Restricted Theses and Dissertations
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Item Embargo Multi-scale Analysis of Surfactant-assisted Enhance Oil Recovery and Carbon Dioxide Geological Utilization(2024-07-19) Liu, Benjieming; Chen, Zhangxing; Aguilera, Roberto; Maini, Brij; Husein, Maen; Rui, ZhenhuaEver since the first industrial revolution, the rising trend of energy consumption and greenhouse gas (GHG) emissions never stopped, contributing to the pressing global issue of global warming. The society still has a chance to prevent the worst of climate change’s future harm. Therefore, balancing the increase in energy demand while controlling carbon dioxide (CO2) emissions has become a common goal for humanity. In the oil and gas industry, surfactants have been recently regarded as a viable chemical additive to enhance oil recovery (EOR) and carbon capture, utilization, and storage (CCUS). However, the performance of surfactants in engineering fields has often been assessed too simplistically based on observed changes in their behaviors or properties. In order to provide an in-depth fundamental understanding of surfactant-assisted EOR and CCUS processes across multiple scales, in this thesis, essential mechanisms, including displacing performance, adsorption, diffusion, wettability, miscibility, and feasibility in field applications, were studied by experimental methods, molecular dynamics (MD) simulations, and numerical reservoir simulations. In detail, a) the impact of clay minerals on oil detachment from quartz surfaces during surfactant-assisted thermal recovery processes was evaluated; b) a generalized surface modeling procedure of wettability transition on quartz surfaces was proposed to accurately predict a contact angle on sandstone formations; c) the effect of nanoconfinement on the minimum miscibility pressure (MMP) of a CO2/shale oil/surfactant system was investigated; d) a feasibility case study of a novel CO2-switchable surfactant flooding project was conducted on a targeted reservoir. The results of this thesis proved the versatility of surfactants in EOR and CCUS. It is found that clay minerals are not always detrimental to oil recovery. In fact, some clay contents can enhance an oil detachment process by influencing a spatial distribution of surfactant molecules in nanopores. The proposed generalized surface modeling procedure of quartz wettability in this thesis provided more accurate results than a traditional treatment that fully hydroxylates surface atoms. It successfully captured the trend of wettability transition on a quartz surface while considering a series of parameters, including a surface hydroxyl group density, temperature, surfactants, and crude oil. It was also found that the presence of surfactants can reduce the CO2-shale oil MMP. MMP can be further decreased when considering the nanoconfinement effect, as it intensifies CO2-surfactant interactions and inhibits the tendency of CO2 molecules to self-aggregate. Additionally, applying a CO2-switchable surfactant in chemical flooding significantly increased oil recovery, offering an eco-friendly method for oil production. To conclude, this dissertation deepens the understanding of surfactants in EOR and CCUS at multiple scales. It provides helpful guidance on surfactant-assisted engineering processes in the chemical and petroleum industry.Item Embargo Clustering-Assisted Observation Domain Optimization for GNSS Multi-Fault Detection and Mitigation(2024-07-15) Haque, Fahimul; Dehghanian, Vahid; Fapojuwo, Abraham; Dehghanian, Vahid; Fapojuwo, Abraham; Nielsen, Jorgen; O'Keefe, Kyle; Messier, Geoffrey; Alves, PauloWith the rise of autonomous and semi-autonomous vehicles, effective fault detection and mitigation (FDM) methods have become essential in meeting the integrity requirements for precise and reliable Global Navigation Satellite System (GNSS)-based positioning. In scenarios involving multiple faulty observations, the existing GNSS-only statistical FDM methods are ineffective or impractical due to either theoretical model limitations or high computational costs. Additionally, supervised learning-based FDM approaches introduced in recent years do not meet the existing and emerging industry requirements due to dependence on large amounts of diverse training data, the accuracy of the offline labeling process, or high computational complexity. In this dissertation, a novel GNSS multi-fault detection and mitigation method is developed that achieves a balance between computational complexity and performance. The proposed method incorporates an Expectation Maximization (EM) framework to jointly estimate an approximate maximum likelihood of states and latent model parameters in the presence of observation outliers, i.e., faults. However, the EM algorithm is known for its high computational complexity. To reduce the computational complexity of EM, an importance sampling step based on unsupervised clustering is introduced. As demonstrated by the results and analysis herein, the proposed method outperforms the existing Least-squares Residuals-based single-fault method, achieving an average improvement of up to 48% in positioning accuracy. Additionally, the computational complexity of the proposed method is an order of magnitude lower than the state-of-the-art Solution Separation method. The improved performance and the lower computational complexity of the proposed method make it a suitable candidate for integration into modern standalone real-time GNSS applications.Item Embargo Analysis of Viral Variants and Biomarkers in Hepatitis B Virus (HBV) and Hepatitis Delta Virus (HDV) Coinfected Individuals(2024-07-02) Presbitero, Alexandra; Coffin, Carla; Hynes, Michael Francis; van Marle, Guido; Jenne, CraigHepatitis B virus (HBV) and hepatitis Delta virus (HDV) coinfection can cause the most severe form of viral hepatitis in humans. The HDV needs HBV to disseminate, co-opting HBV surface antigen (HBsAg) during assembly. Both viruses have error-prone replication leading to increased variability. We aim to compare clinical and viral outcomes in a contemporary cohort of HBV/HDV coinfected (HBsAg positive and HDV antibody (anti-HDV) positive) vs. HBV monoinfected (HBsAg positive, anti-HDV negative) individuals. Viral variants, HBV biomarkers, HBV DNA, and quantitative HBV surface antigen (qHBsAg) were assessed. Nucleic acid related antigen (NRAg) and HBV core antibody (qAHBc) were quantified by ELISA. HDV RNA/HBV DNA was tested by qPCR. HBV S, X, and HDV delta gene were analyzed by Sanger and Next Generation Sequencing (NGS) and MEGAX. In this prospective study, 25 anti-HDV+/HBsAg+ patients (median age 41y (SD10), 10 females, mostly Asian (n=10) and HBeAg negative (n=19), with median 5 years follow-up (range 1-10). The known HBV genotypes (GT) (n=16) were 3A, 10D, 3E, and known HDV GT (n=19) were 1 (n=16), 2 (n=1), 5 (n=2). Data was compared to a contemporary cohort of 20 HBV monoinfected patients (median age 45y (SD10), 7F, mostly Asian (n=15), with HBV GT 2A, 3B, 12C, 2D, 1E, all HBeAg (-). Single nucleotide polymorphism (SNP) analysis of the HBV S to date in 11/20 by Sanger sequencing showed no mutations, but 3/20 showed X gene variants. Similarly, HBV X NGS analysis in 2 patients showed 16 mutations and 18 S variants in 9 patients. NGS analysis of S gene showed 6 unique mutations not found in the HBV/HDV coinfected cohort. In 25 HBsAg+/anti-HDV+ patients, 19 are HBeAg(-), with low-level HBV viremia, high qHBsAg, and 23/25 HDV RNA+. NGS and SNP analysis showed unique HBV S/X variants. The X and/or S mutations detected correlate with severe liver disease, impaired replication, HCC development, decreased antigenicity and vaccine escape. We found unique SNPs/variants and increased diversity over time in the HDV gene. In summary, this study provides novel data on HBV and/or HDV viral sequence changes in a cohort with high risk of liver disease progression over long-term follow-up.Item Embargo Assessing Motor Adaptation Following Adolescent Sport-Related Concussion(2024-07-03) Stuart, Devon Walter; Dukelow, Sean; Cluff, Tyler; Kirton, Adam; Emery, CarolynConcussion is a mild traumatic brain injury that is common for adolescents participating in sports. Sport-related concussion can be acquired through biomechanically diverse mechanisms of injury, leading to diverse damage to the brain that can result in cognitive, sensorimotor, and/or vestibular impairments. Currently there are no gold standard tools for clinicians to use when diagnosing, managing, and making clearance to play decisions following sport-related concussion. When examining individuals following suspected concussion and when making clearance decisions to play, we postulated that an assessment task that engages distributed, global brain networks to capture concussion-related neurological impairments would be useful. Motor adaptation is a brain function important for sport participation that requires engagement of sensory, motor, cognitive, and association regions of the brain, leading us test this brain function. This thesis examined motor adaptation impairments in adolescents at two timepoints: within 10 days postinjury (Experiment 1), and after obtaining medical clearance to return to sports (Experiment 2). Group level differences in all tested task parameters were seen within 10 days of sport-related concussion, with approximately one-in-four participants exhibiting overall impairments in motor adaptation. When medical clearance to return to play was granted, group level differences were no longer seen compared to healthy controls. However, approximately one-in-four participants who were medically cleared exhibited overall impairments in motor adaptation. Taken together, our results suggest that motor adaptation may be a valuable brain function to assess during the clinical management of sport-related concussion, especially given the relevance of motor adaptation within sport. Further, robotic tools were shown to be capable of detecting subtle neurological deficits after sport-related concussion.Item Embargo Experiences of Racism and Race-Based Traumatic Stress Symptoms Among People of Chinese heritage in Canada: The Moderating Role of Resilience(2024-07-09) Guo, Zixin; Jin, Ling; Zhao, Xu; Guo, ShibaoPeople of Chinese heritage in Canada face historical and ongoing racism, which has been exacerbated since the onset of the COVID-19 pandemic. Theories suggest that experiences of racism may lead to race-based traumatic stress symptoms; however, this association has not been examined among Chinese people in Canada. Furthermore, most research has focused on the adverse effect of racism on poor mental health symptoms, little is known about protective factors in the link between racism and race-based traumatic stress symptoms. To this end, I aim to explore the protective role of resilience from both aspects of individual resilience (i.e., an individual’s characteristics that enable them to bounce back from adversities) and collective resilience (i.e., the availability of practical and emotional support from the community). The purpose of this thesis is to explore how resilience protects against the adverse effect of racism on race-based traumatic stress symptoms among people of Chinese heritage in Canada. A sample of 367 adults who self-identified as of Chinese heritage in Canada (e.g., 46.59% women; Mage = 33.9) completed self-report questionnaires. I adopted SPSS PROCESS Model 1 to examine the moderating effect of individual/collective resilience on the relationship between experienced racism and race-based traumatic stress symptoms. The results showed that more experiences of racism were significantly related to increased race-based traumatic stress symptoms. Collective resilience buffered the adverse effects of racism on race-based traumatic stress symptoms, while individual resilience did not moderate this association. These findings suggest that collective resilience, rather than individual resilience, mitigates the negative impacts of racism on race-based traumatic stress symptoms. This study highlights the necessity of recognizing the experiences of racism and its adverse impacts on the mental health of Chinese people in Canada. Furthermore, it underscores the importance of fostering collective resilience and community-based support systems among people of Chinese heritage in Canada.Item Open Access MIL-100(Fe)-Based Composites for Photocatalytic Dye Degradation: Harnessing UV and Visible Light with Enhanced Performance(2024-07-03) Hosseini, Seyedehfateme; Kim, Seonghwan; Mahinpey, Nader; Kim, KeekyoungThis study explores the photocatalytic degradation efficiencies MIL-100(Fe)-Based composites under both UV and visible light. The synthesized ZnO/MIL-100(Fe), ZnO/Ni@MIL photocatalysts were assessed based on their ability to degrade Rhodamine 6G (R6G), a cationic dye. The main aim of integrating MIL-100(Fe) into ZnO nanoparticles is to enhance the surface area of the photocatalyst to improve adsorption and photocatalytic performance, which is crucial for effective dye degradation. Under UV light, ZnO/MIL-100(Fe) exhibited the highest degradation efficiency, achieving complete degradation within 60 minutes. This exceptional performance is attributed to the enhanced adsorption and charge separation and transfer between ZnO and MIL-100(Fe). ZnO/Ni@MIL-100(Fe) followed closely with a 96% degradation efficiency, highlighting the role of Ni nanoparticles in enhancing photocatalytic performance through improved adsorption kinetics and charge carrier dynamics. Under visible light, ZnO/Ni@MIL-100(Fe) demonstrated the highest efficiency, reaching nearly 98% degradation within 60 minutes following by ZnO/MIL-100(Fe) with 88% degradation efficiency. This superior performance is due to the synergistic effects of enhanced light absorption and electron scavenging of Ni nanoparticles. Both synthesized composites exhibit significantly higher efficiency compared to ZnO NPs, MIL-100(Fe), and Ni@MIL-100(Fe). The findings suggest that ZnO/Ni@MIL-100(Fe) is a highly effective photocatalyst under visible light, while ZnO/MIL-100(Fe) excels under UV light. This study underscores the potential of these composites for practical applications in environmental remediation, driven by their enhanced photocatalytic activities and adsorption properties, primarily due to the increased surface area provided by MOFs.Item Embargo Investigating the association between prenatal provider specialty and postpartum glucose testing in people with gestational diabetes: a retrospective analysis of a population-based Canadian cohort.(2024-07-03) Charlong, Kathleen Mackenzie; Metcalfe, Amy; Rabi, Doreen; Cuthbert, ColleenBackground Gestational diabetes mellitus (GDM) increases future risk of type 2 diabetes and cardiovascular disease. Diabetes Canada guidelines recommend postpartum glucose tolerance testing for everyone with GDM, yet uptake is low. Most evidence of barriers to testing comes from international sources and may not be generalizable to the Canadian perinatal context. Canadian maternity care providers include general practitioners (GPs), obstetricians (OBs), and registered midwives (RMs), with care models that differ from each other and from international providers of the same titles. There is a need for Canadian population-based studies exploring systems-level factors associated with low postpartum screening uptake. Methods We used de-identified population-based data on all births in Alberta, Canada between 2017 and 2018. We identified prenatal care provider specialty, glucose testing incidence, and cohort demographics. The study outcomes were 1) reciept of the gold standard protocol: oral glucose tolerance test (OGTT) within 6 weeks to 6 months, and 2) any glucose test occurring within 6 weeks to 1 year postpartum. We used logistic regression, adjusted for clinically relevant covariates, to estimate an association between test uptake and provider specialty. Results From 105,691 births we identified a GDM cohort of 9,884 eligible births. Cohort proportions of each prenatal care provider were OB (58.6%), GP (38.5%), and RM (2.9%). Overall test incidence was low; 22.2% (95% CI: 21.4 – 23.1) received gold standard testing and 53.9% (95% CI: 52.9 – 54.9) received any testing. When compared to the OB group, people in the GP group were less likely to receive follow-up testing (ORGS= 0.86, 95% CI: 0.77 – 0.95; ORAny= 0.88, 95% CI: 0.81 – 0.96). Those with RM care were also less likely to receive follow-up testing (ORGS= 0.67, 95% CI: 0.46 – 0.96; ORAny= 0.88, 95% CI: 0.67 – 1.15) when compared to the OB group. Discussion The overall proportion of people receiving postpartum glucose testing was low, indicating that efforts to improve screening uptake should be targeted to all care providers.Item Embargo The evolution of a pattern language of feedback in medical education(2024-07-03) Patocka, Catherine; Ellaway, Rachel; Cooke, Lara; Ma, IreneFeedback is embedded within the fabric of medical education. Although the literature refers to feedback as if it were well-defined, in practice what feedback means can vary greatly. Consequently, it remains a source of consternation for learners and teachers as a process fraught with paradoxes. When done well, feedback can improve performance, however it can also have highly variable outcomes. Through an in-depth examination of feedback, my research has acknowledged the challenges presented by it and other equally polysemic concepts. My research has considered the philosophical, theoretical, and methodological assumptions underpinning our existing approaches to feedback and in response I present a path to a more inclusive approach through the application of pattern theory. To approach the task of applying pattern theory, I adapted scoping review methodology to develop a pattern system of feedback in medical education which includes 36 pattern representations. Through a comparative case study, I applied the pattern system to models of feedback, and I provided validity evidence for the pattern system. By outlining the connections between pattern representations within it, I also began to elaborate the pattern system into a pattern language. Finally, I used a case study research methodology to develop a thick description of the challenges of bringing this novel theory-informed conceptual framing of feedback into a more practical space. In all this work, I have advocated for generative (rather than successionist) models of explanations of feedback and lay the foundations for exploring the intersection of realist inquiry and pattern epistemology. Feedback is used as an illustrative case throughout this thesis. The pattern system of feedback I developed, my documentation of the disjointed discourses of feedback in medical education, and my description of this evolving pattern language of feedback can all serve to advance thinking and theory building in this conceptual space. Furthermore, my use of various methodologies to tackle this polysemic concept is, I will argue, a viable approach for studying other fuzzy concepts in our field. As such, not only can my work provide insights into feedback, but it also provides opportunities to explore other equally vexing problems.Item Embargo Reconstructing locomotion in fossil rodents using semicircular canal morphology(2024-07-03) Hou, Lily; Cote, Susanne; Rolian, Campbell; Bertrand, Ornella C.; Theodor, Jessica; Cote, Susanne; Rolian, CampbellAnatomical structures vary among mammals with different locomotor behaviours, including sensory structures such as the semicircular canals (SCCs) in the inner ear. Recent research suggests that SCC morphology correlates with different locomotor behaviours in various extant and extinct mammalian taxa, but there is a lack of research on rodents, the most speciose and diverse mammalian group. In this thesis, an extant sample of rodent SCCs from 98 individuals across seven different locomotor behaviours (arboreal, fossorial, gliding, ricochetal, semiaquatic, semifossorial, terrestrial) was used to understand the correlations between SCC morphology and locomotion. The extant dataset was then used to create a Canonical Variates Analysis Model to predict probable locomotor modes in fossil rodents with unknown locomotor behaviours. Fossil rodent material consists mostly of craniodental remains; hence reconstructing fossil locomotion has been challenging. The fossil sample contains 7 specimens from four different rodent species from Napak, Uganda (site age: 20 Ma). This thesis provides the first micro-computed tomography scans of the SCCs from Diamantomys luederitzi, Paranomalurus bishopi, Paraphiomys pigotti, and one unidentified small thryonomyoid. The extant model predicted that Diamantomys luederitzi was semifossorial, Paranomalurus bishopi was semiaquatic, Paraphiomys pigotti was terrestrial, and the small thryonomyoid was terrestrial. While the model performed well with predicting specialized locomotor behaviours, the model should be complemented with postcranial and skull morphology for generalist forms of locomotion as it is difficult to distinguish the morphology between generalist locomotor categories.Item Embargo The Impact of a Patient Navigator on Readiness Assessment Scores in Youth Transitioning to Adult Health Care in Alberta(2024-07-01) Patton, Megan; Samuel, Susan; Dimitropoulos, Gina; Anthony, Samantha; Patten, ScottPurpose At 16-19 years of age, youth with chronic medical conditions transition from their pediatric specialist to an adult specialist. Youth often feel unprepared for this transfer of care making transition preparations crucial. Transition readiness assessments may have a role in guiding transition preparation. The Transition Readiness Assessment Questionnaire (TRAQ) is the most strongly validated readiness measurement, however, longitudinal examination of TRAQ scores is required to investigate the tool’s suitability to assist in a successful transition. Methods With a patient-oriented approach, this dissertation explored the impact of a patient navigator on TRAQ scores at three-time points within the Transition Navigator Trial (TNT). Transition Research Advisory Council (TRAC) members were partners in this work to highlight the perspectives, opinions, and expertise of those with lived experience of transitioning to the adult health care system. Guiding principles of patient-oriented research (POR) were applied to engage TRAC members meaningfully throughout all phases of the research. Special considerations must be made when engaging youth such as allowing for flexibility throughout the partnership, ample opportunities for mentorship, and reciprocal learning, as such the Youth Engagement Conceptual Model was implemented in conjunction with the guiding principles. This study used data collected as part of the TNT, a pragmatic randomized controlled trial testing the effectiveness of a patient navigator intervention for youth transitioning to adult healthcare. A total of 129 participants were included in this quantitative analysis. Comparisons between the control and intervention group were performed with a Mann-Whitney U test. A mixed-model analysis with random intercepts was used to explore the relationship between access to a patient navigator, time, and TRAQ scores. Results At baseline, there was no significant difference in mean TRAQ scores between the intervention and control group (β=0.05, p = 0.58, 95% CI -0.12, 0.22). Irrespective of treatment allocation, mean TRAQ scores did increase over time between both baseline to 12 months (β=0.54, p<0.001, 95% CI 0.44, 0.63), and baseline to 24 months (β =0.68, p<0.001, 95% CI 0.59, 0.78). In our sample alarmingly we note that only 56% of AYA were scoring > 4.0 (‘ready’ for transition as defined by the TRAQ) 24-months post enrollment into the study, which is between one to two years after their transition to adult care. Youth partners played a crucial role in providing insights into the study results, particularly in understanding the lack of significant findings. Discussion This study sought to examine the change in TRAQ scores in a longitudinal study between those assigned to a patient navigator intervention versus care as usual. We found that access to a patient navigator intervention did not significantly impact the rate of change in TRAQ scores. Our study underscores the criticality of partnering with youth in quantitative studies to ensure outcomes and analyses are relevant and impactful in addressing the needs of this population.Item Embargo Regulation of K+ -dependent Na+/Ca2+ -exchanger subtype 4, NCKX4, by palmitoylation(2024-06-28) Al-Khannaq, Maryam; Lytton, Jonathan; Braun, Andrew; MacDonald, Justin; Leslie, Elaine; Krawetz, RomanMammalian K+-dependent Na+/Ca2+-exchangers (NCKX), encoded by the SLC24 gene family, are Ca2+ extrusion proteins crucial for Ca2+ homeostasis. NCKX4 is widely expressed, particularly in the brain, and is significant in visual and olfactory sensory neurons, neuronal satiety pathways, and dental enamel formation. The regulation of NCKX4 remains largely unexplored. Investigating dynamic regulation of NCKX4 will further our understanding of Ca2+ homeostasis in biological functions and may identify therapeutic targets for eating disorders. Palmitoylation is a post-translational modification that regulates many features of membrane proteins. This study investigates NCKX4 regulation by palmitoylation and examines its effects on NCKX4 cellular localization and function. Understanding NCXK4 palmitoylation is of fundamental importance for advancing our knowledge of transporter regulation and function. Using Acyl-RAC and palmitate-based click-chemistry methods, it was found that approximately 14% of NCKX4 is palmitoylated in both endogenous and transfected systems. This level of palmitoylation was dynamically regulated and could be decreased and increased by inhibitors of palmitoylation (2-bromopalmitate; 2BP) and depalmitoylation (palmostatin B; palmB), respectively. Palmitoylation sites were determined using site-directed mutagenesis of six cysteines, two of which (C118S and C425S) significantly reduced the level of NCKX4 palmitoylation. However, the C118S/C425S double mutant did not eliminate all palmitoylation, indicating the presence of additional palmitoylation sites in NCKX4. The cellular localization of palmitoylated NCKX4 was examined using palmitate-based click-chemistry combined with proximity ligation. Palmitoylated NCKX4 is distributed across multiple cellular membrane compartments. The effect of palmitoylation on NCKX4 cellular localization was examined using 2BP and PalmB with Na+/K+ -ATPase as a plasma membrane marker. The data show a significantly higher fraction of NCKX4 is found in the plasma membrane when palmitoylation is inhibited with 2BP. The effect of palmitoylation on NCKX4 activity was investigated using a Ca2+ imaging assay in HEK293T and MEB4 cells treated with 2BP and PalmB. No significant difference was found in the activity NCKX4 under these different conditions. In conclusion, NCKX4 is palmitoylated at several sites on the protein. The extent of palmitoylation is dynamically regulated, and palmitoylation affects NCKX4 cellular distribution, while it has no measurable effect on aggregate NCKX4 Ca2+ transport activity.Item Embargo Optimization of Autonomous Goods Delivery Systems in Urban Areas(2024-06-21) Lamb, Jacob Steven; Wirasignhe, Chan; Waters, Nigel; DeBarros, Alexandre; Saidi, SaeidThe freight sector is growing: disruptions in this sector have accelerated and are coming under more public scrutiny than other technological changes in the past. Autonomous goods delivery technologies are such a disruption, vehicles with no human on-board that can travel along roads, sidewalks, or in the air. Without the constraint of a human driver, many different forms and functions of vehicle can be created. It is uncertain the type or design of autonomous vehicle that will be best suited for exactly what scenarios, the strategies that will be used to operate them, and the supporting infrastructure changes that will be needed to best accommodate them. This thesis provides planning tools for this change that industry and government can utilize for better, quicker, and more transparent decisions. These methods also allow for sensitivity analysis and the impacts of technology changes to be considered and investigated. The impacts that uncrewed aerial vehicles (UAVs) and sidewalk autonomous delivery robots (SADRs) will have on the optimal locations of micro-fulfilment centers (MFCs) and mothership vans (MSs) are analyzed. It is found that the sensitivity of the relationship between stock-turnover by area and the optimal number of MFCs is a barrier to the adoption of UAV and MFC systems. Moreover, delivery time-windows are shown to be a primary motivating factor in the adoption of UAVs and the areas of a region that are most cost-effective for the switch to UAV and MFCs are the areas furthest from existing logistics centers. For SADRs working with MS, two distinct deployment strategies are identified and compared, then the breakeven cost points for these strategies are analytically determined and expressed in a decision matrix table. A series of sensitivity analysis scenarios shows how exurbs and further suburbs of urban areas are most cost-effective to move to MS with SADR systems. Finally, UAVs and SADRs are compared simultaneously, and a mixed fleet system considered and optimized with conventional vans. The numerical study of Singapore shows that increasing the autonomy of UAVs and SADRs is a key barrier for more widescale adoption.Item Embargo Pericyte deficiencies in a foxf2 loss of function mutant(2024-06-26) Graff, Merry Faye; Childs, Sarah; McFarlane, Sarah; Grewal, SavrajPericytes are critical players in vascular development and disease but are not widely studied in the context of cerebral small vessel disease, a vascular condition related to stroke that progressively weakens brain microvessels. Foxf2, a pericyte-expressed gene, is involved in vascular stability and reduced FOXF2 is associated with increased stroke risk and CSVD prevalence. Here, I use a zebrafish foxf2a loss of function mutant as a genetic model of CSVD to show pathological alterations in brain pericytes. Not only are there fewer brain pericytes across the lifespan, but these pericytes also exhibit morphological abnormalities like increased soma size, process length and degeneration. These abnormalities manifest differently in adult brains, and blood vessel defects are evident. I show that embryonic pericyte defects are not the result of decreased pericyte density but a combination of cell-autonomous and non-cell-autonomous effects. A downstream target of foxf2a, loxl2b, is downregulated in foxf2 mutants. While loxl2b mRNA is sufficient to boost brain pericyte numbers, mutants for this gene do not show an obvious phenotype, suggesting a more complicated role. This thesis sheds light on novel lifespan defects in mutant brain pericytes, potentially contributing to vascular destabilization, and opens new avenues for studying genetic forms of human cerebral small vessel disease.Item Embargo Innovative Universal Severity Classification System for Natural Disasters(2024-06-25) Caldera, Hallupathirage Jithamala; Wirasinghe, Sumedha Chandana; Kattan, Lina; Ruwanpura, Janaka Yasantha; Saidi, SaeidAssessing the true impact of natural disasters is complex, varying by type, location, and time period. Natural disasters, ranging from minor fires to cataclysmic super-volcanic eruptions, universally affect living beings and their habitats. No single factor captures all aspects of impact, as different factors convey varying perspectives on severity, and not all factors are equally significant. Disasters are frequently categorized based on criteria like fatalities or financial damage, but existing classifications often lack a scientific foundation to capture the overall impact, leading to inconsistent measurements and management. The absence of a coherent, globally accepted standard for communicating disaster severity complicates effective disaster management, as varied interpretations hinder unified response efforts. Diverse scales, such as the EF-Scale for tornadoes and the VEI scale for volcanic eruptions, are used to measure disaster magnitude. Various stakeholders—emergency responders, humanitarian aid workers, medical personnel, insurance managers, media, and civilians—employ different scales and terminologies, creating coordination challenges. Disconnected measurement systems cause confusion, hinder relief and mitigation efforts, delay resource allocation, and can lead to political and social instability, affecting international security and relations and causing long-term negative impacts for affected regions. To address these issues, this dissertation introduces the Dis-Utility-Based Universal Disaster Severity Classification System (DUDSCS), a novel framework for assessing and comparing the severity of natural disasters. The DUDSCS integrates both quantitative and qualitative criteria, the former employing 'dis-utility functions' to identify key severity factors and their relationships. Factors such as fatalities, injuries, homelessness, affected populations, and economic damage are evaluated to provide a comprehensive measure of event severity. The development of the DUDSCS involved a six-step methodology, starting with the adoption of 'random dis-utility theory' derived from choice modeling in random utility theory. A global survey captured perceptions, resulting in over 6,000 responses used to calibrate and validate the dis-utility model. Additionally, an in-depth analysis of over 13,000 historical disaster records and their probability distribution helped establish the system's quantitative criteria. By offering a consistent, multidimensional assessment tool, the DUDSCS enhances communication and coordination among stakeholders. By addressing inconsistencies in disaster terminologies and providing a common communication platform, the DUDSCS promotes better-prepared, more resilient communities. The qualitative classification system, while originally in English, can be adapted to other languages using clear definitions for each level based on impact degree, circumstances, fatalities, injuries, and damage. A color-coding system assists disaster recovery workers who may be illiterate or unfamiliar with the local language, enabling effective communication and response in foreign regions. This ensures that all individuals, regardless of language or literacy barriers, can understand and respond to disasters efficiently. This scale captures varying levels of severity, making it a valuable tool for diverse stakeholders, including policymakers, disaster managers, insurance estimators and researchers. The DUDSCS framework provides a new 0 to 10 scale for event severity, where zero indicates minor impact and ten signifies partial or full extinction. The research includes a case study on the COVID-19 pandemic, demonstrating the system's applicability and addressing key gaps in disaster literature. The system aligns with global frameworks such as the Sendai Framework for Disaster Risk Reduction 2015-2030, contributing to targets related to reducing disaster impacts on lives, economies, and infrastructure. Despite challenges such as data biases and predictive limitations, this comprehensive, statistically sound DUDSCS marks a significant advancement in disaster impact assessment and management, fostering informed decision-making and effective resource allocation for disaster preparedness and response.Item Embargo Highly Dexterous Robotic Insertion Tube for Enhanced Minimally Invasive Surgical Procedures(2024-06-24) Topham, Matthew Jory; Amrein, Matthias; Federico, Salvatore; Willetts, Lian; Betram, John E.A.Current surgical robotic and endoscopic systems permit minimally invasive access to numerous anatomical sites and have demonstrated many benefits by improving diagnostic capabilities, patient outcomes, and treatment efficiency. These advances are not without limitations, as current systems are designed for access to a narrow range of anatomical sites through the requirement of specific sites of entry (natural conduits or straight-line access) and minimal dexterity. Here, I propose to greatly broaden the capabilities of surgical robotic systems through the creation of a highly dexterous and discretely configurable robotic insertion tube for enhanced minimally invasive surgical procedures. A priority of this system, which I term Serpento, is usability in small settings, including remote and rural communities. As such, this system is designed to be cost-effective and suited for mass production. The ability to assume a vast number of discrete and defined configurations allows Serpento to provide access to currently inaccessible tissue and travel independently of natural conduits (i.e. the colon). At its core, the robotic insertion tube underlying Serpento is comprised of a sequence of several hundred ring components, that are each individually addressable teeter-totter mechanisms. The unique structure, formed by the assembly of these components, improves the maneuverability of the system, which allows it to precisely follow complex access paths. Furthermore, a central channel may contain tubes for suction, for example, or to allow for the advancement of tools as seen in current endoscopes. Serpento has become a tangible possibility through computer-aided design (CAD), 3D printing, and assistance by Dr. Matthias Amrein and Dr. Salvatore Federico. Ultimately, the innovative work behind Serpento has demonstrated promising results, laying the foundation for its advancement from a conceptual design to a feasible technology.Item Embargo Examining Chronic Post-Stroke Aphasia Recovery Using Non-Invasive Brain Stimulation and Neuroimaging(2024-06-24) Low, Trevor A; Dukelow, Sean; Goodyear, Bradley; Kirton, AdamAphasia, an impairment in language processing, affects approximately one-third of stroke survivors immediately after stroke and up to 50% will have long-term impairments. Rehabilitation of aphasia at the chronic phase is possible, though outcomes are variable and often minimal. Novel therapeutic approaches and an increased understanding of the neurobiology supporting recovery are needed. Chapter Two assessed the safety and feasibility of combining repetitive transcranial magnetic stimulation (rTMS) with high-intensity Multi-Modality Aphasia Therapy (M-MAT) in chronic post-stroke aphasia (n=20). This novel combination therapy was determined to be feasible and safe in chronic post-stroke aphasia. On the basis of all participants benefiting from M-MAT regardless of rTMS allocation, we used resting-state fMRI (Chapter Three) and diffusion-weighted MRI (Chapter Four) to examine functional and structural connectivity associated with changes in speech production. In individuals that made positive, significant changes in naming, pre-treatment functional and structural connectivity of left hemisphere temporal and parietal language regions were associated with greater treatment-related improvement in naming. Additionally, naming improvements were associated with decreases in functional connectivity of bilateral posterior temporoparietal regions with frontoparietal, sensorimotor and visual networks at post-treatment. In Chapter Five, we conducted a randomized controlled trial investigating the efficacy of rTMS plus M-MAT on aphasia severity in a larger cohort of chronic stroke participants (n=43). Delivery of rTMS combined with M-MAT resulted in significant supplemental improvements in aphasia severity compared to sham plus M-MAT at follow-up. This demonstrates that rTMS is a promising adjuvant therapy for M-MAT in chronic stroke. Chapter Six investigated the neural basis of adjuvant rTMS effects using overt naming fMRI. Participants who received rTMS with M-MAT demonstrated dynamic functional reorganization over time, resulting in increased recruitment of left hemisphere perisylvian and temporoparietal regions at 15 weeks compared to sham. These data demonstrate potential mechanisms for the behavioural improvements observed following rTMS plus M-MAT. This thesis provides evidence to support the efficacy of rTMS plus M-MAT for improving chronic post-stroke aphasia. In addition, this thesis advances our understanding of the structural and functional brain architecture that supports aphasia recovery. These behavioural and neuroimaging results are important for the advancement of post-stroke aphasia rehabilitation.Item Embargo The Safety and Feasibility of Transcranial Direct Current Stimulation for the Treatment of Chronic Cervicogenic Headaches(2024-06-24) Jobin, Kaiden D.; Debert, Chantel; Smith, Ashley; Schneider, Kathryn; Kirton, AdamCervicogenic headaches (CGH) are a highly debilitating condition whereby individuals primarily experience neck pain, headaches, and impaired neck function. Onset occurs frequently after whiplash injury, concussion, and degeneration of the cervical joints. Although therapies such as pharmacotherapy and exercise provide relief to some patients suffering from CGH, many patients do not find benefit from these interventions alone. Neuromodulation therapies such as transcranial direct current stimulation (tDCS) have recently shown promise in other headache and pain conditions. As such, we designed a double-blinded, sham-controlled, randomized trial to consider the safety and feasibility of tDCS combined with exercise therapy (ET) for patients with chronic CGH. Secondarily, we sought to explore the efficacy of active tDCS/+ET compared to sham tDCS/+ET on outcomes evaluating headache, pain, quality of life, and neck function. We found this intervention to be both safe and feasible for individuals with CGH, demonstrating high recruitment, retention, and adherence as well as no serious adverse events. Furthermore, we found significant group-time interactions favouring the active tDCS/+ET group with respect to headache intensity and frequency as well as pain and fine motor control of the deep cervical flexors. From these findings, a larger, adequately powered, clinical trial is warranted.Item Embargo Some Contributions to Understanding the Heterogeneity of Treatment Effects in Stroke Trials(2024-06-20) Ademola, Ayoola; Sajobi, Tolulope; Hildebrand, Kevin A.; Hill, Michael D.; Thabane, LehanaBackground: Stroke is a neurological disease that is the third leading cause of death and the tenth-largest known cause of disability-adjusted life years in Canada. Fortunately, clinical trial evidence has identified a few treatments that improve patients’ outcomes, resulting in faster reperfusion, better functional outcomes, lower mortality rates, and improved quality of life. Despite the overall positive benefits of these interventions, there remain differences in the impact of the treatment at the individual level, with some patients experiencing positive benefits and others showing neutral or adverse effects of interventions. Such heterogeneity of treatment effects (HTE) could be attributed to differences in patients’ socio-demographic or clinical characteristics, study designs, inclusion/exclusion criteria, and geographic or regional healthcare systems. Conventional statistical approaches for accounting for within-study and between-study HTE have primarily relied on within-trial subgroup analysis and meta-analysis. However, these approaches are limited because they are based on restrictive distributional assumptions, which may only be tenable in some clinical trials. Methods: This dissertation investigates relevant methodologies for characterizing and accommodating treatment effects within- and between-study heterogeneity in stroke trials. The specific objectives of this dissertation are to: 1) assess the credibility of subgroup analyses reported in published stroke trials; 2) investigate the comparative performance of methods for subgroup identification in clinical trials with binary endpoints when there is no a priori knowledge of patients’ characteristics associated with HTE, and 3) examine the performance of random-effects models when synthesizing evidence from trials with different study design characteristics. This study uses a combination of knowledge synthesis methodology and computer simulations to address these objectives. For objective 1, we conducted a systematic review to examine the credibility of reported subgroups in stroke trials. We used the Instrument for Assessing the Credibility of Effect Modification Analyses (ICEMAN) checklist to evaluate the quality of the subgroup analyses conducted for each study. For Objectives 2 and 3, computer simulations were used to examine the comparative performance of subgroup identification methods for identifying relevant variables/biomarkers associated with HTE in clinical trials of binary endpoints and meta-analytic methods for synthesizing treatment effects obtained from explanatory and pragmatic trials, respectively. Results: The systematic review of reporting quality of subgroup analyses in stroke trials revealed that the credibility of reported subgroup analyses is poor, with most studies not providing a priori rationale for the type and number of subgroup analyses conducted. Among all the subgroup identification methods investigated, the model-based recursive partitioning (MOB) method had the best control of Type I and higher statistical power to detect HTE. The random-effects model based on t-distribution (robustRE) and the mixture random-effects model (mixRE) are more appropriate for meta-analysis data with substantial HTE. However, the conventional random-effects model (RE model) remains reliable for estimating pooled treatment effects in data with moderate HTE. Conclusion: Understanding and capturing treatment effect heterogeneity is critical for generating evidence about treatment effectiveness in clinical trials. More statistical methods that account for heterogeneity in the study population and design characteristics are recommended to analyze and synthesize evidence from clinical trials.Item Embargo An Examination of Patients’ Experiences with Navigation Services in Alberta’s Healthcare System(2024-06-20) Rabi, Sarah; Tang, Karen; Santana, Maria; McBrien, Kerry; Dimitropoulos, GinaBackground: The concept of patient navigation (PN) was first envisioned to assist marginalized cancer patients access appropriate and timely healthcare resources. While this understanding of PN may still hold for a subgroup of programs today, the expansion of PN over the past 30 years has resulted in a diverse set of interventions with distinct care settings, patient eligibility criteria, navigator training, and program objectives. Noting this, our study sought to better understand how PN has evolved by gathering information on patients’ perspectives and interactions with PN programs across Alberta. Our objectives were to (i) explore patients’ current experiences with PN programs, and (ii) identify the features of PN felt to be of particular value to patients. Methods: To address these objectives, we conducted an interpretive descriptive study to collate the experiences of adult patients with longitudinal exposure to Albertan PN programs (involvement for greater than or equal to one month). Participant recruitment occurred via key informant sampling with navigators across Alberta. One-on-one semi-structured interviews were conducted to explore patient experiences with PN and their understanding of it as a broader concept. Inductive thematic analysis and interpretive exercises were subsequently performed to construct a coherent message from the data. Continued collaboration with two patient partners was maintained throughout the study to ensure responsiveness to patient priorities. Results: This study involved 23 participants with experience using nurse navigators, transition navigators, and lay community health navigators. Irrespective of navigation type, the participants’ stories were tethered by their navigators’ promotion of seamless and personalized care, as well as their ability to seemingly humanize the healthcare system. This was accomplished through a set of participant-identified navigator characteristics, including approachability, accessibility, and comprehensive systems knowledge. While the identified functions and characteristics of navigators were consistent across participants, how these components were operationalized varied based on the program’s setting and the particular needs of each patient. Conclusion: As a patient-centred intervention, understanding patients’ experiences and valuations of PN is critical to distilling the essence of the intervention. This research directly addresses ongoing knowledge gaps surrounding contemporary understandings of PN, particularly from patients’ perspectives.Item Embargo Applications of Machine Learning to the High-Dose-Rate Cervical Brachytherapy Workflow: Applicator Prediction and Late Toxicity Modelling(2024-06-20) Stenhouse, Kailyn; McGeachy, Philip; Roumeliotis, Michael; Yanushkevich, Svetlana; Wilms, Matthias; Rink, Alexandra; Roumeliotis, MichaelCervical cancer is a significant global health issue, with brachytherapy being crucial for treating locally advanced disease. Brachytherapy involves inserting an applicator through the vaginal cavity to escalate radiation dose to the affected areas. Applicator geometries vary and impact the achievable dose distribution. Limited criteria exist to guide applicator selection, making it dependent on physician experience, presenting challenges in selection consistency and outcome variability. Suboptimal treatment may increase the likelihood of adverse effects post-treatment that impact quality of life. Additionally, there are currently limited comprehensive predictive models for treatment toxicities based on multi-institutional datasets. Machine learning can identify complex relationships and generate predictive models, and thus this thesis explored it’s potential to enhance the cervical cancer brachytherapy workflow by developing tools that assist physicians in making more informed treatment decisions. We first developed a decision-support tool for selecting the optimal treatment applicator, including hybrid interstitial needle arrangement. Using algorithm comparison and analyzing feature importance on retrospective data, we identified that boosted tree-based models combined with geometric features of the target volume provided the highest predictive accuracy. These models, validated through a prospective study, demonstrated comparable accuracy to expert radiation oncologists, with accuracies of 70% for applicator prediction and 82.5% for hybrid interstitial needle prediction. Machine learning predictions improved organ-at-risk dose compared to clinical predictions, demonstrating potential dosimetric benefit. Using a robust, multi-institutional dataset, we developed a Bayesian network approach to model late treatment toxicities, aiding in personalized and adaptive treatment strategies. We first developed a customized simulated annealing framework for optimizing network structures, integrating expert knowledge to ensure generated models have a logical structure that represent current clinical understanding. This framework demonstrated predictive performance comparable to out-of-box optimization methods, while providing a highly interpretable network structure. We explored potential clinical applications of these networks, including risk stratification, risk factor identification, and centre bias analysis. This thesis highlights novel applications of machine learning in supporting key aspects of the brachytherapy workflow for cervical cancer, potentially enhancing treatment quality and consistency, reducing treatment errors, and providing powerful clinical decision-support tools to physicians.