Restricted Theses and Dissertations

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This collection is the result of a joint project between the Faculty of Graduate Studies and Libraries and Cultural Resources which provides Graduate students with the opportunity to archive their thesis with University Archives in our digital repository.

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    The Clinical Utility of a Novel Multi-Modal Assessment Battery for Acute Sport-Related Concussion
    (2024-04-19) Bertagnolli, Jalena Ashley; Benson, Brian; Dukelow, Sean; Smith, David; Richer, Lawrence
    Objective: To determine the clinical utility of a novel, multimodal, assessment battery in detecting acute post-concussion impairment relative to baseline performance. Study Design: Prospective observational cohort study. Subjects: Four hundred thirty-one elite ice hockey, alpine and freestyle ski, artistic swimming and luge athletes (mean age: 15.7 years (range: 14-36 years), male: 349, female: 82) over one athletic season (2022-2023). Observation Technique: Standardized multimodal baseline assessments including electroencephalography (EEG) utilizing the NeuroCatch® 1.0 device, postural sway using the tri-axial accelerometer Protxx® device, cardiovascular exercise from a bicycle ergometer and sustained handgrip strength were completed in the pre-season and then repeated for any athlete sustaining a sport-related concussion within seven days of injury. Outcome Measures: Directional bootstrap paired t-tests and binomial tests adjusting for multiplicity using Bonferroni correction were used to assess changes in performance between baseline and post-concussion test results for the following four primary assessments of interest: 1) quantitative EEG event-related potentials (N100, P300, and N400 amplitude and latency) (NeuroCatch), 2) quantitative assessment of postural sway with eyes open and eyes closed using a physiological vibration acceleration (phybrata) sensor (Protxx), 3) concussion symptom exacerbation (≥1 on a 10-point visual analogue rating scale) during a submaximal bicycle ergometer assessment, and 4) change in heart rate during a 30-second, 30% maximal handgrip strength contraction. Results: Forty-six athletes were diagnosed with a concussion by a sport medicine physician during the study period. Neither amplitude nor latency for N100, P300 or N400 event-related potentials demonstrated a significant group difference between baseline and post-concussion assessments. Athletes demonstrated a significant group difference in postural sway between baseline and post-concussion timepoints using the phybrata sensor for sway power ratio, with a moderate effect size (dav= 0.491) (baseline: 1.4 ±0.5W, post-concussion: 1.9 ±1.4W, p=0.005). Fifteen (68.2%) of the 22 athletes completing post-concussion exercise assessments experienced worsening symptoms, with two additional athletes unable to initiate exercise due to significant symptom burden (p<0.001, large effect size PR= 0.972). Furthermore, no significant difference was observed for change in heart rate during the handgrip strength task. Conclusions: A novel phybrata motion sensor objectively evaluating postural sway and standardized submaximal cardiovascular assessment evaluating symptom exacerbation demonstrated significant clinical utility in detecting impairment within seven days of an acute sport-related concussion, while event-related potentials (N100, P300, N400) and heart rate change during a sustained handgrip task did not.
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    The location and functional role for the K+-dependent Na+/Ca2+-exchanger, subtype 4 (NCKX4), in mouse brain
    (2024-04-18) Hassan, Mohamed Tarek Ahmed; Lytton, Jonathan; Schnetkamp, Paul; Borgland, Stephanie
    The K+-dependent Na+/Ca2+ exchanger (NCKX) family has emerged as a major regulator of Ca2+ homeostasis. The family comprises five members (NCKX1-5) that are involved in various neuronal functions. In this thesis, I focus on the fourth member (NCKX4) in the brain. While gene expression analysis and immunoblotting of brain lysates demonstrated high expression of NCKX4 in the brain, the regional distribution of the protein product across the brain is unknown. In Chapter 2, I map the expression of NCKX4 throughout the mouse brain. My data reveal that NCKX4 demonstrates distinct and intense expression in multiple areas involved in crucial functions such as learning and memory, reward processing, movement, and cerebrospinal fluid production. Of interest, NCKX4 expression in the choroid plexus epithelial cells (CPECs) exhibited unexpected intracellular distribution. In Chapter 3, I investigate how NCKX4 contributes to the normal function of CPECs by examining the intracellular structure at which NCKX4 is located and changes induced in Nckx4–/– mice, such as CPEC morphology, CSF composition and secretion, and CPEC subcellular Ca2+ dynamics. My data suggest that NCKX4 is partially localized with markers associated with acidic compartments like endo/lysosomal and secretory vesicles, and loss of NCKX4 may lead to alterations in CSF protein composition. However, no changes in CPEC morphology, CSF ionic concentrations, lateral ventricles volume, or Ca2+ activity were found in Nckx4–/– mice. Finally, based on previous reports that link NCKX4 to Alzheimer’s disease and my data (Chapter 2) that show high expression of NCKX4 in hippocampal mossy fibers, in Chapter 4 I investigate the involvement of NCKX4 in learning and memory through a battery of behavioural experiments. Nckx4–/– mice demonstrate deficits in contextual memory formation and recall as well as less anxiety when placed in an open field. No difference was found in the performance of Nckx4–/– mice in novel object recognition task or Barnes maze compared to wildtype controls. The data presented in this thesis provide an expression map in the brain, with an unexpected subcellular location within CPECs, and reveal undiscovered roles for NCKX4 in neuronal function. Many of these results warrant further investigation.
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    Modeling of Antimicrobial-Resistant Enterococci Exposure Risks in Canadian Beef Cattle Production System Using Existing Data
    (2024-04-17) Strong, Kayla; Checkley, Sylvia L.; Checkley, Sylvia L.; Kastelic, John Patrick; Otto, Simon James G.; Reid-Smith, Richard; Waldner, Cheryl Lynne; Lhermie, Guillaume; Noyes, Noelle
    Antimicrobial resistance occurs when microbes change, and antimicrobials previously used to treat them are no longer effective. Antimicrobial resistance presents a global risk to health and food safety, with previously treatable infections becoming increasingly costly and challenging. Antimicrobial resistance is a quintessential One Health issue, given its impact and drivers across human, animal, and environmental health, and requires transdisciplinary interpretations and solutions. This thesis considers methods of risk interpretation using a case study of antimicrobial-resistant Enterococcus spp. within Canadian beef production systems. Five objectives were considered: (1) to identify factors associated with antimicrobial-resistant enterococci within Canadian beef production systems; (2) to construct an integrated assessment model for interpretation of factors potentially associated with antimicrobial-resistant enterococci; (3) to construct a risk profile for interpretation of risks associated with antimicrobial-resistant enterococci in Canadian beef; (4) to construct a Bayesian model for interpretation of enterococci resistance within beef production; and (5) to describe integrated strengths and weaknesses of modeling approaches. Factors assessed for association with antimicrobial-resistant Enterococcus spp. within Canadian beef production systems included antimicrobial and nutritional supplement administration to cattle, environmental factors, and type of processing plant. Resistance trends were often nuanced to unique gene and phenotypic resistance. Patterns varied by species of enterococci. When data were available, the integrated assessment model utilized crude odds ratios extracted from identified factors. Limited data for baseline seeding and factor inclusion limited the model's interpretability. Recommendations and best practices are proposed for future model applications. The risk profile was developed to meet the Codex 77 guidelines and demonstrated the scarce evidence of enterococci resistance transference from beef products, and limited human pathogenicity of enterococci from foodborne consumption. The risk profile highlighted the need for Canadian surveillance studies of enterococci in food products for more informed decision-making. The Bayesian model incorporated available evidence with current estimates of enterococci resistance trends, integrating expert opinion within the model. The model suggests that less than 0.3% of beef products carry antimicrobial-resistant E. faecalis. Individual models and risk discussions uniquely fill niches in resistance discussions and interpretations but were insufficient for providing a holistic interpretation required by stakeholders across the production chain. Drawing findings from multiple reports supported a better understanding and enhanced decision-making.
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    Study of Electrochemical Methane Oxidation to Oxygenates
    (2024-04-10) Al-Attas, Tareq Ali Salem; Kibria, Md Golam; Thangadurai, Venkataraman; Karan, Kunal; Roberts, Edward (Ted) PL; Birss, Viola Ingrid; Morales Guio, Carlos Gilberto
    Methane (CH4), a primary component of natural gas, plays a vital role in energy and chemical production. However, conventional methods of chemical production tend to be resource-intensive and often result in the release of CH4 through venting or flaring in oil and gas operations. Decentralized technologies that leverage renewable energy can mitigate CH4 emissions while generating revenue. Electrochemical oxidation of CH4 (eCH4OR) into valuable fuels and materials offers a flexible solution that can operate in varied conditions. Nevertheless, achieving desirable outcomes at scale is challenging due to the high energy requirements for breaking the C–H bonds of CH4. This thesis focuses on developing catalysts for high-rate and selective electrooxidation of CH4 while also aiming to deepen our understanding of the reaction mechanism. Drawing inspiration from iron (IV)-oxo (FeIVO) metalloenzymes that activate C–H bonds, a copper-iron-nickel (CuFeNi) catalyst for selectively oxidizing CH4 into formate using a peroxide-assisted pathway is presented. The synergistic effect of the metals to selectively oxidize CH4 is explored by in situ spectroelectrochemical studies (i.e. XANES and UV-Vis) and density functional theory (DFT) calculations. Specifically, the analyses revealed the presence of high valent FeIV as the active site for CH4 oxidation, attained by the reactive oxygen species generated during the partial oxidation of H2O2 at low overpotentials compared to water oxidation reaction (OER) on nickel. Furthermore, the critical role of copper in preventing the overoxidation of valuable oxygenates to CO2 was revealed. We achieved a formate faradaic efficiency of ~42% at a current density of 32 mA cm−2 (i.e., partial current of ~13 mA cm−2) and a low applied potential of 0.9 VRHE. Additionally, the thesis examines the reaction pathways of the eCH4OR using hematite (α-Fe2O3) as an electrocatalyst. Different electrochemical and in situ spectroelectrochemical techniques, including ATR-SEIRAS, EIS, and PTR-TOF-MS, were employed to comprehend the mechanism of this reaction. The electrochemical oxidation current density uncovered non-faradaic adsorption of CH4 molecules at lower applied potentials. The non-faradaic adsorption of CH4 molecules was further confirmed through ATR-SEIRAS. In situ ATR-SEIRAS also revealed the presence of the FeIVO species and CH4 oxidation intermediates, correlating them with the applied potential. Thisanalysis unveiled the formation of oxygenated products, including CH3OH, HCOOH, CH3COOH, and their corresponding intermediate adsorbed species, such as •OCH3, •OCOH, and •OCOCH3. Notably, C–C coupling between –COCH3 and –CH3 via ketonization resulted in CH3COCH3 formation. PTR-TOF-MS supported our findings by confirming that acetone is the primary liquid product generated, achieving a faradaic efficiency of 6.3% at 2.3 VRHE. This result is attributed to its formation by coupling acetate and formate intermediates. Consequently, we developed proposed reaction pathways for the selective electrooxidation of CH4 to C1-C3 products. The thesis extends to present techno-economic and life-cycle assessments of electrification options for CH4 utilization. Initially, the study highlights the economic viability of electrifying reformers and boilers in traditional technology. A futuristic scenario discusses one-step methanol synthesis via the direct eCH4OR and illustrates the impact of cell voltage and electricity prices on the calculated minimum selling price of methanol. For instance, methanol production can be profitable at electricity prices below ¢4 per kWh at a total operating cell voltage of 2.0 V. The analysis establishes electricity emission goals to maintain net CO2 emissions within the acceptable range for current methanol synthesis. It is shown that the emissions intensity of the electricity source must be under 181 kgCO2 per MWh for the electrochemical route.
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    Investigating the Built Environment’s Influence on Child Active Transportation Injury and Prevalence
    (2024-04-11) HubkaRao, Tate; Hagel, Brent; Nettel-Aguirre, Alberto; Cloutier, Marie-Soleil
    Background: Motor-vehicle collisions (MVCs) are a leading cause of Canadian child active transportation injuries. Specific built environment features may reduce child injury risk while increasing active transportation prevalence; however, few studies exist evaluating the effectiveness of these features specific to this age group. Further, it is important to understand how built environment features can influence community and school wide child active transportation injuries and prevalence. Methods: Using a modified stepped-wedge trial, Chapters 3 and 4 investigated the influence of installing specific built environment features on traffic speed and volume, active transportation prevalence, and caregiver perceptions of safety. Chapters 5 and 6 used machine learning recursive partitioning trees to predict the number of child active transportation related MVCs, and the proportion of elementary students using active transportation to school, based on the built environment within respective geographical areas. Results: Chapter 3 found traffic calming curbs and in-street signs were associated with a reduction in traffic speed, depending on time-period. No significant changes in traffic volume were found immediately following installation. In-street signs were associated with a reduction of active transportation prevalence in the morning, and an increase in the afternoon. Chapter 4 found traffic calming curb installation was associated with higher proportions of caregiver perceptions of safety. Some respondents showed higher proportions of reported children walking to school at intervention locations. Chapter 5 found built environment features such as signalized intersections were predictive of annual collisions. Chapter 6 showed population density to be important in predicting active transportation prevalence to school. Conclusions: Results of this thesis support calls for a systems approach to road safety. The variability in characteristics of the urban environment that are associated with child active transportation safety and prevalence suggests that no single intervention would be as effective as a more holistic and comprehensive approach. Specific features such as traffic calming curbs and in-street signs, coupled with reductions of major roadways and increases in population density, may, together, have a considerable and lasting effect on improving active transportation safety for Canadian children.