In photodynamic therapy (PDT), a nano particle (NP), is placed within the body and is illuminated with light from outside the body. Normally, the light that gets absorbed by the NP can produce high energy oxygen molecules which will chemically react with and destroy most organic molecules that are next to them, like tumours. This type of light therapy can also be employed to release small drug molecules from the surface of the NP. PDT can be far less expensive than radiotherapy or surgical operation and post operative care. Furthermore, PDT recovery typically requires hours or days rather than weeks, and does not leave a toxic trail of reactive molecules throughout the body as is the case with chemotherapy. This is because the light is targeted at the precise location of the NPs. PDT therefore, is potentially a non-invasive procedure for treatment of diseases, growths and tumours. Additionally, NPs with multiphoton upconversion properties are useful for the diagnosis and treatment of cancer and hold great promise for biosensing and bioimaging. Dr. John-Christopher Boyer is involved in designing the next generation of multifunctional NPs capable of both imaging and selectively targeting cancer cells using photodynamic therapy based on molecular switches. The ultimate goal of his project is to develop nanoparticles with photon upconversion properties, and apply them in sensitive cancer detection. Consequently, a focus of his current research project is to evaluate the performance of the upconverting NPs when applied to sensitive detection and treatment of prostate cancer. Dr. Boyer’s research could significantly enhance Canada’s position in nanomedicine, and developments in this area may well revolutionise medical practice in cancer detection and treatment over the coming years.
Program: Trainee
Measuring equity in the use and financing of prescription medicines
The use of prescription drugs outside of hospitals is not addressed in the Canada Health Act or by any legislation that would ensure national standards for accessibility. As a result, public pharmaceutical insurance programs designed to provide access to prescription medicines outside of hospitals have evolved independently in each province and territory. In May 2003, BC instituted Fair PharmaCare, an income-based catastrophic drug coverage program which links individuals’ private financial contributions to the costs of their medicines (either out-of-pocket or through their private insurance), with their household income. Current research suggests that the implementation of income-based drug coverage has shifted the financial burden away from public sources toward private ones, which raises several important questions regarding equity. Using data from three comprehensive, population-level health care databases, namely: 1) the BC PharmaNet; 2) the British Columbia Linked Health Database (BCLHD); and 3) Fair Pharmacare registration files, Ms. Hanley is investigating the degree of income-related inequity in medicine use before and after the BC policy change in the general population, and in specific subpopulations (e.g., drug use after myocardial infarction). The analysis of specific subpopulations will allow for evaluation of the use of essential medicines and of medications known to be safe and effective. Further, it will enable greater needs standardization. Additionally, she is evaluating the redistributive effect of the policy change on income distribution in BC, specifically focusing on determining inequity in pharmaceutical financing among individuals of equivalent incomes. Taken overall, the results of the project will provide timely and relevant evidence to federal and provincial policy makers, as well as all Canadians, when Pharmacare reform is increasingly on the policy agenda.
Functional characterization of T cells and T regulatory cells in Inflammatory Bowel Disease
Crohn's disease and ulcerative colitis, two forms of Inflammatory Bowel Disease (IBD), are disorders believed to be caused by the cells of the immune system mistakenly attacking the tissues of the digestive tract. This phenomenon, known as autoimmunity, leads to massive inflammation of the affected area and consequently causes severe pain, diarrhea, bleeding and other debilitating symptoms. With few treatments and no cure to date, this disease continues to impact both the general population and our health care system. Current research suggests that the inflammation associated with IBD is caused by self-reactive immune cells called T cells that attack the gut tissue, along with a loss of T regulatory cells (Tregs), which act to 'turn off' the immune system. Furthermore, flagellin, a protein present on all motile bacteria including the microflora found within the intestine, may also contribute to the establishment of IBD associated inflammation through its influence on T cells and Tregs. Indeed, studies have shown an immune response is generated against flagellin in 50 percent of patients with Crohn’s disease. However, the nature of these responses remain largely uncharacterized. Megan Himmel's research aims to optimize a novel method of identifying T cells and Tregs which are specifically reactive to flagellin, in order to study their function and their possible contribution to the pathogenesis of IBD. This work may lead to a novel diagnostic marker for IBD, as well as further insight into the immune mechanisms contributing to this disease. Furthermore, Ms. Himmel’s research will provide important insight into the overall role of T cells and Tregs in the establishment and progression of IBD in humans, with the ultimate goal of establishing methods to therapeutically manipulate the balance of pathogenic versus regulatory immune responses.
Identifying biomarkers associated with the diagnosis and illness progression of mood disorders
Despite decades of extensive genetic and pharmacological research, the pathophysiology of Bipolar disorder (BD) remains elusive. Consequently, a growing number of studies are focusing on the molecular biology underlying BD, and some consistencies with respect to possible mechanisms of action have emerged, including: (1) altered cerebral energy metabolism; (2) decreased expression of the mitochondrial electron transport chain (mETC), complexes I-V subunits in prefrontal cortex, hippocampus and lymphocytes; (3) increased protein oxidation in the prefrontal cortex and serum; (4) higher levels of lipid peroxidation in the cingulte cortex and serum; (5) increased levels of DNA oxidative damage in hippocampus and lymphocytes; (6) alteration in the balance between anti-inflammatory/ pro-inflammatory cytokines; and (7) decreased levels of brain derived neurotrophic factor (BDNF) in the hippocampus and serum. These findings highlight the fact that oxidative damage and neurotrophic factors are present in both the brain and periphery, and suggest that oxidative stress and BDNF could be potential biomarkers for mood disorder. Dr. Ana Andreazza is working as part of a collaborative network in Canada, Brazil, Australia and Portugal, that is studying a large sample size of patients with mood disorders (bipolar disorder and depression), in order to determine whether mitochondrial dysfunction, oxidative stress markers, cytokines and BDNF levels may be used as biomarkers of progressive illness. As a secondary objective of their studies, Dr. Andreazza and colleagues will correlate their findings on the oxidative stress with cognitive impairment, accelerated aging (i.e. telomere shortening), and decreased levels of neurotrophic factors. In addition to identifying biomarkers that may be used to follow progressive illness, the results of this work may represent significant therapeutic targets. In the larger picture, the discovery of biomarkers for mood disorders and their incorporation into clinical decision-making could dramatically change the future of mental health care.
Mind Wandering in Individuals with Schizotypal Personality Traits
Disruption of attention is a hallmark symptom of schizophrenia, and it has been shown that people with schizophrenia exhibit reduced levels of sensitivity in processing external stimuli. However, it has also been suggested that healthy individuals do not process external stimuli when they are ‘mind wandering’ to the extent that they normally would when they are paying attention to the task-at hand. That schizophrenia and mind wandering both involve reduced sensitivity to ongoing events in the external world suggests they may be closely related. Therefore, it is possible that the processing deficits associated with schizophrenia are related to levels of mind wandering. Julia Kam is investigating mind wandering states in healthy individuals who may be vulnerable to developing schizophrenia with the purpose of determining whether abnormal levels of mind wandering are consistently evident across the entire spectrum of disorders in which schizophrenia is present. A key implication of this study is that varying levels of mind wandering and the brain wave counterparts observed in the general population may be considered as indicators for the potential development of schizophrenia. Given that schizophrenia has a strong genetic component, these ‘indicators’ may serve to identify healthy individuals, especially relatives of patients with schizophrenia, who are themselves at higher risk for developing the disorder. This is an important first step in implementing preventive interventions for such high-risk individuals. Once identified, persons considered at-risk may then benefit substantially from programs that highlight protective factors and increase awareness of risk factors, all of which are intended to prevent the development of schizophrenia.
Magnetoencephalographic (MEG) investigation of cortical processing in children born very preterm
Children born very preterm (less than 32 weeks from conception), commonly have difficulties with learning and attention that frequently lead to problems in their academic performance. Very little is known, however, about how the brain activity of very preterm children differs from that of children born at full term. Currently, it is known that children born very preterm experience considerable pain-related stress during lengthy hospitalization following birth. This stress is associated with higher levels of cortisol production, the primary stress hormone in humans, during infancy and toddlerhood. It is possible that these high cortisol levels may contribute to changes in brain development. Dr. Sam Doesburg is characterizing alterations in brain function and structure in a group of very preterm children, now aged 7.5 years. His research is part of a larger, ongoing longitudinal study investigating the effects of pain-related stress experienced during neonatal intensive care on neurodevelopment in very preterm children. Using a technique called magnetoencephalography (MEG), Dr. Doesburg will examine the brain activity of the children while they perform a visual memory task, and use magnetic resonance imaging (MRI) to map brain activity onto brain structure to investigate connections between different brain regions. This research will provide new knowledge about brain function and structure in very preterm children, and how stress experienced very early in life is related to brain development. Determining specific information about brain activity in these children during mental activity could also help to devise better treatment strategies to help overcome the learning and attention difficulties this vulnerable group of children experience.
Sensory contributions to motor deficits after stroke: What is the role of the unaffected cortex in motor recovery?
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.
An Innovative Approach to Providing Patient Care: Examining the Role of the Nurse Practitioner in Primary Care Group Medical Visits
As the Canadian population ages, primary health care has increased its focus on the prevention and management of chronic disease in the elderly. However, access to primary care providers such as family doctors has become more difficult in recent years. Consequently, nurse practitioners (NPs) are increasingly delivering primary health services for people with chronic disease through what’s called the group medical visit (GMV). GMVs are a model of care delivery in which primary care is offered in a group format, instead of single patient/provider format. GMVs are being implemented across BC as part of the practice support program aimed at improving the primary health care system in the province. Past work indicates that patients and providers of GMVs are satisfied with GMVs. However, research on their effectiveness is limited. Laura Housden is examining the role of NPs in providing GMVs in BC and whether or not the GMV format is associated with quality patient care, such as patient self management of disease and chronic disease health indicators. To that end, she is conducting in-depth interviews with NPs currently providing GMVs. Direct observation of GMVs will be undertaken to better understand the process of the visit and context of the appointments. Chart audits will also be done to determine quality of care. The results of Ms. Housden’s research will provide a greater understanding of the role of NPs in providing GMVs, as well as the effectiveness of this care model in reaching and caring for people with chronic illnesses. Ultimately, this information could help to inform public health policy in BC.
Evaluation of a Proposed Revision of the HCR-20 Violence Risk Assessment Scheme.
Violence is a serious public health concern. It embodies a considerable societal burden and its individual cost, in terms of both physical and mental health, is enormous, whether it pertains to victims, perpetrators or those close to them. Currently, legal, forensic and psychiatric institutions are confronted with the difficult task of determining whether a specific individual may be at risk of harming others. Violence risk assessments are conducted in order to find a way to reduce or manage that risk, either in the community or within institutions. Because the decisions made by mental health professionals during such assessments have serious consequences, it is essential that the decision-making processes be scientifically and clinically sound. The Historical/Clinical/Risk-Management-20 (HCR-20) represents one of the most researched and established instruments used to assess risk for community and institutional violence in offenders, civil psychiatric patients, forensic psychiatric patients, as well as males and females with mental illness, personality disorder or substance abuse problems. Since the development of the HCR-20 in 1997, a large body of data on its efficacy has been collected, and the authors concluded that some revisions were necessary. Diana Strub’s research involves an evaluation of a subscale of the revised HCR-20 assessment scheme in its entirety on a new sample of 150 individuals (i.e. offenders and mentally disordered offenders), about to be released into the community. Her work has implications for violence risk reduction and management for individuals with mental illness, personality disorders, correctional involvement and/or substance abuse problems. Such violence prevention strategies are expected, in turn, to considerably reduce physical and mental health concerns for those at risk, their victims and those close to them, as well as alleviate some of the burden placed on the health care system.
A cross-national evaluation of opioid dependence treatment service systems in Canada and the United States
Methadone maintenance treatment (MMT) is the most effective form of treatment for opioid dependence, a chronic, recurrent disease. However, the availability and means by which MMT is delivered varies greatly, both locally and internationally. Understandably, the resulting accessibility, quality and comprehensiveness of care provided through the various treatment practices have important public health implications, and require careful consideration. Notably, there are vast differences between the drug treatment systems in California and British Columbia. Treatment for opioid dependence remains restricted in California due to regulatory constraints on treatment settings, (i.e. registered drug treatment centres), and physician practice, (i.e. limits on the number of patients per physician). Nonetheless, treatment through drug treatment centres may offer some advantages. In comparison, access to MMT in BC has improved following administrative transfer from the federal government to provincial colleges of physicians and subsequent deregulation through the introduction of community-based treatment (i.e. office-based prescription and dispensation in community-based pharmacies). Community-based treatment may maximize access, albeit at a relatively high cost, although the economic merits of maximizing access are well-established. Building on his earlier research in this area, Mr. Nosyk is working to identify differences in patient characteristics, treatment outcomes and costs of opioid dependence treatment systems in both the countries, with a specific focus on the performance of the treatment systems in terms of effectiveness, efficiency and equity. The knowledge gained from his research can be extended to estimate the health and economic impact of introducing treatment services at the population-level, and corresponds with long-term recommendations to expand services to provide more comprehensive treatment for substance users in BC.