VictorJuiz/thesis huggingface dataset:
The Antioxidant Status of Breast Milk in Women with and Without Gestational Diabetes Mellitus
Keywords: Antioxidants
Breast milk (BM)
Gestational diabetes mellitus (GDM)
Normoglycemic (NG)
Pregnancy
Total antioxidant capacity (TAC)

Gestational diabetes mellitus (GDM) is associated with reduced total antioxidant capacity (TAC) in blood, but association of GDM with breast milk (BM) TAC and antioxidants is unknown. Therefore, BM TAC, α-tocopherol, ascorbic acid, and β-carotene concentrations were compared in GDM (n=8) and normoglycemic (NG) women (n=10) in a cross-sectional study. This study found no differences between BM TAC and antioxidant concentrations in women with GDM versus NG. BM α-tocopherol correlated significantly with TAC (p = 0.011) in NG and ascorbic acid correlated significantly with TAC (p = 0.040) in GDM. BM β-carotene in the combined group (p = 0.005) and in NG (p = 0.003) correlated significantly with β-carotene consumption. The results suggest that GDM has no association with BM TAC and antioxidant concentrations. The correlations between BM TAC and antioxidants differed in GDM versus NG for α-tocopherol and ascorbic acid suggesting that unmeasured antioxidants differ in GDM versus NG.
Validation of Sirtuin 3 as a Neuroprotective and Neurorestorative Target in the Mutant Human A53T α-synuclein Rat Model of Parkinson’s Disease
Keywords: Adeno-associated virus
Mitochondria
Neuroprotection
Parkinson's Disease
Sirtuin 3
Substantia Nigra

Mitochondrial dysfunction plays a major role in the progressive and pathological development of Parkinson’s disease (PD). Mitochondrial protein deacetylase sirtuin 3 (SIRT3) assists in controlling bioenergetic and antioxidation processes by regulating mitochondrial enzyme acetylation levels. Based on this, overexpression of SIRT3 in the substantia nigra pars compacta (SNc) was assessed for its disease-modifying and cytoprotective effects in a well-accepted, adeno-associated virus (AAV) model of PD. SIRT3-myc AAV was infused into the SNc before or after A53T AAV induction of parkinsonism and analyzed at three and six-week time points. Results suggested that at six weeks, SIRT3 overexpression significantly reduced parkinsonian deficits, localized to the mitochondria, and displayed deacetylase function. Overall, the beneficial effects of SIRT3 demonstrate its disease-modifying implications for PD.
The Use of High-Dose Riboflavin to Limit Topotecan Efflux in Milk: A Proof-of-Principle Study in Mice and Cells
Keywords: Breast cancer resistance protein
Drug transfer
Lactation
Riboflavin
Riboflavin transporter
Topotecan

Various mechanisms mediate transport of compounds into milk throughout lactation. Breast cancer resistance protein (BCRP) is one of the apically expressed transport proteins in mammary epithelial cells and it extrudes vitamins, like riboflavin, and many xenobiotics, including topotecan, into breast milk. The purpose of this project was to determine whether using pharmacological doses of riboflavin can limit xenobiotic accumulation into milk. By elucidating the mechanisms of milk production, mothers could continue drug therapy while reducing risk to suckling infants. Mouse models with adequate riboflavin levels showed that topotecan-riboflavin interactions at Bcrp were not associated with significant changes in topotecan accumulation in milk. Two cell models were optimized and ultimately one of the two cell lines exhibited significantly higher topotecan retention when treated with the known, chemical Bcrp inhibitor Ko143. This proof-of-principle study indicates that riboflavin administration does not significantly interrupt extrusion of the potent Bcrp substrate topotecan into breast milk.
Long-Term Perceived Engagement and Research Priorities Among Chronic Kidney Disease Stakeholders: A Qualitative Study
Keywords: Chronic kidney disease
Patient engagement
Patient-oriented research
Qualitative research

Despite increasing engagement of patients and other stakeholders in the research process, little is known about its impact, particularly over the long term. In this qualitative descriptive study, we sought to explore how stakeholders who participated in a chronic kidney disease (CKD) research prioritization exercise two years earlier viewed their engagement experience and the research priorities. Through thematic analysis of interviews with 23 participants across stakeholder groups (patients, caregivers, healthcare providers and policymakers) and levels of engagement (steering committee, workshop and wiki), we identified four themes related to perceived engagement and three themes related to views on the CKD research priorities and prioritization process. Our findings highlight important considerations to support meaningful engagement in research prioritization, including roles and expertise, representation, and communication, and characterize ways in which individual priorities can change over time. Findings may contribute toward optimizing the design and conduct of future research engaging patients as stakeholders.
Has De-listing Routine Eye Examinations Increased the Use of Primary Care Providers for Ocular Diagnoses?
Keywords: Health Policy
Primary Care
Routine Eye Examinations

Purpose: In 2004, Ontario de-listed routine eye examinations for individuals aged 20-64. Post-delisting, affected individuals pay out-of-pocket or have the costs covered by private insurance for eye care. To avoid payments, patients with eye problems may visit a government-insured primary care provider (PCP) for help and/or for a referral to see a government-insured optometrist/ophthalmologist. We investigated if PCP utilization for eye diagnoses increased among affected Ontarians post- versus pre-delisting. Methods: PCP utilization for eye diagnoses from 2000-2014 was assessed using administrative data and interrupted time series analysis. Eye diagnoses were identified using ICD-9 diagnostic codes. Results: Post-delisting, PCP utilization for eye diagnoses significantly increased among affected Ontarians (20-39 group: 30%, p
MiRNA-106a is a Novel Regulator of Radiation Resistance through Targeting LITAF and ATM in Prostate Cancer
Keywords: ATM
LITAF
miR-106a
Prostate cancer
Radiation resistance

Prostate cancer (PCa) recurrence is a major clinical problem after radiotherapy, particularly in high-risk disease. MicroRNAs are small non-coding RNAs that regulate gene expression and are involved in many aspects of cancer. We hypothesize that miR-106a confers radioresistance in PCa. MiR-106a was significantly overexpressed in prostate tumours relative to normal prostate samples, and in high-grade tumours compared to low- and intermediate-grade specimens. MiR-106a overexpression increased survival and proliferation after radiation compared to control cells, by reducing senescence. Tumour xenograft experiments confirmed that miR-106a increases tumour growth after radiation compared to control tumours. LITAF was identified as a target of miR-106a. LITAF knockdown recapitulated miR-106a-induced radioresistance. MiR-106a overexpression and LITAF knockdown led to ATM promoter activation, with increased transcript and protein levels. ATM inhibition using KU-55933 resensitized miR-106a cells to radiation by inducing senescence. This work identifies miR-106a and LITAF as novel modulators of PCa radioresistance, through upregulation of ATM.
Species Diversity and Preferred Attributes of Trees: A Case Study of the Private Urban Forest in the Greater Toronto Area
Keywords: Ecological integrity
Residential landscapes
Socio-ecological relationships
Species diversity
Tree attributes
Urban forest

Healthy urban forests should have a diverse, native assemblage of species to support ecological integrity and reduce vulnerability to stressors. Since most urban trees are located on private property, landowner preferences for urban trees have a significant impact on the urban forest. Recent studies indicate that landowners select tree species based on aesthetic or functional attributes, without considering species diversity or ecological integrity. To examine the impact of landowner decisions, this study explores the relationship between property-level diversity metrics and aesthetic and functional attributes. Field inventories of trees on residential properties were conducted in Oakville and Markham, Ontario, and the results were analyzed along with residents’ knowledge, attitudes, and corresponding household characteristics gathered through a written survey. Few significant relationships were found in the statistical analysis, indicating that the residents’ decision-making process is complicated and requires further study.
Navigating Athlete Citizenship: The Negotiation of Rights, Roles and Responsibilities by Canadian Olympians
Keywords: athlete citizenry
athlete citizenship
athlete responsibilities
athlete rights
citizenship
Olympism

Forms of citizenship expand beyond those based on nation-state to involve populations at both sub-national and transnational levels (Roche, 2002; Yuval-Davis, 2006; Sindic, 2011). This research examines the athlete citizenry including (1) institutionalized meanings related to rights, roles, and responsibilities of high-performance athletes; and (2) the range of meanings of athlete citizenship negotiated by athletes. Document analysis and interviews with athletes and key informants have been deployed to synthesize an athlete citizenship framework. Findings from this research are: (1) athletes express a sense of belonging to a transnational community of high-performance and Olympic athletes; thus, it is possible to derive a definition of athlete citizenry by examining the athlete community through broader models of citizenship; (2) further work is needed to uphold and expand athletes’ rights; (3) athletes with recent high-performance success tend to engage in social initiatives to derive ‘deeper’ meaning from their sporting experiences.
Effect of Continuity of Care on the Risk of Developing Multimorbidity in Ontario, Canada between 2001 - 2015: A Retrospective Cohort Study
Keywords: chronic conditions
continuity of care
multimorbidity

Identifying modifiable, population-based factors for the prevention of multimorbidity is necessary to protect the health of patients and avoid unnecessary healthcare system costs. This study explored whether relationship continuity of care delays the onset of chronic conditions in patients from Ontario, Canada. Health administrative databases were used to assemble the cohort (N= 166,665) that was followed retrospectively between 2001 - 2015. A cause-specific hazards regression modelling approach was used to estimate the effect of continuity treated as a time-dependent exposure on the risk of developing multimorbidity and subsequent conditions adjusted for age, sex, place of residence, patient enrolment, income, and the number of physician visits. Estimates revealed that the risk of developing a second, third, and fourth condition was 8%, 10%, and 11% lower for patients with high versus low continuity, respectively. Therefore, efforts should be made to reduce the burden of multimorbidity by focusing on continuity of care.
Removal of N-nitrosodimethylamine (NDMA) Precursors During Drinking Water Treatment
Keywords: Biofiltration
DBP
N-DBP
NDMA
NDMA FP
Ranitidine

Technologies that are effective for natural organic matter and contaminant removal (i.e., coagulation) have been largely unsuccessful for the removal of N-nitrosodimethylamine (NDMA) and its precursors. A growing number of drinking water treatment plants that use chloramines for secondary disinfection have reported NDMA in finished water due to the reaction of chloramines with small nitrogen-containing molecules such as dimethylamine (DMA). This research examined the impact of pilot-scale biofilter operation on NDMA formation potential. The results of this study suggest that the use of biofiltration provides removal of NDMA precursors, regardless of filter operation. Ranitidine was also spiked at pilot scale to evaluate the ability of biofilters to remove a specific NDMA precursor and to confirm results using ambient influent waters. No significant difference (α = 0.05) was found in terms of NDMA FP removal due to filter operation strategy or empty bed contact time (EBCT).
approf: A Non-intrusive Call Hierarchy Profiler for Distributed Systems
Keywords: Distributed Systems
Failure Diagnosis
Logs

Runtime call graph profilers, like gprof [16], are widely used as debugging tools to identify performance bottlenecks. However, the intrusive nature of existing call graph profilers prevents them from being used continuously on production systems. This thesis presents approf , a non-intrusive tool that is capable of reconstructing an approximate runtime call hierarchy of method calls solely from existing application logs. At its core, it determines the call hierarchy by using a model that contains only classto-method invocation relationships extracted from the headers of the application’s compiled bytecode classes, avoiding the expensive static analysis required to extract a more rigorous method-to-method invocation model. The key property of this class-to-method model resembles a Bloom filter [12]. Using a few intuitive heuristics to improve the accuracy, we found approf is over 99% accurate in constructing call hierarchies while processing logs at approximately 50 MB/s per CPU core.
Development and Characterization of Novel Therapeutic Biologics to Enhance Immune Targeting of Clear Cell Renal Cell Carcinoma
Keywords: Bi-specific T cell engaging antibody
Carbonic anhydrase IX
clear cell renal cell carcinoma
Immunotherapy

Metastatic clear cell renal cell carcinoma (ccRCC) remains incurable with low 5-year survival rates despite various targeted therapies and checkpoint immunotherapy. Owing to the tumours’ immune sensitive nature and ubiquitous expression of a tumour-associated antigen carbonic anhydrase IX (CA9), this thesis exploits a novel immunotherapy strategy to target ccRCC using dual-specificity antibody T-cell engagers (DATEs). The CA9 DATEs were designed to engage human cytotoxic T cells against ccRCC cells by simultaneous binding to CD3 and CA9. My in vitro cytotoxicity co-culture results demonstrate that the CA9 DATEs potently redirected human T cells to lyse target cancer cells in an antigen-dependent manner across a panel of patient-derived ccRCC cell lines. In addition, T cell activation and cytotoxicity markers were up-regulated in concordance with cancer cell lysis. Collectively, my thesis provides proof-of-concept results with CA9 DATEs that can be further examined in pre-clinical models as a potential treatment strategy for metastatic ccRCC.
Motion Corruption Detection in Dynamic Contrast-Enhanced MRI of the Breast
Keywords: Computer-Aided Diagnosis
Image Registration
Machine Learning
Medical Imaging
Motion Corruption Detection

Motion corruption can result in difficulty identifying lesions, and incorrect diagnoses by radiologists in cases of breast cancer screening using DCE-MRI. Although registration techniques can be used to correct for motion artifacts, their use has a computational cost and can lead to a reduction in diagnostic quality rather than the desired improvement. In a clinical system it would be beneficial to identify automatically which studies have severe motion corruption and poor diagnostic quality and which studies have acceptable diagnostic quality. We have developed an automated method of estimating the degree of mis-alignment presents in a DCE-MRI study of breast screening. Two predictive models were investigated in this study and validated on a labeled dataset from radiologists denoting cases suffering from motion artifacts that affected image interpretability. We have managed to identify motion corrupted cases on our clinical dataset with an area under the AUC curve of 88%.
Decimation and Analysis: An Internal Bleeding Detection Framework for 3D Ultrasound
Keywords: 3D ultrasound
hemoperitoneum
segmentation
trauma
ultrasound

This thesis proposes a decimation-analysis (D-A) framework for detecting internal bleeding in 3D ultrasound medical scans. The structure consists of two main components: decimation, in which an input volume is reduced to suspect regions, and analysis, in which feature extraction is performed on said suspect regions. The D-A framework was designed to identify intuitive, easily-identiable features of blood pools as an aid for obtaining more complex shape information that can be assessed and matched to "library" data created from training volumes. The D-A framework is presented here for its concept and structure rather than for its actual performance, as rigorous, accurate testing was beyond the scope of the thesis; however, access to accurately segmented ground truth volumes (something missing during the experiment) would enable more in-depth development and validation of the framework.
Functional Genomic and Chemical Biology Analysis of Echinocandin Resistance in Candida albicans
Keywords: antifungal
Candida albicans
echinocandin
fungus
Hsp90
resistance

Candida albicans is a leading cause of invasive fungal infections, with mortality rates of ~40%. Effective treatment is hindered by the paucity of antifungal drugs and the emergence of resistance. My research exploits genetic and chemical screening approaches to uncover new therapeutic strategies to enhance the efficacy of the newest class of antifungals, the echinocandins. By screening mutant libraries collectively covering ~45% of the C. albicans genome, I identified 16 regulators of echinocandin tolerance, nine of which also modulate resistance. I identified a new role for the CCT chaperonin complex, which I found to modulate echinocandin susceptibility through actin. By screening 736 protein kinase inhibitors, I identified seven compounds that potentiate echinocandin activity. Chemogenomic profiling highlighted Yck2 and Hrr25 as potential targets of the most potent inhibitor, GW461484A. Future chemical validation of GW461484A targets and examination of in vivo utility will further uncover its therapeutic utility in combination with echinocandins.
Gap-Talk: How the “Achievement Gap” Reproduces Settler Colonial Constructions of Race within the Ontario Public School System
Keywords: Achievement Gap
Critical Race Theory
Opportunity Gap
Policy analysis
Settler Colonialism

The purpose of this study is to explore how the discourse of “achievement gaps” operates within settler colonialism. This study approached critical policy analysis (CPA) through a settler colonial theoretical lens and Critical Race Theory. Together, these theoretical frameworks provide a more comprehensive understanding of the ways in which racism and settler colonialism operate within schools and education institutions. By using critical discourse analysis (CDA), I looked at documents from the Toronto District School Board (TDSB) addressing the achievement and opportunity gaps. This analysis shows how these documents construct the notion of achievement as racialized in a way that upholds white settler property rights. The discourse of achievement gaps functions as a settler technology to include/exclude individuals simultaneously into the settler sector of the population. These findings have significant implications for those in educational policy research and practice interested in examining and addressing issues of power and inequality.
Investigating the Efficacy of Meditation and Mental Rehearsal on EEG BCI Performance in a Pediatric Context
Keywords: BCI
brain-computer interface
children
Electroencephalography
meditation
pediatric

The present study investigated the short-term effects of mindfulness meditation on brain-computer interface (BCI) performance in a pediatric context. The vast majority of previous BCI research has focused on creating more effective machine-learning algorithms. However, further improvements in user training are sorely needed. Mindfulness meditation is a promising methodology owing to its potential to increase an individual’s mental control. Twelve able-bodied children between the ages of 10 and 18 years were recruited. An auditory-tactile P300-BCI was designed for each individual participant. Each participant completed two sessions, one with 15 minutes of meditation preceding BCI operation and the other without. BCI control entailed an auditory-tactile oddball task. An average accuracy of 80.66%+11.68% was achieved across participants without meditation, while five participants exhibited significantly improved accuracy following meditation training. Using time-frequency features and a Gaussian Naive Bayes classifier, meditative and rest states were differentiated with an accuracy of 83.94 %+13.00%.
Using Component Air Leakage Models to Predict the Post-Retrofit Airtightness of a High Rise Residential Building: A Case Study
Keywords: Air Leakage
Airtightness
CONTAM
Factorial Analysis
Modelling
Monte Carlo

In this study, CONTAM 3.2, a modeling software that uses component air leakage rates, was used to estimate post-retrofit improvements in airtightness. A 12 storey residential building in Vancouver, British Columbia was studied. Pre- and post-retrofit airtightness data were used to assess the accuracy of the model predictions. Using a heuristic and two formal approaches, a pre-retrofit model was calibrated. Next, using the calibrated model and the specified airtightness data associated with the retrofit measures, post-retrofit airtightness was estimated using two approaches. Modelling results were then compared to the post-retrofit airtightness data. Using the factorial analysis and Monte Carlo approaches it was found that the best estimates were within 36% of the measured airtightness. While modeling can be an effective estimation tool, it is likely that the model developed here underestimated airtightness improvements because the retrofit measures were more airtight than specified by the designers.
Evaluation of Maximum Entropy Moment Closures for Predicting Radiative Heat Transfer Phenomena
Keywords: Combustion
Heat transfer
Maximum entropy
Moment closures
Radiation

This study considers an evaluation of moment closures based on the principle of maximization of entropy (MN, where N refers to the order of the closure) for providing approximate solutions to the radiative heat transfer equation (RTE). Several representative tests cases in both one- and two-dimensions are considered whereby the predictions of the MN models are compared to those of the discrete ordinates method (DOM) as well as the more commonly used spherical harmonics solutions (PN, where N refers to the order of the approximation) in terms of accuracy. More specifically, the present analysis is concerned with the lower-order approximations of the hierarchy of the MN closures, namely M1 and M2 and, for comparison purposes, the P1 and P3 spherical-harmonic closures are also considered. The potential of the M1 and M2 closures is explored and discussed for a range of problems involving radiative heat transfer in gray media.
Investigating the Role of Primary Cilia in Neuronal Apoptosis
Keywords: Abortive Cell Cycle
Apoptosis
Neurodegeneration
Neuroprotection
Primary Cilia
Retinal Ganglion Cells

Primary cilia are microtubule based, solitary emanations of the cell body present in most mammalian cells. The organelle nucleates from the basal body, which is also necessary for cell division, and thus inhibits cell cycling by its construction. It is recognized that neurons enter a detrimental cell cycle process called abortive cell cycling in a number of neurodegenerative diseases and following acute central nervous system injuries. However, it is unknown if primary cilia are retracted during this process and if their stabilization can inhibit the progression of this apoptotic cell cycle. Herein, we demonstrate that cilia are ablated in-vitro and in-vivo following injury. Furthermore, inhibition or knockdown of the proteins that disassemble the cilia increased neuron survival while forced cilia resorption enhanced cell death. Primary cilia may offer novel targets to inhibit apoptosis, which has implications for future therapeutic strategies for incurable neuronal pathologies.