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Systemic Treatment, Subjective Cognitive Function, and Survival in Prostate and Breast Cancer: Evidence from Patient Reported Outcomes and Real-World Data
No full textProstate and Breast cancer are the most commonly diagnosed malignancies and the
second leading causes of cancer-related death for men and women, respectively. In the United
States, there are more than 3.5 million prostate cancer survivors, and more than 4 million breast
cancer survivors, with these populations projected to continue to grow in the coming years.
Improvements in screening practices, earlier detection, and advancements in treatment have
prolonged survival among those diagnosed across both cancer sites. For cancer survivors with
metastatic prostate cancer and those with hormone receptor-positive (HR+) breast cancer,
systemic hormone therapies play a critical role in reducing mortality by targeting distinct
biological pathways. Despite these therapeutic advancements, there remains a limited
understanding of the long-term role hormone therapies play in cancer survivorship, particularly
with respect to sustained use. In addition, methods for measuring treatment adherence using
real-world data are not well established. This dissertation aims to bridge these research gaps by
investigating various aspects of cancer survivorship, with a focus on the long-term use of
systemic hormone therapies and on measuring adherence in real-world settings.
In Chapter 1, we utilized data from the International Registry for Men with Advanced
Prostate Cancer (IRONMAN) to examine the association between first-line systemic hormonal
treatment and subjective cognitive function trajectories among men with metastatic hormonesensitive
prostate cancer (mHSPC). We fit joint longitudinal and survival models for two
subjective cognitive function scales administered to IRONMAN patients at enrollment and during
follow-up for up to 2 years. We found that there was no evidence of worse cognitive decline over
time for individuals treated with androgen deprivation therapy (ADT) plus androgen receptor
pathway inhibitors (ARPIs), nor ADT + chemotherapy, when compared to individuals treated
with ADT monotherapy. Our study suggests that additional systemic hormonal therapies used to
treat mHSPC survivors do not negatively impact subjective cognitive function.
In Chapter 2, we further examined subjective cognitive function near diagnosis and
longitudinal trajectories and their association with mortality in the IRONMAN registry, among
those with metastatic prostate cancer. This association was evaluated by fitting joint longitudinal
and survival models for a follow-up period of up to 4 years. The findings from this study
revealed that poor subjective cognitive function near diagnosis and longitudinally was
associated with higher mortality. Our study highlights that subjective cognitive function can
provide an additional point of intervention to improve overall survival in this patient population.
In Chapter 3, we compared measurements of adherence for endocrine therapy when
using electronic health records (EHR) and health claims data among a population of 79
hormone receptor-positive breast cancer survivors. We investigated whether there were
differences across race and ethnicity, primary language spoken, and insurance status. We
found that when adherence is measured using only EHR data, adherence estimates are
consistently higher than when measured from health insurance claims data. Our study highlights
the importance of data source selection when assessing adherence to endocrine therapy and
that EHR and claims data offer complementary insights.
In conclusion, investigating research questions that extend beyond survival to
encompass life after diagnosis, while also highlighting the need to refine approaches to
measuring treatment adherence, is essential for informing care for cancer survivors. This work
provides a foundation to facilitate research and interventions aimed at enhancing the well-being
and quality of life of the continuously growing population of prostate and breast cancer
survivors.Population Health Science
Investigating Differential Binding Stabilities of MHC-E Restricted Epitopes in SIV Vaccination
No full textHIV continues to pose a global health challenge and has prompted extensive research into exploring effective vaccine strategies. Previous breakthroughs in simian immunodeficiency virus (SIV) vaccine development using a rhesus CMV vector recombinant for SIV antigen (RhCMV 68-1/SIV) showed unprecedented sterile immune clearance against SIV challenge.
Subsequent studies sought to determine the underlying mechanism of protection in this promising prophylactic vaccine strategy. An unconventional, MHC-E-restricted subset of CD8+ T cells was identified and shown to be necessary for protection. However, RhCMV 68-1/SIV vaccine-identified SIV epitopes identified by Hansen et al. lack canonical primary anchor residues, present low or negligible binding to human HLA-E, and thus do not support stable HLA-E/B2M complex formation. This inconsistency raises questions about their role and functionality in RhCMV 68-1/SIV vaccination. We therefore performed a comprehensive and direct comparison of SIV peptide binding to human and rhesus MHC-E. This thesis study aims to evaluate the binding characteristics and stability of RhCMV 68-1/SIV vaccine-identified SIV epitopes in complex with a panel of rhesus macaque and human MHC-E orthologs, specifically Mamu-E*02:04, Mamu-E*02:11, and HLA-E*01:03. The objective is to validate whether these SIV epitopes demonstrate comparable binding to Mamu-E and HLA-E, or if there is enhanced stability for Mamu-E as opposed to HLA-E. If the latter holds true, with Mamu-E exhibiting superior stability in complex with vaccine-identified SIV epitopes, it could explain the mechanism of vaccine efficacy but indicate challenges in translating this vaccine success to human clinical applications. If Mamu-E and HLA-E show similar binding to RhCMV 68-1/SIV vaccine-identified SIV epitopes, then alternative mechanisms of vaccine-mediated protection should be explored. To accomplish these goals, Mamu-E and HLA-E were recombinantly expressed in prokaryotic expression systems and refolded to form MHC-E/B2-microglobulin complexes prior to performing in vitro SIV peptide loading reactions. Thermostability assays using Differential Scanning Fluorimetry were conducted to compare the stability of Mamu-E and HLA-E complexes in the presence of excess SIV peptides. By examining the interactions between the vaccine-identified SIV epitopes and MHC-E molecules, this study aims to clarify the underlying mechanisms of the observed vaccine efficacy thereby facilitating its translation into the human clinic. Our findings reveal that the majority of vaccine-identified SIV epitopes do not stabilize either Mamu-E or HLA-E alleles. Given this weak or insignificant stabilization, it is likely that direct presentation of vaccine-identified SIV epitopes by MHC-E is not the primary mechanism of protection introduced by RhCMV68-1/SIV vaccination.Graduate Educatio
Just Economics: Inequality and Political Culture in Cross-National Perspective
No full textEconomics is widely viewed as a key participant in the construction of the pathologies of market societies. Critical scholars in fields such as Science and Technology Studies (STS) see it as the black sheep of the social sciences. Economics is characterized as promoting a view of society entirely through the prism of markets, individual self-interest and the imperative of growth at the expense of other values such as equality or human rights. In this dissertation, I look at the work of inequality economists at the Poverty Action Lab (J-PAL), World Inequality Lab (WIL), and the Delhi School of Economics to portray a different picture of the field. These subsets of economists are explicitly committed to values of tackling poverty, reducing inequality and promoting human rights and social development, but they define the problem of inequality differently and propose very different solutions for it.
It remains a puzzle how—despite these cross-national differences—economics, a field long seen as promoting efficiency over equality, comes to be accepted as a source of solutions to the problem of inequality. I argue that economists gain legitimacy to address inequality by constructing a field of expertise that I call “just economics.” This economics is just in three ways: it gets the right answers (as in the French expression, c’est juste!); it aims toward normatively desirable (i.e. just) ends; and it is “just” economics, providing neutral policy advice that leaves citizens free to make their own normative decisions. Just economics taps into cross-national differences in what makes for good evidence and morally desirable outcomes in the eyes of experts and lay citizens in a given political culture. I draw on co-productionist scholarship in STS to show how just economics appeals to culturally-embedded understandings about whose responsibility it is to taking on problems of inequality, the extent to which the problem is one of social structure or individual agency, and the appropriate institutional channels through which responses should be coordinated.
I develop this argument in thematically connected chapters. Chapters 1-2 take up economists’ own disciplinary self-awareness, showing how the discipline has adopted different thought styles to get at right answers, specifically, causal, historical and experiential approaches. I describe how economists draw on experiments, statistics and experiences in order to satisfy their reflexive questions about their own expertise. Chapters 4-6 are country case studies of approaches to inequality in the United States, France and India, as a question of opportunity, distribution, and rights, respectively. In the United States, a privatized welfare model focuses on unlocking “poverty traps” and making the poor into good entrepreneurial capitalists. In France, the system of social welfare is oriented toward reducing the potential for class conflict, and focuses on the use of expertise to inform reasoned public debates about inequality. In India, the rights-based approach is rooted in the country’s constitutional “Directive Principles,” realized through contemporary efforts in activism and legislation to secure socioeconomic rights. Chapter 7 explores how these different thoughts styles synergize with distinct constituents of the social compact—markets, states and (civil) society—while Chapter 8 looks at education as a specific policy domain where these styles are mobilized to implement visions of a just society. Inequality, I conclude in Chapter 9, is more than a statistical property to be studied by expert social scientists: By comparing approaches to inequality cross-nationally, I show that how we address inequality through policy rests on disparate understandings of science, politics and faith in society.Public Polic
Entangled Ritual and Architectural Practices at North Saqqara
No full textThis doctoral dissertation challenges some prevalent assumptions about ancient Egyptian funerary architecture. Using the cemetery of North Saqqara as a case study, I question the idea that ancient Egyptian tombs were only built to bury the dead, and show evidence that the elite mastabas of the earliest dynasties were used for rituals before interment took place. The structures were eventually transformed for the funeral, which required changing fundamental aspects of the buildings. In their previous shapes, the structures included spaces large enough to gather crowds, and doubled accesses that enabled the circular movement of people.
While the North Saqqara plateau was one of the most important sites during the Early Dynastic Period of Egypt, our understanding of it has been hindered by the limited documentation available to the scientific community. This doctoral dissertation contextualizes the unpublished archives of the archaeological excavations carried out at the site in the 20th century, which contain information about more than 160 excavated but unpublished structures. I complement the documentation of Cecil M. Firth and Walter B. Emery with data gathered in two season of topographic survey at the site. Using a high accuracy GNSS receiver and digital photogrammetry, I undertook a detailed topographic survey. As a result, I was able to trace the whereabouts of many of the structures whose plans were kept in the archives, succeeding in reconstructing a sizable portion of the missing plan of the site.
In the last part of the dissertation, I suggest a method to research the function of the spaces of the mastabas in their various stages of construction and use. In view of the very limited evidence about the rituals, I suggest studying the agency of the structures to affect the sensorial perceptions of the people involved in the rituals as an avenue to inquire about how the spaces could have been used. Specifically, I provide a series of case studies where I researched how four structures built during the First and the Second Egyptian dynasties shaped sound in certain ritual scenarios. Sounds produced in the mastabas were transformed as they traveled through space, from their source to their full dissipation. How sound was heard depended on the frequency of the sound emitted, as well as on the specific shapes and construction materials used in the structures.Near Eastern Languages and Civilization
The Effect of the US–China Trade War in a Neighboring Least-Developed Country
Get PDFapplication/pdfIDP000986_001This study empirically examines the effects of US tariffs against China on exports to the United States from Laos, a least-developed country bordering China. Using monthly firm-level trade data from January 2018 to December 2020, we found that all firms in Laos, except those of US origin, benefit on average from trade diversion in the US market. In particular, rising exports by foreign firms other than US-origin firms are not attributable to the transshipment of Chinese products. For example, China-origin firms that expand exports to the US do not import products from China. However, Lao firms’ exports to the United States appear to increase through the transshipment or minor processing of Chinese goods, although the scale of these exports is negligible. Moreover, Lao exporters increased their exports to the United States without reducing exports to non-US countries.technical repor
We All Have Bright, Blundering Eyes
No full textIn the weeks leading up to an important photo shoot, Anna Pierce, a portrait photographer, is called home to help her parents. She discovers that her family has been keeping her father’s failing health a secret. Anna struggles to come to terms with her father’s mortality amidst what she perceives to be the smallness of her hometown. As she juggles the demands of her job with her father’s escalating periods of turmoil, another unexpected truth comes to light that shatters everything Anna thought she knew about her family. This is a story of flawed, but deep, familial love that must reconcile itself to the past or risk being broken apart forever.Extension Studie
Liberationist Ethics and the Origin of Self-Regard
No full textThis is the inaugural work of liberationist ethics, which is a living dialogue with contemporary religious, philosophical, and cultural discourses and their interlocutors. I provoke questions of selfhood, vitality, and misery in the human condition and in religion. In particular, this work explores the origin of self-regard and how I (the very consciousness of ourselves) emerges as both a personal subject (bound as a social creature) and a universal subject (bound as a spiritual mode of being).
Liberationist ethics approach consciousness (or I), the individual person (oneself), community (you), and God (the greater) with deep concern for ethical relationship, irreducible subjective personhood, and dignified human flourishing.Author's Origina
Entrepreneurial Strategy and Learning
No full textLearning is a cornerstone of competitive advantage, especially in entrepreneurial contexts. Despite extensive research on entrepreneurial learning methodologies, we still lack understanding of fundamental constraints that limit learning effectiveness. This dissertation investigates key structural obstacles that hinder effective entrepreneurial learning: resource constraints, uncertainty, interdependencies, and bounded rationality. It provides novel insights into how these barriers manifest and interact in entrepreneurial contexts. The first study reveals a counterintuitive relationship between experience and strategic foresight: as entrepreneurs add features to successive products, the total interdependencies grow faster than their ability to anticipate them, leading to increasingly inaccurate forecasts. The second study reveals how novel recombination, while often associated with opportunities for outsized returns, also incurs the cost of managing novel complexity—obscuring the time and resources required for execution and increasing the risk of bridge financing and shutdown. The third study identifies a “mediocrity trap," in which firms launching lower-quality products receive ambiguous feedback and, as a result, persist longer despite negative market signals. This study challenges assumptions about learning with minimum viable products and rapid pivoting. Together, these studies highlight critical tensions in entrepreneurial learning and demonstrate that many learning challenges stem from structural barriers rather than purely cognitive limitations. This integrated perspective contributes to scholarly understanding of entrepreneurial strategy while offering practical approaches for entrepreneurs seeking to navigate these barriers and learn under constraint.Business Administratio