48670 research outputs found
Sort by
Inequalities In The Structure And Delivery Of U.s. Health Care
Get PDFAlthough healthcare inequalities by race-ethnicity and nativity have been widely explored, more research is needed to investigate how these inequalities result from structures of racial stratification and immigrant exclusion operating within U.S. health care. My dissertation employs hand coded restricted-access medical record data, linked survey data, and rich administrative data to examine the factors generating healthcare inequalities experienced by both patients and physicians. I contextualize these inequalities within a broader U.S. landscape characterized by structural racism and nativism. In the first chapter, I examine the impact of state immigration policy contexts on healthcare access of U.S. agricultural workers representing various racial-ethnic identities and legal statuses between 2005-2012. I find state-level immigration policy contexts are strongly associated with healthcare access among documented non-White Latinx agricultural workers, who report lower levels of healthcare access and greater barriers to care-seeking in increasingly restrictive policy contexts. In the second chapter, I use hand coded electronic medical record data to examine provider-patient communication disparities. Black and Latinx patients are less likely than White patients to receive provider communication regarding a new incidental medical finding diagnosis. This disparity may reflect interpersonal racism between providers and patients of color, resulting from the perpetuation of racial mythologies in medicine. In the third chapter, I use geocoded data from the American Medical Association to explore whether subgroups of international medical graduates (IMGs) experience career stratification based on their country of medical education. I find IMGs trained in developing countries chart more marginalized U.S. career paths relative to those trained in developed countries, suggesting that nativism and racism within the medical profession intersect to disadvantage physicians from developing countries, who often are also people of color. My dissertation generates empirical evidence to show how racism and nativism operating within the U.S. healthcare system generate inequalities among people of color and immigrants. These findings have important implications not only for our understanding of racial inequality and social stratification broadly, but also for informing policy and intervention to promote equity within U.S. health care
Methods For Comparative Effectiveness Research With Real World Data
Get PDFElectronic health records (EHR) contain a wealth of information that can potentially be used for research. EHR is particularly valuable for accelerating comparative effectiveness research, which seeks to estimate the relative benefit of alternative treatments in real-world settings. However there are also many challenges and limitations to conducting research with EHR-derived data, including measurement error, systematic differences between EHR and trial populations, and differential quantity and quality of data available across patients. In this dissertation, we first investigate the performance of several methods for mitigating bias due to measurement error applied to propensity scores created from error-prone covariates and provide recommendations for which methods to use in certain scenarios. Next, we develop a method to augment a randomized clinical trial with EHR data in order to create a hybrid control arm. This new method, data-adaptive-weighting, has promising properties when compared to more standard methods as well as another more recent propensity score-based method. Finally, we investigate the scenario of informed presence bias in longitudinal data, which arises when some subjects have more information in the EHR than others based on their intensity of utilization. We extend current work and explore several scenarios in which adjusting for biomarker values obtained at both pre-scheduled and patient-initiated visits in order to determine when there is risk of bias. For each topic we applied alternative methods to real-world EHR-derived data to demonstrate practical implications of alternative approaches in realistic settings
Three Essays In Economics, Education Policy, And Inequality
No full textThis dissertation presents findings from three studies focused on (a) identifying inequalities in student access and success across the P-20 landscape and (b) evaluating policies as mechanisms to reduce barriers and effectively improve educational and economic opportunity. First, I present findings from Giving Credit Where Credit Is Due: Causal Impacts of Reverse Transfer Associate Degrees on Education and Labor Market Outcomes (joint with Lauren Russell), where we leverage a difference-in-differences design applied to administrative data from Tennessee to estimate effects of reverse transfer degrees on students’ GPA, college credits attempted, credits earned, labor market participation, and earnings, as well as eligible cohorts’ baccalaureate attainment. Our results represent the strongest evidence to date on these widely adopted credentials but suggest they have minimal-at-best impacts on students’ short- and intermediate-term outcomes. Second, in The Power of \u27Free\u27 College: Reducing Racial and Socioeconomic Inequalities in College Expectations, I leverage the High School Longitudinal Study of 2009 to test whether promise programs raise high school students’ expectations to ultimately complete a college degree. With difference-in-differences and lagged dependent variable strategies, I find large increases in students’ college plans following the adoption of promise programs, with the greatest gains among low-income and racially minoritized students. This is the first study to identify this key mechanism by which promise programs may increase subsequent college-preparation and college-going behaviors. Finally, in Defining, Observing, and Describing \u27Non-Submitters:\u27 Evidence from the Common App Universe on Students Who Start but Do Not Complete a College Application, I provide the first documented evidence on students who begin a college application but never complete it. With novel data from the nation’s largest application provider, I find that non-submission behaviors vary widely by student, parent, school, community, and other dimensions and identify important predictors of non-submission status that policymakers and future researchers can leverage to target tailored college application supports. Each of these studies not only fills an existing gap in knowledge but also lays the foundation for future empirical work and provides actionable insights for policymakers and practitioners alike
Preparing One’s Act: Performance Supports And The Question Of Human Nature In Early China
Get PDFSince the 20th century, Chinese institutions have been recovering a growing number of ancient objects, among which figure manuscripts produced during the Warring States (453–221 BCE) era. These are the protagonists of this dissertation. Chapter 1 articulates the overarching goal of my study: the importance of rigorous philological and intellectual engagement to promote the significance of these manuscripts in and beyond the study of early Chinese history. In Chapter 2, I analyze manuscripts produced around 300 BCE as what I call “performance supports,” rather than self-contained philosophical and historical essays. My notion of performance supports incorporates observations about the composite nature of early Chinese manuscripts, but better accounts for other textual features, such as errors, abrupt endings, list-like passages, etc. Chapter 3 discusses the implications of my thesis. I show how performance supports were used in practices of knowledge management that relied on, but went beyond, the written medium. I explore oratory, recitation, literary compositions, and writings used to organize and retrieve knowledge. Second, I compare performance supports to other Warring States texts, so as to highlight the peculiarities of both groups and confirm that the concept of performance support is not an ad-hoc solution. Chapter 4 focuses on the performance support *Natural Dispositions Come from Endowment 性自命出, and reconstructs ways in which this manuscript functioned as the basis for central philosophical debates on human nature during the Warring States period. The dissertation is completed by a new philological study of *Natural Dispositions
Deep Learning And Uncertainty Quantification: Methodologies And Applications
Get PDFUncertainty quantification is a recent emerging interdisciplinary area that leverages the power of statistical methods, machine learning models, numerical methods and data-driven approach to provide reliable inference for quantities of interest in natural science and engineering problems. In practice, the sources of uncertainty come from different aspects such as: aleatoric uncertainty where the uncertainty comes from the observations or is due to the stochastic nature of the problem; epistemic uncertainty where the uncertainty comes from inaccurate mathematical models, computational methods or model parametrization. Cope with the above different types of uncertainty, a successful and scalable model for uncertainty quantification requires prior knowledge in the problem, careful design of mathematical models, cautious selection of computational tools, etc. The fast growth in deep learning, probabilistic methods and the large volume of data available across different research areas enable researchers to take advantage of these recent advances to propose novel methodologies to solve scientific problems where uncertainty quantification plays important roles. The objective of this dissertation is to address the existing gaps and propose new methodologies for uncertainty quantification with deep learning methods and demonstrate their power in engineering applications.
On the methodology side, we first present a generative adversarial framework to model aleatoric uncertainty in stochastic systems. Secondly, we leverage the proposed generative model with recent advances in physics-informed deep learning to learn the uncertainty propagation in solutions of partial differential equations. Thirdly, we introduce a simple and effective approach for posterior uncertainty quantification for learning nonlinear operators. Fourthly, we consider inverse problems of physical systems on identifying unknown forms and parameters in dynamical systems via observed noisy data.
On the application side, we first propose an importance sampling approach for sequential decision making. Second, we propose a physics-informed neural network method to quantify the epistemic uncertainty in cardiac activation mapping modeling and conduct active learning. Third, we present an anto-encoder based framework for data augmentation and generation for data that is expensive to obtain such as single-cell RNA sequencing
Kat6a Initiates An Epigenetic Transcriptional Control Module To Drive Oncogene Expression In Acute Myeloid Leukemia
Get PDFAcute myeloid leukemia (AML) is one of the most lethal blood malignancies but in lack of therapies targeting leukemia-specific dependencies. Epigenetic programs are often dysregulated in acute myeloid leukemia (AML) and help enforce an oncogenic state of differentiation arrest. Thus, targeting epigenetic vulnerabilities suggests a new angle of developing AML therapeutics. To identify key epigenetic regulators of AML cell fate, we performed a differentiation-focused CRISPR screen in AML cells. This screen identified the histone acetyltransferase KAT6A as a novel regulator of myeloid differentiation that drives critical leukemogenic gene expression programs. We show that KAT6A is the initiator of a newly-described transcriptional control module in which KAT6A-catalyzed promoter H3K9ac is bound by the acetyllysine reader ENL, which in turn cooperates with a network of chromatin factors to induce transcriptional elongation. Inhibition of KAT6A has strong anti-AML phenotypes in vitro and in vivo, suggesting that KAT6A small molecule inhibitors could be of high therapeutic interest for mono or combinatorial differentiation-based treatment of AML.This work provides new insights of how epigenetic writers and readers cooperate to maintain oncogenic programs. The mechanistic discoveries would also shed light on studies of other types of cancer. Besides significant biological and clinical implications, this work also provides a methodology paradigm for using high-throughput screen to explore cell fate determination in other biological systems
Preaching Prosperity: Pentecostals And The Transformation Of American Evangelicalism, 1946 – 1988
No full textOver the course of the twentieth century, Pentecostalism grew at a staggering rate in the United States and profoundly reshaped the American religious landscape. Yet, it remains sorely understudied by historians, particularly in its broader relationship to and impact on evangelicalism and the Religious Right. This dissertation traces Pentecostal movement building in the United States from the depths of the Great Depression to the end of the Reagan era. It shifts focus away from the East and West coasts and towards Oklahoma, which served as a key space for the development of the Prosperity Gospel in the postwar period. Through the spread of the Prosperity Gospel, the rise of powerful Pentecostal television networks, and in their relationship to political actors and state institutions, Pentecostals shaped how evangelicals came to understand questions of inequality and the role of government in their lives. Between the 1940s and the 1960s, Pentecostal laypersons and evangelists wrestled control away from denominational leaders in their churches and embraced health and wealth as the divine right of the spirit-filled believer. These upheavals had a profound impact on the social structure of Pentecostalism. From the 1960s onwards, white Pentecostals actively broke with segregationist politics and started to integrate African Americans into their revivals and education institutions and onto their television programs and speaking circuits. Yet, Pentecostal evangelists understood inequality as a spiritual battle rather than an outcome of social and material power and centered faith alone as the only solution to racism and poverty. In the final third of the twentieth century, Pentecostal media empires became key promulgators of anti-welfare narratives that opposed government attempts to challenge discrimination and inequality. At the very moment when questions of inequality and its causes became most contested, the Prosperity Gospel provided an alternative explanation for the persistence of racial and economic inequality. This not only shaped evangelical attitudes to capitalism and created coalitions between Pentecostals and conservative political actors but produced a cultural infrastructure for neoliberalism
Evaluating Brain Derived Extracellular Vesicles As Diagnostic Biomarkers Of Traumatic Brain Injury
No full textMild traumatic brain (TBI) injuries are difficult to diagnose with standard imaging techniques, and currently lack adequate biomarkers for disease diagnosis and monitoring. The heterogeneity of TBI etiology challenges efforts to discover sufficiently robust and accurate molecular biomarkers of TBI endophenotypes. While much progress in this area has been made using protein-based biomarkers of neuronal and astrocyte cell damage for grading injury severity, biomarkers indicating the activation of specific underlying pathologic processes are needed to evaluate and suggest personalized interventions. The work of this thesis aims to investigate the diagnostic potential of brain derived extracellular vesicles (EVs), a diverse class of lipid enclosed nanoparticles shed from virtually all brain cell types with molecular cargo reflecting the state of their origin cells. We utilize an emerging strategy known as Track Etched NanoPOre (TENPO) to enrich for EVs based on their expression of Glutamate Ionotropic AMPA Receptor Subunit 2 (GluR2) and predominantly originating from neurons, and those expressing GLutamate ASpartate Transporter (GLAST) and predominantly originating from astrocytes. We combine this technology with tools of molecular biology – namely ultrasensitive protein detection and next-generation sequencing of microRNA – to analyze the molecular cargo of these EV populations. We demonstrate using plasma samples obtained from mild TBI patients and healthy volunteers that TBI elicits alterations in the distribution and expression of EV molecular cargo and illustrate that different EV populations and plasma possess independent, yet potentially complimentary information on the state of the injured brain. We also show that this independence of molecular information across EV populations and in plasma persists over time in a swine model of rotational acceleration based TBI. Together, the work of this thesis suggests brain derived EV populations may be well suited to provide therapeutically meaningful information about an individual’s TBI currently inaccessible with traditionally studied protein biomarkers or brain imaging modalities
A Melting Fossil: Constituting Planetary Time In The Cryosphere, 1815-1980
No full textA Melting Fossil traces how, since the nineteenth century, naturalists and scientists have used ice as a natural chronometer to understand the deep past and future of the Earth. Using archival sources that span two centuries and three continents, this project argues that through ice, Earth scientists have refashioned their conceptualization of deep time from something slow, lumbering, and uniform to something much more capricious—a shift that has profoundly shaped social understandings of environmental change. By tracing how scientific assertions about temporality have materialized, and how this materialization determines (and limits) cultural notions of and political actions on the past and future of the planet, A Melting Fossil reveals how deep time has expanded beyond the purview of the Earth sciences to form an epistemological frame for human-environment relationships
Human Tissue-Engineered Nigrostriatal Pathway Encased In Hyaluronic Acid For Axon Tract Reconstruction In Parkinson\u27s Disease
No full textThe motor symptoms of Parkinson’s disease (PD) are caused by the loss of dopamine in the striatum that occurs after the death of dopaminergic neurons in the substantia nigra and their axon fibers along the nigrostriatal pathway. The ideal treatment strategy would rebuild the neuronal and axonal structure of the pathway in an anatomically correct way, which may lead to better restoration of basal ganglia connectivity and dopamine regulation. We developed a reconstruction strategy termed the tissue-engineered nigrostriatal pathway (TE-NSP), which consists of a tubular hydrogel with a collagen/laminin core that encases an aggregate of dopaminergic neurons and their axon tracts. The TE-NSPs are fabricated in vitro to resemble the nigrostriatal pathway for subsequent implantation to restore the pathway. Here we sought to advance the TE-NSPs in terms of their hydrogel encasement, cell source, and clinical translatability. The TE-NSPs were fabricated with hyaluronic acid (HA) hydrogels as a more bioactive and tunable encasement, human iPSC-derived dopaminergic neurons as a clinical cell source, and dimensions fit for various cell densities and axon lengths. We implanted these human TE-NSPs in a rat model of PD and characterized the animals with histology, voltammetry for striatal dopamine release, and motor function tests. HA hydrogels and human iPSC-derived neurons could be used to create TE-NSPs that had a nigrostriatal-like cytoarchitecture, dimensions matching rat brain scales and clinical design criteria, proper dopaminergic phenotypes, and the capacity for dopamine release and innervation of striatal neurons. Implanted TE-NSPs exhibited robust survival, preservation of axon tract integrity, and dopamine release functionality even after 6 months. Rat-scale TE-NSPs led to localized improvements in dopamine and innervation in the dorsal striatum, while constructs with quasi-human dimensions exhibited significant growth into the striatum at 6 months. Further work is needed to show definitive therapeutic benefits and to understand the mechanism of reconstruction with TE-NSPs. Still, this dissertation represents the first demonstration of the replacement of a long-distance brain pathway in a preclinical model using engineered micro-tissue made with human cells