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Item Embargo In vivo kinematic outcomes of cervical total disc arthroplasty using dual fluoroscopy: A longitudinal collective case study(2024-12-19) Bangsboll, Emily Merle; Ronsky, Janet Lenore; Swamy, Ganesh; Roach, Koren Elaine; Duncan, Neil AlexanderIntervertebral disc degeneration of the cervical spine is prevalent in aging adults with symptomatic cases often requiring surgical intervention. Cervical total disc arthroplasty (cTDA) is a surgical treatment for disc degeneration that aims to preserve natural motion of the spine and avoid adjacent segment degeneration. Despite low re-operation rates associated with cTDA, patient outcomes vary, and kinematic effects remain poorly understood. Understanding these effects via in vivo characterization could help address complications of cTDA and improve patient outcomes. This study implemented dual fluoroscopy to evaluate pre- and post-cTDA intervertebral rotations, translations, and endplate proximities to assess the impact of cTDA on in vivo cervical spine kinematics. Five asymptomatic control participants and two surgical participants undergoing cTDA were recruited. Participants underwent computed tomography and dual fluoroscopy imaging during dynamic movements. Model-based tracking matched subject-specific vertebral bone models to each dual fluoroscopy sequence with high accuracy (0.97 mm and 1.4°) and intervertebral rotations, translations, and bone-to-bone proximities were computed. The control pilot study verified the data collection and processing protocols yielded baseline data consistent with literature, although there was notable variability for some trials. Post-cTDA rotation patterns were similar to those of the controls, suggesting increased mobility at both treated and adjacent motion segments. Translations also increased post-cTDA, with some magnitudes exceeding one standard deviation above the control means, potentially indicating instability. Proximity measures indirectly described local disc height and illustrated the coupled motion patterns throughout movement, further emphasizing the value of three-dimensional in vivo kinematic approaches for studying the cervical spine. These kinematic measures have the potential to elucidate the complex coupled motion of the cervical spine post-cTDA and will be valuable for informing future artificial disc designs.Item Embargo Exploring Women's Experiences of ADHD, Medication and Motherhood(2024-12-19) McGillion, Brenna Janet; Milaney, Katrina; Ducey, Ariel; Rankin, JoannaPurpose: The purpose of this study was to explore women’s experiences of ADHD, medication, and motherhood in Alberta, Canada. There is a lack of research that accounts for women’s decision-making processes related to continuing or discontinuing ADHD medication leading up to and during pregnancy. Methods: This qualitative study was guided by feminist disability theory. Fifteen semi-structured interviews were conducted with women who were 1) diagnosed with ADHD, 2) mothers or were thinking about becoming mothers, 3) had personal experiences with ADHD medications, 4) 18+ years old, and 5) were English-speaking. The development of the research questions, recruitment strategies, and approach to data collection and analysis were informed by the values of feminist methodology. Results: Three themes and one sub-theme were identified from the interviews: 1) Benefits of diagnosis 2) Feeling unsupported by healthcare providers 3) I am not enough a. Impairment and disablism reduced confidence about being a mother Conclusion: This research demonstrated that ADHD is a gendered experience that is influenced by various factors. There is a great deal of uncertainty and complexity in the decision-making processes surrounding ADHD medication and pregnancy that require careful attention and care from healthcare providers. There is a need to prioritize care and research for disabled women, especially when it comes to managing ADHD with or without the use of medication leading up to and during pregnancy.Item Embargo MULTICASE ANALYSIS of STRATEGIC RESPONSES to PRICE SHOCKS in UPSTREAM OIL and GAS(2024-12-17) Richardson, Robert Ray; Keyhani, Mohammad; Osiyevskyy, Oleksiy; Schulz, Robert AdolphPrice shocks in every industry can cause significant concerns about an affected firm's ability to service debt, pay dividends, maintain staff, and meet contractual obligations. How firms behave and how those behaviours affect the firm, both in terms of its firm-specific performance and its competitive performance, is of significant interest to both academics and practitioners. The concerns of a price shock are magnified in the upstream oil and gas industry, where the naturally declining, geographically-fixed assets must be continuously replaced, yet both the financial capabilities of firms and the economic viability of projects are significantly reduced. Such a price shock causes this upstream industry to undergo an innovation trajectory change, where the industry leaves its status quo and enters a rapidly changing environment and where Dynamic Capabilities may become a crucial determinant of the strategies deployed. Non-vertically integrated upstream oil and gas firms are particularly affected by the price shock as they do not have offsetting business units and revenues to mitigate the risks or provide alternative investment opportunities that their vertically integrated counterparts do. This multi-case, theory-building analysis examines the differential behaviours, and effects of those behaviours, of four large non-vertically integrated upstream Canadian oil and gas firms during the 2014 oil price collapse. This study finds a wide range of behavioural combinations, such as how and when these firms used retrenchment, managed their long-term debt and debt governance, used equity issuances, and engaged in acquisitions and divestments. Further, this thesis also finds that each firm’s behaviours affected itself differently concerning changes in production levels, firm structure, and firm-specific financial performance, ultimately leading to changes in their competitive performances. The conclusion of this thesis identifies that two firms possibly deployed Dynamic Capabilities to increase their competitive performance by strategically altering firm direction at the onset of the price shock, while the other two firms only used ad hoc methods or best practices and did not improve their competitive performance. A Dynamic Capabilities subcategory termed Dynamic Response Capabilities is defined and presented.Item Embargo The role of Atp11a in uterine biology(2024-12-12) Krala, Alexa Taylor; Hemberger, Myriam; Dean, Wendy; Cobb, John; Childs, SarahPregnancy is a complex physiological process relying on precise coordination of molecular events which are crucial to the well-being of both the mother and the developing fetus. Uterine dysfunction can have critical implications for fetal development, with an estimated 75% of failed pregnancies attributed to implantation defects (Cheng et al., 2023). ATP11A, a phospholipid flippase, has been identified to play a key role in placental function, ultimately leading to fetal heart developmental defects in knockout (KO) mouse embryos. It was even observed that >30% of wildtype pups presented with heart development defects when their mother was heterozygous for the Atp11a gene (Radford et al., 2023). The current project investigates the molecular consequences of Atp11a gene loss in uterine function. During my project, I corroborated a profound sub-fertility phenotype in Atp11a+/-females. I then assessed uterine functionality in Atp11a KO females (generated through placental rescue) using bulk RNA-sequencing and a series of histological analyses. RNA-sequencing data from uterine samples indicated that the uterine epithelial layer is most sensitive to the loss of Atp11a. Furthermore, samples staged closer to E4.0 were more greatly impacted by the loss of Atp11a compared to samples staged E3.5, identifying a critical window during the peri-implantation period during which ATP11A is of great importance. In addition, immunofluorescence staining results from Atp11a KO females demonstrated that various defects are present in the luminal epithelium of the uterus, the site of embryo implantation, ranging from a disorganized morphology of the columnar epithelium to the mis-expression of key transcription factors and hormone receptors. Moreover, I found a stark reduction in staining intensity of SOX9 in the uterine glands, a marker of epithelial progenitor cells that help replenish both the glandular and luminal epithelium. These data implicate the epithelial compartment as a key culprit for the reduced reproductive success of Atp11a-depleted females. Moreover, RNA-sequencing data from placental samples showed that Atp11a heterozygosity in the uterus-derived maternal part of the placenta even has a profound impact on the transcriptome of placental trophoblast. No parent-of-origin or sex specific effects were evident. Taken together, my findings indicate that Atp11a deficiency causes uterine dysfunction, specifically affecting the epithelium which is, importantly, the site of implantation. These perturbations are most profound at E4.0, which is the beginning of the narrow window of receptivity. As a result, this may lead to early implantation failure, thus explaining the sub-fertility phenotype that is observed even in heterozygous females. In milder cases where pregnancy is established, Atp11a function in uterine glandular epithelial cells may lead to an abnormal development of the placenta that, in turn, likely underlies the increased incidence of fetal congenital heart defects. My data will help to gain a better understanding of the causes of infertility as well as idiopathic congenital heart defects, with a long-term prospect of discovering targeted interventions to mitigate such developmental defects in pregnancy.Item Embargo Therapeutic Cuddling in Critically Ill Kids: THE ChICKs Studies(2024-12-13) Lee, Laurie A; Fiest, Kirsten; Doig, Christopher; Birnie, Kathryn; Letourneau, Nicole; Brockway, Merilee; Montgomery, CarmelPain, agitation, delirium, and analgosedation exposure, consequences of pediatric critical illness, are associated with negative sequelae including increased mortality, length of stay, anxiety, post-traumatic stress disorder, impaired neuro-cognitive development, and reduced health-related quality of life, among others. Therapeutic cuddling is a potential intervention to address pediatric intensive care unit (PICU) pain, agitation, delirium, and analgosedation exposure. It involves physical contact such as cuddling, snuggling, or hugging, between a caregiver and child. Despite evidence of benefit in critically ill neonates and hospitalized and healthy children, there is a paucity of literature in critically ill children. The aim of this dissertation was to understand the current state of PICU pain, agitation, and sedation, and inform the development and evaluation of therapeutic cuddling as a potential intervention to address these consequences of pediatric critical illness. To achieve this, theory and methodology from implementation science, knowledge translation, and epidemiology were employed. In the first manuscript, we conducted a systematic review of the prevalence of pain, agitation, and sedation in PICUs. We found variability in measurement, conceptualization, and reporting, with prevalence estimates of 45-82% for pain, 2-42% for agitation, and 9-62% for oversedation. The second manuscript is a secondary analysis of five point-prevalence studies on early acute rehabilitation (PARK-PICU studies) aimed at describing the prevalence of therapeutic cuddling and potential safety events in PICUs from North America, South America, Europe, and Australasia. Multilevel multivariable logistic regression identified patient-level variables associated with therapeutic cuddling. The prevalence of therapeutic cuddling was 37.4%, and the prevalence of potential safety events was 2.8%. The third manuscript is a mixed methods cross-sectional survey based on the Theoretical Domains Framework administered to healthcare professionals in Canadian PICUs aimed at understanding important barriers and facilitators to therapeutic cuddling. Identified barriers included beliefs about risk and safety, staffing, and lack of prioritization of therapeutic cuddling. The most important facilitator was family participation. The results of these three manuscripts address knowledge gaps related to the prevalence of pain, agitation, and sedation and the current state of therapeutic cuddling in critically ill children. Together these provide a foundation for the development and evaluation of therapeutic cuddling as a potential intervention to address PICU pain, agitation, and analgosedation exposure.Item Embargo Unraveling Stability: Using Dynamic Optimization to Understand Muscle Co-contraction Strategies While Walking on Uneven Surfaces(2024-12-17) Al-Shimari, Banin; Asmussen, Michael; Edwards, Brent; Manocha, Ranita; Manske, SarahAll humans are unstable in the mediolateral direction, and this instability is made worse when walking on uneven surfaces. To compensate for the instability, several strategies are utilized by the neuromuscular system, one being muscular co-contraction. An overwhelming majority of studies utilize EMG data to quantify co-contraction. However, muscle force and EMG are not always directly correlated. Furthermore, some studies have shown a lack of correlation between quasi-stiffness and muscle co-contraction using an EMG-only method. Therefore, the first objective of this thesis was to examine the muscular co-contraction strategies utilized on mediolaterally uneven surfaces and to compare muscle co contraction measures obtained from muscle moments using a dynamic optimization procedure (EMG-Track), with co-contraction measures derived from EMG data (EMG-Based). Our additional objective was to determine correlations between our EMG-Track method with subtalar joint quasi-stiffness using muscle pairs and muscle group moments (i.e., pronators and supinators of the subtalar joint). On average EMG-Track was better able to detect differences in co-contraction across mediolaterally uneven surfaces and speeds. Muscle group co-contraction was more consistently correlated with quasi-stiffness than muscle pair co-contraction. Furthermore, for muscle group co-contraction, we observed positive correlations before heel strike, and negative correlations following heel strike. These conclusions have important implications for other populations such as older adults, where co-contraction interpretations can alter therapeutic interventions.Item Embargo Maladaptive Trained Immunity: New Insight into the Pathogenesis of Inflammatory Bowel Disease(2026-12-17) Bartlett, Alexandria; Khan, Nargis; Yipp, Bryan; McKay, DerekInflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is increasing globally and in Canada. IBD causes debilitating symptoms and significant economic strain on healthcare systems. Despite treatment advances, no universally effective therapy exists. Chronic uncontrolled inflammation of the intestinal mucosa remains the hallmark of the disease. A dysregulated immune response, particularly involving innate immune cells like macrophages, plays a central role in the pathogenesis of IBD. However, the mechanisms driving inflammatory macrophage activation are poorly understood. Recent studies suggest that innate immune cells, such as macrophages, can develop "immunologic memory" after exposure to microbes or pathogen signals. This memory, termed trained immunity (TI), boosts the immune response to future threats. While TI is protective against infections, it may worsen and drive disease progression in chronic inflammation disorders like IBD. To address this knowledge gap, we investigated the role of the bone marrow (BM) hematopoietic stem cells (HSC) and progenitors as a source of trained inflammatory and damage-inducing macrophages in an experimental model of acute colitis. Chemical-induced colitis models showed an expansion of HSCs in the BM and their biasedness towards myelopoiesis, as evidenced by increased granulocyte-macrophage precursors (GMPs). Further, macrophages derived from these altered BM precursors (BMDMs) displayed a pro-inflammatory phenotype at the baseline, without ex vivo stimulation, compared to BMDMs from untreated mice. After a four-week rest period to allow inflammation to return to baseline, we found that BMDMs from rested mice were significantly more pro-inflammatory, as evidenced by increased IL-6, IL-1b, and TNF-a secretion and enhanced glycolytic metabolism. In vivo, these rested mice exhibited heightened inflammation upon secondary challenge with DSS or lipopolysaccharide (LPS). Additionally, chimeric mouse experiments revealed that the trained immune phenotype persisted in the BM compartment for up to 14 weeks post-initial DSS exposure. Our findings suggest that TI within the BM is a critical factor in the development and persistence within a model of colitis and, therefore, may be relevant to inflammation in IBD. This study provides new insight into the role of HSCs in IBD pathogenesis and highlights the BM as a potential target for future therapeutic intervention.Item Embargo Improving the Accuracy of Microwave Breast Imaging with Multipath Information(2024-12-12) Price, Sarah Nicole; Fear, Elise; Murari, Kartikeya; Yanushkevich, SvetlanaMicrowave imaging is a new medical imaging modality that is used to estimate and track changes in the dielectric properties (i.e. permittivity and conductivity) of tissue. It has shown promise in clinical applications like breast imaging as it is comfortable, safe and low-cost. However, due to the complexity of breast tissue a signal can travel more than one path through different tissue to get from a transmitter to a receiving antenna. This phenomenon is called multipath propagation. This work explores the potential of using multipath information to improve the permittivity estimates in microwave breast imaging. To extract the multipath information from the signals, the Hilbert-Huang Transform (HHT) was used. Data from simple simulations and phantoms with inclusions were analyzed to understand the signal shapes and patterns around an inclusion using the HHT. From these scans, multipath signals were detectable from their distinct characteristics in the time-frequency domain. From there, the signals from more complex scenarios were analysed to ensure the HHT was still effective in a realistic environment. With all these findings a signal processing algorithm was developed and applied to simulation, phantom and human data. When applied to the simulation and phantom data, the algorithm proved to be better at determining the size and permittivity of inclusions when compared to 2D projections of the models. Finally, when applied to patient data, the algorithm demonstrated strong potential to create images with improved clinical information and was useful in tracking changes in the breast tissue over time. Overall, this work demonstrated the necessity of incorporating multipath information into the signal processing algorithms of microwave imaging systems.Item Embargo Towards Robust Treatment Planning in Permanent Breast Seed Implant Brachytherapy(2024-12-13) Guebert, Alexandra; Quirk, Sarah; Meyer, Tyler; Beattie, Tara; Kirkby, Charles; Phan, TienIn permanent breast seed implant brachytherapy, radioactive palladium-103 seeds are implanted into the breast to treat early-stage breast cancer. Despite promising outcomes, adoption of this technique is limited by the resources and expertise required. Clinically, treatment planning requires manual optimization, and specialized skills. This thesis endeavours to improve this process by investigating the impact of delivery uncertainties on dosimetry and providing recommendations for constructing PBSI treatment plans that are robust to uncertainty. We developed a Monte Carlo algorithm to simulate PBSI delivery uncertainty. Using this simulator, we quantified the impact of random and systematic needle placement uncertainty for three idealized spherical clinical target volumes (CTVs) of varied volume. At clinically anticipated levels of uncertainty, introducing systematic errors less than 10 mm results in changes to target coverage of less than 5%, indicating that the planning target volume (PTV) margin is sufficient to account for systematic errors. Additionally, we present expressions that can be used to estimate the expected coverage based on a given institutional seed placement uncertainty. The simulation algorithm was used to produce 3000 simulated post-implant dose volume histograms for 109 patients who had received PBSI at one of two treatment centres. The simulated target coverage was used to quantify the robustness of each treatment plan. We analyzed correlations between planned PTV and ETV (evaluation target volume) DVH indices, and the simulated ETV coverage. The planned ETV D90% was found to exhibit the strongest correlations to median target coverage leading us to recommend that the ETV D90% be assessed at treatment planning. Correlations between geometric characteristics related to the implant volume, and simulated target coverage were assessed, finding that smaller ETV volumes exhibited more variability in simulated target coverage. A strong correlation was observed between the mean ETV-PTV margin and simulated target coverage. For 90% probability of delivering at least 90% of the prescription dose to at least 90% of the target volume, a planned ETV D90% of 124 Gy and a mean ETV-PTV margin of at least 6 mm are recommended.Item Embargo Anxious Echoes: Empire, Abolition, and the Romantic Consciousness(2024-12-05) Khalid, Muhammad Talal; Sigler, David; Sigler, David; Joseph, Clara; Wagner, MartinThis thesis interrogates the contradictions that permeate abolitionist rhetoric in the works of Coleridge, Blake and More, resisting any straightforward reading of moral progress or political emancipation. These writers do not merely reflect on the moral imperatives of their time; they challenge the very frameworks of reason, faith, and national identity upon which abolitionist discourse often relies. Abolition, as articulated in their works, emerges not as an unproblematic good but as an ambiguous, unsettling process fraught with contradictions. Coleridge’s oscillation between radical idealism and conservative restraint reveals a fundamental anxiety about the transformative power of liberation, suggesting that emancipation might unleash chaos rather than freedom. Blake's apocalyptic imagery destabilizes conventional conceptions of power, merging the roles of oppressor and oppressed, in a surreal vision where resistance and complicity are inextricably linked. More’s fusion of evangelical fervour with rational discourse exposes the hypocrisy within British national identity, destabilizing the ideological pillars that uphold both slavery and the concept of British moral superiority. Her rhetoric, while outwardly appealing to reason and faith, uncovers fissures within these concepts, pushing the limits of what rationality and virtue mean in a society complicit in slavery. Rather than resolving into a coherent moral triumph, abolitionist rhetoric in these texts unravels into unsettling discursive space, where the very concept of liberation becomes slippery and paradoxical. Freedom, in this context, morphs into a disruptive force that both upends and sustains the structures of oppression it seeks to dismantle. The idea of emancipation spirals into something volatile—a liberation where the line between the oppressor and the liberated dissolves into a tangled mess of complicity and subversion. The familiar language of moral and rational progress fractures under the weight of its contradictions, revealing a landscape where the boundaries of nation, identity, and virtue are blurred and violently disfigured. In this way, the thesis teaches us to see Romantic-era abolitionist rhetoric not as a singular, coherent force but as a destabilizing, multi-layered process that defies resolution.Item Embargo Reproductive Health Apps: The Benefits and Limitations to User Groups(2024-11-30) Kazakoff, Alissa; Doyle-Baker, Patricia Katherine; Benham, Jamie Laura; Holash, JohnThe global mHealth market is growing at an unprecedented rate and is projected to reach an estimated value of over $187 billion by 2033. Many of these apps focus on women’s health and tracking of the menstrual cycle. The reasons for menstrual cycle tracking are diverse and include increasing awareness of reproductive health and body functions, preparing for different menstruation cycle phases, fertility and family planning, identifying bleeding irregularities, and informing conversations with healthcare providers. Two areas of limited research include user retention and engagement based on known theories and models and whether app use impacts menstrual literacy. The purpose of this thesis was to a) investigate the current state of reproductive health tracking through a scoping review (ScR) and b) explore tracking methods and experiences, motivations for using reproductive health apps, and baseline menstrual literacy in a menstruating population through a cross-sectional survey. The ScR observed users were motivated to engage in reproductive health apps for education, contraception, and conception. Several benefits of app use were identified, like improved menstrual health literacy and helping users feel empowered and prepared for their cycles. However, a number of limitations in current reproductive health apps came to light that negatively impact user experience, such as a lack of regulation, variable quality, inaccurate predictions, and minimal diversity. A social media campaign was then employed to recruit menstruating individuals between the ages of 18-35 to complete an online survey that resulted in 1,359 participants. The participant’s mean age was 26 years (± 5; range 18-35) and 66.4% were app users and 33.6% were non-users. The feasibility of using the TAM to explain menstrual cycle app use was demonstrated. The constructs of perceived usefulness (PU) (<0.001), perceived ease of use (PEOU) (0.001), and trust (0.027) to predict app use were all significant. Confidence in knowledge about the menstrual cycle was negatively associated with app use (OR = 0.80, 95% CI: 0.65-0.98, p = 0.034). Additionally, having sufficient information about menses and symptoms was a significant predictor of app use (OR = 1.32, 95% CI: 1.02-1.71, p = 0.038). To our knowledge, this study is the first to combine the TAM with menstrual literacy and highlight key differences in menstrual literacy and characteristics between app users and nonusers. These results provide valuable insights into this under-researched area of women’s health by offering preliminary data on the factors influencing app use while also informing future research aimed at improving app engagement and menstrual education.Item Embargo Evaluation of Western Canadian Cow-calf Producers’ Attitudes Toward Cattle Handling, Perspectives on Cattle Welfare and Handling Training, and the Relationship Between Handling Training and Attitudes- A Mixed Method Approach(2024-11-28) Lutevele, Nathanael Herry; Ceballos, Maria Camila; Orsel, Karin; King, Meagan; Winder, CharlotteHandlers' attitudes towards cattle and handling influence their handling behaviors. Among the best ways to improve handler’ attitudes and behaviours and positively influence cattle welfare and productivity is through cognitive-behavioural training. This thesis aimed to evaluate the attitudes and perspectives of Western Canadian cow-calf handlers regarding cattle handling and its impact on welfare. It also explored their involvement in handling training, perspectives on training, motivations and barriers to attendance, and how training influenced attitudes. The first study (Chapter 2) interviewed fifteen cow-calf handlers from Alberta, Manitoba, and Saskatchewan to explore their views on cattle welfare, handling, and motivations to improve welfare. It also explored their perspectives on handling training and motivations and barriers to participation. Thematic analysis revealed seven themes: four related to cattle welfare, including their understanding of its complexity, the impact of handling on welfare, drivers for implementing welfare (public and consumer welfare concerns, sense of responsibility, and profitability); and three related to handling and training emphasizing the benefits of low-stress handling and the need for practical, farm-based training. The second study (Chapter 3) surveyed 118 cow-calf handlers to evaluate their handing attitudes, welfare assessment strategies, and participation in handling training. It also evaluated the influence of handling training on handlers’ attitudes. Respondents had a good attitude toward cattle and handling; they agreed on the importance of handling knowledge, patience, and proper handling techniques, and disagreed with aggressive handling practices. Key welfare assessment indicators were body condition score and general health. Economic returns and a sense of responsibility motivated welfare improvement. The relationship between handling training modality and handlers’ attitudes was inconsistent, with untrained respondents displaying positive and negative attitude indexes comparable to those of trained respondents. In conclusion, Western Canadian cow-calf handlers have a good understanding of animal welfare, hold positive attitudes toward handing, recognize the benefits of handing training, and are motivated to participate in such training. They prefer hands-on training that focuses on improving safety and addressing handling challenges. Training should emphasize the importance of patience and focus on modifying attitudes and behaviours. Furthermore, offering training locally at low cost can help increase handler participation.Item Embargo Implementation of an In-Shelter Drug Poisoning Management Program in Calgary, AB: A Qualitative Study of Staff Perspectives and Experiences(2024-11-22) Aryal, Sarina; Tang, Karen; Campbell, David; Milaney, Katrina; Sawatzky, DavidBackground: Substance use has disproportionately impacted people with lived experience of homelessness (PWLEH) and the organizations that support them. Emergency housing shelters continue to experience a significant increase in drug poisoning events, while having limited medical training to appropriately respond to them. In-shelter drug poisoning management programs have emerged as potential solution to this issue, by having on-site medically trained healthcare professionals present to provide emergent medical care for these events. However, limited information exists on the implementation of these program in shelters. Objective: To explore the implementation of the newly implemented in-shelter drug poisoning management program, the Riverfront Dynamic Overdose Response Capacity (DORC) program, through the perspectives and experiences of staff involved in its development and delivery. Methods: A qualitative descriptive study using an ethnographic approach was used for this study. Participants were staff at the Calgary Drop-In Centre including dedicated program staff, program planners, and general shelter staff. Data collection involved interviews and field notes which were analyzed using a thematic analysis approach. Data were coded inductively by two independent coders. These codes were combined to develop themes which were reviewed and refined both individually and within the larger research group. Findings: Twenty staff members involved in the development and delivery of the program participated in 17 interviews and 6 observations. The Riverfront DORC program was perceived to be beneficial in responding to drug poisoning events and other emergent medical needs because of the onsite emergency medical team. However, participants perceived that the program led Riverfront DORC program clients to experience isolation from social or recreational opportunities and other supports found in other areas of the building. Lastly, participants commented on the challenges with the implementation of the program due to micro-and-macro factors such as limited communication between program planners and frontline staff, competing spatial and staffing needs, and conflicting policies around drug use in the building. Conclusion: The findings of this study describe the key aspects of implementation that affected the optimal delivery of in-shelter drug poisoning management programs. Shelters intending to implement similar programs must take into considerations the micro and macro factors that may act as a barrier for successful implementation.Item Embargo Molecular Targeting of High-Risk Pediatric Leukemia: Identification of Targets and Biological Implications for Therapy(2024-11-26) Sharma, Ritul; Narendran, Aru; Childs, Sarah; Neri, Paola; Riabowol, KarlAcute leukemias with KMT2A (mixed-lineage leukemia or MLL) rearrangements are associated with poor prognosis and high relapse rates, particularly in infant and pediatric populations. The outcomes for patients with KMT2A-rearranged (KMT2A-r) leukemia remain suboptimal, underscoring the urgent need for novel, targeted therapeutic approaches. This thesis focuses on disrupting key molecular interactions within the KMT2A fusion protein complex that drives leukemogenesis while characterizing novel preclinical models to facilitate targeted drug discovery. By utilizing established cell line models, cell-based assays and drug combination studies, this study demonstrated the therapeutic potential of inhibiting the interaction between KMT2A fusion protein and a transcriptional kinase, CDK9. In addition, the study demonstrates that targeting CDK9 can decrease venetoclax and steroid resistance in KMT2A-r leukemia. Furthermore, this thesis investigates the biological implications of treatment induced differentiation, with a focus on identifying therapeutic strategies to treat KMT2A-r leukemias. Our results demonstrate that menin inhibitor induced differentiation in KMT2A-r cells carries a distinct inflammatory profile with elevated secretion of HMGB1 and IL-8. These cytokines are associated with promoting migratory responses. In addition, our findings showed a synergistic interaction between menin inhibition and corticosteroids, which is the first line treatment for patients with differentiation syndrome. In parallel, the study evaluates the efficacy of the ETS inhibitor TK216, targeting SPI1 overexpression in pediatric AML and B-ALL leukemias, with the goal of uncovering its therapeutic potential in high-risk pediatric leukemia. The research presented herein offers a framework for developing feasible novel therapeutic strategies for KMT2A-r leukemias, building on a foundation of preclinical modeling and mechanistic insights that may inform future clinical interventions.Item Embargo INVESTIGATING HOW HOST-MICROBE INTERACTIONS INFLUENCE THE PROGRESSION OF TYPE 1 DIABETES(2024-11-25) Abbott, Spencer; McCoy, Kathleen; McDonald, Braedon; Reimer De Bruyn, RayleneThe global prevalence of allergies and autoimmune diseases, such as type 1 diabetes (T1D), has increased significantly over the past 50 years. Epidemiological evidence points to the gut microbiome as being one of the strongest drivers of increased disease incidence. Recent research has described associations between microbiome signatures and disease incidence through the induction of immune responses, however the underlying mechanisms by which the gut microbiome influences T1D progression remains largely unknown. Using gnotobiotic mouse models, this thesis aims to explore the role of host-microbe interactions in T1D development. One way in which the microbiome can modulate autoimmunity is through molecular mimicry. Previous work in the lab identified BacINT36-44, which will be referred to as Integrase, expressed by a commensal strain of Bacteroides as a bonafide molecular mimic to the islet autoantigen, IGRP206-214. Here, we further explored how Integrase expression by bacterial species in the gut influences antigen-specific immune responses in the T1D susceptible non-obese diabetic mouse model. Although microbial Integrase expression did not influence disease incidence in monocolonized mice, antigen-specific T cells were found to significantly modulate microbiome composition in specific-pathogen free mice. Additional analysis suggested that these changes were specific to Integrase expressing species. Integrase expression within the commensal gut microbiome also induced the expansion of antigen specific T cells both locally, within the gastrointestinal associated lymphoid tissue, and systemically, in the spleen. In addition, we sought to further investigate how the transfer of maternal antibodies influences T1D development in the offspring. It is widely accepted that the transfer of maternal antibodies during breast feeding shapes immune responses in the offspring. Thus, we explored how the transfer of maternal antibodies influences immune maturation in response to the microbiome. Together, this thesis reveals how the gut microbiome influences T1D, how molecular mimicry between gut microbes and self-antigens can shape antigen-specific immune responses, and the pathogenic role of maternal antibodies in non-obese diabetic mice.Item Embargo Data-driven needle puncture detection for the delivery of urgent medical care in space(2024-11-21) L'Orsa, Rachael; Westwick, David T.; Sutherland, Garnette R.; Goldsmith, Peter B.; Kuchenbecker, Katherine J.; Sun, Qiao; Majewicz Fey, AnnNeedle thoracostomy (NT) is a surgical procedure that treats one of the most preventable causes of trauma-related death: dangerous accumulations of air between the chest wall and the lungs. However, needle-tip overshoot of the target space can result in the inadvertent puncture of critical structures like the heart. This type of complication is fatal without urgent surgical care, which is not available in resource-poor environments like space. Since NT is done blind, operators rely on tool sensations to identify when the needle has reached its target. Needle instrumentation could enable puncture notifications to help operators limit tool-tip overshoot, but such a solution requires reliable puncture detection from manual (i.e., variable-velocity) needle insertion data streams. Data-driven puncture-detection (DDPD) algorithms are appropriate for this application, but their performance has historically been unacceptably low for use in safety-critical applications. This work contributes towards the development of an intelligent device for manual NT assistance by proposing two novel DDPD algorithms. Three data sets are collected that provide needle forces and displacements acquired during insertions into ex vivo porcine tissue analogs for the human chest, and factors affecting DDPD algorithm performance are analyzed in these data. Puncture event features are examined for each sensor, and the suitability of both accelerometer measurements and diffuse reflectance measurements are evaluated within the context of NT. Finally, DDPD ensembles are proposed that yield a 5.1-fold improvement in precision as compared to the traditional force-only DDPD approach. These results lay a foundation for improving the urgent delivery of percutaneous procedures in space and other resource-poor settings.Item Embargo Essays on Corporate Strategic Adaptation(2024-11-22) Simoes, Sean Cyril Neil; Petricevic, Olga; Verbeke, Alain; Jones, Vernon; Kano, Liena; Moran, Pablo; Bu, MaoliangThe essays in this dissertation utilize transaction cost theory (TCT) and complementary frameworks, namely the resource-based view and dynamic capabilities to explore how firms adapt to their business environment. In Chapter 1, I challenge the prevailing notion that multinational enterprises (MNEs) must adapt to conditions in ‘Bottom of the Pyramid’ (BOP) markets by creating informal institutions. Rather, using the case of India’s digital and financial initiatives, I argue that MNEs should work with governments to develop formal institutions, and leverage these institutions to accurately assess the reliability of BOP customers. In Chapter 2, I explore how MNEs have adapted their international strategies in response to vulnerability created by macro-level decoupling between the U.S. and China. Utilizing elements of the Profiting from Innovation (PFI) framework, I find that the framework helps explain the MNE’s position in the China market. This position along with elements of the PFI framework in turn helps explain firm responses. The remaining chapters explore cases of how firms have adapted in different ways. In Chapter 3, I discuss how Volkswagen failed to adapt its products to the U.S. market which put in place stringent emissions standards, with bounded reliability coupled with a disconnect between headquarters and U.S. personnel, and a lack of controls, contributing to a sustainability crisis. In Chapter 4, I explore how MNE Cummins adapted its global diversity and inclusion strategy and mandated the use of English as a common language in its Indian subsidiaries and joint ventures, including on the shop floor, with benefits for individuals as well as the Indian entities. And in Chapter 5, I explore how Corning, another large MNE, built and leveraged its resources and capabilities to adapt to changing markets, by launching and growing new product families. Using a sample of 23 product families, I find two combinations of causal conditions that help explain this capability to reconfigure Corning’s business. In summary, this dissertation utilizes TCT thinking and associated frameworks to contribute to an enhanced understanding of strategic adaptation by large firms.Item Embargo Respiratory Patterns Recognition and Cough Detection Using Signals from Capacitive Touchpads in Smartphones Commonly Worn in Shirt Pockets(2024-11-14) Gupta, Vedant; Vyas, Rushi; Pandey, Richa; Ginde, GouriThe timely identification of respiratory distress, often indicated by coughs, has become important for public health readiness and response to pandemics like COVID-19, SARS, and Influenza. Traditional methods of monitoring respiratory health, including hospitalization rates, doctor reports, and wearable sensors, have limitations in real-time reporting, extra costs, etc. With smartphones used by 66 out of every 100 persons, they are useful tools in various public health initiatives. Our project studies the use of capacitive touchpad sensors present in smartphones for monitoring respiratory patterns and distress. Specifically, this study examines how different touchpad scan patterns, orientations, and electrode spacings affect respiratory monitoring by detecting capacitive fluctuations. Our measurements with a commercial 5 by 6 element capacitive touchpad sensor array (0.8 cm pitch) worn on the chest or pocket registered fluctuations over the baseline due to cough-related chest surface movements. Furthermore, when the touchpad is placed on the chest or pocket, this method can also detect breathing rate by registering changes in capacitance over the baseline. Through this approach, we were able to measure very low capacitance values (0–100 pF), which are typically challenging to detect with conventional sensors. We also explored how varying electrode spacing impacts the fringing fields in the capacitive touchpad, as different configurations alter the depth and sensitivity of the capacitive field. This investigation allowed us to assess whether specific spacing setups could capture respiratory patterns deeper within body tissue, providing a non-invasive approach to respiratory health monitoring. This pioneering prototype demonstrates the potential for capacitive sensing to offer real-time, accessible respiratory monitoring using widely available smartphone technology.Item Embargo Distributed Deep Learning Methods for Medical Imaging Analysis(2024-10-29) Souza De Andrade, Raissa Cristina; Forkert, Nils Daniel; Wilms, Matthias; Pike, G. Bruce; Barker, KenRecent advancements in deep learning have equipped healthcare professionals with valuable tools to support clinical decision-making and reduce workloads. However, many medical centers lack sufficient datasets to train deep learning models, especially for rare diseases or centers in remote or underserved areas. Although collecting and curating datasets from multiple centers into a centralized repository is commonly employed to solve this problem, this approach is often infeasible due to its costs and privacy regulations that prohibit data sharing. Consequently, many centers and populations will not benefit from cutting-edge artificial intelligence. The distributed deep learning framework proposed in this work addresses these challenges by training accurate models while patient data remains securely stored within its center. Thus, privacy concerns are addressed while collaborative multi-center training is facilitated. A key innovation of this work is the development and evaluation of the travelling model, a method well-suited for scenarios where individual centers have very limited data availability. The travelling model is evaluated across various scenarios, including extreme cases where centers contribute only a single medical image, and is applied to critical medical imaging tasks such as brain age prediction, disease classification, and tumour segmentation. In general, the travelling model effectively increases the overall dataset quantity and diversity without compromising patient data privacy. However, solutions for the inherent acquisition shift biases caused by variations in equipment and protocols across centers and decentralized data quality control are needed to leverage its full potential. Therefore, this work also developed and integrated two novel methods into the travelling model approach, a data harmonization for reducing acquisition shift biases and automated decentralized data quality control. The results of this work demonstrate that the travelling model framework achieved performances comparable to models trained on a centralized repository across all evaluated tasks. Moreover, it performed better than the commonly used federated learning in cases where centers contributed fewer than five datasets. Additionally, the proposed data harmonization method reduced scanner variability by 23%, improving disease classification accuracy by 4%. Finally, the automated decentralized quality control method effectively identified incorrect and low-quality datasets, enabling more robust and reliable model performance.Item Embargo Bicycling Injuries in Children: The Role of the Built Environment(2024-10-28) Aucoin, Janet; Hagel, Brent; Nettel-Aguirre, Alberto; Winters, Meghan; McCormack, GavinBackground: Bicycling has many health benefits for children but can result in injuries, some severe. Additionally, children’s perceptions of injury risk decrease participation. The built environment is associated with the risk of bicycling injury in adults, yet less is known about risks for children who have different bicycling behaviours and locations than adults. This dissertation improves understanding of child bicyclist injury risk factors and perceptions in Canada, with an emphasis on the role of the built environment. Methods: We recruited 333 injured child bicyclists (ages 5-17) who presented to pediatric emergency departments in Vancouver, Calgary, and Toronto from May 2018 - October 2021. Using data from participant interviews and in-person site audits of injury/control locations from the injured child’s route, Chapter 3 used a case-crossover study design to examine associations between built environment characteristics and child bicyclist injuries. Chapter 4 used data from the case-crossover study to explore injury circumstances and examine risk factors associated with severe child bicyclist injuries. In 2021, 40 participants also completed a qualitative interview to explore injured child bicyclists’ perceptions of risk factors and safety (Chapter 5). Results: The results in Chapter 3 provided evidence that unpaved off road locations, presence of debris, poor surface quality, surface grade, and construction were risk factors for child bicyclist injuries. In Chapter 4, motor vehicle involvement and intersections were associated with higher odds of severe injury in child bicyclists. In Chapter 5, child bicyclists shared that some of the factors that contribute to perceptions of safety included sharing spaces with motor vehicles, road design, debris, surface quality, and surface grade. Conclusions: This study adds to evidence suggesting built environment supports are important for increasing bicycling safety for Canadian children. There is a critical need to provide child bicyclists with safe spaces where they are physically separated from motor vehicles and to ensure that routes used by child bicyclists are properly maintained.