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Associations of Socioeconomic Disadvantage with White Matter, Language Development, and Early Indicators of Affective Symptomatology from Infancy to Early Childhood
No full textABSTRACT OF THE DISSERTATION Associations of Socioeconomic Disadvantage with White Matter, Language Development, and Early Indicators of Affective Symptomatology from Infancy to Early Childhood by Nourhan M Elsayed, M.A. Doctor of Philosophy in Psychological and Brain Sciences Washington University in St. Louis, 2024 Professor Deanna Barch, Chair Socioeconomic disadvantage (SESD) is associated with reduced neurocognitive abilities, particularly in language, and reduced integrity in white matter bundles known to subserve language. These findings are important beyond language development, given evidence that cognition and emotion are dynamic processes, whereby the maturation of one process serves as a foundation for higher-level skills. The current study used data collected from 353 youth and their mothers from the longitudinal Early Life Adversity and Biological Embedding (eLABE) study across four time points, beginning at birth through age three, to examine the associations of SESD with expressive and receptive language, white matter development, and indicators of affective symptomatology from birth to age three. The study found that children with more SESD had lower receptive language at age one and slower receptive and expressive language increases between ages one and three. Children experiencing more SESD had lower radial (RD) and axial diffusivity (AD) in the uncinate fasciculus (UNC) at birth but no differences at birth in fractional anisotropy (FA), RD, or AD, in other examined white matter bundles subserving language (e.g., corpus callosum, inferior fronto-occipital fasciculus, superior longitudinal fasciculus). Across white matter bundles, change in microstructure between birth and age three was not associated with SESD. Contrary to hypotheses, there was no evidence that a relationship between SESD and language was via indirect effects of white matter microstructure or that associations between SESD and white matter microstructure were via indirect effects of language. There was no evidence of serial indirect effects by white matter microstructure and language or language and white matter microstructure from SESD to indicators of affective symptomology. These results highlight the early associations of SESD with language. The associations of SESD with language, with concurrent null associations between SESD and white matter microstructure, underscore the need for additional research examining the longitudinal associations between SESD and structural brain maturation across the lifespan
Essays on Financial Economics and Macroeconomics
No full textThe first two chapters of my dissertation focus on sustainable investing and asset pricing, while the third chapter explores macroeconomics, particularly in the areas of incomplete information and monetary policy. In Chapter 1, “A Theory of Green Investing: Driven by Values and Value”, I investigate the real impacts of green investing driven by both ethical values and financial value. Green investing encourages firms to reduce social costs, even in scenarios where green investors lack bargaining power and profit-driven capital is perfectly elastic in supply. The key driver of this impact is the willingness of some investors to sacrifice financial returns, motivated by values. These investors have a warm glow effect from investing in divisions that adopt clean technology, but only when such investments are made with the intention to reduce pollution. In addition, from a value perspective, such impact expands due to its potential to be exempt from regulations and lower return variance. While green investing has the potential to enhance social welfare, it also contributes to structural inequality by transferring financial gains from green investors to firms. Direct regulations outlawing dirty technology are not optimal if it is nontrivial for green investors to find other causes to get a warm glow effect. The results suggest that lobbying could be an alternative for achieving impact investing without incurring structural inequality. In Chapter 2, “Climate Risk Preparedness and the Cross Section”, we develop a theoretical framework to examine the relationship between a firm’s climate risk preparedness and its investment returns within a two-date stochastic general equilibrium production-based asset pricing model. Our analysis shows that, in equilibrium with an interior solution, a firm’s initial climate preparedness is positively correlated with the expected return on equity. We empirically test this theoretical model using a comprehensive set of assets, including stocks, ETFs, anomalies, and portfolios sorted by characteristics. The empirical findings support our theoretical predictions, highlighting the significant role that the constructed preparedness factor plays in explaining the cross-sectional variation in asset returns. In Chapter 3, ``Policy Rule Regressions with Survey Data , we introduce a simple procedure that leverages survey data to rectify endogeneity bias when estimating policy rule coefficients using the ordinary least squares (OLS) method under flexible information assumptions. We decompose policy rule regressors (e.g., inflation and output gap) into their forecasts made before policy decisions and the associated forecast errors. The forecasts are readily available in survey data and, by construction, orthogonal to the forecast errors and policy shocks under complete information. We further orthogonalize the forecast errors to remove the bias in the presence of information rigidities. Using Monte Carlo simulations, we showcase the efficacy of this procedure in a prototypical new Keynesian model under distinct information settings. As an empirical application, we employ Bayesian methods to compare the performance of the standard OLS approach using real-time data and our approach based on survey data in estimating monetary and fiscal policy rules. Marginal likelihood estimates reveal that our approach consistently outperforms across nearly all model specifications considered
Industry Structure and the Macroeconomy
No full textIn this thesis, I examine various causes and consequences of market power and imperfect competition on the aggregate economy. One major channel through which the market structure evolves is mergers and acquisitions (M&A). Mergers can lead to significant increases in market power, yet can have economy-wide benefits too. In the first chapter, I develop a general equilibrium model with imperfect competition to study what drives M&A, and what the aggregate implications of M&A are. I model mergers as a centralized matching process in order to build a theory of who will merge with whom and I match the predictions of the model to merger sorting patterns observed in the data. The calibrated model supports the view that mergers drive higher market power and, on average, do not result in large productivity-enhancing synergies. Despite this, counterfactual analysis shows that mergers tend to increase aggregate productivity, as they reduce misallocation by lowering the overall dispersion of markups, but decrease output and welfare through a higher aggregate markup. In the second chapter, I employ empirical methods to study the effect of mergers on firm-level markups and productivity. The findings of this chapter provide micro-level support to the view that mergers result in higher market power, and on average, do not result in higher productivity. In the third chapter, I consider the effects of state-owned enterprises (SOEs) on aggregate outcomes. SOEs are a common tool used in many countries to address market power, yet concerns exist about the effects these firms have on industry and aggregate productivity. I characterize when SOEs improve aggregate outcomes in terms of their efficiency, relative to a counterfactual privatized firm
Examination of protective mucosal immune responses to viral sexually transmitted infections
No full textSexually transmitted infections (STI) are a prominent global health issue that affect the sexual and reproductive health of billions worldwide. Viral STIs present a particular challenge due to limited availability of treatment options and their frequent establishment of lifelong infection. One of the most common viral STIs is genital herpes, a recurrent ulcerative disease caused by chronic infection with the human alphaherpesviruses, HSV-1 or HSV-2. Women are particularly susceptible to morbidities of infection ranging from increased risk of HIV-1 acquisition to vertical transfer to neonates, for whom infection can be fatal. Previous efforts to develop a prophylactic vaccine for genital herpes have failed in part due to limited understanding of the mechanisms required for protective immunity in the vagina, which is a primary portal of entry for STIs. Furthermore, most investigation into host responses to genital HSV infection has historically only focused on HSV-2. Little is known about immunity during genital HSV-1 infection despite its rising prevalence across the globe and known differences in disease outcomes. To address these questions and more, we use an established female mouse model of genital herpes to study vaginal immunity during primary HSV infection. Through direct comparisons of HSV-1 and HSV-2 vaginal infection, we seek to identify differences in the innate and adaptive immune response to each virus that determine neuronal infection and mucosal pathology outcomes. From these studies, we determined that HSV-1 triggers a faster innate immune response in the vagina than HSV-2, promoting earlier effector T cell responses and enhanced viral control in both the vagina and peripheral nervous system in an IFN-dependent manner. Rapid vaginal NK cell activation after HSV-1 infection appeared to be a distinguishing factor, aiding faster dendritic cell migration and maturation in the draining lymph nodes. Further investigation into the underexplored vaginal NK cell compartment also revealed an unexpected role in restricting genital skin and vaginal mucosal epithelium damage in coordination with neutrophils during HSV-1 infection. This was in stark contrast to the excessive immunopathology caused by neutrophils during HSV-2 infection. Together, these studies contribute deeper understanding of host immunity to two forms of genital herpes infections and reveal insights regarding protective immune mechanisms in the vagina more broadly
Pituitary Adenylate Cyclase Activating Polypeptide and Its Receptor as Novel Therapeutic Targets for Opioid Induced Hyperalgesia
No full textOpioids are commonly prescribed for the treatment of pain and headache disorders. However, chronic opioid use can result in a paradoxical increased sensitivity to pain as well as an extension of pain area known as opioid-induced hyperalgesia (OIH). One field OIH has been clearly identified is migraine, known as medication overuse headache (MOH). While opioids may provide acute relief, chronic use results in increased migraine pain severity and progression of migraine from an episodic to chronic state. The primary treatment is opioid cessation, which is difficult to implement as patients are reluctant to stop treatment they believe is helping them, and they may also experience opioid withdrawal. Opioid cessation has low retention rates, and one study reports a 50% relapse rate within the first year, which can ultimately feed into a pattern of opioid use disorder. There is thus a desperate need to find effective therapies for OIH, and this disorder would benefit greatly from a focused drug development strategy. In this thesis, I provide a greater understanding about the pathophysiology of OIH and MOH and characterize novel treatment options. Using an unbiased proteomic screen, our lab had previously identified the pituitary adenylate cyclase activating polypeptide (PACAP) as a possible target for both OIH and migraine. In Chapter 2 I showed that PACAP alone could induce allodynia at translationally significant doses. I further demonstrated efficacy of a delta opioid receptor (DOR) agonist, SNC80, in reducing PACAP-induced allodynia. I also elucidated the expression of DOR with PACAP and its receptor PAC1 using in situ hybridization and found high co-expression of DOR with the PAC1 receptor. Together, these results suggest that PACAP can cause allodynia, that this allodynia is blocked by DOR, and that DOR may act by inhibiting PAC1 signaling. Previous studies from our lab have demonstrated the effectiveness of a peptide PAC1 antagonist M65 in an OIH model. PACAPergic blockade was shown to decrease migraine clinically. Small molecule PAC1 receptor antagonists and antibodies have different properties to peptides and are worth investigating in our OIH/MOH models. In Chapter 3, I demonstrate that a small molecule PAC1 inhibitor could block established and prevent development of OIH. Additionally, a PACAP targeting antibody also blocked established OIH and prevented development of OIH and MOH. PACAP and the related peptide, vasoactive intestinal peptide (VIP), can both bind to VPAC1, VPAC2, and PAC1. PAC1 has a lower affinity for VIP than PACAP. PACAP may also activate the MAS-related GPR, member B2 (Mrgprb2) receptor. I determined the receptor and endogenous ligand expression of the PACAPergic, and mu and delta opioid receptors, with cell type resolution using in situ hybridization in the trigeminal nucleus caudalis (TNC). The results indicate that of all PACAP receptors, PAC1 had the highest total expression (~90% cells), followed by VPAC2 (~52%), VPAC1 (~45%), and MRGPRB2 (10%). Considering this high expression, approximately 97% of all mu opioid receptor positive cells co-expressed PAC1 in this region. These results suggest that the PAC1 receptor plays an important role in head pain processing regions. Previously our lab had shown upregulation of PACAP in the periaqueductal gray (PAG) in models of OIH and chronic migraine. In Chapter 4, I focused on the role of the PAG in OIH specifically. I determined that among PACAP receptors, PAC1 exhibited the highest overall expression at 66% of all cells, followed by VPAC2 (~44%), VPAC1 (~27%), and MRGPRB2 (15%). Notably, approximately 86% of all mu opioid receptor positive cells were found to also express PAC1. I used excitatory chemogenetic and shRNA knockdown approaches to characterize whether PAC1 in the ventrolateral periaqueductal gray (vlPAG) is necessary and sufficient to produce mechanical hypersensitivity, similar to OIH. Acute excitation of PAC1-expressing vlPAG neurons resulted in freezing behavior and analgesia, but chronic excitation produced sustained mechanical allodynia. We also used a shRNA approach to knockdown PAC1 receptors in the vlPAG. Compared to the control-OIH group, chronic morphine in animals with knockdown of PAC1 in the vlPAG developed OIH to a lesser extent and recovered more quickly. Together, our data suggests that cells expressing PAC1 in the vlPAG are sufficient to induce hyperalgesia and that the chronicity of OIH is partially dependent on activation of vlPAG PAC1 receptors. The results presented in this thesis provide a deeper understanding of the pathophysiology of OIH and MOH and identify DOR agonists, PAC1 antagonists, and PACAP antibodies as potential therapies for this disorder
Socioeconomic Determinants of Health and Well-Being in a Low Resource Setting: A Case of Older Adults Living in a Rural Setting in Northwestern Cambodia
Get PDFThis dissertation examines the associations between socioeconomic factors, and physical and psychological well-being among older adults in Cambodia. Focusing on subjective and objective socioeconomic status (SES) and the mediating roles of social and welfare support, this dissertation consists of three interrelated chapters that address different facets of the relationships. Paper 1 (Chapter 2) investigates the demographic characteristics, socioeconomic factors, and social support structures among older Cambodians. Findings reveal significant gender and age disparities, with women and the oldest adults more likely to experience lower socioeconomic status and weaker social support. Paper 2 (Chapter 3) explores the associations between subjective and objective SES (household wealth and economic fulfillment) and well-being outcomes. Results indicate that economic fulfillment have a stronger association with psychological well-being compared to household wealth, which substantiates the sigificance of ones’ subjective assessment of their economic standing in relation to psychological well-being. Paper 3 (Chapter 4) focuses on the mediating effects of social and welfare support on the SES-well-being relationship. While social support significantly mediates the association of SES with both physical and psychological well-being, welfare support does not appear to play a meaningful role in these relationships. This finding suggests potential inefficiencies in the government welfare system for older Cambodians. Collectively, these papers provide a comprehensive and contextualized examination of how socioeconomic factors, subjective perceptions, and support systems interact to shape well-being outcomes in a post-conflict, low-resource setting. The dissertation contributes to aging research in low- and middle-income countries and offers practical implications for improving social and health interventions for the vulnerable older population
The Role of Piezo1 in Mediating Chondrocyte Cell Signaling and Senescence
Get PDFOsteoarthritis (OA), the leading cause of disability, is driven by articular cartilage degeneration and inflammation. Mechanosensitive ion channels PIEZO1 and PIEZO2 have been implicated in OA progression via calcium signaling in chondrocytes. This study investigates the role of conditional Piezo channel knockout (cKO) in modulating calcium signaling and senescence in OA, particularly under the supra-physiologic inflammatory condition of a high-fat diet (HFD). Using calcium imaging, we found that Piezo1 cKO and dual Piezo1/2 cKO significantly reduced Yoda1-induced calcium signaling, while Piezo2 cKO alone had no effect. Under HFD conditions, Piezo1 cKO showed a non-significant trend toward reduced calcium influx, potentially due to high inflammatory burden or altered Piezo1 expression. Immunohistochemical analysis revealed that Piezo1 cKO significantly attenuated expression of the senescence marker p16, even under HFD conditions, suggesting downstream protective effects. In contrast, p21 expression patterns were inconsistent and appeared influenced by metabolic or stress-related vi pathways outside of senescence. These findings identify Piezo1 as a key contributor to OA related mechanotransduction and senescence, supporting its potential as a therapeutic target and warranting further investigation into combinatorial strategies for OA intervention
The Little Diagram That Could: Geometric Properties and Statistical Applications of Persistence Diagrams in Topological Data Analysis
Get PDFTopological Data Analysis (TDA) is a collection of techniques for data analysis that leverages topological invariants of spaces formed from data points. These methods excel at extracting useful information from noisy or sparse data, making them attractive to many mathematicians, statisticians, and scientists. In this thesis, we explore TDA on three fronts: algebraic foundations, statistical applications, and metric properties. Throughout, the central object of study is the Persistence Diagram (PD), a summary of the changes in homology that occur as one builds simplicial complexes from the data by increasing a parameter
Hauntological Warfare: Explorations in Propaganda, Influence Campaigns, and Online Affect
Get PDFThis thesis, Hauntological Warfare: Explorations in Propaganda, Influence Campaigns, and Online Aesthetics, investigates how ideological power continues to shape contemporary reality through both overt and spectral means. Drawing from concepts like hauntology, psychological operations (PsyOps), and disinformation aesthetics, I examine how propaganda does not simply vanish once its immediate goals are achieved, but instead lingers—reshaping memory, identity, and cultural narratives through what I call hauntological warfare.
My post-conceptual research-based art practice engages this terrain by creating site-specific installations, performances, and media works that make these invisible forces perceptible. Works such as Kill Zones (for Boeing) (2024), r/RoastMe (2024), and Flowers for Heart Mountain (2024) operate as subversive counter-narratives, summoning ideological ghosts embedded in state violence, institutional erasure, and the aesthetics of surveillance capitalism. Drawing from personal experience as a former propagandist for the U.S. Army, my work locates propaganda not only in public messaging but in material culture, digital environments, and domestic space.
Alongside theorists like Mark Fisher, Günseli Yalcinkaya, and Trevor Paglen, I argue that we are living through a shift where soft and hard power converge—where algorithmic content, affective manipulation, and historical amnesia operate as forms of psychological warfare. To investigate this, I introduce the concept of provisional ethnographic installations: absurdist and poetic visual frameworks that purposefully conflate cultural phenomena to reveal their hidden interdependencies. Through this hybrid artistic method, my thesis explores how power operates through concealment—and how art can function as a method of exorcising the ideological phantoms that continue to haunt us