VictorJuiz/thesis huggingface dataset:
Contributions to Minimax Statistical Theory

Complex statistical methods are regularly deployed in high-stakes settings. Examples include policy making informed by epidemiological and economic models, and medical diagnoses and autonomous driving informed by machine learning algorithms. These settings demand an understanding of the risks associated with statistical methods, both when optimistic modelling assumptions are correct and when they fail. One way to quantify these risks is through theoretical guarantees, yet statistical theory often relies on unverifiable assumptions and therefore fails to explain performance in real-world settings. This dissertation provides methods and theoretical guarantees without such limitations across a wide range of statistical tasks, including inference, prediction, and decision making. We study these problems using minimax analysis, determining the best possible performance against worst-case data and distributions, where the notion of worst-case is problem-specific. The considerable flexibility of this approach facilitates, for example, characterizing statistical optimality separate from concrete algorithms, obtaining a precise, non-asymptotic dependence on all relevant features of various decision problems, and establishing results that apply in generality across modelling assumptions. The main contributions of this dissertation are (i) tight bounds on the minimax performance of contextual probabilistic forecasting without any assumptions; (ii) the minimax rates of conditional density estimation for all parametric and nonparametric classes with i.i.d. data; and (iii) the introduction of adaptivity to sequential experiments, including the first algorithm that adaptively exploits causal structure.

Keywords: Adaptivity
Causal
Density estimation
Log loss
Minimax
Sequential
Advisor: Roy, Daniel M
Advanced Diagnostic Imaging and Differentiated Thyroid Cancer in Ontario: Detection, Incidence, Access, and Patient Outcomes

Overdetection of thyroid cancer from increasing use of diagnostic imaging is a leading hypothesis to explain worldwide incidence rate increases in the context of low and relatively stable mortality rates. In this dissertation, I present three studies that investigate factors and outcomes related to use of advanced diagnostic imaging in the incidence of differentiated thyroid cancer (DTC) in Ontario. In the first study, I classified pre-diagnostic pathways with advanced diagnostic imaging procedures as incidentally detected cases (IDCs) (otherwise non-incidentally detected, non-IDCs). I found that a up to 20% and 30% of female and male DTCs were IDCs, and that incidence rate ratios (IRR) for these cases (IRR, females: 3.45, 95% CI 3.00-3.96; males: 3.21, 95% CI 2.65-3.90) increased more rapidly than non-IDCs (IRR, females: 2.49, 95% CI 1.22-5.08; males: 2.38, 95% CI: 2.20-2.58) in the most recent period (2013-2017) compared to earliest (1998-2002). In the second study, I evaluated standardized imaging capacity and geographic access to imaging facilities associated with increasing incidence of IDCs. I found that CT and MRI imaging capacity were associated with higher odds of IDCs among males (odds ratio, OR: 1.26, 95% CI 1.01-1.57) and females (OR: 1.44, 95% CI 1.10-1.85), respectively. Drivetime (per 10 minutes) from patient residence to imaging facility was associated with higher odds of incidental detection of DTC outside rural areas (OR range: 1.06, 95% CI 1.02-1.12 in urban areas to 1.44, 95% CI 1.25-1.66 in large urban areas). In the third study, I used instrumental variable methods to compare five-year mortality and recurrence between IDCs and non-IDCs. While I did not identify a strong instrument—causing imprecise results—the findings show confounding by prognostic and clinical factors which are unavailable in the administrative data. Sensitivity analyses support the design and approach upon identification of a strong instrument. These findings show that use of advanced diagnostic imaging contributes to Ontario’s increases in DTC incidence. As use of advanced diagnostic imaging increases, incidence rates of patients with IDCs will continue increasing. Overall, these findings provide a foundation to conduct future epidemiological, clinical, and health services research of the burden of DTC in Ontario.

Keywords: Diagnostic Imaging
Epidemiology
Incidence
Incidental Findings
Regression Analysis
Thyroid neoplasms
Advisor: Rosella, Laura C.
Essays on Urban and Labor Economics

This thesis investigates the relationship between residential location choice and labor market outcomes. The decision to reside in a particular location is intertwined with labor market opportunities, which are crucial determinants for housing market outcomes. Conversely, any barrier to mobility due to housing policy or finance condition adversely affects workers’ careers, making any housing policy consequential for the labor market. Chapter 1 focuses on the labor market outcomes of negative equity homeowners who face geographical mobility barriers due to economy-wide factors. Using Census data in 2005-2010, the study estimates the mobility response and labor market outcomes of negative equity homeowners to the China trade shock and compares them to other homeowners. The analysis finds no significant difference between the two groups in terms of mobility, employment along intensive and extensive margin, and wages, suggesting that house lock-in effects did not significantly influence the pattern of wages and employment after the China shock. Chapter 2 delves into the mechanisms behind location choice decisions based on labor market prospects and examines the relative weight of spouse career prospects in the location decision of dual-earner, college-educated straight couples. The analysis finds that higher expected wages for husbands in a potential destination makes it more attractive for households, compared to the same increase in expected wages for wives, a gap which monotonically diminishes with age. Several hypotheses are explored, with the division of labor within the household being most consistent with the evidence. Also this difference cannot be interpreted as a difference in spouses’ bargaining power, as the estimated bargaining power from a model including home production shows almost no gender imbalance. Chapter 3 examines the popularity of rent stabilization, a widely advocated housing affordability policy despite its inefficiencies. Contrary to conventional belief, the study finds that the main benefit of rent regulation for tenants is not the protection it provides against higher rent increases over time. Instead, rent regulation is attractive mainly because it is associated with lower quality and less expensive units, which are in higher demand

Advisor: Baum-Snow, Nathaniel
Characterization of T Cell Responses to SARS-CoV-2 following Infection and Vaccination

The COVID-19 pandemic caused by the SARS-CoV-2 virus continues to be a global health crisis. There is an urgent need to understand immune responses against SARS-CoV-2 to develop effective therapeutics and vaccine strategies for controlling infection. While antibodies prevent infection, T cells are critical for controlling and resolving infection. Memory T cell responses are necessary to limit re-infections. While there was a race to probe antibody responses after infection during the early stages of the pandemic, there was notable lack of focus on cellular immunity. This thesis sought to characterize the T cell memory response after SARS-CoV-2 infection and vaccination. In the weeks after symptom onset, I show that all study subjects develop SARS-CoV-2-specific CD4+ T cell responses. However, CD4+ T cells exhibited unusual cytokine profiles characterized by high IL-2 and reduced IFN-γ expression across two separate convalescent cohorts, especially when compared with responses against the more common influenza virus. I demonstrated that SARS-CoV-2 T cell responses persist up to 9 months after symptom onset in most convalescent subjects, and that the atypical cytokine profile that was initially observed is maintained over time. With the advent of COVID-19 vaccines, it became crucial to examine vaccine immunogenicity in immunocompromised individuals who were overlooked during vaccine trials despite being more vulnerable to severe outcomes of COVID-19. Here, I followed a cohort of 124 patients with immune-mediated inflammatory diseases on various immunosuppressive therapies after successive mRNA vaccinations. In this study, I provide compelling evidence that these patients have diminished and less durable vaccine-induced antibody and T cell responses against SARS-CoV-2. In particular, patients on TNF inhibitor therapy exhibited lower levels of virus-specific antibody and decreased T cell responses compared to healthy controls, especially with respect to neutralization responses against variants of concern. Thus, vaccine strategies need to be optimized for this patient population. Altogether, the work in this thesis contributes to our current understanding of immune responses against SARS-CoV-2 by highlighting skewed antiviral T cell responses and reduced vaccine immunogenicity in immunocompromised individuals.

Keywords: adaptive immunity
COVID-19
infectious diseases
SARS-CoV-2
T cells
vaccines
Advisor: Watts, Tania H
John Duns Scotus on Cognitive Acts: Their Causes, Ontological Nature, and Intentional Character

How do we acquire our cognitive acts? What is their ontological status? How are they related to the extramental world? These are only a few of the major questions concerning cognitive acts that puzzled late medieval thinkers, forming one of the most exciting philosophical debates that took place between the second half of the thirteenth and the first half of the fourteenth century. John Duns Scotus (d. 1308) is considered a leading figure in this debate; scholars believe that he “wrought a revolution in the philosophy of mind” by offering “startling new ideas about cognition, making a radical break with his predecessors and contemporaries” (King). Modern scholars of medieval philosophy have devoted much attention to Scotus’s view on the intentionality of cognitive acts, but little on issues such as their origin and ontological status. My dissertation fills this gap. First, I examine Scotus’s new idea of an essential order between object and intellect in the co-causation of the cognitive act (intellectio). Scotus argues that this essential order is required to ensure both the reliability of our cognition as well as the freedom of the knower in the cognitive process. Second, I discuss the theoretical implications of Scotus’s idea that cognitive acts are a special sort of activity (operatio) in the Aristotelian category of “quality” and not of “action.” According to Scotus this explains the intentionality of cognitive acts, that is, how and why cognitive acts are about their objects, and why only the cognition of an existent and actually present object can fully perfect the human intellect, through what Scotus calls a “relation of contact.” This second step will also involve a study of the peculiar terminology Duns Scotus uses, such as the distinction between “objective being” and “subjective being,” as well as the expression “diminished being” (esse diminutum). I conclude that Scotus’s view on the ontological nature of the cognitive act provides a more plausible explanation than the one offered by his predecessors about how the cognitive faculty cognizes the extramental world and gives a more reliable epistemological foundation to human cognition. Finally, I provide a critical edition of question 13 of Scotus’s Quaestiones quodlibetales, his last and most important work on the ontology of cognitive acts and how they relate to the extramental world. A critical edition is indispensable because the best Latin text that is currently availableis very difficult to understand due to textual flaws and omitted passages.

Keywords: cognition
concepts
Duns Scotus
Intentionality
objective being
Quodlibet
Advisor: Pickavé, Martin
Evaluation of Cost-Effectiveness for Lung Transplant and Ex-Vivo Lung Perfusion

Demand for lung transplantation exceeds the supply of suitable donor lungs. Ex-vivo lung perfusion (EVLP) is a technology that enables further objective evaluation of potentially-useable organs, as well as rehabilitation of “marginal-risk” donor lungs, outside the body prior to transplantation, which together may increase organ supply and overcome this bottleneck. However, the decision of whether to fund EVLP and integrate it into lung transplant programs must be supported by evidence that considers the clinical, economic, and humanistic consequences of the technology; for EVLP to justifiably receive healthcare resources, the costs, health outcomes, and incremental cost-utility of the technology must be determined. The goal of this thesis was to conduct an economic evaluation of lung transplantation with versus without EVLP at the largest lung transplant center in North America. Our first study determined the impact of EVLP on the cumulative and phase-specific hospital-perspective costs of lung transplantation in Ontario, Canada. This retrospective before-after cohort study presented a novel methodology for phase-based costing that uses multi-state survival regression to overcome the limitations of conventional costing methods. Study 2 evaluated the impact of EVLP on organ transplantation and patient outcomes, using linked health administrative data from the only adult lung transplantation centre in Ontario, Canada, and identified the health resource and clinical implications of having EVLP available. Study 3 involved a cost-utility analysis using an individual patient simulation. This study used input parameters from our antecedent studies to inform a decision-analytic model that estimates the number of transplants, cumulative lifetime costs, and projected health outcomes expressed as quality-adjusted life-years (QALYs). Results from our observational studies suggest that the implementation of EVLP in the Toronto Lung Transplant Program at the University Health Network has been associated with improved accessibility to transplantation, improvements in several clinical outcomes, but no significant difference in phase-specific or cumulative costs. We found that having EVLP available should be considered cost- effective across a range of commonly accepted cost-effectiveness thresholds. Collectively, this thesis synthesized evidence that EVLP was economically justifiable at our centre; these findings may be used by clinicians, administrators, and other institutional stakeholders involved in resource allocation and funding decisions.

Keywords: Economic Evaluation
Ex-Vivo Lung Perfusion
Health Economics
Health Technology Assessment
Lung Transplantation
Organ Preservation
Advisor: Sander, Beate
Keshavjee, Shaf
Development of Multi-functional Electroactive Fibers for Electrophysiological Application

Recent advances in telemedicine and personalized healthcare have motivated a wave of new developments in wearable technologies targeting continuous monitoring of biosignals. The common limitations of wearables for continuous monitoring are the durability, flexibility and breathability of their biopotential electrodes interfacing the body. Our studies tackle these challenges by proposing flexible, breathable, and washable dry textile electrodes made of electroactive fibers. In this thesis, we developed conductive elastomeric filament (CEF) fibers through melt spinning. Using an industrial scale knitting machine, CEF fibers were directly knitted into dry textile electrodes. Underwear and headband garments with integrated textile electrodes were knitted and electrocardiograms (ECGs) were acquired using the underwear garment and electrooculograms (EOGs) were acquired using the headband. ECG and EOG recordings with textile electrodes were found to have comparable fidelity to that of the gold standard gel electrodes. CEF electrodes were continued to acquire high-fidelity ECGs and EOGs after 30 wash and dry cycles. Smart underwear garments were also used to perform continuous ECG measurements in 5 participants over 24-hour of unrestricted daily activities. Results demonstrated the success of these garments in performing high fidelity continuous ECG monitoring. We also developed novel multifunctional electroactive fibers with various cross-sectional geometries for electrophysiological applications. Different fiber materials with cross-sectional geometry of round, ribbon, and trilobal were coated using poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS) biocompatible conductive ink through a continuous roll-to-roll coating technique. Physico-chemical interactions between the fiber substrates and PEDOT:PSS ink were calculated based on the Owens, Wendt, Rabel and Kaelble (OWRK) method. Coated fibers were knitted into 3D textile electrodes using an industrial knitting machine. The electrochemical impedance spectroscopy, skin-electrode impedance, and ECG signals of the knitted electrodes after repetitive wash cycles were used as criteria to study the electrode’s performance for biomedical applications. The results showed that factors such as capillary force, cross-section of the filaments, and type of polymer materials affect the adhesion properties of the conductive ink to the fiber substrates. Collectively, the results of our studies present novel dry textile electrodes as a promising scalable solution to the challenges of wearable technologies for long-term continuous electrophysiological monitoring applications.

Keywords: Conductive Elastomers
Conductive Fiber
Dry Textile Electrode
ECG monitoring
PEDOT:PSS
Textile Computing
Advisor: Naguib, Hani
Sounding the Alarm: An Exploration of Professionalization within the Ontario Fire Service Focused on the Issues, Challenges, Pressures, and Opportunities for Transforming a Lauded Public Sector Institution

The fire service is highly regarded by the community and is routinely recognized as a highly trusted occupation. The demands placed on the fire service have grown substantially in recent years due to neoliberal pressures, growing fiscal costs, accountability pressures, an expanding emergency response mandate, and the acquisition of additional non-emergency roles. This thesis explores the extent to which these changes are resulting in the professionalization of the Ontario fire service. It employs historical and sociological institutionalism to examine the Ontario fire service as an institution to understand factors influencing its behaviour and shaping its change mechanisms. It uses related theoretical concepts of institutional agency, path dependence, endogenous and exogenous variables, rule makers versus rule takers, and institutional isomorphism to provide insight on how institutional change occurs or does not occur. This study comprised twenty-four interviews with leaders from Ontario and international fire services, the Ontario police and paramedic services, senior municipal officials, labour relations experts and higher education professors. The findings of this study suggest that the Ontario fire service may be approaching a critical juncture whereby it is forced to adapt to neoliberal pressures and pressures for occupational change to remain effective and become more professionalized, despite its entrenched nature as a long-standing hierarchically structured but non-professionalized institution. These pressures combined with growing calls for change are challenging the ingrained status quo. This study contributes to the literature on institutionalism and the professions through its exploration of an understudied institution. While the focus is the Ontario fire service, the findings may have implications for other fire services and similar institutions. It finds tensions between pressures for professionalization on the one hand, and neoliberal fiscal pressures on the other. These complexities contribute to firefighters embodying a quasi-professional status that gains legitimacy from the ‘heroic work’ it undertakes rather than by qualifications or credentials. Furthermore, the post-pandemic workplace and a newer generation of workers are producing institutional pressures that can potentially shift the entrenched fire service. This research sheds light on the Ontario fire service through an academic lens and reveals a complex institution facing a challenging trajectory.

Keywords: Fire service
Firefighters
Institutionalism
Neoliberalism
Profession
Professionalization
Advisor: Wheelahan, Leesa
Novel Approaches for Preclinical Lung Sentinel Lymph Node Mapping

Sentinel lymph node mapping is a technique to identify the first draining lymph node of a solid organ cancer. This node theoretically represents the first potential site of cancer spread, and therefore should be prioritized for biopsy and thorough pathological evaluation. Despite successful adoption of sentinel lymph node mapping as standard-of-care for diseases like breast cancer and cutaneous melanoma, reliable performance for other cancers has proven more elusive. This includes lung cancer, which represents a leading cause of cancer death globally. Proponents of lung sentinel lymph node mapping note its potential utility for guiding therapeutic decision-making and prognostication. Yet prior attempts at lung sentinel lymph node mapping have been complicated by poor performance or technical complexity, even with techniques previously successful in other cancers or preclinical studies. Such failure may reflect a disconnect between prior preclinical research and the anatomic considerations of lung cancer. To that end, a series of experiments were conducted to lay the foundation for future success in lung sentinel lymph node mapping. First, we characterized the performance of dual-modality mixtures of water-soluble computed tomography contrast and near-infrared fluorescent indocyanine green. We found such mixtures preserve the radiopacity of the computed tomography contrast solvent while enhancing the fluorescence of the indocyanine green solute. Second, we leveraged the capabilities of these mixtures for a novel application of lung sentinel lymph node mapping: endoscopic nodal staging, which better reflects the unique anatomic configuration of the intrathoracic lymph nodes. We demonstrated that this novel technique was feasible in healthy pigs, while also identifying key considerations for clinical translation. Finally, we characterized a nodal metastasis model to facilitate more meaningful, future evaluation of lung sentinel lymph node mapping techniques. We demonstrated that this rabbit model formed nodal metastases even with isolated peripheral tumors, mirroring a pattern of disease that would meet the indications for lung sentinel lymph node mapping as currently conceived. The cumulative result of these investigations provides a path to re-explore the potential role of lung sentinel lymph node mapping.

Advisor: Yasufuku, Kazuhiro