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  • As life expectancy increases and populations age, the burden of disease from dementia is becoming an increasingly significant concern worldwide. The goal of this thesis was to support population health decision-making for dementia, including health resource planning and the development of preventative strategies. A population risk tool for predicting dementia risk among community-dwelling older adults was pre-specified, developed and validated using survival methodology and population-based health surveys linked to administrative data in Ontario. The resulting Dementia Population Risk Tool (DemPoRT) is discriminating and predicts dementia risk across a range of health profiles. This algorithm was then applied to a recent national population health survey and used to describe the population risk and future burden of dementia in Canada, and the impact of unhealthy lifestyle behaviours. In five years, there were approximately 450,000 new dementia cases among individuals 55+ years of age in Canada, of which 40% were associated with unhealthy lifestyle behaviours. Lastly, life expectancy and health care utilization of individuals with dementia was investigated. Administrative data was used to identify all individuals with physician-diagnosed dementia in Ontario from 2014 to 2017, and complete period life table methodology was used to estimate life expectancy and the expected health care utilization of individuals from diagnosis to death. Life expectancy at dementia diagnosis was 5.8 years and was longer for women and those diagnosed before the age of 75. Approximately half of this time was spent in long-term care or receiving home care, inpatient care or outpatient care. Development of policy to prepare for and reduce the burden of dementia requires population health planners to have reliable projections of future disease prevalence and resource requirements, and understanding of what subgroups of the population are at the highest risk and have the highest absolute burden. The results of this thesis will support implementation of Canada’s recently-released dementia strategy by providing detailed information about the current and future burden of dementia, and by informing the development of population-based primary prevention strategies.
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  • Postpartum depression is a serious mental illness with onset of symptoms appearing anytime within the first four months after delivery (e.g. irritability, severe sadness, profound feelings of hopelessness, etc.). Environmental toxicants are synthetic (i.e. manufactured) or naturally found chemicals that are not produced by organisms as a result of cellular metabolism (e.g. tobacco smoke, pesticides, etc.). There is limited consideration for how exposure to environmental toxicants can create adverse psychological health effects, specifically postpartum depression. The purpose of this systematic review was to determine if the literature supports a link between exposure to environmental toxicants during the prenatal/perinatal period and postpartum depression and if so, to identify whether there are specific classes of toxicants that provide a higher risk for postpartum depression. Several databases were used to search the online literature, with the following inclusion criteria: articles published in English, publication years between 1995-2018, and with women of reproductive age (15-49 years old). The article selection process comprised of screening each article by title/abstract, followed by screening those articles based on full-text. Six categories of toxicants were identified among the thirty included articles. Active/passive smoke exposure was largely found to increase the risk of developing postpartum depression; dietary supplements provided mixed results; antidepressants demonstrated preventative effects; particulate air pollution was found to be associated with postpartum depression; oral contraceptives (DMPA) exhibited an increase in postpartum depressive symptoms; and organochlorine pesticides had no associative risk. Quality assessments were performed for all of the included articles, with the majority being assessed as satisfactory. This systematic review presents as a foundation for encouraging future research to investigate the link between environment and mental health, in order to attain a greater perspective.
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  • Tumour cells evade immune responses by multiple mechanisms in the tumour microenvironment, including through the expression of immunosuppressive molecules. The programmed cell death ligand 1 (PD-L1) plays a major role in this immunosuppression, and its expression is often up regulated as a result of innate and adaptive resistance mechanisms. Recent studies have discovered that the expression of PD-L1 can also extend to the nanoparticles that are naturally released by these cells, termed extracellular vesicles (EVs). Immune checkpoint inhibitors (ICIs) have shown great promise in blocking these immune-silencing interactions, but they remain hindered by their low response rates and toxic side effects. In addition, it has been found that the presentation of PD-L1 by EVs can be resistant to these established ICI therapies, further limiting their success. Here, we report a novel technique in which the oncolytic virus, Vaccinia virus, can be engineered to produce PDL1- targeting EVs as a form of immune checkpoint blockade. Our results show that our tailored EVs can target and neutralize immunosuppressive PD-L1, leading to enhanced anti-tumour immunity. Overall, this demonstrates the potential of using this technique to generate future EV-based immunotherapies.
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    • Other
  • Neuropeptides are central modulators of many functions including male-specific mating behaviours. Understanding how these chemical messengers modulate the neural substrates are still not well understood but remains important for biological research. In Drosophila melanogaster, two well-defined microcircuits (Longer-Mating-Duration (LMD) and Shorter-Mating-Duration (SMD)), are used to understand the underlying mechanisms of how neuropeptide interactions modulate temporal information in mating behaviours. In our study, we investigated the influence of SIFamide receptor-mediated signaling and its association to both LMD and SMD. We performed several RNAi-based screens where we identified and mapped out seven different types of neuropeptidergic neurons which were found to be important to either LMD and/or SMD. Following this analysis, we highlight three independent signaling pathways which are necessary to describe the cellular mechanics of the neuropeptides involved. Firstly, we infer that synaptic contacts between proctolin and SIFamide neurons in the subesophageal ganglion mediate inhibition in SMD whereas proctoclin as a neuropeptide modulates both LMD and SMD in a non-synaptic manner. Secondly, we describe an existing insulin-related microcircuit that is modulated by the inputs of Dimmed (DIMM), a transcription factor, through adipokinetic hormone, allatostatin A, and leucokinin to exhibit SMD. Thirdly and lastly, we discuss our interpretations of how capability neurons in the central brain resolves a potential disinhibition microcircuit in LMD via olfactory based signaling in the antennae lobe. In summary, our results contribute to establishing a model system to study neuropeptidergic microcircuits in complex mating behaviours.
    Data Types:
    • Document
  • Site layout planning (SLP) is an essential step for having a productive, efficient and safe construction environment. A well-planned construction site helps in increasing the productivity and safety of the construction operations and in reducing the overall cost and duration of the project. The main purpose of SLP is to manage the available spaces on the construction site and to select the most appropriate location for the temporary facilities (TF) needed to complete the project by taking into consideration all the existing constraints between the different TFs and their relationships to the permanent facilities (PFs). Due to its complexity and the wide range of factors and variables included in the site layout planning process, the models discussed in the literature vary in their scope, objectives, and approaches to providing a solution for site layout planning, which decreases the opportunities for studies to build upon each other towards achieving a versatile model to tackle a variety of issues associated with SLP. In general, despite the vast contributions to the site layout planning field of the models found in the literature, there is still room for improvement by fulfilling some neglected requirements and including some functions that are useful in any site layout planning model, which the integration of Building Information Modeling (BIM) with Geographic Information System (GIS) can provide. This thesis presents a methodology for developing a model for site layout planning based on the integration of BIM with GIS in an attempt to develop a versatile and flexible solution (model) to help professionals during the SLP process. This model will support the decisions of planners during the SLP process and allow them to apply their knowledge in planning and designing, in an efficient and timely manner, a construction site that is safer, more efficient and keeps potential conflicts to a minimum. The research methodology includes a comprehensive literature review, collecting all the necessary data related to SLP, PF and TF, model development and implementation. The presented model is designed in a modular format and consists of six modules, 1) a 3D modeling module; 2) a route planning and hauling (RPH) module; 3) an execution schedule time entry (ESTE) module that facilitates the daunting and time-consuming process of creating a 4D model; 4) a 4D modeling module that simulates the progress of construction and helps in placing TFs on the right locations on site; 5) a temporary facilities library (TFL) module, which is developed to facilitate selecting TFs, modeling and placing TFs onsite, and planning the construction site; and 6) a rule-based dynamic conflict detection (DCD) module that detects conflicts and clashes in 2D and 3D and then notifies users about the detected conflicts through various feedback including visual, textual, and tabular, all in one data-rich environment. Also, the presented model will provide users with spatio-temporal analysis and data management capabilities. The successful implementation of this methodology contributes in developing a versatile and flexible SLP model that will provide users with the essential requirements and functions they need for SLP, which can be enhanced and extended to include more modules and functions through further research in this area.
    Data Types:
    • Document
  • In Canada, parole has become increasingly difficult to obtain over the last several decades. This resistance is arguably rooted – at least partially – in a number of high-profile parole violations and changes to both the laws and practices governing parole that are almost certainly a reflection of wider fear of crime and the rise of the risk society. This increased difficulty in obtaining parole should be seen as a concern (rather than the correct or most appropriate response) given that parole is believed to be a major step in the successful reintegration of offenders into the community (Parole Board of Canada, 2016). Within this context, it is intriguing to note the very recent increase in the use of parole in Canada. However, there has been very little academic research conducted to explain or understand this new phenomenon. Given that actual policies and practices governing parole are often influenced by public opinion/attitudes (Roberts, Stalans, Indermaur, & Hough, 2003), one possible explanation may reside in the current knowledge/perceptions of parole held by Canadians. Unfortunately, despite earlier research (Roberts, 2004), our understanding of public attitudes regarding parole is still very limited. In particular, little is known about recent public knowledge of this correctional release procedure and perceptions regarding its use. Through the use of a survey questionnaire, this study presents an updated view of public perceptions and knowledge about parole. Further, it examines potential correlations between these two constructs. The results reveal little public knowledge of parole and generally ‘negative’ perceptions of it. Further, little evidence was found to support the notion that these current attitudes differ in any significant way from findings reported in earlier polls. In conclusion, the recent increase in the use of parole does not seem to be rooted in changes in Canadians’ knowledge or perceptions of it.
    Data Types:
    • Document
  • There have been significant advances in communication technologies over the last decade, such as cellular networks, Wi-Fi, and optical communication. Not only does the technology impact peoples’ everyday lives, but it also helps cities prepare for power outages by collecting and exchanging data that facilitates real-time status monitoring of transmission and distribution lines. Smart grids, contrary to the traditional utility grids, allow bi-directional flow of electricity and information, such as grid status and customer requirements, among different parties in the grid. Thus, smart grids reduce the power losses and increase the efficiency of electricity generation and distribution, as they allow for the exchange of information between subsystems. However, smart grids is not resilient under extreme conditions, particularly when the utility grid is unavailable. With the increasing penetration of the renewable energy sources (RES) in smart grids, the uncertainty of the generated power from the distributed generators (DGs) has brought new challenges to smart grids in general and smart microgrids in particular. The rapid change of the weather conditions can directly affect the amount of the generated power from RES such as wind turbine and solar panels, and thus degrading the reliability and resiliency of the smart microgrids. Therefore, new strategies and technologies to improve power reliability,sustainability, and resiliency have emerged. To this end, in this thesis, we propose a novel framework to improve the smart microgrids reliability and resiliency under severe conditions. We study the transition to the grid-connected operational mode in smart microgrids,in the absence of the utility grid, as an example of emergency case that requires fast and accurate response. We perform a comparative study to accurately predict upcoming grid-connected events using machine learning techniques. We show that decision tree models achieve the best average prediction performance. The packets that carry the occurrence time of the next grid-connected transition are considered urgent packets. Hence, we per-form an extensive study of a smart data aggregation approach that considers the priority of the data. The received smart microgrids data is clustered based on the delay-sensitivity into three groups using k-means algorithm. Our delay-aware technique successfully reduces the queuing delay by 93% for the packets of delay-sensitive (urgent) messages and the Packet Loss Rate (PLR) by 7% when compared to the benchmark where no aggregation mechanism exists prior to the small-cell base stations. As a mitigation action of the utility grid unavailability, we use the electrical vehicles (EVs) batteries as mobile storage units to cover smart microgrids power needs until the utility grid recovery. We formulate a Mixed Integer Linear Programming (MILP) model to find the best set of electrical vehicles with the objective of minimum cost. The EVs participating in the emergency power supply process are selected based on the distance and throughput performance between the base station and the EVs
    Data Types:
    • Document
  • Climate change is a well-known factor driving species range shifts. These shifts are often attributed to the relaxation of harsher climates at the northern range limit. Specifically, lack of cold tolerance as a constraint on range expansion at higher latitudes is one hypothesis. However, few, if any, studies have tested this hypothesis during a critical season: fall, when organisms are subjected to sporadic low temperature exposure but may not have become cold tolerant yet. In this study, I investigated the impact of low temperature on the larvae of the Giant swallowtail butterfly, Papilio cresphontes, at its northern range edge by integrating physiological experiments and species distribution modelling. First, the cold hardiness of the larvae was tested in a laboratory by determining their supercooling point, chill coma temperature and survival at three low temperatures. I found that the supercooling point was -6.6°C, that larvae use a freeze avoidant strategy, and that larvae enter a chill coma at 2.4°C. I also found that exposure to -2°C did not lead to a high rate of mortality, but that larval survival was impeded by temperatures below the SCP with temperatures below SCP (-8°C) produced high mortality (10-12% survival). Second, to determine the importance of low temperatures at a broad scale, I compared species distribution models of P. cresphontes based only on environmental data derived from other sources to models that also included the physiologically-derived parameters I generated experimentally. The modelling revealed that growing degree days and precipitation best predicted the distribution of P. cresphontes. The cold tolerance variables did not explain much variation in habitat suitability of P. cresphontes distribution. As such, the modelling results were consistent with the experimental results: low temperatures in the fall are unlikely to limit the distribution of P. cresphontes. Further investigation into the ecological relevance of the physiological thresholds determined here will improve our understanding of range expansion of P. cresphontes due to climate change. This study demonstrates that a combination of approaches provides a strong test of hypotheses related to the factors that limit species distributions.
    Data Types:
    • Document
  • Typical Parkinson’s disease (PD) is thought to be caused by a combination of genetic and environmental factors. α-Synuclein (SNCA) is central to PD pathogenesis; however, functions of SNCA outside the brain remain largely unknown. We, and others, have found that wild-type Snca expression confers anti-microbial effects in mice by reducing the severity of viral infections. Our aim is to further characterize a role of SNCA in systemic and brain health of the host during infection. We hypothesize that SNCA plays a role in innate defenses and that SNCA gene dosage will modulate outcomes of infection in the brain following pathogen exposure. Intranasal delivery of reovirus in mouse pups causes systemic illness, leading to encephalitis. In this study, intracranial inoculations of reovirus are used to differentiate the relative contribution of Snca-mediated protection in the brain versus the periphery. Two outcomes are monitored: survival and viral titres in select organs. When comparing wild-type Snca, heterozygous, and knock-out mice, I found that Snca expression did not confer any protection with respect to survival or regarding viral brain titres. These results are paralleled by cellular overexpression models. Unexpectedly, the anti-viral property of Snca, which was previously observed systemically with three distinct dsRNA viruses, did not extend to a paradigm where neural cells were directly exposed to reovirus. These results suggest a complex, anti-viral role for Snca in host defenses that may be mediated, in part, outside the central nervous system. Future studies will address whether this occurs in peripheral neurons or cells of hematopoietic lineages.
    Data Types:
    • Document
  • Peu nombreuses, voire inexistantes, sont les recherches en criminologie en lien avec le racisme sexuel et la communauté allosexuelle. Cette étude exploratoire, basée sur un questionnaire auprès d’HARSAH résidant au Canada et utilisant le cyberespace de rencontre, vise à combler cette lacune et à participer au développement du savoir dans ce champ de recherche. En analysant les réponses ouvertes des participants relatives aux expériences de racisme sexuel et à sa perception, ce travail se propose d’estimer l’impact de l’homonationalisme au sein de la communauté gaie. Il en ressort notamment que la perception du racisme sexuel dépend du groupe social auquel on appartient (racialisé ou non racialisé) et que la perception ainsi que la compréhension du racisme sexuel comme phénomène traduisant des réalités profondes ne sont pas toujours claires. Elles le sont, cependant, pour les participants réifiés, pour ceux qui ont partagé leurs expériences de fétichisation et de rejet sexuel. Pour ces derniers, différentes stratégies sont déployées afin de gérer l’impact du racisme sexuel, mais également de la discrimination et de l’exclusion sur la base d’autres critères (religion, apparence physique, etc.). Discrimination et exclusion sont également pratiquées par des HARSAH racialisés entre eux, le racisme sexuel n’étant pas l’apanage du groupe dominant/majoritaire. Un tel constat en vient donc à remettre en question la caractérisation de la population HARSAH comme étant membre d’une communauté au sens solidaire. ABSTRACT Little, if any, research in criminology is conducted related to sexual racism and the queer community. This exploratory study, based on a survey of MSM in Canada using cyberspace dating, aims to fill this gap and to participate in the development of knowledge. By analyzing the participants' responses to the perception and experiences of sexual racism, we attempt to estimate the impact of homonationalism within the gay community. In particular, it appears that the perception of sexual racism depends on the social group to which one belongs (racialized or non-racialized) and that the perception as well as the understanding of sexual racism as a phenomenon is not always clear. However, it is clear for participants who shared their experiences of fetishization and sexual rejection. For the latter, different strategies are used to manage the effects of sexual racism but also of discrimination on the basis of other criteria (religion, physique, etc.). Exclusion is also practised by racialized MSM between them, sexual racism not being occurring solely from the dominant/majority group. This brings into question the characterization of the MSM population as a member of a community in the sense of solidarity.
    Data Types:
    • Other