VictorJuiz/thesis huggingface dataset:
Visual Attention Failures towards Vulnerable Road Users at Intersections: Results from On-road Studies

Crash data indicate that attention misallocation is a major factor in crashes with vulnerable road users (VRUs) at intersections. However, the extent that drivers fail to scan for VRUs at intersections is unknown. This thesis investigates driver visual attention failures toward VRUs at intersections using an instrumented vehicle and eye-tracking equipment. First, analysis of data collected in an earlier on-road study is presented, which informed the design of the main experiment where 26 drivers (ages 35-54; 13 cyclists) made 18 different turns at downtown Toronto intersections, half of which were identified to be higher risk. Almost half of the turns had a visual attention failure; and most were towards cyclists. The failures were significantly more common at higher risk intersections and among non-cyclist drivers. Overall, prevalence of failures is alarming. Further research is needed to generalize these findings. The thesis also provides an overview of the countermeasures on cyclist safety.

Keywords: Cycling Safety
Human Factors
Intersection Safety
Advisor: Donmez, Birsen
Characterization of a Lead Compound Targeting LXRβ for the Treatment of Glucocorticoid-induced Diabetes

A known cause of diabetes is the long-term use of glucocorticoid (GC) drugs which are commonly used to treat chronic inflammation. Our lab has found that co-treatment of GC drugs with an LXRβ antagonist can decrease GC-induced diabetes. Herein, we characterize the pharmacokinetics of a pre-clinical lead candidate drug (LO520) targeting LXRβ that could be used along with GC therapy to prevent the diabetogenic side effects of GC drugs. LO520 demonstrated receptor specificity towards LXRβ in both murine and human LXR plasmid-based expression systems and significantly reduced plasma glucose levels when dosed in the presence of GC drug (dexamethasone, Dex) without altering the desired immunosuppressive effect. Future studies will need to investigate the molecular mechanisms of LO520 in regulating gluconeogenesis and whether the use of LO520 will impact reverse cholesterol transport and the development of atherosclerosis.

Keywords: Drug development
Drug discovery
Molecular biology
Pharmaceutical
Advisor: Cummins, Carolyn L.
Maladaptive and Adaptive Perfectionism and Nonsuicidal Self-injury

Nonsuicidal self-injury (NSSI), which refers to direct and deliberate alteration or damage to bodily tissue without lethal intent, is a prevalent mental health concern among emerging adults. Recent research and theory suggest that perfectionism, particularly a consistent perceived discrepancy between one’s exacting personal standards and reality (i.e., maladaptive perfectionism), may be an important predictor of NSSI engagement. The current study investigated the associations between maladaptive perfectionism, adaptive perfectionism, and NSSI, and explored two mechanisms through which maladaptive perfectionism may lead to NSSI engagement (via self-criticism and depressive symptoms) longitudinally. A sample of 732 emerging adults (70% female) completed an online survey annually over three years. Path analyses demonstrated a significant direct effect from maladaptive perfectionism to NSSI. Depressive symptoms and self-criticism did not mediate the link between maladaptive perfectionism and NSSI. In a secondary analysis, maladaptive perfectionism predicted self-punishment motivations for NSSI over time.

Keywords: emerging adulthood
nonsuicidal self-injury
perfectionism
Advisor: Hamza, Chloe A
Methods Towards Enhancing Divergent Thinking in Conceptual Design

Divergent thinking, an aspect of creativity, is often measured by performance on the Alternative Uses Test (AUT). Beyond its use as a psychological test, the AUT is also societally relevant when finding alternative uses for retired wind-turbine blades, which have limited disposal options. This work firstly describes a method using visual similarity to aid alternative-use concept generation for retired wind-turbine blades. This partially automated method resulted in more relevant reuse concepts than humans performing the same task. The effect of visual stimuli on alternative-use concept generation was explored in our second study where eye tracking was used to observe visual fixation during the AUT. Visual fixation towards multiple views of an object and towards blank space around the object were related to increased divergent thinking. Eye tracking was used to not only reveal where participants looked during the task, but to uncover the cognitive processes underlying their eye movements.

Keywords: Alternative Uses Test
Creativity
Divergent thinking
Advisor: Shu, Li H
Monitoring the Short-term Outcomes of Project-based UXD Community-engaged Learning Courses

Community-engaged learning is an experiential learning approach aimed at addressing community needs while benefitting students and community partners through applied learning opportunities. This research focuses on evaluating community-engaged learning initiatives within the field of user experience design (UXD). Evaluation was done using a mixed-methods approach which considers both students’ and community partners’ perspectives. Findings revealed community-engaged learning benefits for both students and community partners. Students gained UXD competencies, interpersonal skills, and empathy. Community partners garnered useful deliverables and an increased understanding of UXD. Results also suggest community-engaged learning initiatives offer a mutually beneficial experience for students and community partners. Recommendations, informed by the assessment of community-engaged learning initiative costs, are also provided. The primary recommendations include: (1) providing a clear outline of the engagement deliverables and timelines upfront; and (2) extending the timeframe of engagement. This research provides preliminary support for community-engaged learning initiatives among UXD programs.

Keywords: community-engaged learning
community partnerships
user experience design
Advisor: St-Cyr, Olivier
Exploring Approaches used to Identify, Incorporate and Report Patient Preferences in Clinical Guidelines

Introduction: Guidelines improve patient care and outcomes. Research shows that guidelines that address patient preferences are more likely to be used but few do. This study explored approaches used to identify, incorporate and report patient preferences in clinical guidelines. Methods: This study included a scoping review and semi-structured qualitative interviews with guideline developers on approaches used to identify, incorporate, and report patient preferences during guideline development. Results: Twenty-one full-text studies were included in the scoping review. Fifty national and international guideline developers (patients, clinicians, managers) participated in the qualitative interviews. A multitude of approaches were found for identifying patient preferences. Preferences are not being incorporated in all guideline steps, even though developers said they were, and are also being poorly reported in terms of how and where those preferences influence guideline development. Conclusions: More research is needed on approaches to optimize identifying, incorporating and reporting patient preferences in clinical guidelines.

Keywords: clinical guidelines
patient preferences
Advisor: Gagliardi, Anna R
The Impact of Gasoline Fuel Composition on Air Quality

In recent years, particulate matter (PM) emissions from the gasoline direct injection (GDI) engine, are of significant concern due to their associated health effects as well as for climate impacts. Thus, in this thesis, the effect of gasoline fuel composition on GDI engine PM emissions is investigated. The detailed composition of five regular grade (anti knock index, or AKI, 87) and two premium grade (AKI91) fuels currently used in Ontario was studied. In addition, the impact of fuel seasonal changes on gas-phase emissions (i.e. benzene and toluene), and particle-phase emissions, i.e. black carbon (BC), elemental carbon (EC), polycyclic aromatic hydrocarbons (PAHs), and particle number (PN) were also determined using a laboratory GDI engine. The observations showed that all summer AKI87 fuels contained higher aromatics and lower paraffins compared to the winter AKI87 grade which led to higher BC, EC, PN, benzene, and toluene emissions.

Keywords: Black Carbon Emissions
Gasoline Direct Injection Engine
Gasoline Fuel Composition
Particulate Emissions
Advisor: Chan, Arthur W. H.
Structural Abnormalities of the Temporalis Muscle and Tendon in Temporomandibular Disorders

Myalgia of the masticatory muscles is the most common temporomandibular disorder (TMD). Although previous work has explored risk factors, and central and peripheral mechanisms of TMD myalgia (mTMD), the etiology of chronic mTMD pain remains poorly understood. This project aimed to determine whether chronic mTMD is associated with structural abnormalities of the temporalis muscle. We hypothesized that chronic mTMD is associated with a smaller aponeurosis-tendon complex (ATC) of the temporalis. T1-weighted magnetic resonance images of 34 chronic mTMD patients and 34 sex- and age matched healthy controls from two cohorts were studied. The volumes of the temporalis muscle and its ATC were measured via software. In both cohorts, mTMD patients had smaller ATC volumes than controls (all p

Keywords: Myalgia
Temporalis
Temporomandibular disorders
Advisor: Cioffi, Iacopo
Moayedi, Massieh
Training Caregivers to Reduce Spine Flexion using Biofeedback

Back injuries are extremely common among home caregivers due to the use of poor postures while performing daily tasks. Learning to use safer movement patterns may be accomplished with real-time biofeedback. The effectiveness of a two-day intervention - that includes biofeedback and a video - in decreasing time spent in end-of-range spine flexion was evaluated over a two-month period. 20 individuals with no caregiving experience repeated a series of simulated care tasks. Real-time auditory biofeedback was provided to the intervention group (n=10) when their sagittal lumbar spine flexion exceeded a threshold during training trials; the control group (n=10) received no feedback. Participants repeated the tasks again after two weeks and two months. The intervention group maintained decreased end-of-range (80th and 95th percentile) spine flexion compared to controls at both time points. Group performances on box lifting technique, a skill transfer task, and a back-injury prevention questionnaire were also compared.

Keywords: Back injury prevention
Biofeedback
Home caregivers
Posture
Wearable technology
Advisor: Dutta, Tilak
Development and Evaluation of a Navigation Workflow for Radiofrequency Ablation of Spinal Metastases

Bone metastases present in more than 85% of cancer patients at the time of death, with the spine being the most common site. Improvements in radiofrequency ablation (RFA) has adapted this technology for local control of spinal metastases. In this thesis, a navigation workflow for vertebral RFA was developed utilizing software to integrate pre-procedural imaging data with RFA treatment plans and intra-procedural imaging data. An optical tracking camera is utilized to track the RFA probe intraoperatively and to ensure that the final pose matches the prescribed pose. The feasibility of the workflow was evaluated by two spine surgeons in animal studies. The accuracy of the navigation was also tested in phantom and animal models. The developed software yields a clinically feasible workflow similar to the existing systems adopted in procedure rooms. Navigated RFA may improve the safety and efficacy of this procedure, and ultimately enhance quality of life for patients.

Keywords: Bone-targeted Radiofrequency ablation
image registration
procedural navigation
Spinal metastases
treatment planning
Advisor: Whyne, Cari
Yee, Albert
Exhaustive Mapping of Missense Variation in Coronary Heart Disease-related Genes

Coronary heart disease (CHD) is a leading cause of death worldwide. A major risk factor of CHD is high low-density lipoprotein cholesterol (LDL-C), which is the defining feature of familial hypercholesterolemia, a genetic disorder characterized by mutations in genes involved in cholesterol uptake, such as LDLRAP1. The risk of CHD can be reduced by LDL-C-lowering medications called statins that potently inhibit HMG-CoA reductase (HMGCR), the enzyme that catalyzes the rate-limiting reaction of the mevalonate pathway. The study of genetic variation in CHD-related genes may contribute to early detection or prevention of CHD. I exhaustively mapped missense variant effects of two CHD-related genes, HMGCR and LDLRAP1. Proactive maps of human HMGCR may be able to model patient response to statins and identify the statin with the greatest likelihood of efficacy. Proactive maps of LDLRAP1 may identify pathogenic variation of autosomal recessive hypercholesterolemia (ARH) for early diagnosis of ARH.

Advisor: Roth, Frederick P
Photodynamic Therapy of Pancreatic Cancer with Porphyrin-lipoprotein Photosensitizers

Previously, the high-density lipoprotein (HDL) mimicking porphyrin-lipoprotein (PLP) nanoparticle was found to accumulate more in tumours compared to their non-cancerous counterparts in several clinically relevant animal models. PLP demonstrates stability in blood circulation and rapid dissociation upon tumour accumulation to generate fluorescence and photodynamic reactivity. Photodynamic therapy (PDT) has been tested in pancreatic cancer patients with clinically approved photosensitizers; however, none are tumour selective. In this work, using in vitro tests with pancreatic adenocarcinoma cell line (PANC-1) and subcutaneous PANC-1 xenograft and orthotopic PANC-1 mouse models in vivo, it was demonstrated that PLP uptake more in pancreatic tumours compared to non-cancerous tissue. In addition, PLP combined with PDT (PLP-PDT) was effective in tumour destruction in vitro and in chronic studies with the subcutaneous PANC-1 xenograft mice. With the orthotopic PANC-1 mouse model, PLP-PDT treatment induced significantly more damage at the tumour site compared to non- cancerous pancreatic tissue.

Keywords: Animal models
Nanomedicine
Pancreatic cancer
Photodynamic therapy
Porphyrin-lipid
Theranostics
Advisor: Zheng, Gang
Baseline Toronto HCC Risk Index (THRI) and Albumin Predict Low Risk of Hepatocellular Carcinoma (HCC) after Sustained Virological Response (SVR) in HCV Infection

Current guidelines recommend hepatocellular carcinoma (HCC) surveillance for patients with F3/F4 fibrosis after sustained virological response (SVR) with treatment for hepatitis C infection, however not all patients are at equally high risk for HCC. We aimed to identify factors associated with a low enough risk for HCC to forego ongoing surveillance. Patients with F3/F4 fibrosis and SVR were included. Data were collected at start of treatment and Toronto HCC risk index (THRI) combining age, sex, and platelets was calculated. Patients were followed from end of treatment until first HCC occurrence. Of 1,131 patients, 50 (4%) developed HCC over median (IQR) 1.9 (0.6-3.8) years. On multivariable Cox regression, baseline THRI≥160 (HR=2.71, P=0.001) and albumin≤40 g/L (HR=3.05, P=0.001) predicted increased HCC risk. Among hepatitis C patients with F3/F4 fibrosis and SVR, patients with baseline THRI

Keywords: Hepatitis C
Hepatocellular carcinoma
Sustained virological response
Advisor: Feld, Jordan J
Elucidating the Regulatory Role of PHIP1 in Activated T Cell Metabolism and Immunity

Metabolic and transcriptional pathways in T-cells are intricately woven to affect cell fate decisions and functions downstream of T-cell activation. We proposed that an understudied epigenetic and transcriptional co-regulator previously implicated in insulin signaling, growth and aerobic glycolysis, PHIP1, could provide further means to explore the crosstalk between metabolism and gene regulation in coordinating T-cell responses. We found that upon activation, PHIP1 is significantly upregulated in T-cells and demonstrates both nuclear and cytoplasmic expression, but almost exclusively localizes in the nucleus during quiescence. PHIP1-siRNA-mediated knockdowns showed that PHIP1 regulates critical genes involved in T-cell metabolism, survival and effector/memory formation, for optimal transcriptional remodeling during activation. Data trends indicate memory-specific inhibition and/or preference for effector-like responses in PHIP1-deficient T-cells, although additional in-depth studies are required to confirm this. Further investigations can potentially implicate PHIP1 as a novel candidate to reprogram T-cell metabolism and differentiation and thus enhance or temper cellular immunity.

Keywords: Gene regulation
Immunometabolism
PHIP1
T cell activation
T cells
Advisor: Rozakis-Adcock, Maria
Peptide-based Approach toward the Inhibition of a Bacterial Multidrug Resistance Efflux Pump

Efflux proteins allow multidrug resistant bacteria to pump out antibiotics before they can exert their toxic effect(s). The E. coli membrane protein AcrB is the archetypal member of the most efficient superfamily of efflux pumps. Since AcrB forms a trimer in order to properly function, we have proposed to inhibit AcrB using a novel strategy in which synthetic peptides are designed to mimic the transmembrane (TM) oligomerization interface and thus outcompete the critical helix-helix contacts. In this thesis, we demonstrate that peptides designed from the AcrB TM1/TM8 interaction site inhibit efflux of an AcrB fluorescent substrate as well as allow current antibiotics to work more effectively. Biophysical analysis confirmed the partitioning of the peptides into membranes. Systematic variations in the peptide sequences highlighted key functional helix-helix interactions that are likely to stabilize the AcrB trimer. This work represents a foundation for developing a peptide-based inhibitor against the protein.

Keywords: AcrB
Antibiotic resistance
efflux
efflux pump inhibitor
peptide
RND
Advisor: Deber, Charles M
Inequities in Black et Blanc: Textual Constructions of the French Immersion Student

This thesis is an investigation into Toronto and Ontario French immersion policy, curricula, and other related documents in order to understand if and how current documents contribute to the over-representation of White middle-class students in French immersion. The study found that French immersion policies, curricula, and documents evidenced a middle-class bias due to lack of resources, transportation and promotional materials, and location of programs. It had a White bias through its Eurocentric curricular content. The documents of this study also privileged English above all other languages, and families who were not newcomers. The documents did not entirely mirror the population in French immersion in terms of gender, home language and special education needs. Equity documents highlight that steps are being taken toward a more inclusive immersion program, but there is still much to do, especially in terms of dismantling and transforming hierarchies.

Keywords: bilingualism
education
French as a second language
French immersion
sociolinguistics
Advisor: Heller, Monica
Sefa-Dei, George J
Identifying Chemical Modulators of C. elegans Stress Response for Use as Tools and Potential Anthelmintics

Parasitic nematodes currently plague around two billion people. Resistance has developed against nearly all anthelmintic classes in agriculture. Towards identifying novel anthelmintic, we proposed that if nematode stress response mechanisms are chemically inhibited in stressful conditions, affected animals would become more susceptible to killing by stressors encountered during their lifecycles. From literature, we identified GFP reporters of canonical stress response pathways. I screened our custom worm active library of 485 unique structures with C. elegans and identified 18 compounds that suppress elicited reporters and/or exert synthetic lethality in stressful conditions. Wact-128 and wact-204 were identified as promising hits. They suppress elicited oxidative stress response and kill synthetically with oxidative stress. Through characterization of their mechanism of actions, I found evidence for wact-128 and wact-204’s inhibitory activity on the SKN-1-mediated oxidative response pathway. Chemicals that selectively inhibit nematode’s SKN-1-mediated pathway may be developed into novel anthelmintic or adjuvants for existing anthelmintic.

Keywords: Drug discovery
Drug screen
Genetic screens
Model organism
Parasitic helminths
Synthetic lethality
Advisor: Roy, Peter J
Familial Aggregation of Executive Functioning in Borderline Personality Disorder

Borderline personality disorder (BPD) is a psychiatric disorder characterized by impulsivity, emotional dysregulation, and deficits in executive functioning (EF), but the extent to which EF deficits runs in BPD families remains poorly understood. The current study examines the multivariate familial aggregation of EF indices in probands with BPD, first-degree biological relatives, and healthy controls. Discriminant function analyses reveal that interference resolution and response inhibition performance are key to discriminating BPD probands from relatives and controls, while a pattern of less efficient problem solving and difficulty manipulating mental information discriminates probands and relatives from controls. Moreover, psychiatrically nonaffected relatives demonstrate a pattern of resilience to familial psychiatric risk, substantiated by stronger response inhibition and abstraction abilities despite less efficient problem solving. Future research should explore the associations between EF and maladaptive trait dimensions—like impulsivity and emotional dysregulation—to advance dimensional conceptualizations of psychopathology and elucidate the BPD phenotype.

Keywords: borderline personality disorder
cognition
executive functioning
familial aggregation
impulsivity
phenotype
Advisor: Ruocco, Anthony C
Pharmacological Mechanisms of Interhemispheric Signal Propagation and its Disruption in Schizophrenia and Depression

Altered interhemispheric connectivity, linked to deficits of gamma-aminobutyric-acid (GABA) neurotransmission and transcallosal microstructure, is implicated in the pathophysiology of schizophrenia (SCZ) and major depressive disorder (MDD). Objectives: First, we investigated the neurochemical mechanisms of interhemispheric signal propagation (ISP) using combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) with pharmacological modulation in healthy participants. Next, we assessed differences of TMS-evoked ISP between SCZ, MDD, and healthy participants. Hypothesis: It was predicted that ISP would be selectively modulated by the GABAB receptor agonist baclofen and altered in SCZ patients only. Results: Baclofen was the only pharmacological agent that altered and reduced ISP. Additionally, ISP was elevated in both SCZ and MDD patients compared to healthy participants. Conclusions: ISP is modulated by GABAergic neurotransmission and altered in SCZ and MDD. This provides a fundamental step to characterize the mechanisms of TMS-evoked ISP and identify treatments for disorders in which transcallosal signal transmission is dysfunctional.

Keywords: Corpus Callosum
Depression
Electrophysiology
Schizophrenia
TMS-EEG
Transcranial magnetic stimulation
Advisor: Daskalakis, Zafiris J