VictorJuiz/thesis huggingface dataset:
Risk of Stroke in Older Women Treated for Early Invasive Breast Cancer, Tamoxifen vs. Aromatase Inhibitors: A Population based Retrospective Cohort Study

Tamoxifen and aromatase inhibitors are treatment options for women with breast cancer and evidence on the risk of stroke is important in choosing between these two options. A systematic review of two randomized controlled trials and their nine related trial reports showed different methods for adverse event reporting and inconsistent estimates of stroke risk. In an observational cohort study of 5443 Ontario women, aged 66 years or older with early stage breast cancer, 86 ischemic stroke events (1.6%) occurred during follow-up of 5 years. There was no statistically significant difference in the risk of stroke between the hormone therapy groups [adjusted HR for tamoxifen compared to AI 1.330 (0.810, 2.179)]. Results were similar across cardiovascular disease risk groups and were robust to different follow up periods and analytic methods. This study suggests that there is no significant difference in stroke between these treatment options.

Keywords: Stroke
Breast Cancer
Tamoxifen
Aromatase Inhibitors
Anastrozole
Letrozole
Population
Cohort
Retrospective
Administrative Databases
Advisor: Rochon, Paula A.
Investigation of a Putative Secondary Binding Site between the Broadly Neutralizing Monoclonal anti-HIV-1 Antibody and its Antigen gp41

One potential approach to vaccine development against HIV involves generating an immunogen that can elicit the production of broadly neutralizing monoclonal antibodies (bnmAbs), which target specific sites on the HIV-1 envelope. Using site-directed mutagenesis and ELISA assays, this thesis investigates the idea of a secondary binding site of one of the bnmAbs, 2F5, as suggested by previous studies that identified residues Asp64, Thr65, and Arg82B on 2F5 that are recognized by its anti-idiotypic antibody 3H6. Results show that 2F5 binds only very weakly to the gp41 ectodomain in its post-fusion conformation. However, a small but significant difference was observed between the binding of the mutants and the T-20 peptide, a fusion inhibiting drug. Due to the limited effect, the results need to be confirmed using more quantitative techniques and more optimal conformations of the antigen, but raise the prospect that design of immunogens to elicit HIV-specific antibodies might have to incorporate this novel interaction site.

Keywords: HIV-1
broadly neutralizing antibodies
gp41
2F5 Fab
Advisor: Pai, Emil F.
Coordinated Land Use and Transportation Planning – A Sketch Modelling Approach

A regional planning model is designed to facilitate coordinated land use and transportation planning, yet have a sufficiently simple structure to enable quick scenario turnaround. The model, TransPLUM, is built on two existing commercial software products: the Population and Land Use Model (PLUM); and a four-stage travel model implemented in a standard software package. Upon creating scenarios users are able to examine a host of results (zonal densities, origin-destination trip flows and travel times by mode, network link flows, etc) which may prompt modification of a reference land use plan and/or network plan. A zonal density-accessibility ratio is described: an index which identifies the relative utilization of a zone and which could serve as a coordinating feedback mechanism. The model was implemented for a pilot study area – the Winnipeg Capital Region. Development of a baseline scenario is discussed.

Keywords: land use
transportation
planning
model
scenario planning
winnipeg
sketch
Advisor: Miller, Eric
An Assessment Tool and Interactive Simulation for Using Healthcare Personal Protective Equipment

In healthcare, personal protective equipment (PPE) are sometimes misused due to improper skill acquisition or skill decay before clinical practice. Training is often didactic or web-based but it is unclear whether these methods transfer to effective physical performance. There is no standard method to evaluate these competencies and scheduling or space restrictions can limit physical practice. A Delphi survey produced relevant checklist and global rating items for evaluating use of PPE. Principles from skill learning and human-computer interaction were combined with the survey results to develop an interactive computer-based simulation for procedural practice of these skills. The assessment tool differentiated between experienced and newly-trained users and demonstrated inter-rater reliability. Learners rated their satisfaction with the simulation similar to a provincial online tutorial and pilot studies with the simulation demonstrated that learners practiced for a longer period when using the simulation as compared to the provincial online tutorial.

Keywords: Infection control
Delphi
checklist
global rating
computer
practice
Advisor: Carnahan, Heather
Global Quantitative Proteomic Profiling through 18O-labeling in Combination with MS/MS Spectra Analysis

By integrating the simplicity of 18O-labeling and the low signal-to-noise of MS/MS spectra with supporting software and combining them with global shotgun protein identification, a robust quantitative pipeline has been created that avoids the disadvantages of other quantitative approaches. Test mixtures of labeled and unlabeled peptides were subjected to LC-MS/MS profiling experiments. Software programs were developed and applied to automatically determine protein ratios between two samples while applying a correction for incomplete labeling. The measurement of relative abundance at the product ion (MS/MS) level, instead of at the full scan (MS) level, is shown to provide excellent accuracy and sensitivity. Ratio distributions approached the expected means, allowing empirical derivation of confidence level cutoffs for determining statistically significant fold-changes in protein abundance. A set of stringent criteria for detecting spurious ratios based on consistency checking between unlabeled and labeled y-ion pairs was found to highlight putative false positive identifications.

Keywords: proteomics
mass spectrometry
quantitative
stable isotope
profiling
protein
labeling
quantification
Advisor: Emili, Andrew
Optimizing Enzymatic Preparations of Mechanical Pulp Through the Characterization of New Laccases and Non-productive Interactions Between Enzymes and Lignin

The overall objective of this research is to identify and optimize enzymatic applications that have the potential to degrade middle lamella lignin, so as to decrease economic and environmental costs associated with the production of mechanical pulp. Non-productive binding of enzyme to lignin in lignocellulosic biomass reduces enzyme availability and efficiency. The elucidation of non-productive binding behavior between hydrolytic enzymes and lignocellulosic substrates could significantly improve the efficiency of corresponding industrial bioprocesses. The first part of this report presents a study that characterizes non-catalytic interactions between enzymes and fibre. The second part of this report presents the biochemical and mutational studies of a novel, small laccase SCO6712 from Streptomyces coelicolor. The findings from this research support the design, control, and optimization of enzymatic treatments of lignocellulosic fibres in the pulp and biofuel industries.

Keywords: mechanical pulp
laccase
xylanase
lignin
non-productive binding
SCO6712
Advisor: Master, Emma
Effects of Varenicline on Cue-reactivity in Individuals with Concurrent Tobacco Dependence and Heavy Alcohol Use: A Randomized, Double-blind, Placebo-controlled Trial

BACKGROUND: Alcohol and tobacco misuse and dependence are highly comorbid disorders. Varenicline alleviates symptoms of cigarette craving while preventing nicotine from binding to nicotinic acetylcholine receptors, thereby reducing nicotine’s reinforcing effects. Recent studies have shown that varenicline decreased alcohol self-administration in animal models and in one human study of heavy-drinking smokers. AIMS: To assess the effect of two-week varenicline (0.5-2mg) vs. placebo administration on cue-induced craving for tobacco and alcohol in smokers with heavy alcohol use (n = 24). METHODS: Subjects participated in two study visits where nicotine and alcohol craving and withdrawal were assessed with self-report questionnaires under four conditions (abstinence/one cigarette/neutral cues/tobacco-alcohol cues). RESULTS: Two-week administration of varenicline reduced tobacco-alcohol cue-induced cigarette cravings and reduced emotionality aspects of alcohol craving after smoking a cigarette compared to abstinence in heavy-drinking smokers. CONCLUSION: It is possible that varenicline may have particular advantages as a smoking cessation aid in heavy drinkers.

Keywords: Varenicline
Cue reactivity
Tobacco
Alcohol
Advisor: Busto, Usoa
Contextual Processing of Objects: Using Virtual Reality to Improve Abstraction and Cognitive Flexibility in Children with Autism

Background: The current study investigated the efficacy of a novel virtual reality-cognitive rehabilitation (VR-CR) intervention to improve contextual processing of objects in children with autism. Contextual processing is a cognitive ability thought to underlie the social and communication deficits of autism. Previous research supports that children with autism show deficits in contextual processing, as well as deficits in its basic component abilities: abstraction and cognitive flexibility. Methods: Four children with autism participated in a multiple baseline single-subject study. The children were taught how to see objects in context by reinforcing attention to pivotal contextual information. One-on-one teaching sessions occurred three times per week for approximately two weeks. Results: All children demonstrated significant improvements in contextual processing and cognitive flexibility. Mixed results were found on the control test. Changes in context-related behaviours were reported. Conclusions: Further studies using virtual reality to target specific cognitive impairments in children with autism are warranted.

Keywords: autism
virtual reality
cognitive rehabilitation
single-subject design
executive function
cognitive flexibility
Advisor: Reid, Denise
Construction of Lentivirus Vectors for Modulating Intrinsic Dendritic Cell Properties

Dendritic cells (DCs) are promising mediators of anti-tumour immune responses. Unfortunately, a major hindrance to the development of highly effective DC vaccines is their short lifespan. Tumour antigen presentation may also not be optimal. We hypothesize that the introduction of exogenous survival factors (SFs) would prolong DC longevity and that modulation of TAA glycosylation will improve antigen presentation. To this end, we have constructed bicistronic lentivectors (LVs) encoding the xeno Tumour-Associated-Antigen (TAA), rHER-2/neu, and one of five candidate SFs. We demonstrated that our LVs can effectively protect transduced DCs from apoptosis when subjected to apoptosis-inducing conditions. TAA glycosylation has been proposed to obstruct the processing and presentation of peptides on MHC molecules. To address this second issue, we have engineered a LV that encodes a partially deglycosylated rHER-2/neu. Overall, we have generated the tools to alter intrinsic DC properties, which we believe will be integral to improving DC vaccine efficacy.

Keywords: dendritic cells
lentivirus
gene therapy
cancer immunotherapy
HER-2/neu
dendritic cell longevity
antigen n-glycosylation
lentivector
Advisor: Medin, Jeffrey A.
An FPGA-based Accelerator Platform for Network-on-chip Simulation

The increased demand for on-chip communication bandwidth as a result of the multi-core trend has made packet-switched networks-on-chip (NoCs) a more compelling choice for the communication backbone in next-generation systems. NoC designs are sensitive to many design parameters—hence the study of new NoCs can be time-intensive. We propose DART, a fast and flexible FPGA-based NoC simulation architecture. Rather than laying the NoC out directly on the FPGA like previous approaches, DART virtualizes the NoC by mapping its components to a generic NoC simulation engine. This approach has two main advantages: (i) since it is virtualized it can simulate any NoC; and (ii) any NoC can be mapped to the engine without the time-consuming process of rebuilding the FPGA design. We demonstrate that an implementation of DART on a Virtex-II Pro FPGA achieves over 100x speedup over the cycle-based software simulator Booksim, while maintaining the same level of simulation accuracy.

Keywords: network-on-chip
computer arhictecture
FPGA
simulation
Advisor: Steffan, J. Gregory
Jerger, Natalie Enright
Novel Properties of SP cells in STS, and How They May Be Targeted to Develop Potential Therapies

Tumours contain heterogeneous cell populations. A population enriched in tumour-initiating potential has been identified in soft-tissue sarcoma (STS) by the isolation of "side population" (SP) cells. In this study, we compared the gene expression profiles of SP and non-SP cells in STS and identified Hedgehog (Hh) and Notch pathways as potential candidates for the targeting of SP cells. Upon verification of the activation of these pathways in SP cells, using primary tumor xenografts in NOD-SCID mice as our experimental model, we used the Hh blocker Triparanol and the Notch blocker DAPT to demonstrate that the suppression of these pathways effectively depleted the abundance of SP cells, reduced tumour growth, and inhibited the tumour-initiating potential of the treated sarcoma cells upon secondary transplantation. The data provide additional evidence that SP cells act as tumour initiating cells and points to Hh and Notch pathways as enticing targets for developing potential cancer therapies.

Keywords: Cancer
Stem Cell
Soft-tissue sarcoma
sarcoma
Notch
Hedgehog
Therapy
Advisor: Alman, Benjamin
Health Utilization Patterns of Colonic Stents in Colorectal Cancer: A Retrospective Population-based Cohort Analysis

Introduction: This study describes the patterns of use and processes of care following colonic stent insertion for patients with colorectal cancer (CRC) in clinical practice. Methods: Ontario residents who had a colonic stent placed for CRC between 2000–2009 were identified using linked administrative databases. Baseline patient, physician, and institutional characteristics were extracted. The cohort was followed for death and health services utilization post-stent. Results: Two hundred twenty-five patients were identified. Median overall survival post-stent insertion was 199 days (interquartile range [IQR] 153-282). Eighty-five (38%) patients required a subsequent intervention (abdominal surgery, restenting, and/or dilatation). Median intervention-free survival was 75 days (IQR 59-91). Following stent insertion, the average rate of ER visits was 2.4 visits per person-year of follow up (95% CI, 2.2-2.7) and the overall average days spent in hospital was 19 inpatient days per person-year (95% CI, 18-19). Conclusions: In clinical practice, many patients required another intervention shortly after stent insertion; however, the rate of post-stent ER visits and inpatient hospital days was low.

Keywords: Colorectal cancer
Stent
Obstruction
Advisor: Paszat, Lawrence
Modelling Jet Nebulizers to Estimate Pulmonary Drug Deposition

Administration of medication directly to diseased lungs reduces adverse systemic side effects. For cystic fibrosis, jet nebulizers are the standard aerosol delivery system since they can aerosolize drugs that require relatively large volumes of liquid. Selection of the appropriate nebulizer for a given drug is crucial to ensure delivery of the therapeutic dose. This selection, ideally, requires knowledge of the pulmonary drug deposition (PDD). The gold standard for accurately measuring PDD is nuclear medicine techniques, which exposes the subject to radiation and therefore cannot be used repeatedly to test multiple devices. An alternative is to characterize the nebulizer using in vitro experiments and estimate the device’s in vivo performance. However these techniques are time-consuming and can only collect data for one breathing pattern and drug-device combination. Therefore this study is to formulate mathematical models for jet nebulizers that can estimate PDD based on the drug-device combination and patient’s breathing patterns.

Keywords: Aerosol Medicine
Clinical Engineering
Advisor: Coates, Allan
Learning to Adjust to the Canadian Graduate Classroom: A Multiple Case Study of the Participation of Four Chinese Graduate Students in Classroom Discussions at a Canadian University

This study investigates how 4 newly admitted Chinese international graduate students participate in classroom discussions at a Canadian university. This qualitative research provides rich descriptions of their backgrounds and classroom participation, as well as their voices related to their classroom experiences. Framed by Language Socialization Theory, the study examines the classroom contexts where the students are socialized, particularly the social relations in the classroom that influence the 4 students’ participation. The study also investigates the role of the 4 students’ agency in the negotiation of access and participation in classroom discussions, as well as their identity formation in classroom communities. The findings of this research highlight the co-constructed and bi-directional nature of language socialization. The 4 students’ classroom experiences are not only shaped by their educational, cultural and social backgrounds, but are also jointly constructed by local contextual factors in Western classrooms. Pedagogical implications are also discussed.

Keywords: second language learning
classroom discussions
classroom participation
studying abroad
Advisor: Gagne, Antoinette
Ideology and Reality: Putting Belief and Behaviour in Context

This paper investigates how belief, social power, and ideology work together to create the subjectivities and social structures that guide our behaviour. Phenomena such as cognitive shortcuts, memory, bias, empathy, and dissonance are used to trace the effects of power and ideology on social construction and role-taking behaviour. Research on mass opinion in the United States is then used to identify the effects of information and salience on construction. Different conceptions of ideology and interest, drawn from the work of Hume, Marx, Gramsci, Althusser, Foucault, and others were referenced to explore the larger social dynamics of ideas and structures. Academic, ethical, and democratic implications are investigated at different points. The paper concludes by connecting parenting style to moral development in order to find strategies for resisting the tendency towards institutional behaviour.

Keywords: power and cognition
Advisor: Trifonas, Peter
Migration Stories: Experiences of Recently Arrived Latino Youth in the Canadian Public School System

The purpose of this study is to investigate, through narrative analysis, the arrival stories of Latino/a immigrants into the Canadian school system, and to examine how their migration experience influences their identification process. The data to be analysed was collected during interviews conducted for the Proyecto Latin@ project; a research that looks into the perspectives of Latino/a youth towards school desertion and their experiences as Latino/a students in Canada. Interviews analysed included students with recent arrival dates into Canada ( < 3 years at the time of interviews). Their narratives displayed a shift in ideology as students internalized the dominant discourse and present a conundrum for students struggling in school. This analysis attempts to add to the growing body of knowledge on the specific difficulties faced by the Latino/a youth upon their arrival into Canada, as well as how their identities develop and shift during this process.

Keywords: Latino
identification
immigration
Advisor: Gaztambide-Fernandez, Ruben
Research Use and its Impact on Secondary Education: Take-up of Different Knowledge Mobilization Strategies

This project is based on a study supported by the Canadian Education Association. The project examines how research activities have been implemented and carried out in nine secondary school districts across Canada. The main research questions are to understand how school districts organize to embed knowledge from external research in their secondary schools and to understand the impacts of small-scale interventions intended to increase the use of research in secondary schools and districts. This thesis documents a part of the greater project with a focus on educators’ knowledge about two main areas related to secondary school improvement: success factors for students and student pathways/trajectories. Data were collected through questionnaires, teleconference calls and individual communication with district leaders. The study concludes that it is difficult to know the impact of the interventions; impact seems modest but a few key elements have been identified that facilitate take-up of the research activities.

Keywords: knowledge mobilization
research use
research activity
Education
Advisor: Levin, Ben
Coupled Interface Modes for Nonlinear Interaction in Periodic Layered Media

This thesis proposes the platform for the observation of a new type of electromagnetic interface mode, Coupled Interface Mode, and studies the utilization of this mode in second order nonlinear interaction in AlGaAs. The dispersion relations for theoretical examination of the modes are developed and used to design a waveguide structure that accommodates a three wave mixing process utilizing coupled interface modes. The waveguides are fabricated according to optimized fabrication recipes and characterized for linear and nonlinear properties. Second harmonic generation is adopted for the demonstration of nonlinear interaction, due to its convenient experimental set-up. Three different laser sources are used to pump the waveguides and second harmonic light is generated and characterized. Coupled interface modes in conjunction with other types of modes also existing within the same structures, offer the possibility to explore three-wave mixing processes such as sum and difference frequency generation.

Keywords: Coupled Interface Modes
Second Order Nonlinear Interaction
Advisor: Helmy, Amr S.
From Greek School to Greek's Cool: Heritage Language Education in Ontario and the Aristoteles Credit Program - Using Weblogs for Teaching the Greek Language in Canada

Heritage Language Education is considered the cornerstone of Canada’s multiculturalism policy. In Ontario, the mission to preserve the cultural capital of the various ethnic communities is carried out primarily by non-profit organizations and groups with limited official support. My thesis is the autobiographical inquiry of an internationally educated teacher who is involved in a Greek language credit program in Toronto. My commitment to understanding the needs of the new generation of learners guided me through a series of professional development initiatives and the creation of an educational blog which is currently used by students, parents and teachers of the Aristoteles Credit School. By presenting my experiences as I navigated the multidimensionality of HLE in Ontario, I hope to offer a case of a bottom-up reform attempt which is based on transformative pedagogy and brings heritage language education to the epicentre of community activity and educational change in the 21st century.

Keywords: heritage language education
transformative pedagogy
bilingualism
blogs in education
multiculturalism
Greek language
computer supported collaborative learning
learning communities in education
multiliteracies
heritage languages in Canada
Advisor: Trifonas, Peter