliated with Harvard Medical School Disclaimer: The opinions expressed by the author(s) are in no way affiliated with the Institute of Medical Science or the University of Toronto. Comments are welcome at theimsmagazine@ @IMSMagazine







Letter from the Editor

ocial media is revolutionizing the way we communicate. As blogging and social networking sites continue to grow in popularity, anyone with Internet connection can have access to a multitude of information quicker than ever before, and interact with people all around the world with the touch of a screen. Within the scientific community, social networking is convenient, offers opportunities for international collaboration, and is an easy approach to remain up to date with new findings. But is this all a good thing? Much of the information available to the scientific community is also made public so quickly that it may not be properly reviewed and may depict incorrect information. In this issue of the IMS Magazine, Adam Santoro reviews the importance of accurately communicating scietific findings to the general public in his perspective piece, Science: Fact or Fiction. You can also learn about how a shift in online communication may affect our person-to-person interactions in the article by S. Amanda Ali: Social Ineptitude: From social butterfly to social outcast, do you know where you stand? These are both fascinating reads that will definitely get you thinking—and possibly influence your behaviour. In addition, we present our feature on the number one killer in young people, Blunt and Penetrating Traumatic Injury. Here, with the help of renowned experts Dr. Ori Rotstein, Dr. Sandro Rizoli, Dr. John Marshall, Dr. Michael Cusimano, and Dr. Andrew Howard, we discuss prevention strategies, acute care, and post-traumatic injury management. From molecules to motor vehicle accidents, we hope you will gain a better understanding of this intense, fascinating field.

Natalie Venier

Editor-In-Chief Natalie Venier is a fourth year PhD Candidate at the Institute of Medical Science. She is currently studying prostate cancer chemoprevention at Sunnybrook Health Sciences Centre.

I also recommend reviewing our article—created in collaboration with IMS Director, Dr. Allan Kaplan—regarding the IMS’ new Strategic Plan, which provides an overview of the 5-year structure for our department. Please also be sure to read highlights from this year’s Summer Undergraduate Research Program and the many accomplishments of our talented summer students. To conclude, I would like to thank Dr. Allan Kaplan and the IMS department for their ongoing support, and congratulate our design team on their outstanding efforts in the production of this issue. I must acknowledge the phenomenal IMS Magazine team for their creativity and dedication, which have been integral to our production. Lastly, I strongly encourage comments and feedback letters as we continue to aspire to bring you the best of the IMS.

Photo by Paulina Rzeczkowska.


Natalie Venier Editor-In-Chief, IMS Magazine IMS MAGAZINE FALL 2012 TRAUMA | 06



9 9 16

Ori Rotstein Lecture in Translational Research

23 30

IMSSA Apartment Crawl

2012-13 CIHR Master’s Award applications due to IMS (5pm) 2013-14 Joseph-Armand Bombardier CGS Master’s Scholarship applications due to IMS (5pm)

2013-14 Ontario Women’s Health Scholars Awards applications due to IMS (5pm)

DECEMBER IMS Annual Holiday Party University officially closed for winter break. Happy holidays!


7 10 18

IMS ANNOUNCEMENTS Ori Rotstein Lectureship in Translational Research This year’s Ori Rotstein Lectureship will be held on November 9th, 2012, from 7:15-11am, with a lunch reception to follow. It will be taking place at the Toronto Western Hospital, TWH Auditorum, 2nd Floor West Wing. All are welcome and strongly encouraged to attend. IMS Office Staff We are very pleased to announce Michelle Rosen as our interim Student and Faculty Affairs Coordinator! Michelle has been with the IMS since June 2012 and officially accepted the maternity leave replacement position this past September. Michelle brings with her a wealth of knowledge in program administration, digital design, and development and student services. She will continue in her role as Student Awards Administrator, Faculty Appointments Coordinator, and as the lead administrative contact for the MSC 1010/1011Y course. Please join us in officially welcoming Michelle to the IMS! We are pleased to announce the arrival of Baby Boy Blackwood! Kaki Narh Blackwood, IMS Student and Faculty Affairs Coordinator, gave birth to a healthy baby boy, weighing 7 pounds, 9 ounces at 9:08 am, on October 10th. Congratulations to Mom and Dad on their first child! May little Nathan fill your hearts with joy in the days and years to come. The IMS is pleased to announce the much-awaited permanent Departmental Assistant, Elena Gessas. Elena joins us with over 6 years of experience at Princess Margaret Hospital, having previously worked as the Radiation Oncology Fellowship Program Coordinator. Her current role includes administering the Summer Undergraduate Research Program (SURP), serving as student liaison assistant for federal and provincial awards, reception & general inquiries, room bookings, and much more. Once again, welcome Elena—we’re thrilled to have you on board!

University officially re-opens IMS New Student Orientation and Reception Final date for PhD and MSc defenses to be eligible for June 2013 convocation Welcome Michelle Rosen and Elena Gessas!



Photos courtesy of the IMS Office.

13 24

at a glance...


IMSSA ANNOUNCEMENTS Movember is here! Join the IMSSA moustache-growing team—“I-Mo-S.” Movember is an annual, month-long event involving the growing of moustaches during the month of November to raise awareness of prostate cancer and other male cancer initiatives. Join our team at or search IMoS from the portal. Get growing, donate generously, and have fun! Come out on Friday, November 23rd for the IMSSA Apartment Crawl! Meet fellow IMS students in a more personal setting—their apartments! We’ll be hitting up three student’s residences in groups of 15 for a round of drinks (courtesy of IMSSA) before meeting up at a collective location to party the night away. This is a great time to socialize with fellow students and meet new people, so don’t miss out! Contact for tickets. Tickets will also be sold at the first year IMS Thursday seminars. Join us for some holiday cheer at the annual IMS Holiday Party on Thursday, December 13th, 6-11pm (Music Room, Hart House) featuring festive cocktails, hors d’oeuvres, raffle prizes, and live entertainment. Entrance is free for IMS students and faculty and $10 for non-IMS attendees. Feel free to RSVP to if you are able to attend!

AWARDS & SCHOLARSHIPS 2012-13 CIHR Master’s Award (CIHR CGSM) Due Date: November 9th, 2012 The Canada Graduate Scholarships Master’s Awards administered by CIHR (CGSM) are intended to provide special recognition and support to students who are pursuing a Master’s degree in a health related field in Canada. These candidates are expected to have an exceptionally high potential for future research achievement and productivity.

MODULE HIGHLIGHT Qualitative Research Objectives:

For questions on CIHR funding guidelines, how to apply, and the peer review process, please contact the CIHR directly. Email: Telephone: 613-954-1968 Toll-free: 1-888-603-4178 Fax: 613-954-1800.

Students will gain a basic understanding of qualitative research principles, methodologies, and applications. The module will focus on guiding participants through the challenges of conducting qualitative studies in health professions. For more information visit portal.

2013-14 Ontario Women’s Health Scholars Awards


Due Date: November 30th, 2012 The Ontario Women’s Health Scholars Award is administered by the Ontario Council of Graduate Studies (OCGS) on behalf of Ontario government ministries. It is open to Master’s students, Doctoral students, and Post Doctoral Fellows. Funded by the Ontario Ministry of Health and Long-Term Care, a Scholar Awards Program in Women’s Health has been established to ensure that Ontario attracts and retains pre-eminent women’s health scholars.

Dr. Carol-Anne E. Moulton, Staff Surgeon, Hepatobiliary Surgical Oncology, University Health Network Associate Professor, University of Toronto Scientist, The Wilson Centre

For more information visit: About > Chairs and Awards. Or stay tuned to your UTmail+ e-mail address for IMS award announcements.

Find out more about faculty on the IMS faculty database at http://www.ims.

2013-14 Joseph-Armand Bombardier CGS Master’s Scholarships Due date: November 16th, 2012 The Joseph-Armand Bombardier CGS Master’s Scholarships funding opportunity seeks to develop research skills and assist in the training of highly qualified personnel by supporting students in the social sciences and humanities who demonstrate a high standard of achievement in undergraduate and early graduate studies. For more details about this award, stay tuned to your UTmail+ e-mail address for IMS award announcements. For more award opportunities visit Opportunities > Awards. *Please note: the IMS has internal deadlines for major federal and provincial awards that may differ from deadlines listed on the Ulife website.

For information on IMS news and events, please see: For more information on IMSSA/IMSSA-related events, please visit: Please send your comments and suggestions to:

You can stay up to date on IMSSA events and workshops by checking out the IMSSA website at, or you can join their Facebook group at Institute of Medical Science (U of T).



Continental Breakfast

7:30 am

Welcome Dr. Thomas K. Waddell, Head, Division of Thoracic Surgery, UHN

7:35 am

Introduction of the Ori Rotstein Lecturer Dr. Allan S. Kaplan, Director, Institute of Medical Science

7:40 am

8:30 am

9:00 am

9:45 am

10:00 am

11:00 am

The Ori Rotstein Lecture by James E. Mitchell, MD, NRI/Lee A. Christoferson Professor and Chairman of the Department of Clinical Neuroscience at the University of North Dakota School of Medicine and Health Sciences Title: “The Impact of Obesity on Surgical Outcomes: The Experience of Bariatric Surgery” Questions and Answers

IMS Student Presentations: David Piccin, PhD and Jeff Wilson, MD


Ethical Issues in Bariatric Surgery: Panel Discussion Moderator: Dr. Ori D. Rotstein, Surgeon-in-Chief, St. Michael’s Hospital Panelists: Dr. James E. Mitchell, MD, Ori Rotstein Lecturer Kyle Anstey, Senior Bioethicist, UHN Linda Wright, Director of Bioethics, UHN Lunch Reception

November 9, 2012 7:00 am – 11:00 am Toronto Western Hospital / TWH Auditorium / 2nd Floor West Wing

Translational research and interdisciplinary graduate education that advance human health


Director’s Message T

he IMS Magazine continues to be the showcase publication of the Institute of Medical Science student body. Congratulations and thanks again to Natalie Venier and her staff for all their hard work, as well to Marika Galadza for her assistance in this project.

This eighth issue of the magazine focuses on traumatic injury and includes several articles by IMS faculty discussing a spectrum of important trauma care research. Specifically, feature contributions include those by Drs. Rotstein, Marshall, Cusimano, Rizoli and Howard—some of the top global experts in the trauma field. In addition, the magazine features an expert opinion piece by Dr. Berge Minassian on rare genetic diseases, and a concise summary of the new IMS Strategic Plan. The department has now identified the IMS faculty members who will be leading each of our five strategic initiatives. These faculty leads are as follows: Faculty Engagement—Mingyao Liu; Unique Program Offerings—Howard Mount; Interdisciplinary Connectedness—Cindi Morshead; Enriching the Student Experience—Brenda Toner; and Strengthening Identity—Allan Kaplan and Vasu Venkateswaran. There will be a Core Team meeting on Friday, November 30th from 9am12pm at the Faculty Club to roll out the implementation strategy for these five initiatives. All IMS faculty and students are invited to become involved in this exciting process. Please make very effort to attend the Ori Rotstein Annual Lecture in Translational Research on Friday, November 9th, 7:15-11:00am at the Toronto Western Hospital Auditorium. The lecture will be given by Dr. James Mitchell, the NRI/Lee A. Christofferson MD Professor and Chair of the Department of Clinical Neuroscience at the University of North Dakota School of Medicine and Health Sciences. He is also the Chester Fritz Distinguished University Professor and President and Scientific Director of the Neuropsychiatric Research Institute. His lecture is entitled “Obesity and Surgical Outcomes: Research on Bariatric Surgery.” The lecture will be followed by student presentations, a panel discussion on the ethics of bariatric surgery, and an opportunity to engage in discussion over lunch. There have been a number of important recent administrative changes at IMS that I would also like to address. We would like to welcome our new Departmental Assistant, Elena Gessas, and our new interim Student and Faculty Affairs Coordinator, Michelle Rosen, as part of the administrative staff at IMS.

Allan S Kaplan, MSc, MD, FRCP(C) Director, IMS

Allan S. Kaplan, MSc, MD, FRCP(C), became the IMS Director in July 2011. He is currently the Chief of Clinical Research at the Centre for Addiction and Mental Health (CAMH), Vice Chair for Research in the Department of Psychiatry, and Professor of Psychiatry in the Faculty of Medicine. He is also a Senior Scientist at both CAMH and the Toronto General Hospital Research Institute. He was the inaugural holder of the Loretta Anne Rogers Chair in Eating Disorders at the University Health Network from 2002 to 2010.

Best wishes for a successful academic fall period and holiday season.

Photo by Mohammed Sabri.


Allan S Kaplan MD FRCP(C) Director, Institute of Medical Science



IMS Strategic Planning at a Glance A Guide for Students and Faculty By Zeynep Yilmaz

many stakeholders as possible by asking a series of questions that stakeholders felt were important for the IMS to address. Each member of the core team identified three people to interview, and the interviewees consisted of members of the IMS, Faculty of Medicine, University of Toronto, provincial and federal governments, and funding agencies. The process generated over 100 responses, and this information was collated and brought to the table at the IMS Strategic Planning Retreat in January 2012, which was open to all IMS students and faculty.

“What is strategic planning, and why did the IMS need this?”

Dr. Kaplan shares one aspect that stood out to him throughout the strategic planning process: “Many interviewees stated that the IMS was unique in its personal touch with

Strategic planning involves putting together a roadmap of goals regarding where the IMS should be in the next five years and a roadmap of how to get there. The IMS had never formed a strategic plan previously, and having a concrete plan allows the department to make informed decisions about where to invest resources and energy. Dr. Kaplan emphasizes the importance of this process, adding, “When it is done right, strategic planning is really a way in which people can come together and work toward a common vision.” “What was the process of strategic planning?” The groundwork for the strategic planning started in the Fall of 2011. With the approval of the IMS Executive Committee, The Potential Group was chosen as the strategic planning consultants for their inclusive, engaging, and bottom-up approach. “In some strategic plans, work is done by the consultants in a top-down manner,” explains Dr. Kaplan, “but in our case, the majority of the work was carried out by the students and faculty in the Core Team, under the guidance of the consultants.” After hiring the professionals, a core team of 35-40 IMS students and faculty members was established with the goal of engaging as 11 | IMS MAGAZINE FALL 2012 TRAUMA

“Uniqueness” will focus on creating unique program offerings in translational research that will set the IMS apart from other graduate departments. students, dealing with each student’s needs as such needs come up. Graduate coordinators in particular were identified for their approachability.” Through this process, the main initiatives for the strategic plan were developed. Since then, the core team has met to discuss implementation procedures and identified leads for each initiative. Dr. Kaplan highlights the accountability in the process: “The goals were meant to be very concrete and quantifiable, so that we can assess in a year and in five years from now whether we have accomplished our goals.” “What kind of changes can I expect to see in the near future and in the long-term?” First, the IMS logo has been revised with a new tagline: “Translational Research and In-

terdisciplinary Graduate Education that Advance Human Health.” Five key words have been identified for each of the strategic initiatives: (1) uniqueness; (2) connectedness; (3) presence; (4) belonging; and (5) engagement. “Uniqueness” will focus on creating unique program offerings in translational research that will set the IMS apart from other graduate departments. “The first step is already underway, as the IMS has put forward a proposal for a new a Master’s program in Translational Research,” says Dr. Kaplan. “This is different from courses and workshops; it is the first such degree-granting program of its kind in Canada, and there are only a few others like it in the world.” This Master’s program is projected to start in September 2014. Future plans include the possibility of establishing a joint MBA/PhD in conjunction with MaRS and Rotman School of Business. The goal of “connectedness” is to strengthen interdisciplinary connections. Although a number of collaborative programs exist, this theme will take it one step further by creating academic clusters, which will encourage and enable interdisciplinary collaborations. According to Dr. Kaplan, “Five years from now, our goal is that every student will be aligned with one of these clusters, which will facilitate research and networking, as well as give them a sense of belonging; the goal is to create a meaningful home for students and faculty.” “Presence” will tackle the issue of identity and branding. “Believe it or not, some Faculty of Medicine members have never heard of the IMS!” exclaims Dr. Kaplan, emphasizing that the department needs to focus on strengthening its identity locally, nationally, and internationally. “The new tagline will serve as the first step in clarifying what the IMS is about, and it will keep us on track to become the global centre for excellence in translational research training.” Other long-terms plans under this theme include creating an alumni database and fundraising activities.

Photo courtesy of the IMS.


any of you are aware that IMS recently had its first strategic planning. The brochures highlighting the strategic priorities have been widely circulated, and if you haven’t seen them, you can pick up your copy at the IMS office. As with every new process, there are questions about how the proposed changes will affect IMS students and faculty members. With the assistance of Dr. Allan S. Kaplan, Director of IMS, I have compiled a guide to the IMS Strategic Plan with answers to some of the most commonly asked questions:



A Vision and Strategy for the Institute of Medical Science Becoming the Global Leader in Graduate Education to Improve Human Health through Translational Research

“Belonging” will focus on student experience: although the IMS Students’ Association (IMSSA) does an outstanding job in bringing students together, the goal is to increase the academic, social, and networking activities for our student body. “Engagement” will address the issue of faculty involvement. “Although we have over 500 faculty members, only a small minority are actually active in important IMS activities,” says Dr. Kaplan. One goal is to expand the number of faculty involved in IMS Committee work, and expand the number of workshops offered to faculty related to helping them become more effective supervisors.

Given that students are the most important stakeholders, Core Team members interviewed many IMS students and graduates to capture their IMS experiences.

Planning Core Team. In addition to direct student involvement through the IMS Executive Committee and the Strategic Planning Core Team, IMSSA conducted a survey to identify the needs of the students and where they would like to see the IMS in the next five Translational research and interdisciplinary graduate years. education that involved advance in human health “Were students this process?” Students played a crucial role in the entire strategic planning process. I was lucky to be one of the student representatives involved, and I can proudly report that there were as many students as faculty in the Strategic

Given that students are the most important stakeholders, Core Team members interviewed many IMS students and graduates to capture their IMS experiences. Each initiative is co-led by one student to ensure that

student engagement is sustained throughout the implementation process. “Even the strategic planners mentioned how impressed they were with the level of engagement of the students,” comments Dr. Kaplan, especially considering that one of the biggest challenges in strategic planning is engaging students and faculty. “How may I be involved in the future steps of the strategic planning?” Although the initial stage of the strategic planning is complete, it doesn’t mean that our work is done. Dr. Kaplan encourages the IMS community to contact initiative leaders and find out how they can get involved. “We need as many students and faculty members as possible to get involved in implementing these strategic goals. The strategic planning process cannot be accomplished without the ongoing engagement of everyone in the IMS.”




TRAUMA OVERVIEW TRAUMA INTRODUCTION & STATISTICS Traumatic injuries are the leading cause of North American death in persons ≤ 44 years old, and an estimated 90% of all traumatic injuries are avoidable. strategies are of critical importance to Canadian health care. Trauma and Injuries, Canadian Institute for Health Information (

Injuries by Body Region 30.1%






13.9% 6.0%

Spine Upper Extremity Lower Extremity External Other

1.4% 2.9%


8.8% 12.6%

Number of Trauma Cases

Penetrating Burns Blunt



% Injuries by Type 93.7

4482 562


of these cases resulted in death

Injuries by Age Group

<20 13.8%

Source for all statistics in this overview, unless otherwise indicated: Ontario Trauma Registry Comprehensive Data Set, Canadian Institute for Health Information (2010-2011).

total number of trauma cases

20-34 18.8%

35-64 64+ 36.7%


Information visualizations by Melissa Cory.

Neck Thorax


INTERDISCIPLINARY TEAM A patient that requires medical care from a trauma centre requires the care of an “intensivist, neurosurgeon, general surgeon, orthopedic surgeon and a transfusion medicine specialist all within a few hours. Add to this mix a critical care nurse, a pharmacist, a respiratory therapist, and a social worker. No other hospitalized patient needs such resources brought to them over such a short period of

INJURY SEVERITY SCORE an overall injury severity score for patients with multiple injuries: scores ≥ 16 indicate severe traumatic injury.

Mortality by Injury Severity Score Number of Non-Fatal Cases

communication and teamwork.” Trauma Services: Annual Report, St. Michael’s Hospital (2009).



Number of Deaths

4.8% 19.7%

16-24 Motor Vehicle Crashes Intentional All Other Falls




De Mestral C, Dueck AD, Gomez D, Haas B, Nathens AB. (2012). Associated injuries, management, and outcomes of blunt abdominal aortic injury. Journal of Vascular Surgery, 56(3): 656-660.

treatment for life-threatening injury, with the most time-critical interventions performed early.”


Injuries by Gender



% External Cause of Injury 10.7


The ATLS program involves two main steps: 1) Primary survey: initial patient assessment—follow “ABCDE” A: airway maintenance with cervical spine protection B: breathing and ventilation C: circulation with hemorrhage control D: disability (neurologic evaluation) E: exposure and environmental control 2) Secondary survey: head-to-toe evaluation of trauma patients Guidelines For Essential Trauma Care, International Society of Surgery and International Association for the Surgery of Trauma, World Health Organization (2004).

Information visualizations by Melissa Cory IMS MAGAZINE FALL 2012 TRAUMA | 14



Saving Hope & Preventing Trauma fatigue or lethargy, a change in sleep patterns, behavioural or mood changes, and trouble with memory, concentration, attention, or thinking. The person may lose consciousness. If loss of consciousness is involved, the duration is often short—measured in seconds or minutes. A CT or MRI scan is usually negative and most patients can recover from mild TBI without any sequelae. A small number of these patients have prolonged disability, but it is not known exactly why these patients suffer with symptoms for so long. It is clear, however, that the likelihood of showing permanent neuro-cognitive effects, such as depression and personality change, is positively correlated with the number of mild TBI events experienced.

Adjunct Scientist, Keenan Research Centre, St. Michael’s Hospital Professor of Surgery, Education and Public Health, University of Toronto


elative to its burden on society or the amount of research on HIV and cancer (see Figure 1), traumatic brain injury (TBI) has not drawn the research attention it deserves. Recently, increased media attention has changed the amount of research devoted to understanding TBI, but there is still a long way to go to fully grasp the ramifications of this “silent epidemic.”

Stanley Zhang, BM, CRA

Types of TBI

Injury Prevention Research Office, Division of Neurosurgery, St. Michael’s Hospital Research Coordinator, Cusimano Lab

TBI can be classified in many different ways. The commonest classification is based on severity, which ranks the extent of brain damage and symptoms manifested clinically (as measured by the level of the patient’s Glasgow Coma Score (GCS) shortly after injury) as mild, moderate, or severe. Mild TBI is the most common, and fortunately, the extent of damage to the brain is usually limited. Symptoms may include headache, confusion, nausea, lightheadedness, dizziness, blurred vision or tired eyes, ringing in the ears, bad taste in the mouth,


Severe TBI is the least common and these patients, by definition, present in coma. These injuries are often the result of traffic trauma, severe falls, violence, or workplace injury. Violence can be both an antecedent to TBI as well as a consequence of TBI. Young men are particularly at risk of severe TBI and violence. Outcome from severe TBI often depends on a variety of factors, such as the level of the patient’s GCS, brainstem function, and age. Recovery back to baseline health is unlikely and death may occur. Treatment and prevention of TBI Significant research on brain injury relates to interventions administered after an event has

Photos by Brett Jones

Michael Cusimano, MD, MHPE, FRCSC, DABNS, PhD, FACS

In moderate TBI, the patient often has impaired consciousness of a greater degree for a longer period of time. As recovery from injury progresses, symptoms similar to those seen in mild TBI can occur, but they usually are more severe and longer lasting. These patients usually have a positive CT or MRI scan. Furthermore, patients often have persisting sequelae that can be picked up on physical or neurocognitive assessments and often have persisting changes such as cognitive deficits or issues with impulse control.

FEATURE occurred. One aspect of this work focuses on preventing secondary injury—such as progressive hemorrhage and ischemia—by providing rapid emergency responses and immediate surgery. Indeed, our modern medical systems are organized around the prevention of secondary events. Another component of TBI research deals with the rehabilitation of these patients to optimize their return into society. Neurosurgeons are involved primarily in the first component and in extending their findings to the rehab phase. However, most neurosurgeons realize that prevention of brain injury will inevitably have a better outcome than even the most ideal cures. This is exactly where Dr. Michael Cusimano believes we need to focus our energy: we need to intervene before the TBI event occurs. In North America, neurosurgeons have recognized the importance of TBI prevention for 20 years and have formalized it through an organization called ThinkFirst / Pensez D’Abord. In Canada, Dr. Charles Tator and Dr. Michael Cusimano have been the most vocal proponents of TBI prevention. As a neurosurgeon and professor of Neurosurgery, Education and Public Health, and full IMS member, Dr. Cusimano also founded the Injury Prevention Research Office at St. Michael’s Hospital more than 15 years ago; education and knowledge translation are essential to injury prevention, and Dr. Cusimano sought to make it a focus of the Research Office.1-7 The goal of his research is to understand the “who,” “when,” “where,” “why,”

and “how” of TBI at all severity levels, and to study the effectiveness of methods to prevent TBI.8-14 Dr. Cusimano has published several works about TBI in ice hockey and other sports. He was once a “lone voice,” often ostracized by colleagues a decade ago, when his review of the literature concerning TBI in hockey called for a ban or at least major modifications regarding body checking in the sport. Since then, many papers have supported this stance. Last year, the National Hockey League instituted “Rule 48” which bans hits to the head, and many youth hockey leagues followed suit. Dr. Cusimano currently leads a major CIHRfunded grant exploring the potential relationship between violent behaviour in Canadian society and TBI, and more specifically, the common modifiable risk factors of both. Investigators seek to develop and evaluate knowledge translation strategies to prevent TBI and violence, particularly in populations deemed most vulnerable. The project is undertaken by a multidisciplinary team of roughly 30 ambitious scientists in seven institutions across Canada and is centered at St. Michael’s Hospital in Toronto. Overall, the team is exploring the antecedents and upstream factors associated with TBI and violence in Canadian society to provide an evidence base for their prevention, influence knowledge translation into factors like public policy and engineering pertaining to injury

Figure 1. Comparison of Pubmed publications on traumatic brain injury with HIV and cancer over the last seven decades.

prevention, and to set in motion further research to understand and correct the problem. In short, the research team aims to save hope and prevent TBI. For more information on the above study— Traumatic Brain Injury and Violence: Reducing the risks, improving the outcomes— please visit: research/tbi_violence_study.php and www. To cultivate the next generation of neurosurgeons and clinical researchers, Dr. Cusimano is actively looking for research personnel at all levels, from summer students, to research assistants and postdoctoral fellows.

References 1. Cooke DJ, Cusimano MD, Tator CH, Chipman ML. Evaluation of the Think First Canada Smart Hockey Brain and Spinal Cord Injury Presentation Video. Injury Prevention 2003;9:361-366. 2. Isaac D, Cusimano MD, Mansfield E Chipman M, et al. Child Safety Education and the World Wide Web: An Evaluation of the Content and Quality of Online Resources. Injury Prevention 2004;10:59-61. 3. Echlin PS; Cusimano MD. A prospective study of concussion education among two elite junior age ice-hockey teams: implications for sports concussion education. Neurosurgical Focus 2010; 29(5):E6. 4. Cusimano MD; Kwok J. Skiers, Snowboarders, and Safety Helmets. JAMA 2010;303(7):661-662. 5. Cusimano MD, Josse JM. The Effect of a Skiing/Snowboarding Safety Video on the Increase of Safety Knowledge in Canadian Youth--a Pilot Study. International Journal of Circumpolar Health 2006;65(5):385-388. 6. Cusimano MD, Taback NA, McFaull SR, et al. Research Team in Traumatic Brain Injury and Violence: Effect of bodychecking on rate of injuries among minor hockey players. Open Med. 2011;5(1):e57-64. 7. Cusimano MD, Chipman M, Glazier RH, et al. Geomatics in Injury Prevention: the science, the potential and the limitations. Injury Prevention 2007;13(1):51-56. 8. Ray JG, Moineddin R, Bell CM, et al. Alcohol Sales and Risk of Serious Assault. PLOS Medicine 2008; 5:1-7. 9. Cusimano MD, Mascarenhas AM, Manoranjan B. Spinal Cord Injuries Due to Diving: A Framework and Call for Prevention. Journal of Trauma Injury, Infection, and Critical Care 2008;65:1180-1185. 10. Rinner C, Cinnamon J, Cusimano MD, et al. Online Map Design for Public Health Decision Makers. Cartographica 2009;44(4):291-302. 11. Cinnamon J, Rinner C, Cusimano MD, et al. Evaluating Web-based Static, Animated, and Interactive Maps for Injury Prevention. Geospatial Health 2009;4(1):3-16. 12. Cusimano MD, Marshall S, Rinner C, et al. Patterns of Urban Violent Injury: a spatio-temporal analysis. PLoS ONE 2010;5(1):e8669. 13. Harris MA, Reynolds CC, Winters M, et al. The Bicyclists’ Injuries and the Cycling Environment study: a protocol to tackle methodological issues facing studies of bicycling safety. Injury Prevention 2011;17(5):e6. 14. Cusimano MD, Luong WP, Faress A, et al. Evaluation of a Ski and Snowboard Injury Prevention Program. International Journal of Injury Control and Safety Promotion 2012 Jan 9. [Epub ahead of print]





Why is Road Traffic Injury

a Difficult Problem to Solve?

probably feel quite safe on the road, so why does road traffic injury persist as a serious issue? Car occupant deaths are a predominant problem in North America and Europe. However, 90% of road deaths occur in lowand middle-income countries, and vehicle occupant deaths are a minority of the total vehicle deaths in these countries. Non-occupants—specifically, pedestrians, cyclists, and motorcyclists—bear the brunt of road traffic injuries, although the proportions vary substantially by country.

Andrew Howard, MD, MSc, FRCSC Pediatric Orthopedic Surgeon Hospital for Sick Children Associate Member, IMS


million people will die on the roads this year across the world. The World Health Organization (WHO) declared a decade of action on road safety from 2011 to 2021, with the aim of decreasing road deaths by half. When the decade was declared, 1.2 million road deaths occurred per year with a projection of 1.9 million deaths per year by 2020. The WHO hopes to bring this number down to 0.9 million lives lost per year—an aim that would save a million lives annually and 5 million lives total before the decade is out. Huge strides have been made in North America to make cars safer for occupants. The cars we drive can be driven into a rock face at 40 km/hour without hurting the driver, which perhaps explains the drop in driver and occupant deaths over the past decades in North America and Europe. Most of us


Effective interventions exist for all types of road injuries. Reducing impact speed from 35 km/hour to 25 km/hour reduces the risk of killing a pedestrian by 80%. Better road and city design reduces pedestrian crashes by 25%. Seatbelts, child restraints, motorcycle helmets, and bicycle helmets reduce deaths and head injuries by more than 50%. Moreover, drunk-driving programs reduce crash rates, and graduated driver licensing reduces crash rates among the young. Organized trauma systems reduce death rates even in high-income countries where good hospitals are available. Making trauma care available throughout low- and middleincome countries would massively reduce death and disability. Furthermore, provision of emergency and essential surgical care, including trauma care, has recently been shown to be highly cost effective when compared to widely accepted health interventions such as care of HIV, tuberculosis, and malaria.

“Making trauma care available throughout low- and middle-income countries would massively reduce death and disability.”

Implementation of interventions to reduce pedestrian, cyclist, and motorcycle deaths and injuries is scattered across multiple jurisdictions—health, justice, and transport at a minimum. Even in well resourced and well governed countries, the prevention of trauma falls through huge cracks between jurisdictions. The University of Toronto and Institute of Medical Science have considerable research output across the spectrum of road traffic injuries—from invention of innovative child safety seats based on detailed biomechanical analyses, to novel geographically based analyses of pedestrian safety interventions, to data on trauma system effectiveness. However, too much of our research is concentrated where the funding is concentrated—in highincome countries. We are a Canadian university with excellent international connections and a recently reasserted global outlook. We understand why road traffic injury is a difficult problem to solve—but we also understand that orienting our research towards low-income countries and aligning with international organizations will allow us to play our part in reducing road deaths this decade, and saving a million lives per year. For more reading on road traffic injury prevention, please visit World Health Organization: Violence and Injury Prevention at www.who. int/violence_injury_prevention.

References World Health Organization. Global status report on road safety (2009). Available from: prevention/road_safety_status/2009/en/index.html World Health Organization. One-year progress update: Decade of Action for Road Safety 2011-2020 (2012). Available from: html World Health Organization. World report on road traffic injury prevention (2004). Available from: violence_injury_prevention/publications/road_traffic/world_ report/en/index.html

Photo courtesy of Dr. Andrew Howard


Q & A with...

Dr. Barto Nascimento MSc, MD

Dr. Sandro Rizoli. Here, I was working to develop a clear understanding of how to best manage patients who present with trauma-induced coagulopathy— a disorder in which blood fails to clot normally, resulting in heavy and prolonged bleeding after traumatic injury—and I developed an appreciation of critical care and transfusion research. Q What is it like to work in the acute trauma setting? A: It can be extremely intense and demanding because you have to always be prepared to attend to patients coming into emergency. Having said that, it is a very exciting field that is incredibly rewarding.

The former IMS graduate sat down with us at Sunnybrook Health Sciences Centre—one of Canada’s largest trauma centres—to discuss his path, research, and the future of his field. Q: You are joining the trauma staff at Sunnybrook Hospital as an assistant professor of surgery. How did you get to where you are today? A: It has been quite a journey. I completed my medical school and surgical residency training in Brazil. After a few years of working in trauma and general surgery there, I moved to Canada and completed a series of fellowships in Trauma Research, Critical Care Medicine, and Transfusion Medicine. I then joined the IMS, and completed my MSc with focus on clinical epidemiology under the supervision of

Q: Do you enjoy your work? What is the most rewarding aspect? A: I love it. Often patients present in emergency with life-threatening problems that can be easily managed—for example, breathing difficult due to a collapsed lung. Here, it’s amazing to see how a simple procedure can have a major and immediate impact that can save a life. When a family member approaches you and thanks you for saving their son or daughter’s life. That is the most rewarding aspect of my work; you get a real sense that you have made a difference.

death in young people, so there still remains work to be done. It is definitely a highly demanding job, but it also is very fulfilling. Q: Do you envision any major changes for the future of the trauma field? A: Although traumatic injuries will likely remain an important cause of mortality among young people in the foreseeable future, significant changes in the number of motor vehicle fatalities are predicted. There are many new regulations and mechanical safety features that are being developed to prevent motor vehicle accidents. I imagine that this will lead to a reduction in the number of trauma cases, as motor vehicle accidents account for a large portion of traumatic injuries. For a full discussion on coagulopathy, please see pages 21-22. Interview by Natalie Venier

Q: Do you recommend this field for someone starting their medical training? A: Yes. Traumatic injury remains the leading cause of

Patient Perspective Dealing With Traumatic Injury Q&A Photo by Paulina Rzeczkowska. Image courtesy of, ID#129088

By Salvador Alcaire It was 9:00am on Monday, April 4th, 2011 and I was on my way to my lab meeting, ready to present. As I do every morning, I rode along Toronto’s busy College Street on my motorcycle towards Mount Sinai Hospital. As I signaled to switch lanes and angled to move, my front tire suddenly slipped on the streetcar tracks—as if in slow motion, I went down on my left side, slamming my shoulder first, then head, followed by the pain of my leg being dragged along concrete with a 500 lb motorcycle over it. Fortunately, the driver of the car directly behind me slammed on the brakes before hitting me. After what seemed like a short time, the ambulance arrived and my vital signs were checked: ‘what is your name?’ and ‘how many fingers am I holding up?’ were some of the diagnostic questions asked as part of onsite, acute care. At the

hospital, immediate precautions were taken to ensure protection of my spinal cord from damage. Following X-rays and CT scans, it was clear that my spine was unharmed, but my ankle was dislocated, impacted, and severely broken with multiple fractures, including longitudinal and oblique fractures of the tibia and fibula. Acute care involved immediately re-locating the ankle and same-day surgery. Before corrective surgery, my ankle was stabilized by external fixation, which involved rods and pins extending from the bone externally to maintain, align, and stabilize the fractures. A week later, I underwent reparative surgery, which involved drilling a system of three distinct plates and multiple nails to properly align and allow healing of the fractures. Following almost five months on crutches and with my ankle and calf encased by a protective boot, I could finally—albeit painfully and slowly—walk again. The long-term ramifications of my injury include learning to walk again, development of early arthritis

(cartilage in the ankle was completely destroyed), chronic pain, and dealing with large plates in the ankle. Some of these issues were addressed during half a year of physiotherapy, but indeed, a year and a half later, the metal plates still remain in my ankle and will eventually be removed by surgery. Chronic pain also continues to be a problem, as well as limited flexibility of the ankle itself. Although I incurred a major bone break, I fortunately had prevented further injury by taking a motorcycle course and using protective equipment while I was riding. I wore a certified helmet, heavy-duty motorcycle jacket, gloves, jeans, and leather boots, which helped prevent any lifethreatening or open-wound injuries during the accident. Finally, while traumatic accidents do happen, prevention and preparation can mean the difference between life and death as exemplified by my own experience.




Resuscitation of the Trauma Victim Early intervention impacts on patient outcome

Professor and Associate Chair of Surgery, University of Toronto


ivilian trauma represents a significant health care problem. It ranks first among diseases in terms of years of life lost and fourth in overall mortality.1 Virtually any physician, when asked about the initial management of the trauma victim, will rhyme off the mnemonic- the ABCs- Airway, Breathing, Circulation. All represent critical components of the early interventions aimed at sustaining life until necessary definitive treatment of the injury occurs. The restoration of circulating blood volume in patients who have had significant blood loss related to the trauma is primarily intended to ensure that oxygen delivery to vital organs in the body is sustained. With timely and appropriate interventions, including transport to designated trauma centres, morbidity and mortality in the trauma victims can be minimized but not totally prevented. 19 | IMS MAGAZINE FALL 2012 TRAUMA

Several models have been proposed to explain the clinical course of patients sustaining major trauma and developing organ dysfunction later on during their hospitalization. Among these, the “two-hit” model has evolved as a paradigm of human disease explaining the development of late organ injury following survival of an initial sublethal trauma insult.3 In the context of hemor-

rhagic shock, the “two-hit” model suggests that shock/resuscitation primes the immune system for increased responsiveness to a second delayed inflammatory stimulus, and the resulting excessive tissue inflammation leads to organ injury. This hypothesis was supported by early studies from the scientists at the University of Colorado.4 These investigators took blood from both normal individuals and from trauma patients and studied the responsiveness of circulating neutrophils to stimulation. They showed that trauma neutrophils were profoundly more responsive to stimulation than those from normal controls. This observation firmly established in man the concept that shock/resuscitation might serve to predispose trauma victims to subsequent organ injury by making their immune response more exuberant. Based on these clinical observations, several groups including our own, established in vitro and in vivo model systems to study the “two-hit” hypothesis as it relates to lung injury following shock resuscitation.5,6 Using these models we have studied both mechanisms of injury and potential treatment strategies. Our early work focused on model development. We reported that resuscitated hemorrhagic shock in rodents serves as the initial or priming event for the development of endotoxin-induced lung injury. Interestingly, while neither shock nor low dose endotoxin alone caused injury, the sequential insults of shock/resuscitation (S/R) followed by intratracheal endotoxin lead to marked lung neutrophil accumulation and profound lung injury. This phenomenon is measured by lung leakiness and histopathological changes. In these studies, we further demonstrated that macrophages in the lung following S/R elaborated far more proinflammatory molecules in response to endotoxin than naïve animals. Among these, the chemokine cytokine-induced neutrophil chemoattractant (CINC), the rat homologue of Interleukin,8 was shown to be responsible for the excessive lung neutrophilia and the resulting injury. S/R was

Photo by Laura Feldcamp

Ori D. Rotstein, MD

While most early deaths are due to uncontrolled blood loss and brain injury, delayed mortality often occurs related to progressive deterioration of vital organs, so called “Multiple Organ Dysfunction Syndrome (MODS).” The precise reason why organs throughout the body fail following trauma, even though they have not actually been injured during the initial traumatic event, has been the subject of intensive investigation over the past few decades. One prevailing concept is that major trauma induces a “systemic” inflammatory response and this overwhelming and sustained inflammation in the various organs leads to injury and deterioration of function. Any organ can be involved in this inflammatory response, but the lung, kidney and liver seem to be particularly common targets. In particular, lung dysfunction occurs frequently in trauma victims. In its fullest manifestation, lungs exhibit profound infiltration with inflammatory cells, particularly neutrophils, which injure the lung tissue causing leakiness of the vasculature and flooding of the lungs with fluid. This clinical scenario, called the Acute Respiratory Distress Syndrome (ARDS) has been shown to be an important contributor to late morbidity and mortality.2 Our research group has a longstanding interest in understanding how hemorrhagic shock followed by resuscitation is able to render patients more susceptible to the development of MODS and in particular, lung injury. We have focused our work on understanding the mechanism of these events with a view to developing and testing new therapeutic approaches first in animal models and then in humans.

FEATURE shown to cause earlier and heightened nuclear translocation of the transcription factor NF-ÎşB in lung alveolar macrophages, leading to increased transcription of the a number of proinflammatory genes including CINC and tumour necrosis factor. Several studies have shown that the generation of oxidative stress is central to this priming event. Ischemia/reperfusion of the GI tract with the generation of the circulating xanthine oxidase has traditionally been implicated as the source of oxidative stress. However, recent studies by investigators at the University of Pittsburgh have suggested that neutrophil (PMN) derived reactive oxygen species generated through activation of the PMN NADPH oxidase system may also be important.6 Furthermore, we observed that, not only was the heightened response due to increased proinflammatory molecules, but the failure of the lungs to generate an antiinflammatory response also appeared to be contributory. Interleukin 10, normally upregulated by endotoxin, failed to increase in response to endotoxin in cells recovered from animals following S/R, and in addition, exogenous IL-10 administration proved protective in this model. Together, these finding suggested the possibility that intervention during shock/resuscitation might prove beneficial in preventing macrophage activation. We therefore investigated a number of interventions that were initiated during the resuscitation phase, with a view to preventing lung injury. Among these, the use of a hyperosmolar resuscitation strategy proved most interesting. In a series of animal studies, we investigated the ability of 7.5% hypertonic saline (HTS) used as a resuscitation fluid to alter lung injury in our two-hit model. In these studies, hypertonic saline resuscitation prevented lung injury by impairing lung neutrophil accumulation.7 This beneficial effect appeared to be due to a number of mechanisms. Relevant to those discussed above, we showed that HTS resuscitation prevented elaboration of oxidants from the gastrointestinal tract during S/R and by doing so, prevented priming of lung macrophages for increased responsiveness to endotoxin.8 We also found that HTS had a profound direct effect on neutrophils. HTS-treated neutrophils were incapable of expressing their surface adhesion molecules and were therefore unable to bind and transmigrate into the lung tissue,

thereby further mitigating pulmonary injury. This worked spawned a number of studies by our group and others to investigate whether HTS could prevent ischemia/reperfusion injury of other organs including the heart, the liver, the gastrointestinal tract and the brain. In each of the organs, HTS was shown to lessen neutrophil sequestration and minimize injury. These studies in the animal setting really begged the question as to whether resuscitation with HTS in trauma patients with hemorrhagic shock might minimize organ injury and improve outcome. With Dr. Sandro Rizoli’s research group at Sunnybrook Health Sciences Centre, we performed a pilot study investigating the ability of HTS resuscitation in trauma victims to alter the immune system, in an anti-inflammatory manner as we had shown in rodents. Using a randomized, controlled and double-blinded protocol, the studies demonstrated that HTS exhibited profound anti-inflammatory effects in man, including reducing both neutrophil and macrophage activation following shock/ resuscitation.9 Obviously, the small number of patients studied in this pilot investigation was insufficient to judge mortality endpoints. However, these studies set the stage for a multicenter North American collaborative study aimed at looking at the ability of HTS resuscitation to improve outcome in trauma victims. The results of these clinical studies have recently been published. While HTS has clear immunomodulatory effects in man, the studies clearly demonstrated that HTS administrated as a resuscitation fluid in trauma patients did not significantly improve mortality or lessen traumatic brain injury.10 The precise reason for this outcome is not clear, but it likely speaks to the complexity of the trauma patient and the fact that a short-lived transient intervention may be insufficient to exert clear benefit in this patient population. Moving forward, the potential anti-inflammatory effect of HTS may have benefits in other ischemia/reperfusion settings, a question that bears investigation in man. While HTS did not prove to be effective in the trials, the progression of studies from fundamental through to clinical trials is an excellent example of translational research. During these investigations, we learned a great deal about the mechanisms underly-

ACUTE CARE ing development of lung injury in patients sustaining hemorrhagic shock. These may suggest alternate approaches in the future to lessen organ injury in this patient population. It is also important to observe that this basic and applied research was predominantly the work of Surgeon-Scientist trainees working in the laboratory. These individuals are ideally suited to discover new solutions to clinical problems by applying their knowledge of disease to the generation of hypotheses aimed at understanding pathological processes and defining new treatments. This is an important mandate of the Institute of Medical Science, one that is key to medical discovery and improved patient care.

References 1. Gross CP, Anderson GF, Powe NR The relation between funding by the National Institutes of Health and the burden of disease N Engl J Med. 1999; 340: 1881-1887. 2. Ciesla DJ, Moore EE, Johnson JL, Burch JM, Cothren CC, Sauaia A. The role of the lung in postinjury multiple organ failure. Surgery. 2005; 138: 749-757. 3. Moore FA, Moore EE. Evolving concepts in the pathogenesis of postinjury multiple organ failure. Surg Clin North Am. 1995; 75; 257-27. 4. Botha AJ, Moore FA, Moore EE, Fontes B, Banerjee A, Peterson VM. Post injury neutrophil priming and activation states: therapeutic challenges. Shock. 1995; 3; 157-166. 5. Fan J, Marshall JC, Jimenez M, Shek PN, Zagorski J, Rotstein OD. Hemorrhagic shock primes for increased expression of cytokine-induced neutrophil chemoattractant in the lung: role in pulmonary inflammation following lipopolysaccharide. J Immunol. 1998; 161; 440-447. 6. Fan J, Li Y, Levy RM, Fan JJ, Hackam DJ, Vodovotz Y, Yang H, Tracey K J, Billiar TR, Wilson MA. Hemorrhagic shock induces NAD(P)H oxidase activation in neutrophils: role of HMGB1TLR4 signaling. J Immunol. 2007; 178: 6573-6580. 7. Rizoli SB, Kapus A, Fan J, Li YH, Marshall JC, Rotstein OD. Immunomodulatory effects of hypertonic resuscitation on the development of lung inflammation following hemorrhagic shock. J Immunol. 1998; 161: 6288-6296. 8. Powers KA, Zurawska J, Szaszi K, Khadaroo RG, Kapus A, Rotstein OD. Hypertonic resuscitation of hemorrhagic shock prevents alveolar macrophage activation by preventing systemic oxidative stress due to gut ischemia/reperfusion. Surgery. 2005; 137: 66-74. 9. Rizoli SB, Rhind SG, Shek PN, Inaba K, Filips D, Tien H, Brenneman F, Rotstein O. The immunomodulatory effects of hypertonic saline resuscitation in patients sustaining traumatic hemorrhagic shock: a randomized, controlled, double-blinded trial. Annals of Surgery. 2006; 243; 47-57. 10. Bulger EM, May S, Kerby JD, Emerson S, Stiell IG, Schreiber MA, Brasel KJ, Tisherman SA, ROC Investigators et al. Out-of hospital hypertonic resuscitation after traumatic hypovolemic shock: a randomized, placebo controlled trial. Annals Surg. 2011; 253; 431-41.



Understanding Excessive Bleeding in Trauma Patients

Treating Coagulopathy

The primary goal of Dr. Rizoli’s research is on the translation of the basic science and pathophysiology of hemorrhagic shock and blood transfusion all the way to large-scale clinical trials amongst trauma patients.

Sandro Rizoli, MD, PhD, FRCSC, FACS Professor of Surgery and Critical Care Medicine University of Toronto De Sousa Trauma Research Chair President, Trauma Association of Canada Trauma Surgeon, Sunnybrook Health Sciences Centre Scientist, Sunnybrook Research Institute


Traumatized patients rapidly become coagulopathic: they cannot clot appropriately, which leads to profuse bleeding and sometimes death. It was initially thought that traumatized patients became coagulopathic because of dilution and loss/consumption of clotting elements. However, in 2003, Brohi and colleagues1 proposed a primary (or inherent) defect in coagulation (or hemostasis) as being responsible for the early trauma coagulopathy, which can be worsened by dilution. Though this paper brought our understanding of trauma-related coagulopathy much further, the mechanisms leading to early (first few hours) trauma coagulopathy are poorly understood and are the focus of my research.

Research I - A look into the mechanisms of coagulopathy A few studies by our group at Sunnybrook Health Sciences Centre (SHSC), which includes Dr. Callum (Transfusion Medicine), Dr. Nascimento (Surgery), Dr. Reis (Clinical Pathology), Dr. Trpcic and Dr. Coroux (Research), have shown that following the trauma, the body releases both a potent anticoagulant called Activated Protein C (APC) and a fibrinolytic agent called tissue Plasminogen Activator (tPA).2,3,4 TPA is used clinically in patients with myocardial infarction and stroke to lyse the clot and allow flow

of blood to ischemic heart/brain. It is the combination of APC and tPA that result in an anticoagulated trauma patient—a patient who is incapable of forming strong enough clots to stop bleeding. The anticoagulation can occur in varying degrees and promptly “dissolves” (lyse) clots that are formed. This phenomenon is called hyper fibrinolysis.5,6 In addition, our team discovered that the “antidotes” to APC and tPA, such as PAI-1 and TAFI, are depressed, worsening the anticoagulation and excessive fibrinolysis. The combination of multiple hemostatic defects that vary over time and in response to different medical interventions result in a very complex picture. It also explains why it is so difficult to study trauma coagulopathy, particularly soon after the trauma. Furthermore, precisely identifying the hemostatic defects may change how each patient is treated. There is no prescribed formula on how to best treat these patients since there is so much variation and the ideal treatment must be tailored to the present needs of each individual patient.

The first cause of death among these patients is severe head injury and the second is bleeding, which is also the first cause of preventable death. Another problem in treating coagulopathic patients is that the laboratorial diagnostic tests have many limitations.7 Firstly, many

Photo by Paulina Rzeczkowska


hile cancer and cardiovascular disease strike mostly elder people, trauma strikes the young when they are at the peak of their productive lives—trauma is the leading cause of death in Canadians below the age of 40. The first cause of death among these patients is severe head injury and the second is bleeding, which is also the first cause of preventable death.


ACUTE CARE says can take days for the results to be ready, making them useless for directing the resuscitation of patients immediately after trauma. Secondly, there are only a few tests that can be done immediately after a trauma; these tests still take time to be done—often around one hour—which is enough time for the patient to die. Thirdly, they only evaluate particular portions of the hemostasis and there is no lab test to measure hyper fibrinolysis soon after the trauma. To overcome these problems, we have been studying two similar equipments including thromboelastography (TEG) and thromboelastography (ROTEM) in trauma.8 These tests can be done at bedside, provide results in a matter of minutes, and give a picture of the whole hemostasis—from the initiation of clotting, to clot propagation, amplification, and lysis. At SHSC these machines are kept in the laboratory that is linked to the trauma room, operating room, and blood bank via large screens. The results are displayed in real time on these large screens as the test is being done. In using this equipment, clinicians can use the resulting graph to immediately identify which coagulation problems are occurring in a particular trauma patient and treat them—a truly “custom made treatment.” TEG and ROTEM are the only tests that diagnose hyper fibrinolysis in “real life trauma resuscitation.”5 Our team is conducting research to find TEG/ROTEM levels that, once reached, will automatically set off the blood bank to prepare blood products even before the physician requests them. The goal of this project is to reduce the time between diagnosing life-threatening coagulopathy and its treatment. It also allows the physician to focus on resuscitating the coagulopathic patient instead of wasting time interpreting lab tests and later ordering blood products.

Research II - Focus on Clinical Trials In 2007, a series of retrospective studies9,10 proposed that all traumatized patients who

are massively bleeding should be resuscitated with “whole” blood instead of saline solutions. Whole blood is obtained by transfusing patients with 1 unit of red blood cells for every 1 unit of plasma for every 1 unit of platelets (or 1:1:1 resuscitation). While this proposal rests on a sound rationale, so far no studies have conclusively proven this to be beneficial. These retrospective studies have methodological limitations (biases) limiting their power. There is also concern with the fact that blood is scarce, expensive, and has significant side effects (e.g. respiratory distress syndrome).

...the ideal treatment must be tailored to the present needs of each individual patient. Our research team just finished the first randomized controlled trial (RCT) in the world, comparing 1:1:1 with standard resuscitation. Trying to enroll a massively bleeding patient (thus near death) while being actively resuscitated is very difficult and required major logistic planning and collaboration from many different groups within SHSC. In this study we did not find a survival advantage to 1:1:1. The manuscript is under consideration by a major journal. Very recently, we started enrolling patients into a new multicentre RCT along with 11 other hospitals in the United States to test— once for all—whether 1:1:1 is the best way to resuscitate massively bleeding trauma patients. This study is funded by the National Institutes of Health, Canadian Institutes of Health Research, and Defense Research and Development Canada. It will take four years to complete and over 500 patients will be enrolled. We hope it will conclusively demonstrate the best way to resuscitate these patients.

Summary The studies done by our group does at SHSC are all clinical in nature. The focuses are on understanding the mechanisms leading to early trauma coagulopathy and the best ways to diagnose and treat bleeding and coagulopathic patients. Our hope is to reduce the enormous burden of trauma worldwide.

References 1. Brohi K, Singh J, Heron M, Coats T: Acute traumatic coagulopathy. J Trauma. 2003 Jun;54(6):1127-30. 2. Jansen JO, Scarpelini S, Pinto R, Tien HC, Callum J, Rizoli SB: Hypoperfusion in severely injured trauma patients is associated with reduced coagulation factor activity. J Trauma. 2011 Nov;71(5 Suppl 1):S435-40. 3. Rizoli SB, Scarpelini S, Callum J, Nascimento B, Mann KG, Pinto R, Jansen J, Tien HC: Clotting factor deficiency in early trauma-associated coagulopathy. J Trauma. 2011 Nov;71(5 Suppl 1):S427-34. 4. Tien HC, Scarpellini S, Callum J, Tremblay L, Rizoli S: Assessing response to changing plasma/red cell ratios in a bleeding trauma patient. Am J Emerg Med. 2010 Jan;28(1):120.e1-5. 5. Cotton BA, Harvin JA, Kostousouv V, Minei KM, Radwan ZA, Schöchl H, Wade CE, Holcomb JB, Matijevic N: Hyperfibrinolysis at admission is an uncommon but highly lethal event associated with shock and prehospital fluid administration. J Trauma Acute Care Surg. 2012 Aug;73(2):365-70. 6. Rizoli S, Nascimento B Jr, Key N, Tien HC, Muraca S, Pinto R, Khalifa M, Plotkin A, Callum J: Disseminated intravascular coagulopathy in the first 24 hours after trauma: the association between ISTH score and anatomopathologic evidence. J Trauma. 2011 Nov;71(5 Suppl 1):S441-7. 7. Dzik WH, Blajchman MA, Fergusson D, Hameed M, Henry B, Kirkpatrick AW, Korogyi T, Logsetty S, Skeate RC, Stanworth S, MacAdams C, Muirhead B: Clinical review: Canadian National Advisory Committee on Blood and Blood Products--Massive transfusion consensus conference 2011: report of the panel. Crit Care. 2011;15(6):242. Epub 2011 Dec 8. 8. Scarpelini S, Rhind SG, Nascimento B, Tien H, Shek PN, Peng HT, Huang H, Pinto R, Speers V, Reis M, Rizoli SB: Normal range values for thromboelastography in healthy adult volunteers. Braz J Med Biol Res. 2009 Dec;42(12):1210-7. Epub 2009 Oct 30. 9. Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, Sebesta J, Jenkins D, Wade CE, Holcomb JB: The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma. 2007 Oct;63(4):805-13. 10. Holcomb JB, Jenkins D, Rhee P, et al: Damage control resuscitation: directly addressing the early coagulopathy of trauma. J Trauma. 2007 Feb;62(2):307-




Posttraumatic Injury

We Have Met the Enemy, and He is Us:

Why Do Hospitalized Trauma Patients Die? care unit (ICU). In the absence of neurologic injury, however, the leading cause of late death and disability following trauma is a process called Multiple Organ Dysfunction Syndrome (MODS). This is characterized by progressive, though potentially reversible loss of vital organ function involving the lungs, kidneys, and circulatory system. First described almost 40 years ago,2 MODS encompasses the body’s response to injury over time, and reflects the successes and failures of contemporary critical care.

John Marshall, MD Departments of Surgery and Critical Care Medicine Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael’s Hospital Department of Critical Care Medicine, University of Toronto

MODS manifests differently in each organ. In the lung there is increased interstitial edema and an influx of activated neutrophils, resulting in impaired oxygen uptake into the blood, producing Acute Respiratory Distress Syndrome (ARDS) (Figure 1). In the kidney, a combination of altered blood flow, apoptosis of renal epithelial cells, and interstitial edema results in impaired excretion of fluids and solutes and a rising creatinine level. Dysfunction of the circulatory system is characterized by reduced perip eral vascular tone, increased endothelial permeability, and various degrees of myocardial depression, while hematologic dysfunction manifests in

increased intravascular coagulation resulting in depletion of clotting factors, and leads to reduced platelet counts. Prognosis is directly related to the number of failing organs and the severity of derangement within each organ system (Figure 2). Early studies of the development of MODS in patients following trauma focused on the role of occult infection, which often arises within the peritoneal cavity.3 With an evolving understanding of the biology of inflammation, it is apparent that although infection, along with tissue trauma or ischemia, can be the antecedent to MODS, the syndrome develops because of the systemic activation of an acute inflammatory response. The biologic processes underlying this response are complex, and the interested reader is referred to more detailed reviews.4,5 Briefly however, conserved microbial products such as endotoxins, or certain intracellular molecules such as heat shock proteins, bind to pattern recognition receptors on host immune cells, predominantly monocyte/macrophages and neutrophils. These receptors target intracellular signalling pathways that lead to the repression or activation of thousands of dif-

Devastating injuries to the brain or spinal cord account for a number of deaths amongst those patients who survive the initial traumatic event and are admitted to an intensive 23 | IMS MAGAZINE FALL 2012 TRAUMA

Figure 1. Photomicrograph of the lung in ARDS. Characteristic microscopic features of ARDS include massive neutrophil influx (thin arrows), microvascular thrombosis (thick arrows), and fibrin deposition in the interstitium (clear arrows). All of these impede gas exchange across the alveolus into the pulmonary capillary bed, and so hypoxemia is a defining feature of the clinical syndrome.

Photos courtesy of Yekta Dowlati


raumatic injuries resulting from motor vehicle crashes, falls, and war or urban violence are among the leading causes of preventable death in the world today. Trauma is responsible for more than 5 million deaths each year world-wide, disproportionally affecting the young and people from low income regions.1 Some of these deaths are a consequence of lethal and non-modifiable events – decapitation, rupture of the heart or a major blood vessel, devastating injury to the brain, etc. – however, advances in prehospital care and early resuscitation have enabled the survival of patients who previously would have died, and in the process, created new and potentially modifiable challenges for the attending clinician.



Figure 2. Radiographic features of the lung in ARDS A plain xray of the lung of a patient with ARDS reveals diffuse patchy infiltrates affecting all lung zones (Figure 2a). However a CT scan (Figure 2b) reveals the process to be much less homogeneous, with consolidation in the dependent zones (black arrow), reflecting collapse and pooling of secretions in a patient nursed supine, and air cysts in the anti-dependent zones (black arrow), reflecting over-distention of lung units by positive pressure ventilation.

ferent host genes,6 and to the cellular release of hundreds of biologically active mediator molecules that have both pro- and anti-inflammatory activity. These mediators then evoke cellular responses such as the generation of nitric oxide leading to relaxation of vascular smooth muscle and vas odilatation, expression of tissue factor on endothelial cells leading to intravascular coagulation, and activation of signalling pathways resulting in apoptosis of epithelial cells and lymphocytes. The consequences of this process result in MODS. In the lung, for example, increased permeability of the pulmonary capillaries and alveolar epithelium results in interstitial edema while endothelial cell activation leads to microvascular thrombosis. Epithelial cell death or apoptosis increases, and activated neutrophils are recruited to the injured lung, exacerbating the local inflammatory injury. Fibrin deposition in the alveolar wall renders the normally delicate alveoli thick and less distensible (Figure 1). All of these processes lead to impaired oxygen uptake from the alveoli, and are responsible for the clinical changes known as the Acute Respiratory Distress Syndrome (ARDS). The lung injury of ARDS and the generalized organ system dysfunction of MODS arise from more than the body’s response to the initial insult. Supportive care in the ICU can itself cause further inadvertent tissue injury. Plain radiographs of the lung of a patient with ARDS reveal diffuse patchy infiltrates – one of the defining characteristics

of the syndrome (Figure 2a). Computerized tomography of the lung, however, reveals consolidation in dependent lung zones resulting from the fact that patients are nursed supine in the ICU, and cystic changes in antidependent regions, a result of overdistention and rupture of alveoli by positive pressure ventilation (Figure 2b). Recognition of the potentially modifiable component of ARDS that results from ICU care led to an alternate name for the syndrome – ventilator-induced lung injury, or VILI – and studies have shown that lung protective ventilatory strategies can attenuate organ injury and apoptosis,7 reduce the inflammatory response,8 and increase survival.9 Other examples of the inadvertent consequences of ICU support abound. The administration of fluids in the setting of increased capillary permeability causes edema, and contributes not only to pulmonary dysfunction, but also to myocardial, renal, and central nervous system dysfunction.10 Sedation and analgesia predispose patients to muscle weakness and extend the time spent on the ventilator and in the ICU. Total parenteral nutrition can induce liver injury, and the use of broad spectrum antibiotics promotes the emergence of resistant organisms, superinfections, and infections such as C. difficile colitis. Indeed MODS is the quintessential iatrogenic illness: it only develops because medical intervention has succeeded in preventing a rapid death, but it evolves further because of the direct and indirect consequences of that intervention.11

The survival of severely injured trauma patients has improved dramatically over the past century. This improvement is largely a consequence of advances in transport and regionalization of care of injured patients, of effective early resuscitation, of improved surgical management strategies including the wider adoption of damage control approaches, and of the development of effective means of organ system support in the ICU. Further improvements will come from a recognition that the unsolved frontier lies within – from a better understanding of the endogenous host innate immune response that results in post-resuscitation organ injury, and of the iatrogenic consequences of medical care that exacerbate that injury.

References 1. Chandran A, Hyder AA, Peek-Asa C (2010) The global burden of unintentional injuries and an agenda for progress. Epidemiol Rev 32: 110-120. mxq009 [pii];10.1093/ epirev/mxq009 [doi]. 2. Baue AE (1975) Multiple, progressive, or sequential systems failure. A syndrome of the 1970s. Arch Surg 110: 779-781. 3. Fry DE, Pearlstein L, Fulton RL, Polk HC (1980) Multiple system organ failure. The role of uncontrolled infection. Arch Surg 115: 136-140. 4. O’Neill LA, Bowie AG (2007) The family of five: TIRdomain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol 7: 353-364. 5. Marshall JC, Charbonney E, Gonzalez PD (2008) The immune system in critical illness.Clin Chest Med 29: 605-16, vii. S0272-5231(08)00087-7 [pii];10.1016/j. ccm.2008.08.001 [doi]. 6. Calvano SE, Xiao W, Richards DR, Felciano RM, Baker HV, Cho RJ, Chen RO, Brownstein BH, Cobb JP, Tschoeke SK, Miller-Graziano C, Moldawer LL, Mindrinos MN, Davis RW, Tompkins RG, Lowry SF (2005) A network-based analysis of systemic inflammation in humans. Nature 437: 1032-1037. 7. Imai Y, Parodo J, Kajikawa O, de Perrot M, Fischer S, Edwards V, Cutz E, Liu M, Keshavjee S, Martin TR, Marshall JC, Ranieri VM, Slutsky AS (2003) Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome. JAMA 289: 2104-2112. 8. Ranieri VM, Suter PM, Tortorella C, de Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS (1999) Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome. A randomized controlled trial. JAMA 282: 54-61. 9. Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A, for the ARDS Network (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342: 1301-1308. 10.Prowle JR, Echeverri JE, Ligabo EV, Ronco C, Bellomo R (2010) Fluid balance and acute kidney injury. Nat Rev Nephrol 6: 107-115. nrneph.2009.213 [pii];10.1038/ nrneph.2009.213 [doi]. 11. Marshall JC (2010) Critical illness is an iatrogenic disorder. Crit Care Med 38: S582-S589.




Tetyana Pekar

STREAM MSc candidate SUPERVISOR Dr. Mei Zhen

Writing Through Science


or most graduate students, thesis defense preparations can elicit mixed emotions. It is not uncommon for anxiety to follow the initial period of elation as the reality of thesis writing sets in. For a rare few, like Tetyana Pekar, thesis writing is a far less daunting process, and is in fact, rather enjoyable. Although early in her career, she already has ample experience in writing and editing. Combined with her genuine passion for science, Pekar makes scientific writing seem effortless. Pekar first gained exposure to research during her undergraduate education in neuroscience at the University of Toronto. She was drawn to science because she values critical thinking and appreciates the importance of the scientific method as a tool to explain the world around us. She commented, “To be the first to discover or to understand some aspect of nature—no matter how small—is really a privilege.” While completing her undergraduate degree, Pekar was fine-tuning her writing and editing skills by contributing to two peer-reviewed undergraduate journals: the Journal of Undergraduate Life Sciences (JULS) and

the Journal of Young Investigators (JYI). Her writing skills were quickly acknowledged, and she was awarded the 2009 National Sciences and Engineering Research Council (NSERC)-JULS Best Review Article Award for her article on the genetic and neurobiological etiology of anorexia nervosa.1 Pekar currently studies neuroscience at the Samuel Lunenfeld Research Institute in Mount Sinai Hospital. Her work in elucidating the role of an evolutionary conserved protein kinase in neuronal development and function in C. elegans has earned her a Julie Payette NSERC Research Scholarship, awarded to the top 24 Master’s level applicants across Canada, in addition to other notable honours. Outside of her studies, Pekar continues to have a strong interest in eating disorders. Earlier this year, she created a blog called Science of Eating Disorders (SEDs; http://www. SEDs’ goal is to make peerreviewed eating disorder research accessible and understandable for the public. While other eating disorder blogs focus primarily on the process of recovery, Pekar wanted to focus on translating and disseminating the

findings of eating disorder research. What makes SEDs especially unique is that all bloggers—three at the time of writing this article—have both a science background and a personal history of struggling with an eating disorder, allowing the articles to be enriched by their personal experiences. “It is the most rewarding thing I have ever done,” Pekar said about the SEDs project. “To get comments from readers saying, ‘Thank you from the bottom of my heart for writing this article,’ is so rewarding.” She added with a laugh, “Besides, I can do this in my spare time to get a break from reading papers about worms!” Outside of her lab work and blogging, Pekar actively participates in other endeavours that have helped her develop her writing and editing skills. She is a private tutor for individuals seeking to improve their writing, study biology, and prepare for the GRE. Pekar is also an Assistant Managing Editor for the IMS Magazine, and has co-authored multiple peerreviewed publications, including one in the distinguished journal, Nature Neuroscience.2 Currently in the midst of thesis writing, I asked Pekar about her plans following the completion of her Master’s degree. She expressed a desire to take the knowledge she has gained from her degree in the IMS and apply it to public policy. She elaborated by explaining that she wishes to use the critical thinking and research skills she has developed throughout her scientific training to help progress and promote evidence-based public policies. While defending her thesis later this year may mark the end of Pekar’s journey in the IMS, it is clear that this is only the beginning of her bright future in a field that will undoubtedly benefit from her strength in writing and communication. By Danielle DeSouza

1. Pekar, T. (2009). Genetic and neurobiological etiology of anorexia nervosa. University of Toronto Journal of Undergraduate Life Sciences (JULS), 3:79-81. 2. Cole, C.J., Marcaldo, V., Restivo, L., Yiu, A.P., Sekeres, M.J., Han, J.-H., Vertere, G., Pekar, T., Ross,P.J., Neve, R.L., Frankland, P.W. and Josselyn, S.A. (2012). MEF2 negatively regulates learning-induced structural plasticity and memory formation. Nature Neuroscience, 15:1255–64.


Photo by Laura Feldcamp




Dr. Antonio Strafella MD

ginning of his successful career in Canada. “I was only planning on staying in Canada for the one year fellowship,” reflects Dr. Strafella, “but it was a great time to enter the field with the advancement of deep brain stimulation as a new treatment for Parkinson’s disease.” As a post-doctoral fellow and assistant professor at the Montreal Neurological Institute at McGill University, he expanded into positron emission tomography, a method that now forms a critical component of his research studies. Strafella maintains an active research program, supervising IMS graduate students and post-doctoral fellows that come from around the world to work with him. He closely mentors his students, saying that he “learns just as much from his students as they do from [him].” Current research projects in his group range from the investigation of cognitive impairments and impulse control disorders in Parkinson’s disease to microglial activation and neurological structural and functional connectivity in Parkinson’s patients.

Photo by Yekta Dowlati


r. Antonio Strafella is a successful clinician-scientist within the Institute of Medical Science (IMS) and a Canada Research Chair in Movement Disorders and Neuroimaging. Strafella is a neurologist at the Toronto Western Hospital, an associate professor in the IMS, and a senior scientist in the Division of Brain Imaging and Behaviour Systems—Neuroscience at the Toronto Western Research Institute and the Research Imaging Centre at the Centre for Addiction and Mental Health. Strafella uses his interactions with patients to drive new research questions, maintaining an research laboratory that uses cutting edge neuroimaging techniques to study Parkinson’s

disease. He is internationally recognized for his work on the cognitive and behavioural symptoms of Parkinson’s disease—symptoms that Strafella points out “remain largely untreatable and can reduce a patient’s functioning and quality of life sometimes even more than the motor symptoms of the disease.” Strafella traces his interest in Parkinson’s disease back to his days as a medical student at the University of Bologna, in Italy. He was immediately drawn to the study of movement disorders, completing his residency in neurology and a PhD on the neurophysiology of motor control. A fellowship at the UofT with Dr. Peter Ashby marked the be-

As a researcher in a competitive field that is constantly advancing, Strafella is always thinking about the next way he can use neuroimaging to expand our understanding of Parkinson’s disease. To young researchers beginning their academic careers, he says, “You have to be aware that what you are working on now will likely be outdated in five years, and to come up with new ways to tackle new problems requires thinking outside the box.” This approach has not been lost on international funding agencies—Strafella’s innovative research ideas are funded by the Canadian Institutes of Health Research, the Parkinson Society of Canada, and the Michael J. Fox Foundation, to name a few. Strafella anticipates that there will be major advances in Parkinson’s disease research within the next few years, as new radioligands are developed to better visualize early changes in the brain. “The key with imaging will be the ability to identify patients in the very early stages of the disease before symptoms appear, to facilitate treatment of cognitive changes that happen in the later stages of Parkinson’s disease.” With IMS researchers like Strafella at the helm, these critical advances may very well begin at UofT. By Nancy Butcher


Book Reviews Excellent

Worth missing a day at the lab

Very Good

Try to squeeze in between experiments

Arrowsmith tracks the career trajectory, interpersonal relationships, passions, and pitfalls of an American man who sees scientific research as his calling. Martin Arrowsmith, exposed to medical practice at a young age while working at the rural office of a drunken elderly doctor, becomes fascinated with tools and textbooks. Martin attends medical school, but here he scorns his classmates, professors, and the medical educational system in general. He admires only rogue-like characters who are not constantly concerned with wealth and social status, such as the renowned German bacteriologist Max Gottlieb. Ultimately, Gottlieb serves as an inspiration to Martin in the struggle to become a “pure scientist” in a world of ignorance and corruption.

Sinclair Lewis Arrowsmith Penguin Group, 2010; 459 pages


cientific research is often viewed as a means to an end. The goal may be to develop an effective medical therapy, to enhance our quality of life, or to keep us safe and secure. Practical Science is the voice of grant applications, business ventures, political campaigns, and many scientific publications themselves. While the potential value of this applicable form of science is easily comprehensible, lesser understood is the worth of another Science: the kind that is for the sake of science alone. It is this Pure Science—driven only by the desire to seek truth—which Sinclair Lewis explores profoundly in his 1925 Pulitzer Prize-winning novel Arrowsmith. Widely considered to be the first major novel concerned with the culture of science,


Martin’s career involves work as a research assistant for Gottlieb, a rural doctor, a public health official, and a bacteriology scientist. His passion for science drives him tosleepless nights in the lab, where he makes groundbreaking discoveries. In contrast to many of his colleagues, however, Martin does research simply because he enjoys seeking truth. While others constantly pressure him to publish quickly and to commodify his work, Martin always demands more time to confirm his findings and turns down lucrative financial offers. Indeed, Martin aspires to attain the zealous attitude perfected by his mentor Gottlieb, who is described as being “so devoted to Pure Science… that he would rather have people die by the right therapy than be cured by the wrong.” Martin is no hero in his personal life. In a classic scene he announces to two women that he is engaged to both of them at once, and when he is married to Leora, who cares for him unconditionally, he often neglects and sometimes insults her. Martin rarely finds pleasure in socializing with colleagues, and he is often condescending. Altogether, Martin’s attitude contains many features that are still consistent today with stereotypical


Wait for the weekend


Wait until degree is complete

notions of a ‘scientist personality signature’: a hedonist for pure truth, overly consumed with crunching numbers and proving others wrong; a socially inappropriate cynic overly critical of popular culture. Arrowsmith deals with ethical issues that have become magnified in importance in the contemporary science world, such as research misconduct, conflicts-of-interest, and complications of public science communication. It is arguably more difficult today than ever to practice Pure Science, given the ever-increasing growth of ulterior incentives provided by sources that are far-removed from the intrinsic personal desire to seek truth. Lewis’ depiction of Martin as someone who is non-heroic but is to be highly respected for his self-discipline and honesty perhaps signifies that Pure Science alone is not always enough, but is nevertheless of great inherent value. Martin’s extremism is not a single simple answer to the problem of corruption in science, but it cannot be dismissed. In Arrowsmith, Lewis demonstrates that creative fiction can demystify the culture of science in a witty and illuminating manner that is not possible with other approaches. The novel’s messages are more important today than ever and should be considered as science continues to both provide real-world solutions and satiate human curiosity.

Column by Aaron Kucyi

BOOK REVIEWS to modern medical facilities. Many of these unsettling stories take the reader through an array of emotions, from disbelief to anger to sadness. Yet this is not a book about condemnation of wrong deeds by men. Rather than being a collection of sad stories that merely provide proof to the atrocities of which mankind is capable, the stories of these remarkable women are meant to serve as a testament to the human spirit and resilience. If these women could find the courage to not give up, how could the rest of the world not find the courage to act on their behalf?

Nickolas Kristof and Sheryl WuDunn Half the Sky: Turning Oppression into Opportunity for Women Worldwide Random House Publishing, 2010; 320 pages


he title of the book Half the Sky comes from the Chinese proverb “women hold up half the sky.” Yet in the world today, women bear a large proportion of the world’s poverty burden. The lack of access to health services, educational resources, and employment opportunities, as well as violence against women—which remains the most frequent form of human rights violations according to the United Nations—contribute to a vicious cycle of oppression against women. What would the world be like if women from every walk of life are given an equal opportunity to achieve their full potential? In Half the Sky, the husband and wife journalist team Nickolas Kristof and Shannon WuDunn make a compelling case that such a world would be infinitely better than the one that we currently inhabit. To begin their case, Kristoff and WuDunn give a series of personal, intimate portrayals of women who have been victims of oppression. Some of these women were taken from home and forced into unpaid prostitution; some were victims of extreme violence in the name of “family honour”; some were afflicted with obstetric fistula, a severe condition—often leading to a life time of abandonment by society—that is the result of difficult childbirth but is preventable by access

How to act, though, and where to begin? Kristoff and WuDunn provide inspiring examples of people—regular folks such as teachers, students, housewives, and sometimes even previous victims—who, often with little more than a simple idea and strong compassion, decide to confront the challenge and to make a difference. At rare occasions, the difference that is made is at a global policy level affecting multitudes of women; more often than not, however, an organized effort may result in changes in one individual village or a single household. Kristoff and WuDunn argue that an effort as small as a bake sale, made from the bottom up, counts as much as top-down efforts from world eaders. It is difficult for the reader to disagree, given the authors’ accounts of efforts made by these various individuals from different walks of life. Beyond the compelling stories that illustrate the issues and the heartfelt call for action to the reader, Half the Sky also confronts some of the barriers on the road to gender equality at the global scale. The roles of religion, culture, and tradition, as well as the complacent part played by many women themselves in perpetuating the oppression cycle are discussed with honesty and depth. Although the magnitude of the challenge—to stop the oppression of women around the world—is daunting, this book never loses a sense of hope and a positive outlook that differences can be made. Half the Sky is simply a book that should be read by all. Beyond the significance of its topic, it is, after all, a wellwritten, enjoyable and riveting work.

Column by Karrie Wong

What are you reading? Melanie Guenette, MSc candidate, recommends Stiff by Mary Roach “Stiff provides a jaw dropping account of the many uses for human cadavers. From recreating car crashes to running army tests and practicing cosmetic surgery, the possibilities are surprisingly numerous. This book leaves the reader intrigued, if not slightly uncomfortable, and is a good choice for anyone in the health field.” Benjamin Mora, PhD candidate, recommends Consilience: The Unity of Knowledge by Edward O. Wilson “E.O. Wilson strives to show how every domain of human knowledge—ranging from the social sciences and humanities to the religious studies and arts—can and ought to be reduced to fundamental laws of science, neuroscience, and/ or genetics. However, I see no reason why this “consilience” that Wilson aims, hopes and dreams of achieving is necessarily possible. It’s a tantalizing idea, but I feel bound up in skepticism contemplating the overwhelming and daunting complexity on the reductionist playbill—for at least it seems impossible that such randomly chaotic, precarious, unmethodical macro-level operations can be reduced to simple, material laws.” Adam Santoro, PhD candidate, recommends How to Create a Mind by Ray Kurzweil “Ray Kurzweil is a technological innovator and futurist. His ideas often come under scrutiny, since they are predictive (i.e., they are bold hypotheses) and are rarely supported empirically. In How to Create a Mind, Kurzweil outlines a computational neural network theory that he believes holds the key to emulating brain output. Critics come down hard on Kurzweil for not knowing the intricacies of neuroscience, but he would retort they these critics simply miss the forest for the trees. Overall, the details are somewhat unsubstantiated, but the overarching ideas are profound, intriguing, and mind altering.” If you are an IMS faculty member or student and would like to have your book review published in a future issue of the IMS Magazine, please send a 50-word review to



SOCIAL INEPTITUDE riven by the digital revolution, the Information Age is characterized by our ability to easily access and transfer information, an ability that is changing the way we communicate, learn, and conduct business. With any revolution comes fundamental change to society, culture, economy, and politics. Our increasing reliance on internet-based networking is weakening the basic skills we require to effectively interact with other people. This phenomenon is known as social ineptitude. Affecting mainly children and young adults, but touching the lives of everyone in one social setting or another, the prevalence of social ineptitude is on the rise.

come ingrained in our society. In 2009, 32% of wireless customers in Canada had a smartphone, up from 25% in 2008. These people used their smartphone for personal (nonbusiness) purposes 70% of the time, with social media applications being the most frequently downloaded.1 In 2010, 78% of Canadian households reported having a mobile phone, and 50% of households in the 18-to-34 age bracket used mobile phones strictly, with no traditional landline telephone.2 As of this year, Facebook reports having 955 million monthly active users (543 million of which use Facebook mobile products) and 552 million daily active users.3 Making our addiction blatantly obvious, 34% of Canadians would be willing to give up alcohol, 31% would sacrifice chocolate, and 27% would forgo coffee to retain their internet access.4 Finally, this current back-to-school advertisement from Future Shop confirms our indoctrination: Student 1, “I learned to type before I learned to write.” Student 2, “Initial data indicates that ‘Likes’ are better than hugs.” Student 3, “I was born on the internet… true story.”

Texting, tweeting, Facebook use, and the world of web-based communication have be-

The reality? There’s no need to see someone to tell them you like their new haircut; you

By S. Amanda Ali



can simply click “Like” on Facebook when they upload a picture of it the instant they leave the hair salon.

As face-to-face interactions become less frequent, people become less cognizant of acceptable behaviour in social settings. Ineptitude can manifest in many ways, including neglected personal hygiene, poor manners or lack of consideration for others, and the inability to read cues (known colloquially as the inability to “take a hint”). Unfortunately, it’s not too difficult to think of people who commit these offences. Like the person who has persistent bad breath or body odour, or who forgets to wash their hands after using the bathroom, or who coughs without covering their mouth. And the person who walks into your home and opens your fridge, and who interrupts or raises their voice to speak over others instead of speaking in turn, and who keeps others waiting by taking longer than needed when using common equipment–be it the chemical fume hood or a bank machine. Or the person who decides to sit down and continue talking (after you’ve said how much work you need to get done) while you glance at your watch, check your

Photo courtesy of; ID # 1126739

From social butterfly to social outcast, do you know where you stand?

VIEWPOINT cell phone, and/or rigidly stare at the task in front of you. Social ineptitude exists along a spectrum ranging from mild and occasional mistakes to severe and frequent transgressions. An individual may have no difficulty in social settings and still respond to a particular situation improperly, but this only makes them human and capable of error. To be inept is to consistently respond to situations inappropriately, making those around you uncomfortable and less likely to pursue future interactions with you. It is a self-perpetuating cycle because skills regress without practice, so the socially inept are doomed; their inability to engage people limits their opportunities to practice social interaction. Based on our societal norms, social ineptitude is worse when offenders fall into particular categories. Speaking out of turn is more accepted from a child or teenager, and less accepted when it is from an adult (or new Master’s student), because they are expected to know better. Social indiscretion is also less tolerable when coming from a co-worker with whom we are forced to interact. The expectation is that coworkers aim to make good impressions on each other by demonstrating common courtesy, but the reality is that common courtesy isn’t so common anymore. Science careers, among others, select for the socially inept, and then propagate the ineptitude. The television show The Big Bang Theory features astrophysicist Dr. Rajesh Koothrappali who suffers from social anxiety disorder in the form of selective mutism, which prevents him from speaking in the presence of women. The popular culture stereotype of scientists as socially-awkward nerds is evident, but is there any truth to it? Science generates experts on very specific topics, and it can be ostracizing to the individual. Certainly there are collaborative efforts and groups who study the same organ or signaling pathway or gene, but the purpose of a PhD is to train an individual in a particular way of thinking to answer a unique question. To achieve this, a significant amount of time is spent alone at a lab bench or animal facility, or with eyes down on a journal article, or sitting at a computer compiling results and writing reports. Opportunities for social interaction arise occasionally at lab meetings, seminars, and conferences, but these are usually anxiety-provoking events, challeng-

ing scientists to speak in public, defend their work, and actually engage in conversation. While this field probably attracts introverts, even social butterflies can expect to lose some of their skill by the end of the extensive training. Defined by Merriam-Webster as “one slavishly devoted to intellectual or academic pursuits,” a nerd is also a “socially inept person” and as such, scientists are truly nerds.5 But who cares? Social ineptitude is building to the point of compromised language skills and cowardly dating customs. To send messages quickly, texting lingo is commonly used, replacing words like “to” and “too” with the number “2,” or “your” and “you’re” with “ur.” Efficiency is good, but not if the price is literacy. Replacing different words with the same shorthand denies children (and some adults) the practice and comprehension of how each word should be properly used. Furthermore, it is difficult to compartmentalize texting lin-

Social offenders are mostly unaware of the barriers they create between themselves and the outside world. go from proper writing, and these shortcuts may enter into homework assignments or formal correspondences. With this new language comes a new dating strategy. The latest urban legend claims that 1 in 5 relationships now start online. Simply fill in age, height, and hobbies, upload a photo, and start messaging to meet your soul-mate. No effort required for choosing the right outfit, going to the newest social spot, or finding the courage to approach a person in real life. One popular online dating website even offers a test to gauge social ineptitude, recognizing that a large part of its target audience is likely unskilled at socializing. Test results range from the socially obsessed, who collect friendships and consider them as reflective of social status, to social pariah, who are essentially social rejects with no friends.6

cially inept is their complete ignorance of their own ineptitude. Social offenders are mostly unaware of the barriers they create between themselves and the outside world. A study by Kruger and Dunning highlighted the dilemma of being too incompetent to recognize your own incompetence, and social incompetence is no exception.7 If, for example, scientists are surrounded by equally inept scientists, then who corrects whom? Is it the responsibility of parents to teach their children how to behave appropriately in social settings? Should mentors at school and work provide mentees with training and guidance on social skills? Will we ever overcome the discomfort associated with telling an oblivious offender that they have behaved inappropriately in a social encounter? As students become more formally educated and less socially adept, it can be expected that those who demonstrate interpersonal flair in interviews will stand out, and ultimately be successful. So instead of emailing the person sitting across from you, consider speaking up to practise those rusty social skills, and prevent the larynx from becoming a vestigial structure. Disclaimer: The opinions expressed by the author are in no way affiliated with the Institute of Medical Science or the University of Toronto. Comments are welcome at theimsmagazine@gmail. com.

References 1. J.D. Power and Associates 2009 Canadian Wireless Customer Satisfaction Study. [updated 2009 Oct 27; cited 2012 Sep 10]. Available from: pressrelease.aspx?ID=2009242 2. Residential Telephone Service Survey, Statistics Canada. [updated 2011 July 5; cited 2012 Sep 10]. Available from: 3. Facebook Newsroom, Company Info: Key Facts. [updated 2012 June; cited 2012 Sep 10]. Available from: http://newsroom. 4. Rogers Innovation Report: What would YOU give up for the Internet? [updated 9 May 2012; cited 2012 Sep 10]. Available from: 5. Merriam-Webster, An Encyclopaedia Britannica Company. [cited 2012 Sep 10]. Available from: 6. The Social Ineptitude Test, okcupid. [cited 2012 Sep 10]. Available from: 7. Kruger J, and Dunning D. Unskilled and Unaware of It: How Difficulties in Recognizing One’s Own Incompetence Lead to Inflated Self-Assessments. J Pers Soc Psychol. 1999;77(6):112134.

The value of these tests may be underestimated because the worst quality of the soIMS MAGAZINE FALL 2012 TRAUMA | 30


Science Fact

vs. Fiction:

The Public Deserves to Know the Truth


onsciousness is difficult to define. Its relationship to other cognitive phenomena and even its very existence is often debated. Some philosophers, such as Daniel Dennett, believe that consciousness does not exist. Others, such as John Searle, argue that consciousness is a purely biological problem and its ontology can be understood exclusively through science. In addition to the widely varying viewpoints between theologians, philosophers, and scientists, there is often disagreement between individuals within a specific field. The journal Trends in Cognitive Sciences recently published a series of articles in a consciousness-themed issue, and each author had seemingly incompatible viewpoints


about the subject. At the very least, it is obvious that the topic is extremely complicated. A stroll through the science section in your local bookstore, however, will suggest otherwise. In a recent issue of the IMS Magazine I reviewed a book called The Illusion of Conscious Will, which offers a view of consciousness that is increasing in popularity. The author states that consciousness is a mere feeling, and the concept of free, conscious willing is an illusion. He gives evidence from psychological experiments to demonstrate how human behaviour can arise from purely unconscious brain events. He then extrapolates this to the stance that all behaviour can

be explained by unconscious events, and consciousness is just a useful by-product. The ideas and experiments presented in the book were definitely interesting. However, it suffered from a common problem in popular science literature: it forced conclusions from insufficient data, and sensationalized the research. With such a complex topic as consciousness and free will, the results of some neuroscience and psychology experiments do not point to a unified theory of consciousness, and to pretend that they do is disservice the science. When writing for the lay audience, journalists and scientists should strive to explain concepts simply, but they should never resort to inflating conclusions and sensationalizing research. This behaviour gives

Photo courtesy of; ID#15755681

By Adam Santoro

VIEWPOINT the public a flawed view of science, inevitably leaving science to defend itself against those who doubt its efficacy in attaining knowledge about the world. There is a propensity for writers to almost exclusively present their personal thoughts on a topic, often while inflating conclusions to really drive their point home. On the surface, this seems harmless: if it is the author’s own book why should he not be able to present arguments for his own theory? And what about those theories that are obviously true, and fully agreed upon by the scientific community (for example, an author’s personal opinion may be that evolution is true, which is also an opinion that the scientific community holds as a whole)? Texts discussing well established, successful scientific theories should not have to concede page space to opposing theories simply because a few straggling deniers exist. However, for unestablished theories, more care is needed. In the mainstream media (i.e., best-selling books, newspapers, etc.), the target audience is generally uninformed about scientific topics, and even the process by which science makes progress. If an author presents a single viewpoint, the average reader will interpret it as an established fact. Moreover, if the author presents various lines of evidence and forces his own conclusion, the average reader will suppose that scientific progress follows exactly as presented by the author. This is of course troublesome, since even a casual reader of popular science will eventually form doubts: “You talk about a study in mice and you come up with that conclusion of human cognition? How is science any different from believing in the tooth fairy?” Scientists and journalists must communicate unestablished ideas to the mainstream audience with a degree of skepticism and they should always present the appropriate conclusions. If they do not, then readers of science journalism will rightfully doubt the content, and begin to question the authority of science in answering questions about the world. Science should be popularly known as the best method for attaining knowledge; the fact that fields such as Naturopathy and ideas such as Intelligent Design are so prominent among the non-dogmatic, average population is testament to (at least, in part) the failure of scientists and journalists to adequately represent science and research findings.

Often scientists are not to blame; instead, it is the journalists, especially those from newspapers who simply report on topics they find in science journals. How many readers have you heard say, “First they say caffeine is bad for you, then they say it is good for you—why don’t these scientists just decide already”? This is a journalistic error. New studies must always be analyzed within the context of previous research, and journalists must acknowledge that a new study does not immediately usurp previous results. Science does not work this way. Mass confusion among the public will only degrade public opinion about science’s ability to understand natural phenomena. Journalists, and especially scientists who may be involved in the reporting process, must ensure that appropriate conclusions are reported within an already established framework of what is known.

When writing for the lay audience, journalists and scientists should strive to explain concepts simply, but they should never resort to inflating conclusions and sensationalizing research. Scientific discoveries are often sensationalized. Perhaps this arises from ego issues; everyone wants their research to be important. However, sensationalization is just as harmful to the public opinion of science as the declaration of unfounded conclusions. Even worse, prestigious scientific journals aimed towards scientists are often the culprits of sensationalization. If scientific journals cannot get it right, how can newspapers (whose authors often act as lay-person translations to text found in journals)? Reporting a recent “discovery,” the journal Science released a news story proclaiming the end of the concept of junk DNA1 (DNA that has no biological function, often calculated to represent a significant proportion of the genome). This story came about from a recent project called the Encyclopedia of DNA Elements (ENCODE), which stated that, contrary to the junk DNA hypothesis, approximately 80% of the human genome is biochemically active, and hence “functional.” A number of biochemists and molecular biologists, including University of Toronto’s Larry Moran (http://, are actively opposing the conclusions of this project (and for good

reason—for more information, visit Dr. Moran’s blog, as well as an analysis by John Timmer ( most-of-what-you-read-was-wrong-howpress-releases-rewrote-scientific-history/2/). The project used non-standard definitions of “functional,” and the conclusions misrepresented the story the data actually told. Nonetheless, and details aside, why would a prestigious journal write a story claiming that new data from a single project is replacing all previous data used to calculate the proportion of junk DNA? Shouldn’t more care be taken to report the appropriate conclusions of the experiments, expand on the exact definitions used for these controversial terms, and then place the results in the context of previous research? It is once again a matter of skewing results, misinterpreting definitions and data, inflating conclusions, and sensationalizing research. The science section in popular bookstores is larger than ever—they are inundated with best-selling books that promise to provide the lay reader with an understanding of evolution, the brain, physics, psychology, etc. These books are often written by scientific experts with excellent publication records and significant contributions to their fields. Regrettably, a majority of these popular science books present views of scientific topics that are overly simplified, and are presented in a manner that suggests widespread agreement among those “in the know.” This type of reporting fails to sufficiently educate the public on the process of scientific discovery, and is a bane to science as a whole. Scientists and journalists have a responsibility to give science its due justice so that it may attain the rank within society that it deserves. So, the next time you cringe when someone tells you they are “left-brained,” don’t shoot the messenger—aim for the message’s author instead. Disclaimer: The opinions expressed by the author are in no way affiliated with the Institute of Medical Science or the University of Toronto. Comments are welcome at theimsmagazine@gmail. com.

References 1. human-genome-is-much-more-than-j.html



Genomic Medicine for Rare Diseases By Jennifer Rilstone

Dr. Berge Minassian 33 | IMS MAGAZINE FALL 2012 TRAUMA

Dr. Berge Minassian has devoted his career to these orphaned conditions, particularly those that he has encountered in medical

practice as a neurologist. As a clinicianscientist, Minassian strives to provide more than a diagnosis to patients and families dealing with these poorly recognized conditions—he aims to find a cure. As a neurology resident in Los Angeles, Minassian was first propelled to join a research team searching for the causative gene for Lafora disease. Arguably the worst disease of teenage onset, Lafora disease is often diagnosed in early adolescence with the onset of myoclonic seizures, and progresses over the course of several years to include atonic seizures, ataxia, and—most significantly— severe dementia. After about 10 years of protracted suffering, Lafora disease is eventually fatal in early adulthood. “It’s a disease that is horrible clinically, so anything we can do would make a huge, huge benefit and remove a ton of pain from innocent adolescents and their families.” After coming to Toronto and

Photo by Yekta Dowlati.


arly breakthroughs in medical genetics were made through the study of single-gene, fully penetrant Mendelian genetic diseases. With easily characterized patterns of inheritance, these diseases (sickle-cell anemia, Huntington’s disease, Muscular Dystrophy, Cystic Fibrosis; see Timeline on page 13 of our Summer 2012 issue) provided the first models for learning how the alteration of a single nucleotide—residing in a single gene and coding for a single amino acid of a single protein—could severely disrupt the functioning of the human body. Today, the genetic cause of many of the most common Mendelian diseases has been discovered. What remain are the rare diseases—those that appear in just a few families, isolated populations, or even a single family.

CLOSE UP bridging competition between the research group in LA and one at McGill (where Minassian was once a medical student), he discovered the first Lafora disease gene. This was followed later by his discovery of two others, as well one in dogs (see Genomic Medicine: gone to the dogs? on page 39 of our Summer 2012 issue). A diagnosis of Lafora disease can now be confirmed genetically, and research in the Minassian lab continues to uncover the details of the underlying mechanism. Unlike other neurological diseases that can be as complex as the brain itself, Lafora disease is caused by a comparatively simple problem. In Lafora disease, the mechanisms of glycogen synthesis are altered, such that starch-like inclusions (“Lafora bodies”) are instead formed in the dendrites and cell bodies of neurons. Minassian says, “Compared to other brain diseases, it’s a simpler scientific problem. That’s what pushes me ahead. This is a case where we can find a cure for a brain disease.” In fact, simply by blocking glycogen synthesis, researchers in Minassian’s group have successfully cured mice harbouring Lafora disease gene mutations. It is now a matter of translating that work to humans.

Images courtesy of Melissa Cory and Inessa Stanishevskaya.

As with Lafora disease, many rare diseases are the result of very simple biological causes. Common diseases are multifactorial and complex in their pathophysiology; they are often polygenic and may include environmental influences. Minassian prefers to study rare diseases: “To really understand how the brain works, we need experiments in which a single variable is altered at a time. That’s what these rare diseases are—they are experiments of nature where one piece of the puzzle is removed.” Work in Minassian’s lab has also uncovered the genetic cause of a rare muscle disease— X-linked myopathy with excessive autophagy (XMEA). In that disease, subtle changes in the expression of a V-ATPase carrier protein prevent the proper acidification of autophagic vesicles. This process appears to be critical for muscle function, and leads to progressive muscle weakness over the patient’s lifetime. Research in Minassian’s laboratory is now focused on finding ways to reverse this acidification defect. Finally, recent advances in genomic technology have transformed the study of rare dis-

After about 10 years of protracted suffering, Lafora disease is eventually fatal in early adulthood. “It’s a disease that is horrible clinically, so anything we can do would make a huge, huge benefit and remove a ton of pain from innocent adolescents and their families.”

Where successes in the study of rare diseases lead, success for the more common and complex diseases will follow. The ability to rapidly sequence the entire genome of an individual will ensure the capture of nucleotide changes that may have been missed by earlier technologies that assayed genetic markers or sequenced only genetic exons. With new genomic tools in hand, Minassian is embarking upon the search for the genetic causes of the more common, extremely complex epilepsies—including juvenile myoclonic epilepsy, childhood absence epilepsy, and Rolandic epilepsy.

eases from a process that takes many years to being on the verge of clinical use. A major advance in this respect comes from current research in Minassian’s laboratory. A family with an unknown neurological disease was diagnosed using next-generation whole exome sequencing. The mutation—causing a complex, infantile-onset movement disorder in several cousins—interrupts the packaging of dopamine (and related neurotransmitters) in the brain. With biochemical understanding of the mutation’s effect, a treatment was selected from among approved Parkinson’s disease drugs and the patients have experienced a remarkable and sustained recovery. Realization of the promise of genomic medicine for diagnosing rare diseases is imminent. IMS MAGAZINE FALL 2012 TRAUMA | 34


Future Directions with Darlene Homonko, PhD By Tetyana Pekar

“All the advice I was getting was this: if you want to work in industry, go get a postdoc position in industry or in pharmaceuticals,” Homonko told me, laughing as she recalled the story. Exasperated, she would reply, “You don’t get it—I don’t want to work in a lab.” 35 | IMS MAGAZINE FALL 2012 TRAUMA

Much to her mother’s horror, she took on a job working at a golf store—and she liked it. She discovered that she had a natural ability for working with people, especially in a sales environment, and she enjoyed the business and talking about golf. “I was really into golf at that time,” she explains. Homonko grew up in a mixed francophone community in Montreal. She pursued her Bachelors of Physical Education and Health, with a minor in Biology from the University of Rhode Island. Her degree was recognized as a Bachelors of Education by the state, and when she came back to Canada, Homonko set up a physical education program at a small private school in Toronto, where she taught for a year. During her undergraduate studies, Homonko was exposed to exercise physiology, and she realized that what she really wanted to do was study exercise science. And so,

driven in part by her love of the ocean, she enrolled in a master’s program in Exercise Science at Dalhousie University. For her master’s thesis, Homonko studied the ability of glycogen by-products to convert into glucose. The idea was to push the body to use metabolites—such as lactate—as an energy source. “How do you get Kreb’s cycle to turn so that it actually starts using waste products?” Homonko wanted to know if humans, like hummingbirds, used or could use lactate as an energy source when their glycogen stores were depleted. She found that we couldn’t. “The reality is that we are not hummingbirds; we are not polar bears; we are not grizzly bears,” Homonko tells me. “Every animal has a system that’s adaptive for them.” After completing her MSc, Homonko started her PhD at York University, but she felt that the project wasn’t a good fit for her. After completing a year, she took a break from school to work as a laboratory technician at

Photo by Laura Feldcamp


hen Darlene Homonko completed her PhD with the IMS, she knew she wanted to be the person who explained and sold science. But she reasoned that if she wanted to pursue a career in sales, she needed to get some experience— that is, experience beyond selling Girl Guide cookies to her friends and family.

FUTURE DIRECTIONS Toronto Western Hospital. She worked there for several years before deciding to pursue further education. She wanted to make sure that doing a PhD and pursuing a career in research was what she really wanted to do. As she was weighing the pros and cons of further graduate education, she had the good fortune of acquiring a scholarship, and given that she really enjoyed her work in the lab, she decided to enrol in the PhD program at the IMS. But mid-way through her PhD, Homonko realized that she didn’t want to do a series of postdoctoral fellowships and spend so many hours of her day in the lab. As much as she liked the lab, she found that it didn’t inspire her to “get up in the morning [and] make a difference.” Adding to that realization was the fact that Homonko got caught up in a time when grant money and jobs were scarce. “Half-way through [the PhD], the funding really dried up for basic research; money started going into commercial opportunities. You have to ask yourself, if you invest this energy [to do a PhD], what is it that you expect to gain from it? For me, anyway, it gives you more options, opens doors, and develops your critical thinking—but what happens after you graduate?” The problem for Homonko wasn’t figuring out what she wanted to do, as she had an idea; the problem was finding jobs that appropriately blended her passion for science and business. They were uncommon. But she persisted, and following her employment at the golf store, she found a position at the Milestone Medica Corporation (MMC), a $20 million fund created by RBC Technology Ventures and Research Corporation Technologies. Her job entailed identifying investment opportunities, writing up summaries, researching primary indicators of the potential investments, and sifting through the patent database. “It wasn’t until three days later [after starting] that I realized, I’m working at RBC, I’m working at a bank, and I’m working on Bay Street. What am I doing here?” She says the time that she was there was very special and contributed to some of the best years of her life.

“It was such an incredibly inspiring environment. I got to work with fabulously talented people who I still remain friends with today. We inspired each other to succeed and it was an amazing launching pad for future opportunities.” After the MMC fund closed, Homonko worked for a year at the University of Toronto (U of T) Innovations Foundation as their Technology Manager. In that role—among many of her accomplishments—Homonko negotiated and secured the first US-based investment of a U of T Innovations Foundations start-up company. She also managed and developed intellectual property strategies for new commercial opportunities in many industry sectors. In 2005, she took the position of Executive Director at the Golden Horseshoe BioSciences Network (GHBN) to build a regional innovation network that united the biotechnology community in the City of Hamilton, Halton, and the Niagara region. While active, GHBN helped develop and support commercialization projects and “provides strategic direction and access to resources relating to biotechnology.”

She says she loves working in a hospital. “I enjoy working with researchers and making start-up companies, trying to develop new opportunities. I enjoy being at the interface between science and business.” The job leaves her with time for her other passion: fitness. “I’m a fitness fanatic. I spend a lot of my free time exercising and keeping fit: running, skiing, golfing, going to the gym,” Homonko says. She dreamed of being on the Olympic basketball team when she was young, she tells me. She doesn’t seem to mind that the Olympic dream did not come true, but maybe she’s just too busy to mind it; she is focused on training for a marathon in October. I asked Homonko if she had any advice for graduate students, particularly for those who are unsure what career path to pursue. “You have credentials, you have skills and you have opportunity. You should take every opportunity that presents itself to you and see if there is something there that you can then create for yourself. Create a life that you’ll be really thankful that you’ve lived, and you’ll be able to give back to the people and that industry.” “When your career eventually ends, you want to look back and say, ‘That was so fulfilling; I met some fabulous people, and I did some really good work.”

What was a typical day like for Homonko? “In a typical day as an investor, you come in, you read about technologies; you read business plans and evaluate them; meet with entrepreneurs and scientists, clinicians, and engineers; meet people in the financial sector; speak with intellectual property and corporate lawyers, marketers, and investor relations individuals. You spend a lot of time outside of the office.” In her present position as the Senior Business Development Manager at the Office of Technology Transfer & Industrial Liaison for Samuel Lunenfeld Research Institute (SLRI), Homonko works directly with SLRI scientists to identify new technologies and discoveries that have commercial potential. A large part of her job involves working with scientists to identify what’s patentable and what isn’t. IMS MAGAZINE FALL 2012 TRAUMA | 36


Summer Undergraduate Research Program The Institute of Medical Science (IMS), University of Toronto has an exceptional Summer Undergraduate Research Program (SURP) that provides an opportunity for undergraduate science students as well as medical students to be involved in projects relating to biomedical research. There are diverse research areas encompassing a broad continuum of disciplines, from molecular biology and cognitive science to clinical investigation and bioethics. This exceptional program offers a great platform for students to work with distinguished faculty, develop research methodologies, and experience outstanding mentorship. I have had the privilege to serve as Director of SURP for the past two years. It has been an exciting experience and I am looking forward to upholding the torch of success in the years to come. It has been extremely gratifying to see another batch of enthusiastic students participate in the summer research program this year. There were 102 students (both domestic and international) enrolled in the program. Students came from various universities—from as far as Shandong in China to as close as Guelph.

Director, SURP Associate Professor, Department of Surgery, University of Toronto Graduate Coordinator, Institute of Medical Science, University of Toronto Scientist, Division of Urology, Sunnybrook Health Sciences Centre

Highlights of the research day included an inspiring keynote address by Dr. Freda Miller, Professor at the University of Toronto and a cell and molecular developmental neurobiologist at the Hospital for Sick Children. An eminent scientist with over 150 scientific papers, reviews and book chapters, Dr. Miller inspired us with her superb lecture on neural stem cells. Some of her major findings have provided evidence that adult mammalian skin contains an accessible multipotent dermal stem cell population that can generate peripheral neural cells. As a final remark, I would like to thank all the supervisors who contributed valuable time and effort, providing students with the environment, motivation, and guidance to complete their research projects. I would like to express my sincere appreciation to all faculty who served as judges at the research day, as well as to the distinguished researchers for delivering lectures at the weekly seminars. Congratulations to all the students on their research achievements. I wish you the very best in all your endeavours! Vasundara Venkateswaran Director, Summer Undergraduate Research Program


Photo of Dr. Vasundara Venkateswaran by Brett Jones. Photos of SURP Research Day provided by the IMS Office.

Vasundara Venkateswaran MSc, MPhil, PhD

The summer program commenced first week in June and continued until the end of August, concluding with the research day on August 15th, 2012. All students enrolled in the program were provided an opportunity to showcase their findings through oral or poster presentations, and I was thoroughly impressed with the extraordinary student work. Several students were recipients of cash awards and certificates in recognition of their stupendous effort. It was heart-warming to see students beam with excitement when they presented their research—the enthusiasm they exhibited clearly demonstrating their fruitful summer experiences in the laboratories or clinics. They showcased their work with confidence, pride, and responded to the challenging questions posed by the judges.


2012 Speakers for Seminar Series



Dalhousie University


Nick Woolridge, BFA, BScBMC, MSc, CMI Director and Professor, Biomedical Communications, University of Toronto Michael Szego, PhD, MHSc Clinical Ethicist, Joint Centre for Bioethics, University of Toronto Badru Moloo, DVM Director, Animal Resources Centre, University Health Network

Melanie Guenette, Mohammed Sabri, Natalie Venier, Vanessa Zannella Institute of Medical Science Students’ Association


Queen’s University University of Guelph University of Ottawa University of Toronto



University of Waterloo


Xiao-Yan Wen, MD, PhD Scientist, Keenan Research Centre, St. Michael’s Hospital

Alan Moody, MBBS, BA Senior Scientist, Schulich Heart Research Program, Sunnybrook Health Sciences Centre

McMaster University


Katalin Szaszi, MD, PhD Scientist, Keenan Research Centre, St. Michael’s Hospital

Uri Tabori, MD Scientist, Genetics & Genome Biology, Hospital for Sick Children

8 1

Neil Winegarden, MS Head of Operations, Microarray Centre, University Health Network

Art Petronis, MD, PhD Senior Scientist and Head, The Krembil Family Epigenetics Laboratory, CAMH

McGill University


University of Western Ontario York University


Boston University


George Washington University


Hillsdale College


Thomas Jefferson University

7 1

Shondong University Tsinghua University

TOTAL = 102



SuRP Awardees Poster Presentation 1st Place

Honourable Mention

Shayan Cherraghlou Sean Kennedy Jessie Peng Krisanne Stanoulis Lauren Hachem Helen Sokolowski Catharine McCann Hoyee Wan Do Wan Kim Constantine Harmantas

Anna Badner Angela Arisz Michael Wang Henry Ajzenberg Sofia Nastis Jenny Peng Tony Wang Xiaoyu Wang Jeremy Zung Caroline Neel

Oral Presentation Honourable Mention

Jeremy Antonyshyn

Alyssa Lip

Photos of SURP Research Day provided by the IMS Office.

1st Place


Ask the


Expert Tips: Enriching your Graduate Experience Column By Laura S. Park & Brittany N. Rosenbloom

Staying Motivated in the Lab

One of the most drastic changes that students encounter from undergraduate to graduate studies is the independent functioning required to produce their work. Adapting to a flexible, independent research environment can be quite challenging. Thus, staying motivated and setting goals is different from the standard studying for exams or writing assignments for pre-determined deadlines. Common questions from new graduate students include: How do I organize my schedule? How do I keep motivated and on task? Is it normal to feel like I’m making very little progress? How early/late should I come to/ stay at the lab? Listed here are some guidelines to help you find answers that work for you and that can help you keep on track for the new academic year: a) Make a “To-do” list and create deadlines Every day, make a list of all the things that needs to be done for that day, that week, and that month. Set your own timeline and deadlines for experiments, readings, and meetings. Making short-term goals in addition to long-term goals will allow you to continue working towards completion of your degree. As you approach your completion date, it is helpful to work backwards with timelines for thesis writing and completion, thesis submission, and defense date. b) Set frequent meetings with your supervisor Whether they are weekly or bi-weekly, having frequent meetings with your supervisor is important. This will motivate you to complete tasks and summarize your work or re-

sults to update your supervisor. Even if you don’t have results to show, it is a good time to talk about other lab- or school-related issues. c) Talk to lab-mates/friends about your work If you are unsure whether or not you are on the right track, or if you should be doing more work, talking to lab-mates or friends in the program is helpful to monitor your progress and share ideas. d) Take breaks during the day and throughout your program Sometimes we get swamped with work and get carried away. To be productive, make sure you take short breaks throughout the day to refresh yourself. Leave the lab for your lunch breaks or go for a short walk. Also, make sure you use your holidays wisely! e) Go to talks and seminars When we get hung up on our own projects, we can easily lose sight of the big picture of research and our long-term goals. Go to talks that interest you, whether they are related to your project or not. This way, you can continue to be motivated, inspired, and intrigued.

Finding life outside the lab

Though starting in a new lab or on a new research project is typically a fulfilling experience for the curious mind, taking part in some activity—not lab-related—is equally important in maintaining the stamina needed to complete experiments and may encourage a fresher mind during lab time. Choosing activities to clear your mind can range from a workout at the gym, to getting together with non-lab friends, to attending an Institute of Medical Science Students’ Association (IMS

SA) social event. In participating in such activities outside the lab, students have a chance to give their hardworking brains a moment to recuperate—just as an athlete cannot train 24 hours a day, a student cannot run experiments 24 hours a day. After all, the University of Toronto (U of T) is located in a vibrant, multicultural city where there are always exciting events taking place! If you are a new or returning student looking for some new experiences and outlets, you can look within the IMS through the IMSSA website ( ca/) for upcoming events, campus wide using the Graduate Student Union website (, or outside of U of T with city festivals, small venue concerts, and scrumptious restaurants, which can all be found on or

EXPERT TIP A balanced graduate student is a happy, productive one. Make sure to take work breaks and pursue non-lab activities. Do you have a question for the experts? Please send it to (ATTN: Experts).





Past and present IMS Magazine Committee members.

IMS Magazine Committee member Benjamin Mora (middle) doesn’t follow fashion trends, he sets them.

The IMS Magazine sparkles and shines!

Magazine cupcakes brought to you by Nina Bahl, Natalie Venier and Melanie Guenette.


Photos courtesy of Paulina Rzeczkowska.

Past and present members of our amazing Design Team.


CROSSWORD ACROSS 1. Hours worked by some doctors where they might see those who saw the bar close (2 words). 5. A surgical dressing of loosely woven cotton. 6. A contrivance or opening for replacing foul or stagnant air with fresh air. 10. The occlusion of a blood vessel by some undissolved material.

2. The cleaning out of a wound with sterile fluid to remove debris. 3. Warnings used to alert hospital staff to a patient requiring resuscitation (2 words). 4. Used to carry the sick or injured. 7. Replacing lost blood after trauma. 8. The act of forming again, rebuilding. 9. Standard attire for patients and doctors, respectively (3 words). 12. A jarring of the brain, caused by a blow or a fall, usually resulting in loss of consciousness.

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“Piled Higher and Deeper” by Jorge Cham


“Piled Higher and Deeper” by Jorge Cham

11. Temperature, heart rate, blood pressure, etc. 13. Injury caused by a firearm (2 words). 14. A device used for drawing fluid. 15. Necrosis of a region of the heart muscle caused by an interruption in the supply of blood (2 words). 16. A sudden and active manifestation (e.g. SARS). 17. Those being treated in the emergency room. 18. Inflammation of a blind-ended tube that hangs off the caecum. 19. Staff who organizes patients based on their urgency for medical attention. 20. Request of a doctor from another specialty to provide input on a case.