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Worldwide, women struggle to control the timing and spacing of childbearing, resulting in a high number of pregnancies that are unintended. In order to achieve many of the United Nations Millennium Development goals related to maternal and child health, gender equality and HIV prevention, the incidence of unintended pregnancy and its consequences must be significantly reduced. The three papers comprising this dissertation represent distinct analyses related to the general theme of unintended pregnancy among disadvantaged women, with a particular focus on research that is responsive to and can directly inform pressing policy questions. Paper 1 synthesizes the observational evidence on the relationship between use of hormonal contraception (HC) and women's risk of HIV acquisition using quantitative meta-analysis. Given the central role of HC in preventing unintended pregnancy, policymakers and practitioners are struggling to translate an inconsistent body of observational evidence on this question into balanced contraceptive guidance for women, in particular in high prevalence HIV settings such as sub Saharan Africa. Pooled effect estimates from studies that use a comparable approach to identify the effect of use of various forms of HC on risk of HIV acquisition, and adequately address confounding and selection bias, suggest that use of certain forms of HC is associated with an elevated risk of HIV acquisition, but not of the magnitude that would merit complete withdrawal of these methods.Paper 2 capitalizes on a unique study design to examine the role of an unintended birth on women's educational attainment in the United States. Despite over three decades of research, there remains debate over the extent to which reduced educational attainment among women with an unintended pregnancy is a function of childbearing itself, or a consequence of common selection factors that predispose women to both early childbearing and poor socioeconomic outcomes. By exploiting a discontinuity in the timing of presentation for abortion care, this paper compares the incidence of graduation or drop out from school among exchangeable groups of women, half of whom had an unintended birth and half of whom received an abortion. Unlike previous research, this analysis finds no difference in the educational achievements of women who experience an unintended birth and those that experience an unintended pregnancy that they do not carry to term.Finally, paper 3 explores the extent to which minors seeking abortion in the U.S. involve parents and other important individuals in their decision-making process, and how these relationships influence their confidence in and projected coping with their abortion decision. Despite the fact that a majority of states require parental involvement in minors' abortion, little is known about the effect of involving a parent on minors' abortion decision-making and anticipated coping after abortion. This analysis reveals that in the absence of a law mandating involvement, a majority of minors involve parents, primarily mothers, and male partners in their abortion decisions. For a minority of minors, experiencing pressure or lack of support from mothers reduces confidence in their decision and increases their likelihood of anticipating poor coping after an abortion.

Can Vitamin D deficiency contribute to opioid use? Though seemingly unrelated substances, the two interestingly mirror each other in effects and metabolism. Vitamin D deficiency can lead to weakness, pain, and depression. Both can interact with addiction receptors in the brain. For these reasons, some evolutionary thinkers argue sunlight, the primary source of Vitamin D, may have emerged as the very first addiction. In this framework, modern opioid use could mirror sun exposure, but without the benefits and regulation which Vitamin D provides. Thus, one's natural Vitamin D levels may be very important to explaining their interactions with opioids. This paper parallels previous medical and epidemiological literature attempting to demonstrate how Vitamin D mediates the strength of opioids. Using 2003--2004 U.S. NHANES prescription use, health, and demographic data for individuals aged 20 to 84, this paper measures the impact of Vitamin D deficiency on the propensity of opioid use. A control function approach is used, leveraging milk consumption to relieve endogeneity concerns in previous studies. Unlike previous findings, we do not observe any significant effect from Vitamin D levels.

The introduction of Antiretroviral Therapy (ART) in the late 1980s has transformed HIV from a fatal disease into a manageable chronic condition, although challenges like adherence to treatment and broader socio-economic factors continue to impact viral suppression and overall health status among people living with HIV (PLWH). The objective of this dissertation is to examine social (community environments), biological (pain), and psychological (self-perceived quality of life) factors associated with viral suppression among PLWH.The first paper investigates the association between neighborhood and sociodemographic factors and viral suppression among PLWH in Southern California, focusing on areas served by Ryan White clinics. Contrary to expectations, higher walkability scores were associated with lower levels of viral suppression. In line with our hypotheses, longer commute times were negatively associated with viral suppression. Employment showed a positive association with viral suppression, while higher poverty levels and longer work hours negatively impacted viral suppression rates. Additionally, no significant relationships were found between education level, public transportation score, and viral suppression. Given that PLWH often report higher instances of pain and substance use compared to the general population, the second paper explores the association between pain and viral suppression and how substance use modifies this relationship. We found that there was no substantial association between pain and viral suppression among women living with HIV (WLWH) in our cohort. Furthermore, we saw no modification by any type of substance use. The third paper examines the role of quality of life (QoL) on viral suppression and any disparities in this association by race/ethnicity. QoL encompassing physical health, psychological well-being, and socioeconomic stability, has been consistently linked to viral suppression. We found a significant positive association between QoL and viral suppression (aOR: 1.17, 95% CI [1.10, 1.25]). However, the magnitude of this association was shown to vary by racial and ethnic group. The increase in odds of viral suppression per one-point rise in QoL score was greatest among White WLWH and least among Black WLWH. Understanding the individual impact of each factor examined allows for the development of targeted, effective interventions. These findings not only advance our knowledge of HIV management but also emphasize the need for a multi-faceted approach that addresses the specific needs and circumstances of individuals living with HIV.

The widespread availability of antiretroviral therapy (ART) for HIV infection in Sub-Saharan Africa (SSA) has resulted in decreased morbidity, mortality, and transmission of HIV. This region, however, still represents the majority of the global burden of HIV. Furthermore, levels of retention in care and medication adherence, critical determinants of ART effectiveness, are currently suboptimal, and, thus, continue to be the target of many interventions. This dissertation is comprised of three chapters related to understanding ART adherence and interventions to improve it.Chapter 1 quantitatively describes and examines the distribution of poor adherence to antiretroviral therapy in a study of HIV-positive patients in Zambia. In a novel application of the Lorenz curve, a tool used commonly in economics, this analysis characterized the concentration of medication non-possession in a network of clinics in order to identify “hotspots” and predictors of poor adherence. Results extend previous studies by revealing that even though average adherence is high, lapses in adherence are common and concentrated among a minority of patients, and also in certain clinics. This concentration and variability varies with time on ART. Furthermore, a small fraction of patients accounts for the majority of days of medication non-possession, with the size of this group increasing with time on ART. This suggests that targeted interventions may represent a preferable overall strategy as compared to those targeting all patients to improve adherence. Furthermore, there was high variability across clinics suggesting that interventions targeting clinic “hotspots” may also represent an efficient use of resources to improve ART adherence. Chapter 2 presents the results of the first qualitative study to examine conditional incentives for ART adherence and their potential pathways of action among people living with HIV. This study was conducted within a study of conditional food and cash transfers to increase retention in care and adherence to ART among HIV-positive food insecure recent adults in Shinyanga, Tanzania. Although financial and in-kind incentives have been shown to improve outcomes along the HIV care cascade, results are mixed, and there is little evidence about the pathways through which incentives work. Results of this qualitative study and analysis revealed that incentives acted through three primary pathways to potentially increase retention in care and adherence to ART: 1) addressing competing needs and offsetting opportunity costs associated with clinic attendance, 2) increasing motivation and 3) alleviating stress associated with attending clinic, worry about providing for oneself and one’s family, and providing hope for a better future. The first pathway was the strongest, which was consistent with field observations and discussions with local clinic staff, research staff, and Ministry of Health officials. Participants did not report any harmful events associated with the incentives, and reported a variety of beneficial spillover effects on household welfare. Understanding these pathways can help improve design and targeting of future food or cash incentive interventions. Chapter 3 focused on intrinsic motivation within the aforementioned study of food and cash transfers for ART adherence in Tanzania. Some critical of incentives argue that incentives can ‘crowd out’ intrinsic motivation, making the individual less likely to engage in the desired behavior after the incentive is removed, potentially leading to limited durability of effect and causing harm in the long term. This hypothesis was examined among recent antiretroviral treatment initiates in Tanzania by comparing participants’ level of intrinsic motivation before receiving transfers to the level once the transfer period ended. The analysis revealed that, not only did intrinsic motivation not decrease after the transfer period ended, but that the level of intrinsic motivation increased overall and within study arms. Furthermore, the change in motivation did not differ by study arms. As the first study to empirically examine the crowding out hypothesis regarding incentives in a real-world, resource-limited setting, these results suggest that incentive interventions in such settings should not be impeded by concerns of crowding out intrinsic motivation.Together these chapters contribute to improving our understanding of antiretroviral adherence and intervention response. The Lorenz curve and medication possession analysis provides a more comprehensive and detailed measurement and illustration of adherence and its variability across individuals and clinics in Zambia. Such information is critical to targeting and designing future interventions. Next, by examining an ongoing intervention to improve adherence in Tanzania, we were able to elucidate and examine the potential pathways of action of food and cash transfers. Furthermore, we found no evidence that these incentives decreased intrinsic motivation. Knowledge gleaned from this deep exploration of the incentives’ mechanism of action in a real-world setting not only informs refinement of the intervention, but also helps to fill the gap in understanding how and when these interventions may work.

The outbreak of COVID-19 presented an unparalleled risk to public health, leading to urgent scientific efforts in understanding transmission mechanisms and mitigating risks, especially in healthcare settings. This mixed-methods study examines knowledge advancement regarding indoor air quality in healthcare facilities during the pandemic. A systematic literature review of 163 post-COVID studies identifies key research thrusts and 31 recommendations related to building ventilation, air filtration, surface disinfection, and monitoring. Comparison with over 200 pre-pandemic publications reveals both reliance on established infection control principles and unique contributions, such as detecting viral RNA in air and surface samples indicating potential airborne and fomite transmission routes. Additionally, 11 studies are recognized for their novelty and significance through qualitative analysis. Reference network analysis identifies pivotal papers based on centrality metrics, with 5 out of 11 significant papers converging between systematic review and network analysis. Partial convergence between qualitative and quantitative approaches is observed, with discrepancies arising from evaluation criteria differences. Combining subjective qualitative inquiry with objective network analytics provides critical insights into knowledge advancement and scientific communications during extreme crises. The pandemic necessitated rapid mobilization of existing knowledge alongside the cultivation of new evidence to understand the novel SARS-CoV-2 threat. This research suggests that extreme events can accelerate science, but evidence-based rigor remains essential alongside swift action.

Throughout time, throughout the world, epidemic diseases have depleted whole cultures,changed history and been one of the most significant threats to human survival.Medicine and government have worked to limit the spread of and reduce the severity ofdiseases. Mathematics has been an able partner in that fight. Through the use of modeling,mathematics has been able to provide the medical community and civic authorities with informationon size, severity, and spread of the disease. This paper presents the developmentof some key epidemic models, investigates properties of the solutions, and discusses thestability of the disease-free and endemic equilibriums. The Threshold theorem developedby Kermack-McKendrick is derived and the calculation of the reproduction number, R_0 isperformed. The reproduction number predicts the average number of secondary infectionscaused by a lone infected individual in a population composed of all susceptible people.The reproduction number depends on the rate of transmission, Beta, the rate of recovery, gamma, and the size of the susceptible population, S. This paper clearly demonstrates the calculationof the reproduction number which is beneficial for any mathematician desirous ofusing the reproduction number to study infectious diseases and investigate the impact ofvarious disease-fighting tools.

Sudden cardiac death (SCD) is a common manifestation of cardiovascular disease (CVD) which is underappreciated in the CVD literature. Investigations into the CVD risk factors which contribute to SCD have yielded little additional information, and in the majority of the people who succumb to SCD, there are no previous signs or symptoms of CVD. Most of the previously published information on SCD investigates the hours and days leading up to the event but falls short of examining medium- and long-term exposures and SCD. Therefore, the goal of this dissertation was to investigate three ubiquitous environmental exposures and their association with SCD in the medium- and long-term. Prior to engaging in original research, the first paper (Chapter 2) serves as a systematic and in-depth review of the previously published literature on air pollution, temperature, and altitude with SCD. Air pollution, especially particulate air pollution (PM) and ozone, were consistent contributors to OHCA/SCD in the short-term. Likewise, both cold and warm temperatures were associated with OHCA/SCD in the short-term, with effect estimates generally being larger for colder temperatures. All three of the original research papers used time-varying Cox-proportional hazards models to investigate the relationship between the three exposures and SCD. The first original research paper (Chapter 3) focused on an important criteria pollutant, PM, and SCD. PM2.5 and PM2.5-10 both were associated with SCD at different time windows. The second original research paper (Chapter 4) investigated the relationship between 1-month moving average temperature and 12-month moving average temperature and SCD, and it determined that there was an association between both moving averages and SCD. The third original research paper (Chapter 5) addressed a major gap in the literature on altitude and SCD in that there are no studies that investigate the association between altitude of residence and SCD in the general population. Although the association was ultimately null, this result helped clarify that the cardiovascular benefits attributed to altitude in terms of incident myocardial infarction and mortality do not extend to SCD. This dissertation represents an important contribution to the environmental epidemiology and cardiology literature on ubiquitous environmental exposures and SCD. Climate change and pollution are major contributors to CVD mortality, including SCD. Therefore, mitigation strategies both in the US and worldwide are necessary to ameliorate the burden of CVD which is attributable to SCD. Since there is a very narrow time window for treatment of a fatal arrhythmia prior to deteriorating into SCD, population-level interventions to lessen the burden of environmental exposures are critical to reducing SCD.

Antimicrobial resistance (AMR) is a growing global concern that poses significant risks to human, animal, and environmental health. AMR describes organisms, including bacteria, viruses, and fungi, that have become resistant to the drugs used to kill or control them through evolutionary, environmental, or social pressures. The emergence and spread of AMR threaten decades of advancement in reducing morbidity and mortality from many infectious diseases and is one of the most pressing clinical and public health threats. In the United States alone, more than 2.8 million AMR infections occur annually, resulting in over 35,000 deaths and costing the healthcare system over $4.6 billion.Community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are a significant financial burden on healthcare systems and vary across populations. Several studies have documented infection disparities across racial-ethnic categories, economic indicators, and geography. Evidence suggests that differential infection rates are related to social determinants of health such as income, housing, and educational attainment. However, few studies connect infection disparities to the key mechanisms underlying the role of racial-ethnic category, income, or geography in shaping population health. The role of area-based determinants of infection has yet to be thoroughly examined, and addressing the challenges of AMR more broadly will require understanding the social, environmental, and economic processes that shape differential infection incidence. This dissertation explores the systems and determinants associated with disparities in CA-MRSA infection presenting in California emergency departments (ED). The first paper examines the epidemiology of CA-MRSA skin and soft tissue infections (SSTIs) across California from 2016-2019, examining the spatial distribution of infections in a unique neighborhood boundary. CA-MRSA infections are historically associated with densely populated urban areas, but statewide ED data revealed that more rural and mountainous regions of California are experiencing a higher burden of CA-MRSA SSTIs. This highlights a potential change in the epidemiology of CA-MRSA SSTIs and warrants further investigation into identifying at-risk populations and possible infection pathways.Electronic health records (EHR) are an increasingly utilized data source in public health, including throughout this dissertation. However, biases may exist when using EHR data for research, primarily due to the processes that drive whether someone is captured in the EHR. The second paper of this dissertation examines whether small-area inequalities in CA-MRSA infection that are observed in the EHR can be explained by selection bias. Using an agent-based model (ABM) to simulate the dynamics of healthcare-seeking behavior for CA-MRSA infection, we compared the spatial patterns of agents seeking care for their infection in the ED to empirical data. The ABM reproduced the observed infection prevalence for nine of the 21 geographies. The differences in prevalence across geographies did not reach the magnitude in the observed data, and the overall spatial patterns between the two had weak agreement. The results suggest that geographic disparities identified in the observed ED data are due to factors beyond selection bias and healthcare-seeking behaviors. Relative importance analyses point to environmental degradation, percent non-Hispanic white residents, and percent of residents living below the federal poverty level as potentially important determinants.Finally, poverty is an often-cited driver of health disparities, and associations between poverty and CA-MRSA infection are well documented. However, the pathways through which poverty influences infection have yet to be thoroughly examined. The third paper aims to identify mediating variables explaining why area-level poverty is associated with CA-MRSA infection in Californians. Mediation analyses using Bayesian multilevel spatial regression revealed that the association between area-level poverty and CA-MRSA infection could be partially explained by spatial autocorrelation, living in a primary care shortage area, and environmental degradation in the neighborhood. Combined, the mediators explain approximately 6% of the odds of CA-MRSA infection for individuals living in neighborhoods with high poverty rates and 50% of the statistical association between area-level poverty and CA-MRSA infection. The statistical association between area-level poverty and infection was entirely explained by the mediators for individuals living in neighborhoods with low poverty rates. Overall, this dissertation provides insight into the changing epidemiology of CA-MRSA infections in California, the accuracy of using EHR data in public health disparities research, and the mediating variables that explain the association between poverty and infection. Expanding our understanding of the determinants and mechanisms driving AMR and differential CA-MRSA infection incidence is essential for developing effective public health policies and interventions to reduce the burden of these infections. Addressing the challenges of AMR, including health disparities, will require multi-level approaches encompassing upstream facilitators, individual behavior, and social and environmental contexts.

Chronic liver disease is increasingly prevalent with high rates of morbidity and mortality, yet it receives less attention than other similar chronic diseases such as cardiovascular disease and chronic obstructive pulmonary disease. Barriers to timely medical care may preclude diagnosis and management and thus, exacerbate potentially avoidable morbidity and mortality for persons with chronic liver disease. This dissertation explored the extent of health care barriers among adults with chronic liver disease compared to other chronic conditions and identified latent classes derived from different health care barriers to phenotype those at highest risk for recurrent acute care use within the adult population with chronic liver disease in the United States.The first paper, “Evaluation of the Extent of Health Care Barriers among Adults with Chronic Liver Disease vs. Other Chronic Diseases in the United States,” compared estimates of any and the number of health care barriers and the association of recurrent acute care use by prevalence of barriers to care among adults with chronic liver disease versus those with cardiovascular disease and/or chronic obstructive pulmonary disease. Using a multivariable hurdle model, the study found that adults with chronic liver disease were significantly more likely to have any barriers to care (incident rate ratio, 1.12), but such a significant difference did not exist for the frequency of health care barriers. There was a dose-dependent relationship between likelihood of recurrent acute care use and prevalence of barriers to care. Inclusion of chronic liver disease as a high-risk group in future health policies that aim to improve access to care may help reduce challenges that persons with chronic liver disease encounter when seeking timely medical care and potentially reduce preventable acute care use.The second paper, “Identification of Hidden Phenotypes Using Self-Reported Barriers to Care to Predict Risk of Recurrent Hospitalization or Emergency Department Visits among Adults with Chronic Liver Disease in the United States,” identified latent classes within the adult population with chronic liver disease using self-reported barriers to care and assessed each phenotype’s likelihood of recurrent acute care use. The best fitting model to the data included four latent classes or phenotypes: minimal barriers, unaffordability, care delays, and inability to establish care. The study used a multivariable multinomial logistic regression model to identify likelihood of class membership. The unaffordability phenotype was significantly associated with younger age, fair or poor health, functional limitation due to health, and uninsurance. Membership in the care delays class was significantly associated with Hispanics, fair or poor health, and functional limitation due to health. The inability to establish care phenotype was significantly associated with younger age, female sex, functional limitation due to health, and non-private insurance. The inability to establish care group had the highest odds of recurrent acute care use, followed by the care delays and unaffordability groups. An emphasis on risk stratification using health care barriers can potentially help improve interventions that aim to reduce recurrent acute care use among adults with chronic liver disease, particularly for those who struggle to establish care.In summary, both chapters highlighted the prevalence of health care barriers and its association with recurrent acute care use for adults with chronic liver disease. Findings from the second chapter showed the consistent disparity in health care barriers for adults with chronic liver disease versus other chronic diseases and aimed to capture the attention of health policy makers to include chronic liver disease in future iterations of existing health policies or new programs that strive to improve outpatient care access to reduce preventable hospitalizations. The third chapter identified novel phenotypes of persons with chronic liver disease with different associated sociodemographic, health, and insurance characteristics and risks of recurrent acute care use. The third chapter also introduced the concept of using self-reported barriers to care as a way to risk stratify and allocate resources to the most vulnerable individuals with chronic liver disease. Both chapters intend to help improve health care access, reduce preventable acute care use, and potentially improve the morbidity and mortality trends among adults with chronic liver disease in the United States.

Humanitarian crises are increasingly longer in duration and more common. At the end of 2020, over 55 million people were internally displaced worldwide: 48 million due to conflict and violence and 7 million due to natural disasters. Globally, people affected by humanitarian crises are especially vulnerable to exacerbated chronic health conditions due to disrupted health services, irregular medication access, and unpredictable food supplies. As such, humanitarian aid and global health actors have become increasingly concerned with the management of noncommunicable diseases (NCDs) in these widespread and prolonged crises. Venezuela is a unique case as its nutritional context has changed dramatically in the past 10 years due to political turmoil and massive inflation. Prior to the crisis, the burden of cardiometabolic diseases including type 2 diabetes (T2D), hypertension, and obesity were documented to be increasing over time, particularly in urban areas. Over the past few years, however, the NCD burden has been especially hard to quantify, as the Venezuelan government has stopped publishing national statistics since 2016. To better understand the prevalence of cardiometabolic diseases on a national scale, a group of Venezuelan researchers conducted the first nationally representative survey of health called EVESCAM (Estudio Venezolano de Salud Cardio-Metabólica) from 2014-2017 and conducted a follow-up study in 2018-2020. My dissertation uses EVESCAM data to document the management of cardiometabolic diseases among Venezuelans affected by the humanitarian crisis who were not displaced. It also seeks to understand how modifiable risk factors may play a role in management and prevention, to inform future research, interventions, and policy in fragile contexts. Paper One describes the dietary intake of Venezuelans using baseline EVESCAM measurements (2014-2017). My co-authors and I conducted a survey-weighted, nationally representative analysis of dietary, sociodemographic, and clinical data from Venezuelans ≥20 years of age (n=3,402) to understand the prevalence of risk factors for cardiometabolic diseases in this population. Despite a high prevalence of cardiometabolic diseases, adults in Venezuela had not experienced a nutrition transition as observed elsewhere in Latin America. Dietary diversity was low and traditional foods (e.g., arepas and cheese) were still widely consumed, whereas Western foods (e.g., sugar-sweetened beverages) were consumed infrequently. Paper Two compares multimorbidity patterns in Venezuela with Mexico and US Hispanics using three nationally representative datasets: baseline EVESCAM (2014-2017), the 2016 Mexican National Health and Nutrition Survey (ENSANUT), and Hispanics in the 2015-2016 and 2017-2018 U.S. National Health and Nutrition Examination Surveys (NHANES). To compare multimorbidity between these three settings, we conducted logistic regression to understand the role of sociobehavioral factors in odds of multimorbidity and visualized patterns of multimorbidity using the prevalence of the most common two- or three-disease combinations in each country. We found that even during a humanitarian crisis, multimorbidity prevalence among Venezuelans in EVESCAM was lower than that of Hispanics in the US NHANES sample. Paper Three examines changes in diabetes management during the crisis in Venezuela. We first documented the status of type-2 diabetes management in baseline EVESCAM (2014-2017) using the continuum of care framework. We then assessed changes in health system performance over time, from 2014-2017 to 2018-2020. Finally, the association between sociodemographic characteristics and care continuum stage was quantified. Care continua included up to six stages: all diabetes; diagnosed; treated; achieved glycaemic control; achieved blood pressure, cholesterol, and glycaemic control; and achieved aforementioned control plus non-smoking. This study was among the first longitudinal continuum of care analyses for diabetes and documented that while treatment rates declined substantially in Venezuela, management of diabetes was not as severely impacted as expected among individuals in EVESCAM during this humanitarian crisis. Together, these three papers show a variety of quantitative methods to describe and document the state of NCD care in Venezuela, providing important lessons on how NCD management fared in a unique but generalizable crisis setting. Chapter Five highlights the strengths and limitations of this dissertation, as well as the implications of this work and directions for future research.

Abstract: Background: Unhealthy diet is a well-established risk factor for developing many physical health conditions in adolescents (e.g., obesity, type 2 diabetes). Evidence begins to emerge that unhealthy diet might also be implicated in the development of common mental disorders. While there is a plethora of high-quality prospective studies on the association between diet and mental disorders in adults, such studies in adolescents are scarce. The already high and rising burden of mental disorders in adolescents necessitates a careful examination of diet as a potential target for interventions to improve mental health in adolescents. The overarching goal of this dissertation was to estimate the effect of diet (alone and in combination with other lifestyle behaviours, including substance use behaviours) on mental health in Canadian middle adolescents (i.e., 14-17 years old). Methods: The goal has been achieved in a series of four interconnected research papers that utilized data from the Cannabis, Obesity, Mental health, Physical activity, Alcohol, Smoking, and Sedentary behaviour (COMPASS) study – a large longitudinal study which annually collects survey data from ~60,000 grade 9 to 12 high school students in British Columbia, Alberta, and Ontario, and Secondary I-V students in Quebec. Results: The systematic review in Chapter 2 revealed several methodological concerns in existing studies: i.e., inadequate adjustment for established confounders and unnecessary adjustment for intermediate variables, and the need for sensitivity and sex-based subgroup analyses. Studies identified in this evidence synthesis, along with those identified in another ongoing systematic review (PROSPERO CRD42021246478), informed a list of covariates that likely confound the diet-mental health association in adolescents: i.e., mental health at baseline, socio-economic status, age, eating behaviours, lifestyle behaviours (i.e., physical activity, sedentary behaviours, sleep, and substance use behaviours, including tobacco smoking, vaping, cannabis and alcohol use), and social support. Analyses in a sample of 13,887 COMPASS study participants (Chapter 3) were adjusted for this set of confounders. Analyses revealed a small negative effect of sugar-sweetened beverages (SSB) consumption on depressive and anxiety symptoms, as well as a small positive effect of vegetables and fruit consumption on psychological wellbeing. In Chapter 4, the focus was on dietary trajectories in vegetables and fruit and SSB consumption in relation to depressive and anxiety symptoms in a prospective cohort panel of 5,653 COMPASS participants who provided their responses in three consecutive waves of data collection. Analyses showed that the consumption of VF and SSB changed for the worse over time, and that the rate at which these changes happen was associated with the severity of depressive symptoms (but not anxiety symptoms). Finally, in Chapter 5, a holistic approach was taken to account for the synergistic effect that a comprehensive range of co-occurring unhealthy lifestyle behaviours might have on mental health. Indeed, when considered in combination, meeting more recommendations was generally associated with lower severity of depressive and anxiety symptoms at one-year follow-up. Conclusion: The results of this thesis highlight the need for dietary interventions (particularly those implemented at the policy level, such as taxation of SSBs, banning food marketing to children, and subsidizing healthy foods to low-income families, among others) as part of comprehensive population-level primary prevention strategies, which target other lifestyle behaviours as well, to improve mental health in adolescents.

My research is concerned with decision making in the presence of peer spillovers. Peers’ behavior can change each other’s incentives or levy externalities on one another, thereby complicating decision making as well as the estimation of primitives from observations of decisions. In my dissertation, I address instances of the resulting challenges in topics ranging from public health and development economics to the study of making friends and contacts. The first paper explores the optimal distribution of a limited number of preventative treatments (e.g., vaccines) for deadly infectious diseases such as malaria or Ebola among individuals on a network. While the literature in economics has considered the optimal distributions of treatments in the presence of heterogenous treatment effects, the main contribution of my paper lies in accommodating for spillovers in treatments. I extend the empirical welfare maximization (EWM) protocol to do so. EMW estimates an optimal rationing rule using data from a randomized control trial (RCT). I start by explicitly modeling disease propagation on contact networks. In two separate models with distinct assumptions that are separately compatible with malaria and Ebola, I place restrictions on how others’ treatments affect one’s outcome as well as assumptions on the shapes of networks considered. I show that as the size of the experiment grows, EWM assigns the treatments to the same nodes on the network as would a planner with complete information on which nodes had the greatest impacts on the population as a whole. I also show that there can exist no statistical procedure with a faster rate of convergence. The second paper considers the role of incentives in Joint Liability Lending (JLL) microfinance programs. JLL is a common loan contract offered, particularly in South Asia. The basic premise is that participating households organize into groups to receive a joint liability loan. In such a contract, the obligation of repaying the loan falls collectively on the group and not on individual members. If the group fails to repay, the lender refuses to offer any member of the group a loan thereafter. Using a game theoretic model, I am able to demonstrate an atypical inefficiency arising in equilibrium where peer pressure leads to excessive repayment. I demonstrate that this excessive repayment, often heralded as a measure of success of the program, inefficiently shifts the burden of risk on to the participants and away from the lender. I then demonstrate that this results in participants using the loan for inefficiently safe investments rather than investments which would increase their productive capacity. Thus, I argue that the informal incentives in the form of peer pressure that JLL leverages to induce high repayments also lead to incentives that do not allow borrowers to escape poverty. In the final paper, joint with Francesca Molinari, we consider identification and estimation of models of network formation. We construct a sharp identified region for parameters of the network formation game under the assumptions that individuals’ preference are only over local network topologies and not the entire network. In particular, we assume that every individual can have a fixed finite number of links and has preferences from links between nodes up to a fixed finite distance on the network. This allows for testing important drivers of social link formation. During an epidemic, it is very desirable to understand how the network of social interactions evolve as measure like social distancing and quarantining are put into effect. A pre-requisite to doing so is the identification and estimation of network formation games. Hence this paper bridges a gap in the literature on identifying models of network formation.

Introduction/Background: Hispanic subgroups are often grouped under the combined Hispanic global term, preventing us from identifying any differences or disparities within that group that might exist. As California currently has the largest collectively identified Hispanic population in the US at 39%, data maintained for California has an adequate sample for the study of subgroups within this population for differences in health and illness. This paper will examine cancer-related survival involving the eight major cancer sites: colon, rectum, stomach, liver, female breast, prostate, ovary, and cervix. This study aims to discern whether there are differences in cancer-related survival in the following Hispanic subgroups: Mexican, Puerto Rican, Cuban, Southern or Central American, and other Spanish/Hispanic origin. Methods: Data was gathered from the California Cancer Registry (CCR) using 2004-2017 to conduct a retrospective longitudinal population-based cohort study. The following patient characteristics were obtained: race/ethnicity, age at diagnosis, year of diagnosis, gender, insurance type, socioeconomic status (SES), marital status, type of hospital where treatment was received, adherence to treatment status, tumor stage, and tumor grade. Cancer types included both male and female cancers: colon, rectum, stomach, liver, prostate, female breast, ovary, and cervix. A multivariate proportional hazards model was used to perform a cancer-specific survival analysis while controlling for numerous potential confounders. Non-Hispanic white (NHW) cases were used as the comparison group for each Hispanic subgroup. There were no comparisons between Hispanic subgroups themselves. Results: Between 2004-2017, 420,671 cases of cancer were identified. Of these, 306,262 (72.8%) were NHW, 34,897 (8.3%) were Mexican, 647 (0.2%) were Puerto Rican, 698 (0.2%) were Cuban, 9,638 (2.3%) were South or Central American, and 68,528 (16.3%) were other Spanish/Hispanic origins. Compared to NHW cases, Mexican race/ethnicity was associated with better survival for colon (HR 0.89, 95% CI 0.84-0.96, p=0.0008) and liver cancer (HR 0.88, 95% CI 0.82-0.95, p=0.0006), but Mexican race/ethnicity was associated with worse survival for stomach cancer (HR 1.19, 95% CI 1.10-1.27, p

Male infertility is a significant public health problem. Although male factors are estimated to contribute to 50% of infertility, epidemiologic research on predictors of male infertility is scarce, and few modifiable risk factors have been identified. In particular, not much is known about the risk factors that determine semen quality in healthy males attempting to conceive. This dissertation uses data from Pregnancy Study Online (PRESTO), a preconception cohort of pregnancy planners residing in North America, to examine the role of several anthropometric and lifestyle exposures on semen quality. A subset of male participants provided data on semen volume, sperm concentration, and sperm motility using a novel in-home semen testing device. In the first study, we examined the effects of three anthropometric factors, body mass index (BMI), waist circumference, and weight gained since age 17 years, on semen quality. We found that men in the highest categories of BMI and waist circumference had poorer semen quality, particularly sperm concentration, motility, and total motile sperm count. Results were slightly stronger for waist circumference. Adult weight gain, however, was not appreciably associated with semen quality. Few studies have investigated the effect of marijuana use on semen quality. In the second paper we used PRESTO data to investigate the relationship between current marijuana use and semen parameters. We found that current male marijuana use was not appreciably associated with semen quality. Further control for potential confounders, including BMI, had little influence on the study results. In addition, results were similar among non-smokers of tobacco. The third paper focused on sugar-sweetened beverages (SSB) consumption and semen quality. We found that men who consumed higher quantities of SSB had poorer semen quality, particularly lower sperm concentration, total sperm count, and total motile sperm count. Adjustment for caffeine intake or current BMI had little effect on the results; however, the association between total SSB consumption was stronger among overweight and obese men. In conclusion, we observed that higher BMI and waist circumference were associated with decreased semen quality. In addition, increased sugar-sweetened beverage consumption may increase the risk of being classified as having low semen quality. Given that these exposures are common and modifiable, they may be important targets for public health interventions.

The physiological, biological, and metabolic impacts of food insecurity experienced in childhood may influence health throughout the lifecourse. In this three-paper dissertation, we explore whether a cohort of Black and White women’s experiences of childhood food insecurity are associated with their weight in young adulthood, their weight in midlife, as well as the weight of their children. In addition, we also investigate whether a direct federal income transfer program targeting families with children can improve food insecurity parameters in Canada, particularly among economically vulnerable groups. Paper 1 and Paper 2 derive data from one site of the National Heart, Lung and Blood Institute Growth and Health Study (NGHS). NGHS is a longitudinal cohort that recruited 883 9-10-year-old Black and White girls in 1987/8 from Contra Costa County, California. Participants provided health, lifestyle, and anthropomorphic data from annual clinic visits and questionnaires for ten years (through 1997/8). From 2015-2019, researchers re-recruited 624 original participants (ages 36-43) and 559 of their children (boys and girls, ages 2-17) to participate in a second wave, which implemented a retrospective measure to gauge the frequency in which the quantity and diversity of their available food was impacted by resource shortages from ages 5-11. We used responses to characterize experiences of childhood food insecurity.Paper 1 assesses the relationship between childhood food insecurity and Body Mass Index (BMI) in young adulthood (age 18-20) and midlife (age 36-43) among Black and White women. We identified a higher average BMI among Black women reporting moderate childhood food insecurity than Black or White women reporting full food security in young adulthood (N=593) that abated by midlife. As well, a substantially larger average BMI among White women reporting severe childhood food insecurity compared to White women reporting full food security during midlife (N=617). These findings suggest that childhood food insecurity may have a lasting association with weight status and that racial differences and age moderate the relationship between childhood food insecurity and BMI. Paper 2 investigates whether maternal childhood food insecurity is associated with odds of overweight/obesity among offspring (N=483), presenting findings for effect modification by age (continuous), current household food security status (food secure vs. food insecure) and maternal race (Black or White). We found no significant difference in the odds of overweight/obesity among most levels of food insecurity, but significantly lower odds among children whose mothers reported moderate child food insecurity. This relationship was strongest among children currently living in food secure homes, with White mothers, and between the ages of 2-5, respectively. We believe that mothers’ desire to protect their children from their own adverse experiences may serve as a protective factor against food and dietary behaviors that may increase overweight/obesity risk.Paper 3 assesses whether the roll-out of the Canada Child Benefit (CCB), a federal direct income transfer program, offered protection against food insecurity among Canadian households with children among three groups with different income thresholds: households reporting any income (N=41,455), the median income or less (N=18,191) and the Low Income Measure (LIM) or less (N=7,579). Data are derived from the Canadian Community Health Survey (CCHS), an annual, cross-sectional study that collects health, sociodemographic, and health-related information at the sub-provincial level from a representative sample of Canadians. Households with children experienced greater drops in the likelihood of experiencing severe food insecurity following CCB than those without, most dramatically among those reporting the LIM or less, which suggests that CCB disproportionately benefited families most susceptible to food insecurity. As well, that food insecurity may be impacted by even modest changes to economic circumstance, speaking to the potential of income transfers to help people meet their basic needs.

Background: Persons who inject drugs (PWID) are at increased risk for infectious diseases and overdose, and need access to primary care and substance use disorder (SUD) services. Yet, PWID historically have avoided and delayed seeking care, in part due to lacking insurance coverage for services they need and an availability of these services at local clinics. The Affordable Care Act (ACA) made insurance mandatory and included SUD services as an essential health benefit.Objectives: This dissertation research sought to examine the impact of the implementation of the ACA on the use of SUD treatment (Chapter 2) and primary care services (Chapter 3) among PWID in San Diego. It also sought to understand the changes in offering of SUD services at community and free primary care clinics after this health reform was implemented (Chapter 4). Methods: This dissertation is comprised of three papers assessing different aspects of health service use among PWID in San Diego County. Papers one and two (Chapters 2 and 3) used data from a longitudinal cohort study of 576 PWID in San Diego (STAHR 2 Study) to determine the impact of the ACA on the use of SUD treatment and the use of primary care services, respectively. Paper three (Chapter 3) used facility-level data on community and free primary care clinics in San Diego County from the California Office of Statewide Health Planning and Development to understand changes in offering of SUD services at these clinics after the ACA compared to before. Results: For paper one (Chapter 2), there was an increase (12%) in use of SUD treatment after the ACA compared to before, with a similar increase (10%) in insurance coverage. The ACA was associated with greater use of SUD treatment among PWID and the strength of this association was not impacted by insurance coverage. For paper two (Chapter 3), there was an increase (4%) in primary care use after the ACA compared to before, with a much larger increase (24%) in those who had insurance coverage. The ACA was associated with greater use of primary care services among PWID and the strength of the association was not entirely explained by an increase in insurance coverage. Paper three (Chapter 4) showed an decrease of 7% in the number of community and primary care clinics that offered SUD services after the ACA compared to before, but an increase in the proportion of patients covered by Medi-Cal and had contact with a substance abuse counselor. Conclusion: These findings suggest that the ACA may have been an effective health policy for increasing access and use of essential health services among PWID in San Diego, and for bolstering SUD services in community and free primary care clinics.

Slums / Informal Settlements (SIS) are data poor environments that also pose one of the greatest global health risks, including a wide range of infectious and chronic diseases, with limited on-the-ground public health intervention. One issue, especially when exploring SIS related land use and environmental changes is the coarseness of the geographic data, which though useful for broader assessments does not provide help for finer scale intervention support. While individual SIS settings differ, leading to geographically differing risks, a common theme running through all such environments is the lack of fine scale dynamically collected data that can guide public health intervention strategies. Understanding the contextualized locations and temporal changes of these types of features, especially those associated with water, sanitation, and hygiene (WASH) are vital if we are to understand the health risks posed.To address the spatial data deficiency in SIS type environments, two new methods were employed: spatial videos (SVs) and spatial video geonarratives (SVGs) were used to investigate localized disease-causing environments for two SIS in Kenya and Ghana. The cost effectiveness of these techniques means that no space should be data unreachable. For each location, a separate research project was presented including justification, local setting, methods and analysis, results, and field collection limitations. All three papers included in this dissertation are original works and employ the use of novel techniques to investigate environments that would have otherwise not have access to such fine scale mapping.

Infertility, defined as the inability to achieve clinical pregnancy after ≥12 months of regular unprotected intercourse, is a growing problem in North America and the world. Estimates place the percentage of couples experiencing infertility at around 15% in North America. Currently, the U.S. health care costs for infertility treatment exceed $5.5 billion, with these costs expected to increase as more couples use assisted reproductive technologies (ART). Additionally, fertility issues are associated with psychological and financial hardship for affected couples, and ART use has been associated with adverse pregnancy outcomes. One vital area of research that has been drastically understudied is male fertility. Male factors are found to contribute to 30-50% of all infertility diagnoses, but the vast majority of studies focus on women. This dissertation uses data from Pregnancy Study Online (PRESTO), a preconception cohort study of pregnancy planners from North America, to examine the role several male exposures have on fertility. In the first study, we examined the association between a history of diagnosed depression, current depressive symptoms, and psychotropic medication (PM) use with fecundability. We found that a history of diagnosed depression, as well as currentvi depressive symptoms, showed slight evidence of an association with decreased fecundability, though this result was compatible with chance. Current psychotropic medication (PM) and antidepressant use were associated with reduced fecundity, particularly among those with current depressive symptoms. Current PM and selective serotonin reuptake inhibitor (SSRI) use mediated part but not all of the relationship between current depressive symptoms and fecundability. In the second paper, we studied the role of testicular heat exposure in declining fertility. We estimated the extent to which selected male heat exposures, including use of saunas, hot tubs, and hot baths; use of restrictive underwear; time spent sitting; use of car seat heaters; use of a laptop computer on one’s lap; and fever within the last 3 months affected fecundability. Additionally, we attempted to create a composite heat score to measure cumulative heat exposure. We found small inverse associations for sauna use, hot tub/bath use, and seat heater use in the winter with fecundability. Additionally, we found evidence of threshold for overall exposure to multiple heat factors. The third paper focused specifically on occupational stress exposure, an understudied source of exposure to stress. These occupational stressors included employment status (employed or unemployed), number of hours worked, time of day mainly worked, and a measure of job independence. We found that working non-daytime shifts and being unemployed were associated with slightly decreased fecundability in men. However, total hours worked per week and job independence score showed little relation to reduced fecundability

In 2019, the Emergency Medical System (EMS) employed over 20,000 personnel in the state of Georgia. EMS personnel were often exposed to unsafe working conditions while caring for injured patients, emphasizing that the workplace served as a potential occupational health intervention site. At the time of this study, there was no surveillance for EMS personnel’s employee wellness or any solutions to improve psychosocial wellness in the workplace in Georgia. The purpose of this quantitative, cross-sectional study was to determine the association of current physical and mental health outcomes in Georgia EMS personnel, as it relates to the presence of workplace wellness strategies and work-related stressors. Our study presented the findings of health help-seeking behaviors and coping skills regarding workplace support by geographic area, gender, age, and license level. The online and paper surveys were distributed to EMS personnel across Georgia’s hospital-based, municipal, and private EMS agencies. The sample included 218 participants who consented to participate in the study. For modeling purposes, the completed sample (114 participants) were included within the full analysis (54.2% completion rate). Descriptive statistics, T-test, F-test, linear, and linear regressions were conducted. During COVID-19, participants reported significant exposure to traumatic incidents at work (N=116, 96%), having low social support (scored 2.93 out of 5 points), and increased use of avoidant coping skills (scored 6.2 out of 8 points). Among all participants, sleep at work was less than 1.7 hours less than when sleep at home (t-test=25.75, p-value

Emerging infectious diseases (EIDs) pose a significant threat to public health, with thefrequency of emergence events increasing in recent decades. The vast majority of EIDs are zoonotic, meaning they transmit between animal and human hosts. We applied methods in genomics, epidemiology, and ecology in field, laboratory, and computational settings to study the dynamics and evolutionary underpinnings of zoonotic transmission and emergence in wildlife and human populations. Specifically, we used statistical modeling to analyze zoonotic risk, developed a DNA methylation assay for estimating chronological age in bats to support age-seroprevalence modeling of bat viruses, and mathematically analyzed pathogen-host coevolution in an adaptive dynamics framework.Prior to this doctoral dissertation research, my master’s thesis highlighted the growingrisk that humans introduce zoonoses to new geographic areas where the imported pathogens can then ‘spill back’ to infect local wildlife. We reviewed ecological mechanisms underlying the emergence of novel enzootic cycles and made the case that modeling approaches can provide critical insights in the face of empirical limitations. This paper set the stage for my doctoral dissertation focus on the interdisciplinary study of zoonotic pathogens. The first dissertation chapter statistically analyzed zoonotic risk across mammalian, directly transmitted zoonotic viruses, delineating host and viral traits predictive of the severity of disease they engender in the human population (‘virulence’) and in their capacity for sustained human-to-human transmission post-emergence. We found that animal hosts most distantly related to humans—in particular, order Chiroptera (bats)—harbor the most virulent zoonoses with a lower capacity for endemic establishment in human populations.The second chapter built off this analysis, increasing our sample size to include avian andvector-borne viruses and additionally analyzing variation in the total number of human deaths caused by each virus (‘death burden’). We found that bats still harbored the most virulent viruses, but death burden did not correlate with any reservoir group and instead, was a function of viral traits. Nevertheless, these statistical analyses suggest that bats offer a study system that is both highly relevant to public health and valuable for understanding the evolutionary and transmission dynamics of zoonotic pathogens.The third chapter presented a hybridization capture-based target enrichment strategy forestimating the chronological age of bats from DNA methylation (DNAm) profiles. Many mechanistic epidemiological and population models in wildlife rely on age data, traditionally estimated via mark-recapture surveys, body measurements, lethal sampling of bone density, or tooth analyses—methods that are often prohibitively resource-intensive, imprecise, or impractical. Our DNAm assay offers a cutting-edge alternative, requiring just a single, noninvasive DNA sample. This chapter is an important first step in increasing epidemiological and population modeling capacity in bat populations.The fourth and final chapter contributed a theoretical perspective to our understanding ofthe evolutionary dynamics of zoonotic transmission and emergence through an adaptive dynamics framework. Specifically, we analyzed how the interplay between parasite-host coevolution, population dynamics, and epidemiology influence the optimal parasite growth strategy and host investment in constitutive (always present and costly) as opposed to induced (activated and costly only upon infection) defense. Critically, we provide the first theoretical framework that considers both coevolutionary and population-level dynamics, examining trends across host competition and natural mortality rates when the parasite does not directly affect host fertility, as well as when the parasite is a castrator. We show that incorporating host-parasite coevolution into our model captures feedbacks between the host immune and parasite growth strategies that are missed when only the host is allowed to evolve. Furthermore, we find that whether the parasite affects host reproduction significantly impacts host-parasite coevolution; when the parasite is a castrator, selection on the host is often largely geared towards minimizing reproductive costs—either by investing in immunity to avoid infection or recover when parasite prevalence is high, or by reducing investment in reproductively costly constitutive defense when the parasite prevalence is low.

Starting late in 2019 in the Wuhan province of China, COVID-19 has become a pandemic in the last few years. We use mathematical and statistical modeling in the hope of proving that self-exciting models perform better than SIR-family models when it comes to modeling in Epidemiology. We take a look at two models, the SQUIDER compartmental differential equation model, and also the HawkesN self exciting process model. For training the SQUIDER model, we minimize the Sum of Square Errors between actual and predicted cumulative cases and deaths, and use weights to account for the cumulative cases, and cumulative deaths, respectively. In forecasting, we use fitted parameter values and the true case counts at the end of each lag, and forecast forward 3-days, and take the RMSE between the estimate forecast and the actual case counts of COVID-19. We fit the HawkesN model by using a Least Squares algorithm to fit the data we have and use an algorithm proposed in another paper to simulate the HawkesN method. Similar to the forecasting of the SQUIDER model, we take 10 3-day forecasting periods with a lag of 1 day through 10 days, and then calculate the RMSE. Taking a look at data from the CDC website, we fit and forecast for Oregon, South Carolina, and Washington State, and indeed see that except for a very few cases, overall the HawkesN process performs a lot better than the SQUIDER model in forecasting the daily cases of COVID-19.

Introduction. Coronavirus Disease 2019 (COVID-19) poses a major global threat to human beings, which has caused devastating consequences of population health, political, and economic crises in many countries. This dissertation was composed of three research activities to study the following aims: (1) review the existing literature focusing on political factors and health outcomes of COVID-19; (2) assess the relationship between democracy and case fatality rate of COVID-19 by controlling for the effect of age, comorbidity, health expenditure, healthcare workforce, and population density; and (3) identify the trajectory pattern cases peak days, deaths peak days, and peak periods. Methods. We accessed data from the World Health Organization (WHO), World Bank, Johns Hopkins University, and the Democracy Index 2019 database. First, we conducted a systematic review that searched three databases and synthesized the articles about democracy and health outcomes of COVID-19. Second, we analyzed data from 148 countries with at least 2,000 confirmed cases of COVID-19 by October 25, 2020. Multiple linear regression was used to examine the association between the Democracy Index and case fatality rate of COVID-19 while controlling for other variables, most notably the age distribution of the population. Lastly, we used the patterns of data at the early onset of COVID-19 from seven countries to estimate the time lag between peak days of cases and deaths. Results. Our first research found that of 170 publications in the databases search, 12 publications were screened for systematic review. Among them, one study reported no association between democracy and health outcomes of COVID-19. Eleven articles claimed there was a relationship between democracy level and outcomes of COVID-19. Two papers reported negative associations between democracy and adverse outcomes of the population, while the other nine articles claimed there were positive associations between democracy and the poor health status of populations. When examining the relationship between democracy and health outcomes of COVID-19, the second research demonstrated that the number of hospital beds, the proportion of population above age 65, and current health expenditure as a percentage of the gross domestic product (GDP) are significantly related to the case fatality rates of COVID-19 across 148 countries (p < 0.05). The Democracy Index was not statistically related to the case fatality rates of COVID-19 when considering all 148 countries analyzed but was negatively associated with case fatality rates among 47 high-income countries. In addition, the healthcare workforce, population density, and comorbidity were not statistically significant among the 148 countries. Finally, the findings in the last research suggested that comparative analyses of data from different regions and countries reveal the differences between peaks of cases and deaths caused by COVID-19 and the incomplete and underestimated cases in Wuhan. Different countries may show different patterns of cases peak days, deaths peak days, and peak periods. Error in the early COVID-19 statistics in Brazil was identified. Conclusions. This research is the first to our knowledge to study the relationship between democracy and health outcomes of COVID-19 across countries with large sample sizes. According to the multicountry data, the cross-sectional study suggests that enhancing healthcare system facilities is vital to improving clinical outcomes. Protecting the population older than 65 and adjusting the health expenditure budget may need to be considered. The findings suggest that in high-income countries the higher democracy index is associated with more deaths from COVID-19, perhaps due to the decreased ability of the government to control the movement and behavior of its citizens. Besides, the simulated graphical trajectory method identifies statistical biases in surveillance data. This approach incorporates all sources of available data and provides a robust method to characterize the time course of an infectious disease. Regions and countries beginning with high mortality rates from the COVID-19 epidemic will suffer a long, painful period of the disease epidemic. Where the mortality rate is relatively high, healthcare professionals should prepare for a longer period of fighting this pandemic. Data quality is key to case fatality rate estimation which is needed by policymakers to make correct and timely critical decisions.

Research focusing on neighborhood effects on health often fails to connect aspects of the neighborhoods which contribute to disparities, and the mechanisms in which social processes and the built environment affects the lives of individuals. The purpose of this dissertation is to explore the neighborhood risks affecting health and well-being for the pediatric population in Akron, Ohio, through novel methods in geospatial technologies. Within the context of injury prevention and childhood lead exposure, I explore factors which impact children living in Akron through the collection, mapping and analysis of data at a granular spatial scale. The first of the three studies is focused on the use of spatial video in assessment of child behaviors and injury surveillance for active school transport immediately before, during and after an intervention (at three time periods) as part of International Walk to School Day at one Community Learning Center (CLC) in Akron, Ohio. This paper analyzes data generated from coding spatial video in a GIS for variables related to child characteristics, activity, location, and the surrounding environment to identify behaviors and aspects of the built environment which may contribute to unintentional injuries during active school transport. The focus of the second study is to investigate aspects of properties that may contribute to lead exposure through the development of an Environmental Lead Index (ELI). Spatial video was coded for the presence of eight variables and summarized to create a number value. Blood lead levels, extracted from the EMR as lead test results, were used to assess the validity of the ELI. Additional insights into the challenges affecting this diverse pediatric population, such as a residential mobility rate over 70 percent, are provided through a descriptive analysis of the study population, which includes a growing immigrant population. The last paper concentrates on the challenges associated with residential mobility in a pediatric population, as it relates to childhood lead exposure using statistical and geospatial analysis. For this study data extracted from the EMR includes all addresses recorded within the patient record, during a three and half year period. Statistical and geospatial analysis is conducted at the patient level and the property level. Spatial analysis provides insight into distance moved and identifies addresses which house more than one child with an EBL. Visualizations are provided to highlight spatial patterns in patient mobility. The results of the nuanced and granular approaches applied here include methodologies for collecting and analyzing data, both qualitative and quantitative, that advance sub-neighborhood scale health research, and at the same time will provide data to support community advocacy and policy decision-making.

Adherence to medications for HIV prevention and treatment is essential to reducing HIV transmission risk and improving health outcomes. Adherence to these medications remain insufficient in several key populations, however. Understanding how partnership types and dynamics may encourage or hinder HIV medication adherence is necessary to improving adherence rates among important sub-groups, including young men who have sex with men (YMSM), serodiscordant couples, and adolescent girls.My first paper identified the partnership and housing factors associated with adherence to oral PrEP among YMSM. PrEP adherence was relatively low in the study, declining from 46% at baseline to 39% at study conclusion. PrEP adherence was significantly associated with increasing age (OR=1.35; 95% CI: 1.14, 1.60), and race (African-Americans vs. other OR=0.37, 95% CI: 0.21, 0.66). Relationship type, length, and depth, number of partners, and partner’s HIV status were not significantly associated with adherence. PrEP adherence was associated with housing insecurity, including ever being kicked out of the home (AOR=0.43; 95% CI: 0.18, 1.04), and the Housing Insecurity Index (AOR=0.64; 95% CI: 0.44, 0.93). PrEP adherence was also associated with privacy, including number of people living in the residence (AOR=0.82; 95% CI: 0.71, 0.95), sleeping in a private bedroom (AOR=2.10, 95% CI: 1.01, 4.40), and the Lack of Privacy Index (AOR=0.82; 95% CI: 0.71, 0.95). YMSM did not modify their PrEP-taking depending on relationship risk. Housing insecurity and lack of privacy may hinder PrEP adherence among YMSM.My second paper determined whether HIV viral suppression was associated with partnership status and partnership support among HIV-positive individuals and serodiscordant couples in Brazil. Viral suppression did not significantly differ between HIV-positive partnered (79% virally suppressed) and unpartnered (76% virally suppressed) individuals. Among individuals in partnerships, viral load suppression was significantly associated with having partners who attended monthly visits (AOR=2.99; 95% CI: 1.00, 8.93); among women in partnerships, viral load suppression was significantly associated with having a partner who actively reminded them to take ART (AOR=2.67; 95% CI: 1.04, 6.88). Practical measures of social support, including attending monthly visits and reminding a partner to take ART, may improve viral suppression among HIV-positive individuals in serodiscordant partnerships.My third paper assessed the product, relationship, and sex factors that affect acceptability of a vaginal ring (VR) for HIV prevention among adolescent girls aged 15 to 17 years. Product factors were most frequently mentioned as barriers to VR acceptability. Many participants reported concerns about the large size of the VR upon first impression, and some reported pain with VR insertion. Several participants reported concerns regarding cleanliness of the VR, particularly during menstruation. Relationship factors rarely appeared to act as barriers to VR acceptability; the majority of participants disclosed VR use to their sexual partners, and positive reactions from sexual partners regarding the VR were common. Emotional and/or physical discomfort surrounding VR use during sex was mentioned occasionally as a potentially barrier to VR acceptability.Relationship factors appear to be important in several populations for adherence to HIV-related medications. YMSM in high-risk sexual relationships may not modify PrEP-taking, leaving them at risk for HIV acquisition. Among serodiscordant couples, practical measures of partnership support may improve ART adherence and promote viral suppression. While adolescent girls most often reported that product-related factors inhibited VR acceptability, lack of partnership disclosure, negative partner reactions, and discomfort during sex may hinder VR acceptability among some girls.

Poor nutrition is a leading cause of disease and death in the United States and around the world. Two key types of poor nutrition are food insecurity (a lack of reliable access to nutritious food) and obesity (excess adiposity). They are both prevalent, costly, and can have serious health consequences. This dissertation focuses on these interrelated public health nutrition issues, using rigorous epidemiological methods to examine their health effects and identify policy and programmatic approaches that may meaningfully reduce their burden in the population. We first examine the potential impact of voluntary sugar reduction targets for packaged foods and drinks set by the National Salt and Sugar Reduction Initiative. Using nationally representative data from the National Health and Nutrition Examination Survey, we find that the targets are expected to result in meaningful reductions in added sugar intake among children and the initiative is not projected to widen existing diet-related disparities. Next, we examine the longitudinal relationship between food insufficiency – a screener measure related to food insecurity – and cardiovascular disease risk factors using data from the Coronary Artery Risk Development in Young Adults Study. We find that experiencing food insufficiency appears to worsen health over time, particularly among women and for obesity-related measures such as BMI and waist circumference. Finally, we leverage administrative data from the Massachusetts Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) to examine shopping patterns related to redemption of food package benefits. We find that retail-based initiatives may need to target a wide range of store types in order to reach all WIC households and that efforts aimed at improving redemption may be especially important for WIC shoppers relying on superstores. While the focus and scope of these papers varies, they each identify drivers and points of intervention for food insecurity and obesity. This work underscores the importance of conducting epidemiological research to aid in the development of policies and programs to reduce the burden of food insecurity and obesity in the population.

Leishmaniasis is a neglected tropical disease which affects millions of people every year across 6 continents. Current antileishmanial drugs have become less effective due to resistance, have a high toxicity, and are too expensive for many lower socioeconomic countries. New drug candidates can be explored and synthesized by natural drug synthesis and high throughput screening (HTS). This paper aimed to explore both methods in search of novel antileishmanial compounds. For the natural product approach, the ABC ring of berberine will be optimized to improve its antileishmanial properties. For the HTS approach, a piperazine based small molecule has been synthesized and will be evaluated for its antileishmanial properties.

Healthcare-associated infections (HAI) are a major cause of morbidity and mortality and a public health priority. However, standard procedures and comprehensive guidelines for HAI outbreak detection and response are still needed. This hybrid thesis describes what is known about HAI outbreaks in the introduction, reviews the HAI outbreaks reported to New Mexico Department of Health (NMDOH), in the first paper, and then in the second paper examines how established methods for detecting infectious disease outbreaks perform in identifying Clostridium difficile infection (CDI) outbreaks in long-term care facilities (LTCF) in Bernalillo County, New Mexico, and finally, it closes with our overall conclusions at this time from this work. Our main findings are that gastrointestinal illness, most commonly norovirus, in LTCFs is most likely to be reported and that in LTCFs the least complex threshold method performs with the highest sensitivity and specificity in detecting possible CDI outbreaks.

Among Aboriginal people of Australia, diagnosis rates of sexually transmissible infections (STIs) are an example of the health disadvantage faced by this population. Diagnosis rates are between three and 50 fold higher than non-Indigenous Australians. Further there is a trend of divergence in HIV diagnosis rates, and in 2015 rates were more than double in the Aboriginal population than non-Indigenous rates. Despite much effort to reduce both incidence and prevalence of STIs in the Aboriginal population, there have been limited success. To contribute to addressing the gaps in research, this thesis examined both causes and impact of interventions to reduce STIs in this population. Chapter 1 is a review of STI epidemiology literature among Indigenous populations. Chapters 2 and 3 are papers from a national survey of 2,877 young Aboriginal people regarding sexual health. Chapter 2 describes the methods, implementation and demographics of the study. Chapter 3 is an analysis of this study, describing prevalence and correlates of participants who reported ever been diagnosed with an STI. Early sexual debut, inconsistent condom use and identifying as gay were significantly associated with a previous diagnosis. Chapter 4 describes Aboriginal peoples’ attendance, testing and positivity outcomes for chlamydia obtained from four primary health care settings. We found highest testing rates in sexual health clinics (80%) and lowest in general practice (5%) and higher positivity rates among Aboriginal people across all settings. Chapter 5 is an analysis of data from the STRIVE study, showing low rates of HIV testing (32%) conducted after a positive diagnosis for other STIs (n=15,260), demonstrating the need for improved clinical governance in this setting. Chapter 6 is a review paper assessing HIV prevention efforts among Aboriginal people in the first 25 years of the epidemic in Australia, and highlights the trajectory forward in prevention. The STRIVE Study Protocol is included in Chapter 7. This stepped wedge cluster randomised trial developed and implemented a sexual health quality improvement program in 68 remote communities with a primary outcome of reduced STI prevalence. Final results are currently being analysed. Finally Chapter 8 contains a number of recommendations directed at research, policy and programmatic levels that may address disparate rates of STIs and HIV in Aboriginal communities.

Little research has examined how economic uncertainty and preferences affect decision-making surrounding fertility intention, contraceptive behavior and pregnancy outcomes –an area where intention-behavior inconsistencies are widely acknowledged. Risk preference are defined as a person’s willingness to assume risk, and time preference as a person’s degree of present bias. Measures of risk and time preferences that underlie decision-making have been linked to health behaviors, especially substance use. There is a long history in social science of examining how these preferences correlate with financial decision-making and behavior, and measures have therefore been included in population surveys to examine economic behavior. Far less frequent are analyses that examine how economic preferences may extend beyond financial behavior to explain behavior in other domains, such as health behavior. Sexual and contraceptive behaviors are influenced by uncertainty surrounding pregnancy risk, pregnancy intention, access to methods, sexual and reproductive control, as well as perception of STI risk. Decision-making theory may therefore be especially helpful to shed light on disparities in unintended pregnancy and contraceptive use.Drawing on behavioral economics, this dissertation expands understanding of uncertainty and reproductive health decision-making in several steps. My three papers examine if there are general decision-making constructs, including risk-taking propensity and degree of present bias that may extend beyond financial decisions to health behavior and ultimately reproductive health outcomes. In the first paper, I review the state of the literature on temporal and risk preferences and sexual and reproductive health. Next, I examine how risk preferences are related to sexual behavior and contraceptive use in the National Longitudinal of Youth (NLSY97). Finally, I examine the relationship between national economic uncertainty and pregnancy intentions and outcomes in the National Survey of Family Growth (NSFG). This work draws on economics, psychology, and social epidemiology.The goal of this research is to contribute to understanding the context of reproductive decision-making and behavior. This work deepens our understanding of the mechanisms underlying choices that drive health behavior. This is an important step towards predicting who will be at highest risk of adverse outcomes and develop models for intervention.

Weight and weight change during pregnancy influence fetal growth and development and may have long-lasting effects on offspring health. Additionally, nearly half of women now begin pregnancy overweight or obese and a wide range of weight is gained and lost during and after pregnancy. In response to these concerns, the Institute of Medicine (IOM) revised its gestational weight gain recommendations in 2009 to include a specific, relatively narrow range of recommended gain for women with prepregnancy obesity. Unfortunately, limited scientific evidence and quantitative methods guided these recommendations. The IOM made several research recommendations, including that studies on the impact of gestational weight gain on a range of child outcomes be conducted in large, diverse populations, and that such studies address the extent to which optimal weight gain differs by maternal prepregnancy body mass index (BMI) and other maternal factors, including maternal race/ethnicity. This dissertation aims to address gaps in our understanding of how pregnancy weight and weight change are associated with child health. The first paper demonstrates two recently developed, quantitative approaches to studying gestational weight gain and determining optimal ranges of weight gain for minimal risk of preterm birth. It also informs whether weight gain recommendations should be tailored to maternal race/ethnicity, which has previously been suggested by the IOM. The second paper identifies longitudinal trajectories of maternal weight from prepregnancy through the postpartum period and assesses the relationship between maternal weight trajectories and offspring obesity in childhood. The third paper determines if maternal history of physical abuse in childhood is related to the risk of offspring overweight in childhood, and whether prepregnancy BMI and gestational weight gain play mediating roles in such an association.These dissertation papers together provide valuable information to help determine ranges of weight gain during pregnancy that minimize risk of adverse infant and child health outcomes. They also intend to stimulate further research to establish a scientific evidence base for creating effective interventions and clinical gestational weight gain guidelines. Promoting healthy weight and weight gain in pregnancy presents a potentially feasible and effective opportunity to improve infant and child health.

In order to win the battle to end the global tuberculosis (TB) epidemic, we need new and better tools. Approximately one-third of the world's population is infected with the TB bacterium, and in 2015 over 10 million people become sick with the disease and almost 2 million people died, meaning TB is now one of the top ten causes of disease worldwide, outranking HIV and malaria. In addition, over 40% of TB cases each year do not get diagnosed or notified. These missed or delayed diagnoses lead to increased morbidity and mortality for those suffering from the disease, and help drive the TB epidemic through continued transmission. The World Health Organization’s (WHO’s) new “End TB Strategy” envisions a 90% reduction in TB incidence by 2035, but in order to achieve this target there is an urgent need to develop, evaluate, and deploy strategies to improve TB case detection in high burden settings.There are numerous barriers to TB case detection, operating at several interacting levels. Those at highest risk of falling ill with TB are disproportionately from poor, disadvantaged, and marginalized populations that are much more likely to face barriers to accessing health care when sick. Those who do fall ill with TB can face numerous economic, geographic, and social/cultural barriers before reaching health care. And once they do reach care, patients can still be hampered by significant provider and health system barriers. To address some of these barriers to TB case detection, my dissertation research focuses on three perspectives on improving case detection for TB: policy, implementation, and social implications. My first paper describes a tool I helped develop for the WHO called ScreenTB that assists National TB Control Programmes (NTPs) to develop TB screening programs well suited to their local epidemic by modeling the potential yields and costs of a variety of approaches to TB screening. My second paper presents the findings from a year-long pilot implementation of a TB screening intervention, “STAMP out TB”, in primary care clinics in Jakarta, Indonesia. My third paper explores the potential social implications of TB case-finding in Dar es Salaam, Tanzania.Together these papers contribute to the field of TB case detection by providing tools for, and information about, the development and implementation of TB case-finding strategies in high burden settings. These three papers also characterize the diversity of my work in this field, as they each represent a distinct skillset that I have acquired during my time at UCSF. Put together, these papers will demonstrate that I have mastered an array of different tools and approaches used in the field of global infectious disease epidemiology.

People are exposed to numerous chemicals daily through the products we use, the food we eat, and the air we breathe. This has been demonstrated by research that indicates virtually all people living in the industrialized world have numerous chemicals in their blood, which has led to growing scientific and public concern over the potential health implications of these exposures. Chemicals, such as phthalates, are a significant public health concern because decades of research have linked them to a wide range of health effects. This dissertation contributes to the literature by assessing how sociodemographic factors influence exposure to phthalate metabolites (Paper 1), and how exposures to phthalates individually (Paper 2) and in combination (Paper 3) affect antibody concentrations (i.e. titers) against organisms that cause infectious diseases. This dissertation utilized data from five cross-sectional cycles of the National Health and Nutrition Examination Survey, a nationally representative sample of U.S. residents one year and old, to prepare three dissertation papers. The first paper assessed how sociodemographic characteristics influenced exposure distributions with a focus on birthplace, age, and sex/gender differences. This study found that overall phthalate exposure has decreased for most metabolites examined between 2003 and 2012. While exposure to phthalates was ubiquitous, foreign-born persons generally had greater exposure compared to U.S.-born persons, particularly for low molecular weight (LMW) metabolites; males typically had greater risk of exposure to high molecular weight (HMW) phthalates; and young persons had greater overall exposure compared to adults. The second paper tested associations between single phthalate metabolite and individual antibody measures against measles virus, mumps virus, rubella virus, poliovirus, Epstein-Bar virus, and Toxoplasma gondii. When examining the association between single metabolites and individual antibody measures, exposure to LMW phthalates was generally positively associated with measles, poliovirus, and Epstein-Barr virus antibodies, respectively. Conversely, HMW phthalates were inversely associated with both rubella and poliovirus antibodies. Males typically experienced immune enhancement while suppression was primarily observed in females.Lastly, the third paper evaluated how co-exposures to phthalate influenced multiple antibody titers simultaneously. This was accomplished with structural equation modeling that showed LMW phthalate metabolites were associated with immune enhancement while HMW phthalates were associated with immune suppression with the exception of mono-ethyl phthalate. If associations are causal, exposure to HMW phthalates could increase a person’s risk to infectious diseases while exposure to LMW phthalates could be immunoprotective, or they could increase susceptibility to autoimmunity and/or allergy.

In the U.S., 45% of adults have at least one chronic condition, and the burden disproportionately affects females, individuals with low socioeconomic status, and certain racial/ethnic minority groups. Obesity is the leading risk factor for many chronic conditions such as diabetes, heart disease, and cancer. Accumulating evidence suggests that chronic inflammation, due to obesity and other stressors, may underlie the initiation and progression of various chronic conditions. The energy-adjusted dietary inflammatory index (E-DII) was developed to assess the inflammatory potential of diet and serve as a tool to study the associations between diet-associated inflammation and development and progression of chronic conditions. Since 2014, over 250 papers have been published describing associations between the E-DII and many mental and physical health conditions. Yet, there is lack of investigation on potential differences in associations between the E-DII and health outcomes by gender, race, ethnicity, and socioeconomic status.The overall goal of this dissertation was to investigate differences in E-DII scores and potential differences in association with health outcomes by gender, race, ethnicity, and socioeconomic status. This research can help inform further studies by demonstrating that gender, race, ethnicity, and socioeconomic status may act as effect measure modifiers for associations that are commonly reported in the literature. For this dissertation, cross-sectional data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey (NHANES) was used. NHANES is nationally representative of the civilian, noninstitutionalized U.S. population and is the only national-level study with nutrient information on dietary intake from foods, beverages, and dietary supplements. This dissertation compared E-DII scores and associations with allostatic load and undiagnosed hyperglycemia among the following groups: (1) females and males, (2) non-Hispanic White, non-Hispanic Black, and Hispanic (3) low, middle, and high income according to family income poverty ratios (i.e., ≤100%, 101 – 399%, ≥ 400%), (4) education level (i.e., less than high school, high school graduate/GED, some college or associate degree, college graduate or above), and (5) occupation group (i.e., management and professional, service, sales and office, manual labor, and not working or retired). Multiple imputation was performed to impute missing values for all aims.For Aim 1, we used linear regression to compare E-DII scores by gender, race/ethnicity, and socioeconomic status. Overall, 63% of U.S. adults reported consuming pro-inflammatory diets. The highest E-DII scores were observed among non-Hispanic Black males, males at or below the poverty level, those with less than high school education, and those working manual labor jobs. In adjusted models within socioeconomic status categories, racial/ethnic differences in E-DII score were attenuated among non-Hispanic Black males and Hispanic individuals compared to non-Hispanic White adults. However, E-DII scores among non-Hispanic Black females remained significantly higher compared to non-Hispanic White females.For Aim 2, we used logistic regression to estimate associations between E-DII and high-risk allostatic load scores among gender, race/ethnicity, and socioeconomic status groups. High E-DII scores were associated with 19-74% higher odds of high-risk allostatic load with variation by groups. Higher E-DII scores were significantly associated with higher odds of high-risk allostatic load among non-Hispanic White individuals and Hispanic males (p0.05). Racial/ethnic differences were attenuated within models stratified by socioeconomic status variables, and significant associations between E-DII and allostatic load were only observed among those with higher levels of education, income, and occupation. For Aim 3, we used logistic regression to estimate associations between E-DII and undiagnosed hyperglycemia among age, gender, race/ethnicity, and socioeconomic status groups. Overall, higher E-DII scores were associated with higher odds of undiagnosed hyperglycemia among females (OR=1.52 [95% CI: 1.25, 1.85]) and males (OR=1.49 [95% CI: 1.22, 1.82]). In adjusted strata-specific models, higher E-DII score was significantly associated with higher odds of undiagnosed hyperglycemia among non-Hispanic White males only and males ages 30-39 years, 50-59 years, and 60-69 years (p < 0.05). By socioeconomic status indicators, higher E-DII score was significantly associated with higher odds of undiagnosed hyperglycemia mainly among males with higher levels of education, income, and occupation (p < 0.05).This dissertation demonstrated differences in E-DII scores by gender, race/ethnicity, and socioeconomic status. Effect modification was observed for the associations between the E-DII and allostatic load and undiagnosed hyperglycemia. Not all associations were statistically significant, but effect sizes by groups differed by 19-120%. Observed differences in effect sizes of associations by sociodemographic factors may help explain the heterogeneity observed in the current E-DII literature. Further studies are warranted to investigate differences in health effects from diet-associated inflammation among groups that tend to have higher levels of sustained chronic inflammation due to disadvantage, adversity, and stress (e.g., females, racial/ethnic minorities, individuals with low socioeconomic status). Prospective designs to determine temporality can better inform the impact of anti-inflammatory diets on health outcomes.

This paper examines the association between term low birth weight (TLBW) and individual-level exposure to NO2 and whether this association differs by neighborhood-level physical and social factors. Data consisted of birth records (n=97,200), measures of neighborhood-level social disadvantage, racial and ethnic segregation, and greenness. Unconditional logistic regressions revealed that exposure to high NO2 levels in the third trimester is compatible with a weak positive association with TLBW after adjusting for maternal age, birthplace, race/ethnicity, smoking; infant sex; parity; and prenatal care payment type (aOR= 1.02, 95%CI=0.95, 1.09). To examine the presence of interaction, the model was re-run for each neighborhood covariate to include a product term. Evidence of a negative interaction between NO2 and greenness was found. The odds of TLBW when NO2 is high and greenness is low was lower compared to when NO2 is low and greenness is high, corresponding to a point estimate of 1.00 (95%CI: 0.74 1.34) when exposure to high NO2 levels is stratified at low NDVI.

This paper presents a model for a resource-efficient daily data analysis dashboard developed in the Santa Barbara County Public Health Department during the 2020 COVID-19 pandemic (SARS-COV2). The model provides a framework for data presentation, which may be adapted to the needs of other county public health departments or similar emergency management districts. It was developed between March and May 2020 to provide an overview of data in Santa Barbara County, an area on the Central Coast of California with a population of 442,000. The main benefits of the model are the speed with it can be built out, the limited amount of time required to update data (10-15 minutes per day), and the graphical analysis it automatically generates from this data. It also offers a simple way to compare local data with state and national predictive models, a vital tool for any public health department in planning appropriate disaster response measures.

Lung cancer (LC) is still one of the most frequent cancers with a high related mortality. Their prognosis is directly proportional to the stage at the time of diagnosis. Seventy percent are currently diagnosed in advanced or locally advanced stage (higher than stage III), making a cure unlikely for the majority of patients. Developments in LC treatment are significant however they do not seem to be enough to reverse the current situation, at least, in a short period of time. Despite recent advances in treatment, primary prevention and early diagnosis appear to be the key to reduce the incidence and mortality of this disease. Many countries have developed LC screening programs based on the results of clinical trials published in recent years. The aim of this paper is to review the latest results of the NEderlands Leuvens Longkanker Screenings Onderzoek and compare them with the findings of the National Lung Screening Trial. We address the question whether it is necessary to continue discussing the evidence regarding LC screening. In both trials, there is a clear impact on LC mortality but, with a modest reduction in over all mortality. Undoubtedly, the benefit of screening can be expected to grow as low-dose computed tomographys are performed over longer periods of time.

Globally, 16 million children, about 11% of all births, are born to women aged 15 to 19 each year. Young mothers and their children bear a heavier burden of poor health and social outcomes compared to families in which the mother began childbearing later in life. The majority of teenage births occur in low- and middle-income countries. However, most research on interventions to improve outcomes among teenage mothers and their children is completed in high-income, Western countries. The social, economic and cultural contexts surrounding adolescent pregnancy and parenthood vary widely across countries. As a result, it is important to assess whether programs and policies that appear effective in high-income, Western countries maintain their effectiveness in other settings, where the majority of early childbearing occurs. The goal of this dissertation is to identify programs and policies that improve outcomes for adolescent mothers and their children. The first paper explores what it means to be an adolescent mother in rural Mexico by comparing indicators of socioeconomic status, maternal wellbeing and parenting practices of adolescent and older mothers, documenting social perceptions of young motherhood, and understanding young mothers’ perceptions of motherhood using quantitative and qualitative methods. The second paper uses a cluster-randomized controlled trial of a parenting education program, Educación Inical, in Mexico to assess whether the estimated effect of the parenting program on parenting behaviors and child cognitive development varies by the age at which the mother began childbearing. The final paper explores the association between having a child in center-based child care and parenting stress and child behavior among adolescent mothers and their children in Chile. The studies presented here find no evidence of improved outcomes among adolescent parents or their children of a parenting education program or center-based child care support. As such, interventions that have shown promise in Western countries and among populations not limited by age at first birth may not be easily transferable to young mothers in other settings. This research highlights an important gap in understanding how best to support adolescent mothers and their children. These studies also point to the need for research that clarifies adolescent mothers’ sources of adversity and opportunity in varying cultural, social and economic settings in order to appropriately target programs and policies. Additionally, it is critical that research on the impact of programs and policies that are hypothesized to improve outcomes for adolescent mothers and their children take place in locations where the majority of adolescent pregnancy and parenting occurs. Understanding what works to improve outcomes for adolescent mothers and their children across a range of contexts is necessary to meet the needs of millions of families who reside outside of where the evidence base has traditionally focused.

Background: Food insecurity is the state of being without reliable access to enough food for an active, healthy life. While the relationship between food insecurity and weight gain has been inconsistent in children and men, food insecurity is consistently associated with chronic distress and higher weight status among women. The primary goal of this dissertation is to assess the associations between food insecurity and weight gain and obesity in low income Latino children, and food insecurity and unhealthy weight gain among a California representative sample of pregnant women. Seventeen percent of American children are obese, making childhood obesity one of the most prevalent health challenges American children face. Forty-eight percent of women in America gain weight in excess of the Institute of Medicine’s (IOM) gestational weight gain guidelines; over 56% of obese women and 51% of white women gain in excess of the IOM guidelines, making these groups especially vulnerable. Three studies have found evidence that obesity may stem from early life exposure to food insecurity, although no study has examined if early exposure to food insecurity is associated with obesity in late childhood and early adolescence. Only one study has assessed if transitioning to and from food insecurity is associated with growth in children and they found that changing food security status may affect boys and girls differently. Additionally, only three studies have assessed the association between food insecurity and gestational weight gain among pregnant women and they have found positive and null associations. Identifying if there is an association between food insecurity and weight status among low income Latino children and pregnant women would inform programs such as the Special Supplemental Nutrition Program for Women, Infants, and Children that aim to alleviate food insecurity and promote healthy weight gain in these vulnerable populations.Methods: The Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study collected information from Latino mother-child dyads from pregnancy to age 12. The first paper in this dissertation analyzes 243 mother-child dyads from CHAMACOS to assess longitudinal associations between exposure to food insecurity in the first years of life and changes in growth and obesity status from age 2 to 12 by implementing linear and logistic regression models. The second paper analyzes 204 children from CHAMACOS, and investigates the longitudinal associations between food security status, changing food security status, and persistency of food insecurity with changes in growth and obesity status by implementing generalized estimating equations. The third paper applies linear and multinomial logistic regression models to investigate the cross sectional association between food insecurity and gestational weight gain among 12,097 women from California’s Maternal Infant Health Assessment (MIHA), a random sample survey of English- or Spanish-speaking women in California who recently had a live birth. Conclusion: Early life exposure to food insecurity in the first two years of life was associated with growth in childhood differentially between boys and girls at different times, even up to ten years after the food insecurity was experienced. Household food insecurity was associated with decreased growth in childhood and transitioning to and from food insecurity was also negatively associated with growth. During pregnancy, food insecurity was significantly associated with increases in gestational weight gain among non-Hispanic African American women. However, these changes in weight status did not translate into changes in obesity status or gaining excessive weight during pregnancy according to the IOM gestational weight gain guidelines. The associations between food insecurity and growth in children were modified by age and gender while the associations between food insecurity and gestational weight gain were modified by race/ethnicity. Of the few studies that have previously examined the relationships between food insecurity and weight status among Latino children and pregnant women, very few tested for effect modification by age, sex, and race/ethnicity. Therefore more studies that consider differential influences of food insecurity on weight are needed before we can conclude food insecurity is not associated with obesity or excessive gestational weight gain in these vulnerable populations.

Background: Weight gained during childbearing has significant implications for maternal and child health. Both too much and too little weight gained during pregnancy can result in adverse outcomes. Recommendations for ideal gestational weight gain (GWG) have been developed by the Institute of Medicine, but achieving these standards remains a challenge. Better understanding of the wider context in which women experience pregnancy may aid in the development of novel interventions to improve trends in healthy GWG. Neighborhoods define one such dimension of women’s wider context that is emerging as a promising factor in this area of research. However, limited work has considered long-term exposure to neighborhood environments or the role of women’s perceptions of their neighborhood environments in relation to either inadequate or excessive GWG.Methods: This dissertation explores the associations between long- and short-term exposure to neighborhood social and socioeconomic context and GWG using data from the 1979 National Longitudinal Survey of Youth. It additionally investigates associations between objective and perceived measures of neighborhood social context in relation to GWG. The first paper investigates associations between long-term, cumulative neighborhood socioeconomic deprivation and GWG. The second paper investigates associations between objectively measured and perceptions of point-in-time neighborhood social environment and GWG. Objective neighborhood social environment is measured using neighborhood socioeconomic deprivation. Perceived neighborhood social environment is assessed from women’s self-report of problems within their neighborhood environment. The final paper in this dissertation conducts a systematic review of the literature to characterize the reporting error associated with use of self-reported, pregnancy-related weight in efforts to move the field toward developing bias correction techniques to address methodological limitations of this measure. While not directly related to understanding neighborhoods and GWG, this issue is relevant to future studies in this area that rely on self-reported weight.Conclusion: The papers included in this dissertation illustrate the importance of considering both long-term and short-term measures of neighborhood social context in order to fully understand how neighborhood environments impact inadequate and excessive GWG. In particular, long-term measures of exposure to neighborhood environments should be more fully considered in order to better understand how neighborhoods can support healthy GWG. Interventions based on this improved knowledge of the environment in which women experience weight gain during pregnancy may improve GWG outcomes and health trajectories of both mother and child. Future studies in this area may also benefit from more rigorous study of variation of reporting error in self-reported pregnancy-related weight by maternal characteristics, which will aid in the development of bias correction techniques for these widely used measures.

Drawing examples from over 100 English- and Spanish-language popular dailies and weeklies between January 1855 and December 1866, my dissertation, “Poems in the U.S. Popular Press, 1855-1866,” argues that mid-nineteenth-century newspaper poems constitute a vital but still understudied form of public discourse. I define public discourse as political conversations, debates, and representations for reasoning that take place in the public sphere. I make this case in archival detail in four chapters. Chapter 1 focuses on celebrity poets as part of the media culture created by editor Robert Bonner in his blockbuster story paper the New York Ledger. Chapter 2 shifts from the East to the West coast, recovering the hemispheric Spanish-language poems in the first Spanish-language newspaper in California after the Mexican-American War, El Clamor Publico (the Public Outcry). Chapters 3 and 4 excavate the robust but largely unknown archives of newspaper poems circulating across the U.S. concerning the Panic of 1857 and the New York City cholera epidemic of 1866. This project is significant to the field of U.S. literary history, including the growing scholarship on the Latinx nineteenth century, for two primary reasons. First, the archive of periodical poems has not been completely recovered, categorized, or situated with respect to the larger currents of nineteenth-century public and print cultures. Second, scholars of the Latinx nineteenth century, including Rodrigo Lazo, Jesse Aleman, and Kirsten Silva Gruesz, have begun piecing together histories of the cultural productions of Latinx people using valuable but still incomplete archives. My dissertation contributes to the necessary work of reading Spanish- and English-language newspaper poems as related acts of public discourse reflecting a diverse U.S. media culture.

Lymphatic filariasis (LF) is one of the major public health problems in Papua New Guinea (PNG), with an estimated 1 million people infected, and 3 million at risk of infection out of a population of 5.8 million people PNG has recently restarted efforts to eliminate LF as part of the global elimination program. Like other countries, the success of the elimination requires good monitoring and evaluation to be conducted by the Mass Drug Administration (MDA) program, and for it to be tailored to the epidemiology and local environment in areas where transmission remains. This project seeks to advance the progress of LF elimination with improved evaluation of the MDA program by identifying barriers to drug coverage and markers of program effectiveness. In this paper, we focused on (i) Identifying the social and biological barriers against the successful implementation of the MDA program in the Dreikikir District of East Sepik province and ii) Understanding the distribution of the infection during and after MDA using genetic markers to understand the limits of population drug coverage. Our results showed high program drug coverage over 70% one-year post MDA, across 7 treatment sites implementing 1 round of MDA in 2015. A Knowledge, Attitude and Practice (KAP) survey showed a high proportion of households had knowledge of LF and the MDA program. However, results from 16 KAP focus groups among 4 of the communities showed limited comprehension and understanding of LF and MDA. The main barriers were the misunderstanding of information received during MDA and LF awareness programs. Further investigation of the genetic diversity of Wuchereria bancrofti (Wb) in the communities which previously implemented MDA in 1996 and 2008 showed variable haplotypes within infected individuals prior and 10 years post MDA. Both unique and persistent Wb strains were identified across the communities. The high genetic variability indicates ongoing transmission even after the completion of five rounds of MDA and evidence that infection and transmission was approaching elimination thresholds in some communities. This result suggests an ongoing public problem for communities in East Sepik Province, and highlights the value of this tool for future LF elimination monitoring.

The Surgeon General classifies sexual minorities (i.e., lesbians, gay men, bisexuals) as a high-risk population for suicide. This three-paper dissertation sought to contribute to an understanding of suicide risk among sexual minorities by investigating sexual orientation differences in both distal (i.e., stigmatization) and proximal (e.g., access to firearms) cofactors of suicide. Specifically, the studies investigated: (Study 1) the impact of neighborhood-level structural stigma on changes in psychological distress among sexual minorities following a statewide vote to ban same-sex marriage, (Study 2) sexual orientation differences in gun ownership and gun safety policy beliefs, and (Study 3) sexual orientation differences in lethal method used in suicide. Data were drawn from three unique datasets, including the California Quality of Life Survey (Study 1; N=7,421), the General Social Survey (Study 2; N=4,554), and the National Violent Death Reporting System (Study 3; N=59,075). Statistical analyses were conducted in R and SAS 9.4 with analytic methods across studies including univariate and bivariate analyses, quasi-experimental methods, multivariate logistic regression adjusted for confounding, and complex survey weighting incorporating propensity score methods. Results from Study 1 demonstrated that sexual minorities residing in neighborhoods where a majority of constituents voted in favor of a same-sex marriage ban had a statistically significant mean psychological distress reduction in the time period immediately after the vote (=-4.06, 95% CI: -7.38; -0.73), with post-hoc analyses demonstrating that increased social support might have partially influenced the direction of these unexpected findings. Study 2 findings demonstrated that gay/bisexual men were more likely to endorse a gun safety law (aOR=3.24, 95% CI: 1.79 - 5.88) and less likely to report guns in the household (aOR=0.34, 95% CI: 0.18 - 0.65) than heterosexual men. Among women reporting a household gun, lesbian/bisexual women were more likely to be the personal gun owner (aOR=3.97, 95% CI: 1.43 - 11.03) than heterosexual women. Results from Study 3 showed that sexual minorities who died by suicide had reduced odds of death by firearm (aOR=0.62, 95% CI: 0.51 - 0.75) and increased odds of death by hanging (aOR=1.36, 95% CI: 1.14 - 1.63) and drug/poison ingestion (aOR=1.30, 95% CI: 1.04 - 1.62) as compared to the reference group of suicides; however, these patterns varied by gender. Findings from this dissertation demonstrate that sexual orientation differentially impacts distal (i.e., psychological responses to structural stigma) and proximal (i.e., access to firearms, use of lethal method in suicide) risk factors for suicide. Results from the research reported here can inform public health and clinical interventions to reduce suicide risk among sexual minorities.

Background: An estimated 3% of untreated group A beta hemolytic streptococcal (GABHS) pharyngitis can lead to rheumatic fever (RF), resulting in rheumatic heart disease (RHD) and other serious nonsuppurative sequelae of infection. Prevalence of disease is disproportionate with the greatest burden among children and adolescents of developing countries; an estimated 95% of RF and 79% of RHD cases are from low income countries. Accurate diagnosis and prompt antibiotic treatment of GABHS pharyngitis is a simple and effective strategy for primary prevention of RF and RHD. Accurate diagnosis is difficult without laboratory testing due to similarities in signs and symptoms with other causes of pharyngitis.Due to financial constraints, laboratory capabilities are often limited, forcing many physicians in low and middle income countries (LMICs) to either prescribe antibiotics indiscriminately or rely on clinical prediction rules (CPRs). CPRs provide a practical alternative for diagnosis in the absence of laboratory testing. However, few CPRs have been derived specifically for LMICs. Studies have shown that CPRs can be cost effective in hospital settings, but few have been conducted for children from LMICs. Methods: Children 2-12 years of age presenting with complaint of sore throat were enrolled in four urban university pediatric outpatient clinics from September 2001 to August 2005 in Rio de Janeiro, Brazil, Cairo, Egypt; Riga Latvia and Zagreb, Croatia. The diagnostic component of the study (Chapters 4-5) consisted of generating CPRs for the 1,993 children enrolled in the study. It also consisted of external validation of a) published CPRs from the literature, and b) study developed CPRs. The cost effectiveness analysis component of the study (Chapter 6) assessed the cost effectiveness of the CPR developed for Egypt versus five alternative diagnostic and management strategies.Summary: The dissertation consists of findings from three papers (Chapters 4-6). In paper 1 (Chapter 4), five different CPRs were developed for use in Egypt, Brazil, Latvia, Croatia, and the combined study population. In paper 2 (Chapter 5), external validation of published and study CPRs suggested country specific CPRs were better in the population for which they were developed. In paper 3 (Chapter 6), Culture Only was the most cost effective strategy at baseline estimates; however, the Egypt CRP was cost effective when sensitivity and specificity were at or above 88%.

Neurocysticercosis (NCC), a parasitic infection of the human central nervous system with the organism Taenia solium is an important, yet neglected, global public health problem causing preventable disability such as seizure and stroke in those infected. NCC symptoms vary widely, based upon the number and location of lesions, and can be difficult to identify and diagnose. NCC is a reportable disease in Los Angeles County. However, there is limited understanding of NCC disease burden in Los Angeles County due to reporting barriers. This dissertation is presented in three papers. The first paper examines case reporting and demographics of probable NCC cases identified in a Los Angeles community hospital through review of computerized tomography (CT) brain scan reports performed during 2012 that describe evidence of lesions highly suggestive of NCC infection. The study identified 303 probable NCC cases and found that 7 of the 11 cases reported to Los Angeles County Department of Public Health in 2012 were from the study site.The second paper describes the presenting symptoms and mortality data of identified probable NCC cases. The study found that 3.9% of cases presented with seizure upon admission to the hospital and that death occurred in 3.9% of cases. The most common presenting symptom was headache (24.7%). The third paper analyzes the rate of prior and acute stroke in the 303 probable NCC cases. The study found that 28.3% had evidence of prior stroke and 13.2% had evidence of acute stroke on CT brain scan performed during their admission to the hospital. NCC infection was also shown to be statistically significant as an independent risk factor for acute stroke when other known stroke risk factors were controlled for. The odds of acute stroke for probable NCC-infected persons were nearly 25 times that of noninfected NCC persons in this study.The research presented here improves the understanding of NCC disease burden in Los Angeles County, demonstrates differences in NCC presenting symptoms, and demonstrates that NCC infection is an independent risk factor for acute stroke.

The ability of women to safely and effectively control their fertility is a critical health and human rights issue. Family planning provides a range of health, social, and economic benefits for women and their families, yet more than 200 million women worldwide who wish to delay or limit their childbearing are not using any method of contraception. The global health community has recently seen renewed interest in promoting family planning use worldwide. This increased focus on family planning raises questions about how best to deliver reproductive health services to the women who need them, which requires a clearer understanding of how women make decisions about their fertility and how such decisions are carried out.This dissertation explores the reasons why women's stated fertility intentions do not always align with their fertility behaviors or outcomes. The first paper explores the concept of unmet need for family planning by using both quantitative and qualitative methods to better understand why women who want to prevent a pregnancy choose not to use contraception in Luanda Province, Angola. The second paper considers the social context in which women make decisions about their pregnancies in a post-abortion care context in Zanzibar, Tanzania. The third paper examines how women's experiences in early childhood shape their risk of unintended pregnancy later in life in the United States.These dissertation papers provide three distinct examples of how researchers' and policy makers' perceptions of women's reproductive decision-making may fail to recognize or address crucial determinants of fertility intentions, behaviors, and outcomes. In particular, they highlight the importance of considering women's fertility decisions within the context of their full reproductive lives, and point to the need for further research to better understand how such decisions shift over the course of women's lives. Policies and programs that can accommodate how these decisions are formed and changed over time are necessary for ensuring that all women have the right to make decisions about their reproduction and to enact these decisions in safe and effective ways.

This dissertation examines the relationships between immigration and the incidence of tuberculosis (TB) disease and prevalence of TB infection in California and in the United States (U.S.). The majority of TB cases in California occur among foreign-born persons from countries with high TB burdens. Although the incidence of TB is declining, the decline among immigrants has stalled, and relationships of this trend with changes in immigration patterns are not well characterized. Census data suggest that immigration to California has undergone notable transitions since the 1990s that have shaped the volume, demographic and socioeconomic composition of immigration streams to the state. The first two papers of this dissertation explore the relationships between changes in immigration and the incidence of TB using the decomposition method, and an innovative application of cohort analysis. The third paper examines the only nationally representative survey of new immigrants in the U.S. to determine gaps in TB screening and to assess the prevalence and risk of latent TB infection (LTBI) in immigrant subgroups by country of origin. This unique data source allowed for the assessment of important immigration, health, and socioeconomic variables.The decomposition of the recent decline in the incidence of TB among the foreign-born in California shows that changes in the population composition associated with immigration shifts made a modest contribution to the decline, with the majority of the decline due to group-specific declines in rates. There was a notable difference between Hispanics/Latinos and Asians/Pacific Islanders, whereby the impact of immigration shifts was much greater in the former group. The cohort analysis shows that waves of immigration have had varying impacts on the incidence of TB in California, some cohorts contributing to increasing incidence, and others to decreasing incidence. This suggests that the slowing in the decline of the incidence of TB may be due, in part, to immigration cohort entry effects. Identifying cohorts with elevated risk of TB can help develop and test hypotheses on the epidemiologic reasons for the observed effects, and can provide an evidence base for selecting demographic subgroups in which to prioritize TB screening. The TB screening uptake and TB prevalence analysis confirmed gaps in testing for TB that varied significantly by country of origin. Substantial variation in the prevalence and risk of LTBI was also found, which may inform public health efforts to prioritize the targeted testing and treatment to specific subgroups of highest risk.

Cryptococcal meningitis (CM) is a wide-spread, yet under-recognized, fungal opportunistic infection occurring primarily among people living with advanced HIV/AIDS. While vast advances in understanding the pathogenesis and treatment options for CM have reduced mortality, major gaps remain in understanding factors that contribute to mortality rates of 12-20% in the first two weeks. The intent of this dissertation was to contribute towards the efforts to address these gaps and provide evidence that could further improve short and long-term recovery from HIV-associated CM in sub-Saharan Africa. The first paper was focused on mortality in the days after CM diagnosis and understanding whether lumbar punctures (LPs) to reduce intracranial pressure also reduce mortality. Raised intracranial pressure is common in CM patients and contributes to many of the disease's signs and symptoms. Two hundred forty-eight HIV-positive, CM patients from Uganda and South Africa were evaluated for the occurrence of therapeutic LPs and mortality within 11 days of CM diagnosis. Analysis was conducted using a marginal structure model, with time-varying exposure. The results suggest that undergoing at least one repeat LP reduced 11-day mortality by 69% (95% CI: 18% to 88%), adjusted for heart rate, CSF fungal burden and altered mental status. This beneficial effect was independent of the baseline CSF opening pressure, demonstrating that increases in intracranial pressure may be common among all CM patients and that all patients may benefit from an additional LP during initial therapy. The second paper was aimed at investigating baseline demographic and clinical features predictive of CM treatment success. The recommended initial treatment regimen for CM rapidly reduces infection; however, nearly 50% of CM patients will continue to have viable fungus in their central nervous system at the end of therapy. Being able to predict patientutcomes has many advantages including optimizing treatment for each patient and reducing drug toxicities. One hundred seventy-seven HIV-positive, CM patients undergoing 2 weeks of antifungal treatment, including amphotericin B and fluconazole, were evaluated for sterility of a CSF culture by the end of therapy. The baseline CSF quantitative fungal burden was a strong and practical predictor of achieving CSF sterility, along with the rate of fungal clearance over the first week of treatment, and the baseline hemoglobin. Information on the baseline burden of infection could be used to tailor the duration of treatment, thus avoiding unnecessary toxicity and treatment costs for individuals with a lower burden of infection and potentially shifting resources to allow for more aggressive treatment of high-risk patients. The third paper aimed to understand the consequence of residual fungal infection at the end of initial antifungal therapy in terms of mortality in the first weeks and months after 2-week therapy ends. Among 154 HIV-positive individuals surviving the initial 2-week phase of therapy, there was no evidence that either the presence or the amount of residual cryptococcal infection in the CSF had an association with mortality in the following 3 weeks or 6 months. It is possible that a higher dose of fluconazole used at the end of amphotericin therapy in the present cohort may have contributed to the lack of association. The objective of this dissertation was to expand the understanding of CM treatment and recovery in resource-limited settings. The results suggest that additional benefits could be gained from the use of therapeutic lumbar punctures during the acute phase of treatment, the possibility of customizing therapy to further reduce treatment toxicities, and, finally, describing the relationship between residual infection and CM mortality with indirect support for higher doses of fluconazole during subsequent phases of CM therapy.

This paper hypothesizes possible reasons for the existence and necessity of disease. It is not all-inclusive, nor is it promoting disease. This paper includes a thought experiment on what the world could be like without disease, as well as brief analysis of certain communicable diseases.

Background: Vaginal discharge syndrome is a clinical condition characterized by leucorrhea, which can be caused by reproductive tract infections (RTIs). Three RTIs are referred to as vaginal infections: bacterial vaginosis (BV), trichomoniasis (TV), and vulvovaginal candidiasis (VVC). Vaginal infections are known to increase susceptibility to sexually transmitted infections, including HIV, and to be associated with low birth weight and premature birth. The prevalence and incidence of and risk factors for vaginal infections are not well-studied in many settings. Further, the aforementioned consequences of these infections are highly prevalent in many low-income settings, providing ample justification for additional inquiry into the diagnosis and risk factors of these vaginal infections.Methods: The Prerana dataset was collected as part of a prospective cohort study of 898 non-pregnant, reproductive-aged women living in and around Mysore, India between 2005 and 2006. The primary study objective was to evaluate the relationship between abnormal vaginal flora and the incidence of Herpes Simplex Virus - type 2 infection. Participants completed three study visits - conducted at baseline, and at three and six months - each of which involved an interviewer-administered questionnaire in Urdu or Kannada; a pelvic examination; and collection of vaginal and blood specimens for laboratory testing for reproductive tract infections.Analyses investigating separate research aims will be conducted over three papers, as follows: Paper 1: Bacterial vaginosis and risk of Trichomonas vaginalis infection, Paper 2: Epidemiologic features of vulvovaginal candidiasis, and Paper 3: Syndromic diagnosis of vaginal infections using logic regression.Discussion and significance: The Prerana cohort dataset is well-suited to filling in multiple gaps in the research literature. The analyses are among the first to test (or re-test) specific hypotheses concerning vaginal infection using a community-based sample based in a low-income setting. Paper 1 estimates the risk of Trichomonas vaginalis infection associated with the presence of bacterial vaginosis, which fills a conspicuous gap in the research literature. If susceptibility to Trichomonas vaginalis infection is found to be heightened among women with bacterial vaginosis, the burden of sexually transmitted infections attributable to bacterial vaginosis will increase dramatically, given that both conditions are highly prevalent. Next, paper 2 identifies factors associated with increased prevalence of vulvovaginal candidiasis, particularly with respect to the presence of vaginal Lactobacillus. If vulvovaginal candidiasis is associated with decreased presence of Lactobacillus, there will be support for identifying interventions to enhance the presence of Lactobacillus, such as with probiotics, after women are treated with antibiotics. Finally, paper 3 examines the sensitivity, specificity, positive predictive value and negative predictive value of vaginal infections in this population using a World Health Organization diagnosis algorithm. Separate syndromic diagnosis models for vaginal infections are developed using logic regression, a machine-learning procedure; the models are evaluated for their diagnostic performance against laboratory-confirmed diagnoses of vaginal infections. Logic regression models offer the potential to improve upon the performance of the WHO algorithm, using parsimonious models which are easy to develop, comprehend, and implement in clinical facilities in low-income settings.

Type 2 diabetes is a major contributor to mortality and morbidity in the United States. The etiology of this disease is complex and our knowledge of it is incomplete. These analyses sought to increase our understanding of the etiology of type 2 diabetes and to distinguish newly identified risk factors that could someday be useful in clinical risk prediction models. The first paper examined the contributions of novel risk factors to the prediction of type 2 diabetes in the Atherosclerosis Risk in Communities (ARIC) study. There was only modest reclassification of risk with the addition of forced expiratory volume in 1 second (FEV1) to the risk model and a small improvement in the integrated discrimination index (IDI) with the addition of white blood cell count, activated partial thromboplastin time (aPTT), albumin, factor VIII, magnesium, hip circumference, heart rate, and a genetic risk score in the total cohort. In the case-cohort analysis there was no significant reclassification of risk, but the addition of adiponectin, leptin, gamma-glutamyl transpeptidase (GGT), ferritin, inter-cellular adhesion molecule 1 (ICAM-1), and complement C3 to models modestly improved the IDI. A second paper examined the association between sets of genome-wide association (GWA) derived type 2 diabetes score alleles with both incident type 2 diabetes and prostate cancer in the ARIC cohort. We found that these score sets derived from men were not significantly associated with type 2 diabetes in an independent target dataset of women, nor were they associated with prostate cancer in men. Secondarily, we conducted a pathway analysis of our GWA analyses of type 2 diabetes and prostate cancer. We failed to identify pathways significantly associated with both diseases; however, we did identify a pathway statistically significantly associated with type 2 diabetes, the growth hormone signaling pathway. A third paper looked for associations between genetic variants in the Wnt pathway and hemoglobin A1C (HbA1c) levels in the Epidemiology of Hearing Loss (EHLS) and Beaver Dam Offspring Study (BOSS) studies. No Wnt variants were significantly associated with HbA1c. Nor were we able to replicate the associations between three SNPS and HbA1c recently identified in a meta-analysis. This dissertation contributes to our understanding of type 2 diabetes risk prediction by showing that few novel risk factors contribute meaningfully to existing risk prediction and expands our understanding of the etiology of type 2 diabetes by identifying a genetic pathway significantly associated with this disease and its related quantitative traits.