VictorJuiz/thesis huggingface dataset:
Bayesian Inference of Complex Latent Variable Models

This thesis contains three separate chapters motivated by research questions related to public health. The first contribution is in the second chapter, which introduces a novel parameter transformation of anisotropic covariance functions. This transfor- mation relates the anisotropic ratio with the polar radius, and the anisotropic angle with the polar angle. It resolves an issue with the standard parameterization where the anisotropic angle has no meaning in the special case of isotropy, and provides a firmer mathematical framework in which to view isotropic covariance functions as a special case of the anisotropic covariance functions. It also proposes a transformation of the standard deviation and range parameters that renders them approximately orthogonal. The third chapter models the time-varying effect of air pollution. There is increasing interest in modeling air pollution effects as time-varying, and the contribution of this chapter is in proposing two posterior statistics that summarizes its trend over time – stability and momentum. Stability is the standard deviation of== tthis effect over time, and momentum is the proportion of its pairs of differences that are positive. The fourth chapter proposes a model that decomposes daily COVID-19 mortality into the sum of (scaled) skew normal curves. COVID-19 mortality has been heavily studied in recent years, and the contribution of this model is in providing the evolution of these curves and their parameters over a multi-year period. The model has interpretable parameters, including a shape parameter, which quantifies the degree of asymmetry of each skew normal curve. In addition to the methodological developments listed above, the models in chapters three and four provide results that (pending peer review) may be of interest to practitioners. The trend detection model is fit to daily air pollution and mortality data in census divisions across Canada, and finds one region with an increasing trend and one with a decreasing trend. The skew normal model provides a decomposition of daily COVID-19 mortality into skew normal curves in six regions, and the relation of these curves to COVID-19 waves may be of independent interest. Moreover, both of these models can be applied to any health outcome of interest.

Advisor: Brown, Patrick E.
Hedgehog Signaling in Kidney Development and Disease

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) is characterized by a spectrum of structural and histologic abnormalities and is the major cause of childhood kidney failure. During kidney morphogenesis, formation of a critical number of nephrons is an embryonic process supported, in part, by signaling between nephrogenic precursors and Foxd1-positive stromal progenitor cells. Low nephron number and abnormal patterning of the stroma are signature pathologic features among CAKUT phenotypes with decreased kidney function. Despite their critical contribution to CAKUT pathogenesis, the mechanisms that underlie low nephron number and the functional contribution of a disorganized renal stroma to nephron number are both poorly defined. Here, I identify a primary pathogenic role for increased Hedgehog signaling in embryonic renal stroma in the genesis of congenital low nephron number. Pharmacologic activation of Hedgehog signaling in human kidney organoid tissue decreased the number of nephrons and generated excess stroma. Mechanisms underlying these pathogenic effects were delineated in genetic mouse models in which Hedgehog signaling was constitutively activated in a cell lineage-specific manner. Cre-mediated excision of Ptch1 in Foxd1+ stromal progenitor cells, but not in Six2+ nephrogenic precursor cells, generated kidney malformation identifying the stroma as a driver of low nephron number. Single-cell RNA sequencing analysis identified Cxcl12 and Wnt5a as downstream targets of increased stromal Hedgehog signaling, findings supported by analysis in human kidney organoids. In vivo deficiency of Cxcl12 or Wnt5a in mice with increased stromal Hedgehog signaling improved nephron endowment. These results demonstrate that dysregulated Hedgehog signaling in embryonic renal stromal cells inhibits nephron formation in a manner dependent on Cxcl12 and Wnt5a.

Keywords: CXCL12
Hedgehog
Nephron
Organoids
Stroma
WNT5A
Advisor: Rosenblum, Norman D
Essays on Transportation and Housing in the Age of Mass Migration

Between the late 19th and early 20th centuries, millions of immigrants arrived in the United States seeking a better life. These newcomers brought with them diverse cultures, traditions, and languages, and contributed to the growth and development of the American economy. At the same time, migrants' pathways were influenced by the transportation and housing infrastructure they encountered along the way. This dissertation considers migrants' economic contributions and outcomes from the perspective of housing and transportation. The first chapter investigates the impact of housing regulation on the health and economic outcomes of mostly immigrant residents. I exploit variation arising from the Tenement House Act of 1901, which imposed minimum housing standards on new construction in New York City, to show that legislation improved children’s health and changed neighborhood composition. Although lower income households in treated neighborhoods were more often displaced relative to their higher income counterparts, tenement legislation is nonetheless responsible for two additional years of life in treated children who stayed. The second chapter examines the impact of the transition to steamships on immigrant destination choices and the resulting effects on innovative activity in the United States. Since sea surface winds between origin and destination were a determining factor in travel time by sail, the reduction in travel time when transitioning from sail to steam depends on exogenous wind patterns (Pascali 2017). Using newly transcribed data on international migrations from 1830 to 1880, I exploit the disproportionate decrease in between-country travel times to show that a one percent decrease in travel time increases the number of migrants by two percent. I find evidence that steamship induced migrants increased county-level innovation such that a one percentile increase in immigrant share among counties led to 0.49 more patents. This dissertation sheds new light on the experiences of immigrants during this pivotal period in American history, offering insights into the ways in which regulation and technology influenced the lives of those who sought a better future in the United States.

Keywords: housing
immigration
regulation
transportation
Advisor: Eli, Shari
Baum-Snow, Nathaniel
The Search for Novel Anthelmintic Targets: Characterizing Alternative Metabolic Pathways in Caenorhabditis elegans

Around a quarter of the human population is infected by parasitic helminths which also infect and place a large economic burden on the agricultural industry. Unfortunately anthelmintic resistance is a growing problem. Helminths survive long periods of low to no oxygen in their hosts, but their anaerobic metabolism has yet to be fully characterized. The goal of this project has been to characterize the anaerobic metabolism of C. elegans, a roundworm closely related to a large class of parasitic worms, by combining systematic metabolomics with a structural biology approach in order to find selective drug targets. Fumarate reduction has been previously identified as the primary source of ATP for C.elegans as well as many helminths in low oxygen environments, such as during host infection. Rhodoquinone (RQ) is an essential small molecule which is closely related to ubiquinone (UQ). While UQ is essential for the canonical, aerobic electron transport chain (ETC) which generates the majority of ATP in most animals, RQ is essential for fumarate reduction and is the fulcrum of anaerobic metabolic pathways more generally, here referred to as RQ-dependent metabolism (RQDM). In this thesis, I established a new methodology for inducing fumarate reduction in C.elegans with cyanide (KCN) which increases ease of study. I have found that wild-type C.elegans treated with KCN have the elevated succinate levels characteristic of fumarate reduction in helminths. In RQ-deficient mutants treated with KCN, succinate levels are reduced while its precursors, malate and fumarate, are elevated. This confirms the structure of the hypothesized fumarate reduction pathway in a whole animal. This finding was replicated when Complex I, which is likewise required for fumarate reduction, was inhibited by rotenone. By combining statistical analyses of metabolites in animals where fumarate reduction was disrupted in different ways with a list of known RQDM enzymes, I identified twelve (12) genes which are required for RQDM, four (4) of which have helminth-specific residues near their active site and one (1) of which is not found in hosts. These discoveries provide a new list of high-priority candidates for anthelmintic drug targets.

Keywords: ANOVA
Anthelmintics
C.elegans
Helminths
LC-MS
PEPCK
Advisor: Fraser, Andrew
Robust Machine Learning by Transforming and Augmenting Imperfect Training Data

Machine Learning (ML) is an expressive framework for turning data into computer programs. Across many problem domains---both in industry and policy settings---the types of computer programs needed for accurate prediction or optimal control are difficult to write by hand. On the other hand, collecting instances of desired system behavior may be relatively more feasible. This makes ML broadly appealing, but also induces data sensitivities that often manifest as unexpected failure modes during deployment. In this sense, the training data available tend to be imperfect for the task at hand. This thesis explores several data sensitivities of modern machine learning and how to address them. We begin by discussing how to prevent ML from codifying prior human discrimination measured in the training data, where we take a fair representation learning approach. We then discuss the problem of learning from data containing spurious features, which provide predictive fidelity during training but are unreliable upon deployment. Here we observe that insofar as standard training methods tend to learn such features, this propensity can be leveraged to search for partitions of training data that expose this inconsistency, ultimately promoting learning algorithms invariant to spurious features. Finally, we turn our attention to reinforcement learning from data with insufficient coverage over all possible states and actions. To address the coverage issue, we discuss how causal priors can be used to model the single-step dynamics of the setting where data are collected. This enables a new type of data augmentation where observed trajectories are stitched together to produce new but plausible counterfactual trajectories.

Keywords: Algorithmic Fairness
Distribution Shift
Machine Learning
Out-of-distribution Generalization
Reinforcement Learning
Representation Learning
Advisor: Zemel, Richard
Spatial Stimulus Response Compatibility, but Not Response Effort, Influences Perceptuomotor Decision-making

Decision-making is fundamental and is often perceptuomotor in nature. For example, one performs reach-to-grasp movements to donuts judged to be of high quality based on perceptual information (e.g., colour, texture) arising from the glaze. Parallel models of perceptuomotor decision-making are based on a coupled/integrated view such that decision-making can be conceptualized as a competition between potential responses - action planning occurs simultaneous with the gathering of sensory evidence and a decision is made once the competition between responses is resolved. This integrated view opposes serial models in which action is the output of a separate module activated after decision-making has ended. The studies presented herein were designed to determine if modulations made to the motor system (i.e., the system enacting the decision) influenced the sensory evidence needed to enact one perceptual judgement over another. As a general hypothesis, if perceptual-cognitive-motor systems supporting decision-making are inherently coupled, then manipulating the competition between potential responses should bias decision-making behaviour. Study 1 included three experiments designed to test the influence of response activation on decision commitment by manipulating the level of response activation via mechanisms associated with spatial stimulus-response compatibility. Results revealed that participants displayed a bias towards the more active response - less evidence was needed to make the decision associated with a spatially consistent action goal. Study 2 included four experiments designed to test the influence of response effort on decision-making by manipulating reaching effort in an explicit manner via the use of resistance bands. In contrast to previous work revealing a choice bias away from options associated with implicitly higher effort, no consistent bias away from the explicitly higher effort decision was observed in any Study 2 experiment. The dissertation provides novel evidence for decision commitment occurring when a competition between potential responses is resolved and provides a contextual factor that may mediate the relationship between response effort and perceptuomotor decision-making. Overall, when making a perceptuomotor decision, biases to the competition between responses can bias perceptuomotor decision-making outcomes with the spatial characteristics of the stimulus and response being a stronger biasing factor than the effort related differences between responses.

Keywords: Decision commitment
Decision-making
Effort
Motor activation
Perceptuomotor decision-making
Spatial compatibility
Advisor: Welsh, Timothy N
Justifying the Line in the Sand: Remoteness in Canadian Tort Law

The Supreme Court of Canada imported preexisting remoteness rules into Canadian tort law without justifying why they apply in the distinctively Canadian negligence framework endorsed in Cooper v. Hobart. This paper attempts to justify remoteness in this framework. Justifying remoteness as a standalone policy tool is unsatisfactory because it cannot explain why remoteness requires a reasonable foreseeability standard nor that remoteness operates as a fair limit on liability. Justifying remoteness in relation to the duty of care is satisfying. Remoteness supports the duty of care by allowing decision-makers to identify sufficiently general categories of duty of care that apply beyond the individual facts of the case. They can then confirm or deny liability by particularizing the risk at the remoteness stage. This ensures the framework applies as intended, adheres to decision-makers’ sense of justice, and achieves fair and socially useful results.

Keywords: Duty of Care
Foreseeability
Negligence
Remoteness
Tort Law
Wagon Mound
Advisor: Benson, Peter PB
Learning from ‘Experts’ at Canadian Stroke Rehabilitation Distinction Sites: Implications for the Management of Patients with Complex Care Needs

Background: Health care systems use standardized approaches to effectively reduce costs and deliver high-quality care. However, there is a growing subset of “complex” patients whose care trajectories deviate from the expected clinical pathways. These patients often require customized care to address their multiple concurrent health and social issues. In stroke rehabilitation settings, clinicians provide care for a high proportion of patients with complex care needs. At Canadian Stroke Distinction sites, clinicians provide measurably excellent care in accordance with the Stroke Rehabilitation Best Practice Recommendations (SRBPR), despite the limited applicability of these recommendations for complex care needs. Methods: The primary purpose of this thesis was to understand how expert stroke rehabilitation clinicians recognize and manage the care for patients with complex care needs. A secondary aim was to explore how clinicians developed the expertise to manage the care of these patients. To address these aims, we (1) conducted a critical appraisal of professional competency frameworks for stroke rehabilitation clinicians, to assess the degree of guidance for managing complexity in practice; (2) conducted an interpretive description study, which explored the perspectives of stroke rehabilitation clinicians, organizational and health system key informants; (3) conducted a critical appraisal of the SRBPR to locate recommendations relevant to the care of patients with complex care needs. Findings: There is minimal guidance in macro-level sources (e.g., competency frameworks, SRBPR) to support clinicians in caring for patients with complex needs. From interviews, we learned that (1) recognizing complexity is routine work for clinicians, (2) clinicians used workarounds to manage complexity, and (3) clinicians perceived and worked to bridge a difference between organizational processes and the realities of patient care. We noted misalignment between clinician perceptions of most patients as complex, and organizational efforts to plan for complexity, which estimate 20% of patients to be complex. Conclusion: There is a need to better define and account for the needs of patients deemed as complex, at macro- and meso-levels, in ways that support clinicians to better leverage their expertise in care delivery.

Keywords: complex adaptive systems
complex patients
interpretive description
qualitative research
stroke rehabilitation
Advisor: Nelson, Michelle
Berta, Whitney
Soil Specific Interpretation of the Cone Penetration Test

The Cone Penetration Test has quickly and rightfully claimed its position as a popular site investigation tool in geotechnical engineering. Like all penetration tests, CPT results need to be interpreted into engineering parameters. In granular soils, the state parameter, which is the key driver of soil behaviour is explicitly the target of interpretation in applications such as liquefaction assessment in tailings. Any other application that depends on density or dilatancy implicitly depends on the state parameter. Existing empirical methods are almost entirely based on clean sands and completely or partially miss the significant dependency of the interpretation on intrinsic properties of soils. Use of calibration chamber tests to create soil-specific correlations are prohibitively expensive, and numerical models of the CPT have had limited success due to the complicated nature of the deep penetration problem.This dissertation presents a full model of the Cone Penetration under drained conditions using a critical state based constitutive model. The constitutive model, NorSand, was implemented in a Finite Element platform (ABAQUS) capable of handling large deformations. The real geometry of the CPT was modelled with contact elements and analyses were performed utilizing an Arbitrary Lagrangian Eulerian formulation. To create a predictive tool, calibration of soil behaviour and the contact friction were done in a completely forward manner. Drained triaxial compression tests were analyzed to investigate the level of potential error in calibration due to test imperfections. More than 300 calibration chamber tests were then modelled for validation. A parametric study was done to create a practice-ready interpretation method for obtaining the in-situ state parameter from CPT tip resistance. The method is the first well-validated technique that can generate soil-specific correlations beyond clean sands given its mechanistic framework.

Keywords: ABAQUS
CPT
Drained
NorSand
Simulation
Advisor: Ghafghazi, Mason
Black Superintendent Leaders Navigating the Ontario Education System

AbstractThis qualitative research study answered the following question: What are some strategies and considerations that Black superintendent leaders use to navigate the Ontario education system? I investigated how Black superintendents define their own strengths, behaviours, and attitudes, as well as the strategies they used to navigate the educational system despite the barriers presented by racism and oppression. I draw on historical and current studies on Black leadership and interviews to provide a deeper understanding of the multifaceted work of Black superintendents as they navigate the Ontario education system. I interviewed nine Black superintendents with various experiences from district school boards in Ontario and highlighted common themes, leadership experiences, challenges, and opportunities. I learned from their experiences and identities, as well as where they live, work, and learn. They shared the strategies that they use to navigate the organization, their positionality, their relationships, and their job and assigned duties. Historical data has shown that where and how Black leaders live, eat, walk, and work has always been about navigating oppressive systems that create barriers for some while privileging others. Findings indicated that all the Black superintendents used strategies such as networking, mentorship, family, preparation, and community supports to navigate relationships, the education system, positionality, and their assigned jobs or roles. All Black superintendents talked about Black excellence and leaving a legacy for all students to succeed. They also talked about Black fatigue and the emotional toll that leading while being Black took on them. They also spoke with pride about how networking and sharing the strengths and opportunities in their community and affinity groups supported their leading and learning.

Keywords: Anti-Black racism
Black leadership
Black superintendent
Education system
Leadership experiences
Ontario District School Board
Advisor: Campbell, Carol