En Afrique sub-Saharienne, les femmes et les filles sont particulièrement vulnérables à l’infection parle VIH. L’infection par le VIH est une menace importante pour la santé reproductive de cettepopulation. Les études de recherche présentées dans le cadre de cette thèse ont été conduites enAfrique de l’Ouest et avaient pour objectifs principaux : i) Estimer la prévalence de la violenceperpétrée par le partenaire intime selon le statut sérologique ; ii) Estimer l’incidence de grossesseaprès la mise sous traitement antirétroviral ; iii) Déterminer l’effet de la grossesse après la mise sousARV sur le risque de décès, de progression de la maladie à VIH et d’être perdu de vue. Nos résultatsnous montrent que la prévalence de violence physique et sexuelle perpétrée par le partenaire intimeest plus élevée auprès des femmes VIH-positives qu’auprès de celles non-infectées (63,1 vs. 39,3%,p=0.01 and 69,7 vs. 35,3%, p=0.01, respectivement). De plus, l’incidence brute globale de premièregrossesse après la mise sous ARV en Afrique de l’Ouest est de 2,9 par 100 femmes-années(IC95% :2,7 – 3,0). Auprès des jeunes femmes âgées de 25-29 ans cette incidence peut être de 4,7per 100 femmes-années (IC95% :4,3 – 5,1). Finalement, la grossesse après la mise sous ARV réduitle risque de décès ou de progression de la maladie à VIH (aHR : 0,61, CI95% : 0,40-0,92) ainsi que lerisque de devenir perdue de vu (aHR : 0,74 ; CI95% : 0,60-0,92) des femmes ouest-africaines infectéespar le VIH. La prévalence de violence perpétrée par le partenaire intime est très élevée auprès desfemmes infectées par le VIH et cela pourrait entrainer des conséquences négatives de santé de cesfemmes. La grossesse est un évènement fréquent auprès des femmes VIH positives sous ARV qui ades répercussions importantes sur le statut de santé des femmes séropositives. L’intégration desprogrammes de prise en charge maternelle dans les services de prise en charge du VIH doit êtrepriorisé en Afrique sub-saharienne. / HIV infection in sub-Saharan Africa is a major public health threat particularly for girls and women ofreproductive age. The research presented in this thesis was conducted particularly in West Africa andthe specific objectives are i) to estimate the prevalence of intimate partner violence according to HIVserological status; ii) to estimate the incidence rate of pregnancy following ART initiation; iii) todetermine the effect of pregnancy after ART initiation on the risk of death, HIV-disease progressionand loss to follow-up. Firstly, in Togo, According to our findings, the prevalence rates of lifetimephysical and sexual violence (IPV) among HIV-infected women were significantly higher thanamong uninfected women (63.1 vs. 39.3%, p=0.01 and 69.7 vs. 35.3%, p=0.01, respectively).Secondly, Among HIV-infected West African women, the crude incidence of first pregnancy afterART initiation was 2.9 per 100 women-years [95% confidence interval (CI): 2.7 to 3.0] and it could beas high as 4.7 per 100 women-years (95% CI: 4.3 to 5.1) among women aged 25-29 years old. Finally,pregnancy after ART initiation appeared to reduce the risk of death or HIV-disease progression(Adjusted Hazard Ratio [aHR] =0.61; 95%CI: 0.40-0.92) and the risk of becoming LTFU at M48(aHR=0.74; 95%CI: 0.60-0.92) among West African HIV-infected women. Intimate partner violence ishighly prevalent among HIV-infected women and it may have negative repercussions on their healthstatus. Pregnancy is a common event after ART initiation and it might have repercussions on thehealth status of HIV-infected women. The design of safe motherhood programs addressed to HIVinfectedwomen and its integration within HIV care services must are a public health priority in sub-Saharan Africa.

Secular trends in breast cancer incidence in younger women suggest environmental factors, like exposure to environmental chemicals, may play a role in rising incidence. One of the strongest risk factors for developing breast cancer, next to family history, is high mammographic breast density, which is defined as the proportion of fibroglandular breast tissue relative to fat as seen on a mammogram. Phthalates, a ubiquitous endocrine disrupting chemical, have the potential to interfere with endogenous hormones like estrogen and androgens. There is growing evidence from animal and epidemiologic studies indicating distinct periods of heightened susceptibility to endocrine disrupting chemicals throughout the life course, particularly during critical windows of breast development. Exposure to hormonally active environmental chemicals like phthalates may be a modifiable risk factor for breast cancer, therefore reducing or eliminating exposure could have substantial public health benefits. The overarching goal of this dissertation was to assess the relationship between exposure to phthalates during two critical windows of susceptibility, the prenatal and pregnancy periods, and its effect on breast tissue composition in adolescence and adulthood. First, a comprehensive review of epidemiologic studies summarized the body of evidence for the association between phthalate exposure and intermediate markers known to be in the causal pathway of breast cancer risk (age at breast development, menarche, and breast tissue composition). This systematic review of the literature aimed to identify potential patterns of evidence by outcome and timing of exposure. Evidence from this review suggested that phthalate exposure during the prenatal and childhood periods may play a role in altering menarche. Findings for phthalate exposure and age at breast development were inconclusive. There was a considerable lack of epidemiologic data on phthalate exposure and breast tissue composition throughout the life course. Based on one study, there is a potential association between phthalate exposure during pre-puberty and altered breast tissue density in adolescent girls. No study assessed the relationship between phthalate exposure during the prenatal or pregnancy period and subsequent breast tissue composition. Second, an examination for the association between prenatal phthalate exposure and breast tissue composition measured in adolescence (Chapter 3) and the association between phthalate exposure during pregnancy and breast tissue composition measured during or after the postpartum transient period (Chapter 4) aimed to address this major gap identified from the comprehensive review. The empirical chapters of this dissertation used data from an ongoing longitudinal birth cohort study of mothers and their children conducted by the New York City Columbia Center for Children's Environmental Health and the Breast Cancer and the Environment Research Project (CCCEH-BCERP). The CCCEH-BCERP study cohort has prospective data on nine phthalate metabolite concentrations measured during the third trimester of pregnancy and breast tissue composition measured in a subsample of mother-daughter dyads. Notably, we used novel non-invasive methods (optical breast spectroscopy) in this younger cohort of mothers and daughters to objectively measure specific components of the bulk breast composition before mammography screening age. There was significant evidence of altered breast tissue composition in both mothers and daughters. For daughters (n=127, mean age 15.2 ± 1.9 years), prenatal exposures to select low molecular weight (LMW) and high molecular weight (HMW) phthalate metabolites altered overall breast density in opposing directions, which appears to be driven by significant altered percent breast water. There was a significant association between higher prenatal levels of a LMW phthalate metabolite (monobutyl phthalate) and lower levels of overall breast density (adjusted β = -0.32; 95% CI: -0.51, -0.13) and significant association between sum of di(2-ethylhexyl) phthalate (∑DEHP), a HMW phthalate metabolite, and higher levels of overall breast density in girls (adjusted β = 0.20; 95% CI: 0.05, 0.34). For mothers (n=133, mean age 41 ± 5.3 years at follow-up), there was a significant association between two LMW phthalate metabolites and lower levels of percent breast collagen. Additionally, there was a significant inverse relationship between levels of mono-(3-carboxypropyl), a HMW phthalate metabolite, and percent total hemoglobin of the breast (adjusted β =-0.03; 95% CI: -0.06, 0.00, p=0.05). Overall, this dissertation increased our understanding of the impact that exposure to phthalates during critical windows of susceptibility may have on specific components of the breast. Reducing exposure to both HMW and LMW phthalates may have an impact in reducing breast cancer risk, particularly for girls prenatally exposed, as there was stronger evidence of higher overall breast density and percent water from exposure to select HMW phthalates. Future prospective studies should confirm these results as findings might provide an opportunity for modifying potential breast cancer risk.

Although there has been a great deal of research in the areas of social networks, social support and well-being over the past two decades, little of that research has been cross-cultural, and virtually none has been carried out in countries outside the West. The present study attempted to describe the structure and functioning of the social networks of a group of relatively modern urban Moroccan women, and the associations among their social networks, social support, physical health and psychological well-being. Extensive interviews were conducted with 108 married or previously-married women who were living in a middle-class neighborhood in Rabat, Morocco. Subjects were asked to identify social network members, defined as friends, family or others who provided various types of support in typically encountered life situations, or with whom the subject had negative interactions. Standardized self-report instruments were used to assess physical and psychological well-being, and to assess the occurrence of stressful life events. Additional observational data were collected on respondents' neighborhoods and immediate physical surroundings. A model describing the interactions between well-being, network structure and network function was tested using factor-analytic and set-regression techniques. Stressful life events predicted reduced physical well-being. Enhanced psychological functioning was predicted by reciprocity in relationships, marital satisfaction, and to a lesser degree, practical and emotional support. Contrary to predictions, patronage support was associated with both enhanced physical and psychological well-being. Results were generally consistent with Conservation of Resources (COR) theory, which predicts that the uniformly large and well-functioning networks found in this study would produce effect sizes that were small, but consistent with Western research findings.

Uganda has experienced substantive shifts in HIV prevention and treatment resulting in marked declines in HIV incidence and mortality rates across the country despite being among the top 5 highest new prevalence rates for HIV transmission and infection among women (Uganda Ministry of Health, 2019). Prior research has revealed that fear of stigma and discrimination, disclosure of HIV status, and quality of services are key factors in women’s healthcare decisions and care-seeking behaviors (Akatukwasa et al. 2021; Lancaster et al., 2016; Grossman & Stangl, 2013). Yet, there continue to be significant knowledge gaps regarding the mechanisms through which intersectional stigma exacerbates health outcomes for people living with HIV. This dissertation draws on baseline data, from the Kyaterekera project an efficacy trial testing the effects of a structural intervention on the HIV-health outcomes of women engaged in sex work within the Masaka region, Uganda. Using an explanatory sequential mixed method design, this study utilized Structural Equation Modeling (SEM) to test the direct and indirect effects of intersectional stigma on mental health, while also evaluating mechanisms (i.e., social support and quality of care) through which stigma impacts mental health, treatment adherence and subsequent viral load. There were no direct or indirect effects of intersectional stigma on mental health, but intersectional stigma was positively associated with social support. Additionally, depression and adherence were negatively associated with viral load. Next, in-depth interviews (n=52) explored personal and community-level factors that may influence women’s care-seeking attitudes and overall health decisions. The following themes were most salient for women: 1) disclosure risk, 2) Intersectional community stigma permeates marginalized women’s health decisions, 3) adaptive behaviors and coping strategies are essential to maximizing care experiences, and 4) the Care Seeking Cost-Benefit Tradeoff. Through an integrative framework, quantitative and qualitative findings were then juxtaposed through a joint display and found to be predominantly complementary (McCrudden, M. T., Marchand, G., & Schutz, P. A., 2021). Findings suggest that a positive association between intersectional stigma and social support may underscore the significant long-term effects of living with HIV. Moreso, holding other stigmatized social statuses. Moreso, this link between intersectional stigma and social support may be due to women anticipating the likelihood of experiencing community-level/interpersonal stigma with HIV disclosure and extensive contact with their social support network. Also, more contact with social networks, particularly those in which stigma norms and discriminatory attitudes are pervasive on the community/ interpersonal level (or perceived to be so) may account for the positive associations between HIV stigma and social support. Sex work had a higher degree of concealability than HIV. As such, sex work was disclosed less frequently than HIV to healthcare providers, family, and friends due to anticipatory community stigma. Despite the finding that the explanatory sequential design produced no direct or indirect effects of intersectional stigma on mental health or viral load via SEM, the exploratory analysis provides substantive insights into the negative impact of HIV-related intersectional stigma on women’s care-seeking experiences and broader health decisions. Women’s care-seeking attitudes and behaviors reveal the intrinsic adaptive skills, strength, and resilience they possess to address individual health needs despite known barriers to care. Overall, this study provides further support for holistic interventions that can enhance and build resilience and successful adaptive strategies to mitigate the effects of HIV-related intersectional stigma.

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Environmental exposure levels are often sufficiently disparate between populations such that there is little or no overlap, complicating our ability to ascertain the full dose-response curve and as such create informed regulatory policy.I reviewed the literature on methods available to address non- and partially-overlapping exposure distributions, drawing from both epidemiology as well as other relevant disciplines to describe the universe of proposed solutions. I also used the case study of maternal PCB-153 exposure and birthweight, utilizing real-world and simulated data to explore our ability to ascertain “true” dose-response curves from observational data given the limited cohort-specific exposure ranges. I investigated the importance of controlled and uncontrolled confounding as well as the impact of sample size on our ability to ascertain a “true” underlying dose-response curve. Pooling and meta-analysis were useful to increase the heterogeneity of exposure distributions despite imperfect confounding control and heterogenous confounding structures across cohorts. The analyses also serve as continued evidence of the challenges of making population-wide inferences from study samples with restricted exposure ranges as well as the danger of pooling multisite data without sufficiently accounting for heterogeneity in both exposure level and distribution of confounders. These results highlight the limitations of using both individual studies and systematic reviews of environmental chemicals, and emphasize the need for pooling and meta-analysis to widen exposure distributions that in turn permit us to accurately capture the negative effects of these environmental chemicals.

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The relationship between the PQ-segment slope on ST-segment depression during vigorous exercise was examined in 26 apparently healthy females between 18 and 26 years of age. Each subject performed 2 submaximal cycle ergometer exercise tolerance tests (trial A and trial B) on nonconsecutive days wherein the following variables, as delta scores, were measured; P-wave amplitude (microvolts), PQ-segment slope (uV!sec), and J-point at 0 and 60 msec (uV). Each variable was measured by both visual and computer averaging. The degree of reproducibility within and between trials differed for the visual and computer averaged measures. Generally higher reproducibility was found with computer averaging particularly within trial B (r =0.63-0.89, p<O.OI). Trial b served as a basis for assessment of PQ-segment slope effect on ST segment response. Computer analysis of frequency distribution for responses revealed a greater frequency of downsloping PQ-segment with clinically significant ST-segment depression (>50 uV) at both 0 and 60 msec after the J-point in lead II. However, there was a greater percentage (91%) of flat PQ-segment slopes with clinically significant ST-segment depression at J-point 0 msec in lead V5. These findings suggest possible influence of lead selection on the measurements of the PQ-segment slope and ST-segment. Implication of clinical application would be to use lead VS for diagnosing CHD and by measuring ST-segment depression at J-point 60 msec. However when screening exercise ECG tests in apparently healthy women use J-point at 0 msec. / Master of Science