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EVALUATION OF COVARIATES ADJUSTMENT APPROACHES ON ESTIMANDS OF TIME-TO-EVENT OUTCOMES
Get PDFIn clinical research, the hazard ratio (HR) is widely used to interpret treatment effects, yet it can produce misleading results due to its non-collapsible nature in non-linear models. To circumvent this issue, we recommend alternative measures like the differences and ratios of restricted mean survival times (RMST) and milestone probabilities, which are both logically coherent and collapsible, making them more interpretive and clinically meaningful. Our research involves a detailed simulation study of various statistical methods in the context of two-group randomized clinical trials, emphasizing the importance of adjusting for baseline covariates to improve analysis accuracy. We examine methods such as adjusted Cox regression, Kaplan-Meier estimators with Inverse Probability Weight (IPW), and Targeted Minimum Loss-based Estimation (TMLE), comparing them against standard unadjusted techniques. Our findings indicate that while all adjusted methods tend to slightly underestimate effects and show over-coverage, they maintain adequate statistical power. Specifically for milestone probabilities, all adjusted methods gave unbiased estimates except for TMLE, which displayed notable bias and lower power. In situations with imbalanced subgroups, adjusted methods surpassed unadjusted ones in performance. This study's insights are further illustrated using data from the OAK trial, showcasing the practical application and relevance of these adjusted methods in real-world clinical trials
Environmental Peacebuilding: An Opportunity to Create Sustained Peace and Stability Through Climate Resilience
Get PDFThe narrative around environmental issues leading to increased conflict has become very prominent and is raising alarm bells globally. This discourse has helped push researchers to think through this connection and has been beneficial in invoking new fields of study, such as environmental peacebuilding. Environmental peacebuilding is an emerging field that focuses on using environmental issues as an avenue for peace instead of conflict. Given the developing stage of the field, there is a unique opportunity to explore the potential of environmental peacebuilding and its broader applications. The following research examines environmental peacebuilding's role in establishing sustained peace and stability by promoting climate resilience. This research aims to first understand the connections between environmental peacebuilding, climate resilience, and sustained peace and stability. It then aims to explore if and how environmental peacebuilding could be used to manage the increasing risks of climate change.
Topic Triangle
The topic triangle below provides a visual guide for the connections between environmental peacebuilding, climate resilience, and sustained peace and stability that are explored within this research. The first connection suggests that implementing environmental peacebuilding practices in fragile states can both promote climate resilience and promote sustained peace and stability. The second connection suggests that climate resilience can promote sustained peace and stability in addition to contributing to positive environmental peacebuilding. The third connection suggests that sustained peace and stability can in turn promote climate resilience. The solid arrows indicate a direct increase from one pillar to another while the dotted arrows indicate an input from one pillar to another. The proposed theory is that environmental peacebuilding can create sustained peace and stability through establishing climate resilience. The diagram also shows that in addition to the main flow, many of the connections become positive feedback loops which consequently increase the inputs and outputs of the other pillars
AMYLOID, TAU, AND NEURODEGENERATION: ISOLATING PRECLINICAL TARGETS OF AD
Get PDFAlzheimer's disease (AD) is the most common form of dementia among older persons and is characterized by a progressive decline in memory and other cognitive functions (Blennow et al., 2006). Pathologically, AD is defined by the accumulation of amyloid plaques and neurofibrillary tangles leading to neuronal degeneration and progressing atrophy (McKhann et al., 2011). Amnestic mild cognitive impairment (amnestic MCI) is a transitional state between normal memory function and dementia, with faster progression to AD than in healthy controls (Petersen, 2004; Petersen et al., 2001). Some older adults report subjective memory complaints (SMC) despite normal memory assessments, which may predict cognitive decline and precede MCI by about 15 years (Reisberg & Gauthier, 2008). These pathological and clinical changes form a diagnostic trajectory from normal cognition to AD (Ewers et al., 2011). Given the growing focus on quantifying preclinical pathological changes, this work presents a series of experiments utilizing the Amyloid, Tau, and Neurodegeneration (ATN) framework proposed by Jack et al. (2018) to investigate the biomarker profile of individuals with an SMC. These experiments utilize fluid and structural biomarkers to investigate these changes in a sample from normal older adults, older adults with an SMC, and patients with amnestic MCI. The first experiment (Chapter 2) demonstrates that structural biomarkers can quantify an SMC. The second experiment (Chapter 3) shows a relationship between ATN fluid markers, structure, and cognition. These findings support previous research situating an SMC as a relevant indicator of pre-MCI decline on the AD continuum
Inhabiting Masculinities: Kinship, Friendship, and Unemployment Under Military Occupation in Kashmir
No full textThis dissertation ethnographically explores how militarization and unemployment shape young men’s webs of relations in Indian-occupied Kashmir. Understood by state-led development initiatives as potential militants and by family members as having failed kin obligations, how do Kashmiri young men come to inhabit the everyday? This study traces young men’s itineraries between a village in rural Indian-occupied Kashmir and urban employment opportunities in New Delhi. I consider how young men attempt to manage financial precarity and the depredations of the state through their kin and friend groups, while also tracing how these intimate relations produce betrayals and doubts which further open young men to the violence of the occupation. Considering then moments of leisure among these young men, I describe their collective moods, living temporarily as if free of family and occupation alike. Taking seriously the stories they told, the breaks they took from household obligations, and the imagination of other loves and life trajectories, we may see masculine intimacies as generating possibility for young men in the present. In the interstices of occupation, young men experiment with alternate senses of masculinity from those envisioned by development-as-peacebuilding policy.
Although recent work in Kashmir Studies has acutely documented how Kashmiri subjects are victimized by the Indian military’s predations, and how Kashmiris sustain resistance to the occupation, less attention has been granted to Kashmiri strategies in securing themselves in the everyday that is itself fragile. Through a method of accompaniment and multi-sensorial attunement, I move anthropological engagements with colonization beyond the resisting or collaborating subject, towards the fraught work of sustaining intimate relations. In this way, my work also unsettles the assumptions undergirding the “youth bulge” theory in Development and Conflict Studies, which links high male youth unemployment with increased political violence. Situating unemployed youth within a wider set of relations than just their political affiliations, my research ethnographically traces how financial precarity is dispersed and refracted through kin and friend groups, rather than borne by the lone subject of political ideology. Further, my work demonstrates how, even when futures are foreclosed, intimacy may yet birth collective possibility in the present
FACTORS FOR SUCCESS AND BARRIERS, YOUTH ACHIEVEMENT IN COMMUNITY-BASED ORGANIZATIONS: A STUDY OF SCOUTING
Get PDFYouth who obtain the highest levels of achievement in community-based organizations (CBO) like the Boy Scouts of America can find themselves with more social capital and expanded opportunities for higher education and careers. However, youth do not enjoy these opportunities and benefits equally across socioeconomic, racial, and ability groups. Many factors contribute to a scout's ability to persist to the highest levels, and some barriers inhibit persistence. Using an online survey, the Baltimore Area Council (BAC) of the Boy Scouts of America was the sample group for this study. A 36-question survey was sent to 211 Scoutmasters in the BAC. Sixty-four surveys were returned, and 57 were usable. The findings of the study showed that three key factors influenced the persistence of Scouts to reach the rank of Eagle Scouts. The factors were parental involvement, engagement of Scout leaders in the bigger picture of Scouting beyond their units, and inclusion challenges. The conceptual framework for this study places emphasis on education as a solution. The training modules presented in the last chapter were designed based on the factors and barriers identified in the study
Constitutional Silence: To Delegate or Not to Delegate, That is the Question
Get PDFOn June 28th, 2024, the most cited administrative law case, Chevron U.S.A. Inc. v. Natural Resources Defense Council, Inc. (NRDC) from 1984 was overturned. In this paper, both quantitative and qualitative analyses are used in order to gain insight into the ideologies of congressional delegation. The first chapter lays down the framework for discussing different differences and their interaction with federal agency decision making. The second chapter discusses the analysis of Martin-Quinn scores and past judicial decisions to inspect the Supreme Court's opinion of the now-overturned Chevron doctrine and what may come to replace it. The third and last chapter inspects the constitutional aspect of delegation, the Founding Fathers' intentions, and subsequently the idea of the separation of powers and constraints of the government. Due to the decision of Loper Bright Enterprises v. Raimondo not clarifying what the replacement of the Chevron doctrine will be, this provides an opening for whichever doctrine or ideology will replace Chevron. This results in a very large constitutional question, as there is no mention of delegation within the Constitution. With the Constitution silent to the question of delegation, it must either be amended or inferred. This paper finds that there needs to be significant clarification either from Congress, the Supreme Court, or the Constitution, in order to resolve the constitutional question of delegation
Cross-species Integration of Single Cell RNA Sequencing data
No full textSingle-cell RNA sequencing (scRNA-seq) has revolutionized genomic studies, enabling detailed transcriptomic profiling across many species, including humans and various model organisms. However, existing methods for integrating scRNA-seq data across species are often inadequate, struggling with data heterogeneity and failing to capture conserved biological signals effectively. In our study, we developed a novel integration approach that iteratively refines the selection of both highly variable and conserved genomic features to enhance cross-species comparability. A real data analysis indicates that our method slightly outperforms established techniques like Seurat4CCA, especially in terms of conserving biological variance across species, thereby enhancing the accuracy of integration between different species. This demonstrates feasibility of our approach and suggests its broader application in genomics, potentially benefiting biological and medical sciences by providing a more accurate tool for using animal models to study molecular and cellular mechanisms of human diseases
BYSTANDER ACTIVATION OF CMV- AND EBV-SPECIFIC T CELLS FOLLOWING SEASONAL INFLUENZA VACCINATION IN HEALTHY ADULTS
No full textBystander activation of T cells is a phenomenon where T cells are activated in a non-specific, T cell receptor (TCR)-independent manner. This has been documented in various human diseases as well as in mouse models. Cytomegalovirus (CMV), a member of the human herpesvirus family, increases in prevalence with age and persists in a latent state throughout an individual's lifetime once established. Growing evidence suggests that CMV infection contributes to immunosenescence. Understanding the effects of CMV on human immune responses to unrelated diseases or vaccinations is crucial. While the body of research examining the impact of CMV on influenza vaccine responses in older adults is growing, gaps still exist in understanding how influenza vaccination modifies T cell responses to CMV. Our study investigated the bystander activation of T cells to CMV and EBV in individuals vaccinated with the trivalent influenza vaccine (TIV), focusing on the production of IFN-g, IL-2, and granzyme B. The results indicated that after stimulation with CMV UL-83, there was a significant increase in the percentage of CD4+ IFN-g+ T cells and CD8+ IL-2+ TEMRA T cells post-vaccination. Conversely, following stimulation with CMV UL-55, there was a significant decrease in the percentage of CD8+ IFN-g+ IL-2- T cells and CD8+ IFN-g+ TEMRA T cells post-vaccination. Additionally, stimulation with CMV NR9308 resulted in a significantly higher percentage of CD4+ IL-2+ central memory T cells post-vaccination. Similarly, when stimulated with PepMix and EBV NR9308, the percentage of CD8+ IFN-g+ naïve T cells significantly increased post-vaccination. Our study provides insights for enhancing seasonal influenza vaccine formulations and delivery strategies tailored to vulnerable populations
Challenging the American Mental Health Paradigm: Acknowledging Collective Experience
No full textMental health remains one of the most neglected areas of American healthcare. By now, many are aware that the COVID-19 pandemic led to a sharp increase in cases of anxiety and depression, thereby exacerbating the outcomes of a long-standing mental health crisis. In this thesis, I address a pressing concern: racial and ethnic minority populations are experiencing disproportionately worse mental health outcomes, yet are less likely to have access to, seek out, and utilize effective resources. Modern mental health care has had devastating consequences on the health of minority populations. Although it is well documented that structural racism underlies the inequities experienced across all areas of healthcare, the current mental health paradigm is not meeting the needs of communities disproportionately affected by the mental health crisis. The purpose of this thesis is to reframe mental health from a sociopolitical lens and address the unique barriers that prevent people of color from utilizing mental health resources. In this paper, I argue that we ought to rethink the current mental health care paradigm by shifting from an individualistic to collective understanding of mental health, and challenging traditional roles of psychotherapists where I offer the view that psychotherapy can serve as a form of social activism
Borrowing in Domestic and International Markets: Crowding Out and Cyclicality
Get PDFThe first chapter studies the effect of government issuance on private issuance during banking crises using transaction-level bond and loan data from 66 countries between 1991 and 2017. Governments rarely issue loans, preferring to issue in bond markets. Firms, on the other hand, receive most of their financing from banks. During banking crises, as the supply of domestic loans decreases, firms switch to issuing bonds in domestic markets. Using a novel instrument based on maturing debt to overcome the potential endogeneity of government issuance, I find that firms must compete with the government for funds in the domestic bond market and are crowded out from this market as a result. This happens not only in developing countries, but in advanced countries as well. I also show that firms with the ability to tap foreign debt markets switch to these markets when crowding out occurs in domestic bond markets. Lastly, I show that more developed domestic bond markets mitigate, but do not eliminate, the degree to which crowding out occurs.
The second chapter studies the relationship between firm financing and the business cycle by considering distinct debt components, firm sizes, and country heterogeneities. The paper examines the cyclical patterns of firm financing through both correlation-based and panel data analyses, using a dataset spanning 66 countries over 30 years. I use the financing behavior of firms in United States as a benchmark with which to compare firms of other advanced countries as well as emerging countries. I find that, consistent with previous research, total debt is procyclical for all but the largest firms in the United States. However, firms of all sizes in the United States issue bonds countercyclically and loans procyclically in domestic markets. In other advanced countries, only the largest firms display countercyclical bond and loan issuance domestically, while issuing loans procyclically abroad. Emerging countries do not exhibit any discernible cyclicality patterns.
The third paper is joint work with Graciela Kaminsky and Shiyi Wang, and examines the impact of increases in sovereign borrowing on firms' ability to access international capital markets. Our paper analyzes episodes of imperfections in international capital markets, both those that diminish and enhance credit markets. Using a structural VAR approach, we identify shocks to government issuance by imposing that government issuance does not affect contemporaneous GDP growth. This is because we examine longer-term maturity issuance which typically is not used immediately. We identify market imperfections in the financial center as well as those originating in the periphery. The former captures collapses and booms in global liquidity. For the latter, we examine episodes of high and low sovereign credit risk as well as episodes of high and low sovereign debt. We find that, in emerging countries, government issuance decreases the ability of firms to tap international capital markets (crowding out) during collapses in global liquidity and periods of high sovereign risk. In advanced countries, we find that government issuance boosts firm issuance (crowding in) during periods of high sovereign debt and periods of low sovereign risk