VCHRI Kudos: June 2011 CIHR announcements

CIHR Operating Grants (results of the January 2011 competition)

• Rosemary Basson, UBC/VGH Sexual Health Lab
  $480,388 for, Stress Hormones, Mood and Women's Sexual Desire

  Abstract: Many women worry that they have too little sexual desire and some find this very distressing. Although men's sexual desire is related in part to the testosterone in their bodies, this has not been shown to be true for women. We have found in women who are distressed with a low sexual desire, lower levels of certain hormones that can produce testosterone. But these hormones have other actions as well, for instance they are also stress hormones. Additionally, they can affect our mood and tendency to be depressed. This study is to investigate stress hormones (measured in the saliva and nail clippings), and stresses that occurred in childhood including abuse or other negative experiences in women with and without low sexual desire. As well we will carefully measure symptoms of low mood, for example unhappy thoughts, feeling irritable or sad, in women with and without low desire problems. We will need to exclude women who have current depression. In conclusion, we want to understand the meaning of these lower hormones (like DHEA) in women with low sexual desire so that we can better focus our treatment

  Co-Investigators: Lori Anne Brotto (VGH Sexual Health Lab), Allan Young (Mood Disorders Centre), Albert Petkau (UBC), Alessandra Rellini (University of Vermont), and Joanne Weinberg (UBC).



• Helen Burt and Martin Gleave (Vancouver Prostate Centre)
  $291,892 for, Intravesicular nanoparticulate drug delivery systems for application in bladder cancer.

  Abstract: Bladder cancer is the fifth most common cancer in Canada and the incidence is increasing. Superficial disease is treated by surgical removal of tumors and the intravesical instillation of chemotherapy agents, usually mitomycin C, directly into the bladder via a catheter. However, the highly impermeable barrier presented by the superficial umbrella cells of the bladder wall seriously limit drug uptake and effectiveness of intravesical chemotherapy and patients require life-long surveillance, usually with repeated interventions. New therapeutic approaches are urgently needed. We have developed tiny, spherical nano-sized particles that are very highly branched and possess a core that can carry a payload of docetaxel and a surface that can be modified with positively charged amine groups. These nanoparticles show markedly superior bladder tissue drug levels and efficacy in a mouse model of superficial bladder cancer and we believe this may be explained by the amine coated nanoparticles causing shedding of the surface barrier cells. We also found that, following removal of the nanoparticles and washing of the bladder tissue, the superficial cell layer was regenerated extremely rapidly, within hours. The goal of this translational research is to develop these unique drug nanoparticles for potential treatment of patients receiving intravesical chemotherapy after surgical resection of tumors. The objectives are to investigate the processes leading to superficial cell shedding and recovery, to determine the uptake and distribution of the drug and nanoparticles in bladder and tumor tissue and to evaluate the efficacy and toxicity of the drug loaded nanoparticles in mouse models of superficial bladder cancer.

  Full Team: Co principle investigators: Marcel Bally and Donald Brooks (from UBC Centre for Blood Research), and Andrew Minchinton (BC Cancer Agency). Co-investigator: Alan So (Vancouver Prostate Centre)



• Piotr Kozlowski, Vancouver Prostate Centre
  $627,332 for, Multi-parametric MRI for prostate cancer diagnosis and prognosis

  Abstract: Prostate cancer remains one of the most common cancers in North American males and second leading cause of cancer related deaths in men. It is estimated that this year 25,500 men will be diagnosed in Canada alone with upwards of 4,000 deaths. Owing to the widespread use of screening tests, many more less advanced, localized, lower risk prostate cancers are being detected. This prompted increased interest in focal therapy as an alternative to the traditional therapies of surgery and radiation therapy. However, the ultimate success of focal therapy relies on proper patient selection and adequate characterization of the tumour's location, extend and histological grade. We have shown that a combination of different Magnetic Resonance Imaging (MRI) techniques have significantly better accuracy of prostate cancer diagnosis than either technique alone. We propose to further develop this MRI technology. Specifically, we will develop a technique called Magnetic Resonance Elastography (MRE). This technique allows non-invasive measurements of mechanical properties of tissue, and is often called "remote palpation". We believe that the combination of MRE and the MRI techniques we have developed so far will significantly improve prostate cancer diagnosis. In addition, we will develop a computer program capable of accurately predicting the tumour's location, volume and pathological grade based on the MRI/MRE measurements. The combination of the proposed MRI/MRE technology with this computer program will facilitate patient selection for focal prostate cancer therapy. We also propose to test the ability of this technology to predict outcome of the combined modality treatment.

  Co-Investigators: Larry Goldenberg and Silvia Chang from the Vancouver Prostate Centre, as well as Edward Jones, Mehdi Moradi, and Tim Salcudean from UBC Engineering.



• Diane Lacaille, Arthritis Research Centre
  $470,356 for, A randomized controlled trial evaluating the effectiveness of the Making It Work program at preventing work loss and improving at work productivity in employed people with inflammatory arthritis.

  Abstract: People with inflammatory arthritis, commonly have to stop working, with major consequences to their quality of life. Yet, few services exist to deal with employment. We have developed and pilot tested a novel intervention to help people with inflammatory arthritis remain employed. Results were very favourable. For the program to become widely available and health policy planners to agree to fund it, we need to demonstrate its effectiveness. In a randomized controlled trial, we will compare work outcomes in 263 employed people receiving a web-based version of our program compared to 263 receiving usual care, along with printed material about work and arthritis.

  Co-Investigators: Catherine Backman, John Esdaile, and Linda Li (from the Arthritis Research Centre), Carlo Marra (Providence Health Care Research Institute), Monique Gignac (Toronto University Health Network), Charles Goldsmith (Simon Fraser University).



• Brian Macvicar, Brain Research Centre, was awarded 2 grants:
  (1) $827,540 for, Calcium signaling in astrocytes in neurovascular control

  Abstract: There has been a revolution in our understanding of the regulation of both brain function and cerebral blood flow. Over the past 10 years it is clear that astrocytes, the support cell of the brain that outnumber neurons, can modify neuronal activity and directly alter blood flow through cerebral blood vessels. The maintenance of cerebral blood flow at levels to match the metabolic demands of the brain is critical for a healthy brain. Inappropriate decreases in cerebral blood flow can lead to dementia and in severe cases neuronal damage. Work from the previous grant has shown the mechanisms by which astrocytes modulate cerebral blood vessels. Under conditions of increased metabolic demand and lower oxygen astrocytes causes arteriole dilations. In contrast when brain tissue is well oxygenated constrictions are triggered. The work in this grant will investigate the mechanisms in addition to metabolism that control whether astrocytes cause constrictions or dilations. Understanding these mechanisms may provide therapeutic avenues to prevent pathological changes in cerebral blood flow.

  (2) $805,404 for, Synaptic and Nonsynaptic modulation of neuronal excitability

  Abstract: The research proposed in this grant will investigate novel types of interactions between neurons that are important for generating the aura of migraines, in causing the neuronal swelling underlying cytotoxic brain edema and in allowing the immune cells of the brain, called microglia, to sense when intense activation and damage occurs in nearby neurons. Each of these pathways involves a new form of transmitter release and reveals the potential cytotoxic impact of ionic disruptions in nerve cells.




• Jessica McAlpine, OvCare (co-PI Sohrab Shah, BC Cancer Agency)
  $563,330 for, Genomic Disruption in High-Grade Serous Ovarian Carcinomas: Steady State or Continuous Drift?

  Abstract: In North America, ovarian cancer is the leading cause of death due to gynecological malignancies and 75% of women with advanced ovarian cancer are not expected to survive beyond five years. High-grade serous ovarian cancers account for 70% of ovarian cancer cases. These cancers are thought to be chromosomally unstable, which means their genomes are highly susceptible to the introduction of large-scale genetic mutations and rearrangements on a continual basis. This assumption stems from the observation that the chromosomal makeup (karyotype) of ovarian cancers is extremely abnormal. Recent results from our group suggest that this presumption is incorrect. It seems that ovarian cancers undergo a period of chromosomal instability very early on as the cancer is being established which leads to the abnormal karyotype. At the time of disease diagnosis, however, these cancers have already reached a state of chromosomal stability. Thus, with respect to large-scale genomic changes, recurrences and metastases are almost identical to the original tumour. We have found, however, that small-scale changes corresponding to single letter DNA alterations continue to occur as tumours evolve. This finding represents a moment of recognition that 'the emperor has no clothes' with respect to the study of ovarian cancer. For this project, we will conduct an in-depth study of multiple tumour samples from 10 cases of high-grade serous ovarian cancer to determine the extent of genetic variability between tumours and try to discover how these cancers acquire chromosomal stability. We will also compare these results to early precursors of ovarian cancer from the fallopian tubes, to identify when chromosomal instability occurs in cancer evolution. The results of this work could reveal why a large proportion of ovarian cancers do not respond to treatment or develop treatment resistance and has important implications for the development of new treatments for this disease.

  Co-Investigators: Cyril Blake Gilks (OvCare and Genetic Pathology Evaluation Centre) and David Huntsman (OvCare and BCCA).
  
  
• Peter Reiner, Brain Research Centre
  $190,185 for, Public Attitudes toward pharmacological cognitive enhancement.

  Abstract: Four cardinal concerns are commonly raised in neuroethical discourse when experts weigh in upon the uneasiness that the public might have about pharmacological cognitive enhancement, namely safety, distributive justice, coercion, and authenticity. Much ink has been spilled in discussing these issues, but at the present time there is much more information available regarding expert opinions on the topic than public opinion. The mission statement of the National Core for Neuroethics states that our objective is, in part, 'to align innovations in the brain sciences with societal, cultural and individual human values'. In order to align innovations with these values, it is imperative that we ascertain what those values are. We suggest that probing public attitudes regarding cognitive enhancement is a critical tool for determining what the public's concerns, enthusiasms, fears and hopes are regarding technologies that affect their brains. Moreover, given the hypercognitive society in which many modern humans live, cognitive prowess is amongst the most prized of human traits. The experiments outlined in this proposal represent our efforts at systematically probing public sentiment towards cognitive enhancement.




• Yu Tian Wang, Brain Research Centre
  $733,985 for, Investigation into the molecular mechanisms mediating excitotoxicity - developing novel post-stroke therapies

  Abstract: Stroke is the third leading cause of death in North America, and the leading cause of disability and represents a huge economic and social cost. Stroke is a brain attack from a sudden loss of blood supply to the brain that occurs when the blood supply to a specific part of the brain is suddenly interrupted (ischemic) or when a blood vessel in the brain either bursts or is blocked. Cells in the affected brain die when they no longer receive oxygen and nutrients from the blood, leading to the symptoms and disabilities of stroke patients. However, effective pharmacotherapy that directly protects brain cells from stroke insults is still lacking. Our objectives are to achieve a better understanding of the molecular mechanisms by which stroke insults produce brain cell damage, and thereby develop novel pharmacotherapies. Using cellular models of stroke, we have identified a molecule called PTEN (a lipid phosphatase) as an essential step in the signaling cascade initiated by stroke insults that causes brain cells to die. By understanding the mechanisms by which stroke insults causes the PTEN nuclear translocation, we have been able to devise a novel drug to specifically disrupt this stroke-induced PTEN nuclear translocation, and thereby to reduce stroke-induced brain cell death. We propose further validation using several animal models of stroke if the new drug we developed can be used as a new and effective post-stroke pharmacotherapy. We expect that the completion of our proposed study will help to bring this drug to the point where it can be tested in human stroke patients. Because this therapeutic is specifically designed to target the stroke-related neuronal death process, without affecting normal function of the brain cells in affected areas, it is expected to have minimal side effects. Studies as such can be expected to lead to better stroke therapies and hence, will directly impact the health of Canadians and reduce mortality and morbidity from stroke.




• Youwen Zhou, Skin Care Centre
  $340,314 for, Abnormal Activation of Thymocytes High-Mobility Group Box Protein (TOX) in Cutaneous T Cell Lymphomas: Pathogenic Significance and Clinical Applications.

  Abstract: Cutaneous T cell lymphomas (CTCL) are cancers that are developed from the CD4+ subset of the mature T lymphocytes in the skin. Although rare, these cancers are highly aggressive in advanced stages, causing high mortality because there are no curative therapies at present. These cancers are difficult to diagnose because of lack of sensitive and specific markers. Further the molecular events leading to the initiation and progression of skin lymphoma cells remain unclear. Our laboratory recently discovered a previously unrecognized marker, TOX (which stands for thymocytes high mobility group box protein), that is abnormally activated not only in late stage disease but also in the earliest form of skin lymphomas. In the current study, we will perform a series of experiments to answer two questions: (1) Can TOX protein serve as a sensitive and specific diagnostic marker for skin lymphoma cells? Currently, the lack of such a marker is a major bottleneck in the treatment and research of skin lymphomas; and (2) Is TOX abnormal activation a cause for the development of skin lymphomas? Not only does this study have the potential of identifying a specific diagnostic marker for skin lymphomas, it also offers the unique possibility of clarifying how skin lymphomas develop, thus facilitating therapeutic development for skin lymphomas, which remain incurable at present.

  Co-Investigator: Xiaoyan Jiang (BC Cancer Agency)

• Kevin McElwee.
  Title: Regulation of hair cycle and wound healing by alpha-v-beta-6 integrin. ($564,090)

  Abstract: More than 30 million patients in North America receive steroid drug treatment. The therapeutic indications are widespread but side effects are common and of great importance to patients. Chronic glucocorticoid therapy induces detrimental effects in several tissues including the skin where it causes skin atrophy. When encountering an accidental or surgical trauma, impaired tissue repair is one of the serious complications of glucocorticoid therapy. Glucocorticoids affect almost every phase of wound healing due to their inhibitory effects on gene expression in various cells involved in healing. Transforming growth factor-beta 1 (TGF-ß1) is a naturally-occurring molecule which regulates skin inflammation and tissue maintenance. It serves as a strong inhibitor of hair follicle stem cell growth and has been directly implicated as a significant factor in hair growth regulation. TGF-ß1 is produced as an inactive molecule and needs to be activated to function. One of the main activators of TGF-ß1 is an integrin that is expressed on the epithelial cell surface. We have recently demonstrated that this integrin is localized in hair follicle stem cells where it could keep these cells quiescent via TGF-ß1 activation. Our work has also demonstrated that mice engineered to lack this integrin (ß6-/-) have accelerated hair growth and delayed hair regression. In addition, steroid-impaired wounds heal significantly better in ß6-/- mice than in normal mice. The aim of this research proposal is to further investigate the role of this integrin in hair stem cells and healing of steroid-impaired wounds. Our hypothesis is that this integrin naturally suppresses stem cell proliferation in hair follicles. When patients receive corticosteroids, these drugs further inhibit stem cells delaying reepithelialization of wounds. Use of inhibitors of this integrin could potentially reduce stem cell suppression and provide a useful therapeutic tool to improve outcomes of steroid-impaired wound healing.

  Additional team members: Hannu Larjava (Principle Investigator) and Lari Hakkinen, both from UBC.



• Erin Michalak and Lakshmi Yatham.
  Title: Investigation of Metacognition in Bipolar Disorder and its Association with Functional Outcome and Quality of Life ($210,271)

  Abstract: Increasing understanding of the specific cognitive impairments that affect patients with bipolar disorder is critical as these difficulties are likely to identify patients who show poorer everyday functioning and quality of life. Knowledge of these core cognitive deficits can also facilitate development of treatments that improve these specific impairments as well as overall patient functioning and quality of life. To date, research in bipolar disorder has determined that many patients show difficulties in traditional cognitive abilities such as attention, memory, and executive functioning. One thing that all these skills have in common is that they evaluate how well an individual is able to process external information about the world (e.g. words, stories, pictures, etc.). In contrast, the field of metacognition involves the study of a person's ability to reflect on their internal world, namely their own thinking skills. Thus, whereas traditional skills measure a person's performance on a task, metacognitive tasks measure a person's ability to evaluate their own cognitive skills and performance. Despite the fact that metacognitive deficits are strongly implicated in bipolar disorder, such methodologies have not been integrated into bipolar research. The goal of the present research is to investigate whether patients with bipolar disorder show abnormalities in metacognition characterized by poor awareness of their own cognitive performance. A secondary goal is to assess whether these metacognitive abnormalities predict poorer everyday function and quality of life in patients. Finding such a connection would be important because it would 1) alert clinicians to assess an important symptom in patients with bipolar disorder, and 2) provide new direction for development of novel treatments that target the metacognitive abnormalities and also improve daily functioning and patient quality of life.

  Principle Investigator: Ivan Torres (UBC)



• Andrew Churg, Harvey Coxson, Annette McWilliams, and Joanne Wright.
  Title: Why are women at increased risk of COPD? ($696,825)

  Abstract: Over the past 20 years, the number of women with chronic obstructive pulmonary disease (which was in the past called "chronic bronchitis", "emphysema" or "smokers' lung") in Canada has more than doubled such that in 2011 the number of women with COPD exceeds the number of cases in men. When women develop COPD, they are more short of breath, have poorer quality of life and experience more frequent hospitalizations and exacerbations than male patients even though female smokers on average smoke less than male smokers. In the proposed research program, we will figure out why women are at increased risk of COPD and how female sex hormones may affect in the breathing tubes that may lead to lung disease.

  Principle Investigator: Donald Sin (James Hogg iCAPTURE Centre, at St. Paul's Hospital)
  Additional co-investigators: Delbert Dorscheid (iCAPTURE), Stephen Lam and Wan Lam (BC Cancer Agency), Shu-Fan Man (Providence Health Care Research Institute), Donald Morrish.



• Craig Mitton.
  Title: Partnering for Change: Understanding the Contribution of Social Entrepreneurship to Primary Health Care Transformation ($540,961).

  Abstract: We know that we need strong, effective primary health care services in order to improve the health of the population and create an effective health care system over the long term. We also know that partnerships and networks among communities, health services and health care providers are needed for widespread changes in primary health care to occur. Although we know what is needed, we do not yet have good evidence about how to make these changes over the long term across a health region. The purpose of this research is to understand how networks of partners can be engaged to transform primary health care at community and regional levels. Partners include doctors and other health care providers, community organizations, municipal leaders, the ministry of health, and the regional health authority. The Northern Health Authority in British Columbia is leading a process with its partners to improve primary health care services, beginning in six communities across northern BC. In this research, we will use the lens of social entrepreneurship to examine how primary health care system change actually takes place over a period of four years in these six communities and across the region. We will examine the process of change by interviewing individuals who are involved in the change, examining documents such as minutes of meetings and the results of evaluations, and considering statistics on the use and effectiveness of health services. The research team will describe how the relationships, partnerships and networks within and beyond the communities actually help or hinder changes in services. Through this research we will learn how partnerships and networking contribute to changes in health services and how health care systems can be aligned to better serve the needs of the population, especially in rural and northern Canada.

  Additional team members: Principle Investigators Martha MacLeod, Margo Greenwood, Neil Hanlon, Suzanne Johnston, Catherine Ulrich. Co-investigators Stephen Brown, David Butcher, Tanis Hampe, Patricia Reay, David Snadden.
  Host Research Institution: University of Northern British Columbia.



• Emma Guns.
  Title: Antiandrogenic and antiproliferative effects of diindolylmethane (DIM) and ring-substituted analogs (ring-DIMs) in androgen-dependent and -independent human prostate cancer cells in vitro, and in vivo using real-time imaging technology. ($345,661).

  Abstract: Numerous studies have shown the protective effects against cancer of high vegetable consumption, particularly that of cruciferous vegetables of the Brassica family (broccoli, cauliflower, cabbage). These vegetables contain high amounts of the compound indole-3-carbinol (I3C), which is converted in the body to a metabolite, diindolylmethane (DIM). DIM has more potent anti-cancer properties than I3C, and studies have shown that it is effective against a variety of cancers, including that of the prostate. Hormone-dependent prostate tumors grow under the influence of the potent male sex hormone dihydrotestosterone (DHT). Current treatment of these prostate tumors involves drugs that block the action of DHT on the androgen receptor (AR antagonists), or those that prevent the production of DHT by inhibiting the enzyme, steroid 5-alpha-reductase (SRD5A inhibitors). DIM acts as an AR antagonists and this is thought to be one possible way in which it inhibits prostate cancer growth. Preliminary results using cancer cell lines (in vitro) suggest that a group of synthetic derivatives of DIM, called ring-DIMs, have more potent anticancer properties than DIM. Furthermore, these ring-DIMs appear to be effective against hormone-dependent as well as -independent prostate cancer cells. This suggests that they are excellent candidates for detailed studies of their mode of anti-prostate cancer action and biological effectiveness in vivo. The present research proposal wishes to determine whether ring-DIMs are effective in vivo by testing their anticancer activity in mice that carry bioluminescent human prostate tumor cells (xenografts). These cells produce light, so the location and growth of the tumor can be easily monitored using an imager, without the need to sacrifice the animals periodically to assess tumor progression. Experiments using prostate cancer cell lines in culture will assess various mechanisms of anticancer action to better understand how ring-DIMs work in tumor cells.

  Principle Investigator: Thomas Sanderson
  Host Research Institution: INRS-Institut Armand-Frappier (Laval)

CIHR Team Grant program

1. Jerilynn Prior (CeMCOR), in the CIHR Team Grant in Bone Health category.
   Title: Progesterone, Bone Formation & Strength

   Abstract: Osteoporosis and fractures cause pain and disability. Annual fracture costs are now $1.9 billion¹. This Bone Team is led by Dr. Jerilynn Prior (BC)and clinician-scientists from coast to coast. Fractures occur because bone loss is faster than its replacement-this weakens bone. Bone loss and gain are linked. So all therapies that stop bone loss also stop bone gain. Previous research by Prior and others show that progesterone increases new bone formation. A forearm "pQCT" test measures bone strength that predicts future fracture. This Team proposes two 2-year studies testing progesterone vs./with usual osteoporosis therapies while measuring bone density & pQCT. These are the 1st studies of pQCT and progesterone. Bone loss occurs in women with hypothalamic amenorrhea or regular cycles & unseen stress-related problems with egg release/low progesterone. These reversible changes are treated with birth control pills (Pills). Young women, ages18-35, of normal weight will have a 50:50 chance of taking progesterone for 14 days/cycle or Pills. A previous Prior study showed a 2% 1-year bone gain with a progesterone-like therapy-44% resumed normal periods. The expectation is that cyclic progesterone will cause pQCT bone gain & cycle recovery-Pills will not. Early postmenopausal women are rapidly losing bone. Women at moderate 10-year fracture risk, ages 45-60, of normal/overweight will all be treated with a bisphosphonate, a standard bone therapy. All will also have a 50:50 chance of taking progesterone or placebo. The expectation is that those who take bisphosphonate plus progesterone will gain more pQCT strength than those on bisphosphonate alone. This Team Bone research will discover new knowledge to share with the public and health providers using on-line, government agencies and physician and consumer education. This Team will generate new information to improve bone strength and fracture prevention for all Canadians.
   ¹ www.osteoporosis.ca/index.php/ci_id/8867/la_id/1.htm

   Co investigators: Angela Cheung (University Health Network, Toronto), Christine Hitchcock (CeMCOR), Christopher Kovacs (Memorial University of NFLD), Suzanne Morin (McGill) and Jo Welch (Dalhousie University)



2. Andrei Krassioukov (ICORD - International Collaboration on Repair Discoveries) and Janice Eng (ICORD) in the "Chronic Disease Risk and Intervention Strategies" category.
   Title: Improving cardiovascular health for Canadians living with spinal cord injury: effects of exercise, sex differences, and targeted clinical education

   Abstract: Annually, over 1000 Canadians sustain a traumatic spinal cord injury (SCI) and unwittingly join more than 41,000 Canadians living with this chronic and debilitating injury. The estimated annual costs of care in Canada exceed $1.5 billion. Recent data reveal that people with SCI are developing chronic diseases at younger ages and at greater rates than the able-bodied population. This alarming trend appears to be caused by inactivity-related illnesses, particularly cardiovascular (CV) disease, which is the main cause of death and disease in people with SCI. Exercise training has the potential to improve strength, performance, and well-being among people with SCI. However, we have little information on the CV effects of training in people with SCI. People with SCI respond differently to exercise. There are also important differences in CV disease between men and women: we do not yet know if this is true for people with SCI, or if men and women with SCI will need to approach exercise differently to improve CV health. This is information that we urgently need to develop exercise programs that will be effective in improving CV health for Canadians living with SCI. The goal of this proposal is to improve CV health for people with chronic SCI through optimized exercise and targeted education. This project gathers a diverse team of 13 prestigious scientists working at 6 Canadian universities. We will use both animal models of SCI and training in people with SCI to examine the effects of exercise on CV risk. We will also determine whether educating health care providers on specific CV problems associated with SCI will help to reduce the financial burden of care, and improve treatment, of people with SCI. By providing important information on exercise training, and targeted education to clinicians, this project will reduce chronic disease and improve CV health for Canadians living with chronic SCI.

   Co-Principle Investigators: Victoria Claydon (Simon Fraser University), Audrey Hicks (McMaster University), and Milos Popovic (University of Toronto).

Randomized Controlled Trials Mentoring Program

Teresa Liu-Ambrose (Centre for Hip Health and Mobility) and Penny Brasher (Centre for Clinical Epidemiology and Evaluation).
Mentee: Meghan Donaldson (Centre for Hip Health and Mobility) ($140,000 over 2 years)
Title: Physical activity interventions to improve "successful ageing" among vulnerable seniors.

Abstract: The 2006 Canadian Census reported that 1 in 7 Canadians is over the age of 65-a record. In January 2011, the first of the Baby Boomers (born between 1946 -1965) turned 65 years old. This generation, approximately 1/3rd of the population in 2006, will significantly contribute to the expected doubling of seniors over the next 25 years. The Oxford dictionary defines mobile as "movable; not fixed; free or able to move or flow easily". Poor mobility is a common consequence of aging. It is estimated that among men and women aged 65 years and older, 20% will go on to have poor mobility over the following 4 years. Mobility has been linked to the idea of "successful ageing". The built environment or "urban form" is broadly defined as all buildings, spaces, and products that are created or changed by people. The relationship between the built environment and health is a relatively new area. However, a few studies have shown that there is a positive relationship between the built environment and health (i.e. "better" built environment, "better" health). Physical activity is an attractive way to increase the number of people who are ageing successfully, by improving their mobility. It can be relatively inexpensive, for example walking, and it is thought to improve not only mobility but also the health of the heart, muscles, brain and, improve quality of life. But, it is very hard to convince people who are not used to being physically active, for example vulnerable seniors, to do so. In fact, according to a 2011 report from Census Canada, almost 80% of Canadian seniors do not meet physical activity guidelines. Many studies to date have used complicated physical activity programs that may not translate well to the "real world" setting. The purpose of this Mentoring Program is to develop a simple and sustainable physical activity intervention, while considering the role of the built environment, that will increase the number of people who are "ageing successfully".

Catalyst Grant (Ethics): New Investigators and Mid-Career Investigators Transitioning into Ethics

Jude Kornelsen (Centre for Rural Health Research) with coPI Chloe Atkins (University of Calgary)
Title: Best Ethical Practices in Managing Uncertainty in Medical Diagnosis: An Investigation of Ethical Principles Applied to Decision Making

Abstract: Current diagnostic models in medical practice do not adequately account for patient symptoms that cannot be classified. Standard medical practice involves issuing diagnostic tests based on a range of possibilities within a reasonable index of suspicion to classify symptoms within a disease based framework. This is the precursor to treatment where possible. At the moment of perceived saturation where all diagnostic possibilities have been excluded, physicians confront uncertainty. This raises profound ethical queries for clinicians, medical culture, patients and society and has profound implications on the course of care. This ethics framed research will examine how clinicians and patients conceptualize an ambiguous diagnosis within a disease based framework. Specific objectives include; 1.Understanding how physicians respond in terms of non-maleficence and beneficence in the context of lack of clear diagnostic and treatment options 2.Understanding how physicians conceptualize patient autonomy and dignity in the context of lack of clear diagnostic and treatment options 3.Understanding how physicians conceptualize truth-telling in the context of lack of clear diagnostic and treatment options 4.Understanding physicians' communicative intent and the content of discourse in the context of uncertainty 5. Documenting the experience of patients who are 'not yet diagnosed' and 6. Documenting the resources available to patients who are 'not yet diagnosed'. This qualitative study will be done using a trans-disciplinary research approach bringing together a sociologist, a political theorist and clinicians to ensure an 'on the ground' perspective is integrated into knowledge generation. The research will be carried out through in-depth, open-ended interviews to document physicians and patients' experiences of ambiguous diagnosis, guided by a phenomenological framework

Co-Investigators: Keith Brownell (U of Calgary) and Robert Woollard (UBC).

Planning Grant in Nutrition, Metabolism & Diabetes

Ben Chew, Vancouver Prostate Centre
Title: The Role of Gut Bacteria in the Pathogenesis and Prevention of Kidney Stone Disease

Abstract: The purpose of this meeting grant is to facilitate an international cross-disciplinary collaboration of varied physicians and basic scientists with the goal of improving the treatment for patients suffering from kidney stones. This collaboration is needed because no definitive therapy exists to consistently prevent kidney stones which affects 33 million North Americans and cost the medical system billions of dollars per year. The goal of our research is to alter gut bacteria to change dietary absorption of kidney stone elements in patients suffering from recurrent kidney stones. There is evidence that patients with kidney stones have an imbalance in their gut bacteria. Identifying differences in gut bacteria of patients with and without kidney stones will help direct therapy. Gut bacteria (known as the "microbiome") are known to alter what is absorbed from food and transported across the gastrointestinal tract into blood. Once altered foodstuffs are filtered by the kidney, compounds such as calcium and oxalate may form kidney stones. We will utilize DNA identification techniques that can identify specific gut bacterial species (metagenomics) that traditional microbiology culturing techniques have been unable to identify. Traditional microbiology culturing techniques are only capable of identifying 1% of the gut bacteria. Gut bacteria have been shown to play a critical role in diseases such as inflammatory bowel disease and obesity. By identifying specific gut bacteria more commonly found in normal controls, we plan to change the gut bacteria in kidney stone patients to alter the gut metabolism of compounds that contribute to kidney stones. This technique of "stool transplantation" previously has been shown to alter obesity in experimental mice, and has recently been used clinically in diseases such as C. difficile colitis. This novel approach of directed stool transplantation will potentially provide consistent relief for patients with recurrent kidney stones.

Co-Investigators: Dirk Lange (Vancouver Prostate Centre) and Marshall Stoller (University of California, San Francisco)

New Investigator Salary Award - Recognition Prize in Research on Aging

Teresa Liu-Ambrose, Centre for Hip Health and Mobility
Title: Role of exercise on cognition and function in seniors with vascular cognitive impairment.

Abstract: The proposed study primarily aims to assess whether a six-month, three times a week, aerobic exercise training program has a positive impact on both cognitive and everyday function (i.e., the ability to perform activities of daily living such as managing one's money or preparing meals) among adults with mild cognitive deficits due to mini-strokes. We are facing an outbreak of dementia due to the world's aging population. Currently worldwide, 24.3 million people have dementia and one new case of dementia occurs every 7 seconds. As a result, it is very important that we identify strategies that can delay the onset and slow the progression of dementia. Cerebrovascular disease is the second most common cause of dementia in older adults. Results from high quality research studies suggest that reducing vascular risk factors, such as high blood pressure and high cholesterol, may slow down the progression of cognitive decline due to mini-strokes -- known as vascular cognitive impairment. Hence, aerobic exercise, such as running and brisk walking, may be a very promising strategy against vascular cognitive impairment. Aerobic exercise not only decreases vascular risk factors but may also improve brain structure and function. The impact of the proposed work can be significant. Delaying the onset of dementia by one year would reduce the number of cases by 9.2 million by 2050 in the United States alone. For the person with vascular cognitive impairment, delaying the progression of the disease preserves his/her ability to live independently and quality of life. Based on the success of past research looking at the positive impact of aerobic exercise on cognitive and brain function, the likelihood of translating these benefits to people with vascular cognitive impairment is high.

CIHR Network Catalyst Knowledge Translation

Erin Michalak, Mood Disorders Centre
Title: Improving care and wellness in bipolar disorder: a collaborative knowledge translation network. This Network grant will support Dr. Michalak's interdisciplinary research team - the Collaborative RESearch Team to study psychosocial issues in Bipolar Disorder (CREST.BD) and will enable the program to grow from a provincially focused team into a national network. As a national network, CREST.BD will step into a leading role nationally and internationally in understanding psychosocial factors and treatments that translate into improved care and wellness in people with BD. For additional details about this grant click here; for more information about CREST.BD click here.

Co-Investigators: Elliot Goldner (Simon Fraser University), Mark Lau (Child and Family Research Institute), James Livingston (BC Mental Health and Addiction Services), Gregory Murray (Swinburne University of Technology, Melbourne, Australia), and Vytas Velyvis (Ontario Shores Centre for Mental Health Sciences).

Technical Abstract: Bipolar disorder (BD), formerly known as manic-depression, is a condition characterised by repeated episodes of depression and over-elated mood (known as mania or hypomania). The disorder affects over half a million people in Canada and results in substantial costs to the health care system. Medication treatments are, are for many people, an important part of living well with BD. However, research evidence indicates that psychological and social factors (psychosocial factors) are also important to wellness and quality of life (QoL) in people with BD. Our team, the Collaborative RESearch Team to study psychosocial issues in Bipolar Disorder (CREST.BD) was established in 2007. We are unique in that we specialise in the translation of knowledge about psychosocial factors in BD. Importantly, CREST.BD members include people who live with BD and their health care providers. Our team has produced particularly strong research findings in relation to four areas: (1) Self-management strategies; (2) Psychosocial treatments; (3) QoL; and (4) Stigma. Here, we request CIHR Network Catalyst funding to achieve our vision and to support our growth from a provincially-focused (British Columbian) team into a national network. In doing so, we will create a leadership role for Canada in terms of translating knowledge about psychosocial factors into improved care and wellness in people with BD.

Proof of Principle (Phase I - Drug Development)

Neil Cashman (VCHRI Brain Research Centre) and Robert Hancock (UBC)
Title: Novel anti-inflammatory treatment for Amyotrophic Lateral Sclerosis
Amount: $160,000

Abstract: Amyotrophic lateral sclerosis (ALS) , also known as Lou Gehrig's disease, is a fatal neuromuscular condition that currently affects approximately 30,000 people in North America. In ALS, deterioration of upper and lower motor neurons causes gradual muscle paralysis and atrophy, affecting mobility, speech, swallowing and eventually respiration. Half of affected individuals are dead within 3 years, with less than 20% surviving for more than 5 years. There is a strong connection with inflammation in the brain possibly triggered through activation of specialized defence cells termed microglia. Indeed there is evidence of microglial activation in human postmortem brain and spinal cord tissue, and PET scanning of the brain of ALS patients strongly suggests a role for inflammatory cascades in ALS pathology. Thus excessive inflammation in the brain through microglia activation likely contributes to motor neuron dysfunction, injury and loss, and hence, to disease progression. We are proposing here to further develop an exciting new drug from the innate defence regulator peptide family, which has demonstrated efficacy in suppressing inflammation in a broad range of inflammatory situations including an animal model of severe ALS. Here we will determine whether specific formulations enhance effectiveness and also determine the optimal dosing schedule and amount.

1. CIHR Catalyst Grant: Pilot Projects in Aging - Social Dimensions of Aging

   Teresa Liu-Ambrose (Centre for Hip Health and Mobility) along with co-investigators Jennifer Davis (Centre for Clinical Epidemiology and Evaluation), Linda Li (Centre for Hip Health and Mobility), and Karim Miran-Khan, received a $49,985 CIHR Catalyst Grant to support a pilot project in aging, entitled, Can the Otago falls prevention program be delivered by video? A feasibility study.

   Abstract: Falls are a common among older adults and are the third leading cause of chronic disability worldwide. About 30% of community-dwellers over the age of 65 experience one or more falls every year. Although not all falls lead to injury, about 20% require medical attention and 5% result in fracture, with one-third of those being hip fractures. Key risk factors for falls include impaired balance and weak muscles. Exercise can reduce falls by improving older adults' balance and muscle strength. Specifically, New Zealand researchers designed a physical therapist-delivered, home-based strength and balance training program. This intervention - the Otago Exercise Programme (OEP) - is an exercise training program with strong evidence for falls reduction in older adults. However, in Canada, there is a shortage of licensed physical therapists - especially in rural communities. This combined with the fact that older adults who live in rural areas face an increased risk of falls indicate that there is an obvious need to identify other methods of delivering effective falls prevention strategies, such as the OEP. Hence, in this proposed study, we aim to assess the feasibility of delivering the OEP by an interactive video (i.e., DVD) rather than by physical therapists only.

2. CIHR Partnerships for Health System Improvement (PHSI)

   Stirling Bryan (Director, Centre for Clinical Epidemiology and Evaluation) and Craig Mitton (Centre for Clinical Epidemiology and Evaluation) are co-investigators on a 3‑year "Partnerships for Health System Improvement" grant entitled, Evidence, values and priority setting methods in cancer control. The team is led by Stuart Peacock of the BC Cancer Agency.

   Amount: $290,630 from CIHR; $75,000 from Michael Smith Foundation for Health Research.

   Abstract: The overarching aim of this study is to examine how we can combine evidence and public values to set priorities for cancer control programs (including prevention, screening, treatment and palliative/supportive care). Its objectives are to: (a) develop better methods for identifying, interpreting and applying evidence in different cancer control decision-making contexts; and (b) better understand if, when, and how public engagement and public values should play a part in priority setting processes for cancer control. The study will consist of five phases:

   1. Refining an existing model for evidence-based decision making to focus on cancer control, and to explicitly incorporate public values.
   2. Conducting a national survey of cancer control decision-makers, focusing on how evidence and public values are used in priority setting.
   3. Conducting in-depth case studies of current cancer control priority setting processes in two Canadian provinces, to explore how evidence and public values should be combined when setting priorities for cancer control.
   4. Conducting pilot public engagement exercises in two Canadian provinces.
   5. Developing a decision-support tool for priority setting processes in cancer control.
   
   This study will result in guidance for decision makers on how to integrate evidence and public values in their own priority setting and resource allocation processes. By bringing together key cancer control researchers, decision-makers and members of the public, the work will seek to inform resource allocation across cancer prevention, screening, treatment and palliative care programs. The study will be based at the Canadian Centre for Applied Research in Cancer Control (ARCC), and carried out by a highly experience team of researchers and decision-makers from British Columbia and Ontario.

   Full Team:

   Principal Investigator: Stuart Peacock of the BC Cancer Agency.
   Co-Investigators: Stirling Bryan (Director, Centre for Clinical Epidemiology and Evaluation); along with Michael Burgess (UBC), Mark Dobrow (University of Toronto), Jennifer Gibson (University of Toronto), Jeffrey Hoch (University of Toronto and the Centre for Research on Inner City Health, St. Michael's Hospital), and Craig Mitton (Centre for Clinical Epidemiology and Evaluation and the UBC School of Population Health).

3. Partnerships for Health System Improvement (PHSI)

   Stirling Bryan (Director, Centre for Clinical Epidemiology and Evaluation, (C2E2)) is co-principal investigator with Ramin Mehin (Fraser Health Authority) on a 3-year $430K Partnerships for Health System Improvement grant entitled, Why are so many patients dissatisfied with knee replacement surgery? Exploring variations of the patient experience.

   Amount: $339,600 from CIHR and $100,000 from Michael Smith Foundation for Health Research
   Abstract: Knee replacement surgery is the most requested joint replacement surgery in Canada. Knee replacements in Canada among those aged 55 to 64 tripled for men, and more than tripled for women, between 1995 and 2005, and will continue to increase in response to the needs of an aging population. As knee replacement surgery is a costly and high-demand procedure, decision makers are faced with the difficult challenge of how to provide high quality patient care that is equitable, efficient, cost-effective, and provided on a timely basis. To date, research and policy making have focused on satisfactory outcomes and satisfied patients - the approximate 80 percent who experience significant improvement in knee joint pain reduction and increased mobility following knee replacement surgery. Until very recently, less attention had been given to patients who are dissatisfied with their outcomes, even though they comprise about 20 percent of knee replacement patients. Recent research has identified several causes of poor outcomes and patient dissatisfaction, but we don't conclusively know why patients are dissatisfied with their outcomes, how these factors combine, or how they contribute to the patient experience. We therefore propose to study the factors that lead to variation in the patient experience with knee replacement surgery, by interviewing patients and having them complete questionnaires on their knee replacement experiences. The question of variation is important for different audiences:

   1. patients, who want to be able to carry out normal, everyday activities
   2. physicians, who want their patients to recover fully
   3. health care administrators, who need to apply scarce health care dollars where they will yield the greatest benefit
   4. policy makers, who are accountable to the population

   Full Team:

   Principal Investigators: Stirling Bryan (Director, C2E2) and Ramin Mehin (Fraser Health Authority)
   Co-Investigators: Jennifer Davis (C2E2); Laurie Goldsmith (SFU); Richard Sawatzky (Trinity Western; UBC visiting Assoc Prof); Michael Wasdell (Fraser Health)

1. Knowledge Synthesis Grant - PA: Financing, Sustainability and Governance

   Craig Mitton (Centre for Clinical Epidemiology and Evaluation): $100,000 for, Synthesizing knowledge on disinvestment processes in health care

   Abstract: With the down turn in the world economy in 2008, public sectors across the globe have been forced to undertake unprecedented constraint. In health care, this comes on the heels of many years of growth, thus the change in direction has not only been in stark contrast to recent practice, but in many cases decision makers do not have the necessary skills to implement disinvestment processes in a robust and evidence based manner. In fact, the whole area of disinvestment in health care, from both academic and practical perspectives is in its infancy. This project will seek to synthesize knowledge on disinvestment processes in health care. There are three objectives:
   1. produce a taxonomy of the ways in which disinvestment is understood by researchers and decision makers;
   2. compile an inventory of empirical cases of attempted disinvestment in health care;
   3. develop a tool to assist decision makers in implementing disinvestment processes.
   Through this project we will synthesize knowledge in an area of critical importance and also produce new knowledge in the form of a tool to assist in the implementation of such activity. The proposed work will make a novel contribution to the literature and will have direct practical value for health care decision makers struggling to live within their means. The lessons learned from this project will be relevant to decision makers not only in times of constraint but also when organizations return to more healthy balance sheets. That is, the concept of disinvestment is one that needs to be embedded in resource management practice regardless of the broader fiscal environment. Decision makers require a stronger set of tools to support resource allocation activity. Part of this puzzle is in understanding disinvestment processes. This project will deliver a synthesis on disinvestment and develop a tool to assist decision makers in this very real and critical component of system sustainability.
   Full Team: Stirling Bryan (Centre for Clinical Epidemiology and Evaluation), Stuart Peacock (BC Cancer Agency), Iestyn Williams (University of Birmingham)

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2. Meetings, Planning and Dissemination Grant: Aging

   Pierre Guy (Centre for Hip Health and Mobility): $7,836 for, A Canadian Hip Fracture Registry: Finding the "right" things to measure.

   Abstract: Canada annually spends $650 million to care for its 25000 citizens who sustain a hip fracture that year. This figure may underestimate all hip fracture costs as it is limited to the 1st year of care and will likely rise as the aged segment grows and survival improves. These strong statements however remain unconfirmed by our inability to track hip fracture costs over time. Beyond economic estimates, hip fractures greatly impact individuals and their families as approx. 20% of people die in the year that follows and 50% lose mobility. Our ability to better the outcome for patients and society is limited by the lack of meaningful information we continuously collect on this condition. The next apparent logical steps involve establishing a system which tracts predictors of outcomes following hip fracture to inform best practice and guide policy. We therefore set out to establish the British Columbia Hip Fracture Registry (BCHFR) within our provincial system, with a goal to one day roll out nationally. PROPOSED ACTIVITIES: We propose a 2-part plan as foundations to develop the BCHFR. This includes (i) an expert panel of key stakeholders to develop the dataset collected by the BCHFR; and (ii) a community forum aimed at engaging the community in discussion about hip fractures and at identifying additional outcomes of interest to fellow citizens. We plan these activities for February 2011 with subsequent Knowledge Transfer as we finalise the dataset by incorporating the panel and community recommendations. The community forum will additionally inform the public on the prevention, care, and outcomes of hip fracture, and will serve to present our work-to-date on the Registry. Our key stakeholders involvement strategy aims to develop a dataset which not only informs clinician best practices, and identifies knowledge gaps for researchers, but also informs government-level policy regarding the treatment and rehabilitation of hip fractures through timely and relevant data.
   Full Team: Maureen Ashe and Kelly Lefaivre from Centre for Hip Health and Mobility, and Anna Chudyk.

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3. Meetings, Planning and Dissemination Grant: Knowledge Translation Supplement

   Teresa Lui-Ambrose (Centre for Hip Health and Mobility): $65,819 for, Promoting Resistance Training to Tone the Aging Body & Mind

   Abstract: Cognitive decline among seniors is a pressing health care issue. Effective pharmacologic treatment of mild cognitive impairment and dementia remains a major medical challenge. Hence, effective primary prevention strategies of cognitive decline - such as targeted exercise training - would greatly benefit individuals and society. In 65 to 75 year old community-dwelling women, we demonstrated that 12 months of progressive resistance training once- or twice-weekly improved selective attention and conflict resolution, relative to twice-weekly balance and toning exercises. However, the prevalence of resistance training among seniors is low. Reasons include public health policy not emphasizing resistance training and misinformation. Thus, the knowledge translation challenge here is to: 1) change the perception of resistance training for seniors (i.e., reduce misinformation); and 2) provide base knowledge in progressive resistance training prescription/uptake for seniors. Therefore, our primary objective is to create an online video library that will show seniors, medical students, physical therapists, and fitness instructors/personal trainers why progressive resistance training is important for healthy aging, including the maintenance of cognitive function, and how to adopt/prescribe this type of exercise training safely and effectively.
   Full Team: Lynn Beattie, Brain Research Centre; Jennifer Davis, Centre for Clinical Epidemiology and Evaluation; Linda Li, Centre for Hip Health and Mobility & Arthritis Research Centre)

   Boris Sobolev (Centre for Clinical Epidemiology and Evaluation) and Adrian R Levy (Providence Health Care): $92,550 for, Disseminating SIMCARE results to other services and jurisdictions.

   Abstract: The proposed activities include: (1) KT conference in Vancouver with decision makers in cardiac care from Nova Scotia, Quebec, BC; (2) KT conference in Halifax with orthopedic surgeons and decision makers from Nova Scotia; (3) publication of the proceedings of the two conferences; (4) website development, hosting, maintenance; (5) book development (editor, typesetting, subject index); (6) development of knowledgebase in healthcare evaluation using simulation experiment; and (7) launching a new publication series.
   Full Team: Nathaniel Bell, Centre for Clinical Epidemiology and Evaluation and VGH Trauma; Guy Fradet, VGH Cardiology; and Lisa Kuramoto, Centre for Clinical Epidemiology and Evaluation)

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4. Meetings, Planning and Dissemination Grant PA: Institute of Infection and Immunity

   Neil Cashman (Brain Research Centre): $25,000 for PRION 2011: The New World

   Abstract: PrioNet, in partnership with the Alberta Prion Research Institute, is proud to present PRION 2011, the world's largest prion research congress. This event will take place in Montreal in May 2011, marking the first time that PRION will take place outside of Europe. The PRION 2011 congress will draw over 600 prion researchers to Canada for a valuable exchange of knowledge and expertise, creating unique opportunities for nurturing and further enhancing strong Canadian research collaborations with partners around the world. The congress will fuel discussions on a broad spectrum of topics in the field of prion research, from surveillance and control, to prion structure and function, to diagnostics and therapeutics. The three and a half day program for the congress includes renowned guest speakers, exhibits, workshops, panels, networking activities, student development, and poster sessions. Where permitted, speaker presentations will be recorded and posted on the NeuroPrion website after the event is complete. A conference proceedings will be produced in partnership with the prestigious journal PRION. To help cover the overall costs of this major event, we are requesting $25,000 of support. This amounts to approximately 5% of the total estimated budget for PRION 2011, which is $550,000 based on 600 attendees. As past PRION congresses illustrate, the calibre of oral abstract submissions and guest speakers, depth and breadth of poster presentations from a range of disciplines, and quality of papers submitted for the proceedings, in addition to the international element, enable a high level of knowledge exchange and a great potential to develop the kinds of collaborations that facilitate advancement in this area of research. Please refer to the "Detailed Activity Description" included in this application for complete details.

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5. Meeting Planning and Dissemination: International Research Collaborations

   Teresa Lui-Ambrose (Centre for Hip Health and Mobility): $22,400 for, Seizing the Opportunity: Planning & Developing Future Directions in Aging Research Using the CLSA

   Abstract: The Canadian Longitudinal Study on Aging (CLSA) is the largest, national, long-term study of adult development and aging in Canada. The goal of the CLSA is to assemble a cohort of 50,000 Canadians aged 45 to 85 years to be followed for at least 20 years. Core CLSA data set includes demographic as well as measures of physical functioning, psycho-cognitive functioning, social functioning, and perceived well-being. Hence, the CLSA provides an exceptional platform for research on aging, especially since it allows embedded ancillary studies. In 2011, the CLSA will initiate Phase III of data collection. Of the 10 comprehensive data collection sites across Canada, two will be in Greater Vancouver, BC. Specifically, starting in early 2013, the Brain Research Centre (BRC) located on the University of British Columbia (UBC) campus will be a data collection site for 1,500 BC participants who will be tracked at three-year intervals. This provides a unique opportunity for BC researchers to collaborate nationally and internationally to develop and initiate embedded ancillary CLSA studies. Our research team has a strong background and specific interest in the interplay between physical activity, cognitive function, mobility, and aging, with a focus on economic evaluations. Hence, we aim to organize a two-day research symposium that will include prominent National Institute Aging researchers with extensive experience in longitudinal studies (e.g., Cardiovascular Health Cognition Study, Women's Health and Aging Study) so that we can develop and initiate leading edge ancillary CLSA studies that will broadly: 1) Explore cognitive function as a precursor, mediator, and outcome in the CLSA study population; 2) Explore physical activity as a precursor, mediator, and outcome in the CLSA study population; and 3) Explore the independent and interactive effect of cognitive function, physical activity, and mobility on successful aging in the CLSA study population.
   Full Team: Lara Boyd, Brain Research Centre; Jennifer Davis, Centre for Clinical Epidemiology and Evaluation; Linda Li, Centre for Hip Health and Mobility & Arthritis Research Centre; and Heather Stewart (Fraser Health).

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   January 2011 CIHR Funding Announcements

   1. Operating Grants: Canadian Institutes for Health Research (CIHR) awarded investigators affiliated with VCHRI approximately $6.2 Million through the September 2010 Operating Grant Competition. This particular round was highly competitive.

      Congratulations, and our apologies if we have missed anyone.

      Lara Boyd, Brain Research Centre: $320,000, for Duration of Changes in Intracortical Excitability and Diffusion Abnormalities after Transient Ischemic Attack

      Abstract: Approximately 25% of strokes are preceded by a mini-stroke, or transient ischemic attack (TIA). A TIA occurs when people experience stroke-like symptoms that rapidly disappear and the risk of future stroke after a TIA is very high. However, TIA is very difficult to accurately diagnose, since the symptoms of TIA disappear so rapidly and there are several conditions that have similar symptoms, but are not TIA (e.g., TIA-mimic). Information from magnetic resonance imaging (MRI) can be used to help identify TIA, but only a percentage of people with TIA have abnormal MRIs. A brain stimulation technology, called Transcranial Magnetic Stimulation (TMS), provides information about the activity of different types of cells in the brain. Disruptions in brain activity have been shown to occur shortly after TIA, but it is not known whether these disruptions are related to abnormal MRIs after TIA, if these disruptions are permanent, or if they differ in people with TIA compared to people with TIA-mimic. The purposes of this study are 1) to test if disruptions in brain activity are related to abnormal MRIs after a TIA, 2) to test how long brain activity remains changed after a TIA, and 3) to test if these changes can help distinguish TIA from a TIA-mimic. We will use both TMS and MRI in individuals with TIA and TIA-mimic. Participants will complete the first session of TMS and an MRI within two weeks of their symptoms and several follow-up sessions within the following two months. This will allow us to test how long changes in brain activity last after a TIA. The results of this study will provide information about new ways to identify people at high risk of stroke and have the potential to improve stroke prevention strategies after TIA.
      Co-investigators: Jodi Edwards, Alex L Mackay, Alexander Rauscher, Manraj S Heran, Oscar Benavente.

      Dr. Boyd's study is also featured on the VCHRI webpage.

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      Jeff Brubacher, Emergency Medicine: $920,000, for Cannabis and Motor Vehicle Crashes: A Multicentre Culpability Study

      Abstract: Marijuana is the most commonly used illicit drug in Canada and many drivers, especially young adults, report driving after using marijuana. Although there is abundant experimental evidence that marijuana, either alone or in combination with alcohol, impairs the skills required for safe driving, real world data on the contribution of marijuana to car crashes is mixed. This uncertainty hinders the ability of traffic safety policy makers to develop effective, evidence based, traffic laws or road safety campaigns targeting people who drive while impaired by marijuana. The primary objective of the study proposed here is to determine whether injured drivers who used marijuana before a car crash are more likely to have caused the crash than those who did not. Our aim is to improve traffic safety by providing current North American data that can be used to inform the development of evidence based road safety policy targeting people who drive while impaired by marijuana.
      Co-investigators: Gary Andolfatto, Mark Asbridge, Rollin Brant, Stirling Bryan, William Schreiber, Scott Macdonald, Robert Mann, Walter Martz, Roy Purssell, and Olaf Drummer.

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      Janice Eng, Brain Research Centre; ICORD: $520,000 for Beyond VO2peak: Understanding exercise-induced changes in cardiovascular function after stroke

      Abstract pending
      Co-investigators: Penny Brasher, Ken Madden, Ada Tang, Teresa S Tsang, Andrei Krassioukov.

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      Kurt Haas, Brain Research Centre: $680,000 for In vivo imaging of visual stimulation-evoked dendritic arbor growth and synaptogenesis in the CNS: Role of synaptic transmission and downstream signaling in brain circuit development

      Abstract: It is becoming clear that numerous common and devastating neurological disorders, like Autism Spectrum Disorders, Schizophrenia and Epilepsy can be caused by abnormal brain development. Here, we propose to employ advanced imaging techniques to directly image brain structural growth during critical periods sensitive to disruption, in order to understand normal and pathological brain circuit development. These imaging techniques provide high-resolution 3D images of brain neurons and movies of neuron growth as brain circuits are formed. In addition, using fluorescent dyes sensitive to neuronal firing, we propose to directly image network activity in the awake brain. By controlling activity and gene expression of individual brain neurons, we are able to test the roles of external and intrinsic factors in regulating structural and functional growth. Results will identify novel proteins involved in developmental brain plasticity that may offer new targets for developing therapeutics or preventative treatments to counter developmental neurological disorders.

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      Judy Illes and Lynn Beattie, Brain Research Centre: $330,000 for Aboriginal Wellness in Alzheimer Disease: Intersections of Science and Tradition

      Abstract: In Canadian Aboriginal communities there are few culturally relevant resources dedicated to Alzheimer Disease (AD). Education about symptoms and disease progression can help people prepare for the life changes associated with AD. Without such information, Canadian Aboriginal people will be limited in their ability to plan for this disease and, overall, their health may suffer. We are working with a particular First Nation whose members are at risk for a familial AD that occurs around age 50. Some members inherit a unique genetic mutation that leads to AD. In the face of predictive genetic testing, the need for culturally relevant information is even more pressing. Most Canadian resources explain AD as a brain illness, but this explanation does not align with Indigenous worldviews that balance physical, emotional, mental and spiritual wellness. We anticipate that culturally relevant informational resources based on Indigenous concepts of wellness and illness will improve the understanding of AD prediction, diagnosis, and care. We will work with members of this Nation to: 1. Elucidate how members explain AD within a holistic framework that values both scientific knowledge and traditional teachings. To do this, we will facilitate Sharing Circles and Family Interviews with members of this Nation, and we will interpret the findings in collaboration with the research participants. 2. Synthesize the findings in a preliminary report and, through an iterative process with the community, discuss and further interpret the results. 3. Create a final resource report that leads to improved understanding of AD prediction, diagnosis, and care for members of the Nation, clinicians, academics and policy makers. Our research will bring together traditional teachings and scientific understandings. It will contribute to Canadian knowledge of Aboriginal health and wellness, rural and remote health, AD, and intersecting challenges in the science of the brain, genetics, and ethics.
      Co-investigators: Wendy Hulko, Richard Vedan, Elana Brief.

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      Gang Li, Skin Sciences: $750,000 for The role of tumour suppressor ING1b in genomic stability upon replication stress.

      Abstract: The incidence of skin cancer has been increasing rapidly in the past few decades. Although it is well known that ultraviolet light is the primary environmental factor for skin cancers, the exact molecular mechanisms responsible for skin cancer development is still largely unknown. Recently, we have found that the tumour suppressor ING1b plays an important role in genomic stability upon replication stress including ultraviolet radiation. In this proposal, we will investigate the molecular mechanisms of ING1b in recovery of DNA replication and genomic stability. We will also use in vivo animal model to examine if ING1b-deficient mice are predisposed to UV-induced skin cancer development. This project will provide new insights into the molecular mechanisms on ING1 tumour suppressor in genomic stability, which may lead to novel strategies for cancer prevention and treatment.

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      Teresa Y. Liu-Ambrose, Centre for Hip Health & Mobility: $730,000 for Action Seniors! An RCT of Secondary Falls Prevention in Community-Dwelling Senior Fallers.

      Abstract pending
      Co-investigators: Karim Miran-Khan, Meghan G Donaldson, Jennifer C Davis, Carlo A Marra, Wendy L Cook, Ryan E Rhodes, Penny Brasher, Peter Graf.

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      Martin J. McKeown, Pacific Parkinson's Research Centre: $300,000 for Dynamic Striatal/Cerebellar interactions in Parkinson's Disease

      Abstract: Parkinson's disease (PD) has been considered a "classic" basal ganglia disease, and dominant models of the last two decades have examined the role of altered basal ganglia function in PD. However, it is becoming increasingly clear that solely focusing on abnormal basal ganglia function cannot explain many disease features that are vitally important to those affected: the significant variability in the progression of the disease, why PD subjects with tremor tend to have a more benign prognosis and reduced motor complications of treatment, and why tremor often does not respond to dopaminergic therapy. This work proposes to answer these questions by investigating the complementary role the cerebellum plays in PD. By using functional magnetic resonance imaging (fMRI) and manual tracking tasks, we will determine how cerebellar function becomes altered when the basal ganglia are affected by PD. In addition to explaining many features of PD, this work may spawn new rehabilitation strategies, and provide novel targets for future drug therapies.
      Co-Investigators: Z. Jane Wang and Meeko Oishi.

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      Timothy H. Murphy, Brain Research Centre: $950,000 for Probing the circuits responsible for stroke recovery with light-mediated circuit monitoring and manipulation in mouse models

      Abstract: Reductions in blood flow to the brain of sufficient duration and extent lead to stroke, which results in damage to neuronal networks and impairment of sensation, movement, or cognition. Although stroke damage can be devastating, many patients survive the initial event and undergo some spontaneous recovery which that can be further augmented by rehabilitative therapy. It becoming clear that the ability of patients to recover is in part mediated by the ability of the brain circuits to adapt in a process called plasticity. My lab will apply new light-based techniques to address how the brain's sensory and motor circuits adapt in response to stroke. The brain is organized much like a circuit diagram within a computer with discrete wires or connections. However, none of the brain circuits or cells have color-coding or labels which enable technicians to service them. Here, using new genetic technologies we will employ strategies, which label select mouse neurons with fluorescent proteins, which enable them to glow under particular wavelengths of light. Not only can the glowing neurons be found by light, but they can also be controlled by light using new light-sensitive protein ion channels, which transmit light energy into excitation or inhibition. Using these fluorescing neurons, which can be controlled by light, we plan to unravel how the brains sensory and motor system adapt following damage due to stroke. We hope that by understanding how the brain can partially cope with stroke damage that this knowledge can be exploited to help patients through innovative brain stimulation or rehabilitative strategies. We have now devised new strategies for both exciting and inhibiting the brains of mouse models of stroke damage to aid these studies. Overall, our goal is that through insight into natural sensory and motor system adaptation novel treatments will ensue, permitting better lives for those affected by diseases such as stroke.

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      Paul Rennie, Vancouver Prostate Centre: $690,000 for In Vivo siRNA Knockdown of Androgen Receptors to Treat Advanced Prostate Cancer

      Abstract: It is estimated that more than 100,000 Canadian men are currently living with prostate cancer and that this year almost 25,000 will be newly diagnosed and over 4,000 will die of this disease, making it the most commonly diagnosed non-skin cancer in men and one of the leading causes of cancer-death. If caught early, it is frequently curable by surgical removal of the prostate or by radiation treatment. However, it often recurs with accompanying metastatic spread to bones. This advanced form of the disease is usually managed with treatments referred to as medical castration that prevent the synthesis of androgens like testosterone or obstruct their ability to bind and activate the androgen receptor in the prostate cancer cell. These treatments block the growth promoting effects of androgens and activate cell death processes in the cancer cells. Unfortunately, the cancers eventually become resistant and progress to the lethal, castration-resistant state with an androgen receptor that is now active despite very low levels of circulating androgens. With previous support from CIHR, we have shown that knocking down this androgen receptor using a specific RNA interference approach inhibits this progression and even causes complete regression of some castration-resistant tumours. We have also shown that we can package these RNA interfering molecules into liposomes, inject them into prostate tumour-bearing animals, and see a reduction of prostate tumour growth. Thus, the main objective of this renewal application is to develop better and more efficient ways to deliver these RNA interference molecules for targeting and knocking down the androgen receptor in castration-resistant prostate tumours. We anticipate that the combined strengths and expertise of the Cullis and Rennie labs will continue to perform synergistically to accelerate development of these delivery systems and have a major impact on the survival of men with advanced, castration-resistant prostate cancer.
      Co-investigators: Pieter Cullis.

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   2. $2.5M Emerging Team Grant: Regenerative Medicine and Nanomedicine

      Martin Gleave (Vancouver Prostate Centre) and David Huntsman (OvCare and BCCA) are part of a seven-member team that received $2.5 million to investigate Personalized siRNA-Based Nanomedicines

      Abstract: The ability to treat cancer is severely limited by the variability and complexity of the disease. The genetic mutations that cause cancer in one patient are often not the same mutations that cause cancer in other patients. Consequently, many cancer therapies are ineffective in large groups of patients.

      Advanced therapeutic technologies, known as nanomedicines, are for the first time, allowing scientists to rapidly and specifically target those genes that may be the cause of a patient's disease. This proposal seeks to combine these advanced diagnostic and therapeutic technologies to develop methods that will eventually allow physicians to prescribe nanomedicines that are most effective for an individual patient. To accomplish this, we have brought together expert investigators in advanced cancer genomics and advanced targeted nanomedicines to strengthen Canada's capacity to treat cancer in this promising way.

      The full research team: Pieter Cullis (UBC biochemistry); Marcel Bally, (BCCA); Marco Ciufolini (UBC Chemistry); Karen GELMON (BC Cancer); Martin GLEAVE (VCHRI, Vancouver Prostate Centre); Carl Hansen (UBC Phys, Centre HighTHruput Bio); and David Huntsman (BC Cancer and VCHRI).

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   3. Proof of Principle (Phase II) grant

      Harvey Lui, Skin Care Centre (with Haishan Zeng and David McLean from BC Cancer Agency) $601,082 entitled Development of a laser Raman spectroscopy system for melanoma detection. ($308,800 from T-Ray Science Inc., industry partner)

      Abstract: Skin cancer is the most common cancer and the rates are continuing to rise at a staggering 3% per year. One in seven Canadians will develop a skin cancer during their lifetime. Over 3.5 million cases are diagnosed annually in the USA. The American Cancer Society estimates that about 68,130 new melanomas will be diagnosed in the United States during 2010. Melanoma is lethal in 85% of cases after metastasis. However, when diagnosed very early, survival rate can be 99% - highlighting the need for sensitive screening and early detection. Currently identification of melanomas is an art best performed by trained dermatologists. The definitive diagnosis ultimately requires excision of the suspect lesion, an undesirable and in many cases not practical solution especially in individuals with many suspect lesions. Hence there is a need for a device that can rapidly screen and distinguish melanomas from other more benign lesions. We have developed a technology called laser-Raman spectroscopy that measures molecular vibrations of skin tissue in vivo. The obtained optical signals can be used to derive biochemical information of the skin site measured. These biochemical information changes with malignancy transformation. Therefore, it can be used for accurate non-invasive melanoma detection. We have collected clinical data with this device from more than 912 skin lesions and an intermediate analysis has demonstrated great potential of this device for melanoma detection (diagnostic sensitivity of close to 100%, while still maintaining a false positive rate of only ~30%). The objectives of this project are (1) to conduct a detailed data analysis of the 912+ lesion spectral database to confirm the clinical utility and diagnostic accuracy of our new technology for melanoma/skin cancer detection and (2) to develop a simplified, optimized, and cost-effective, clinical device to facilitate next phase multi-centre clinical trials and subsequent commercialization.

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   4. MD/PhD Program Grant

      Lynn Raymond (Brain Research Centre). $264,000 (over 6months)

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   August / September 2010

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   Congratulations to the following VCHRI investigators, who were awarded funds from CIHR and its partners this month:

   Dr. Sandra Jarvis-Selinger - $100K Knowledge Synthesis Grant

   Title: Home-Based Telehealth for Chronic Disease Management: Synthesis of Knowledge, Gaps and Priorities
   Co-Investigators: Joanna Bates, Daniel Horvat, Scott Lear

   Dr. Maureen Ashe, received 2 prizes on the strength of her 2010 New Investigator grant, (Mobilizing Evidence into Action to Improve Health Outcomes of Vulnerable Seniors):

   • New Investigator Recognition Prize-Research on Aging ($10,000)
   • New Investigator Knowledge Translation Supplement ($5,000)

   Dr. Mark Fitzgerald (Centre for Respiratory and Critical Care, VCHRI; VGH Lung Centre) was awarded the $200,000 Pfizer Operating Grant in Disease Prevention and Management, for the grant entitled: Assessing Chronic Obstructive Pulmonary Disease (COPD) knowledge, beliefs, and health literacy in Chinese Immigrant adults in the Greater Vancouver Area (GVA): A population-based disease management study

   Co-Investigators: Kendall Ho, Rosemin Kassam, Arminée Kazanjian, Nadia Khan, Stephen Lam; Maureen Mayhew, Margaret McGregor, Donald Sin.

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   July 2010

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   CIHR Team Grant in Physical Activity, Mobility and Health

   John Esdaile, of the Arthritis Research Centre and Centre for Hip Health and Mobility, was awarded $2.5 Million for the research program entitled, IMPAKT-HIP: Investigations of Mobility, Physical Activity, and Knowledge Translation in Hip Pain.
   VCHRI Co-Investigators include Jolanda Cibere, Bruce Forster, Don Garbuz, Michael Gilbart, Jacek Kopec, Allen Lehman, Linda Li, Alex Mackay, Heather McKay, David Wilson.

   The team will investigate how certain types of physical activity can cause hip osteoarthritis (OA),

   OA occurs when cartilage, the tissue that lines the ends of the bone, becomes damaged. It is the most common form of hip arthritis and is responsible for more than 90% of the 21,000 hip replacements done in Canada every year. Recently, subtle deformities of the hip have been linked to hip OA, and it is believed that physical activity can combine with the deformity to cause hip damage.

   Using state of the art MRI techniques, the Team aims to show how activities, such as hockey, soccer and cycling, can combine with one or more of these deformities, to cause cartilage damage and eventually lead to OA. This research will generate the new knowledge needed for major breakthroughs in the prevention, detection and treatment of hip OA.

   The collaborative team includes researchers from four medical specialties (orthopaedics, rheumatology, physiotherapy, radiology), six research disciplines (basic and clinical sciences, population health, epidemiology, biostatistics, health services research and knowledge translation), as well as stakeholders from the arthritis community.

   Other local and national coPIs: Hubert Wong (UBC & St Paul's Hospital), Michal Abrahamowicz (McGill), Carolyn Emery (U of Calgary).

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   June 2010

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   Researcher Kudos: $13.3 million in CIHR funding awarded to VCHRI investigators

   Congratulations to the following VHCRI investigators and teams, who were awarded over $13.3 million from the Canadian Institutes for Health Research in June.

   Canadian Institutes for Health Research (CIHR)

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   1. CIHR Operating Grants:
      Results of the March 2010 competition, including Priority Announcements and Bridge Funding

      VCHRI investigators were awarded 16 operating grants totalling $7.8 million dollars through the March 2010 Open Operating Grant Competition, representing a $3million dollar increase over each of the last 2 rounds of funding.

      Thanks to a large number of applications, this was a highly competitive round (just an 18% success rate nationwide) and many high-scoring applications were not funded.

      Congratulations to the following investigators and our apologies if we missed anyone.

      Yossef Av-Gay, Immunity and Infection Research Centre
      $745,180 for, Molecular analysis of Mycobacterium tuberculosis Signalling.

      Jason Barton, Brain Research Centre
      $442,997 for the grant, Face expression and identity processing in the occipitotemporal cortex.

      Lara Boyd, Brain Research Centre
      $257,115 for, Interhemispheric contributions to neuroplasticity and motor learning after stroke.

      Ann Marie Craig, Brain Research Centre
      $895,858 to investigate, Molecular dynamics at the postsynaptic density.

      Vincent Duronio, Immunity and Infection Research Centre
      $665,920 for the grant, MCL-1: Functions in the nucleus regulating cell cycle and DNA damage response.

      David Huntsman, director of the VCHRI Ovarian Cancer Research Program (OvCare)
      $541,640 for, Mutations in the SWI/SNF chromatin remodelling complex genes: an alternative mechanism for ovarian carcinogenesis.

      Gang Li, Skin Sciences and Hair Lab
      $100,000 for, The role of tumour suppressor ING1b in genomic stability upon replication stress.

      Harvey Lui (Director Skin Sciences and Hair Lab) and coPIs Tim Lee and Haishan Zeng from BC Cancer Agency)
      $85,212 for, Depth-sensitive low-coherent speckle technique for skin lesion differentiation.

      Orson Moritz, Brain Research Centre
      $786,560, to conduct In-vivo analysis of mechanisms of cell death in inherited retinal degeneration.

      Alice Mui, Immunity and Infection Research Centre
      $390,802 to investigate Small molecule SHIP agonists for inhibiting the phosphoinositide 3-kinase pathway.

      Torsten Nielson, Immunity and Infection Research Centre
      $289,885 to investigate CSF1 pathway inhibitors in tenosynovial giant cell tumors and leiomyosarcoma.

      Jerilynn Prior, Director of the Centre for Menstrual Cycle and Ovulation Research (CeMCOR)
      $371,134 for the RCT, Oral Micronized Progesterone for Perimenopausal Vasomotor Symptoms.

      Lynn Raymond, Brain Research Centre
      $805,334 for the proposal, Altered balance of synaptic/extrasynaptic NMDA receptor signaling in Huntington disease.

      Helen Tremlett, Brain Research Centre
      $384,367 for Pregnancy, beta-interferon exposure, and long-term disability in Multiple Sclerosis.

      Garth Warnock, Immunity and Infection Research Centre
      $380,862 to investigate the Effects and Mechanisms of B7-H4 Pathway on Inhibition of the Development of Type 1 Diabetes.

      David Wilson (Centre for Hip Health and Mobility) and Alex McKay (MRI Research Centre):
      $676,920, for Imaging-based assessments of knee mechanics.

   2. CIHR Team Grant: Vision, Hearing and Communication Disorders

      Drs. Kevin Gregory-Evans, Joanne Matsubara, Cheryl Gregory-Evans, and Orson Moritz (all members of the Brain Research Centre and the Centre for Macular Research) were awarded $1.5 million to investigate novel molecular approaches to treat diseases of the retina, the tissue most commonly damaged in blinding diseases. This was one of only 3 grants awarded nationwide.

      They aim to identify new molecules that will prevent common causes of retinal damage (such as cell death, protein misfolding, and inflammation) while also investigating new ways to deliver these therapies. A unique aspect of their approach is to test the effectiveness of new therapies in combination. While drug combinations are common in the treatment of diabetes, hypertension, and cancer, it has never been assessed in retinal diseases.

      Grant title: CIHR Team in novel molecular approaches in the treatment of retinal disease
      Funds: $1,500,000 over 4 years.

   3. CIHR Team Grant: Terry Fox New Frontiers Program in Cancer

      A team of investigators lead by Dr. David Huntsman, director of the VCHRI OvCare program and a researcher with the BC Cancer Agency, has been awarded more than $3.1 million through a Terry Fox Foundation program that supports "breakthrough research that could lead to innovative ways to prevent, diagnose, or treat cancer".

      Background: Cancer has proven a complex puzzle to solve because most common cancers do not have a single cause. Instead, they result from a combination of many different genetic changes (or "mutations"), only some of which will be present in any given patient.

      The situation is very different in rarer tumours, where all patients develop the tumour because of the same identical mutation. This direct cause-and-effect means that once researchers have identified the genetic mutation that causes the tumour, they can map all the resulting clinical and biological changes to a single genetic cause. This approach helps us to understand the mechanism at the root of rare tumours, while at the same time, revealing basic principles of cancer biology.

      Proposed research: Huntsman's team has proposed to study 12 "simple" tumours that lack effective diagnostics and treatments. They will identify the specific mutations that cause the cancerous behaviour in each of the 12 tumours types, and then determine how the mutation changes the cells' normal biology. This will demonstrate their potential as treatment targets.

      This work will lead to direct improvements in diagnosis and ultimately the treatment for Canadians who have rare cancers and provide insights into the biology of common cancers.

      The highly collaborative team includes: VCHRI cancer researcher Torsten Neilsen; Samuel Aparicio, Peter Lansdorp, and Marco Marra from BC Cancer Agency; Carl Hansen from UBC/BCCA; Poul Sorensen (UBC/BCCA); and T. Michael Underhill (UBC Biomedical Research Centre).

      Grant title: CIHR Team in the genomics of forme fruste tumours: new vistas on cancer biology and management
      Funds: $3,126,365 over 3 years.

   4. CIHR Aboriginal Health Intervention Operating Grant:

      Dr. Sandra Jarvis-Selinger was awarded $917 thousand dollars for the proposal, "Building pathways to health careers for Aboriginal youth". This was one of only 3 successful proposals (from a pool of 28) to be funded through the Aboriginal Health Intervention program.

      Aboriginal youth are dramatically under-represented in post-secondary education, particularly the health sciences. With only 9% of Aboriginal students eligible for post-secondary entry there are tremendous barriers to change. Dr. Jarvis-Selinger, an expert in technology-enable learning, plans to combine old-fashioned mentoring relationships (long known to have a strong positive influence on academic achievement and self-confidence) with online communications technology to create an "eMentoring" program that will connect Aboriginal youth with inspirational role models they may otherwise be unable to meet.

      The eMentoring pilot program will be aimed at youth in grades 6-10. Mentor-student relationships will last a minimum of one year, and consist of online activities that address some of the barriers Aboriginal students face in their transition to post-secondary education. Specifically, the researchers aim to determine: 1) how best to implement an eMentoring model in First Nations communities; 2) how mentors and youth interact with each other; and 3) how eMentoring can promote awareness, interest and enrolment in post-secondary health science programs.

      The Team: Dr. Sandra Jarvis-Selinger is the Assistant Director of both the VCHRI Technology Enabled Knowledge Translation Investigative Centre, TEKTIC, and the UBC Education, eHealth Strategy Office.
      The core team also includes: TEKTIC members Kendall Ho (VCHRI), Lesley Bainbridge (UBC), Michal Fedeles ( SFU), and Helen Novak Lauscher; as well as Robert Woollard (UBC), James Andrew (UBC), Francis Brown, and Timothy Michel (Aboriginal Coordinator at UBC Accounting Club).

      Grant title: eHealth Mentoring: Building pathways to health careers for Aboriginal youth
      Funds: $917,897 over 3 years.

   5. Meetings, Planning and Dissemination Grant: Musculoskeletal Health, Arthritis, Skin and Oral Health

      Dr. Youwen Zhou, from the VCHRI Skin Sciences and Hair Lab was awarded $20,000 in support of the "Pigmentation Melanoma Research Conference" to be held in Vancouver (Sept 30th- Oct 3rd 2010). Co-investigators include Harvey Lui, Kevin McElwee, Catherine Van Raamsdonik and Haishan Zeng.

      The conference will bring together basic researchers and clinician scientists to review the latest developments in melanocyte research, in both normal physiology and diseases states. The goals are to facilitate collaboration between pigment researchers and other research groups in order to further integrate basic and clinical research, and to formulate consensus strategies for future areas of research that are most likely to generate clinical breakthroughs.

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   May 2010

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   The following VCHRI members were awarded CIHR "Meetings, Planning and Dissemination Grants" in May 2010. These awards support activities beyond traditional recurring meetings or conferences, and are intended to help build and sustain Canadian research in priority areas.

   • Maureen Ashe and Kenneth Madden, Centre for Hip Health and Mobility, for "Understanding the Role of Sedentary Behaviour and Type 2 Diabetes Mellitus on Seniors' Bone Health."
   • Heather McKay, Director, Centre for Hip Health and Mobility: "Measure what can be measured and make measurable what cannot be measured", to develop a novel, non-traditional framework for measuring and reporting the impact of health research, on health. (The team includes Linda Li, Karim Miran-Khan, Kerry Byrne from VCHRI, as well as Stephen Robinovitch (SFU), Joan Sims-Gould, and Paul Stolee (University of Waterloo).
   • James Wright, for "Bringing Best Evidence to Front-line Clinicians'. Along with co-investigators Vijaya Musini and Aaron Tejani, Wright aims to establish a collaborative knowledge exchange environment between hospitalists, clinical pharmacists, and academic researchers in order to facilitate adoption of best practices based on high quality research syntheses.
   • Jude Kornelsen and Karen Bartlett (UBC School of Environmental Health): "The Challenge of Low Prevalence Infectious Diseases: Towards a National Research Agenda".

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     October 2010

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     CIHR Meeting, Planning and Dissemination Grants
     $10K-$25K grants to bring together diverse expertise to develop new technologies and future research goals.
     • Bill Miller (GF Strong Rehabilitation Centre) and Alex Mihailidis (University of Toronto)
       $25K, one year
       Co-Investigators: Louise Demers, Laura Hurd-Clarke, Ronald Kirby, Janice Polgar, François Routhier
       Title: CanWheel Think Tank on International Approaches to Improving Power Mobility
     
     
     
     • John Ansermino and Guy Dumont
       $10K one year
       Co-Investigator: Charles Larson
       Title: Cell phone oximetry workshop: Canadians working towards improved anesthesia safety around the world
     
     CIHR Team Grants in Sleep and Circadian Rhythms
     • Najib Ayas
       $1,433,129 over 5 years
       Co-Investigators: Fernanda Almeida, Stirling Bryan, Sidney Fels, Mark Fitzgerald, John Fleetham, Jonathan Fleming, Mila Kwiatkowska (Thompson Rivers), Ismail Laher, Alan Lowe, John Mancini, Carlo Marra, Frank Ryan, Andrew Sandford, William Sheel, Stephanus Van Eeden,
       Title: Respiratory Sleep Disorders Research Team
     
     
     
     • Peter Soja
       $1,985,000 over 5yrs
       Co-Investigators: Michael Chase, John Peever, B. R. Sastry
       Title: Effects of age and apnea on cognitive and sensorimotor processes during sleep and wakefulness
     
     CIHR Emerging Team Grant: Alliances in Mobility in Aging
     • Heather Mckay, Stirling Bryan, Lawrence Frank
       $1,500,000 over 6 yrs
       Co-Investigators: Maureen Ashe, Philippa Clarke, Craig Mitton, Antonio Paez, Ryan Rhodes, Vicky Scott, Joan Sims-Gould
       Title: Walk the Talk: Transforming the Built Environment to Enhance Mobility in Seniors
     
     

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     April 2010

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     In April, CIHR announced the following funding awards, totaling $1.83 Million. Congratulations to all, and our apologies should we have missed anyone.

     Collaborative Health Research Projects (partnership between CIHR and NSERC)

     VCHRI-affiliated researchers are leaders or team members of 3 successful applications:

     • $436,800 to Aziz Ghahary and Frank Ko (UBC Engineering, Department of Metal and Materials) will develop and validate a novel wound healing system. The proposed wound covering will be composed of a nanofibre system (developed by KO) that provides controlled release of antifibrogenic factors (discovered by Ghahary). The final product will greatly reduce severe scarring in burn victims, and will also have uses in surgical wound healing and treatment of other fibrotic conditions.
     • $295,169 for the project, Image guidance for radical prostatectomy. The team is lead by Tim Salcudean (UBC Electrical and Computer Engineering) with a strong presence from the Vancouver Prostate Centre: Larry Goldenberg, Silvia Chang, Christopher Nguan, and Piotr Kozlowski are all co-Investigators. The groups aims to develop and validate sophisticated surgical guidance tools that will allow surgeons to identify the exact boundaries of prostate tumours. Improved accuracy and completeness of tumour removal will prevent recurrence of cancer, as well as complications such as impotence and incontinence.
     • York N.H. Hsiang, Department of Vascular Surgery, is a coInvestigator on this project led by Ken Takahata of the UBC Department of Electrical and Computer Engineering. The team was awarded $600,063 to develop "smart stents" for wireless monitoring of vascular disease. These stents contain wireless sensors and will offer an innovative, non-invasive and cost-effective method for early detection of complications.

     CIHR New Investigator:
     Maureen Ashe, PhD, Assistant Professor within the Department of Family Practice and an investigator at the Centre for Hip Health and Mobility, received a CIHR New Investigator Award. Her research will add a novel dimension to post-discharge hip fracture management among seniors, by incorporating falls risk and bone health follow-up with an evidence-based exercise program within a dedicated clinical service. The award is worth $300,000 over 5 years.

     Operating Grant, "Knowledge to Action" stream:
     Erin Michalak (Assistant Professor in the Mood Disorders Centre) along with co-principle investigator Sagar Parikh (University Health Network, Toronto) and a team of co-investigators, have received $200,000 for the grant entitled, "Quality of life, stigma and bipolar disorder: A collaboration for change". Bipolar disorder is characterized by repeated episodes of depression and elated mood. Historically, BD research has focused on its biological causes and using medications to treat it. In contrast, Michalak's collaborative team has targeted the role of psychological and social factors in bipolar disorder, with a focus on maintaining health and wellness. This grant will support a program of knowledge translation activities that highlight the importance of assessing quality of life and stigma in bipolar disorder.

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