VictorJuiz/thesis huggingface dataset:
Causal Variance Decompositions for Evaluating Healthcare Provider Performance
Keywords: Causal inference
Hospital profiling
Quality indicator
Variance decomposition

There has been a growing interest in striving for accountability and transparency in healthcare by quantifying and comparing the performance of providers. This requires measuring the quality of care provided to patients, which is often done using disease-specific quality indicators (QIs). Before considering intervening and improving quality gaps identified by using QIs, the chosen indicator has to demonstrate existing differences in the quality of care. Therefore, the overarching aim of this thesis is to develop metrics that assess the usefulness of QIs in identifying existing differences in the quality of care provided between providers. This can be achieved by decomposing and quantifying the overall variation between providers in a causal inference framework. The first objective is to develop a three-way causal variance decomposition to attribute observed variation in care received into that causally explained by hospitals’ performance, the patient case-mix itself, and unexplained variation. In the context of surgical cancer treatments, the performance variations can be due to hospital and/or surgeon level differences, creating a hierarchical clustering. The second objective is to generalize the causal variance decomposition for several exposure hierarchies. For this purpose, I derive a decomposition of the observed variation in care received into four parts, explained by patient case- mix, causally explained by hospitals’ performance, causally explained by surgeons’ performance, and unexplained variation. While the use of variance decompositions can demonstrate differences in quality of care, causal mediation analysis can be used to investigate the care pathways that lead to these differences in performance between hospitals. Combining these two approaches enables decomposing between-hospital variation in an outcome-type indicator into two parts: the part that is mediated through a specific process of care and the part that is due to all other pathways. The third objective is to derive a causal mediation analysis decomposition of the between-hospital variance into three parts, the natural indirect effects, the natural direct effects, and a covariance-type term. Model-based estimators are formulated for the variance decompositions, and their performance are investigated through simulation studies. All methods are demonstrated in real data applications in Ontario kidney cancer data.
Carrying Places: How Elementary Students Contest Historical Asymmetries and Grow Relational Knowledge About Land/land Through Origin Stories
Keywords: Indigenous histories
practitioner research
settler colonialism
social studies
subject and relational formation
Treaty education

This practitioner research study explored how grade three students understood their relationships to the histories, places, and peoples of where they live. Specifically, I examined how students experienced settlerhood and what happened when they travelled outside of official curriculum and into the flow of treatyhood. My theoretical framework drew on important tenets from within Indigenous worldviews, the operational structure of settler ontologies, and how the body of knowledge for both of these is articulated through origin stories. I demonstrated how the Ontario social studies/ history curriculum embodies a settler grammar that structures how students understand the world. Instead of reproducing settler-normative experiences and creating settler subjects by habituating students into settler traditions, I went outside of settler ontology in order to interrupt the process of settler-making by teaching through Indigenous histographies. My empirical study was grounded in the methods and perspectives of practitioner research, which centers, illuminates, and troubles the interlaced relationships in classrooms and mobilizes knowledge production from the viewpoints of teachers and students. As their teacher, I paid attention to the overlapping layers of their subjectivities through stories of themselves with each other. My intention was to help develop explicitly relational forms of interacting with others in the world. Because students’ own storied presences were on contested lands, I invited students to share their life stories and intermesh them with etiological Indigenous stories. Students also learned about settler origin stories of the nation. They developed awareness of Land and places, learned from their own repertoires of cultural knowledge, and utilized their relationalities in-place to learn from the confluence of story. Students incorporated treaty teachings that folded Indigenous sensibilities into their repertoire of understanding—despite the ongoing erasure of these worldviews by machination of the settler state. I troubled the issues I encountered in my research, illuminating the contradictions and tensions that resulted when I taught about Indigenous sensibilities to Land. In conclusion I highlight the incommensurable conundrum of representation of Indigeneity within settler colonial structures and pose further questions about how to devise relational lenses through which students might view the world.
Advanced Microfluidic Platforms for Studying the Stromal Compartment of Pancreatic Cancer Tumor Microenvironments
Keywords: Mass Spectrometry
Microfluidics
Organ-on-a-Chip
PDAC
Stroma
Tumor microenvironment

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease of the exocrine pancreas, with treatment resistance attributed to the aggressive biology of the tumor microenvironment (TME). Interactions between activated pancreatic stellate cells (PSCs) and pancreatic cancer cells (PCCs) give rise to dense fibrotic masses (stroma) and the concomitant avascularity and hypoxia within the TME alters metabolic activity and mediates infiltration of T cells and chemotherapeutic agents. While many studies have investigated the mechanisms of stroma-mediated treatment resistance, these effects are still not well understood. There is thus an urgent need for more accurate models of the TME stromal compartment.In the last decade, the synergistic combination of microfluidic technologies with 3D cultures have resulted in Organ-on-a-Chip (OOC) technologies that leverage the microscale manipulation of fluids to achieve precise spatiotemporal control of 3D tissues. However, many of these systems remain in the proof-of-concept stage due to complex fabrication steps, and sealed architectures that significantly limit methods of analysis and data collection. Therefore, more advanced microfluidic platforms for studying the stromal compartment of the PDAC TME are required, that can provide not only optical access but also non-destructive physical access for more detailed assessments of mechanical and metabolic properties. The main objective of this thesis is to develop and characterize the stromal compartment of a novel PDAC-on-a-Chip model, using an openable multilayer microfluidic architecture that enables traditional image-based analysis as well as on-chip mechanical stiffness testing and sample extraction for small molecule detection. We first tested multilayer and phaseguide-separated channel layouts and combined these features to develop a novel microfluidic architecture that permitted 3D diffusive interactions. A modified version was used to develop a PDAC-on-a-Chip model where hydrogel-embedded PSCs were cultured with PCCs in an openable device that provided direct access to the hydrogel compartment. Our model displayed hallmark characteristics of PDAC including PSC activation, stiffening of the matrix, and collagen content increase. We also identified potential contributions to metabolic pathways via mass spectrometric analysis of extracted gel samples. These advanced platforms have thus demonstrated the potential to deepen our understanding of PDAC through modeling and analysis of more complex TME stromal characteristics.
New Probes of Hidden Sectors: From Colliders to Cosmology
Keywords: Beyond the Standard Model
Cosmology
Phenomenology

We begin by reviewing the development of the Standard Model of particle physics, and the challenges it faces today. We argue that, based on considerations of naturalness, it is well-motivated to study the signatures of hidden sectors as models of Beyond the Standard Model (BSM) physics, and present three of our own studies that engage in this endeavour. First, we develop methods to identify the production mechanism of long-lived particles produced at the Large Hadron Collider (LHC) using the proposed MATHUSLA detector, finding that it can do so accurately with only a few dozen detections. Second, we devise a strategy to search for Soft Unclustered Energy Patterns (SUEP) produced in exotic Higgs decays at the LHC, using unsupervised machine learning methods. We find that the High-Luminosity LHC can be sensitive to Higgs branching ratios to SUEP down to 1%. Finally, we present an analysis of constraints on the parameter space of atomic dark matter from large-scale cosmological observations, setting new bounds on the scale at which the dark sector must decouple.
Rethinking the Characterization of Nanoscale Field-Effect Transistors
Keywords: Electrical Characterization
Electrical Hysteresis
Electron Transport
Nanoscale Field-Effect Transistor
Quantum capacitance
Zero Temperature Coefficient

Standard methods for calculating transport parameters in nanoscale field-effect transistors (FETs), namely carrier concentration and mobility, require a linear connection between the gate voltage and channel conductance, however, this is often not the case. One major reason often overlooked is that shifts in chemical and electric potential can partially compensate each other, commonly referred to as quantum capacitance. In nanoscale FETs, capacitance is often unmeasurable and an analytical formula is required, which assumes the conducting channel as metallic and common methods of determining threshold voltage no longer couple properly into transport equations. As present and future FET structures become smaller and have increased channel-gate coupling, this issue will render standard methods impossible to use. This thesis discusses the validity of common methods of characterization for nanoscale FETs, develops a universal model to determine transport properties by only measuring the threshold voltage of an FET and presents a new parameter to easily classify FETs as either quantum capacitance-limited or metallic approximated charge transport. Another major factor affecting transport characteristics that is often ignored in literature is electrical hysteresis from localized trap states and, in combination with the proposed universal characterization model, novel techniques are introduced to measure and remove the errors associated with these effects. Additionally, a hysteresis model is developed and, combined with new experimental techniques, used to extract total concentration of trap states and their average energy. This model is used to explain discrepancies seen in literature with regards to gate voltage sweep rate dependence of hysteresis itself. Temperature dependence of electrical characteristics is also analyzed and a theoretical model was developed to explain a phenomena known as the zero-temperature-coefficient (ZTC) and how it relates to fixed oxide charges in the semiconductor channel oxide of an FET. Ultimately, this body of work helps explain several major discrepancies generally ignored in literature regarding nanoscale FET electrical characterization and provides novel experimental techniques and theoretical models to more accurately determine key metrics for characterizing transport in these devices.
Hierarchical Imaging and Computational Analysis of Three-Dimensional Vascular Network Architecture in the Entire Postnatal and Adult Mouse Brain
Keywords: brain vasculature
neuroscience
vascular biology

Background: The cerebrovascular network plays a vital role in brain development, normal brain function, and various central nervous system (CNS) disorders. Nevertheless, the effects of recently discovered (anti)angiogenic markers, genes, and pharmaceutical targets on cerebrovascular architecture remain largely unknown. Additionally, there is a lack of quantitative data and imaging approaches to study cerebrovascular architecture and morphology at sub-micrometer resolution across the entire brain. Our objective is to bridge this gap between the molecular and morphological levels by establishing a novel neuroimaging pipeline that enables objective quantification and visualization of cerebrovascular network architecture at ultra-high resolution. Methods: Here we present a step-by-step method for hierarchical imaging and computational analysis of vascular networks in entire postnatal and adult mouse brains. The method involves resin-based vascular corrosion casting, synchrotron radiation microcomputed tomography imaging, and 3D computational network analysis. Results: We visualized and quantified the cerebrovascular architecture in early postnatal(n=10, postnatal day 10) and adult (n=10, postnatal day 60) brain vascular corrosion casts, including a separation between capillaries and non-capillary vessels. Our analysis revealed significant changes in cerebrovascular morphology from the early postnatal stage to adulthood, including an increase in vascular volume fraction, branchpoint density, branchpoint degree, and vessel tortuosity, combined with a decrease in vessel segment diameter, length and volume, branchpoint diameter, extravascular distance, and the average adjacent segment angle as a measure of vessel directionality. A genetic knockout model of the known anti-angiogenic molecule Nogo-A confirmed the applicability of our method to study the effects of individual genes on vessel morphology. Conclusion and Future Directions: Using the novel neuroimaging pipeline presented in this thesis we provide a morphological atlas of the entire mouse brain vasculature at both the postnatal and adult stages of development. The presented methodology enables researchers to objectively quantify cerebrovascular morphology before and after pharmacotherapy or intervention in various experimental models of cerebrovascular disease. Targeted graph-based machine-learning approaches, such as link prediction algorithms and arteriovenous identity classification, can be integrated and our approach has the potential to be extended to human ex-vivo resected brain tissue or postmortem settings.
Beyond the Twilight Zone: The Restructuring and Resurrection of Zombie Firms
Keywords: credit markets
deep learning
natural language processing
restructuring
zombie firms
zombie recovery

Zombie firms are businesses with operating profits that are sustainably insufficient to cover their debt servicing costs. The existence of zombie firms crowds out growth opportunities for other healthy firms and thus distorts overall economic growth. Despite their economic importance, however, the question of what factors enable certain zombie firms to survive while others fail has yet to be addressed in the extant literature. Thus, I propose focusing on an important but hitherto overlooked aspect of zombie firms—their restructuring activities. I first use a financial statement-based measure of restructuring charges to infer the prevalence of restructuring activities and find that activities that help a firm clean up its business operations and improve transparency are an important determinant of zombie resurrections. I then investigate the types of restructuring activities that determine the revival of zombie firms. I employ a pre-trained deep learning language model, FinBERT, to construct measures for business and financial restructuring. I find that business restructuring that improves the operational efficiency of zombie firms and improves revenues helps resurrect zombie firms, whereas financial restructuring alone does not appear to contribute to their resurrection. Furthermore, survival analysis suggests that business restructuring shortens the duration of a firm’s zombie status. Finally, I find that recovered zombie firms become more efficient than non-recovered zombie firms.
Local Delivery of PACAP Attenuates Inflammation and Promotes Functional Recovery in a Mouse Model of Stroke Injury
Keywords: Electrostatic controlled release
Hydrogel
Inflammation
Nanoparticle
PACAP
Stroke

Ischemic stroke leads to the activation of resident microglia and astrocytes in the brain parenchyma. It was previously thought that immune activation after ischemia is wholly detrimental to stroke recovery. We now know that these cells can activate endogenous repair mechanisms to promote neural regeneration. Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide implicated in both modulation of inflammatory processes and neuroprotection after ischemic stroke. However, its short in vivo half life and dose limiting side effects hinder its therapeutic potential. Here, we address these limitations with a biomaterial-based approach for the local, non-invasive delivery of PACAP to the stroke injured brain. A nanocomposite comprised of poly(lactic-co-glycolic) nanoparticles in a hyaluronan and methylcellulose hydrogel enabled the sustained release of PACAP. The electrostatic interactions between negative PLGA and positive PACAP facilitated encapsulation-free controlled release with nearly 100% peptide loading. The release profile could be tuned over a two-week period by manipulating the surface charge of the nanoparticles, and consequently the adsorption-desorption kinetics between the peptide and nanoparticles in the hydrogel. The vehicle was implanted epicortically in endothelin-1 stroke injured mice, which released PACAP into the tissue over a 10 day period. The epicortical delivery of PACAP improved forelimb strength and motor control one month post stroke. The treatment decreased apoptosis and attenuated both microglia and astrocyte activation within the first week of stroke injury, and drove remaining microglia towards a pro-repair phenotype for the duration of release. These findings suggest that PACAP’s neuroprotective and anti-inflammatory properties improved the functional recovery of treated animals. This work demonstrates that immune modulation with therapeutic peptides is an effective strategy for stroke treatment. This vehicle enables therapeutic peptides and proteins to enter the central nervous system effectively and non-invasively. The electrostatic adsorption controlled release system is amenable to not just stroke treatment, but for disorders of the central nervous system more generally.
Economic Insecurity, Work, and Mental Health among Gay, Bisexual, and Queer Men: A Critical Narrative Inquiry into Precarious Work
Keywords: Employment
LGBTQ
Mental Health
Narrative
Poverty
Qualitative

Precarious employment has proliferated across Western capitalist economies and is associated with economic insecurity and poorer health. This dissertation investigated precarious employment among lesbian, gay, bisexual, transgender, and queer (LGBTQ+) people through an exploration of what is known (scoping review) and what more can be learned from precariously employed LGBTQ+ workers (narrative inquiry).A scoping review guided by an intersectional framework found that LGBTQ+ people were overrepresented in precarious forms of work, including underemployment and part-time work. Additionally, they experienced hostility and discrimination when looking for employment and in the workplace that contributed to increased labour market precarity. A community-engaged narrative inquiry was then conducted among 20 gay, bisexual, and queer men experiencing precarious employment in Toronto, Canada. Guided by political economy frameworks, Polkinghorne’s narrative analysis was used with attention to plotlines, characters, settings, and temporality within and across participants’ stories. A new story was constructed that provides rich insights into lived experiences and the meanings of these experiences among participants, as well as the structural conditions that shape these experiences and meanings. Two analyses were conducted using this method. The first analysis explored labour market experiences and identified the mechanisms that led participants into precarious employment and economic insecurity. Cisheteronormativity, alongside racism, xenophobia, and ableism, shaped participants’ experiences from adolescence to adulthood through LGBTQ+-adversity in adolescence, overt and perceived discriminatory practices in hiring, and harassment and discrimination on the job. Participants’ stories illustrate unique ways that LGBTQ+ people might be particularly susceptible to exploitative labour markets. The second analysis explored the relationship between precarious employment and mental health. Results illustrate a cyclical pattern whereby participant’s adverse adolescent experiences associated with LGBTQ+-related discrimination negatively impacted their mental health, which in turn shaped their employment trajectory. Upon entering the labour market, precarious employment was exacerbated by mental health challenges and, subsequently, precarity exacerbated these challenges. This dissertation addresses the dearth of scholarship in three primary areas: occupational health among LGBTQ+ populations, LGBTQ+ poverty, and LGBTQ+ employment. Implications inform labour market policies and social service and public health practice when supporting LGBTQ+ people experiencing mental health concerns, economic insecurity, and employment challenges.
College Contract Faculty in Ontario: Professional Identities and Precarious Employment
Keywords: College
Faculty
Part-time
Precarious
Professional
Teaching

Partial-load college faculty simultaneously occupy insider/outsider positions in their respective higher education institutions. How do they perceive the relationship between their employment status and their work as educators? In recent scholarship, it has been argued that part-time faculty occupy liminal positions as simultaneous professionals and precarious labourers in higher education. None of the literature attends to how part-time college faculty (a cohort that makes up 70%+ of Ontario’s college faculty) who specifically aspire to full-time teaching positions think about their work and professional identities, much less in the context of the province of Ontario, Canada. Through semi-structured and open-ended interviews with ten partial-load college faculty who aspire to full-time teaching positions across three colleges in the Greater Toronto Area (GTA), this study asks faculty to reflect upon the relationship between their conditions of employment and their work as educators. How partial-load college faculty think about their work and professional identities has direct import for what continues to be the foundational mission, purview, and day-to-day activities of colleges – teaching and learning. Holland, Lachicotte, Skinner, and Cain’s (1998) identity theory provides the framework for enabling a nuanced analyses as to how partial-load college faculty think about, make sense of, and narrate their experiences in the liminal space of precarious professionals. The results of this study show that partial-load faculty are largely excluded from the pedagogical communities of their departments and institutions and that every aspect of their work as educators (curriculum development, professional development, and relationships with colleagues) is negotiated and filtered through their precarious status. This research sheds light on the centrality of partial-load college faculty on the enactment of curriculum in colleges as well as explores how various stakeholders can make meaningful change to address the professional goals and curricular inclusion of this significant teaching cohort.