Alcohol: a recently identified risk factor for breast cancer

Acknowledgements: I thank Dr. Barbour Warren, arriet Richardson and Alison James for their helpful input.

Investigating the Association Between Computer-Mediated Communication (CMC) and the Health of Canadian Young People: A Mixed Methods Study

Canadian young people are increasingly more connected through technological devices. This computer-mediated communication (CMC) can result in heightened connection and social support but can also lead to inadequate personal and physical connections. As technology evolves, its influence on health and well-being is important to investigate, especially among youth. This study aims to investigate the potential influences of computer-mediated communication (CMC) on the health of Canadian youth, using both quantitative and qualitative research approaches. This mixed-methods study utilized data from the 2013-2014 Health Behaviour in School-aged Children survey for Canada (n=30,117) and focus group data involving Ontario youth (7 groups involving 40 youth). In the quantitative component, a random-effects multilevel Poisson regression was employed to identify the effects of CMC on loneliness, stratified to explore interaction with family communication quality. A qualitative, inductive content analysis was applied to the focus group transcripts using a grounded theory inspired methodology. Through open line-by-line coding followed by axial coding, main categories and themes were identified. The quality of family communication modified the association between CMC use and loneliness. Among youth experiencing the highest quartile of family communication, daily use of verbal and social media CMC was significantly associated with reports of loneliness. The qualitative analysis revealed two overarching concepts that: (1) the health impacts of CMC are multidimensional and (2) there exists a duality of both positive and negative influences of CMC on health. Four themes were identified within this framework: (1) physical activity, (2) mental and emotional disturbance, (3) mindfulness, and (4) relationships. Overall, there is a high proportion of loneliness among Canadian youth, but this is not uniform for all. The associations between CMC and health are influenced by external and contextual factors, including family communication quality. Further, the technologically rich world in which young people live has a diverse impact on their health. For youth, their relationships with others and the context of CMC use shape overall influences on their health.

Access Point Association Coordination in Densely Deployed 802.11 Wireless Networks

Dense deployment of wireless local area network (WLAN) access points (APs) is an important part of the next generation Wi-Fi and standardization (802.11ax) efforts are underway. Increasing demand for WLAN connectivity motivates such dense deployments, especially in geographical areas with large numbers of users, such as stadiums, large enterprises, multi-tenant buildings, and urban cities. Although densification of WLAN APs guarantees coverage, it is susceptible to increased interference and uncoordinated association of stations (STAs) to APs, which degrade network throughput. Therefore, to improve network throughput, algorithms are proposed in this thesis to optimally coordinate AP associations in the presence of interference. In essence, coordination of APs in dense WLANs (DWLANs) is achieved through coordination of STAs' associations with APs. While existing approaches suggest tuning of APs' beacon powers or using transmit power control (TPC) for association control, here, the signal-to-interference-plus-noise ratio (SINRs) of STAs and the clear channel assessment (CCA) threshold of the 802.11 MAC protocol are employed. The proposed algorithms in this thesis enhance throughput and minimize coverage holes inherent in cell breathing and TPC techniques by not altering the transmit powers of APs, which determine cell coverage. Besides uncoordinated AP associations, unnecessary frequent transmission deferment is envisaged as another problem in DWLANs due to the clear channel assessment aspect of the carrier sensing multiple access collision avoidance (CSMA/CA) scheme in 802.11 standards and the short spatial reuse distance between co-channel APs. To address this problem in addition to AP association coordination, an algorithm is proposed for CCA threshold adjustment in each AP cell, such that CCA threshold used in one cell mitigates transmission deferment in neighboring cells. Performance evaluation reveals that the proposed association optimization algorithms achieve significant gain in throughput when compared with the default strongest signal first (SSF) association scheme in the current 802.11 standard. Also, further gain in throughput is observed when the CCA threshold adjustment is combined with the optimized association. Results show that when STA-AP association is optimized and CCA threshold is adjusted in each cell, throughput improves. Finally, transmission delay and the number of packet re-transmissions due to collision and contention significantly decrease.

An investigation of sugar-sweetened beverage consumption among Canadian youth

Background: Consumption of sugar-sweetened beverages (SSBs) is an important public health problem in Canada, especially among adolescents. Estimates show that rates of SSB consumption are particularly high in the northern territories, especially in Nunavut. This is concerning given that regular SSB consumption is associated with obesity, diabetes and tooth decay, among other health concerns. Objectives: This thesis has two objectives. The first is to describe SSB consumption patterns among adolescents from Nunavut specifically, all three territories combined and the provinces.The second is to determine the association between individual and cumulative school food programs and SSB consumption. Methods: Data were obtained from the Health Behaviour in School-aged Children study (HBSC); a cross-sectional survey of Canadian youth in grades 6-10. All frequencies for food and beverage consumption were obtained from a 7-day food frequency questionnaire. SSB consumption consisted of a composite measure including soft drinks, sports drinks and energy drinks. The types of school food programs were obtained from an administrative questionnaire filled out by each school’s Principal or delegate. Multilevel multivariate Poisson regression models were used to examine the associations between school food programs and SSB consumption. Results: Youth from Nunavut consumed the most SSBs (53.1% in 2010 and 55.0% in 2014 were daily consumers), followed by youth from the territories (31.1% in 2010 and 27.0% in 2014), then youth from the provinces (24.3% in 2010 and 19.1% in 2014). No significant relationships were found between school food programs and daily SSB consumption. Two school food programs were weakly associated with weekly SSB consumption: nutrition month activities (RR=0.93,CI=0.89, 0.98) and healthy options in the snack bar (RR=1.07, CI=1.01, 1.14). Conclusions:Rates of SSB consumption were highest among Nunavummiut youth followed by youth from all three territories combined and then the provinces. Little association was found between school food programs and SSB consumption among Canadian youth in grades 6-10. These findings point to the need for examining other determinants and potential areas for intervention, for reducing SSB consumption among Canadian youth, particularly in high consumer sub-populations.

LibQUAL+ Survey 2004 @ Queen's University Library : analysis of results

Queen's University Library was one of 202 libraries, including 57 members of the Association of Research Libraries (ARL), to survey its users in spring 2004 using the LibQUAL+ survey instrument. LibQUAL+ was designed by ARL to assist libraries in assessing the quality of their services and identifying areas for improvement. # Overall: Queen's scored higher than the average for all ARL participants and 1st among the 2004 Canadian participants. This relatively high rating is due to very high scores in the dimensions of Library as Place and Affect of Service. However, there is considerable need for improvement in the area of Information Control where Queen's rated well below the ARL average. # Affect of Service: Queen's strong overall ratings are supported by the many respondent comments praising customer service throughout the system. The ratings and survey comments indicate greatest appreciation by faculty and more experienced students (e.g. graduate students) for the instruction and on-site services provided by the libraries. The ratings also indicate that undergraduates, growing up with the web, want and expected to be able to access library resources independently and do not value these services as highly. The comments also indicated some specific areas for improvement throughout the library system. # Library as Place : All Queen's libraries except for Law ranked well above the ARL and Canadian averages. Overall, Library as Place ranked lowest in importance among the service dimensions for all ARL participants including Queen's. Comparative analysis of LibQUAL results since the survey began shows a decline in “desired” ratings for Library as Place. However, undergraduates continue to give strong "desired" ratings to certain aspects of Library as Place and a relatively high rating for "minimum expected" service. The comments from Queen's survey respondents and ARL's analyses of focus groups indicate that undergraduates value the library much more as a place to study and work with peers rather than for its on-site resources and services. # Information Control: This is the area in greatest need of attention. While it ranked highest in importance for all user groups by a wide margin, Queen's performed poorly in this category. Overall, Queen's ranked far below both the ARL average and the top three Canadian scores. However, the major dissatisfaction was concentrated in the humanities/social sciences (Stauffer primary users) and the health sciences (Bracken primary users) where the overall rating of perceived service quality ranked below the minimum expected service rating. Primary users of the Education, Engineering/Science and Law libraries rated this service dimension higher than the ARL average. The great success of the Canadian National Site License Program (CNSLP) is reflected in the high overall rating generated by Engineering/Science Library users. The low ratings from the humanities and social sciences are supported by respondents' comments and are generally consistent with other ARL participants.

Gross and net nitrogen transformation rates and availability in late summer in tall shrub and birch hummock ecosystems of the Canadian low Arctic

Climate change is occurring most rapidly in the Arctic where warming has been twice as fast as the rest of the globe over the last few decades. Arctic soils contain a vast store of carbon and warmer arctic soils may mediate current atmospheric CO2 concentrations and global warming trends. Warmer soils could increase nutrient availability to plants, leading to increased primary production and sequestration of CO2. Presumably because of these effects of warming on shrub ecosystems, shrubs have been expanding across the arctic over the last 50 years, Arctic shrub expansion may track or cause changes in nutrient cycling and availability that favour growth of larger, denser shrubs. This study aimed at measuring gross and net nitrogen cycling rates, major soil nitrogen and carbon pool sizes, and elucidating controls on nutrient cycling and availability between a mesic birch (Betula nana) hummock tundra ecosystem and an ecosystem of dense, tall, birch (B. nana) shrubs. Nitrogen cycling and availability was enhanced at the tall shrub ecosystem compared to the birch hummock ecosystem. Net nitrogen immobilization by microbes was approximately threefold greater at the tall shrub ecosystem. This was in part because of larger microbial biomass nitrogen and carbon (interpreted as a larger microbial community) at the tall shrub ecosystem. Nitrogen inputs via litter were significantly larger at the tall shrub ecosystem and were hypothesized to be the major contributor to the higher dissolved organic and inorganic nitrogen pools in the soil at the tall shrub ecosystem. The results from this study suggest a positive feedback mechanism between litter nitrogen inputs and the enhancement of nitrogen cycling and availability as a driver of shrub expansion across the Arctic.

Single Canadian mothers of Jamaican heritage share experiences about their children's education

This thesis examines the experiences of four single Canadian mothers of Jamaican heritage with respect to their children’s education. Four themes suggested in the literature—beliefs, practices, barriers, and supports—guided the research. The interviews with the mothers largely confirmed previous research in the field. As such, all the mothers believed that it was a shared responsibility between parents and teachers in supporting children’s education. The mothers’ practices included primarily at-home support and to a lesser extent at-school support but did not include strict discipline. The barriers most salient for these mothers were lack of time and resources. To help overcome these barriers, the mothers relied on domestic kin networks. From these findings, the thesis provides implications for both research and practice.

Investigation of the effect of intrauterine inflammation and infection on fetal brain injury using human and animal models

In recent years, increased focus has been placed on the role of intrauterine infection and inflammation in the pathogenesis of fetal brain injury leading to neurodevelopmental disorders such as cerebral palsy. At present, the mechanisms by which inflammatory processes during pregnancy cause this effect on the fetus are poorly understood. Our previous work has indicated an association between experimentally-induced intrauterine infection, increased proinflammatory cytokines, and increased white matter injury in the guinea pig fetus. In order to further elucidate the pathways by which inflammation in the maternal system or the fetal membranes leads to fetal impairment, a number of studies investigating aspects of the disease process have been performed. These studies represent a body of work encompassing novel research and results in a number of human and animal studies. Using a guinea pig model of inflammation, increased amniotic fluid proinflammatory cytokines and fetal brain injury were found after a maternal inflammatory response was initiated using endotoxin. In order to more closely monitor the fetal response to chorioamnionitis, a model using the chronically catheterized fetal ovine was carried out. This study demonstrated the adverse effects on fetal white matter after intrauterine exposure to bacterial inoculation, though the physiological parameters of the fetus were relatively stable throughout the experimental protocol, even when challenged with intermittent hypoxic episodes. The placenta is an important mediator between mother and fetus during gestation, though its role in the inflammatory process is largely undefined. Studies on the placental role in the inflammatory process were undertaken, and the limited ability of proinflammatory cytokines and endotoxin to cross the placenta are detailed herein. Neurodevelopmental disorders can be monitored in animal models in order to determine effective disease models for characterization of injury and use in therapeutic strategies. Our characterizations of postnatal behaviour in the guinea pig model using motility monitoring and spatial memory testing have shown small but significant differences in pups exposed to inflammatory processes in utero. The data presented herein contributes a breadth of knowledge to the ongoing elucidation of the pathways by which fetal brain injury occurs. Determining the pathway of damage will lead to discovery of diagnostic criteria, while determining the vulnerabilities of the developing fetus is essential in formulating therapeutic options.

Analysis of Lipoprotein(a) Catabolism

Elevated plasma concentrations of lipoprotein(a) [Lp(a)] have been identified as an independent risk factor for vascular diseases including coronary heart disease and stroke. In the current study, we have examined the binding and degradation of recombinant forms of apolipoprotein(a) [r-apo(a)], the unique kringle-containing moiety of Lp(a), using a cultured cell model. We found that the incubation of human hepatoma (HepG2) cells with an iodinated 17 kringle-containing (17K) recombinant form of apo(a) resulted in a two-component binding system characterized by a high affinity (Kd = 12 nM), low capacity binding site, and a low affinity (Kd = 249 nM), high capacity binding site. We subsequently determined that the high affinity binding site on HepG2 cells corresponds to the LDL receptor. In the HepG2 cell model, association of apo(a) with the LDL receptor was shown to be dependent on the formation of Lp(a) particles from endogenous LDL. Using an apo(a) mutant incapable of binding to the high affinity site through its inability to form Lp(a) particles (17KΔLBS7,8), we further demonstrated that the LDL receptor does not participate in Lp(a) catabolism. The low affinity binding component observed on HepG2 cells, familial hypercholesterolemia (FH) fibroblasts and human embryonic kidney (HEK) 293 cells may correspond to a member(s) of the plasminogen receptor family, as binding to this site(s) was decreased by the addition of the lysine analogue epsilon-aminocaproic acid. The lysine-dependent nature of the low affinity binding site was further confirmed in HepG2 binding studies utilizing r-apo(a) species with impaired lysine binding ability. We observed a reduction maximum binding capacity for 17K r-apo(a) variants lacking the strong lysine binding site (LBS) in kringle IV type 10 (17KΔAsp) and the very weak LBS in kringle V (17KΔV). Degradation of Lp(a)/apo(a) was found to be mediated exclusively by the low affinity component on both HepG2 cells and FH fibroblasts. Fluorescence confocal microscopy, using the 17K r-apo(a) variant fused to green fluorescent protein, further confirmed that degradation by the low affinity component on HepG2 cells does not proceed by the activity of cellular lysosomes. Taken together, these data suggest a potentially significant route for Lp(a)/apo(a) clearance in vivo.

ROLE OF CAVEOLIN-3 IN THE MODULATION OF HERG POTASSIUM CHANNEL

The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (IKr) that is important for cardiac repolarization. Previously, we have discovered that hERG channels rapidly internalize in low extracellular K+ ([K+]o). In cell culture, this process is driven by the endocytic protein, caveolin-1 (Cav1), which is an integral player in the caveolae-dependant endocytosis pathway. However, in the heart, Caveolin-3 (Cav3) is, in fact, the predominant form in the myocyte, and thus may play a direct role in regulating hERG expression in the heart. Thus, I hypothesize that this reduction of hERG conductance in cardiac myocytes derives from the presence of Cav3, which is integral regulator of hERG homeostasis innately in the heart. To investigate the effect of Cav3 on hERG, I overexpressed Cav3 in human embryonic kidney 293 (HEK-293) cells stably expressing hERG channels. Cav3 overexpression significantly and specifically decreased both the hERG current amplitude and the mature channel expression in normal culture conditions. Co-immunoprecipitation analysis and confocal imaging demonstrated an association between hERG and Cav3 in HEK cells as well as rat and rabbit cardiomyocytes. Mechanistically, I discovered that Cav3 possesses a faster turnover rate compared to Cav1, and can enhance hERG degradation through up-regulating mature channel ubiquitination via the ubiquitin ligase, NEDD4-2. Knockdown of Cav3 in neonatal cardiac myocytes also enhanced hERG expression. My data indicate that Cav3 participates in hERG trafficking, and is an important regulator of hERG channel homeostasis in cardiac myocytes. This information provides a platform for future intervention of the hERG-induced type-2 long QT syndrome (LQTS).

Calling for resistance: The political economy of Indian and Canadian call centre industries

Call centres have in the last three decades come to define the interaction between corporations, governments, and other institutions and their respective customers, citizens, and members. From telemarketing to tele-health services, to credit card assistance, and even emergency response systems, call centres function as a nexus mediating technologically enabled labour practices with the commodification of services. Because of the ubiquitous nature of the call centre in post-industrial capitalism, the banality of these interactions often overshadows the nature of work and labour in this now-global sector. Advances in telecommunication technologies and the globalization of management practices designed to oversee and maintain standardized labour processes have made call centre work an international phenomenon. Simultaneously, these developments have dislocated assumptions about the geographic and spatial seat of work in what is defined here as the new international division of knowledge labour. The offshoring and outsourcing of call centre employment, part of the larger information technology and information technology enabled services sectors, has become a growing practice amongst governments and corporations in their attempts at controlling costs. Leading offshore destinations for call centre work, such as Canada and India, emerged as prominent locations for call centre work for these reasons. While incredible advances in technology have permitted the use of distant and “offshore” labour forces, the grander reshaping of an international political economy of communications has allowed for the acceleration of these processes. New and established labour unions have responded to these changes in the global regimes of work by seeking to organize call centre workers. These efforts have been assisted by a range of forces, not least of which is the condition of work itself, but also attempts by global union federations to build a bridge between international unionism and local organizing campaigns in the Global South and Global North. Through an examination of trade union interventions in the call centre industries located in Canada and India, this dissertation contributes to research on post-industrial employment by using political economy as a juncture between development studies, critical communications, and labour studies.

Characterization of Glucocorticoid Receptor Promoter Methylation in Breast Cancer

Epidemiological studies have identified psychological stress as a significant risk factor in breast cancer. The stress response is regulated by the HPA axis in the brain and is mediated by glucocorticoid receptor (GR) signalling. It has been found that early life events can affect epigenetic programming of GR, and methylation of the GR promoter has been reported in colorectal tumourigenesis. Decreased GR expression has also been observed in breast cancer. In addition, it has been previously demonstrated that unliganded GR can serve as a direct activator of the BRCA1 promoter in mammary epithelial cells. We propose a model whereby methylation of the GR promoter in the breast significantly lowers GR expression, resulting in insufficient BRCA1 promoter activation and an increased risk of developing cancer. Antibody-based methylated DNA enrichment was followed by qPCR analysis (MeDIP-qPCR) in a novel assay developed to detect locus-specific methylation levels. It was found that 13% of primary breast tumours were hypermethylated at the GR proximal promoter whereas no methylation was detected in normal tissue. RT-PCR and 5’ RACE analysis identified exon 1B as the predominant alternative first exon in the breast. Tumours methylated near exon 1B had decreased GR expression compared to unmethylated samples, suggesting that this region is important for transcriptional regulation of GR. It was also determined that GR and BRCA1 expression was decreased in breast tumour compared to normal tissue. Furthermore, the relative expression of GR and BRCA1 measured by qRT-PCR was correlated in normal tissue but this association was not found in tumour tissue. From this, it appears that lower GR levels with associated decreased BRCA1 expression in tissues may be a predisposing factor for breast cancer. Based on these results we propose a role for GR as a potential tumour suppressor gene in the breast due to its association with BRCA1, also a tumour suppressor gene, as well as its consistently decreased expression in breast tumours and methylation of its proximal promoter in a subset of cancer patients.