VictorJuiz/thesis huggingface dataset:
Essays in Health Economics

The influence of individual healthcare providers on healthcare utilization has important implications for healthcare systems and cost savings policies. Primary care physicians may be particularly influential because they have central, coordination roles in medicine, yet little is known about their impacts on healthcare utilization. This dissertation provides new empirical evidence on two fundamental questions. First, to what extent do differences in practice styles of individual primary care physicians, as measured by their patients' spending, explain variation in healthcare utilization? Second, do patients incur switching costs in the form of temporarily higher healthcare utilization when they switch PCPs? Specifically, I study the long-run and short-run effects of switching to different primary care physicians on patient healthcare utilization among traditional fee-for-service Original Medicare patients who are ages 65-99 in the United States./nIn the first chapter, I show that patients who switch from a primary care physician whose other patients have low utilization to one whose other patients have high utilization experience increases in long-run utilization, whereas patients who switch in the opposite direction experience decreases. Regardless of the direction of the change, patients experience short-run increases in utilization around the switch. Using a model that includes both patient and physician fixed effects, I find that differences in primary care physician practice styles, as measured by spending, explain about 2% of the variation in long-run total utilization and about 13% of the variation in long-run primary care utilization within regional markets./nIn the second chapter, I estimate the short-run effects of switching primary care physicians on patient utilization. I focus on patients who involuntarily switch because their physicians relocate or retire, such that the timing of the switches is exogenous. Each primary care physician switch leads to approximately $500-725 in additional total utilization, and 20-30% comes from temporary increases in primary care utilization. Combining my findings from these two chapters, I construct counterfactuals and find that policies that reallocate patients across primary care physicians could potentially be counterproductive due to modest long-run savings and substantial short-run switching costs. Finally, I discuss potential mechanisms that could generate these switching costs and their welfare implications.

Advisor: Handel, Benjamin R
Card, David
Integrated regulation at the levels of mRNA, translation, and protein in Saccharomyces cerevisiae

Gene expression in eukaryotes is tightly controlled to determine cell identity and function, and to drive complex differentiation and developmental programs. Each step in the gene expression process can be regulated to influence the final outcome and thus, a comprehensive view of gene expression changes at multiple levels is required for full understanding of the regulation of gene expression. To investigate how the cell integrates regulatory mechanisms at multiple levels to achieve precise and coordinated regulation of gene expression, we combined genome-wide techniques and traditional methodologies to obtain key measurements of gene expression and to dissect the contribution of each step in determining gene expression levels. In chapter 2, we focus on how ribosomal deficiencies alter gene expression. We probed the changes of mRNA abundances, translation rates, and protein abundances in a panel of ribosomal protein mutants and observed changes that were both specific to individual ribosomal proteins and dose-dependent with degree of translation deficiency. We also observed strong evidence of compensatory regulation, including at the transcriptional and protein degradation levels, and distinct cellular responses to loss of small and large ribosomal subunit components. Three current models have been proposed to explain the specific phenotypes associated with loss of ribosomal proteins in diseases of ribosome deficiency, or ribosomopathies, and our data revealed evidence to support all of these models, albeit to differing extents. In chapter 3, we describe a novel regulatory mechanism in which the protein levels are determined by identity, instead of levels, of the transcripts. We collected parallel measurements of mRNA, translation, and protein through a timecourse in yeast meiosis and discovered that the toggling between canonical transcript isoforms and long undecoded transcript isoforms regulates the outcome of gene expression for 380 genes. In chapter 4, we study the regulation of ribosome biogenesis (RiBi) genes and show that global inhibition of translation de-represses RiBi mRNA transcription in a condition-dependent manner. In summary, in three different contexts, we report a surprisingly high degree of integration between different levels of gene expression, highlighting the importance of parallel measurements of different gene expression intermediates to interpret the link between gene expression and cellular outcomes.

Advisor: Brar, Gloria A.
Human Behavior and Myopia

Refractive errors (e.g. nearsightedness or farsightedness) are the product of a mismatch between the axial length of the eye and its optical power, creating blurred vision. Uncorrected refractive errors are the second leading cause of world-wide blindness. One refractive error currently holding tremendous scientific interest is myopia (or near-sightedness), mostly due to its rising prevalence worldwide and associated ocular disease burden. That the increase in myopia prevalence has been rapid, occurring over a short period of time, suggests environmental influences in addition to genetic influences on eye growth. In this dissertation, the evidence for influences of genetic and environmental factors related to myopia development are presented as well as a discussion of the possible role of nutritional and body-metric factors through an analysis of NHANES data. Key environmental factors that have implicated in myopia development and/or progression relate to near work and outdoor activity, however traditional studies investigating these factors rely on subjective questionnaires. Possibly related to this limitation is the fact that no strong risk factors for myopia development have been described to date. The dissertation research presented here is novel in that it utilized objective technologies, including wearable technologies, to investigate the relationship between the dynamics of habitual indoor and outdoor behaviors, including the lighting characteristics experienced, to myopia presence and severity in young adult university students in both an academic and non-academic period.

Advisor: Wildsoet, Christine F
Raza y nación. Procesos de construcción de identidades nacionales en España (1750-1833)

This Doctoral Dissertation explores the transition that took place in the eighteenth century from the figure of the king as the symbolic representative of the nation to the recently created category of the citizen as the new national metaphor all over the western world. The necessity of creating a positively racialized model of citizen that would serve as a symbolic representative of the nation followed the racial zeitgeist of the time, dictated by imperial expansion together with the creation of new systems of thought such as scientific racism, geographic determinism, or phrenology. Spain, former hegemonic power during Early Modern Europe, was expelled from Modern Europe in the eighteenth century, being displaced for the first time to a racialized southern European periphery at a time when race matched power. Intellectual battles fought through the first stages of the Printed Press and the Encyclopedia, used propaganda to build or destroy national identities. Through an extensive study about foreign views of Spain by France, England, and Latin America, and their reception in Spain, this doctoral dissertation explores Spanish attempts to dislocate Northern European eighteenth and nineteenth centuries epistemologies by creating alternative networks of knowledge and proposing a model of empire where race was not used as a political ideology, with the aim of re-branding itself in the new nation-building landscape of the time.

Advisor: Iarocci, Michael P.
The Accelerating Universe, the Landscape, and the Swampland

The accelerating expansion of the universe is a portal for us to understand the physics at the very fundamental level. It’s a phenomena that is apparently IR but intrinsically UV. In this dissertation we investigate various aspects of the accelerating universe in the context of the string landscape and swampland. In the first part of the dissertation, we investigate if the observed small and nearly scale-invariant primordial cosmic perturbation is typical in the landscape of vacua after imposing anthropic selections on them. We propose a scenario that combines new-inflation-type models with the landscape, in which our universe had been trapped at a meta-stable vacuum and underwent a precedent inflation. We argue that the initial inflaton field value is typically non-zero because of the quantum fluctuation created during the precedent inflation. Imposing anthropic constraint on the initial condition, together with certain distributions of inflation model parameters that are physically well- motivated, makes the observed small and nearly scale-invariant spectrum typical. In a latter part of the dissertation, we discuss the quintessence model building in supergravity, in light of the recently proposed de Sitter swampland conjecture. Particularly, the conjecture claims that the scalar potential V in any consistent theory of quantum gravity should satisfy the constraint |∇V | ≥ cV where c is a positive number of order one. If true, positive cosmological constant (even metastable one) cannot be obtained in string theory and dark energy needs to be described by an evolving scalar field, i.e. quintessence, within supergravity. We demonstrate that by imposing a shift symmetry on the Kahler potential, one can embed any quintessence models into supergravity while avoiding the fifth force constraint and protecting the flatness of the quintessence potential from supersymmetry breaking, which are the two main obstacles when constructing quintessence models in supergravity. In addition, the small energy scale of quintessence is technically natural in this setup. In the last part of the dissertation, we discuss the phenomenological implications of swampland conjectures on both inflation and dark energy, using the fact that the conjectures are universal throughout the whole field space. We show that the refined de Sitter conjecture, along with multi-field inflation, opens up the opportunity for observations to determine if the dark energy equation of state deviates from that of a cosmological constant.

Advisor: Murayama, Hitoshi
Boundaries of the Hindsight Bias

The hindsight bias may not be as robust as previously believed. Also known as the “knew-it-all-along effect” (Fischhoff, 1975) the hindsight bias refers to the inability for individuals to remember their previous state of knowledge after learning an outcome. Researchers have found people fall victim to hindsight biases in a variety of domains, including general knowledge (Fischoff, 1977; Wood, 1978), medical decisions (Arkes, Wortmann, Saville, & Harkness, 1981), and political outcomes (Fischhoff & Beyth, 1975). Multiple failures to debias, with methods including informing participants about the bias (Fischhoff, 1977) and manipulating participant perspective (Wood, 1978) further grew the reputation for the strength of this bias. However, we must interpret older results in the behavioral sciences with new perspective on the importance of sample size and statistical power (Ioannidis, 2005). This dissertation proposes to investigate when and why hindsight bias fails to appear, and what it means for the psychological processes underlying the hindsight bias, and more broadly, the interpretation of older psychological research.

Advisor: Moore, Don A
Turning Autophagy On and Off through the Class III PI-3 Kinase

Autophagy (self-eating) is an essential process for cellular self-renewal. The class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) is central to autophagy initiation. The V-shaped architecture of the four-subunit version of PI3KC3-C1 consists of VPS34, VPS15, BECN1, and ATG14. Chapter 2 shows that a putative fifth subunit, NRBF2, is a tightly-bound component of the complex that profoundly affects its activity and architecture. NRBF2 enhances the lipid kinase activity of the catalytic subunit, VPS34. We used hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) and negative stain electron microscopy to map NRBF2 to the base of the V-shaped complex. NRBF2 interacts primarily with the N-termini of ATG14 and BECN1 and activates VPS34 through its N-terminal MIT domain./nThe ability of NRBF2 to activate the lipid kinase of VPS34 via an allosteric mechanism had not been determined. Chapter 3 shows precisely where the MIT domain of NRBF2 binds to PI3KC3-C1, that one copy of the MIT domain is insufficient for activation, and that full activation requires a second copy of the MIT domain. Dimeric NRBF2 cinches around the conformational flexible catalytic arm of the complex and stabilizes the lipid kinase domain of VPS34 and the putative kinase domain of VPS15./nMembrane targeting of the BECN1-containing class III PI 3-kinase (PI3KC3) complexes is pivotal to the regulation of autophagy. Chapter 4 describes how a cryptic membrane binding site within BECN1 was identified. First, the interaction of PI3KC3 complex II and its ubiquitously expressed inhibitor, Rubicon, was mapped to the first β sheet of the BECN1 BARA domain by hydrogen-deuterium exchange and cryo-EM. The interaction determinants were confirmed in cell-based assays of PI3KC3 activity and autophagy. These data suggested that BARA β sheet-1 unfolds to directly engage the membrane. This mechanism was confirmed using protein engineering, giant unilamellar vesicle assays, and molecular simulations. Using this mechanism, a BECN1 β sheet-1-derived peptide activates both PI3KC3 complexes I and II, while HIV-1 Nef inhibits complex II. These data reveal how BECN1 switches on and off PI3KC3 binding to membranes. The observations explain how PI3KC3 inhibition by Rubicon, activation by autophagy-inducing BECN1 peptides, and inhibition by HIV-1 Nef, are mediated by the switchable ability of the BECN1 BARA domain to partially unfold and insert into membrane.

Advisor: James, Hurley H
The Pivot to Canonisation: Fayḍ Kāshānī and the Safavid Hadith Discourse

This dissertation consists of an inquiry into Shiʿi hadith, focusing on Muḥsin Fayḍ Kāshānī (1599–1680) as its central figure, Safavid Iran (1501–1722) as its period of interest, and hadith canonisation as its main theme. Fayḍ was a seventeenth-century polymath and the compiler of an influential hadith compendium entitled al-Wāfī. Completed in 1658, al-Wāfī is unique in that it was the first major Shiʿi hadith compendium to have appeared since the Istibṣār of al-Ṭūsī (d. 1067), compiled six centuries earlier. Al-Wāfī is also the first work to provide a comprehensive commentary on the Imāmī hadith corpus collectively referred to as the Four Books (al-kutub al-arbaʿa), namely al-Kulaynī’s al-Kāfī, Ibn Bābūya’s Man lā yaḥḍuruhu ’l-faqīh, and al-Ṭūsī’s Tahdhīb al-aḥkām and al-Istibṣār. While in recent years various aspects of Fayḍ’s thought have been briefly explored, his writings on hadith remain largely neglected. This dissertation attempts to present a detailed study of Fayḍ’s approach to hadith as a compiler, exegete, theologian, and jurist. It examines al-Wāfī’s structure and content, sources and influences, and the principles that direct Fayḍ’s hadith authentication, compilation, and interpretation. In pursuing this line of enquiry, this dissertation contextualises al-Wāfī within Fayḍ’s extensive writing oeuvre as well as the wider Safavid hadith discourse. This includes a study of the emergence of the Four Books as the locus of discussions regarding the authenticity of Shiʿi hadith corpus during the sixteenth and seventeenth centuries./nIn addition to examining al-Wāfī’s relation to the historical development of arguments related to the authority of the Four Books amongst Safavid scholars, this dissertation addresses the issue of the canonicity of Shiʿi hadith as discussed in Fayḍ’s writings. Based on its examination of Fayḍ’s attempts at providing a definitive hadith compendium, this study concludes that certain elements within his thought – such as privileging a report’s content (matn) over its documentary evidence (sanad) as the most reliable means of hadith authentication – problematize the claims of canonicity for any particular corpus of hadith including his own./nIn investigating how the discipline of hadith was envisioned by one of its leading practitioners, this study also opens a window onto the vast panorama of theological views, exegetical principles, and theories of hadith authenticity that have continued to shape Shiʿi thought to the present. This dissertation represents a necessary step towards a larger project of writing a reception history of the Four Books from the eleventh century to the present and investigating the factors that have contributed to their consolidation as the most authoritative sources of Shiʿi hadith.

Advisor: Ahmed, Asad Q
Synthesis and Characterization of Redox-Active Metal–Organic Frameworks

This dissertation documents efforts to use a variety of synthetic approaches to generate new redox-active metal–organic frameworks and improve the properties of known frameworks. Chapter 1 introduces the field of metal–organic frameworks and discusses observed redox activity of metal nodes and organic linkers. Additionally, the application of the Langmuir-Freundlich gas adsorption model and the use of IAST selectivity calculations to quantify and predict gas sorption in metal–organic frameworks are discussed. Chapter 2 discusses the successful targeted synthesis of the templated, mixed-metal framework Fe–Zn(dobdc) with proposed short-range order in the metal distribution. This ordered system demonstrates thermal stability for O2 adsorption compared to both monometallic Fe2(dobdc) and nontemplated Fe~Zn(dobdc) via a suite of in situ techniques. Chapter 3 documents the first isolation of the highly oxygen-sensitive framework FeII(H2gallate)∙2H2O. This unusual material exhibits remarkable permanence of crystallinity upon exposure to air as shown by single-crystal-to-single-crystal diffraction experiments. Isothermal gas adsorption measurements reveal an unparalleled selectivity for ethylene over ethane stemming from size exclusivity in narrow framework pores. The redox activity of this system is leveraged to tune gas sorption properties in a mixed-valent isomer: FeII/III(Hxgallate). Chapter 4 details efforts to apply several different solvent-free synthetic approaches to the synthesis of both iron- and early transition metal-containing frameworks. Melt based reactions are used to obtain a layered two-dimensional solid, Fe(bzimid)2, as well as the crystalline metallocene-derived materials Cr–bzimid and V–bzimid. A high-temperature metal-powder-based synthetic route is successfully applied for the first time for an iron-based metal–organic framework in the case of Fe(imid)2. Additionally, air- and solvent-free ball milling is shown to increase reaction yields for metal–gallate frameworks and provide evidence of redox activity in the gallate linker. Lastly, Appendix A details the design and use of the Breen adapter, a glass tube adapter with important uses in the field of metal–organic frameworks.

Advisor: Long, Jeffrey R
Energy and Entropy in Quantum Field Theories

Energy conditions play an important role in constraining the dynamics of quantum field theories as well as gravitational theories. For example, in semi-classical gravity, the achronal averaged null energy condition (AANEC) can be used to prove that it is always slower to traverse through a wormhole than to travel around via its exterior. Such conditions prevent causality violations that would lead to paradoxes. Recent advances have been made in proving previously conjectured energy conditions directly in quantum field theory (QFT) as well as in uncovering new ones./nThis thesis will be an exploration of various energy inequalities in conformal field theories (CFTs) as well as semi-classical quantum gravity. At the core of this work lies the recently proved quantum null energy condition (QNEC). The QNEC bounds the null energy flowing past a point by a certain second shape derivative of entanglement entropy. We will demonstrate that the QNEC represents a deep connection between causality, energy and entanglement in quantum field theories. We explore this connection first in the context of holographic CFTs. Calculations in holographic theories will lead us to conjecture that the so-called diagonal QNEC is saturated in all interacting QFTs. We will then provide further, independent evidence that this conjecture holds for all CFTs with a twist gap by explicitly calculating shape derivatives of entanglement entropy using defect CFT techniques.

Advisor: Bousso, Raphael
Democratizing Web Automation: Programming for Social Scientists and Other Domain Experts

We have promised social scientists a data revolution, but it has not arrived. What stands between practitioners and the data-driven insights they want? Acquiring the data. In particular, acquiring the social media, online forum, and other web data that was supposed to help them produce big, rich, ecologically valid datasets. Web automation programming is resistant to high-level abstractions, so end-user programmers end up stymied by the need to reverse engineer website internals—DOM, JavaScript, AJAX. Programming by Demonstration (PBD) offered one promising avenue towards democratizing web automation. Unfortunately, as the web matured, the programs became too complex for PBD tools to synthesize, and web PBD progress stalled./nThis dissertation describes how I reformulated traditional web PBD around the insight that demonstrations are not always the easiest way for non-programmers to communicate their intent. By shifting from a purely Programming-By-Demonstration view to a Programming-By-X view that accepts a variety of user-friendly inputs, we can dramatically broaden the class of programs that come in reach for end-user programmers. Our Helena ecosystem combines (i) usable PBD-based program drafting tools, (ii) learnable programming languages, and (iii) novel programming environment interactions. The end result: non-coders write Helena programs in 10 minutes that can handle the complexity of modern webpages, while coders attempt the same task and time out in an hour. I conclude with a discussion of the abstraction-resistant domains that will fall next and how hybrid PL-HCI breakthroughs will vastly expand access to programming.

Advisor: Bodik, Rastislav