VictorJuiz/thesis huggingface dataset:
Incidence and prognosis of post-traumatic headache in adults

Post-traumatic headache (PTH) is a common debilitating symptom after mild traumatic brain injury (MTBI) or concussion from motor vehicle collisions (MVC), falls, sports concussions and other trauma. It is also a common whiplash-associated disorder (WAD). PTH is one of the most poorly understood headache disorders in terms of its burden, pathophysiology, and prognosis. The primary objective of my thesis was to investigate the incidence and prognosis of PTH. To achieve this, I conducted a systematic review, and developed two prediction models by analyzing data from a population-based, incidence cohort study on traffic injuries from Saskatchewan, Canada. Finally, I used data from an insurance cohort of Swedish incident traffic injuries to validate my prediction models. My systematic review revealed sparse literature on the incidence and prognosis of PTH. The incidence of PTH varied across studies because the methods and populations studied were very different. The review suggested that pre-existing headache, younger age, and post-traumatic stress disorder (PTSD) are associated with delayed recovery from PTH. From my analysis of the Saskatchewan cohort, I found that the incidence of PTH is highest among young females, with an annual incidence of 734 per 100,000 (95% CI 731.5â 736.6) in 1999. I developed two separate prediction models for PTH and the nonrecovery from all injuries six months after a MVC. The models are based on patient and clinical characteristics that are routinely collected during an initial clinical encounter. Some common predictors between the models included older age, poorer current health, and lower recovery expectations. The predictive abilities were similar for both models (c-statistic: 0.73). The models were externally validated in a population of traffic-injured adults from Sweden. This thesis provides the first evidence synthesis on the incidence and prognosis of PTH. It also presents the first sex-, age-, and sex-age-stratified estimates of population-based incidence rates of PTH following MVC and proposes prediction models for recovery at six months in adults with PTH. This information advances the field of PTH by indicating important gaps in the literature, and providing recommendations for improving the prediction of outcomes for adults who present with PTH within 30 days of a traffic collision.

Keywords: brain concussion
post-traumatic headache
prediction model
prognosis
Advisor: Cassidy, J. David
Speculative Methodologies Emergent Literacies: Walking Writing as Research-Creation

My dissertation develops, extends, and experiments with theories of emergence to think ethico-politically about cultural productions, literacy practices, and pedagogies. Theoretically informed by process philosophy, new materialisms, and affect theories this dissertation focuses on three reading, writing, and walking research-creation events. The first research-creation event is a multi-participant marginalia project inspired by Friedrich Nietzsche’s ‘eternal return’ (an ‘affirmation’ that emerged during a walk). The second research-creation event is an in-school project with high school English students that centers on emergent publics, literacies, and ethico-political matters of concern that arose through walking and writing. The third research-creation event is a long-distance walking-writing post-card project that queers the relationship between walking, chance encounters, and the politics of saying yes to whatever turns up. I employ a more-than-representational approach to writing as a further engagement with theories of emergence and their relevance to qualitative research methodologies in the field of education.

Keywords: Literacy
Post-Qualitative Methodology
Public pedagogy
Research-creation
Walking
Writing
Advisor: Springgay, Stephanie S
Education in the Age of Fracture: A Historical Analysis of the Development of Ontarioâ s 2013 and 2015 Canadian and World Studies Curriculum Documents

This dissertation examines how the concept of “disciplinary thinking” became a focus of Ontario’s revised 2013 and 2015 Canadian and World Studies curriculum documents. It begins with a history of curriculum studies that highlights the focus of contemporary curricular scholarship on the challenges of living life in “the age of fracture.” It then offers a history of “historical thinking” as a pedagogical concept, illustrating that this concept had the potential to address many of the issues associated with life in the age of fracture. A close analysis of the 2013 and 2015 curriculum documents, however, reveals that the promise offered by disciplinary thinking has not been fulfilled. This raises the obvious question: why has this occurred? The final chapters of this dissertation answer this question by analyzing the process that led to the Canadian and World Studies curriculum documents. In the end, this dissertation argues that while the curriculum development process used by Ontario’s Ministry of Education appears to be inclusive and neutral, it is in fact an example of a Foucauldian “technology of governmentality”. In making this argument, this dissertation draws particular attention to the Ministry of Education’s pre-occupation with perceived performance gaps and the need for students to develop their ‘human capital’ in order to survive in a 21st century that is seen as increasingly competitive. This dissertation concludes by questioning the ability of the revised Canadian and World Studies program, as described in the curriculum documents, to prepare students for life in the 21st century, arguing that the focus upon gaps and human capital has led to a curriculum that fails to fully prepare students for life in contemporary Canada.

Keywords: Curriculum History
Disciplinary Thinking
Foucault
Governmentality
Historical Thinking
History of Education
Advisor: Sandwell, Ruth W
Endothelial Dysfunction and Microvascular Injury in Life-Threatening Diseases

Endothelial activation and dysfunction contributes to multiple life-threatening disorders including malaria, sepsis, acute lung injury (ALI) and viral haemorrhagic fevers. It represents a common pathway of injury leading to microvascular leak, multi-organ failure, mortality and long-term deficits in survivors. The detection of circulating biomarkers of the activated endothelium may enable the early detection and triage those at risk of severe disease, improving clinical outcome and prognosis. Here we investigated three life-threatening diseases (high altitude pulmonary oedema (HAPE), cerebral malaria and malaria-induced ALI) with a focus on the Ang/Tie2 pathway and its role in endothelial activation and microvascular leak. In each example, we defined the relationship of the Ang/Tie2 axis to disease pathobiology and where possible, explored mechanism and interventions based on genetic and pharmacological strategies. In a prospective case-control study of climbers developing altitude illness, we investigated mediators of endothelial activation, vascular tone and cell stress. Specifically, we show that the endothelial activation markers (endothelin-1 and soluble kinase insert domain receptor) are correlated with HAPE. We next investigated these pathways in malaria-induced cerebral microvascular injury, using in vivo and ex vivo approaches. Specifically, we show that genetic deletion of microRNA-155 enhances endothelial quiescence, blood-brain barrier integrity and survival. We suggest that these observations are likely associated with Ang/Tie2 axis dysfunction. Moreover, anti-miR-155 preserved endothelial integrity and reduced microvascular leak, induced by patient sera. Finally, we investigated these pathways in malaria-induced ALI, using sera from children with malaria-induced respiratory distress, and pre-clinical animal models. Specifically, we show that an association with Ang/Tie2 axis dysregulation and pharmacological activation of the Ang/Tie2 axis in vivo improves survival and decreases pulmonary vascular leak. In summary, these studies suggest common mediators of endothelial activation and dysfunction that play a critical role in maintaining vascular integrity, reducing microvascular leak and improving outcome from multiple different insults.

Keywords: Acute Lung Injury
Cerebral Malaria
Endothelium
Host Response
Infectious Diseases
Malaria
Advisor: Kain, Kevin C
Multivariate Bayesian Control Chart with Dual Sampling Scheme

Recently, there has been a growing interest among industrial practitioners and researchers for applying economically designed control charts in quality control, condition monitoring, and condition-based maintenance (CBM). Control charts are powerful tools for process control which are used extensively to ensure the process stability over the production run. It has been proved that traditional control charts are not optimal and the control chart parameters should be determined based on the posterior probability that the process is out of control. Design and development of Bayesian control charts in both quality control and CBM applications are the main focuses of this thesis. Traditionally, in designing of a control chart, the observations are collected periodically. However, in many real applications, high sampling cost is associated with collecting observable data, therefore, it could be beneficial to monitor the process/system less frequently when it is in a healthier state and more frequently when a sample shows some indication of a change in the process/system state. The motivation of this thesis comes from such applications when collecting observations is costly, and observations carry partial information about the process or system state. To overcome the drawback of period monitoring, this thesis proposes an optimal control problem in Bayesian framework which uses a novel sampling strategy referred to as dual sampling scheme (DSS) and dual control limits. The system/process is monitored less frequently using a longer sampling interval when the posterior probability is below the warning limit. If the posterior probability exceeds the warning limit, switching to the shorter sampling interval occurs. If the posterior probability exceeds the control limit, the system/process is stopped and full inspection is performed. The proposed model is formulated in both semi-Markov decision process and renewal theory frameworks to obtain the optimal control chart parameters as well as the minimum long-run expected average cost per unit time. For the first time in quality control literature, an explicit formula is derived for computation of average time to signal for multivariate Bayesian control chart with DSS. In addition, the closed-form expressions are derived for system residual life and reliability as functions of the posterior probability statistics.

Keywords: Bayesian Control Chart
Condition-based Maintenance
Economic design of Control Charts
Quality Control
Semi-Markov Decision Process
Advisor: Makis, Viliam
Development and Validation of a Novel Method for the Strengthening and Toughening of Irradiation-Sterilized Bone Allografts used in Orthopaedic Reconstructions

Reconstruction of large skeletal defects is a significant and challenging issue. Large defects can occur due to bone cancer, revision arthroplasty and traumatic injuries. Reconstruction using structural bone allograft is often implemented to repair large skeletal defects. However, sterilizing bone allografts by using gamma-irradiation, which is considered as the most effective sterilization method, causes collagen damage and leads to brittle and weak bone. Our lab has begun to develop a technology, by using a ribose treatment prior irradiation, which protects the bone from the irradiation-induced damage. The aim of this project was to test and verify the ribose treatment through extensive mechanical testing to confirm the effects of our novel method. In addition to the mechanical testing, failure and collagen analysis was performed to understand the protective mechanism of the ribose pre-treatment. Ribose pre-treatment improved the mechanical properties of irradiation sterilized human bone in a pre-treatment concentration-dependent manner. The 1.2M ribose pre-treatment provided >100% of ultimate strength of normal controls and protected 76% of the work-to-fracture (toughness) lost in the irradiated controls. Similarly, the ribose pre-treatment improved the thermo-mechanical properties of irradiation-sterilized human bone collagen in a concentration-dependent manner. Greater free radical content and pentosidine content were modified in the ribose treated bone. The pre-treatment also protected 146% of the fatigue life that was lost in the irradiated controls. Furthermore, using the method of pre-treating bone with ribose prior to irradiation sterilization has some potential to improve irradiation sterilized bone allograft quality while also ensuring the effectiveness of the sterilization process. Collectively, our results suggest that ribose treated bone could be used in the clinical setting and providing bone and tissue banks with allografts with mechanical properties similar to or better than native bones to facilitate bone repair and regeneration.

Keywords: Allografts
Bone
Collagen
gamma-irradiation
Ribose
toughness
Advisor: Grynpas, Marc
A Biophysical Study of Fluoroacetate Dehalogenase

Fluoroacetate dehalogenase (FAcD) is a homodimeric enzyme and belongs to the a/Ă hydrolase protein superfamily. It possesses the ability to cleave C-F bonds and so is capable of using the simplest fluorocarbon, fluoroacetate, as its main source of carbon. The underlying mechanistic details that allow this enzyme to perform C-F cleavage are still unknown. However, details into building a mechanistic model for the type of asymmetric cooperative behavior observed in FAcD are slowly being revealed. In the following studies, I use FAcD as a model system to study its catalytic reaction mechanism focusing on the enzymatic coordinate pathway and the dynamics of various states along the pathway. As well, I use FAcD as a suitable choice to study irreversible enzymatic reactions via time-resolved crystallography (TRX) experiments. Using a series of biophysical techniques I analyze structure, function, and dynamics of both the ground state and transient higher energy states. It was demonstrated using X-ray crystallography that there is subtle structural asymmetry between the individual subunits in the apo state of the enzyme. This asymmetry becomes more pronounced during catalytic activity whereby entropic loss from substrate binding in one protomer is compensated by an increase of entropy and a loss of structural waters in the other. Kinetic measurements of FAcD revealed that during titrations involving excess substrate the enzyme undergoes substrate inhibition. Biphasic chemical shifts identified by NMR indicated a secondary binding site, which was confirmed via crystal structures of various complexes of a catalytically slow mutant (Y219F). This secondary binding site decreases transmission along the allosteric pathway, which could be mapped using rigidity-based transmission allostery (RTA) analysis. Using FAcD as a model system for method development I applied fixed target approaches for time-resolved crystallography (TRX). Using light activation of a caged-substrate, I could verify that structural asymmetry first observed using a series of mutants is still conserved. As well, structural features of the active site and cap domain change from one time-point to the next and corroborate previous results. Taken together, this data shows nuanced mechanistic insights into the structural enzymology of a homodimeric enzyme.

Keywords: Crystallography
Enzymology
NMR
Serial time-resolved crystallography
Advisor: Pai, Emil F
PROTEOMIC ANALYSIS OF THE RESIDENT CELL TYPES IN THE HEART: A FOCUS ON THE FIBROBLAST AND ITS SECRETED PROTEOME

The cardiac fibroblast (CF) is a key cellular component of the heart, being reported in some cases as the largest cell population in the heart. CF play a major role in the homeostasis of the tissue, being involved in extracellular matrix (ECM) maintenance and turnover. It is also important in the heart's pathophysiology and stress response as CF are secretory cells that affect other cell types in the heart. This thesis includes studies that investigate how the CF proteome is altered during hypoxic stress. In brief, proteomic analysis of the CF identified 6163 proteins with subsets altered due to hypoxia. Of particular interest was the CF secreted proteome, which when introduced caused an altered response to hypoxia/reoxygenation in cardiomyocytes. Additionally, it was investigated how the CF differed at the proteome level to the other resident cell types in the heart: the cardiomyocyte (CM), endothelial cell (EC), and smooth muscle cell (SMC). This was in an effort to identify alternative cell type-enriched markers to identify the specific cell type contributors of proteome changes in the heart, which is generally performed at the tissue-level, where cellular resolution of these changes is lost. The second set of proteome studies identified 367 FB-enriched, 97 CM-enriched, 340 EC-enriched, and 52 SMC-enriched proteins. We rank ordered cell-specific enrichment of proteins via magnitude and significance of enrichment. With enrichment data being the most pronounced in FB, we then validated expression of multiple highly-ranked candidates (GRB2, AKR1B1, and PRDX1) in myocardial infarction tissue sections. Immunofluorescent staining showed higher expression in the highly fibrotic infarct scar of 4-week post-MI relative to border and non-infarct regions, confirming the cellular enrichment of our candidates. Potential markers of each cell type have been validated by HPA and immunofluorescent imaging of MI.

Keywords: Cardiac Fibroblast
Cardiovascular
Exosome
Mass Spectrometry
Proteomics
Secretome
Advisor: Gramolini, Anthony O
Characterization of Warm Autoimmune Hemolytic Anemia

Warm autoimmune hemolytic anemia (wAIHA) is characterized by premature clearance of red blood cells (RBCs) mediated by autoantibody binding. Lack of mechanistic insight into wAIHA development has resulted in absence of disease specific therapies and novel diagnostic methods, and is further complicated by a heterogeneous patient population, with respect to disease severity and autoantibody specificity. To gain a broader understanding of the systemic implication of wAIHA, cytokine analysis of 54 patients was undertaken; this work uncovered a set of 11 cytokine wAIHA biomarkers, which suggest a mechanism for sustaining autoantibody production driven by increased functioning of T follicular helper cells and deregulation of T-follicular- and T-regulatory cells. Interestingly, elevated levels of TNFÎą and IL-6 have been implicated in other autoimmune diseases, and have been targeted therapeutically. A method for detection of direct antiglobulin test negative (DAT (-)) wAIHA using western blotting, was developed to facilitate detection of immune mediated hemolysis in wAIHA patients with low autoantibody titer. The methodâ s high sensitivity (100%) enabled detection of natural autoantibodies on the membrane of healthy RBCs. The existence of two previously identified subtypes of wAIHA, Type I characterized by preferential binding of autoantibodies to aged RBCs; and Type II characterized by autoantibodies with non-discriminant autoantibody binding to young and old RBCs, was confirmed using percoll density fractionation. Interestingly, aberrant phosphorylation of RBC membrane protein band 3, was observed: Type I RBCs exhibited elevated levels of band 3 phosphorylation, while Type II RBCs presented with diminished or absent phosphorylation, suggesting that wAIHA Type I and II arise due to divergent mechanisms. Post-transcriptional silencing of band 3 mRNA, mediated by RNA-induced silencing complex Argonaute 2, was uncovered in a reticulocyte enriched RBC fraction, in healthy controls. In summary, this work points to a divergence in the development of wAIHA, which is supported by both biochemical and cytokine data. The presence of protein specific translational repression in circulating erythroid cells, suggests their potential role in RBC homeostasis and pathology.

Keywords: Ago
anemia
band 3
RISC
wAIHA
warm autoimmune hemolytic anemia
Advisor: Branch, Donald R
“We’ve only lost things”: Lost Objects and Dispossession in Novels about the Japanese Canadian Internment

Novels about the Japanese Canadian internment are obsessed with things, often depicting collectors and hoarders who have heightened relationships to the objects around them. Analysing Jessie L. Beattie’s Strength for the Bridge (1966), Joy Kogawa’s Obasan (1981), Kerri Sakamoto’s The Electrical Field (1998), and Frances Itani’s Requiem (2011), this thesis argues that the novels’ preoccupation with things indicates how integral things are to subjectivity, as well as how painful and traumatic losing one’s belongings can be. Renewing our attention to the material, as the novels indicate, this project analyses the multiple and complex meanings of the objects in the novels in order to fill-in the contours of the internment, bringing into view the difficulties of an often overlooked or misunderstood experience. Whereas the internment predominantly appears as a matter of property losses for which the population could be compensated, this project offers a revised view that appreciates dispossession and the loss of property as a particularly difficult and traumatic experience, and as a violence purposefully intended to eradicate the Japanese Canadian population from the west coast. Evoking phenomenological, psychoanalytic, and Marxist thinkers, I argue that ownership and private property are not about personal gain but deeply social comportments that help individuals understand themselves as uniquely part of history and uniquely responsible for the world. My analysis of the novels further demonstrates how a deep sense of trust that is necessary for entering into the world and into social relationships fundamentally depends on stable relationships with objects. To this end, I suggest rethinking issues involved in accommodating others (refugees and exiles) in terms that appreciate that such trust and sense of responsibility are at stake. Moreover, I argue that, even when characters are able to carry on with their lives, the trauma of displacement and dispossession remains, and that we should try to keep this in view in order to respect and appreciate the plights of others more fully. Finally, this thesis contributes to ethical debates by proposing an ethics of materialism, whereby I argue that attending to material items can forge stronger relationships to the world and to each other.

Keywords: Asian Canadian Literature
Collecting
hoarding things
Japanese Canadian Interment
Kogawa
Sakamoto
Itani
New Materialism
Transitional objects
Advisor: Patrick, Julian