VictorJuiz/thesis huggingface dataset:
The Impact of Disease Progression on Health-related Quality of Life Outcomes in Patients with Oligo-metastatic Disease post Stereotactic Body Radiotherapy

AbstractIntroduction There is a paucity of published health-related quality of life (HRQOL) outcomes in patients receiving stereotactic body radiotherapy (SBRT) as a treatment option for oligo-metastatic disease (OMD). Methods 107 OMD patients who received SBRT in a phase II single arm research ethics board approved study were analyzed. The study hypothesized that a different HRQOL pattern of change from baseline exists in patients with disease progression by 12-months compared to those without progression by 12-months. Results A statistically significant (SS) decline in the mean Global Health QOL score (73 (SD 21.8) to 67.2 (SD 27.1), p=0.04) of the entire population at the 12-month follow-up from baseline was found, with no SS difference in the mean GHQOL change score between patients who progressed and did not progress (-0.8 vs -8.8, p=0.07). Conclusion Patients who progress by 12-months do not have a SS difference in mean GHQOL change score compared to non-progressors.

Keywords: HRQOL
Oligo-Metastatic
Radiotherapy
SBRT
Advisor: Bezjak, Andrea
Intracellular Interactions of the Hedgehog-signalling Pathway Receptor, Patched-1

The Hedgehog (Hh)-signalling pathway is an evolutionarily-conserved signalling cascade that upon dysregulation causes lethal defects and is implicated in various neoplasms. Organized in the primary cilia, the principal receptor for the Hh-pathway, Patched-1, in the absence of Hh-ligand indirectly inhibits the activities of a seven-pass transmembrane protein, Smoothened, subsequently altering the transcriptional effectors, the Glioma-associated homolog Proteins. The mechanisms that control the subcellular translocation of Ptch1 and Smo into the primary cilia is not well understood. To elucidate this mechanism, we developed and characterized a fusion mutant Ptch1 protein modified with a biotin-ligase BirA, that constitutively localizes to primary cilia and represses Hh-signalling. Using proximity-dependent biotinylation and MS, we identified approximately 200 ciliary factors related to cilium assembly, trafficking, regulation, and ciliopathies. Investigating the interactions of Ptch1 in the primary cilia provides an understanding of the regulatory role of the cilium on Hh-signalling, while helping to develop targeted gene therapy.

Keywords: Hedgehog-Signalling
Mass spec
Patched-1
Primary Cilia
Smoothened
Advisor: Hamel, Paul A
Investigating Adenosine-to-Inosine RNA Editing in Rett Syndrome Neurons

Rett syndrome (RTT) is a neurodevelopmental disorder (NDD) caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. Loss of MECP2 impacts transcription, translation, and post-transcriptional mechanisms governing these processes. Adenosine-to-inosine (A-to-I) RNA editing by ADAR enzymes is one such post-transcriptional process altered in other NDDs, yet no current literature examines editing in RTT. Using RTT patient induced pluripotent stem cell (iPSC) derived neuronal RNA-seq datasets, I address this gap and show increased global and novel editing in RTT that is not recapitulated in adult Mecp2 KO mice. Human TRAP-seq editing analysis show editing sites overlapping RNA-binding protein (RBP) motifs and microRNA binding sites in the 3’UTR along with a depletion of ribosomal engagement in RTT. Underlying these changes is a trend towards increased cytoplasmic localization of the ADAR1 p110 isoform. Overall, this works provides novel insight into A-to-I RNA editing in RTT patients.

Keywords: A-to-I editing
MECP2
Neurodevelopmemt
Rett Syndrome
RNA editing
RNA-seq
Advisor: Ellis, James
Hepatic PKC-δ and p38? MAPK Mediate Free Fatty Acid-induced Liver Fat Accumulation and Triglyceride Secretion

Elevated plasma free fatty acids (FFA) have been implicated in Non-alcoholic Fatty Liver Disease (NAFLD). While increased PKC-δ activity has been observed in FFA-induced insulin resistance, and its activation of p38? documented in hepatocytes treated with FFA, its role and mechanism in FFA-induced hepatic lipid metabolic dysregulation has not been studied in vivo. 12-14 weeks old liver-specific PKC-δ knockout (PKC-δKO) and p38? MAPK knockout (p38?KO) mice were infused intravenously with an oleate and palmitate mixture (2:1) for 48 hours. To confirm the mechanism of PKC-δ action, PKC-δ was overexpressed in WT and p38?KO mice. Both PKC-δKO and p38?KO mice were protected from FFA-induced hepatosteatosis and increased triglyceride secretion. Furthermore, we showed that unexpectedly, PKC-δ might not mediate FFA-induced hepatosteatosis via liver-specific p38? MAPK. These findings suggest that both PKC-δ and p38? inhibitors could be effective in treating NAFLD and mitigating the metabolic effects of elevated FFA observed in obese humans.

Keywords: free fatty acids
hepatosteatosis
NAFLD
obesity
p38
PKC
Advisor: Giacca, Adria
Explanation-driven Frameworks for Data Augmentation and Supervised Contrastive Learning in Image Classification

Data augmentation and supervised contrastive learning represent two techniques that contribute to state-of-the-art performance in image classification. Unfortunately, techniques like random masking and random augmentations used in data augmentation and supervised contrastive learning respectively may occlude key image content that can be misleading for training. In addition, explanations generated by models trained on augmentations with random operations are not necessarily faithful with respect to model predictions (e.g., an irrelevant part of the image may be explained as the reason for the classification). In this work, we suggest more intelligent frameworks based on state-of-the-art explanation techniques that seek to ensure that semantic content relevant to the image classification is preserved during augmentation. First, we show how explanation-driven techniques can be used in a generic data augmentation procedure that is agnostic to the image classifier being used, which yielded overall better explanation faithfulness. Second, we show how explanation-driven techniques can be integrated directly into a state-of-the-art supervised contrastive learning pipeline, which yielded improved classification accuracy, explanation faithfulness, robustness to adversarial perturbations of image content, and probabilistic calibration under distributional shift.

Advisor: Sanner, Scott
An Analysis of Anti-Asian Stereotypes and Racist "Tweets" Linked to the COVID-19 Pandemic

The COVID-19 pandemic and the popularity of social media platforms have combined to increase expressions of stigma, discrimination, and racism against East Asian communities. The purpose of this study is to develop a better understanding of pandemic-related anti-Asian sentiment found on social media platforms. To achieve this goal, a total of 4,000 tweets were randomly selected from over 600 million tweets to analyze for emergent themes. Results reveal that there are five themes: blaming and assigning responsibility, reactivated historical stereotypes, oppressive government, political, and unspecified direct insult. One supplementary theme is identified to capture tweets with potentially stigmatizing content. Theoretical and practical implications are discussed.

Keywords: Anti-Asian hate
COVID-19 pandemic
Social media
Twitter
Advisor: Gillis, Joseph R
A Segmented Gate Driver Design for SiC Power MOSFETs with Optimized Driving Pattern

An external gate resistance (RG) is often employed to limit the charging speed of the gate capacitance in power transistors to avoid unwanted ringing oscillation. Currently, one solution is to use segmented gate drivers during switching to dynamically adjust RG can minimize ringing while maintaining the fast-switching speed of the transistor. The timing for the dynamic RG pattern is critical to the device performance. Traditionally, this pattern is determined via a time-consuming trial-and-error process. This thesis proposes a method to automatically determine the timing intervals by monitoring the gate signal via a sensor to detect change in the slope of a particular waveform. Experimentally, an RG profile between 2.5 and 10 Ω can keep the gate undershoot under 1 V for a 20-0 V transition for a SiC power MOSFET (GR40MT33N). The ringing is suppressed to less than 5% of the applied gate voltage while maintaining a switching speed of 194 ns.

Keywords: Automatic optimization
Ringing suppression
Segmented gate driver
Advisor: Ng, Wai Tung WT Ng
Oriko: A Simulator for Energy Harvesting Systems and Intermittent Computing

The Internet of Things (IoT) is a fast-expanding class of computing devices that have applications everywhere from health monitors to satellites. However, many IoT devices cannot rely on conventional methods of powering the device due to their generally small form-factor and need to operate wirelessly. Thus a new class of devices emerges, capable of harvesting energy from its environment instead of relying on wall power or large, heavy batteries.However, environmental conditions are unpredictable and often result in frequent power losses. Energy harvesting systems require special software, hardware, or both, to recover from unexpected shutdowns while maintaining program progress and correctness. This work introduces Oriko, a simulator that helps developers design systems to overcome the challenges of working with energy harvesting systems and showcases how to design for application specific optimization targets.

Keywords: Energy Harvesting
Microcontroller
Simulator
Solar
Advisor: Enright Jerger, Natalie
The Effects of Sodium-Glucose Co-transporter 2 Inhibition on Plasma and Urine Ketones in Type 1 Diabetes

Background: Adjunctive-to-insulin SGLT2 inhibition (SGLT2i) in type 1 diabetes (T1D) has meaningful metabolic benefits but can increase risk of ketoacidosis. Knowledge gaps include understanding ketone metabolism with and without SGLT2i treatment in T1D, and whether ketoacidosis risk in females is physiological or behavioral.Methods: Metabolomic analysis of plasma and urine beta-hydroxybutyrate and acetoacetate from stored baseline and 8-week eu- and mild hyper-glycemic samples in the 40-person single-arm Adjunctive-To-Insulin Renal MechAnistic (ATIRMA) trial of empagliflozin. Results: A significantly greater production of ketones even during mild hyperglycemia compared to euglycemia was observed, but this was compensated by increased urinary excretion leading to similar plasma concentrations. However, SGLT2i attenuated this increased excretion, resulting in higher plasma concentrations, particularly in females. Conclusions: Even mild hyperglycemia is associated with greater ketone production, compensated by urinary excretion. SGLT2i further exaggerates excess production and impaired excretion especially in females, indicating physiological rather than behavioral risk for ketoacidosis.

Keywords: empagliflozin
ketone
SGLT2
type 1 diabetes
Advisor: Perkins, Bruce A
Abundance Estimates for the Last Remaining Population of Blue Racer (Coluber constrictor foxii) in Canada

Estimating the size of endangered populations is a critical component for species-specific conservation management. My study used capture-mark-recapture analyses to produce population size estimates for the endangered population of Blue Racer (Coluber constrictor foxii) in Canada. Over two years, racers were captured and implanted with passive integrated transponders on Pelee Island on 15 sampling occasions. The robust design was used to produce estimates of the current population's abundance, survival, and capture probabilities. I estimated racer abundance to be 122 (95% CI = 58-256) individuals at its lowest and 182 (95% CI = 118-281) individuals at its highest. Further analyses of historical and current data using POPAN and Peterson models suggested a potentially declining trend in abundance over the last twenty years. As this population continuously faces the threats of habitat loss and anthropogenic activities, I recommend that this Blue Racer population receive continued monitoring and conservation efforts.

Keywords: Blue Racer
Conservation
Endangered Species
Mark-recapture
Population Estimate
Robust Design
Advisor: Rollinson, Njal
Role of the mTOR Pathway and Autophagy in Mediating PARP Inhibitor Sensitivity in Small Cell Lung Cancer

Small cell lung cancer (SCLC) is an aggressive form of lung cancer with a dismal 5-year survival rate of 7%. Despite initial response rates (70-80%) to DNA damaging agents, patient relapse accompanied with treatment resistance is inevitable. Poly (ADP)-ribose inhibitors (PARPi) are a novel therapy that has been evaluated for SCLC treatment and are in clinical trials. There is increasing interest in identifying targetable factors involved in PARPi sensitization for combinatorial therapeutic strategies. This study shows that the mTOR pathway mediates PARPi sensitivity in SCLC cells through CRISPR genetic screens. We hypothesized that the constitutive activation of mTORC1 suppresses pro-survival autophagy. We used functional genetic validation with shRNAs to knock down the TSC1/2 complex and observed significant sensitization of SCLC cells to PARPi. Our data support that pharmacologically inhibiting autophagy is synergistic with PARPi in SCLC cells, creating a novel avenue for developing combination therapies to improve overall survival for SCLC patients.

Keywords: autophagy
metabolism
mTOR
NAD
PARP
small cell lung cancer
Advisor: Lok, Benjamin H
Teachers' Peacebuilding and Holistic Pedagogies in Secondary Alternative "Behavioural" Classrooms in Ontario

In Ontario, some “behavioural” students (often members of marginalized groups) are placed in Educational and Community Partnership Program classes. ECPP’s intent is to transition students back into mainstream classrooms after meeting their needs for special care or rehabilitation. One programming directive is that ECPP students be taught social skills. Peacebuilding pedagogies are promising avenues through which teachers can do so, while building community and restoring students’ trust in the school system. Through literature review, interviews with four ECPP teachers, and analysis of policy documents, this thesis explores two questions: 1) What do purposively selected teachers of secondary “behavioural” alternative students know and do about teaching conflict resolution and peacebuilding skills (what does this mean to them, and how are they incorporating relevant pedagogies into their classrooms)? 2) What has helped and hindered these teachers’ efforts? The analysis of ECPP Program policy and practice concludes with recommendations for improving these environments.

Keywords: at-risk
behavioural students
conflict resolution
dialogic pedagogy
holistic education
peacebuilding
Advisor: Bickmore, Kathy
Pre and Post Predator Encounter Defensive Traits in a Nearctic Macromoth Community

Moths can possess primary and secondary defenses, which act to reduce predator encounters or increase the chances of surviving an encounter, respectively. I considered various categorical and continuous defensive traits, at the species level and after controlling for phylogeny, in a Nearctic macro-moth community. I found that camouflaged moths were more nocturnal, conspicuous moths more diurnal, and that contrasting moths had larger body sizes than camouflaged moths. And that while conspicuous caterpillars become camouflaged, conspicuous, or contrasting moths, camouflaged caterpillars tend become camouflaged adult moths. I also found that conspicuous caterpillars were more likely to be spikey than were camouflaged caterpillars. Last, while I found that moths with two neurons/ear had larger maximum acoustic safety margins than moths with one, I found no difference in acoustic safety margins of nocturnal and diurnal moths, nor between moths that emerged in mid-summer, when bat activity is highest, versus late spring emerging species.

Advisor: Ratcliffe, John
Examining the Effectiveness of the CARD (Comfort, Ask, Relax, Distract) System on Improving Student Experiences during School-based Vaccination Clinics: Results of a Randomized Cluster Trial

Background: Needle fear and pain can be exacerbated in school-based vaccination clinics when students are unprepared and fear cues are not systematically minimized. The CARD system (Comfort, Ask, Relax, Distract) incorporates evidence-based strategies to mitigate fear and pain. We examined CARD’s effectiveness in reducing student fear, pain and related symptoms during school vaccinations. Methods: Randomized cluster trial in 40 Wellington-Dufferin-Guelph schools during fall 2019. Schools were randomly assigned (1:1) to CARD or control. Students reported fear, pain and dizziness scores. Nurses reported coping tools used and post-vaccination reactions. Results: 1424 of 1919 students across participating schools were vaccinated at school. Fear and pain were lower in CARD vs. control: OR 0.65 (95% CI 0.47-0.90) and OR 0.62 (95% CI 0.50-0.77), respectively. No CARD students fainted compared to 0.8% control (p=0.02). Dizziness or post-vaccination reactions did not differ. Coping tools were used more frequently in CARD schools. Discussion: CARD reduced stress-related symptoms during school-based vaccinations.

Keywords: Fear
Needles
Pain
Pediatrics
Vaccines
Advisor: Taddio, Anna
Anticoagulant Use in Older Patients Receiving Home Palliative Care: A Retrospective Cohort Study

Objective: To describe the prevalence of anticoagulant use and identify predictive factors for anticoagulant discontinuation among home palliative care recipients in Ontario.Methodology: Linked administrative population-based healthcare databases were used to identify and study home palliative care recipients ≥66 years old in Ontario from 2010-2019. The prevalence of anticoagulant use was calculated. Multilevel models were used to study patient and provider factors associated with early anticoagulant discontinuation following initial home palliative care consultation. Results: 98,089 older adults initiated home palliative care from 2010-2018, among whom 15.5% were taking anticoagulants. By multilevel logistic regression, few patient or physician characteristics—and neither comorbidity nor indications for therapeutic anticoagulation—were associated with discontinuation. Mean discontinuation rates by physician quintile ranged from 7-49%. Conclusion: Among home palliative care recipients, anticoagulant use is common and discontinuation may relate largely to physician preference. Further study on the risks and benefits of anticoagulants in this population is warranted.

Keywords: anticoagulants
deprescriptions
palliative care
terminal care
Advisor: Laupacis, Andreas
Identity Navigation and Understanding in Demographic Surveys

This study is concerned with how undergraduate students in disciplines related to Science, Technology, Engineering, and Math (STEM) select responses when answering demographic surveys, especially in cases where they are unable to map their identity onto provided responses. Fifteen undergraduate STEM students at various stages of their degrees were interviewed, and three types of demographic survey responses were identified: (1) alignment, (2) misreporting, and (3) misalignment. Students’ responses to questions about race and ethnicity, racialization/person of colour identification, first-generation/first-in-the-family, and disability were especially likely to be influenced by tensions between their self-determined identity and an identity that is placed onto them by others. Based on the findings, an adaptation of Tourangeau et al.’s (2000) Components of Survey Response model is proposed. The findings have implications for furthering the understanding of the survey response process, how to ask sensitive questions, and limitations of current demographic survey questions.

Keywords: Demographic Survey Design
Disability
Equity
Diversity
Inclusion
Access
First-generation
Identity
Race
Advisor: Childs, Ruth A.
Investigating the Effects of Near-Streamflow Regions on Temperate Region Lake Ice

This study uses a combination of modeling and fieldwork to investigate the relationship between stream outflows and lake ice in Central Ontario, by focusing on Clear and MacDonald Lakes in Haliburton Forest and Wild Life Reserve. A network of waterproof temperature sensors (HOBO pendants and tidbits) were submerged 1 – 4 m below the water level, and Reconyx outdoor digital cameras were installed around the outflows at both lakes. Results indicate thinner or no ice, and an earlier spring ice-off closer to the outflow regions. Incorporating an additional heat flux in the lake ice model to represent the near-streamflow heat sources, 9.5 Wm-2 for 2017 – 2018, and 20.5 Wm-2 for the 2018 – 2019, led to more accurate simulations of the lake outflow regions. Overall, results show that the near-streamflow region ice is unsafe for recreation most of the winter season, highlighting the need for accurate ice information and awareness for users.

Keywords: Hydrology
Ice
Ice safety
Lakes
Outflows
Streamflow
Advisor: Brown, Laura
Fazli: Identity and Wisdom in a Pakistani Adult with Autism

This study explored life of Fazli, a highly successful adult with autism in Pakistan, and the role of wisdom and identity in his life, using a mixed-method case study analysis. Fazli is an assistant professor at a renowned university in Pakistan and is an international and regional self-advocate for autism since 2006. A pragmatic, pluralist, method that included thematic, biographical and Interpretative Phenomenological Analysis, and statistical analyses were used analyzing Fazli’s interviews, audio diaries and answers to self-report questionnaires about wisdom, identity and quality of life. As per McAdams’ narrative identity theory, his life narrative exhibited high levels of personal agency. Although Fazli exhibited many traits of wisdom including high cognitive abilities, reflectivity, mastery, affection and openness, and had better life outcomes compared to other autistic individuals, nevertheless, his quality of life is low. Stigma, lack of recognition and inequitable monetary benefits all contribute to his poor quality of life.

Keywords: ASD
Autism
Identity
Pakisan
Quality of Life
Wisdom
Advisor: Ferrari, Michel
Hole Edge Enhancement in 3D Point Cloud Obtained with Structured Light

Measuring hole edges with structured light (SL) is challenging. In industrial practice, a coordinate measurement machine (CMM) is used by touching hole edges manually with a probe, which is laborious and time-consuming. This article reports a new method to reconstruct 3D edge points directly from images. A new edge detector based on subtracted edge and shortest path (ED-SESP) is proposed. It can remove spurious edges and link broken edges by making full utilization of the weak gradient information neglected by traditional edge detection algorithms. A two-stage stereo matching method is proposed to avoid ambiguous matching by using a dynamic programming algorithm to optimize the matching of edge points tangent to the epipolar line. Experiment results with various industrial parts demonstrated that our proposed method can achieve 0.080 mm measurement accuracy compared to CMM-measured data, while the traditional SL-based method can only achieve 0.645 mm measurement accuracy.

Advisor: Sun, Yu