Chronic obstructive pulmonary disease (COPD), has generally been thought of as a ""man's disease."" However, there has been a substantial increase in the prevalence and mortality of COPD in women recently, with a tripling of the female mortality rate over the past 20 years compared with a stable mortality rate in men over that same time period. The increased prevalence and mortality of COPD in women has been attributed to an increase in smoking rates in women, which began over 50 years ago. Recent studies have shown that women may be more susceptible to the effects of cigarette smoke compared to men. In addition, there is evidence to suggest that a gender bias may exist with respect to diagnosis; specifically, that women may be more likely to be diagnosed with asthma, and men with COPD, regardless of their underlying condition. Furthermore, studies have shown that a smaller proportion of women compared to men are not referred for diagnostic testing for COPD, or do not receive optimal pharmacotherapy. Using data from the BC Linked Health Database and the PharmaNet database, Dr. Pat Camp is conducting an in-depth analysis of the management and health outcomes of COPD in women compared with men. The goals of Dr. Camp's research are designed to identify gender differences with respect to diagnostic test utilization, hospitalization rates and medication usage. Dr. Camp is also investigating what, if any, impact age and region of residence have on diagnostic testing, medications and hospitalizations in people with COPD. The results of Dr. Camp's research will allow for specific messages and targeted interventions to be developed that facilitate better care and improved quality of life of people living with COPD.
Program: Trainee
Optimal timing of delivery for pregnancies with pre-existing hypertension
Chronic high blood pressure in pregnant women is associated with serious maternal and fetal complications such as poor growth, early separation of the placenta, and stillbirth. Consequently, the recommendation has been made that all women with chronic high blood pressure be considered candidates for induced delivery to reduce the risk of complications that may occur with allowing pregnancies to continue to later gestational ages. However, the optimal gestational age at which the infants should be delivered is currently unknown: delivering too early may increase the risk of respiratory complications for the infant at birth, while delaying the induction of delivery increases the risk of stillbirth. Dr. Hutcheon’s research centres on the development of a methodology to help determine the optimal gestational week for delivery. Data on maternal characteristics and pregnancy outcomes obtained from the US population birth registry as well as Canadian Birth Registries will be reviewed with a focus on the occurrence of either a serious birth complication for the newborn (such as seizures or need for prolonged assisted ventilation), or stillbirth. Among women with pre-existing high blood pressure, the risks of a poor pregnancy outcome will be calculated for each week of gestation between 36 and 42 weeks of pregnancy. Statistical models will be used to determine the gestational age range for birth during which risks to the infants are lowest. These analyses will then be repeated to determine the timing of delivery that minimizes risks of serious complications for the mother. With childbearing at older maternal ages increasing in Canada, the number of pregnancies complicated by high blood pressure is expected to increase. The results of Dr. Hutcheon’s project will help provide guidance to physicians as to the best time to deliver pregnancies complicated by pre-existing high blood pressure and, as a result, help minimise the number of adverse pregnancy outcomes in the Canadian population.
Neural Mechanisms of Reward Learning and Cognitive Control in Children with Attention Deficit Hyperactivity Disorder
Attention Deficit Hyperactivity Disorder (ADHD), is characterized by its behavioural manifestations including difficulties with attention, hyperactivity and impulsivity. It is one of the most common childhood disorders with a prevalence rate of three to seven percent of school-aged children. ADHD carries a significant impact not only on children diagnosed with this disorder, but also on their families, schools, communities and the health care system. Numerous theories of ADHD have focused on deficits in executive functions, specifically cognitive control and the inability to inhibit inappropriate behaviours. Neuropsychological and neuroimaging studies in children with ADHD support a theory of frontal-subcortical dysfunction: specifically, a dysfunction in the midbrain dopamine (DA) system that may result in an impaired midbrain DA system and reinforcement learning, or the ability to learn to modify behaviour on the basis of rewarding and punishing stimuli in the environment. Furthermore, recent developments in reinforcement learning theory indicate that the midbrain DA system carries Reward Prediction Error (RPE) signals. Carmen Lukie is investigating how a midbrain DA system for reinforcement learning may be impaired in children with ADHD. This study follows on from her earlier research which showed that children with ADHD are particularly sensitive to the saliency of rewards. Specifically, she found that RPE signals in children with ADHD are modulated by the context in which feedback is given, and differs from what is observed in typically developing children. The current study will replicate this finding, while correcting for the limitations of the earlier study. Ultimately, the results of this research could lead to the development of novel, more effective behavioural and pharmacological treatments. Further, the research may expand to include individuals with substance abuse, pathological gambling, conduct and borderline personality disorders.
Targeting the Ras/MAPK pathway for treatment of high-grade pediatric brain tumors
Brain cancer is an extremely aggressive disease that remains difficult to cure and carries a high mortality rate. Every year, more than 3,500 children in North America are diagnosed with this disease. Brain tumours are the most common solid tumours and the second leading cause (after leukemia), of cancer-related deaths in children. The majority of patients (80 percent), with the more aggressive forms of brain tumours will survive less than two years. Surgical removal of brain tumours is challenging for a number of reasons, and complete removal of cancer cells is virtually impossible. The chemotherapeutic agent Temozolomide (TMZ), is used in patients with aggressive brain cancers however, in a subgroup of patients this drug does not work effectively because they are resistant to it. Furthermore, recent research shows that TMZ is not generally very effective at eliminating pediatric brain tumour cells. Consequently, certain ‘survivor’ tumour cells become ‘seeds’, generating more cells that subsequently form a new tumour. Cathy Lee’s research focuses on a protein called PLK1, which is essential to the cell division process in cancer cells. Many researchers have shown that PLK1 levels are higher in cancer cells than in normal cells and that tumour cells require this protein for survival. When this protein is eliminated, cancer cells either die or their growth is suppressed. Importantly, normal cells do not seem to be greatly affected by PLK1. Ms. Lee’s research will provide a deeper understanding of this protein. In related research, Lee will examine the ‘seeds’ of brain tumours, called ‘brain tumour initiating cells’, with a view to determining a way to prevent their expansion and induce cell death. The results of her research will improve our understanding of pediatric brain cancers and allow future design of novel, alternative therapeutic strategies that benefit patients’ health and improve the way we currently treat this devastating disease.
Structural analysis of proteins involved in bacterial cell wall biosynthesis
Antibiotics play an essential role in the treatment of bacterial infections. However, the overuse of antibiotics has resulted in the emergence of numerous drug resistant strains of important human pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE). These, and related bacteria, represent major threats to human health if tools cannot be developed to combat these so called “”superbugs””. Potential targets for the development of these new antibacterial treatments include the enzymes involved in the production of the bacterial cell wall. Robert Gruninger’s research is focused on characterizing distinct aspects of cell-wall biogenesis. By clarifying the three dimensional structure of these enzymes, it will be possible to design drugs that will block their function, and combat the development and spread of “superbugs”.
Identifying clinically relevant biomarkers in lymphoma using next-generation sequencing
Lymphomas are a class of cancers that generally derive from blood cells known as B-cells that are present within organs called lymph nodes. Similar to other cancers, lymphoma tumours can be surgically removed. However, patients often relapse after surgery because, inevitably, a small number of cancer cells remain in the body. Diffuse large B-cell lymphoma (DLBCL), is one of the most common types of lymphoma. Sophisticated techniques that allow one to view the abundance of genes (expression,) or the genetic code (DNA sequence), of cancer cells can reveal clinically relevant distinctions between cases of DLBCL. This type of grouping is important because, for example, patients with one subgroup of lymphoma known as the ABC variety appear to have an inferior response to current standard therapies compared to those with the more common GCB variety of DLBCL. The signals that define distinct subtypes of cancers are often referred to as biomarkers and their presence or absence can, in some cases, be tested in a clinical setting. Ryan Morin is focusing his research on the identification of new biomarkers in cancer cells from a clinically diverse group of lymphoma patients. Additionally, Mr. Morin’s research will focus on the identification of genes that have been damaged by somatic mutations, and thereby the identification of genes important to the development of DLBCL. By cataloguing the identified cancer driver mutations, it may be possible to use their signatures to define new subgroups of lymphoma with distinct characteristics. Marrying this information to new biomarkers may help determine whether any new biomarker is associated with positive (i.e. cure), or negative (i.e. relapse), clinical outcomes. Finally, the identification of biomarkers and specifically somatic mutations altering protein function may reveal possible vulnerabilities of a cancer cell to specific drugs. For example, a mutation that results in activation of an oncoprotein may allow a clinician to choose an appropriate drug that inhibits that protein. Further, if no drugs are available, these findings may spur the development of new drugs to specifically target the mutated or activated proteins responsible for malignancy.
Molecular dissection of the Campylobacter jejuni regulatory system CprRS and its control of key aspects of pathogenesis and biofilm formation
Campylobacter jejuni is the leading cause of bacterial food poisoning in the developed world. Infection with C. jejuni typically presents as severe gastroenteritis, termed campylobacteriosis, and presents as intense, often bloody, diarrhea, vomiting, fever and stomach cramps. Prior infection correlates strongly with autoimmune disorders such as irritable bowel syndrome, reactive arthritis and alarmingly, Guillain-Barré syndrome. Furthermore, antibiotic resistance is skyrocketing in C. jejuni isolates, and an effective human vaccine is not presently available. Currently, very little is known about the virulence mechanisms of C. jejuni. Even less is understood about how this fastidious organism survives and thrives in hostile environments, including those associated with environmental transmission and in vivo stresses such as acid, bile and the immune system. In her research, Sarah Svensson is characterizing the CprRS (Campylobacter planktonic growth regulation) two-component regulatory system (TCRS). TCRS represents ideal targets for antibiotic treatment due to their omnipresence in bacteria (and not humans) and control of phenomena related to virulence. By determining 1) genes that comprise the CprRS regulon; 2) how information is relayed from the environment through CprRS and connected regulatory proteins to elicit the appropriate physiological response; and 3) how survival strategies such as biofilm formation are controlled by CprRS, will contribute to our understanding of what makes apparently fragile bacterial pathogens such as C. jejuni so prevalent. As a result, this work will also provide a framework for design of novel infection control antimicrobial treatment, and vaccine strategies for an underappreciated bacterial pathogen.
The influence of technology on pedestrian safety behaviour
The use of personal electronic devices, such as cell phones and Pods, in everyday situations is a growing safety concern, and there is a common belief that all personal electronic devices threaten pedestrian safety in the same way, that is via distraction. However, recent data indicate that cell phones and iPods influence pedestrian safety behaviours (e.g. looking both ways before crossing a street), in qualitatively different ways, and that cell phones and iPods have different effects on an individual’s behaviour in naturalistic contexts. Building on her earlier research in this area, Sophie Lanthier’s current project will test the hypothesis that cell phone and iPod users are affected differently by these devices: specifically, that cell phone users’ conversations absorb general-purpose attentional resources (i.e. they are distracted from their environment), which increases their likelihood of being in an accident, whereas iPod listeners are not distracted by their music, but rather the music limits auditory input from the environment, rendering them unable to hear unexpected events that could occur after they begin to cross the street. This inability to adapt to a potentially important change in the environment (i.e. a car that has just turned onto the street), could increase an iPod user’s likelihood of being in an accident. This study will help to identify what cues individuals rely on to monitor changes in their environment and how personal electronic devices influence one’s ability to use these cues. With this information firmly in hand, methods to reduce risk in pedestrian behaviours can be undertaken.
The Positive Illusory Bias (PIB) in parents with and without Attention-Deficit/Hyperactivity Disorder (ADHD)
Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common psychological conditions in childhood. This disorder is characterized by inattentiveness and/or hyperactivity or impulsivity. Children with ADHD can have major difficulties in important areas of their life, such as in relationships, in their family, and at school. In addition, although treatments are available for this disorder, none of the treatments are without problems and they are of limited long-term effectiveness. Recent studies show that adults can also have ADHD. These adults are at risk for conduct problems, substance abuse, relationship difficulties, driving impairments, employment issues, academic deficits, and poor parenting. Thus, ADHD has negative consequences for both the individual and society. However, as with children, much remains to be done to improve the success of treatments for adults with ADHD. Children with ADHD overestimate their abilities in areas in which they are actually deficient. This is called a Positive Illusory Bias. It is well-known that children are typically optimistic, but the bias of children with ADHD is different from this normal optimism in three major ways. First of all, children with ADHD have a greater absolute positive bias than children without ADHD in that their self-perceptions are even more positive than the self-perceptions of children without ADHD. Secondly, in contrast to those without ADHD, the positive illusions of children with ADHD do not serve to enhance the children’s motivation, endurance, or performance. Finally, children with ADHD maintain their positive illusions even in the face of clear contradictory evidence while the positive illusions of those without ADHD move closer to reality after receiving feedback. Clearly, the Positive Illusory Bias found in children with ADHD is qualitatively different than the self-enhancing optimism generally found in children, and it may have detrimental consequences for the performance of these children and for their motivation to engage in treatment. To date, no research explores the existence of the Positive Illusory Bias in adults with ADHD. In particular, no studies have tested whether the Positive Illusory Bias found in children with ADHD also exists in parents with ADHD. Given research showing that children with ADHD are likely to have parents with ADHD, it seems crucial to examine this question. If a Positive Illusory Bias does indeed exist in parents with ADHD, then these adults may have less motivation to seek or maintain treatment for managing both themselves and their children. For instance, if adults with ADHD hold overly positive views of their parenting, they will be less likely to use parenting programs and services. This could have a negative effect on the outcome of their children. My research will test whether parents with ADHD have a Positive Illusory Bias in the areas of work, relationships, intelligence, and parenting. Female participants who are mothers will be recruited into two groups: a group of mothers with ADHD, and a control group of mothers without ADHD. The diagnosis of ADHD will be determined by information provided by the participant and by someone who knows the participant well (e.g. a spouse). All mothers will complete a self-perception questionnaire that inquires about the four previously-mentioned domains of functioning. The other informants (those who know the mother well) will complete the same questionnaire, answering the questions in reference to the mother. The ratings of the other informants will then be compared to the self-ratings of the mothers. It is predicted that differences in discrepancies between self and other ratings will be larger in the ADHD group than the control group. I will also assess whether the mother is depressed, whether her child has ADHD, and whether the mother has a tendency to respond in a socially desirable manner, so that these variables can be controlled for in analyses of the discrepancy scores. Knowing whether a Positive Illusory Bias exists in adults and more specifically, parents with ADHD can lead to improvements in relevant treatments. For instance, this Positive Illusory Bias may contribute to treatment resistance, whether the treatment is ultimately for the adult or for their child, and it may be possible to develop and utilize specialized techniques to bring the positive self-perceptions of parents with ADHD more in line with reality before beginning treatment. Moreover, consideration of the Positive Illusory Bias as a predictor of treatment response will allow for more informed problem-solving on the part of the clinician in response to resistance to treatment from the client. As such, although there are a number of ways in which the Positive Illusory Bias in parents with ADHD may contribute to improved treatment for this disorder, it is necessary to first answer the question of this study, which is whether or not this bias exists in parents with ADHD.
Exposure assessment for women’s occupational exposure to carcinogens and other hazardous substances
Studies that have evaluated workplace exposure to hazardous chemicals and associated health outcomes have traditionally focused on men in male dominated jobs such as manufacturing and other heavy industries. Consequently, women weren’t generally included in the earlier studies and the industries in which they worked weren’t regarded as important. This, in turn, negatively affected women’s access to workers’ compensation compared with men, especially with respect to injuries, stress and lung diseases from asbestos. However, the research focus has recently shifted to include the changing role of women in the workplace and subsequent hazardous materials exposure that might adversely affect their health. The CAREX study, currently underway in Canada, is a national surveillance project aimed at estimating the number of Canadians exposed to environmental and workplace carcinogens. Cheryl Peter’s research will augment the CAREX project by looking at how these types of exposures differ between men and women. Her study identifies research gaps in women’s occupational health in general, and industries or jobs where women are more susceptible to exposures or adverse health outcomes specifically. The results of this study will help improve the health of female workers by identifying women at higher risk of exposure to hazardous chemicals, and may also help to prevent future health problems, including cancer. Further, Ms. Peter’s data will inform researchers with respect to improved research methods and recommendations on improvements for future studies, accounting for differences in exposures on the job between men and women.