Restricted Theses and Dissertations
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Item Embargo Encapsulation of an Organic Phase Change Material in Wheat Straw Derived Cellulose by Spray Drying(2025-01-27) Ulrich, Anna; De la Hoz Siegler, Hector; Lu, Qingye Gemma; Mahinpey, NaderPhase change materials (PCMs) have the potential to provide valuable thermal energy storage. However, PCMs are not widely used due to challenges with their implementation. Factors including leakage, high-cost materials, energy-intensive processes, and the presence of potentially toxic chemicals are barriers to the widespread use of PCMs. A promising approach is to use biomass derived materials for the encapsulation of PCMs, providing inexpensive and non-toxic wall materials. Spray drying processes are more favorable for large scale production than other encapsulation methods. Many studies have used cellulose or cellulose derivatives to encapsulate PCMs, however most of these methods pose significant challenges to scale up, either due to costs, toxicity, or difficulties with the method itself. This work aims to develop a process for the microencapsulation of a PCM using biomass derived wall materials and a spray drying process. This involved the isolation of cellulose from wheat straw, size reduction of cellulose, design and testing of a laboratory scale spray dryer, and spray drying of a cellulose stabilized PCM emulsion. It was found that cellulose could effectively be isolated from wheat straw, and several methods for size reduction were promising for encapsulation. In addition, two spray dryer prototypes were developed, which were able to successfully spray dry during testing, however they had low solids recovery. Successful microencapsulation of the PCM in cellulose by spray drying appears to have occurred based on SEM analysis. Further work is needed to improve cellulose size reduction, emulsion formation for encapsulation, spray dryer performance and operation, as well as rigorous evaluation of the produced microcapsules.Item Embargo Driving Behaviours of Older Adults: Insights into Driver Identification and Real-World Navigational Patterns(2025-01-24) Derafshi, Reihaneh; Bayat, Sayeh; De Souza, Roberto; Vrkljan, BrendaMaintaining driving independence is crucial for older adults, yet cognitive decline poses challenges that impact their safety and decision-making on the road. Additionally, the ability to identify drivers based on unique behavioural patterns has significant implications for vehicle security, personalized driver assistance, and road safety. This thesis explores these interconnected themes through two complementary studies that leverage real-world driving data to gain insights into navigational behaviors and driver identification. The first study examines the relationship between cognitive impairment and driving patterns in older adults. Using GPS data from 246 participants, including 230 cognitively normal individuals and 16 with incident cognitive impairment, spatial clustering and hashing algorithms revealed significant differences in driving behaviours. Participants with cognitive impairment demonstrated reduced route variability and reliance on fewer distinct paths to common destinations, offering evidence for driving as a potential digital biomarker for early detection and monitoring of cognitive decline. The second study presents a privacy-preserving methodology for driver identification using gas and brake data recorded during maneuvers. An unsupervised acceleration-based maneuver detection method was developed, followed by a supervised Long Short-Term Memory (LSTM) model for predicting driver identity. Results demonstrated the efficacy of this approach, achieving an average accuracy of 90.9% across crossvalidation folds. The findings highlight the existence of personal driving signatures embedded in gas and brake patterns, offering a scalable and privacy-conscious solution for driver identification. Together, these studies aim to uncover insights into how cognitive health and individual driving behaviours shape real-world navigational patterns, advancing our understanding of driving as both a digital biomarker and a personal identifier. By integrating behavioural analysis with scalable computational models, this thesis advances the potential for personalized driver systems, digital health monitoring, and vehicle security in naturalistic driving environments.Item Embargo Modelling and Validation of a Cable-Assisted Robotic System for Machining Application(2025-01-29) Sajjad, Omer; Lee, Jihyun; Dankers, Arne; Bisheban, MahdisIn the rapidly evolving landscape of manufacturing processes, robotic systems have gained prominence for their precision and efficiency. A cable-assisted robotic system (CARS) tailored for machining operations, offering enhanced stiffness is presented in this thesis. This thesis aims to understand CARS dynamic behaviour by experimentally examining the system under various conditions. These conditions include equilibrium and imbalance states, varying the robot postures, and varying the pulley locations. Understanding the influence of these variables aids in determining the feasibility of such a system. Additionally, the influence of the cables on the systems is examined. Cable types are varied from solid to stranded, as well as the number of cables and the size of the cables. The cable tension is also manipulated and the effects are investigated. The cables act as massless redundant links providing the robot with additional stiffness, however the extent to which additional stiffness is applied needs to be determined. CARS is also examined in a quasi-static state. The quasi-static state differs from the static, impacting the stability limits at the low frequencies and giving a better understanding of the dynamics of the system for machining applications. Finally, CARS is tested in machining by performing chatter tests under the use of different cables. Furthermore, this thesis presents a novel mathematical model for CARS, consisting of a semi-empirical cable model integrated with a serial robot model. The cable properties are identified experimentally, while the robot properties are determined using optimization techniques. The model is derived using the Euler-Lagrange method, and is validated by simulating CARS response and comparing it to the results obtained through experimentation. Finally, the model is optimized using a genetic algorithm to determine the cable configuration that maximizes the dynamic stiffness. These findings have implications for robotic machining applications and broader industrial robotics.Item Embargo Surfactant-Modified Nanoparticles for Enhanced Oil Recovery in Sandstone and Carbonate Reservoirs(2025-01-29) Aboabdulla, Jomaa Ahmed Melad; Nassar, Nashaat; Hassanzadeh, Hassan; Sumon, Kazi Z.; Mohamad, Abdulmajeed; Dejam, MortezaThis work delves into the realm of enhanced oil recovery (EOR) from carbonate and sandstone reservoirs by using cetyltrimethylammonium and alpha-olefin sulphonate (AOS) grafted on silica nanoparticles with low salinity water (LSW). The research investigates the mechanisms underlying the grafting of surfactants onto silica nanoparticles for carbonates and sandstone core applications, forming surfactant nano-based nanofluids. When coupled with LSW, these nanofluids offer a transformative strategy for chemical EOR. Rigorous experiments were conducted, ranging from material and fluid characterization, interfacial tension (IFT) measurements, wettability assessment using contact angle, spontaneous imbibition, and nuclear magnetic resonance (NMR) measurements and followed with core flooding experiments on different core plug samples both for carbonates and sandstones. For carbonate core plugs, limestone cores consisting of low (50 mD) and higher permeability (200 mD) scenarios were used. For sandstone core plugs, Brea sandstone of permeability in the range of 60-100 mD was used. The outcomes of these experiments clarified key insights into oil recovery. The reduction in IFT, particularly at elevated pH levels, emerged as a critical mechanism. For the case of carbonate reservoirs, while contact angle measurements indicated a significant shift from oil-wet to water-wet conditions, NMR and Amott index measurements indicated no wettability change upon the application of nanofluids. In the core flood experiments, the effectiveness of hexadecyltrimethylammonium bromide (CTAB) alone was contrasted with that of CTAB-grafted silica nanoparticles. For 200 mD cores, CTAB alone had an additional recovery of 22.4% over 6 pore volumes (PV), whereas CTAB-grafted silica nanoparticles at higher pH levels (SE) showed a higher recovery of 34.7%. In the case of 50 mD cores, CTAB alone yielded a recovery of 15%, while SE resulted in 20% of the oil originally in place (OOIP). These findings underscore the unparalleled potential of CTAB-grafted silica nanoparticles at elevated pH levels as a pioneering method, offering an economically viable, efficient, and highly effective approach for implementing surfactant-nanoparticle solutions in carbonate reservoirs, covering both low and high-permeability reservoirs. For the sandstone application, AOS surfactants and silica nanoparticles were tested for EOR applications via a series of tests, facilitating the mobilization of trapped oil. The study presented a new approach to the integration of silica-grafted AOS when dispersed in LSW for EOR applications in sandstone reservoirs. The formulated fluids comprised formation water (FW), LSW, silica nanofluids, AOS surfactant, and AOS+ silica (pH 9). Recovery at the tertiary stage was as follows: FW (0.00%), LSW (1.43%), silica nanofluids (2.85%), AOS (5.71%), and AOS+Silica (pH 9) (15.71%). The significant additional recovery observed in AOS and AOS-assisted nanofluids was attributed mainly to the ultra-low interfacial tension, which resulted in a change in capillary number magnitude (10-5 to 10-3) that facilitated the displacement of trapped oil since the wettability change was not significant. This study demonstrated the potential of integrating AOS-silica nanofluids with low-salinity water for enhanced oil recovery, providing valuable insights for optimizing EOR strategies in sandstone reservoirs. This research contributes significantly to the academic discourse surrounding EOR and holds immense promise for the petroleum industry, heralding a new era of enhanced recovery techniques in challenging reservoirs.Item Embargo Functional Connectivity and Attention Abilities in Pediatric Populations(2025-01-29) Harkness, Kelsey Dorian; Murias, Kara Rochele; Bray, Signe Lauren; Esser, Micheal Joachim; Dyck, Richard HenryAutism and Attention-Deficit/Hyperactivity Disorder (ADHD) are highly heterogeneous neurodevelopmental disorders (NDDs) that are associated with attention and executive function (EF) deficits (Neely et al. 2016; Craig et al. 2016). Despite EF and attention being common deficits, groups of individuals with Autism and ADHD are not easily differentiated from each other or from controls by measures of attention and EF (Cai et al., 2021; Kushki et al., 2019). The process for diagnosis of Autism and ADHD is long and requires considerable resources. To make this process more efficient, a better understanding is required about the types of assessments and cognitive domains that contribute more or less to diagnostic status (which will be explored in Chapter 2). The search for neural correlates of Autism and ADHD, such as differences in functional connectivity (FC) related to diagnostic status, has resulted in highly inconsistent results (Cortese et al., 2021; Liloia et al., 2024). This could, in part, be due to the heterogeneity of symptom severity and presentation in Autism and ADHD (Luo et al. 2019; Dajani et al. 2016). By assessing the neural correlates of specific attention and EF measures transdiagnostically, there may be more consistency in results (Mooney et al., 2024). In the search for neural correlates it is also important to acknowledge the factors that could also influence the brain-behaviour relationship, such as stimulant medication (Schweren et al., 2016; Swanson et al., 2011) (further explored in Chapter 3), or diagnostic status (Zhang et al. 2024) (explored in Chapter 4). The lack of consideration for these factors could also contribute to a lack of convergence in results, thus it is important to understand the factors that could influence the brain-behaviour relationship.Item Embargo PASSAGE: A Computational Workflow for Architectural Material Composition(2025-01-27) Poostchi, Peyman; Oehlberg, Lora; Kolarevic, Branko; Johnson, Jason; Parlac, VeraMaterials have long served as a cornerstone of human creativity and the evolution of our built environment. However, the limited diversity of available materials and the increasing depletion of finite resources, exacerbated by fragmented modeling, analysis, and production processes, highlight the urgent need for integrated and selective methodologies. The emergence of computational media and advanced materials introduces new possibilities, enabling architects to interactively and efficiently conceive, evaluate, and produce well-performing products and processes. This thesis introduces PASSAGE, a comprehensive computational workflow designed to digitally configure, select, and produce material compositions for architectural applications based on customized performance criteria. At the center of PASSAGE lies an interactive workflow that automates the configuration and production of architectural objects through the strategic manipulation of material compositions. This workflow supports designers by an interactive interface, allowing for generation of performance datasets to meet specific user requirements in near-real time. The research presented in this thesis encompasses the design, development, and prototyping of the workflow using existing commercial software and fabrication technologies. The work includes the parametric and simulation modeling of geometry, material properties, and fabrication processes, all of which interact dynamically with a database, the designer, and fabrication machinery to ensure comprehensive control over the design, analysis, and production of architectural object models. The effectiveness of PASSAGE is demonstrated through the development of a visual programing code and a case study focused on the creation of a freeform-heterogeneous chair. This case study, realized through the workflow and a Grasshopper code, serves to evaluate and verify the integrated process from design to production using a 3D printer. The dual goals of this research are to empower architects with an interactive, efficient, and scalable computational workflow and to establish a holistic, integrated approach to material composition of architectural products.Item Embargo Unraveling the Regulation of Plant and Yeast Plastin Proteins: A Structural Determination Study(2025-01-25) Khassan, Oleg; Haji-Ghassemi, Omid; Vogel, Hans J.; Fraser, Marie E.; Williams, Gareth J.L-plastin is a 70 kDa protein normally found in white blood cells, where it plays a pivotal role in the formation of actin-rich protrusions required for cell motility. Interestingly, many cancers hijack the white blood cell’s ability to move around and transform into metastatic cancers by upregulating L-plastin. Despite the potential clinical implications of this protein, the function and regulation of L-plastin remain enigmatic, and its full-length structure has yet to be fully characterized. By elucidating the regulatory mechanism of this proposed cancer biomarker, we may find a new approach to manipulate it and thereby reduce the motility of metastatic cancers. Regulation of the actin-bundling activity of L-plastin has been presumed to involve a structural change brought about by the binding of calcium to the N-terminal calcium-binding region (EF-hands). Intriguingly, in plants and yeast this region seems to be conserved, and yet incapable of sensing calcium. This implies another calcium-sensing mechanism may be involved in its regulation. To gain deeper insights into the regulation of L-plastin, we investigated the EF-hands to identify potential proteins involved in modulating its activity and elucidated the structures of the EF-hands of plant and yeast plastins using X-ray crystallography. Using nuclear magnetic resonance (NMR), we uncovered a calcium-sensing protein, calmodulin (CaM), involved in binding and potentially regulating L-plastin. The high-resolution studies of the EF-hands in plants and yeast suggest unique regulatory mechanisms that could enable plant and yeast plastins to function autonomously, independent of calcium. Identifying new mechanisms for actin-bundling can have a significant impact on the advancement of drug-development for the treatment of metastatic cancers.Item Embargo Development of a Photocrosslinkable Cellulose-based Hydrogel Dressing to address Donor-site Wound Treatment(2025-01-24) Tabatabaei Hosseini, Behina Sadat; Hu, Jinguang; Kim, Keekyoung; Gabriel, Vincent; Badv, Maryam; Lu, QingyeDonor site wounds arise from the extraction of healthy skin for the purpose of skin grafting, employed to address extensive skin loss resulting from deep burns, ulcers, or trauma. Typically, the recovery period for these wounds spans 10-14 days, although individual variations exist, influenced by factors such as the patient's age and nutritional well-being. Post-harvesting, donor site wounds commonly exhibit increased pain levels, attributed to the exposure of dermal nerve endings. Additionally, these wounds are susceptible to infection, scar formation, and functional impairment. Although research indicates that moist dressings offer the best conditions for healing donor site wounds, the currently available dressings often fail to create an optimal environment to reduce pain and speed up recovery. This study aims to develop a bio-based moist dressing designed to manage moisture levels while offering the capability for controlled, localized drug release. Addressing the main limitations associated with the existing dressings—inefficient moisture and pain management— and aiming for immediate and tunable wound coverage, a photocrosslinkable hydrogel dressing was designed. A cellulose derivative was chosen and modified with methacrylate groups to achieve photocrosslinking. The modification process was fine-tuned by adjusting pH and time for optimal methacrylation degree. The modified cellulose was then added to a methacrylated chitosan base to form an interpenetrating polymer network. The mechanical and physical properties were evaluated for each composition of the hydrogel. Additionally, the biocompatibility, antimicrobial, antifouling and hemocompatibility effect of the best performing hydrogel were assessed. Firstly, we successfully modified the cellulose and chitosan components, leading to the formation of a stable and fast crosslinking hydrogel within 1 min. The NMR results indicated a 30% methacrylation degree for the cellulose derivative, outperforming the previously reported values. The tensile strength, rheology, and swelling ratio of the hydrogels were tuneable by adjusting the cellulose concentration in the hybrid hydrogel. Furthermore, the final hydrogel showed excellent antifouling, cell viability and hemocompatibility. In conclusion, our rapid crosslinking hydrogel, derived from modified cellulose and chitosan, addressed critical aspects of donor site wound care. With tuneable properties and proven attributes supporting wound management, it promises advancement in donor site wound treatment.Item Embargo Body Composition Features Associated with Renal Cell Carcinoma: Exploring Molecular Mechanisms(2025-01-13) Hassanvand Jamadi, Robab; Bathe, Oliver; Baracos, Vickie; de Koning, Jason; Hyndman, EricBackground: Renal cell carcinoma (RCC) is the most common form of kidney cancer, with clear cell RCC (ccRCC) being the most prevalent and aggressive subtype. This study seeks to identify body composition features visible on CT scans that are prognostic for ccRCC patients. In addition, I sought to determine if molecular features within the tumor are associated with one feature, sarcopenia. It is known that the clinical and molecular features of ccRCC are distinct in males and females. Therefore, I sought to identify sex-specific clinical and molecular features. Methods: Data from 538 patients with ccRCC were obtained from The Cancer Genome Atlas (TCGA) KIRC (Kidney renal clear cell carcinoma) cohort. Preoperative CT scans were available from The Cancer Imaging Archive (TCIA) for 200 patients. CT images at L3 were analyzed using Slice-O-Matic software to measure muscularity, fat distribution, muscle radiodensity, and fat radiodensity. Prognostic body composition features and clinical factors were identified in a multivariate manner. Subsequently, transcriptomic features in the tumor that were associated with low preoperative muscularity were identified in each sex. Gene set enrichment analysis (GSEA) was used to explore biological processes perturbed in ccRCC associated with sarcopenia. Results: Following a multivariate analysis, clinical stage, high subcutaneous fat density, and sarcopenia were found to be significantly associated with worse survival. Differentially expressed genes (DEGs) were compared in patients with low muscularity (sarcopenia) and high muscularity; the genes were different in males and females. Since sarcopenia was associated with T stage and M stage, DEGs that were also associated with advanced T- and M-stage were removed from the gene list, and only genes that were significantly correlated with skeletal muscle area (SMA) were kept in the final gene list. The final list of sarcopenia-associated DEGs consisted of 78 genes in males and 19 genes in females. GSEA demonstrated positive enrichment of pathways associated with proliferation. Interestingly, oxidative phosphorylation was negatively enriched in males and positively enriched in females, and the epithelial-mesenchymal transition was positively enriched in males and negatively enriched in females. The transcriptomic pattern of the sarcopenia-associated variant (SAV) of ccRCC was confirmed to be associated with a poor prognosis in validation cohorts. In addition, several of the gene sets were found to be enriched in the same manner in a small validation cohort. Conclusion: This thesis provides a comprehensive evaluation of the relationships of various body composition features measurable by CT scan, and overall survival. In addition, sex-specific transcriptomic and biological features of ccRCC associated with sarcopenia were identified.Item Embargo From Palestine to Turtle Island: Essays on TransIndigenous Literatures(2025-01-17) Ababneh, Mahmoud; Prud'homme-Cranford, Rain; Srivastava, Aruna; Vanek, MorganThis manuscript dissertation/thesis explores the relationships between Turtle Island and Palestine, contributing to larger discussions in TransIndigenous studies, global Indigenous studies, and within comparative literary studies fields broadly. From Palestine to Turtle Island: Essays on TransIndigenous Literatures creates a dialogue between Indigenous arts and aesthetics centring Indigenous ways of knowing across nations, specifically on Turtle Island and in Palestine, wherein engaging with narrating history and centring Indigenous voices beyond national and exceptionalist narratives about the U.S., Israel, and Canada as colonial states. While I trace possibilities emancipating from juxtaposing Indigenous histories, I pave the way to question our current moment as an extension of settler colonial structures. This manuscript investigates how writers and artists such as Steven Salaita, Armand Garnet Ruffo, James Welch, Aicha Yassin, Charolette DeClue, and Susan Abulhawa reclaim Indigenous voices and histories, reminding readers that settler colonialism is not a past event. They also present Indigenous stories that are past, present, and futurity, surviving despite settler structures of erasure and silence. Additionally, this dissertation aims to situate Palestinian literary and cultural productions in dialogue with Anishinaabe, Cheyenne, and other productions of Algonquin Indigenous artists of Turtle Island. I examine the productive possibilities of this cross-cultural communication to uncover how Indigenous works challenge dominant narratives and offer pathways for resistance, resilience, and healing.Item Embargo Development and Characterization of Catalysts for Fuel Cell and CO2 Electrolyzer Applications(2025-01-14) Moghaddasisaen, Pezhvak; Birss, Viola; Shimizu, George; Karan, Kunal; Dolgos, Michelle; Marriott, RobertThis thesis explores advanced catalysts for energy conversion, focusing on two key projects. The first project explores doped PtRu catalysts to improve CO tolerance in proton exchange membrane (PEM) fuel cells. Using density functional theory (DFT), Pd- and Rh-doped PtRu catalysts were identified as promising due to their resistance to CO poisoning. These findings suggest the potential to enhance PEM fuel cell anode durability and reduce fuel purification requirements, though experimental validation is needed. The second project focuses on nitrogen-doped carbon catalysts for electrochemical CO2 reduction (CO2RR). Jialang Li’s thesis ([86]) demonstrated that nitrogen doping lowers the energy barrier for CO2 reduction, enhancing catalytic activity. In my study, both Vulcan XC 72-R and CIC-85 were investigated. Untreated carbon black (Vulcan XC 72-R) and CIC-85 were found to be inactive for CO2RR. Acid treatment increased the surface oxygen content but did not significantly enhance catalytic activity. However, when acid-treated Vulcan car- bon or CIC-85 was subjected to high-temperature ammonia treatment, substantial nitrogen doping was achieved, as confirmed by advanced surface characterization techniques. My results show that increased oxygen content from acid treatment facilitated greater nitrogen incorporation during ammonia doping, significantly improving CO2RR activity and selectivity. These findings highlight the role of oxygen content in enabling higher nitrogen doping and improving performance for CO2 reduction. These results contribute to both theoretical and experimental advancements in the development of catalysts for sustainable energy applications.Item Embargo Identifying Graft Versus Host and Graft Versus Leukemia Allo-Immune Reaction After Stem Cell Transplantation(2025-01-15) Kalra, Amit; Khan, Faisal Masood; Storek, Jan; Lewis, Victor Anthony; Mansoor, AdnanAllogeneic hematopoietic stem cell transplantation (HCT) is a curative therapy for hematological malignancies. Two major allo-immune reactions take place in the recipient after HCT: the beneficial graft versus leukemia (GvL) wherein the donor immune cells identify and eradicate the leukemic cells of the recipient and the graft versus host (GvH) where the donor immune cells react against the normal cells of the host causing a debilitating illness called graft versus host disease (GvHD). The primary objective of this doctoral research was to distinguish between GvH and GvL allo-immune reactions by meticulously profiling the immune recovery at multiple time points post-HCT. Immune reconstitution in both adult and pediatric HCT recipients was evaluated at the transcriptomic level via gene expression profiling of 579 immunity-related genes using NanoString technology and at the cellular level through flow cytometric analysis of cell subset counts. Peripheral blood mononuclear cells from HCT recipients were analyzed at Day14, Day28, Day56, and Day84 posttransplant. An immune signature characterized by higher counts of T cells and overexpressed T cell-related genes, was identified in patients who developed acute GvHD grades 2-4 as early as Day14 posttransplant. The gene expression signature showing overexpressed T cell related genes especially CD161 expressing cytotoxic T cells was validated in an independent validation cohort. T cell counts and related transcriptomes were notably higher in cytomegalovirus (CMV) seropositive donor and recipient (D+R+) patients compared to other serostatus groups. The recovery pattern was similar in both adult and pediatric patients. The influence of CMV D+R+ on T cell reconstitution was not significant at early time points (Day 28) but became evident at 2 and 3 months post-transplant. Signatures indicating a lack of GvL response were observed at 3 months (Day 84) post-transplant characterized by downregulated expression of CD8 Tcell genes, including TIGIT and EOMES in patients at high risk of relapse. While this study succeeded in partially differentiating GvH and GvL allo-immune reactions through temporal and differential T cell gene expression profiling, further comprehensive transcriptomic analysis in larger cohorts is essential for a complete understanding of the separation between GvH and GvL.Item Embargo Devices and computational methods for preclinical mechanistic deep brain stimulation studies in freely moving rodents(2025-01-13) Bisht, Anupam; Murari, Kartikeya; Kiss, Zelma; Whelan, Patrick; Fear, Elise; Voigts, JakobDeep brain stimulation (DBS) is a therapeutic technique used for the treatment of neurological and psychiatric diseases. Optimization and patient-specific application of DBS remain a challenge as mechanisms of the therapeutic action of DBS on the brain remains unknown. Currently, the instrumentation available for preclinical DBS research focused on performing freely moving animal experiments is limited. The proposed work addresses this gap through major improvements of existing devices and the development of supporting computational methods for data analysis. This work has been divided into four aims. Motivated from a previously developed gradient refractive index lens based point detector system, aim 1 involved development of a wireless miniaturized intrinsic optical imaging system (called TinyIOMS- Tiny intrinsic optical monitoring system) to measure changes in hemoglobin concentration from surface regions of the brain (e.g., motor cortex which is the main output center of DBS brain targets). A comparison of signals with a standard wide-field intrinsic optical imaging system was done to validate the signal reliability of TinyIOMS. Further, we showed the hemodynamic signals recorded could be used to distinguish between brain states (sleep vs awake) by performing continuous recordings for about 7 hours to about 2 days (via intermittent recordings). Aim 2 involved investigating motion artifacts for a single f iber system (SFS) that has shown variability in the measured hemodynamic signals (blood flow and oxygen saturation) from deep brain regions (commonly stimulated during DBS) during previous DBS studies. In this work, we showed that while the blood flow signal is sensitive to motion artifacts, oxygen saturation is not. Further, a motion artifact correction algorithm was developed to correct motion artifacts that occur during experiments using a regression-based approach utilizing light at 680 nm, a wavelength that is relatively less sensitive to hemodynamics. Since the biological interpretability of hemodynamic changes during DBS recorded in the SFS signals was limited, one approach is to compare it with well-established signals, e.g., electrophysiology or GCaMP-based fiber photometry. In aim ii 3, we have further extended the SFS design to enable stimulus-locked (e.g., footshocks, DBS) simultaneous recording of both hemodynamics and GCaMP-based fluorescence signals. In aim 4, a previously developed miniaturized DBS device was improved in mechanical and electrical design, and the software was upgraded to enable wireless programming and timed stimulation. This device was used to stimulate a novel target for DBS, the A13 region of the medial zona incerta in rats. We observed that DBS evoked a robust locomotor response with an overall non-noxious behavioral effect which is important data for clinical translation. Overall, this thesis advances the technology for performing electrical stimulation and the monitoring of hemodynamics in freely moving animals.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.