Restricted Theses and Dissertations
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Item Embargo Indigenous Health in Postgraduate Medical Education: Pathways for Enhancing Anti-racism Literacy and Praxis for Advanced Trainees(2025-01-13) Ramé, Ana Karen; Henderson, Rita Isabel; Paolucci, Elizabeth Oddone; Crowshoe, Lynden John; Roach, Pamela; Altabbaa, GhazwanRacism is detrimental to health; it widens gaps in health inequities by marginalizing specific populations and sustaining structures that perpetuate harm. This results in social fragmentation that hampers the capacity of affected communities to achieve well-being. Racial hierarchies tend to characterize aspirations for equity as unachievable, using the complexity of the need to shift institutions, attitudes, and whole cultures to undermine expectations that equity be a core component and not simply an added benefit of a just society. This doctoral thesis aims to mitigate the impact of racism on health disparities experienced by Indigenous peoples in Canada by addressing unequal treatment in health systems through the advanced training of healthcare professionals, specifically medical residents across specialties. It is aligned with the Truth and Reconciliation Commission of Canada’s (TRC) Call to Action #24, which emphasizes the expansion of “skills-based training in intercultural competency, conflict resolution, human rights, and anti-racism” for all health professionals in Canada. Decolonial and anti-racist education are promising pathways explored here for advancing healthcare equity, as they place historical, political, and social experiences at the centre of the learning process and objectives. These pedagogies promote the active involvement of learners, an approach that would seem to suit advanced medical trainees whose programs usually involve practice-based experiential learning mentored by established physicians. Such training also offers the possibility for adult learning approaches known to favour behaviour change, such as critical self-reflection over time. However, medical residency and fellowship training often involve limited exposure to the lived realities of Indigenous patients and, in turn, limited direct feedback or guidance from these. This complicates possibilities for integrating historical, political, and social components of Indigenous-focused anti-racism. This thesis presents a largely qualitative body of work that approaches these dilemmas in three parts. It begins by eliciting guidance from semi-structured interviews conducted in one Canadian province with Indigenous individuals who have accumulated experiences in health systems and health professional training (n=12). It then draws on a document analysis of formal Indigenous training in post-graduate medical education (PGME) across Canada. Finally, it returns to perspectives on health professional learning among advanced medical trainees through semi-structured interviews with non-Indigenous residency preceptors (n=19) and residents (n=14) across specialties. These sources offer insight into Indigenous guidance for PGME training in Indigenous health and anti-racism in Canada, current approaches across medical schools, and needs and possibilities for growing Indigenous-focused anti-racism learning from mentors and mentees within PGME programs. This work emphasizes that addressing anti-Indigenous racism in healthcare is essential for achieving Indigenous health equity. Integrating insights from 45 interviews and the scanning of 1179 curricular documents related to PGME with a close review of 46 containing any form of Indigenous content, this work offers a preliminary index of specialty-specific Indigenous health and anti-racism content as a potential starting point for more refined curricular development. An important implication of this work is greater clarity around how training may incorporate unique dilemmas faced in distinct medical fields and the cultural, social, and geopolitical diversity of Indigenous peoples in Canada.Item Embargo Evaluating the Phenotypic Consequences of DNA-PKcs Deficiency(2025-01-14) Kenny, Jacey; Lees-Miller, Susan; Billon, Pierre; Moorhead, GregoryDNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a serine/threonine protein kinase with a well-established role in the repair of DNA double strand breaks. Similarly, Ataxia-Telangiectasia Mutated (ATM) is a protein kinase that plays a central role in downstream signalling response to DNA damage. DNA-PKcs and ATM are members of the phosphatidylinositol 3-kinase-like protein kinase (PIKK) family, which serve critical roles in the cellular response to DNA damage. To better understand the non-canonical roles of DNA-PKcs and ATM, our lab generated human cell lines with CRISPR/Cas9-mediated disruption of these proteins, marking the starting point of my project. My work demonstrates that loss of DNA-PKcs and/or ATM expression results in slower proliferation compared to parental cells, while inhibition of DNA-PKcs or ATM kinase activity had a comparatively minor effect on cell proliferation. My data suggests that this phenotype is not due to increased apoptosis, endogenous DNA damage or cell cycle defects. Comparison of the metabolite profiles of the matched control and CRISPR cell lines suggested enrichment of amino acids in the HeLa CRISPR DNA-PKcs cells which led me to hypothesize that the CRISPR cell lines have a reduced rate of protein translation. I present evidence that cells deficient in DNA-PKcs and ATM exhibit impaired global, new protein translation, revealing a potentially novel mechanism for the slow growth phenotype. This work adds to a growing body of evidence encouraging further exploration of DNA-PKcs and ATM as therapeutic targets in cancer and other diseases.Item Embargo Correlating Obstructive Symptoms with Stricture Severity in Ileal Crohn’s Disease(2024-11-28) Saunders, Bethany; Lu, Cathy; Bonni, Shirin; Novak, Kerri; Ma, Christopher; Ganesh, AravindCrohn’s Disease (CD) can manifest as inflammatory (non-stricturing), fibrostenotic (stricturing) and fistulizing or penetrating phenotypes. Stricturing CD, the main focus of this thesis, involves luminal narrowing and, which is often progressive leading to obstruction of the affected bowel segment. Obstructive symptoms (OS) in CD strictures can be assessed using the Stricture Definition and Treatment (STRIDENT) trial-used OS scoring system and CREOLE OS score. Clinically, OS are typically linked to advanced strictures, strictures can often result in dietary restrictions and surgery. No studies have been published to date, evaluating the severity of CD strictures and OS. Understanding the correlation between symptoms and strictures is crucial as regulatory bodies assess drug efficacy based on symptom response in CD trials. Intestinal ultrasound (IUS) accurately evaluates strictures morphology, with stricture severity and length, using established criteria: bowel wall thickness > 3mm, luminal narrowing (<1cm), with any pre-stenotic dilation (PSD) size (cm). The aim of this thesis based stsudy aims to determine if the OS of pain, bloating, nausea and/ or vomiting when comparing among CD phenotypes, and if specific OS correlate with any of the definitive stricture parameters.Item Embargo Acute and Chronic Physiological Responses to Endurance Exercise of Varying Durations: Neuromuscular, Hematological, and Integrative Outcomes(2025-01-10) Tripp, Thomas; MacInnis, Martin; Edgett, Brittany; Gibala, Martin; Manske, Sarah; McNeil, ChrisThe integrative action of several physiological systems supports increased skeletal muscle energy demand during exercise. Physiological systems structurally and functionally adapt when exercise stresses are regularly imposed during a period of training. These adaptations, in turn, reduce the homeostatic stress for a given exercise bout. In particular, the impacts of exercise duration and exercise frequency on acute and chronic exercise responses are poorly understood. During prolonged exercise, physiological systems are activated to support muscle contraction, but metabolite accumulation and substrate depletion inevitably occur. During a training program, the balance between the number of times an exercise stress is experienced and the amount of stress per instance implicates exercise frequency along with duration as factors influencing physiological adaptations. This dissertation sought to address gaps in our understanding of the acute responses to differing exercise durations, and to compare chronic training adaptations when total exercise volume is the same. Study 1(Chapter III) showed that near-infrared spectroscopy measures of muscle oxidative capacity are sensitive to contraction intensity, necessitating intensity controls when the technique is used in future studies. Study 2 (Chapter IV) characterized neuromuscular fatigue kinetics during high-intensity interval training and showed that the largest deficits occur early during exercise, implying that additional exercise stress diminished during later bouts. Study 3 (Chapter V) investigated erythropoietic signalling when exercise duration is doubled. I found that increases in erythropoietin mass were not different after both exercise durations, despite hypervolemia only occurring after longer exercise. Study 4 (Chapter VI) aimed to probe whether the acute differences I found between exercise durations impacted training adaptations. This study showed that both long, low-frequency (a Weekend Warrior pattern) and shorter, high-frequency training similarly improved maximal oxygen uptake, hemoglobin mass, muscle oxidative capacity, and exercise capacity. The findings of this dissertation suggest that for some exercise responses, duration does not substantially augment the magnitude of acute stress/signalling events; however, when comparing different frequencies of exposure to that exercise stress, training adaptations were not different. Future studies should address how this acute stress/signal-to-chronic adaptation discrepancy occurs in the context of exercise duration and training frequency.Item Embargo Optimizing personalized treatment strategies for coronary artery disease using deep learning and reinforcement learning(2025-01-10) Ghasemi, Peyman; Lee, Joon; White, James Alexander; Lee, Joon; White, James Alexander; Har, Bryan Jonathan; Greenberg, MatthewCoronary artery disease (CAD) is a leading global cause of mortality and morbidity, affecting approximately 295 million people and resulting in 9.5 million deaths in 2021. Despite advancements in medical interventions that have reduced CAD mortality in high-income countries, significant challenges remain in delivering optimized, personalized care, particularly in settings characterized by high patient variability. Traditional decision-making in the treatment of obstructive CAD—encompassing percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and medical therapy—relies predominantly on population-level data from randomized controlled trials. However, this approach often neglects individual patient characteristics and the sequential nature of CAD treatments. This thesis employs machine learning (ML), with a focus on reinforcement learning (RL) and deep learning techniques, to improve CAD treatment decision-making. Specifically, it develops an offline RL framework designed to provide personalized treatment recommendations for patients with CAD, utilizing a large cohort from Alberta, Canada. Chapter 3 addresses the challenge of processing high-dimensional clinical data for ML applications. Through extensive experimentation with several unsupervised feature selection techniques, this study identifies the weight-adjusted concrete autoencoder as the most effective method for extracting efficient and interpretable features from diagnostic (ICD-10) and therapeutic (ATC) code databases. The selected features serve as the foundation for the analyses in subsequent chapters. Chapter 4 forms the core of this thesis, presenting an offline RL framework named RL4CAD to optimize CAD treatment recommendations tailored to individual patient profiles. Off-policy evaluation of RL4CAD models demonstrates their superiority over traditional physician-driven decision-making, achieving significant reductions in major adverse cardiovascular events. By using conservative RL models, we balanced the optimal recommendations with the current clinical practice. Moreover, this framework introduces interpretability to RL-based decisions by employing models with limited state spaces and identifying key features that influence outcomes. In Chapter 5, the thesis addresses the challenge of distribution shifts across diverse patient populations, such as variations in sex and treatment site, which complicate the optimization of CAD treatment using RL. By stratifying patient cohorts by these features and independently evaluating physician behavior and RL-derived policies, significant disparities in clinical practices were identified. To mitigate these challenges, transfer learning was integrated into the RL framework, enabling the model to adapt to diverse patient subgroups with minimal data and retraining. This approach effectively addressed distribution shifts, improving the RL models’ capacity to deliver personalized and equitable CAD treatment recommendations in patient populations that they had not been trained on. Collectively, the innovations in feature selection, RL-guided decision-making, and addressing distribution shifts contribute a scalable, data-driven solution for CAD management. By delivering personalized treatment recommendations that account for patient and practice variability, this work advances the potential of RL-driven precision medicine in cardiovascular care. Furthermore, the findings from this thesis establish a foundation for applying RL to other complex and dynamic treatment domains.Item Embargo Applying Dynamic Capabilities in Business Model Innovation: An Exploratory Case Study in a Self-Managing Organization(2025-01-07) Mayer, Matthew; Osiyevskyy, Oleksiy; Woiceshyn, Jaana; Suddaby, Roy; Saunders, Chad; Mihalache, OliDespite a significant amount of literature on business model innovation (BMI) suggesting the importance of organizational design as a firm-level moderator for successful BMI outcomes, few studies have addressed it directly. Self-managing organizations (SMO) are a type of less-hierarchical organization that aims to redefine hierarchical structures, especially the role of traditional managers. Like any firm, SMOs that innovate well may enjoy Schumpeterian entrepreneurial rents and, if effective at continually reconfiguring their resources, may sustain a competitive advantage in line with the dynamic capabilities (DCs) theoretical perspective. Despite practitioners suggesting that SMOs are better at adapting and responding to environmental conditions, few public-facing examples of BMI in these organizations exist in either popular management literature or scholarship. This intensive, exploratory case study researched an SMO that transformed its resources several times to pursue an array of BMIs over time. Interviews, observation and archival data were collected over 18 months. The study results showed that balancing hierarchical tensions, enacting collaborative routines for knowledge creation and configuring a community of leaders are foundational DCs when BMI is practiced in an SMO. In addition to outlining the routines and practices for DCs for BMI in an SMO, the study also proposed a model for how these DCs are applied. For scholars and practitioners, the study discusses the role of a manager, innovation champion and network for SMOs engaging in BMI. In practice, identifiable organizational routines and processes are present, and practices can be strategically selected to enact multiple DCs simultaneously. The exploratory nature of this case study elucidated future research to advance the field of BMI and SMOs.Item Embargo Preconditioning and weaning beef cattle: impacts on health and behaviour of beef calves and cows and the stakeholders’ perspectives(2025-01-09) Mijar, Sanjaya; Orsel, Karin; Pajor, Ed; van der Meer, Frank; Pearson, JenniferWhile preconditioning benefits calf health and performance, its adoption remains challenging due to uncertainties surrounding commingling preconditioned (PC) and auction-derived (AD) calves, as well as various social, financial, and market barriers in the beef industry. Furthermore, limited understanding of weaning stress on beef cows complicates preconditioning efforts aimed at minimizing stress and promoting animal welfare. Chapter 2 determined the impacts of commingling PC and AD calves in the feedlot in varying proportions, revealing that PC calves, regardless of commingling, showed reduced bovine respiratory disease (BRD)-related morbidity and lower treatment rates than AD calves. Chapter 3 investigated calves’ behavioural and physiological responses to stress related to feedlot transitioning, finding that PC calves showed better adaptation to the feedlot environment with increased eating and rumination, though hair cortisol levels did not differentiate stress responses. Chapter 4 explored beef industry stakeholders’ perspectives on preconditioning, identifying key motivators and barriers to its implementation. Five overarching themes were identified: Ranchers’ satisfaction and accountability and Thriving calves as motivations; and Lack of incentives, The quest for preconditioning proof, and Supply shortfall as barriers. Chapter 5 assessed weaning stress in three different weaning methods by measuring physiological and behavioural responses in beef cows, finding that nose-flap (NF) weaned cows exhibited fewer vocalizations, and less walking and pacing compared to abruptly or fenceline (FL) weaned cows. Fenceline weaned cows also had increased fecal glucocorticoid metabolites concentrations post-weaning compared to NF and abruptly weaned cows. Overall, this thesis highlights the health and feeding performance advantages of preconditioning calves outperforming AD calves, irrespective of commingling. This thesis also identifies underlying motivations and barriers to preconditioning adoption, and offers recommendations for strengthening preconditioning verification, fostering trust, and providing financial incentives to encourage broader adoption of preconditioning practices. Additionally, this thesis suggests the need for cow-calf operators to recognize that cows experience weaning stress differently than calves and to select less stressful weaning method aligning with specific ranch goals and production targets. Future research should emphasize extensive commingling protocols, weaning stress impacts on calves in utero and after birth, and a broader survey on preconditioning adoption in Canada.Item Embargo Biochemical Characterization of the Arabidopsis Chloroplast Localized Phosphatase Shewanella-Like Protein Phosphatase 1(2025-01-09) Johnson, Jayde Jarin; Moorhead, Greg; Turner, Raymond; Fraser, MarieShewanella-like protein phosphatase 1 (SLP1) is a newly discovered member of the phosphoprotein phosphatase class of protein phosphatases. In Arabidopsis, SLP1 was previously confirmed to be chloroplast localized. Mass spectrometry based phosphoproteomics analysis of different Arabidopsis lines identified 126 high confidence SLP1 substrates, all of which were predicted/known chloroplast proteins. Identification of 126 substrates suggests SLP1 is a major regulator of chloroplast metabolism. Analysis of the substrates indicated SLP1 preferentially dephosphorylates serine or threonine near acidic residues. Similarly, a chloroplast localized protein kinase, casein kinase 2α4 (CK2), prefers acidic substrate motifs. Interestingly, many of CK2’s substrates are also SLP1 substrates, suggesting SLP1 and CK2 act antagonistically to balance chloroplast phosphostatus. CK2 has been studied for decades, with SLP1 studies beginning only recently. Herein I build on previous biochemical characterizations of SLP1 using phosphorylated peptides in enzyme assays. I use reagents to simulate diurnal fluctuations of redox, pH, and metabolite/protein concentrations in the stroma in vitro and found that SLP1 is activated by chloroplast thioredoxin m. I use structural prediction tools to connect changes in SLP1 activity to structural features such as a predicted disulfide bond. Predictions also suggest which residues may be responsible for preferential dephosphorylation at acidic motifs. The structural predictions guided SLP1 bioinformatics as novel regions of SLP1 were predicted and confirmed through sequence analysis of SLP1 homologues. Then, I explore the SLP1 substrate Calvin Cycle Protein of 12 kDa (CP12), as an example for how SLP1 phosphorylation may play a role in the regulating the Calvin Cycle. I reconstituted the inhibition complex of glyceraldehyde-3-phosphate dehydrogenase, phosphoribulokinase, with wild-type and mutant CP12s in vitro. Using size exclusion chromatography, I observed that the complex formed using phosphomimetic CP12T116D elutes differently from wild-type. Lastly, I generate a proximity labelling construct to explore SLP1 protein-protein interactions. I demonstrate that SLP1 substrates can be labelled with biotin when transiently expressed in tobacco plants. The work here builds on previous studies, identifying areas of chloroplast biology where redox regulation and reversible protein phosphorylation intersect.Item Embargo Fragmented Paths: A Novella and a Journey Through Lands to Find the Self in Home(2024-12-19) Kamangarpour, Golaleh; Mayr, Suzette; Dobson, Kit; Seidel, Jackie LynnThis thesis explores the thematic and narrative intricacies of HomeLand, a novella that delves into the intersections of dreams, memory, and time in the pursuit of identity and belonging. Drawing inspiration from Indigenous and Kurdish philosophies, HomeLand challenges linear conceptions of time and self through a narrative structure that blends magical realism with psychological and cultural exploration. The work questions societal expectations surrounding happiness and fulfillment, drawing on Sara Ahmed’s The Promise of Happiness, and critiques the colonial legacies shaping perceptions of home and identity. Building on these thematic inquiries, the novella engages with Antonio Zadra and Robert Stickgold’s cognitive psychological theories on dreams (When Brains Dream), portraying dreams as pivotal tools for emotional processing, memory integration, and self-discovery. The Aymara philosophy of time, which positions the past as visible and the future as hidden, informs the novella’s fragmented and non-linear structure, reflecting its protagonists’ evolving identities. The thesis situates HomeLand within the broader context of Kurdish literature, addressing how the novella echoes the cultural and historical displacement experienced by Kurdish people while engaging with universal themes of alienation and belonging. Through its narrative, HomeLand interrogates the concept of home, presenting it as both an external and internal construct shaped by personal, cultural, and historical forces. Ultimately, HomeLand argues that the search for home is a fluid and continuous process, highlighting the universal yet deeply personal struggle to reconcile one’s identity in a fragmented world. By integrating insights from literary, cultural, and psychological frameworks, the exegesis positions HomeLand as a contribution to Kurdish literature and as a reflection of the universal human experience.Item Embargo The Effect of the Herbicide Glyphosate on Neurodevelopment and its Influences on Two Genetic Zebrafish Models of Autism(2024-12-27) Lacroix, Rachel; Kurrasch, Deborah; McFarlane, Sarah; Yang, GuangGlyphosate is the world’s most sprayed herbicide, leading to near ubiquity in the environment and increasing exposure for humans and wildlife. Initially glyphosate was thought to be safe for animals since it targets a molecular pathway found only in plants and bacteria, which facilitated the rapid adoption of glyphosate into mainstream agricultural practices. However, growing evidence suggests that glyphosate might be toxic across a wide range of organisms, including humans, leading to growing concerns of glyphosate’s effects on human health. Epidemiolocal findings show a strong correlation between increasing human glyphosate exposure and the rising rates of Autism Spectrum Disorder (ASD) diagnoses, raising the intriguing notion that glyphosate is somehow contributing to the etiology of ASD. The gene x environment hypothesis of ASD suggests that environmental factors, such as herbicides, may interact with autism alleles to perturb neurodevelopment to cause autism. Within this thesis, first I use zebrafish as a model system to characterize the behavioural (Chapter 3) and molecular/cellular (Chapter 4) effects of embryonic exposure to the active ingredient glyphosate alone as well as its commercial formulation RoundUp that also contains a mixture of surfactants that might be toxic. I show that embryonic exposure (10 hours-post fertilization (hpf)-48 hpf) to glyphosate singly or commercial RoundUp causes a range of behavioural deficits, with RoundUp exposed zebrafish showing a stronger phenotype. I also demonstrate that embryonic exposure to RoundUp disrupts neurogenesis and axonogenesis, and causes a concomitant increase in neuronal activity by 5 days-post fertilization (dpf). Next, I use two genetic zebrafish models whereby ASD genes have been mutated. I characterize these ASD lines and test a potential gene x environment interaction by assaying the effects of glyphosate in these zebrafish ASD models (Chapter 5). I show that ASD zebrafish have defects in morphology, behaviour, and brain activity. Behavioural and brain activity phenotypes are modulated with Roundup exposure in a genotype-dependant manner. Combined, these studies demonstrate that glyphosate and its commercial formulation RoundUp is toxic to developing brains in vivo and provide some evidence that exposure to glyphosate-based herbicides might contribute to the increasing rise of ASD diagnoses in children.Item Embargo Troubling the Pixel(2025-01-09) Yeomans, Tanya Michelle; McDermid, Greg John; Mac Namara, Aoife; Stadnyk, Tricia; Xu, Lincoln LinlinMonitoring vegetation recovery in forested environments can be done effectively with satellite time series data. However, most research in this space has relied on Landsat imagery, which has a 30-meter pixel size. Emerging CubeSat technology has much finer spatial resolution and offers new possibilities for monitoring vegetation on small industrial disturbances such as well pads and seismic lines. These features are associated with hydrocarbon exploration and are some of the most extensive disturbances in Alberta’s forests. We used PlanetScope satellite imagery to classify vegetation on small industrial disturbance features across a 309-km2 study area in northern Alberta as either growing or declining, and validated our results with LiDAR data. We found that recovery classification on medium-sized well pad features was significantly better than for medium and narrow linear features. We also found that disturbances in some ecosite types (low-density treed wetland, upland mesic, and upland dry sites) were easier to classify than others (transitional and wetland treed) and that linear features oriented in a north-south direction were easier to classify than those oriented east-west. Our research demonstrated that 58% of pixels on disturbed linear features in our study area displayed some degree of spectral regeneration, alongside 76% of the evaluated pixels on wellpads. We believe that the privilege of working with this emergent imagery comes with a responsibility to think deeply on how we use, transform, and interpret the data. To investigate the intersection between landscape, technology, and people, we employed arts-based research methods to trouble the pixel – the fundamental data unit in our remote-sensing research. By creating a textile pixel and documenting it in our study area, we were able to reflect on the parallel methodologies at play in our work, and to identify practical interventions into our scientific practice that allows us to more deeply engage with our data. This includes providing care instructions for our scientific products, slowing down our processes with manual tasks, and dedicating time to witness our data in-situ. Our hope is that through sharing our experiments in investigating our positionality to remote sensing, others are encouraged to reflect on their own practices.Item Embargo Brain-first versus Body-first: Exploring aspects of gut microbiota in Parkinson’s disease(2025-01-08) Kiani, Pardis; McCoy, Kathy; Sycuro, Laura; Martino, DavideParkinson’s disease (PD) is pathologically characterized by the irreversible aggregation of misfolded α-synuclein protein, forming what is known as Lewy Pathology, which is observed in multiple regions of the brain and gut. The “brain-first” and “body-first” hypothesis proposes distinct patterns of Lewy pathology distribution in the early stages of the disease, which categorizes clinical sub-phenotypes of PD. The “brain-first” sub-phenotype is thought to have predominant involvement of the amygdala, while the “body-first” sub-phenotype involves the enteric nervous system. In mouse models, the microbiota has been shown to be involved in promoting α-synuclein pathology and characteristic motor features in PD. This study aims to investigate whether microbiota from PD patients characterized as “brain-first” or “body-first” sub-phenotypes will induce divergent gastrointestinal functions and motor deficits in human microbiome-associated mice. Human PD microbiome-associated mice were generated by performing fecal microbial transfers from “brain-first” and “body-first” PD donors into germ-free C57BL/6 and dbl-PAC-Tg(SNCAA53T)Snca-/- recipient mice. FMT recipient mice were bred and gastrointestinal and motor functions in these offspring were analyzed. In dbl-PAC-Tg(SNCAA53T)Snca-/- mice, slow intestinal transit, indicative of decreased intestine motility, and increased gastrointestinal permeability were observed in “body-first” group compared to “brain-first” sub-phenotype. No significant motor function differences were detected between the two PD sub-phenotypes in these mouse models. Additionally, male dbl-PAC-Tg(SNCAA53T)Snca-/- “body-first” mice demonstrated a better ability to differentiate preferred odors in the olfactory preference test, whereas those colonized with microbiota from "brain-first" PD patients showed more olfactory dysfunction. Together, these results suggest that gut microbiota from PD patients may influence non-motor impairments associated with PD sub-phenotypes.Item Embargo Bovine Foot Rot and its Microbiological Relationship with Bovine Digital Dermatitis(2025-01-07) Pyakurel, Susan; Orsel, Karin; De Buck, Jeroen; Morck, Douglas Walter; Jelinski, MurrayBovine foot rot (BFR) and bovine digital dermatitis (BDD) are important infectious diseases that cause pain and lameness in feedlot cattle. BFR causes subcutaneous tissue necrosis and is treated using systemic antibiotics whereas BDD affects outer skin layers and is treated using topical treatments, but cases often relapse. Visual diagnosis of BFR and BDD is complicated by inconclusive cases with lesion characteristics indifferentiable as either BFR or BDD. F. necrophorum and Treponema spp. are the bacteria primarily associated with the pathogenesis of BFR and BDD, respectively. Also, several Treponema spp. are found associated with disease stages of BDD, also called M-stages, of which we investigated the active M2 and chronic M4 stages. As reported in Chapter 2, we visually diagnosed cattle as either BFR, BDD-M2, BDD-M4, inconclusive, and healthy groups. We found that the absolute quantity of seven bacterial species associated with BFR and BDD pathogenesis, namely, Fusobacterium necrophorum, Fusobacterium mortiferum, Bacteroides pyogenes, Porphyromonas levii, Treponema medium, Treponema phagedenis, and Treponema pedis, were different among biopsies, swabs, and subcutaneous samples within and between the cattle groups. We also found that routine histology was not effective in differentiating BFR and BDD. Also, a producer survey indicated that the risk factors included in our survey did not increase the odds of cattle being diagnosed with either disease. In Chapter 3, using 16S rRNA gene sequencing on DNA extracted from biopsies, we found that the groups generally had similar bacterial species present, although in different proportions, with the healthy group having the most diverse microbial taxa. . In Chapter 4, using whole genome sequencing and agar dilution assay, we found that most bacterial isolates derived from biopsies from different cattle groups contained tetracycline resistance genes as compared to penicillin and ceftiofur, and phenotypic resistance was also higher for tetracycline as compared to ceftiofur and penicillin. This thesis provides quantitative insights into the potential pathogens and risk factors responsible for BFR and BDD pathogenesis, and the in vitro activities of antibiotics used for treating these diseases, while also demonstrating the comparative effectiveness of diagnostic tools for sample collection and differential diagnosis.Item Embargo Multi-modal Evaluation of Perioperative Hypercoagulability in Orthopaedic Surgery Patients with Metastatic Bone Disease(2025-01-02) Yamaura, Lisa Mariko; Schneider, Prism Steorra; Jenne, Craig N; Monument, Michael James; Skeith, LesliePatients with metastatic bone disease (MBD) are at increased risk for venous thromboembolism (VTE) following orthopaedic surgery. Platelets are critical for thrombus formation, and increasing evidence suggests that the interplay between platelets and inflammation may promote this process. However, in patients with MBD, the extent and duration of post-operative hypercoagulability is poorly understood, and the pathophysiology of VTE in this population remains unknown. We aimed to address these knowledge gaps, and hypothesized that VTE would be associated with hypercoagulability, platelet activation and procoagulation, and elevated concentrations of circulating pro-inflammatory mediators. These hypotheses were tested in 35 patients with pathologic fractures due to MBD who required orthopaedic surgery. Study participants underwent serial phlebotomy over a 6-month post-operative period. Samples were analyzed using thrombelastography (TEG), TEG-based PlateletMapping®, and multiplex immunoassay analyses to quantify the extent and duration of hypercoagulability, platelet receptor pathway activity, and systemic inflammation. For population-specific insight, three subgroup analyses were performed. The 35-participant MBD cohort was dichotomized according to VTE incidence (yes/no) for the first analysis, and then by pathologic fracture type (acute/impending). The third subgroup analysis compared participants with acute hip fractures according to the presence of malignancy (MBD/non-cancer) using a subgroup of 10 participants from the overall MBD cohort, and a subgroup of 10 sex-matched participants without cancer. An additional sub-study was performed in 19 participants from the overall MBD cohort that used high-resolution fluorescence microscopy to visualize the platelet membrane and quantify platelet activation and procoagulation. Findings from this multi-modal study demonstrated that hypercoagulability, platelet receptor pathway hyperactivity, and systemic inflammation were elevated pre-operatively in participants who later developed VTE. This suggests that individuals at high VTE risk can be identified pre-operatively. Additionally, the results of subgroup analyses revealed that participants in the MBD and acute pathologic fracture subgroups were more hypercoagulable than participants in the non-cancer and impending fracture subgroups. Associations between hypercoagulability, platelet activation, and inflammation were observed in patients with MBD, with temporal change in each parameter mirroring the others throughout the study. Therefore, further investigation into platelet- and inflammation-mediated hypercoagulability may uncover novel and/or optimal targets for thromboprophylaxis for patients with MBD.Item Embargo Metabolomics comparison between Delta and Omicron-infected individuals(2025-01-06) Pimentel Guerrero, Eric Iván; Winston, Brent; Lee, Chel; Habibi, Hamid; McDonald, BraedonAt the end of 2019, SARS-CoV-2, the novel coronavirus emerged causing a widespread increase in airway and lung infections that was driven by different viral variants. Only the variants with significant differences in transmissibility, disease severity, reduction in neutralization by antibodies, and reduction in treatment effectiveness were designated as variants of concern (VOC). Among these variants, the Delta and Omicron forms have demonstrated marked differences in transmissibility and disease severity. This study aims to identify the plasma metabolomics differences that characterize Delta-infected compared to Omicron-infected patients, analyze the severity within these SARS-CoV-2 variant infections, and investigate how vaccination status and corticosteroid treatment impacted the plasma metabolomic profiles of these patients infected with these variants. Our hypothesis is that the metabolomic profiles will reveal significant metabolomic differences between the two variants, reflecting their varied clinical outcomes. Furthermore, we hypothesize that the treatments used during each variant’s wave of infection may be reflected in the plasma metabolome of infected individuals. This study demonstrates that not only are there differences in plasma metabolites that distinguish Delta and Omicron-infected individuals, but also that metabolites do differentiate between various degrees of severity.Item Embargo Additive Manufacturing of Continuous Fiber-Reinforced Thermoplastic Composites Using Discrete In-Situ Consolidation(2025-01-02) Elderfield, Nicholas; Wong, Joanna C.H.; Korobenko, Artem; Trifkovic, Milana; Sudak, Leszek Jozef; Shrive, Nigel Graham; Laberge Lebel, LouisAdditive manufacturing using the fused filament fabrication (FFF) process presents a simple, low-cost alternative to traditional methods for producing continuous fiber-reinforced polymer composite parts. However, the current state of this technology is hindered by challenges which prevent industry adoption, including limited material selections, high porosities (>10%), weak interlaminar bonding, and low fiber volume fractions (typically ≤35%). Furthermore, there has been limited exploration of its use for manufacturing non-planar geometries, and methods for accurately modeling the structural behavior of parts are still underdeveloped. This doctoral thesis investigates solutions for addressing each of these challenges. To expand material selection, the production of custom 3D printer filaments is investigated using multi-die pultrusion of commingled yarns. A custom pultrusion system is designed and constructed, featuring a split-die design which enables simple and repeatable adjustment of outlet area to accommodate a wide range of precursor materials. It is observed that reinforcement fibers tend to form tightly-packed clusters during the pultrusion process which resist impregnation by viscous thermoplastic melts. A fiber dispersion metric is devised to quantify the proportion of tightly clustered fibers and estimate the degree of impregnation, which is shown to correlate with flexural modulus and stress at failure. The effects of processing speed and temperature on fiber dispersion are investigated in the production of a carbon fiber-reinforced polyetherimide (PEI) 3D printer filament. It is revealed that impregnation rate is limited by the dispersal speed of fibers away from cluster boundaries, which is impeded by the high viscosity of thermoplastic melts. Achieving acceptable levels of impregnation thereby requires either slow processing speeds or a high degree of commingling between reinforcement and matrix materials in the precursor to reduce initial cluster sizes. To address issues related to porosity, weak interlaminar bonding, and low fiber volume fractions in FFF-processed materials, a discrete in-situ consolidation (DISC) method is introduced. DISC applies localized heat and pressure to individual beads of material after deposition via FFF by pressing and running a heated flat-bottomed tool along each bead’s length. The effectiveness of this process is demonstrated by processing a carbon fiber-reinforced polyamide 12 with a 50% fiber volume fraction, resulting in an 89% reduction in void content and a 640% improvement in interlaminar shear strength in comparison to FFF alone. It is discovered that the porosity of material processed with DISC is highly sensitive to the waviness of fibers in deposited beads, requiring precise synchronization between the filament feed rate and deposition speed to maintain organized fiber networks. When the filament is extruded at a higher rate than the nozzle velocity (i.e., over-extruded) the reinforcement fibers buckle and become wavy, resulting in a disorganized fiber network that accumulates significant strain energy during compaction and deconsolidates rapidly upon the release of pressure. To demonstrate the effectiveness of DISC in the production of non-planar structural components, a rotary axis is incorporated into a custom-built 3D printer and rigid cylindrical shells are manufactured by depositing material onto a rotating mandrel. The first continuous fiber-reinforced multi-turn wave springs are manufactured using this method and are subsequently characterized using cyclical compression testing. To demonstrate a strong end-use application of the FFF and DISC processes, the first additively manufactured bistable slit tube composite shells are produced. These shells, known as deployable booms, have extensive applications in deployable satellite structures due to their ability to be reconfigured between a rigid extended state and a space-efficient stable coiled state. The precise material placement capabilities of the FFF process are used to construct these shells with lattice architectures of various densities. A computational process is introduced which enables automatic generation of finite element models directly from material deposition paths. Homogenization and full-scale modeling techniques are employed to characterize structural behaviors of the deployable booms. The effects of fiber angles, lattice density, and initial shell curvature on the stability and shape of coiled configurations, as well as their impact on flexural rigidity properties, are investigated. Strong agreement is shown between the numerically predicted behaviors and experimental results. Lattice shell architectures are revealed to exhibit higher flexural rigidity properties than continuum architectures on an equal-mass basis. Lastly, bistable shell structures that can coil into unique stable configurations via the tailoring of bead deposition paths are demonstrated. This doctoral thesis presents comprehensive investigations and substantial contributions to the state-of-the-art in the field of additive manufacturing of structural composite parts. It examines many critical aspects of the FFF process, from filament production and additive manufacturing to structural design and end-use applications. Solutions for addressing material quality challenges and geometric limitations are presented, and modelling techniques for accurately predicting structural behaviors of manufactured parts are revealed. By addressing key challenges that have impeded industry adoption, this work has reduced barriers to the broader implementation of FFF technology for structural composite production.Item Embargo Polygenic Risk Scores, Structural Brain Imaging and Quantitative Obsessive-Compulsive Symptom Scores in Clinically Diagnosed Samples of Children and Adolescents with Obsessive-Compulsive Disorder and other Neuropsychiatric Disorders(2024-12-23) Antonyan, Lilit; Arnold, Paul D.; MacMaster, Frank; Long, QuanObsessive-compulsive symptoms include intrusive thoughts and repetitive behaviors. They are common in youth and are reported to be moderately heritable and associated with structural brain changes implicated in their pathophysiology. This study explores the relationship between structural brain changes, genetic variation, and childhood obsessive-compulsive symptom scores in a sample comprising six different mental disorders. Genetic analysis showed potential correlations with large-scale summary statistics to identify relevant polygenic risk markers. We also observed a strong genetic association between obsessive-compulsive symptoms and polygenic risk for anxiety disorder. By analyzing brain imaging data including cortical thickness, surface area, and subcortical volume from clinically diagnosed cases and healthy controls, this research integrates polygenic risk score analysis to assess genetic susceptibility linked to OC traits. We delineate the surface area of the inferior parietal lobule as a promising neuroimaging endophenotype associated with obsessive-compulsive symptoms, revealing potential structural brain changes influenced by genetic markers. These findings contribute to understanding the biological pathophysiology of these traits in children and youth and sets the stage for further investigation in larger samples that may offer deeper insights into the etiology of obsessive-compulsive and other related neuropsychiatric disorders.Item Embargo An Investigation of The Nomological Network of Enterprise Risk Management Effectiveness: The Roles of Transformational Leadership and Organizational Culture(2025-01-06) Ogunsanya, Adedayo Samuel; Ogunfowora, Babatunde; Kleffner, Anne; Halek, Martin; Turner, Nick; Pilbeam, ColinFinance and accounting scholars have largely relied on quantitative models based on archival data to study enterprise risk management (ERM) implementation, frequently neglecting key dimensions of organizational behaviour. To address this gap, this dissertation applies a transdisciplinary approach to investigate how the transformational leadership of the chief risk officer (CRO), the consistency of the risk management culture, and the group potency of the risk management team (i.e., whether members collectively believe that their team can be effective) contribute to ERM effectiveness. Based on survey responses from 449 risk managers and executives across financial institutions in North America, Europe, Africa and Asia, covariance-based structural equation modelling was applied to assess the effects of the independent variables on both subjective and objective measures of effective ERM. The results indicate that the chief risk officer’s transformational leadership, the consistency of the risk management culture, and the group potency of the risk management team have positive direct effects on subjective indicators of an organization’s ERM effectiveness. While the direct effect of the group potency of the risk management team on objective indicators of ERM effectiveness is significant, the direct effect of the chief risk officer’s transformational leadership is positive but not significant. Mediation analysis reveals that the consistency of the risk management culture and the group potency of the risk management team significantly positively and sequentially mediate the relationships between the chief risk officer’s transformational leadership and effective ERM. In other words, organizations with transformational CROs are more likely to have effective ERM programs because they positively influence consistent risk management cultures and the group potency of their risk management teams. These insights contribute to the theoretical understanding of ERM and offer practical guidance for enhancing its implementation in financial institutions.Item Embargo Advanced High-Performance Nanocomposites for Multifunctional Physical Sensors(2024-12-23) Rahman, Md Sazzadur; Kim, Seonghwan; Egberts, Philip; Wong, JoannaComposite materials reinforced with nanometer-sized fillers are widely recognized for enhancing polymer properties and introducing multifunctional capabilities. Nanofiller reinforcement transforms conventional polymers into intelligent materials, offering potential for diverse applications, including electronics, sensors, biomedical devices, aerospace, and defense. This dissertation focuses on the development of soft and rigid nanocomposite materials for multimodal sensors designed for harsh environments and wearable technologies in healthcare and biomedical applications. The research commenced with the fabrication of polymer-derived silicon oxycarbide ceramics (SiOCPDC), reinforced with β-SiC nanopowders (SiCNP) using masked stereolithography (MSLA)-based 3D printing, followed by pyrolysis at 1100 °C. By optimizing SiCNP concentration, a gauge factor (GF) of 6129–8987 was achieved for pressures ranging from 0.5 to 5 MPa, surpassing the sensitivity of existing SiOC ceramics. This cost-effective method makes SiOCPDC a strong candidate for high-performance pressure/load sensing in extreme conditions. Next, a multifunctional hydrogel composed of polyacrylamide (AM) and 2-hydroxyethyl acrylate (HEA), reinforced with zeolite imidazolate frameworks-8 (ZIF-8), was developed. This hydrogel demonstrated excellent mechanical properties, including 808% stretchability, 453.5 kJ/m³ toughness, and minimal hysteresis (2.6%). With a gauge factor of 2.98, it is highly suitable for wearable strain sensing in health monitoring. Finally, a nanocomposite organohydrogel, based on a poly(acrylamide)-co-hydroxyethyl acrylate (PAAm-co-HEA) network reinforced with cobalt imidazole metal-organic framework (Co-MOF), was developed. The organohydrogel exhibited remarkable multifunctional properties, including high stretchability (2225%), toughness, self-adhesion, rapid self-healing, stability over a wide temperature range (-80 to 80 °C), and dual responsiveness for multimodal sensing. It demonstrated capacitive pressure sensitivity (0.75 kPa⁻¹) and thermosensitivity (1.10% °C⁻¹), making it suitable for gait analysis and temperature monitoring. Together, these nanocomposite materials demonstrated significant advancements in high-performance pressure sensing, flexible electronics, and wearable technologies. While the SiCNP reinforced SiOCPDC nanocomposite was utilized for high-performance pressure sensing in extreme conditions, the multifunctional nanocomposite hydrogel and organohydrogel offer robust solutions for wearable sensing systems, providing promising applications in healthcare, biomedical devices, and environmental monitoring.Item Embargo Off the Beaten Path: New Perspectives on the Role of Context for Entrepreneurship and Innovation(2024-12-24) Piercey, Philip James; Saunders, William Chad; Keyhani, Mohammad; Kwon, Seok-Woo; Bagga, Charan Kamal; Siepel, Josh; Saunders, William ChadThis thesis presents new ways of examining the underlying conditions that characterize geographic contexts of entrepreneurship and innovation. Regionalist approaches currently predominate research into the geography of innovation modes. In contrast, this thesis’ first study applies a spatial approach that highlights the role of geographic distance. Logistic regression tests of 4887 Canadian small firms indicate that the learning activities of the science-technology-innovation (STI) mode and the external dimension of the doing-using-interacting (DUI) mode are more likely at close distances from metropolitan regions. Whereas these activities rely on external interactions, the internal activities associated with the DUI mode appear comparatively viable in non-proximal locations. The second study introduces an event-based investigation of entrepreneurial ecosystem evolution. Prior research in this area has been feature-oriented, involving relatively stable aspects of ecosystems. Through its emphasis on discontinuities, event-based research can address the dynamic and chaotic nature of entrepreneurial ecosystems. This study collected social media discourse data to investigate how a potential triggering event, the acquisition of a unicorn firm (i.e., those with an estimated value of $1 billion or more), influenced attitudes in two Canadian ecosystems. Quantitative sentiment analysis and qualitative thematic analysis are combined to reveal that unicorn firm acquisitions are understood via meta-narrative frames. These shape attitudes toward entrepreneurship and the event itself, thereby providing a microfoundations explanation of entrepreneurial ecosystem evolution. Advisory services are a staple among entrepreneurship support organizations, particularly as a means of orienting entrepreneurs to local contexts. The third study sheds light on the discursive processes that engender the use of advice in entrepreneurial decision-making (i.e., advice-taking). Data capturing interactions between advisors and nascent entrepreneurs enabled a qualitative analysis of dialogues from 30 nascent entrepreneurs in Alberta, Canada. The findings first provide a grammatical model of advice sequences. Analysis of these sequences suggest that while iterative co-creation of advice contributes to advice-taking, this outcome can be achieved through alternative sequences as well. The importance of responses, learning signals, and the order of discursive moves, is explained.