Health Sciences - Theses, Dissertations, and other Required Graduate Degree Essays

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The aryl hydrocarbon receptor nuclear translocator (ARNT) transcriptional co-regulator complex: Effects on estrogen and hypoxia signaling

Date created: 
2016-08-11
Abstract: 

The basic Helix-Loop-Helix/PER-ARNT-SIM (bHLH-PAS) domain family of proteins mediates cellular responses to a variety of stimuli. The bHLH-PAS proteins are heterodimeric transcription factors that are further sub-classified into sensory and aryl hydrocarbon receptor nuclear translocator (ARNT) proteins. The ARNT protein is constitutively expressed and heterodimerizes with hypoxia-inducible factors (HIFs) to mediate oxygen-sensing mechanisms and heterodimerizes with the aryl hydrocarbon receptor (AHR) to combat environmental contaminant exposure. Firstly, a reciprocal disruption relationship exists between AHR ligands, like 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and estrogen receptor (ER) ligands, like 17β-estradiol (E2). Ligand-bound ER tethers to the AHR/ARNT transcription factor complex and represses TCDD-inducible gene transcription. However, the tethering paradigm and molecular mechanisms employed by AHR and ARNT at ER-regulated genes remains to be determined. Secondly, thyroid hormone receptor/retinoblastoma-interacting protein 230 (TRIP230) interacts with ARNT and is a coactivator required for hypoxia-regulated transcription. The retinoblastoma protein (Rb) is a negative regulator of the cell cycle and also negatively regulates TRIP230 coactivator potential. Thus, Rb may influence ARNT transcription factor functions via TRIP230. Rb-loss in many solid tumours directly precedes the activation of HIF-regulated genes and correlates with increased angiogenesis and metastasis. As most solid tumours contain regions of hypoxia and only correlative data between HIF/ARNT activity and Rb-loss has been gathered, we have identified a need to rigorously examine the role of Rb-loss in concert with hypoxia in breast and prostate cancer models. In this thesis, I used siRNA technology to knockdown ARNT and AHR expression and found that TCDD-mediated disruption of ER-signalling is AHR-dependent and that ARNT is a coactivator in MCF7 cells and a corepressor in ECC1 cells. Additionally, I used siRNAs and shRNA technology in concert with microarray analysis in LNCaP prostate cancer cells and MCF7 breast cancer cells to delineate the role of the ARNT-TRIP230-Rb transcriptional complex in hypoxia-regulated transcription. I found that Rb-depletion in conjunction with hypoxia exacerbates HIF1-mediated transcription and promotes a more invasive and late stage phenotype in both breast and prostate cancer models. The molecular mechanisms and gene pathways described herein should prove useful for developing chemotherapies for late stage breast and prostate cancers.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Timothy Beischlag
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) Ph.D.

Sexual self-efficacy among adolescent men and women living in an HIV-hyper-endemic setting of South Africa

Date created: 
2017-04-12
Abstract: 

Adolescent women in South Africa face disproportionate HIV acquisition. In this context, evidence remains mixed on whether sexual self-efficacy (SSE)- one’s perceived control in decision-making regarding safe sex, predicts consistent condom use (CCU). Using cross-sectional survey data from 830 adolescent men and women aged 14-19 living in Soweto, South Africa, this thesis conducted gender-based analyses to examine determinants of high-SSE (study-alpha=0.75) and the association between high-SSE and CCU. Results revealed women have higher SSE than men. High-SSE was associated with CCU use for men, but not women. For women, high-SSE was associated with having an adult in the home, and no history of physical violence. Moreover, lower depressive symptomology among women was more predictive of CCU than SSE, indicating that gender-targeted HIV prevention interventions must move beyond individual-level determinants of behaviour to address socio-structural and relational factors influencing syndemic HIV risk among adolescent women in South Africa.

Document type: 
Thesis
Senior supervisor: 
Dr. Robert Hogg
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) M.Sc.

How Much Help? How Much Harm? Working class women’s experiences of prenatal care in East Vancouver

Author: 
Date created: 
2017-03-06
Abstract: 

This project sought to interrogate the institution of prenatal care in East Vancouver through the lived experiences of working class and historically marginalized women. Prenatal care in British Columbia is a complex of institutional policies and practices. This project focused on prenatal visits between pregnant women and their chosen maternity care provider. Through the stories and experiences of nine research participants, this project affords insight into how the work of prenatal care might be improved to better the experiences and health outcomes for working class and historically marginalized women and their newborns. This could include integrating more substantive ways of centering women in the institution of prenatal care and recruiting women as active participants, such as the use of group care and lay health care workers. Pregnancy is a time of great change for working class and historically marginalized women, attempts to reduce social inequity can start with the institutions that provide women care throughout pregnancy.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Nicole Berry
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) M.Sc.

Impacts of a new Greenway on older adult mobility: A mixed-methods analysis in Vancouver, BC

Author: 
Date created: 
2017-04-19
Abstract: 

Our population is aging, and life expectancies are increasing globally. One strategy to promote healthy aging is by creating environments that support physical activity. Using a natural experiment study design, this dissertation takes a mixed-methods approach to capture the impacts of a built environment intervention aimed to increase active transportation among community-dwelling older adults. We captured location-specific travel and physical activity using accelerometers and GPS monitors one year before and after the Comox-Helmcken Greenway was developed, and measured change in weekly transportation-related activity, specific activity along the Greenway, and activity along a comparison corridor. Secondly, we interviewed a subset of these older adults to capture their perceptions of the Greenway. We found no change in weekly physical activity levels, but a decrease in the number of trips along the Greenway. Our interview data suggests this may result from confusion of messaging, the steep slope, and a lack of destinations.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Meghan Winters
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) M.Sc.

A comparison of self-efficacy between pregnant women who use cigarettes versus electronic nicotine delivery systems: A cross-sectional study of participants in the BC Healthy Connections Project

Date created: 
2016-12-15
Abstract: 

Self-efficacy (SE) has been regarded the strongest cognitive determinant of cigarette use during pregnancy, but has yet to be assessed in pregnant women who use alternative modes of nicotine, including electronic nicotine delivery systems (ENDS). Knowing that nicotine is harmful to the fetus, more research on SE in pregnant ENDS users is warranted. Using data from the BC Healthy Connections Project, the purpose of this research was to identify differences in SE between pregnant: cigarette users; ENDS users; combination users (ENDS and cigarettes); and abstainers (no tobacco or nicotine). The relationship between SE and mode of nicotine was examined using multiple linear regression. Due to small sample sizes, ENDS and combination users were collapsed (ENDS/combination users). SE was significantly higher in ENDS/combination users compared to abstainers. No other significant group differences emerged. Results from this research can be used to tailor interventions aimed at reducing fetal exposure to nicotine.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Charlotte Waddell
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) M.Sc.

The Impact of HIV Non-Disclosure Case Law on the Healthcare Engagement of Women Living with HIV in Canada

Date created: 
2016-06-17
Abstract: 

Introduction: In 2012, the Supreme Court of Canada (SCC) expanded the reach of criminal liability for HIV non-disclosure in Canada when it ruled that people living with HIV (PLWH) who do not disclose their HIV status before sex that has a “realistic possibility” of HIV transmission could face criminal charges, suggesting that condom-protected vaginal sex with a low HIV viral load would incur no legal obligation to disclose. This thesis sought to identify the prevalence and correlates of facing a legal obligation to disclose, and to investigate awareness, understanding and perceived healthcare impacts of the 2012 SCC ruling among the diversity of women living with HIV (WLWH) in Canada, involving WLWH as key research partners.Methods: Quantitative data from men and women enrolled in a cohort of PLWH who use illicit drugs in Vancouver (ACCESS), and women enrolled in a community-collaborative cohort of WLWH in British Columbia, Ontario, and Quebec (CHIWOS), were used to meet the objectives of this thesis. Novel community-driven questions assessing awareness, understanding and perceived impacts of HIV non-disclosure case law were incorporated into data collection instruments of both cohorts. Results: Among ACCESS participants who use injection drugs (n=176), WLWH were more likely to face a legal obligation to disclose compared to men in the wake of the 2012 SCC ruling. Among female ACCESS (n=98) and CHIWOS (n=584) participants, awareness of the 2012 SCC ruling (44% and 74%, respectively) and understanding of the conditions under which PLWH may face a legal obligation to disclose (17% and 35%, respectively) were suboptimal. Although most participants were engaged in HIV treatment and care, discussions about HIV disclosure and the law were lacking in healthcare settings, despite participants expressing a willingness and desire to engage in discussions of this nature with providers. Most participants believed that HIV non-disclosure case law might limit the type of information WLWH would share with providers.Discussion: This thesis identified an urgent need to disseminate information about HIV non-disclosure and the law in community and healthcare settings, to ensure WLWH have fundamental information to avoid prosecution and to optimise their health and rights in the current legal climate.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Angela Kaida
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) Ph.D.

Women and antiretroviral therapy adherence: examining the impact of internalized stigma by gender

Author: 
Date created: 
2016-09-21
Abstract: 

Background: Antiretroviral therapy (ART) and ambitious treatment strategies such as Treatment as Prevention (TASP) and 90-90-90 have reduced HIV-related morbidity and mortality among people living with HIV (PLWH), and substantially decreased the likelihood of transmission of the virus to others. The benefits of ART are not felt equally among all PLWH, as PLWH may not be able to maintain ART adherence. This study examines gender differences in ART adherence and the sociostructural and psychosocial factors associated with such differences in British Columbia, Canada. Methods: Quantitative analyses assessed optimal ART adherence by gender, longitudinally and cross-sectionally, using bivariate, multivariate analyses, as well as structural equation modelling. All analyses used data collected from 2000 onward by the BC Centre for Excellence in HIV/AIDS from BC, Canada, with adherence measured using pharmacy refill compliance data. Findings: Gender-based disparities were evident in ART adherence in BC, with a significantly lower proportion of women attaining optimal (≥95%) adherence relative to men (57.0% versus 77.1; p<0.001) regardless of subgroup. Women also experienced far greater sociostructural and psychosocial disparity than men, however food insecurity was the only variable examined that was independently associated with suboptimal adherence among women (adjusted odds ratio [AOR]: 0.364; 95% confidence interval [CI]: 0.181 to 0.734). Psychosocial variables exhibited different effects and interactions for men and women, however, they explained only a low proportion of the variability observed in ART adherence (1.6% and 3.7%, respectively). Disclosure worries was the only psychosocial variable to affect women’s adherence (standardized regression weight [r]: -0.192; p=0.015). Personalized stigma (r: 0.299; p<0.001) and internalized stigma (r: 0.321; p<0.001), however, did have a significant explanatory affect on depression experienced by women. Discussion: Gender-based disparities must be addressed if women living with HIV are to attain optimal health and if we are to achieve the goals of 90-90-90. Addressing aspects of poverty and the greater adversity that women face in this regard would result in a more salient improvement to ART adherence than interventions addressing stigma.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Cari Miller
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) Ph.D.

Parenting and Depression among Homeless Women: Understanding the Mediating Role of Quality of Life

Author: 
Date created: 
2016-08-02
Abstract: 

Homeless mothers represent an extremely vulnerable population. Research consistently revealed that they experience poor quality of life (QoL) and increased depression. Evidence also indicated that increased QoL is associated with improvements in depression. Whether the effect of parenting status on depression is mediated by QoL is unclear. This study, therefore, examined how parenting status affects depression among homeless women, through subjective quality of life (SQoL). This secondary analysis drew from the 325 chronically homeless women who completed the At Home/Chez Soi Study baseline questionnaire. Associations were examined using bivariate analyses and mediation analyses were performed using bootstrapped regression models. SQoL explained the association between parenting and depression; leisure accounted for the largest proportion (27%) of the variance on depression. The findings highlighted the importance of providing supports to homeless mothers, so as to improve their SQoL and depression. Specifically, findings suggested that leisure could partially improve depression among homeless mothers.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Lawrence McCandless
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) M.Sc.

Barriers and facilitators to the integration of services for depression in primary care in Vietnam: the perspective of primary care providers

Date created: 
2016-07-22
Abstract: 

Although evidence suggests that depression is one of the leading causes of morbidity and disability in the world, treatment for depression is often unavailable, especially in low and middle-income countries. This gap in treatment has led to momentum to improve and scale-up services through approaches such as task-shifting. These steps, however, must be carefully considered to ensure that such efforts are appropriate, effective and acceptable for populations being served. This dissertation assesses barriers and facilitators to the integration of services for depression in primary care in Vietnam from the perspective of primary care providers (PHPs) by examining sociocultural considerations and individual, organizational and structural factors that might influence the process of service integration. The study has three components. The first, a narrative review, explores considerations for studying depression cross-culturally and the implications for global depression research. The results suggest that although depression is universally experienced, it varies by cultural context, and improved epidemiological methods that account for these cross-cultural variations are needed. The relationship of social determinants of health to depression must also be further explored. The second component, a qualitative study, examined how depression is conceptualized in Vietnam from the perspective of PHPs. Findings indicate that although depression is not widely recognized or seen in primary care, depression in Vietnam is largely understood in psychosocial terms. Along with efforts to improve screening and help-seeking, the introduction of psychosocial depression interventions in primary care is both appropriate and important. The third component used mixed methods to assess barriers and facilitators to the integration of services for depression in primary care. The findings suggest that although PHPs are motivated to build capacity and deliver services for depression for their patients, systemic factors must be addressed to ensure that PHPs are adequately trained and supported to deliver psychosocial interventions. By integrating an approach that examines sociocultural considerations of depression with individual, organizational and structural factors influencing service integration, this study suggests that a balance is both necessary and possible between approaches prioritizing efficient treatment delivery and those emphasizing the need for contextualization and careful sociocultural consideration. A balance of these approaches should be applied when introducing enhanced depression services cross-culturally.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Elliot Goldner
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) Ph.D.

A Behavioral Ecology Approach to Trade-offs in Reproduction: Modelling Women’s Reproductive Strategies and Empirical Studies of Post-partum Amenorrhea

Author: 
Date created: 
2016-07-26
Abstract: 

Reproductive behaviors are shaped by a plethora of selective pressures, past and present. On an ecological time scale, reproductive “decisions” are made by balancing life-history trade-offs that are dependent on intrinsic and extrinsic factors, such as resource availability and age. Mathematical models are powerful tools that allow for the systematic investigation of such factors, and to test whether selective forces thought to be responsible for particular traits had been correctly identified. In this thesis, I present a dynamic state variable model for the optimization of reproductive scheduling under a range of family and environmental contexts. Next, I test one of the model’s simplifying assumptions, that sons and daughters cost the same to produce and to raise, via secondary data analysis of two existing data sets. These results are discussed in parallel to the benefits of applying principles of evolutionary ecology to public health problems.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Pablo Nepomnaschy
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) M.Sc.