VictorJuiz/thesis huggingface dataset:
Exploring the Functional and Structural Brain Alterations following Youth Concussion Utilizing a Dual-task Paradigm
Keywords: brain function
Concussion
cortical thickness
dual-task paradigm
Functional Near infrared spectroscopy
youth

There are many benefits to sports participation for youth, despite the increased risk of sustaining a concussion. However, return-to-play protocols often fail to capture underlying disruptions in brain function or structure due to their limited ecological validity. Assessments often rely on single dimensional tasks and rarely integrate cognitive-motor components critical in sports. The overall objective of my dissertation was to investigate brain function and structure in youth with concussion using dual task paradigms. Using functional magnetic resonance imaging, the first study evaluated the chronic impact of concussion on grey matter microstructure and the relationship between changes in structure and dual-task performance. Cortical thinning was evident in brain regions critical to task coordination and was associated with poor task performance during dual-task. Switching over to functional near infrared spectroscopy, the second study investigated brain activation patterns during a cognitive-motor task, where youth with concussion exhibited altered activity in fronto-parietal brain regions, which was particularly prominent during the dual-task despite unimpaired task performance. Following two participants with concussion from study two, the third part of this thesis was a longitudinal case study that evaluated whether altered brain activation patterns persisted over the recovery trajectory. In line with study two, the dual-task elicited perturbed activity in more brain regions than the single tasks and these perturbations lingered at 3 months post-injury, despite symptom resolution. The findings suggest that the concussed brain can adapt to maintain dual task performance in the face of increased neural demand. However, interpreting our findings according to the capacity sharing model, there is a likely a limit to this compensation; it is likely that post-symptom resolution, some youth recovering from concussion may not be able to allocate sufficient neural resources to meet the high demands of sport and thereby risk subsequent injury. Taken together, this thesis provides support for a holistic approach to exploring concussion management that integrates brain function measurement during more sport-relevant tasks with the aim of minimizing subsequent concussions and ensuring youth continue to experience the benefits of sports participation.
Scams and Aging: Factors Impacting Effective Decision Making
Keywords: cognitive aging
decision making
fraud
isolation
older adults
scams

The present study investigated the older adults’ unique vulnerability to fraud and scams by understanding the role of social, cognitive, and knowledge-based factors, and testing a prevention paradigm. Studies 1 and 2 built upon preliminary work by examining social and cognitive predictors of prior victimization in community dwelling Chinese older adults. Study 3 examined the most promising factors again in a Canadian sample. The results here suggest that older adults in China who experience more socioemotional disturbance due to isolation may be at higher risk of victimization compared to their peers and compared to those in Canada. To better understand vulnerability, an objective scam detection task was designed for studies 4 and 5. Study 4 examined predictors of detection ability in older and younger adults and found a combined role of cognitive processing and accumulated knowledge after controlling for social and demographic factors. Study 5 used these findings to test a training with feedback paradigm to improve detection ability. Immediately after training, the intervention group performed significantly better than the control group, while the alternative education intervention group did not. However, the gains declined significantly by the three-week follow-up. Collectively, the findings support the need for age-based investigations of fraud vulnerability, the need for objective behavioural measures, and the possibility of knowledge-based interventions albeit with additional improvements.
Unlocking the “Black Box” of Hospital Competition: Multiple Case Studies in Government-Funded and Regulated Health Systems
Keywords: Comparative Health Systems Case-Studies
Continuous Quality Improvement
Health Economics Policy
Health System Design Governance
Health System Performance Benchmarking
Hospital Competition Strategy Reputation

This dissertation explores the phenomenon of competition in healthcare, focusing on highly regulated and publicly-funded settings, specifically two Canadian provinces with very different system structures. Empirical approaches included multiple case studies, interviews, and thematic-analysis. Despite the absence of a profit motive and the threat of market exclusion, competition is present in both systems, even across hospital sites merged into a single provincial authority. Similarities in the manifestation of competition across the two provinces may result from common organizational features and system pressures, including advocacy by hospital/site leaders, scarcity, technological innovations, uncertainty, and stakeholder expectations. However, in line with earlier studies, demand-side factors do not drive competition. Moreover, hospital leaders and referring physicians found information on the quality of care difficult to understand and relied on different strategies to assess care quality. Instead, factors, such as the potential for embarrassment, drove competition among hospitals/sites, underscoring the importance of reputation as a critical element in stimulating and defining competition among hospitals. Competition is also driven by hospital leaders’ intrinsic motivation to improve care quality. These findings align with existing literature and contribute to the literature by revealing clearer conceptualizations and pathways pertinent to healthcare competition. The findings reported in this dissertation also articulate key elements in the regulatory environment, namely health system typology, governance, and policy instruments, the combination of which shapes competition. They show that despite similarities between the systems' competition dynamics, the differences in these system traits create specific forces in each system and create differences in how competition manifests. The dissertation findings also signify the need for organizational legitimacy and pressure to conform to defining competition, further resonating with existing public-sector literature and institutional theories of organization. Despite the highly regulated nature of the Canadian health system, competition is present among hospitals, even when they are part of a single provincial corporation. Furthermore, despite important differences in the regulatory context, there are important similarities in how competition manifests and is perceived in the two provinces studied. The drivers of this competition hold important implications for how health policies can stimulate positive competition and avoid destructive types of competition.
The Politics Behind and the Value of Outbound Student Mobility: Is Canada Missing the Boat?
Keywords: comparative education
higher education
international education
international student mobility
public policy
study abroad

Between 2005 and 2017, outbound student mobility (OSM)—study abroad—increasingly became part of government policy across Europe and the G7 countries. Canada, however, was absent from this OSM policy movement. Instead, its national and provincial governments concentrated on attracting and retaining international students. This study explores Canada’s absence by examining the OSM policy process and the values attributed to OSM by policymakers in key ministries as well as leaders in key advocacy groups. An international comparative study, it comprises six jurisdictions: Canadian federal level, Ontario, Quebec, Germany, England, and France (the latter three as OSM public policy leaders). OSM from a public policy perspective is a virtually unexplored area in internationalization and higher education research. To understand the politics behind and the value of outbound student mobility, this mixed-methods study analyzes 1,940 policy and advocacy documents as well as interview data from 74 participants. It scrutinizes OSM issue-attention at the agenda-setting stage of the policy cycle and uses social discourse analysis to examine the extent to which OSM value-conceptions can be situated within neoliberalism, realism, and/or cosmopolitanism. Notably, it sectorally orients and conceptually differentiates policy and advocacy communities, and renews with societal value-goals as public policy drivers. Findings show that within Canada, the federal level conceptualized OSM as a value for the collective and was outward-looking, while the subnational jurisdictions (responsible for higher education) conceptualized it as a value for the individual and were inward-looking. Importantly, the federal and Ontario governments included a no-value OSM conceptualization. Conversely, each of the leading OSM jurisdictions in Europe overwhelmingly conceptualized OSM as a value for the collective, firmly anchored it historically, and was outward-looking. Finally, for policymakers, this study suggests three elements are needed to successfully implement OSM public policy jurisdictionally: a champion within government, target setting, and systems-level data collection.
Privation of Inclusion, Cordon Minoritaire and Racist Oppression in the Public Sector: A Hermeneutic Exploration of the Ugly Side of Beautiful British Columbia
Keywords: Canada
discrimination
employment
public service
racial discrimination
racism

This dissertation offers a hermeneutic exploration of racialized employees’ lived experiences with racial discrimination at publicly funded places of employment in British Columbia, Canada. Presented in three-paper format, the first article, Self-Identifications and Perceptions of a Phantasm through the Looking-Glass: Tracing Race in Embodied Perceptions, presents a critical illustration of the multitude of ways in which race, as a putative classificatory construct, is phantomic. This paper, through explicating the multifaceted range of meanings produced about race, will also engage in an examination of embodied perceptions of race in these varied and painful articulations. The second paper, Privation of inclusion: An exploration of racialized public servants’ experiences with sabotaged recruitment processes in BC, offers an examination of privation of inclusion at work. Taking the position that the dualistic inclusion-exclusion paradigm fails to capture participants’ lived realities with inclusive exclusions and exclusive inclusions, this article presents privative inclusion as a third space between inclusion and exclusion as a more robust framework for understanding how participants were marked and targeted for differential treatment. The third paper, The body, the stranger and cordon minoritaire: An exploration of racialized civil servants’ lived experiences with contained mobility at work, offers an examination of a particular manifestation of racial discrimination: that of quarantine-like containment of mobility at work. Examining undue restrictions and mobility limitations imposed on participants, this article will use three metaphors – stranger for racialized individuals, body for workplaces and cordon minoritaire as the process of containing the mobility of strangers within the body. Cordon minoritaire is presented as a novel analytical framework to illustrate the ways in which racialized workers’ professional freedoms and career mobilities were restricted in order to quarantine White ecosystems of employment. Consequently, cordon minoritaire machinations created perniciously unequal conditions and fundamentally unjust treatments – depravities that are at odds with whimsical notions of Canada as tolerant, multicultural and morally superior to its neighbour south of the border, the United States of America. Ultimately, and collectively, the three papers included in this dissertation offer nuanced and detailed accounts of microprocesses that perpetrated and perpetuated racial oppression at work, in the BC public sector.
Organotellurium Probes for Mass Cytometry
Keywords: mass cytometry
single-cell
tellurium

Cellular heterogeneity presents one of the most fundamental challenges in our ability to study health and disease. While the existence of cell-to-cell variation in cell systems and tissues has been acknowledged for a long time now, the characterization of cell phenotypes and their biological functions has been limited. One of the most well-established single-cell techniques is mass cytometry (MC)– a technology where multiple cellular biomarkers are measured simultaneously with heavy metal-labelled antibodies in a high-throughput fashion. Equipped with single mass unit resolution, MC allows quantitative single-cell analysis of more than 45 parameters in parallel. In addition, Imaging Mass Cytometry (IMC™️) has been developed to utilize the same metal-tagged probes used in MC for biomarker quantitation in tissue sections with subcellular resolution. Tellurium-based reporters have emerged one of the most important and diverse categories of MC and IMC™️ probes. Specifically, tellurophenes are stable, biocompatible scaffolds that successfully leverage the polyisotopic nature of tellurium, enabling measurements of dynamic cellular states previously inaccessible with traditional MC reagents. This thesis explores three new applications of tellurophene-based reporters in MC and IMC™️. First, a polymeric tellurophene construct was synthesized for the purposes of increasing the parametrization of single-cell suspension MC assays. Antibodies tagged with tellurophene-bearing polymers identified cells expressing the targeted antigen while an isotopically enriched mass tag was prepared for multiplexed immunoassays. Second, a tellurophene-based reagent was developed for immunostaining of low abundance antigens in tissue sections with IMC™️. The staining agent was compatible with alkaline phosphatase-conjugated antibodies allowing robust, sensitive detection of low expression biomarkers via enzymatic amplification. Overall, the staining method complemented IMC™️ workflows and was an improvement over contemporary methods. Finally, tellurophenes are also known to function as effective biomimetics of small aromatic rings. This property was exploited to synthetically incorporate a MC reporter in a clinically approved therapeutic (teniposide). The tellurium labelled derivative exhibited similar inhibitory and cytotoxicity activities to the cognate drug in vitro. MC analysis of drug-treated cells allowed monitoring of cellular uptake. The ability to visualize tissue distribution and cellular accumulation of drug with IMC™️ was assessed in a human pancreatic cancer xenograft model.
Characterizing the Shear Stress-mediated Identity of hiPSC-derived Endothelial Cells
Keywords: arterial-venous specification
endothelial cell
induced pluripotent stem cell (iPSC)
RNA sequencing
shear stress
vascular tissue engineering

Human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) are a promising endothelial cell (EC) source for vascular therapy. They are especially alluring for applications where niche EC types are desired as their lack of tissue-specific maturation may lend plasticity that allows for specification towards distinct endothelial subtypes. Although shear is a crucial component of functional endothelium, few studies have examined the response of iPSC-ECs to shear stress or its impact on iPSC-EC identity. To assess the suitability of iPSC-ECs for tissue engineering applications, this thesis investigated the effects of physiologically-relevant fluid shear conditioning on a commercially available iPSC-EC source; the work herein focused on endothelial properties relevant to the generation of a vascular bypass graft, namely arterial-venous identity, shear sensing, barrier function, and inflammation. The iPSC-ECs were evaluated against similarly conditioned mature endothelial benchmarks and overall presented as more arterial than the mature arterial and venous EC controls in vitro; however, both steady and pulsatile shear conditioning prompted a shift towards venous identity relative to static culture. Pathway analysis from RNA-sequencing of the sheared iPSC-ECs revealed dysregulation of several genes involved in arterial specification processes, although the mechanism(s) driving venous identity with shear remain unclear. Using mature ECs as benchmarks, potential deficiencies in gene expression patterns of endothelial shear sensing elements were identified; validation studies assessing protein expression revealed impaired phosphorylation of junctional mechanosensors. Expression patterns of tight junctions, gap junctions, and adherens junctions as measures of endothelial barrier function, as well as genes related to inflammation were also found to be differentially expressed in the iPSC-ECs compared to mature EC benchmarks. Ultimately, although the iPSC-ECs showed some similarity to the mature EC controls, they did not completely align with any one endothelial benchmark for the metrics assessed in this work. These findings enable us to better define iPSC-EC identity, situate the cells among mature EC cultures, and inform potential applications within tissue engineering involving exposure to fluid flow.
Automatic Tumour Typing based on Patterns of Somatic Passenger Mutations
Keywords: Cancer diagnosis
Chromatin
Deep learning
Somatic mutations
Uncertainty estimation

In cancer, a tumour’s cell of origin is the strongest determinant of its clinical behaviour. While cell of origin is typically clear at the time of diagnosis, 3-5% of cancer patients present with a metastatic tumour and no obvious corresponding primary tumour. Despite advances in molecular testing, imaging, and pathology, the primary tumour site cannot be inferred in the majority of these cases. Recent large- scale analysis of cancer genomes has uncovered strong associations between cancer type and somatic mutations, prompting the use of somatic mutations as a tool for identifying cancer type. While existing approaches have attempted to use cancer-associated mutations, which may be more common in specific cancer types to infer the primary tumour type from the metastatic tissue, these methods have had only limited success. A more promising alternative is to use the association between patterns of somatic passenger mutations and cancer type, by exploiting the relationships between both regional mutation density and cancer type, and mutational processes and cancer type. Somatic point mutations accu- mulate in regions of closed chromatin, and so mutation density provides information about chromatin state, which in turn offers hints about the underlying cell type. As some mutational processes are highly cell-type specific, mutational processes also provide clues about cancer type. In this thesis, I describe a number of deep learning systems for automatic tumour typing based on patterns of somatic passenger mutations. I then address challenges for translating the classifier into clinical scenarios through the use of multiple algorithmic improvements. First, I make use of modern advancements in deep learning to extend the classifier to accurately discriminate between 29 cancer types. I then use a number of sta- tistical methods for assessing the uncertainty in the model’s predictions, and for improving uncertainty quantification. Finally, I make use of information theoretic metrics to use the model’s predictive uncer- tainty to automatically detect cancer samples that come from rare cancer types that the model was not trained to classify. These studies demonstrate the utility of passenger mutations as a tool for identifying cancer type, and address challenges for translating the deep learning classifier into clinical settings.
Imaging Nociceptin Receptor Expression in Cannabis Use and Psychosis using Positron Emission Tomography with the radioligand [11C]NOP-1A
Keywords: Cannabis Use
Nociceptin
PET Imaging
Psychosis

Nociceptin/orphanin FQ (N/OFQ) is a neuropeptide transmitter in the brain that can suppress neurotransmitter release, including dopamine and glutamate. Therefore, dysregulation of nociceptin opioid peptide receptor (NOPr) signaling can result in neurotransmitter imbalance, suggesting its putative role in substance use disorder and psychosis. Furthermore, N/OFQ has been demonstrated to be involved in the brain’s stress response and in cognitive function. This study presents the first investigation of NOPr in these diseases using the highly specific ligand [11C]NOP-1A and positron emission tomography (PET). Study participants with long-term cannabis use and diagnosed as Clinical High Risk (CHR) and First Episode Psychosis (FEP) were included in the present work. The target regions of interest (ROI) include hippocampus, striatum, medial prefrontal cortex and dorsolateral prefrontal cortex. [11C]NOP-1A binding in the clinical groups was not significantly different compared to healthy volunteers. Cannabis users did not differ in [11C]NOP-1A binding from healthy volunteers and there were no significant group by ROI interactions. [11C]NOP-1A binding was not significantly different between FEP and healthy volunteers with no significant group by ROI interaction. [11C]NOP-1A binding was not significantly different between CHR and healthy volunteers with no significant group by ROI interaction. Interestingly, [11C]NOP-1A binding was associated with cognition in healthy volunteers. We report an interaction between group and immediate and delayed memory scores, such that as memory score increases, [11C]NOP-1A binding in the healthy volunteers decreases. This finding is line with preclinical animal studies that demonstrate N/OFQ agonist treatment or NOPr activation inhibits working memory abilities. In addition, [11C]NOP-1A binding is associated with self-reported stress in cannabis users and CHR. We report an interaction between group and chronic stress such that as stress score increases, [11C]NOP-1A binding in the cannabis users and CHR decreases, but increases in HV. This finding is line with studies that have demonstrated that stress mobilizes the nociceptin receptor system. Our results suggest that cannabis users and CHR patients, which are known to have abnormal stress responses, are unable to upregulate NOPr to counteract stress. Therefore, this may suggest NOPr as a novel target for interventions in these populations.