Medicine and Health Sciences Commons^™

Identification Of Dna Methylation Episignatures For Classification And Phenotype/Genotype Correlation In Mendelian Neurodevelopmental Disorders, John Reilly

Electronic Thesis and Dissertation Repository

ABSTRACT: Diagnosis for neurodevelopmental disorders poses numerous challenges, related to the lack of specific findings and limited understanding of clinical impact of the majority of genetic variation. Epigenomics mechanisms involve chemical modifications in DNA that involve a range of cellular mechanisms. DNA methylation is an epigenetic mechanism involving addition and removal of methyl groups to cytosine residues. These methylation signals form episignatures; patterns of methylation that can be used as biomarkers capable of differentiating neurodevelopmental disorders. EpiSigns have enabled molecular diagnosis of a number of genetic conditions, classification of variants of unknown significance, and provided insights into the pathophysiology of …

Host Organizations' Perspectives Of Partnered Global Study-Abroad Programs, Jessica C. Pop

Electronic Thesis and Dissertation Repository

Background: The relationships between sending and host partners in nursing study-abroad programs are crucial to the success and sustainability of these programs. Yet, there has been a paucity of research focused on the global partnerships between sending and host organizations. Most research about study-abroad programs has primarily focused on Global North sending organizations’ perspectives on the educational, social, and career benefits to Global North students with few studies highlighting the perspectives of host organizations from the Global South.

Aim: To explore Global South host organizations’ perspectives about global partnered nursing study-abroad programs.

Research Design: This research study was guided by …

Head’S Up! Examining The Relationship Between Field Of View And Head Position In Ice Hockey Players, Kristine E. Walker

Electronic Thesis and Dissertation Repository

Ice hockey is a dynamic, fast-paced game where players need to be aware of multiple factors, devoting appropriate attention to varying salient aspects to enhance performance. The term “keep your head up” is ubiquitous encouragement because if players do not, their visual field (what they can see) is compromised, performance (what they can do) decreases, and likelihood of injury increases. Head-down behaviour is problematic and is observed at all skill levels. Head position (HP) behaviour has not been quantified objectively in any sport. Through collaboration with an NHL player development coach, their practice-based knowledge and tacit experience informed the direction …

Biomechanical Loading As A Driver Of Synovial Neovascularization And Microvascular Dysfunction In Knee Osteoarthritis, Mckenzie Carter

Electronic Thesis and Dissertation Repository

Synovial inflammation and biomechanical loading are independent risk factors for knee osteoarthritis (OA). However, the relationship between inflammatory and biomechanical factors, specifically if increased biomechanical loading causes synovial inflammation in OA (mechanoinflammation), is not well understood. The purpose of this thesis was to explore the associations of knee load during walking with features of synovial inflammation in knee OA. The knee adduction moment magnitude was associated with increased synovial vascularization and perivascular edema. Synovial fluid from OA patients with high knee adduction moments promoted endothelial cell migration in vitro. Late-stage knee OA synovial fluid caused endothelial monolayer hyperpermeability in …

The Effect Of Modifications To Intermaxillary Orthodontic Elastics On Force Levels And Degradation Over Time, Steven Dent

Electronic Thesis and Dissertation Repository

Introduction: Orthodontic elastics are frequently used in orthodontic treatment but there is little research into how to modify their prescription to improve their performance. The aim of this study was to evaluate potential wear modifications to a standard Class II intermaxillary elastic prescription on force levels and force degradation over time.

Methods: For this in vitro study, Ormco (OR) and American Orthodontic (AO) latex elastics had five modifications made to a standard 1/4”/4.5oz control elastic (Group 1). These included an increase of force level by one unit to 6 or 6.5oz (Group 2); a decrease in lumen size to 3/16” …

"Pain Is What The Patient Says It Is": A Secondary Analysis Of Nurses’ Reflections On The Term Pain Catastrophizing, Riana Longo

Electronic Thesis and Dissertation Repository

Background: Pain catastrophizing is a widely used concept; however, many have argued that it delegitimizes and decontextualizes patients’ pain experiences. Previous studies identified that patients and clinicians think the term is stigmatizing; however, nurses’ perceptions are underrepresented. Nurses offer a unique perspective that is critical to explore to foster positive change and improve patient outcomes. Objectives: This thesis aims to summarize the current literature on pain catastrophizing perspectives from clinicians and patients, analyze nurses’ perspectives, and uncover any underlying issues with the term itself. Methods: This thesis consisted of a two-stage design. The first study is a scoping review that …

Does The Way We Pay Primary Care Providers Influence Emergency Department Use During After-Hours?, Michael Hong

Electronic Thesis and Dissertation Repository

In the early 2000s, Ontario introduced extensive primary care reforms to increase around-the-clock access to comprehensive primary care in response to inadequate access to primary care, including the way Ontario primary care physicians were paid. This thesis investigates the extent to which changes in physician payment could affect emergency department visits. First, a review evaluating the impact of access to primary care on primary care and emergency department utilization was conducted. Secondly, the impact of Ontario’s after-hours premium on emergency department visits was investigated, first within Ontario, then compared to four control provinces. Finally, rates of primary care services and …

The Hepatic Happening: Confronting Waitlist Death In Liver Transplantation, Anita M. Slominska

Electronic Thesis and Dissertation Repository

My dissertation is narrative-based interdisciplinary investigation of waitlist death that focuses on my sister’s wait for a liver transplant and her death 18 years ago. While the period of waiting for a transplant is accompanied by great life-and-death uncertainty, the possibility of dying is often ignored and overshadowed by an emphasis on redemptive narratives and a “second chance at life.” From the beginning, organ transplantation was a field dominated by hope and the fantasy that biomedicine can overcome illness and mortality; as such it is narrowly understood through a lens of progress where loss, failure and death are given little …

The Effect Of Interprofessional Conflict Resolution On Interprofessional Collaborative Practice Among Health Care Provider Teams In Hospitals, Sibylle Ugirase

Electronic Thesis and Dissertation Repository

Client needs and their complexities have increased, challenging multiple professionals to work together within health systems to reach better patient outcomes. Addressing this challenge requires interprofessional collaboration, which, while essential, may also breed conflict given that individuals from various health care disciplines each bring their unique perspectives into teamwork. While some degree of disagreement is expected, team members must be able to resolve conflicts to ensure effective patient care. However, limited information was available that described and clearly defined interprofessional conflict resolution as a concept.

The aim of this study was threefold. This study began with a concept analysis of …

Navigating, Negotiating, And Narrating: Re-Envisioning Patient-Centered Chronic Illness Care, Wilma J. Koopman

Electronic Thesis and Dissertation Repository

Patient-centered care (PCC) is ubiquitous in how we think about patient-practitioner encounters. But such a taken-for granted stance may unknowingly obscure how conversations actually unfold in real life. The purpose of this work is to unravel the disconnect between how patient-centered care is talked about and how it is implemented in the real world. The overarching research question that framed this study was: What are the influences that shape the unfolding of the conversations that occur at chronic illness health encounters and how does this unfolding influence the learning and execution of PCC? The aim of this research was …

Cost-Effective Non-Destructive Testing Of Biomedical Components Fabricated Using Additive Manufacturing, Santiago Fabian Cobos

Electronic Thesis and Dissertation Repository

Biocompatible titanium-alloys can be used to fabricate patient-specific medical components using additive manufacturing (AM). These novel components have the potential to improve clinical outcomes in various medical scenarios. However, AM introduces stability and repeatability concerns, which are potential roadblocks for its widespread use in the medical sector. Micro-CT imaging for non-destructive testing (NDT) is an effective solution for post-manufacturing quality control of these components. Unfortunately, current micro-CT NDT scanners require expensive infrastructure and hardware, which translates into prohibitively expensive routine NDT. Furthermore, the limited dynamic-range of these scanners can cause severe image artifacts that may compromise the diagnostic value of …

Cost-Effectiveness Analysis Of Tpmt Genotype-Guided Azathioprine Treatment Compared To Standard Treatment For Patients With Moderate/Severe Ulcerative Colitis, Ali Unsal

Electronic Thesis and Dissertation Repository

This study assessed cost-effectiveness of pharmacogenomics (PGx)-based azathioprine (AZA) compared to standard AZA therapy for ulcerative colitis (UC) patients in Canada. A patient-level Microsimulation model was developed to compare the lifetime costs and quality-adjusted life years (QALYs) gained by a hypothetical cohort of UC patients with age and sex characteristics. The parameters used in the model were derived from the published literature and costs from the Ontario Schedules of Payments and published sources. The results were summarized in terms of the incremental cost-effectiveness ratio (ICER). Compared to standard AZA, PGx-based AZA care was the dominant strategy with 0.17 incremental QALYs …

Examining The Impact Of Financial Incentive Removal On Physical Activity: A Quasi-Experimental Study Of 584,760 Mobile Health Application Users, Sean Kevin Spilsbury

Electronic Thesis and Dissertation Repository

BACKGROUND: Government interest in using financial incentives (FIs) to stimulate physical activity (PA) is increasing. The cost of longer-term incentive interventions may be prohibitive, however. PURPOSE: To examine the impact of FI withdrawal on PA. METHODS: A 25-week retrospective pre-post quasi-experimental study was conducted with users of a FI-based mHealth app. Users from three Canadian provinces were included. Daily FI were removed in Ontario (ON; intervention) but not British Columbia (BC) and Newfoundland and Labrador (NL; control). Simple linear regression models were used to examine weekly mean daily step count after FI withdrawal. RESULTS: The total sample included 584,760 users …

Searching For The 'Good' In Physiotherapist Practice: Toward An Ethic Of Care, Michelle J. Kleiner

Electronic Thesis and Dissertation Repository

The qualities and practices of a ‘good’ physiotherapist have not been systematically reviewed nor have practitioners’ perspectives been empirically investigated. Understanding what constitutes a ‘good’ physiotherapist has potentially profound implications that may inform professional priorities including education curricula, professional practices, competency profiles, and patient interactions. The research purpose was to examine perceptions of what constitutes a ‘good’ physiotherapist. This dissertation includes four integrated manuscripts. The first is an integrative review to critically examine how physiotherapists and patients describe the qualities of a ‘good’ MSK physiotherapist as depicted in peer-reviewed literature. Six qualities were identified as: responsive, ethical, communicative, caring, competent, …

The Natural History Of Modic Changes - A 5- And 15-Year Follow-Up Study, Parnian Saremi

Electronic Thesis and Dissertation Repository

Modic changes (MCs), defined as bone marrow lesions adjacent to the vertebral endplate seen on MRI, have been associated with back pain. There are different types of MCs, with different histopathological correlates. This community-based study sample comprised 110 men from the Twin Spine Study, with baseline, 5-year, and 15-year follow-up MRIs. Following training and reliability testing, 1320 endplates (T12-S1) were evaluated for MC presence, type, and dimensions at each time point. Results demonstrated that Type 2 Modic Changes (MC2) were the most common type, with approximately half located at the two lowest disc levels. However, Type 1 Modic Changes (MC1) …

Organizational Implementation Of Trauma And Violence Informed Care, Tanaz Javan

Electronic Thesis and Dissertation Repository

For the past several decades, social and health services have increased their efforts to enhance service delivery and close the ‘science-to-service’ (or ‘evidence-to-practice’) gap by implementing effective interventions. At the same time, there has been growing recognition of the prevalence of trauma and violence in the lives of those served and those providing care and the impact of these experiences on service needs and interactions. This study explored the implementation of trauma- and violence-informed care (TVIC), a complex intervention focused on providing safety and choice for service users in the context of their life experiences and conditions, exploring factors that …

Fate Of Registered Studies From London, Ontario, Alex Bi

Electronic Thesis and Dissertation Repository

Introduction: Lack of study publication leads to bias in the scientific literature. It is important to better understand this phenomenon and find methods for mitigation.

Research Question: How many clinical trials registered on ClinicalTrials.gov in London, Ontario are started, completed, and published?

Methods: Data from all studies in the ClinicalTrials.gov registry associated with London, Ontario were collected, from registry conception until the end of 2017. We determined whether these registered studies were published by July 2020 and whether their first publication included their planned primary outcome at all. Main factors associated with non-publication were assessed using multivariable log-binomial regression. Multivariable …

Role Of The Epithelial-To-Mesenchymal Transition (Emt) On Circulating Tumor Cell (Ctc) And Metastasis Biology In Prostate Cancer, Jenna M. Kitz

Electronic Thesis and Dissertation Repository

Prostate cancer is the second leading cause of cancer-related deaths in American men. Most of these deaths occur as the result of metastasis, which is associated with an epithelial-to-mesenchymal transition (EMT). EMT leads to greater migratory/invasive capacity and resistance to therapy. During metastasis and associated EMT, cancer cells shed from the primary tumor and disseminate throughout the body as circulating tumor cells (CTCs) in the bloodstream. CTCs have been correlated with increased metastatic disease, reduced survival, and therapy response/resistance. Assessing CTCs presents an opportunity to study cancer progression/treatment effectiveness from a blood test. However, outstanding questions regarding CTCs and EMT …

Emerging Adult Perspectives On Marijuana Usage And Social Isolation During Covid-19, Avery Kiana Wong

Electronic Thesis and Dissertation Repository

Individuals struggling with emotional distress are twice as likely to use marijuana routinely. Young adults, ages 18 to 24, continue to be at increased risk for accidents, injuries, and poor cognitive functioning when using cannabis regularly, compared to those 24 and older. In addition, studies have shown that increased social isolation further increases the risk of marijuana use in young adults. Previous literature also demonstrated that marijuana is currently being used as a method of treatment for emotional distress. Much of the research conducted to date has focused on the collection of checklist data that has looked at the presence …

Targeting Prostate Cancer Through High Dose Rate Brachytherapy, Christopher Smith

Electronic Thesis and Dissertation Repository

While prostate cancer is not typically an aggressive disease, it can be lethal for some patients. Treatment of the disease has proven to be effective; however, when the disease recurs locally it does so most commonly at the site of the dominant intraprostatic lesion (DIL). An effective treatment method for prostate cancer is high dose rate brachytherapy (HDR-BT). This is a radiation therapy where a radioactive seed is interstitially inserted into the patient to deliver the radiation dose. It was the goal of this work to utilize preprocedural imaging and pathological data from radical prostatectomy specimens to investigate methods to …

Visualization And Manual Segmentation Of The Post-Mortem Human Amygdala Subnuclei Using Ultra High Field Magnetic Resonance Imaging, Sara M. Pac

Electronic Thesis and Dissertation Repository

The human amygdala is composed of 13 functionally and anatomically distinct subnuclei. Because most nuclei are difficult to distinguish at the microanatomical level, they are also challenging to discern macroscopically. In low field strength magnetic resonance imaging (MRI) studies, the amygdala can be identified only in its entirety. Higher resolution scans can be acquired by employing ultra-high field strength MRI acquisition techniques. We present a step-by-step guide for the manual segmentation of the amygdala subnuclei at ultra-high field 9.4T MRI. Post-mortem human brain specimen amygdala prosections fit for the 9.4T MRI bore allowed for the collection of high resolution T2-weighted …

Implementing Health Impact Assessment As A Required Component Of Government Policymaking: A Multi-Level Exploration Of The Determinants Of Healthy Public Policy, Stephanie A. Simpson

Electronic Thesis and Dissertation Repository

It is widely understood that the public policies of ‘non-health’ government sectors have greater impacts on population health than those of the traditional healthcare realm. Health Impact Assessment (HIA) is a decision support tool that identifies and promotes the health benefits of policies while also mitigating their unintended negative consequences. Despite numerous calls to do so, the Ontario government has yet to implement HIA as a required component of policy development. This dissertation therefore sought to identify the contexts and factors that may both enable and impede HIA use at the sub-national (i.e., provincial, territorial, or state) government level.

The …

Exploring The Effects Of Spinal Cord Stimulation For Freezing Of Gait In Parkinsonian Patients, Olivia Samotus

Electronic Thesis and Dissertation Repository

Dopaminergic replacement therapies (e.g. levodopa) provide limited to no response for axial motor symptoms including gait dysfunction and freezing of gait (FOG) in Parkinson’s disease (PD) and Richardson’s syndrome progressive supranuclear palsy (PSP-RS) patients. Dopaminergic-resistant FOG may be a sensorimotor processing issue that does not involve basal ganglia (nigrostriatal) impairment. Recent studies suggest that spinal cord stimulation (SCS) has positive yet variable effects for dopaminergic-resistant gait and FOG in parkinsonian patients. Further studies investigating the mechanism of SCS, optimal stimulation parameters, and longevity of effects for alleviating FOG are warranted. The hypothesis of the research described in this thesis is …

Connexin 43 Contributes To Phenotypic Variability Of The Mouse Skull, Elizabeth Jewlal

Electronic Thesis and Dissertation Repository

The purpose of this study was to determine whether connexin 43 (Cx43) contributes to craniofacial phenotypic variability. Skull shape and variation were compared within and among two heterozygous mutant mouse models (G60S/+ and I130T/+) that exhibit different levels of Cx43 channel function when compared to their wildtype counterparts (~80% and ~50% reduction in function, respectively). Results indicated mutants have significant differences in skull shape compared to wildtype littermates. Similar patterns of shape difference were found in both mutants. Increased skull shape variation and a disruption in the covariation of skull structures were observed in G60S/+ mutants only. These results show …

Development Of An In Vitro Model Of Ischemia Reperfusion Injury In Kidney Transplantation, Ashley Jackson

Electronic Thesis and Dissertation Repository

Kidney transplantation remains the optimal treatment option for patients with end-stage renal disease. We aim to improve organ preservation during transplantation by reducing damage from ischemia reperfusion injury (IRI) using existing clinically approved drugs. In this study, we developed and characterized an in vitro model that mimics the conditions of IRI in kidney transplant as a tool to screen and study the therapeutic effect of drugs in the context of IRI. We recapitulated several key outcomes in IRI in our model, including the induction of hypoxia, cell death, increased expression of damage markers (NGAL, HMBG-1) and pro-inflammatory cytokines in a …

Torque Expression Of Active And Passive Self-Ligating Orthodontic Brackets With Different Stainless Steel Wire Sizes, Jennifer L. Boogaards

Electronic Thesis and Dissertation Repository

This investigation aimed to compare engagement angles and torquing moments generated by stainless steel (SS) wires in three active self-ligating (ASL), one passive self-ligating (PSL), and a conventional twin orthodontic bracket system control. Brackets were tested in simulations of buccal and palatal root torque using four sizes of SS wires (16x22, 17x25, 19x25, 20x20 mil). A custom 3D printed testing apparatus was developed to measure torque. After initial engagement within bracket slots, torquing moments increased with progressive rotation of brackets around wires. In general, the PSL and conventionally ligated systems generated significantly larger torquing moments than ASL systems, especially with …

Delineation Of Ascending Aortic Medial Degeneration Using Diffusion Tensor Imaging, Justin A. Ching-Johnson

Electronic Thesis and Dissertation Repository

Thoracic aortic aneurysms (TAAs) are a life-threatening dilation of the thoracic aorta that can lead to catastrophic dissection or rupture. In TAAs, the structure of the aortic wall is perturbed. Current imaging approaches assess lumen dimensions but lack the ability to delineate aortic wall architecture, a key determinant of aortic integrity. Diffusion tensor imaging (DTI) is an MRI modality which can reveal tissue microstructure through diffusion characteristics. In this thesis I investigated the potential for DTI to evaluate TAA architecture. A porcine model of aortic wall degeneration was developed, and DTI scans were performed on healthy and degenerated porcine ascending …

Women’S Experiences Of Accessing Breastfeeding And Perinatal Health Support In The Context Of Intimate Partner Violence: An Interpretive Description Study, Samantha Larose

Electronic Thesis and Dissertation Repository

Background: Women experiencing intimate partner violence are at a heightened risk of negative perinatal and breastfeeding outcomes. This study explored the experiences of accessing breastfeeding support for women who endorse a history of intimate partner violence. A study of five in-depth semi-structured interviews were completed at 12-weeks postpartum with breastfeeding mothers with a history of intimate partner violence. Findings: Women expressed difficulties in accessing a healthcare provider who had specialized skill in breastfeeding support. Trust in their healthcare provider, built through displays of compassion and competence, was important to mitigate obstacles experienced during care access for this population. Trauma-and-violence-informed care …

The Genetics Of Pain: An Exploration Of Gene-By-Environment Interactions And Their Effects On Pain, Mohamad F. Fakhereddin

Electronic Thesis and Dissertation Repository

The findings presented in this dissertation are part of the bigger SYMBIOME project which aims to use the biopsychosocial model of pain to develop a prognostic clinical phenotype for people that experience musculoskeletal (MSK) trauma. Chapter 2 presents an exploratory analysis to assess the relationships between genetic polymorphisms and pain severity and interference. Early childhood trauma was also explored as a moderator between genetic polymorphisms and pain outcomes. For pain severity, major allele carriers (A/A and G/A) of FKBP5 rs9394314 reported significantly higher scores than minor allele carriers (G/G). Further, major allele carriers who had at least one adverse childhood …

Approaches To Examining The Role Of Auditory Evoked Potentials In Early Language Development, Alyssa Janes

Electronic Thesis and Dissertation Repository

Previous research has suggested a relationship between auditory evoked potentials (AEPs) and spoken language proficiency, but their interactions during the earliest stages of development are not well understood. AEP-Age, an index that estimates the maturity of a child’s AEP relative to same-aged peers, has been effective in investigating this relationship in school-aged children, but has yet to be applied to younger populations. This thesis includes two Stage 1 Manuscripts (Registered Reports) for future studies to (a) assess the utility of AEP-Age to predict chronological age and language ability in 18-48-month-old children, and (b) investigate the relationship between AEP-Age and …