VictorJuiz/thesis huggingface dataset:
Risk Stratification for Lung Cancer Screening using an Epidemiologic, Molecular, and Quantitative Imaging Approach

Lung cancer is the most common cancer in the world and leading cause of cancer mortality globally. This dissertation investigates three complementary aims related to the development of lung cancer and lung cancer screening using data from the UK Biobank, China Kadoorie Biobank, National Lung Screening Trial, International Early Lung Cancer Action Program, Pittsburgh Lung Screening Study, and PanCanadian Early Detection of Lung Cancer Study. Regular screening with computed tomography has demonstrated promising reductions in lung cancer mortality. However, questions remain about the optimal approach to identify high-risk individuals most likely to benefit from screening. Widely-used enrollment criteria exclude light or never-smokers due to an absence of extensive smoking history, despite making up a meaningful proportion of lung cancers. Most findings in lung cancer screening programs are among individuals with ultimately benign determinations. The clinical management of indeterminate screen-detected pulmonary nodules remains an important barrier to optimal screening program efficiency. The lung function analysis in Manuscript 1 identifies important lifecourse exposures that shape the trajectory of pulmonary health for never-smokers and advances our understanding of risk factors for impaired lung function in the absence of primary smoking history. Manuscripts 1 and 2 are based on two of the largest population-based cohorts ever assembled. Methodological contributions of this work includes the development of risk-prediction models for never and ever-smokers, including one of the first models developed specifically in an Asian population, which may help to identify high-risk individuals who would benefit from early detection initiatives. Manuscript 3 is based on data from four international lung cancer screening programs. We performed quantitative image analysis to extract radiological features from medical images to accurately assess indeterminate pulmonary nodules. Contributions of this work include the development of highly-accurate nodule malignancy assessment models based on robust and high-throughput radiomic features, validated across multiple independent screening studies. In summary, this dissertation provides insights into how lifecourse exposures effect pulmonary function among never-smokers, how statistical models can help prioritize high-risk never and ever-smokers for lung cancer screening, and how nodule assessment models based on quantitative image features can improve clinical decision-making and management of screen-detected pulmonary nodules.

Keywords: Biostatistics
Cancer
Cancer screening
Early detection
Epidemiology
Lung cancer
Advisor: Hung, Rayjean J
Campbell, Kieran R
Key Insights into Permeable Interlocking Concrete Pavement: Measuring, Mimicking and Mitigating Clogging

Permeable Interlocking Concrete Pavements (PICPs) are a Low Impact Development technology designed to mimic natural pathways and control rainfall events at the source. As these pavements age, sediments accumulate within their permeable joints, causing them to clog and lose their capacity to infiltrate stormwater. Maintenance of PICPs is a critical practice to ensure long-term functionality. This thesis evaluates restorative maintenance practices for PICP and investigates how sediment characteristics influence clogging processes. To achieve this goal, a novel accelerated clogging method was developed, tested and applied in both field and laboratory experiments. Standardizing clogging methodologies will allow researchers to translate laboratory results more easily into actionable maintenance plans for operational pavements and allow for direct evaluations of new maintenance technologies. The accelerated clogging method was used to evaluate different restorative maintenance techniques, including three street sweeper technologies, a specialized high pressurized air and vacuum technology intended specifically for PICP maintenance and manual pressure washing followed by vacuuming. Each technology restored infiltration rates to above 2,000 mm/hr; however, only the specialized equipment restored infiltration rates to post-construction conditions. When the specialized equipment was re-tested for maintenance capabilities on a surface clogged with on-site (cohesive) soils, it could only restore infiltration rates to approximately 50% post-construction conditions. Lastly, the regenerative air sweeper was retested for early and repeated maintenance, which increased the effective lifespan of the PICP but was unable to prevent eventually clogging of the surface. In a parallel laboratory study, PICP clogging and surface infiltration losses were observed when varying material gradation and type using the same accelerated clogging procedure and exposing the surfaces to cycled wetting and drying. PICPs cells that were clogged with well-graded and cohesive materials lost their surface infiltration rates more rapidly compared to cells clogged non-cohesive or poorly graded materials. Well-graded clogging material allowed coarse sediments to cause early blockages and fine sediments to accumulate near the surface. Simultaneously cohesive sediments agglomerated together, forming a surface crust and attraction to water, limiting the amount of water permeation through the clogged joints leading to decreased infiltration rates.

Keywords: Clogging
Hydraulic Conductivity
Low Impact Development
Maintenance
Permeable Pavement
Surface Infiltration Rate
Advisor: Drake, Jennifer
Investigation of Non-specific DNA Binding by the Type I-F CRISPR-Cas Complex when Bound to Anti-CRISPR AcrIF9

Phages and other mobile genetic elements express anti-CRISPR proteins (Acrs) to protect their genomes from destruction by CRISPR–Cas systems. Acrs usually block the ability of CRISPR–Cas systems to bind or cleave their nucleic acid substrates. Here, I investigate an unusual Acr, AcrIF9, that induces a gain-of-function to a type I-F CRISPR–Cas (Csy) complex, causing it to bind strongly to DNA that lacks both a PAM sequence and sequence complementarity. We show that specific and non-specific dsDNA compete for the same site on the Csy:AcrIF9 complex with rapid exchange, but specific ssDNA appears to still bind through complementarity to the CRISPR RNA. Induction of non-specific DNA-binding is a shared property of diverse AcrIF9 homologues. Substitution of a conserved positively charged surface on AcrIF9 abrogated non-specific dsDNA-binding of the Csy:AcrIF9 complex, but specific dsDNA binding was maintained. AcrIF9 mutants with impaired non-specific dsDNA binding activity in vitro displayed a reduced ability to inhibit CRISPR–Cas activity in vivo. We conclude that misdirecting the CRISPR–Cas complex to bind non-specific DNA is a key component of the inhibitory mechanism of AcrIF9. This inhibitory mechanism is distinct from a previously characterized anti-CRISPR, AcrIF1, that sterically blocks DNA-binding, even though AcrIF1and AcrIF9 bind to the same site on the Csy complex. Investigation into the mechanistic differences between AcrIF9 and AcrIF1 revealed that while AcrIF9 is able to inhibit the Type I-F CRISPR-Cas systems from multiple bacterial species, AcrIF1 is limited to that of P. aeruginosa. Further analysis demonstrated that the differences in specificity between these two Acrs are due to intersubtype sequence variations of the Cas7f protein.

Advisor: Davidson, Alan AD
Function-Space Bayesian Learning: from Gaussian Processes to Bayesian Deep Learning

Bayesian methods provide a general and principled framework to quantify and update beliefs based on prior knowledge and observed evidence. This thesis presents my works about function-space Bayesian learning, whose priors and posteriors are specified and computed over the function-space. This thesis first focuses on Gaussian processes (GPs), a family of traditional function-space Bayesian models. To learn a suitable kernel for the GP prior, I propose a neural network structure that computes expressive kernel compositions. Because this structure is fully differentiable, we can learn the prior kernel from data with end-to-end gradient-based optimization. Moreover, I propose a new variational GP approximation to address computational bottlenecks in variational Gaussian processes. This variational GP achieves substantial improvement in computational complexity and approximates the true posterior with high fidelity. In the next part, I propose a general framework for function-space Bayesian learning that goes beyond GPs. I apply this framework in Bayesian deep learning and demonstrate its ability to train Bayesian neural networks with interpretable function-space priors. Furthermore, by exploiting a function-space perspective, I show that the hidden units in neural networks can be viewed as inter-domain inducing points so that I can draw an equivalence between finite neural networks and sparse Gaussian processes. In the last part, I employ Bayesian models for online memory selection and improve the robustness against imbalanced data streams in continual learning. Finally, I summarize the thesis and discuss potential future directions.

Keywords: Bayesian Deep Learning
Bayesian Methods
Gaussian Process
Machine Learning
Uncertainty Estimation
Advisor: Grosse, Roger
The 1841, 1851, and Mahler Versions of Robert Schumann's Symphony No. 4 in D Minor: A Comparative Investigation into Cyclic Form and Dramatic Structure

While past studies have provided a general comparison of the three versions ofSchumann’s Fourth Symphony, or a more detailed account of orchestrational variances among the first movement(s), this thesis addresses the first and the fourth movements, primarily from a form-functional perspective, and secondarily in terms of dramatic structure / Steigerung characteristics. From a conductor’s perspective, the study informs the formal and expressive clarity of each version’s broad “four-in-one” design. It also evaluates a somewhat more subjective matter, which is the effectiveness of each version’s dramatic transformation from dark and heavy to light and exuberant: a process that manifests most prominently across the duration of the Finale. The dissertation’s first section deals with the first movement in five parts. It reveals that the 1851 version, though lacking the transparency and contrapuntal variety of the original, creates a more expressive higher-level exposition of the work’s melodic content. Moreover, Schumann’s revised final sections clearly depict an evaded reprise for the movement, while the original is less resolute in this characterization. As a result, Schumann’s revision more compellingly points to the Finale for the powerful arrival of the work’s higher-level recapitulation. Mahler’s first movement, in turn, surpasses the 1851 version in creating the clearest large-scale exposition of thematic content, and the most vivid depiction of recapitulatory evasion. The study’s second section focuses on the transition to the Finale and the Finale’s main theme, the subordinate theme, development, elements of recapitulation, and the coda sections. The investigation reveals that the 1841 version forms the least powerful high-level recapitulatory confirmation at the start of the Finale; and, as it is consistent with a relatively light aesthetic across the movement, the least vivid depiction of “relaxant” transformation by the end of the symphony. By contrast, Schumann’s revision creates the strongest large-scale reprise, and expresses the greatest “relaxant” transformation across the movement. Mahler’s version, despite possessing a wonderful Steigerung in the transition to the Finale, actually displaces intensity from the start of the Finale to its end. This ultimately undermines the symphony’s recapitulatory climax, and re-shapes the dramatic narrative to emphasize heroic brilliance at the work’s end.

Keywords: 1841 1851 Mahler Version Schumann op. 120
Gustav Mahler
Reorchestration
Robert Schumann
Robert Schumann Symphony No. 4
Three Versions of Schumann's Symphony No. 4
Advisor: McClelland, Ryan
Strongly Interacting Fermions in a Multi-orbital Optical Lattice

This dissertation discusses the experimental study of strong fermionic interactions in an optical lattice. Ultracold samples of $^{40}$K are prepared in an intricate experimental platform using the combination of various optical and evaporative cooling techniques. The atoms are adiabatically loaded into an optical lattice to realize isolated pair states. Various tools for the coherent manipulation of spin and orbital degrees of freedom of the atoms in the lattice are developed. The inter-particle interactions between pairs are tuned using magnetic Feshbach resonances. Spectroscopic measurements of resonantly enhanced and controllable s-wave and p-wave interaction energies are reported. The measurements extend to the unitary limit of interactions characterized by diverging scattering lengths and universal observables. These measurements show excellent agreements to an exact solution for two harmonically confined atoms interacting via a pseudopotential and numerical solutions using an \textit{ab initio} interaction potential. For p-wave interactions, exquisite experimental control is demonstrated by measuring Rabi oscillations between non-interacting and strongly interacting atomic pairs, which are used to accurately measure highly sensitive properties such as the two-body wavefunction overlap. With the full suppression of three-body loss processes, the lifetime of p-wave interacting pairs is investigated. The experiments demonstrate that losses of p-wave interacting pairs are limited by the intrinsic lifetime of the free-space molecular dimer, resulting in the observation of lifetimes that are fifty times larger than previous measurements in $^{40}$K. The observation, control, and comprehensive understanding of strong fermionic interactions demonstrated in this thesis illuminate a path towards the assembly of new many-body states of matter.

Keywords: Degenerate Fermi Gas
Feshbach Resonance
p-wave interactions
Quantum Optics
Quantum Simulation
Ultracold Atoms
Advisor: Thywissen, Joseph H
On the Manufacturing, Characterization, and Optimization of Melt-stretched Honeycombs

Melt-stretching is a process by which a polymer melt expanded between a set of perforated platens can be made to self-arrange into a honeycomb sandwich panel with integrated face sheets. The resulting architectures are dependent on numerous process inputs including the air ingress locations, the stretching speed and distance, and the rheological properties of the polymer melt. Strain hardening in the polymer melt has been identified as a key factor to enable such honeycombs to form, as well as to determine their non-constant web thickness in both the in-plane and out-of-plane directions. The mechanical behaviour of melt-stretched honeycombs can be understood as a hybridization of a conventional constant-thickness honeycomb with an array of columns at the locations where webs intersect; the significant corner fillets created in this process concentrate structural material at the web junctions. Depending on its relative density and internal material distribution, a melt-stretched honeycomb may exhibit a variety of competing failure modes including plastic collapse and elastic buckling. The varieties of non-uniform material distribution accessible through the melt-stretching process were generally found to reduce mass-specific strength and stiffness in the loading paradigms evaluated. Polymers which produced honeycombs of near-constant web thickness were therefore found to be preferable for lightweight structural applications. Webs in a melt-stretched honeycomb panel can be positioned by manipulating the air ingress locations to tune the mechanical responses of the structure. An evolutionary algorithm was developed for this purpose and showed good effect over a range of design cases. Through many iterations of random change and selective screening, improvements in mass-specific stiffness have been demonstrated on the order of 10% compared to generic honeycombs of the same mass and geometry. Melt-stretching has thus been shown to offer a novel design freedom that is infeasible by conventional honeycomb manufacturing processes.

Keywords: honeycomb
optimization
rheology
sandwich panel
thermoplastic
Advisor: Hibbard, Glenn D
Steeves, Craig A
How Do Work-Family Policies Shape Parents’ Time with Children?

Parents’ time devoted to unpaid care for their children remains persistently gendered and is a key driver of gender inequality at home and work. At the same time, both mothers and fathers report a strong desire for more time with children, driven by norms prescribing an intensification of parenthood. These care pressures may be alleviated by work-family policy, an institutional tool that provides financial and normative imperatives for (re)shaping gendered arrangements of paid work and unpaid care. This dissertation explores how work-family policies aimed at or available to fathers – reserved paternity leave and workplace flexibility – shape parents’ time with children in Canada and the United States. These three chapters innovate on the conceptualization of parent-child time, considering a broader scope of time (total co-present time) and the co-presence of the other parent (solo versus family time). First, I examine how a state-provided reserved paternity leave policy in the quasi-experimental setting of Québec impacts fathers’ and mothers’ time with children. This policy led to a plausibly causal increase in fathers’ “responsibility time,” i.e., solo parenting time across activities when co-present with children. Similarly, this policy led to a plausibly causal increase in mothers’ solo parenting time in routine childcare, likely because of a corresponding decrease in housework time. Second, looking at employer-provided policy, I investigate how workplace flexibility policies are associated with fathers’ time with children in the United States. Flextime (control over start and stop times) and flexplace (work from home or remote work) are associated with increased “family” time with children – when the mother is also present – across activities. Taken together, these studies show that work-family policies aimed at or accessed by fathers can reshape gendered arrangements of unpaid care for children. However, this depends on the policy design (near-universal, state-provided reserved paternity leave versus selective, employer-provided flexibility policies) and the dimensions of parent-child time examined (total co-present time; solo or family time). Ultimately, this dissertation expands knowledge on and presents methodological considerations for the relationship between work-family policies and parent-child time, with key implications for family well-being and gender inequality.

Keywords: Family
Fatherhood
Paternity leave
Remote work
Time use
Work-family policy
Advisor: Milkie, Melissa A
Modeling Isotropic and Anisotropic Diffusion in Aging Brain White Matter with MRI

The cognitive decline that accompanies normal adult aging is associated with degeneration of the brain’s connectivity backbone, the white matter (WM). Age-related WM degeneration includes both (i) neuronal disconnection resulting from a loss of WM fibers and (ii) reduced conduction efficiency among intact neuronal connections resulting from disorganization and degradation of the WM fibers that remain. The development of single-shell diffusion MRI has made it possible to probe WM degeneration in-vivo at its earliest microstructural stages by measuring the anisotropy of the microscopic diffusion of water molecules in WM tissue. Diffusional changes in aging reflect both processes specific to anisotropic WM fibers, such as their disorganization and degradation, as well as elevated isotropic diffusivity that results from extra-fiber processes, such as an enlargement of the extracellular space associated with fiber loss. These two classes of diffusion effects—anisotropic and isotropic—are presumably associated with different cognitive domains, so they can potentially serve as differential targets for preventing and treating pathological aging. Unfortunately, conventional scale-invariant measures of diffusion anisotropy (the most common being fractional anisotropy, FA) inherently conflate anisotropic with isotropic effects. The purpose of this PhD thesis is to investigate diffusion anisotropy measures that, rather than being scale-invariant, are invariant under elevated isotropic diffusivity, so that fiber-specific diffusional changes and elevated isotropic diffusivity can be distinguished. I investigate how these measures can be extracted by fitting both a one- and two-compartment model of diffusion to single-shell diffusion MRI data, and I test a hypothesis that these measures can be used to uncover positive age associations of anisotropy in regions of complex fiber architecture to reflect selective degeneration of secondary crossing fibers. I further devise a mathematical framework for interpreting the outcome of these model fits to single-shell diffusion MRI data, and I derive a nonlinear relationship between the one- and two-compartment models that implicates the sensitivity and explanatory power of their respectively derived metrics to age-related processes. Ultimately, this thesis provides a foundation for understanding how to harness the power of single-shell diffusion MRI data for probing age-related WM degeneration.

Advisor: Chen, Jean
Pasternak, Ofer
The Consequences of Family Stress in the Work-Family Interface: Three Longitudinal Studies in Canada

Although research on the work-family interface has proliferated across multiple disciplines, two significant gaps remain. First, despite recognizing the bidirectional nature of work-family conflict, the antecedents of family-to-work conflict (FWC), compared to work-to-family conflict (WFC), are still far less understood. Second, an emerging body of work has documented the association between WFC and children’s health. However, little is known about conditions that might moderate this focal association. Motivated by these empirical observations, my dissertation seeks to provide new knowledge about the consequences of family stressors—and their moderating contingencies in the work-family interface over time. In Chapter 2, I develop two competing hypotheses to assess the reciprocal relationship between financial strain, work-family conflict, and psychological distress. The results based on a three-wave cross-lagged model demonstrate that financial strain—a prominent chronic family stressor—at wave 1 is associated with FWC at wave 2. However, FWC at wave 2 and psychological distress at wave 3 are unrelated. Furthermore, WFC at wave 2 fully mediates the association between financial strain at wave 1 and psychological distress at wave 3. In line with this, I conduct fixed-effects models to establish the positive association between family stressors—as measured by financial strain, spousal disputes, and relationship dissatisfaction—and FWC over time in Chapter 3. Moreover, by integrating ideas of border theory with the stress process model, I propose that work-family multitasking can be conceptualized as a family-related stressor that might exacerbate the positive association between family stressors and FWC—and gender might further elaborate the narratives associated with the moderating effects of work-family multitasking. Chapter 4 shifts attention to the moderating contingencies of family stressors (i.e., financial strain, household income, spousal disputes, and relationship dissatisfaction) in the association between WFC and children’s problems with school, friends, and health. The results based on random-effects models demonstrate that WFC is associated with higher levels of children’s problems over time, but household income and spousal disputes moderate this focal relationship—and they do so differently for mothers and fathers. Collectively, my dissertation draws upon multiple theoretical perspectives to highlight the central role of family stress in the work-family interface.

Advisor: Schieman, Scott