The accumulation of mutations in the DNA of human cells can lead to tumour formation. More than 80 percent of solid tumours exhibit chromosome instability (CIN) – the property that results in an unequal distribution of DNA to each daughter cell upon cell division. The genetic instability associated with these tumours may allow them to adapt quickly and remain in the body.
Dr. Peter Stirling's research is focused on generating a comprehensive database of genetic mutations that lead to CIN, using the Baker's yeast cell model. The results will then be translated to related human genes. Using yeast to identify candidate human CIN genes has already been successful for a handful of genes and Dr. Stirling's project will extend this effort. The candidate CIN genes identified will provide important insight into the biology underlying tumour formation. Further, the results will validate interesting CIN genes relevant to cancer in human cells and provide greater understanding regarding the mechanisms of CIN for those genes.
Additionally, Dr. Stirling is also working to identify secondary genes whose mutations cause cell death in combination with a CIN mutation. By validating these "synthetic lethal mutant gene combinations" in human cells, Dr. Stirling will have defined drug targets for tumours carrying mutations in a particular CIN gene. And, working in collaboration with researchers at the University of British Columbia, Dr. Stirling will identify small molecules (i.e. drugs,) that selectively kill tumour cells based on the identified second-site mutations. Overall, the results will reveal new aspects of tumour biology, identify new anti-cancer drug targets and contribute to the development of new anti-cancer drugs.
Chronic diseases represent an increasing burden for both the patient and healthcare system. Many people also now have more than one chronic disease. For those people with chronic diseases living in rural areas, the risk for hospitalization is more than 60% greater. These patients and their primary care providers face an enormous challenge in meeting their day-today health needs that patients with chronic diseases have.
Continue reading “Utilization of an Interactive Internet-based Platform for Managing Chronic Diseases at a Distance”
The purpose of this study is to devise a comprehensive strategy for continuous improvement of trauma care system that addresses substantial gaps in the availability of information regarding processes and outcomes of trauma care in British Columbia.
Continue reading “An Integrated Regional Trauma Care Data System Linking Clinical Care and Process Outcome Evaluation”
The purpose of this initiative is to develop leadership capacity in the Canadian health care system. This will be done by identifying and addressing gaps in applied research and practical knowledge within and between the researcher and decision-maker communities. These individuals will be brought together as networks so they can better understand and learn from each other. The networks (one national and five regional nodes) will carry out research on how to identify and apply the qualities of effective leadership in regional settings across Canada and how to adapt the knowledge learned into professional development and degree programs offered in those regions.
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Much has been made over the past fifteen years about the actual or impending shortage of physicians in Canada. The aging of the patient population increases the need, while the aging of the physician population reduces the supply. Recent dramatic increases in the number of medical students being trained in Canada should go some distance in addressing supply concerns. Less well-understood is the potential effect of changes in physicians’ decisions about when, and how quickly, to retire. Despite the fact that retirement decisions can have a large influence on the total available supply of physicians, surprisingly little is known about those decisions. The purpose of this project is to fill in some of those gaps in our understanding.
Continue reading “Exit Strategies: The Timing and Impacts of Physician Retirements”
Sensorimotor deficits after stroke are commonly associated with increased activation in a number of cortical areas in the non-affected hemisphere, including primary motor and sensory cortex. Constraining the unaffected arm in individuals with stroke stimulates recovery in the use of the stroke affected arm, perhaps by reestablishing the balance of excitability between affected and non-affected cortices controlling each arm. However, the specific physiological mechanisms that follow decreasing unaffected arm use are not completely understood. Immobilization of the unaffected limb in stroke patients, by ischemia or anesthetic numbing, results in transient increases in motor function of the hemiparetic upper limb. The benefit of peripheral numbing may work through decreased proprioceptive and tactile inputs to sensory cortex which in turn diminish the overall excitability of the contralesional motor areas; the net result is a reduction in transcallosal inhibition on the affected cortex. However, beyond these preliminary findings, the role of the unaffected sensory cortex in movement deficits after stroke remains largely uncharacterized. Dr. Sean Meehan is investigating whether reducing the efficacy of proprioceptive and tactile inputs from the non-affected hand at the level of sensory cortex using continuous theta burst (cTBS), a variant of transcranial magnetic stimulation (TMS), can result not only in transient improvements in motor performance in the hemiparetic arm but also longer lasting functional changes associated with motor learning. The results of Dr. Meehan’s research may encourage rehabilitative strategies that target both the sensory and motor causes of movement deficits. The addition of sensory specific rehabilitative techniques may allow for even greater increases in function than are currently possible in individuals in the chronic phase of stroke. This line of research offers a promising new avenue for advances in the conceptualization of stroke rehabilitation.
The study addresses the burden of pediatric asthma in BC and the value a short course of oral steroids provides in reducing the acute care burden of asthma. The goal is to implement and evaluate an intervention to reduce the acute care burden of asthma exacerbations.
Continue reading “Reducing the Acute Care Burden of Childhood Asthma on Health Services in British Columbia”
After graduation from medical school, physician education continues in a residency program in the individual's chosen area of specialty (e.g., Surgery, Internal Medicine). Residency programs have grueling schedules with frequent on-call shifts. These shifts are at least 24 hours in length, starting from the morning of one day and extending to the next day. In teaching hospitals, residents often provide first line care and make important decisions independent of direct supervision. Their clinical performance is thus an important determinant of patient safety. Some have argued that shift length should be reduced to a more reasonable amount (e.g. <16 continuous hours) to reduce fatigue and medical errors, and to improve safety.
Continue reading “The Impact of a Resident Work Schedule Change on Patient Safety”
Rheumatoid Arthritis (RA), affects one percent of the general population. Radiographic (x-ray), evidence of bone thinning (osteoporosis), and bony destruction (erosions), in the bone surrounding inflamed joints is an important diagnostic criterion for RA. These changes are present in the hands and feet of 80 percent of people with RA and can have profound implications with regard to the development of hand deformity, functional limitations and the need for restorative joint surgery. Early presentation of destructive bone changes is associated with a more aggressive disease progression and evidence suggests that starting disease-modifying anti-rheumatic drugs (DMARDs), soon after the diagnosis of RA may help prevent some people from developing bone damage. However, not all people with early RA respond to DMARDs, with ‘non-responders’ requiring more aggressive interventions including trials of combinations of different drug treatments or biologic response modifier drugs. Unfortunately, the time delay associated with implementing effective treatment in people with more aggressive or resistant RA means they are at greater risk for permanent bone damage. Current clinical imaging with Dual X-ray Absorptiometry (DXA), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI), can detect bone damage earlier than x-ray but these tools are not able to identify the initial ‘micro-structural’ changes in the early RA hand. Dr. Lynne Feehan is characterizing early ‘micro’ structural hand bone changes over a two-year period in people with newly diagnosed RA using High Resolution – Peripheral Quantitative Computed Tomography (HR-pQCT), a promising new imaging system capable of imaging the very fine bone internal ‘micro’ detail at a resolution equivalent to the diameter of a human hair. The results of Dr. Feehan’s research could improve patient’s early access to appropriate therapy, and thereby improve their quality of life.
Every year, 350 to 500 million cases of malaria occur worldwide, resulting in over a million deaths. The majority of these cases occur in sub-Saharan Africa and are responsible for 25 percent of pediatric fatalities under the age of five. In terms of the financial burden, estimates suggest that malaria costs Africa more than $12 billion annually. The global campaign to control and eradicate malaria requires accurate, rapid and cost-effective diagnostic tools. Inaccurate diagnosis results in patients failing to receive needed treatment as well as an overuse of malaria drugs which could contribute to the emergence of drug resistant strains. Currently, the most accurate diagnostic approach requires a trained technician to count the infected cells in a blood sample under a microscope, which is impractical for low-resource regions. Microfluidic devices have shown great potential for cell sorting applications. Such devices can have high selectivity and sensitivity while still being relatively inexpensive to produce. Ms. Sarah Mcfaul is utilizing microfluidics to construct an automated malaria diagnostic test that will be available as a small portable device, requiring no special training to use. Ideally, this automated diagnostic tool will provide sensitivity and quantitative results equal to microscopy, and will also be inexpensively manufactured in order to be accessible to low-resource regions where malaria is a serious threat. Not only will such a device aid in diagnosing malaria, but it will also track the effectiveness of malaria treatments over time in individual patients, enabling clinics can make the best use of their anti-malarial drugs. This in turn will help to lower the number of deaths from malaria and slow the emergence of drug-resistant strains of this deadly parasite.
