Every year more than 185,000 Canadians die in acute-care settings. Previous research has shown that patient choices regarding care are extensively influenced by factors inherent in the place of death. However, no Canadian research has examined how end-of-life care (EOLC) decisions are influenced and shaped through these factors. The focus of Marian Krawczyk’s research is to examine EOLC decision-making within acute-care settings, specifically in regards to the use of life-extending technologies. Her study examines factors that are overlooked in existing research including the location of communication when discussing EOLC options, differing medical models of palliative care, doctor-patient communication, and the social capital and economic resources of patients. By providing data that examines communication in EOLC in British Columbia, this research seeks to strengthen the ability of health care providers, patients and families to effectively communicate and negotiate patient care choices before and during acute care settings. The research will also increase the ability and efficiency of policy makers in the delivery and distribution of health services. Finally, it may help improve communication and decrease consumer-driven health costs.
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Aging and the Brain: Is reduced function of medial-frontal cortex responsible for motor control deficits in the elderly?
Motor control deteriorates with age. For example, people over the age of 65 commit more traffic errors than younger drivers. However, it remains unclear the extent to which this increased error rate is brought about by failures of high-level cognitive control systems within the medial-frontal region of the brain as opposed to other body/brain systems. Olave Krigolson is assessing the degree to which errors by elderly individuals performing continuous motor tasks result from an impairment of error processing systems within the medial-frontal cortex. He is observing brain activity in this region of cortex during a series of experiments that will test continuous tracking and decision-making abilities—two types of tasks that are important for driving. Olave’s research will improve our understanding of why motor errors occur more frequently among older people. Furthermore, it may help develop novel techniques for assessing the functionality of motor control systems in the elderly.
Cognitive and behavioural characterization of individuals genetically at risk for frontotemporal dementia
Frontotemporal dementia (FTD) is the second most common form of dementia affecting individuals under the age of 65. Characterized by the gradual wasting away of the brain’s frontal and anterior temporal lobes, FTD progressively affects mental function, personality and behaviour, while leaving memory largely intact. Over time, they lose the ability to organize and plan, become emotionally blunted and socially inappropriate, lose insight on the impact of their behaviour, and experience difficulty with speech and language. Currently, there is no cure for FTD and treatment methods are limited. Vulnerability to some forms of FTD has been linked to a specific gene mutation that runs in families. While the symptoms of FTD are well documented, few studies have looked at the characteristics of individuals who carry the mutation but do not yet show obvious FTD symptoms. However, research shows that even when they do not exhibit obvious symptoms of FTD, individuals who carry the gene mutation perform significantly worse on tests that measure frontal lobe functioning than family members who do not carry the mutated gene. Using measures such as cognitive testing, behavioural questionnaires and brain imaging, Amanda LaMarre is seeking to establish clinical markers of FTD in genetically at risk individuals in order to identify and distinguish the earliest symptoms. She hopes that by gaining a better understanding of the development and onset of FTD, her research will provide a base for future research aimed at preventing or slowing the progression of the disease.
The function of putative streptococcal family 41 carbohydrate binding modules in carbohydrate recognition during bacterial pathogenesis
Some carbohydrates act as a “fingerprint” or marker for each cell. These markers allow cells to recognize and talk to each other, which is critical for all aspects of cell development and cell-to-cell interaction. Importantly, carbohydrate markers allow the body to discriminate between substances that belong to the body from those that are foreign in order to determine the appropriate immune response required. Further protection against foreign material is provided by protective layers of mucus at entry points to the body such as the nose, throat and lungs. These layers are derived from carbohydrates. Many disease-causing bacteria are able to attach to, and infect cells, by binding to these carbohydrates. Alicia Lammerts van Bueren is studying how enzymes called glycoside hydrolases enable bacteria to infect human cells and hide from the body’s immune system. Her specific focus is on a glycoside hydrolase found on the surface of both Streptococcus pneumonie, which is the leading cause of pneumonia and bacterial meningitis, and Streptococcus pyogenes, which causes strep throat, necrotizing fasciitis and toxic shock. All these diseases can be fatal if left untreated. Alicia’s research into the carbohydrate binding function of these enzymes may explain how these bacteria cause disease in humans, and potentially lead to new drugs or vaccines to treat bacterial infections, which is particularly important given the rise of antibiotic resistance to streptococcal infections.
Risk Assesment for Oral Cancer Prevention in the Community
Even in countries with the best survival rates, 40-50 per cent of patients with cancer of the mouth (oral cancers) do not survive five years beyond diagnosis and treatment. Late diagnosis plays a major role in this high mortality rate because oral lesions at high risk of progressing to cancer are often difficult to differentiate from lesions that are a result of trauma or infection. Denise Laronde is examining two components central to the development of an effective oral cancer screening program. She is identifying and validating tools that can be used by dental professionals to help identify which oral lesions require follow-up. She is also designing and implementing a pilot education program for dental professionals to help train them in the use of these devices. Transferring this new technology to the community may result in earlier identification of high-risk lesions, and increasing the potential for earlier treatment and ultimately, improved long-term survival.
Characterization and Thrombogenic Contribution of Platelet Microparticles to Pathogenesis of Transient Cerebral Ischemic Attacks and Unstable Angina
Platelets are cells that augment blood coagulation to form blood clots which in some cases can restrict or halt oxygenated blood flow to the heart and the brain, causing a heart attack or stroke. Although drugs like aspirin have an anticoagulant effect that can decrease the chance and severity of a stroke or heart attack, these drugs do not entirely eliminate the risk. Platelets release mini-versions of themselves, called platelet microparticles (PMPs), into circulation, which are not affected by anti-coagulant drugs. The presence of PMPs in blood is a predictor of future blockages in the brain or heart, but their precise role is not clear. Hon Leong is investigating whether PMPs have the same clotting abilities as platelets to determine whether they cause the blood clots that lead to a stroke or heart attack. Hon is examining the structure of platelet microparticles and their ability to bind to other cells and clots. The results potentially may be used to develop more accurate blood tests to predict and detect strokes and heart attacks and, ultimately, new therapies that prevent platelets and PMPs from producing harmful clots.
Involvement of myosin V in glutamate receptor trafficking in neurons
The molecules that are essential for normal brain functions are transported throughout neurons, travelling from the site of their formation to the specific location where they are activated. Defects in the transport and exchange of these molecules may affect brain activity and lead to neurological impairments such as epilepsy and mental retardation. Marie-France Lise is studying Myosin V, a family of proteins that may be important regulators of how molecules travel across neurons and reach their destinations. By characterizing how the Myosin V family regulates transport, she hopes to create a better understanding of how these processes contribute to essential brain development, learning and memory formation.
Elucidating the role of Fa2p in cilliary and cell cycle regulation
The majority of cells in the body contain a microscopic, hair-like organelle projecting from the cell surface called a cilium. Cilia play roles in motility and sensory signalling. In many cells, the disassembly of cilia by the cell is a precursor to mitosis (cell division) and cilia are reassembled by the cell following mitosis. Dysfunction of this structure and process leads to a variety of conditions, including blindness, infertility and polycystic kidney disease. MSFHR funded Moe Mahjoub in 2003 to complete his PhD study of cilia. His previous work showed that the kinase Fa2p is implicated in the regulation of ciliary shedding and assembly, as well as in cell division. He has determined that Fa2p is dynamic, moving to different locations in the cell at different points in the ciliary and cell life cycle. Moe is now working to discover exactly how Fa2p exerts its effects. He hopes his research will provide key insights into the mechanism of various human diseases.
Bayesian propensity score analysis for pharmacoepidemiologic research
Data on prescription claims, health services provided, and hospital discharges are routinely collected in the Canadian health care system for the management of health services. This information is valuable for observational research assessing the effectiveness and safety of drug therapies, allowing more rapid and cost-effective investigations. In addition to yielding large sample sizes with long periods of follow up, they also better reflect the spectrum of medical practice in large populations compared to randomized clinical trials. However, because study participants are not randomly assigned to treatment and control groups through this methodology, findings may be biased if there is inadequate control of the variables. There is a need for new statistical tools to analyze healthcare administrative data. Lawrence McCandless is developing and investigating a new statistical method called a Bayesian propensity score analysis. Through computer simulations, mathematical techniques and models for drug prescribing patterns, the Bayesian analysis will improve the validity of observational investigations of the effectiveness and safety of drugs using large health care administrative databases.
Perfectionism and Social Rejection in the Development of Eating Disorder Symptoms
The causes of eating disorders are complex, yet a number of factors have emerged that may put individuals at increased risk for developing these disorders. These include social factors, such as social exclusion and personality traits, such as perfectionism. With support from a 2003 MSFHR Trainee Award, Brandy McGee studied how perfectionism combines with cultural influences, such as physical ideals suggested in advertisements, to cause eating disorders. Brandy is now exploring how multidimensional perfectionism interacts with experiences of social exclusion to produce eating disturbances. She is testing the hypothesis that social rejection will lead to an upswing in eating disturbances (such as binge eating, thoughts about food, negative mood, etc.) in individuals with high levels of social dimensions of perfectionism, but not in women with low levels of perfectionism. The outcomes of this study will help us better understand how social factors shape health status and enable us to better predict who is at risk for eating problems, and to intervene earlier to promote health.