published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Community Medicine / Doctoral / Doctor of Philosophy

Reducing health disparities and achieving health equity in maternal and infant health is a critical concern for social work and public health stakeholders more generally. This three-paper dissertation is dedicated to exploring program or policy modifiable social determinants of maternal and infant health with a particular focus on vulnerable populations. Paper one explores the influence of household members on women’s sexual and reproductive behaviors. Paper two studies the impact of smoke-free regulations on birth outcomes in Latin America. Lastly, paper three looks at the effects of police use of force, and racialized police use of force, on maternal and infant health. The findings of these papers provide important information to inform programs and policies aimed at improving reproductive health and well-being in the U.S. and Latin America.

This dissertation is an empirical investigation into the roles that different quantifiable and measurable perceptions play in defining individual behavior across a variety of decision-making contexts. In particular, the focus lies on smokers and the choices they make with regard to smoking and beyond. Chapter 1 analyzes a nationally representative sample of adults (23 years and older) in the United States, pertaining to the Annenberg Perception of Tobacco Risk Survey II (1999-2000). It is observed that three dimensions to smoking behavior viz., risk, temporality and addiction, interact to determine the smoking status of an individual. Although previous studies mostly looked into each of these dimensions in isolation, in this chapter, we empirically illustrate how perceptions on risk, time dimensions and addiction, jointly influence the smoking behavior of adults. Chapter 2 casts the smoker in the role of a parent and explores parental behavior towards the general health-risks facing their children. Using the dataset from a survey (2009), conducted in Orlando, Florida, on parents, having at least one child aged between 1 and 16 years, the chapter arrives at two findings relevant for policy: i) In each of the ‗smoker‘ and ‗non-smoker‘ parent categories, parents exhibit equal concern for themselves and their children, and ii) the level of concern shown by smoker-parents, towards health-risks faced by their children, is the same as that shown by their non-smoking counterparts. The analysis in this chapter also affirms the need to incorporate subjective risk assessment in willingness-to-pay (WTP) exercises to facilitate a deeper behavioral analysis of health risk valuation. Lastly, in Chapter 3, we focus on the issue of quantitative assessment of the perception of health risks from smoking. Particular interest lies in understanding how variants of a metric - namely, a survey question - have been employed in academic studies and industry-surveys, in order to measure smoking-related risk-perceptions. In the process of reviewing select tobacco-industry survey iv records, we analyze the implications of different features of this metric, (e.g., use of a ‗probe‘, the ‗Don‘t Know‘ option), and various interview modes (e.g. telephonic, face-to-face), for the estimates of perceived risk arrived at in these studies. The review makes clear that two aspects of health risks from smoking – the risk of contracting a smoking-related disease, as against the risk of prematurely dying from it conditional upon getting affected – have not been jointly explored so far. The dataset obtained from the Family Heart Disease and Prevention Survey (November 2010-March 2011), provides a unique opportunity to explore these two kinds of probabilities, particularly with regard to the risks of lung-cancer from smoking. Chapter 3 concludes by illustrating how individuals evaluate both these aspects of health-risks. While the probability of getting lung-cancer is found to be overestimated in conjunction with previous studies, the conditional probability of premature death is severely underestimated. Additionally, it is found that individuals‘ subjective assessments of either of these risk aspects predict smoking behavior in an identical manner. This calls into question the so-called ‗rationality‘ of smoking decisions with implications for policies designed for the control of tobacco consumption.

Unexpected findings that contradict well-established relationships between exposures and outcomes are often referred to as “paradoxes” in the epidemiologic literature. For example, the “birth weight paradox” refers to the observed protective association between smoking during pregnancy and infant mortality among low birth weight infants. A recent body of literature suggests that this and several other well-known epidemiologic paradoxes can be attributed to collider bias. Collider bias results from conditioning on a variable that is caused by the exposure or shares common cause with the exposure and is caused by the outcome or shares common causes with the outcome. Several recent epidemiology textbooks and methodological studies further suggest that collider bias is the graphical representation of selection bias, suggesting that these two biases are synonymous. This structural approach to bias is conceptually very useful for defining, describing, and identifying selection bias, but it introduces paradoxes of its own due to contradictory conclusions in the selection and collider bias methodologic literatures about their likely impact on study results in terms of magnitude, direction, and strata affected. Resolving these discrepancies is essential for our theoretical understanding of the relationship between selection and collider bias and has important practical implications for how we teach epidemiology, design studies, and evaluate and quantify the potential effects of bias on our results. For example, while patterns of collider bias coincide qualitatively with the birth weight paradox, the magnitude of collider bias would have to be substantial to reverse the sign of the association, contrary to prevailing beliefs that collider bias only minimally affects our results. To date, the plausibility of collider bias as an explanation for the birth weight paradox has not been empirically evaluated using data in which the paradox is observed.Taken together, these inconsistencies and contradictions suggest that our understanding of selection bias and collider bias remains incomplete. The overarching goal of this dissertation was to advance the theoretical and quantitative understanding of the impact of collider bias on study results to clarify the relationship between selection and collider bias. I began by systematically reviewing the methodologic literature on selection and collider bias. I found that selection bias and collider bias are increasingly treated as synonyms, but that conclusions about the magnitude and direction of selection and collider bias, the stratum affected, and the conditions under which the effects of each type of bias were evaluated are highly inconsistent. This suggested that divergent findings about the impact of selection and collider bias might be resolved by considering the impact of collider bias under a broader set of circumstances. I used microsimulations grounded in the sufficient component cause model to examine collider bias not under the null; interrogate why multiplicative interaction appeared central to the impact of collider bias; and clarify which stratum or strata are affected by collider bias. I identified clear patterns for the magnitude, direction, and strata affected by collider bias and successfully reconciled discrepancies with the selection bias literature. This work also enabled me to interrogate both the causal mechanisms and mathematical principles that underlie collider bias, which revealed how collider bias leads to non-exchangeability and when stratifying on a collider results in bias. Finally, I applied this deeper understanding of the mechanisms underlying collider bias to empirically evaluate the plausibility of collider bias as an explanation for the birth weight paradox. Using microsimulations parameterized with 2015 National Center for Health Statistics Cohort Linked Birth-Infant Mortality, I identified scenarios that successfully reproduced the paradox and all observed relationships between smoking during pregnancy, infant mortality, and low birth weight. These findings strengthen the evidence for the role of collider bias in producing the paradox and shed light on the potential magnitude of unmeasured confounding and direct effects of smoking and low birth weight on infant mortality that may be required for the observed magnitude of the paradox to arise. This work clarifies that almost all selection bias is collider bias; that the effects of collider bias vary in magnitude and direction; that selecting on a collider always leads to bias, but this bias may not occur in the stratum that coincides with our analytical sample; and that collider bias may resolve the birth weight paradox, but is unlikely to explain all epidemiologic paradoxes.

published_or_final_version / Community Medicine / Doctoral / Doctor of Philosophy

Indiana University-Purdue University Indianapolis (IUPUI) / Smoke-free legislation in the United States has unintentionally resulted in a decline in alcohol consumption. However, more recently electronic-cigarettes (e-cigs), which are associated with alcohol use, are reportedly being used to circumvent smoking bans. The present study surveyed community dwelling individuals in the United States reporting e-cigs may be used where they drink (N=365, mean age=33.63, SD=9.91, 53.2% female, 78.9% Caucasian) to examine how e-cig use and alcohol consumption varies by the presence of smoking prohibition where one consumes alcohol. Results indicated that smoking prohibition was associated with a greater likelihood of being an ecig user than a cigarette user (OR=3.40, p<.001) and a higher likelihood of being an e-cig user than a dual user (OR=3.37, p<.001). Smoking prohibition was not associated with AUDIT scores (B=-0.06, p=.21), total drinks (B=-.07, p=.19), or average drinks (B=-0.02, p=.76). E-cig users reported significantly fewer average drinks when smoking is prohibited as compared to allowed, t(55)=3.26, p=.002. Overall, current results suggest smoking prohibition is associated with a greater likelihood of being an e-cig user; however, smoking prohibitions are not associated with alcohol consumption and related problems in the current participants, who all reported being able to use e-cigs where they consume alcohol. Future research should address potential conceptual, methodological, and sample limitations in order to better discern this relationship, as this line of research could have important implications for e-cig policy and alcohol use treatment

Indiana University-Purdue University Indianapolis (IUPUI). / Tumor necrosis factor-induced protein 6 (TSG-6) has been shown to mitigate inflammation. Its presence in the secretome of adipose stem / stromal cells (ASC) and its role in activities of ASC have been overlooked. This thesis described for the first time the release of TSG-6 from ASC, and its modulation by endothelial cells. It also revealed that protection of endothelial barrier function was a novel mechanism underlying the anti-inflammatory activity of both ASC and TSG-6. Moreover, TSG-6 was found to inhibit mitogen-activated lymphocyte proliferation, extending the understanding of its pleiotropic effects on major cell populations involved in inflammation. Next, enzyme-linked immunosorbent assays (ELISA) were established to quantify secretion of TSG-6 from human and murine ASC. To study the importance of TSG-6 to specific activities of ASC, TSG-6 was knocked down in human ASC by siRNA. Murine ASC from TSG-6-/- mice were isolated and the down-regulation of TSG-6 was verified by ELISA. The subsequent attempt to determine the efficacy of ASC in ameliorating ischemic limb necrosis and the role of TSG-6, however, was hampered by the highly variable ischemic tissue necrosis in the BALB/c mouse strain. Afterwards in a mouse model of cigarette smoking (CS), in which inflammation also plays an important role, it was observed, for the first time, that 3-day CS exposure caused an acute functional exhaustion and cell cycle arrest of hematopoietic progenitor cells; and that 7-week CS exposure led to marked depletion of phenotypic bone marrow stem and progenitor cells (HSPC). Moreover, a dynamic crosstalk between human ASC and murine host inflammatory signals was described, and specifically TSG-6 was identified as a necessary and sufficient mediator accounting for the activity of the ASC secretome to ameliorate CS-induced myelotoxicity. These results implicate TSG-6 as a key mediator for activities of ASC in mitigation of inflammation and protection of HSPC from the myelotoxicity of cigarette smoke. They also prompt the notion that ASC and TSG-6 might potentially play therapeutic roles in other scenarios involving myelotoxicity.