VictorJuiz/thesis huggingface dataset:
Establishing a Level Playing Field: Development of a Prioritization Framework for Oncology Drugs

Objective This study will develop an oncology drug prioritization framework using multi-criteria decision analysis (MCDA). Methods A multi-stakeholder group identified and weighted key criteria to establish the MCDA framework (MCDA-f). Univariable analyses examined associations between MCDA-f score and pan-Canadian oncology drug review (pCODR) funding recommendations (FR). Sensitivity analysis varied the subjective criteria by ±1 for upper limit (UL) and lower limit (LL) values. Results The MCDA-f includes ten criteria (total score: 300); five are clinical benefit criteria (CBC) (total: 192). When MCDA-f was retrospectively applied to 30 drugs assessed by pCODR, mean MCDA-f score was 99 (LL-UL, 69-147); mean CBC was 54 (LL-UL, 45-77). Higher CBC scores were associated with positive FR (t-test p=0.004), with similar trend for MCDA-f (t-test p=0.07). Sensitivity analyses supported the base case results. Conclusion Using a structured and explicit approach, an oncology drug prioritization framework was constructed that can identify high impact drugs for funding.

Advisor: Leighl, Natasha B
Effects of Self-regulated Strategy Development on the Writing Performance and Sense of Self-efficacy of Postsecondary English Language Learners

English language learners (ELLs) comprise a growing contingent in North American postsecondary institutions. However, success in postsecondary requires competence in written expression, a taxing activity for most ELLs. To foster writing development, this study adapted the strategy instruction model of Self-Regulated Strategy Development (SRSD; Graham Harris, 1996) to teach strategies for research writing and vocabulary expansion. Six postsecondary ELLs received 36 hours of instruction over six weeks. Collecting data through a mixed methods design, the study measured performance gains as high as 10%, which, though moderate, contribute to growing evidence for the effectiveness of SRSD among postsecondary ELLs. Participants also reported positive transformations in their sense of self-efficacy alongside elevated confidence and lowered anxiety and stress. The study highlights the importance of guiding postsecondary ELLs through the framework of writing strategy instruction and suggests that SRSD may benefit writers by both teaching new strategies and validating existing writing practices.

Keywords: ELL
postsecondary
second language writing
self-efficacy
Self-Regulated Strategy Development
strategy instruction
Advisor: Piccardo, Enrica
Endothelial Heterogeneity: A Role for Epigenetic Pathways in Constitutive Gene Expression

Endothelial cells (ECs) have distinct gene expression and morphology depending on their location in the vasculature. A prevailing assumption is that these differences are largely caused by environmental factors, which differentially modulate gene expression in an otherwise homogeneous cell population. Here, we investigated the mechanistic basis for heterogeneity in EC gene expression and its functional importance, using P-selectin as a model gene. We found that heterogeneity exists basally in P-selectin protein expression across several human EC types. RNA FISH also showed heterogeneity in SELP transcription in isogenic populations of human umbilical vein endothelial cells (HUVEC). Differential proximal promoter DNA methylation, in part, accounted for this protein and RNA heterogeneity. In vitro methylation of the SELP promoter repressed transcription in episomal promoter reporter transfections. Importantly, promoter methylation was shown to be mitotically heritable. Using informative heterozygous SNPs in the SELP gene, we also report that P-selectin is monoallelically expressed in HUVEC.

Keywords: DNA methylation
Epigenetics
Gene regulation
Heterogeneity
P-selectin
Vascular biology
Advisor: Marsden, Philip A
Acquired Low Immunoglobulin Levels and Risk of Clinically Relevant Infection in Adult Patients with Systemic Lupus Erythematosus Cohort Study

Infection is a leading cause of mortality in systemic lupus erythematosus (SLE). Low immunoglobulin levels might be a potential risk for infection. We aim to examine the effect of acquired hypogammaglobulinemia on risk of infection in adults with SLE. Methods: We used Toronto Lupus Cohort to compare adult SLE patients who had acquired any low immunoglobulin levels to those who did not with respect to infection using time to event analysis. Several propensity score methods were used to improve group balance. Results: Patients with hypogammaglobulinemia had longer disease duration, more proteinuria and history of lupus nephritis. Low IgA levels increased the risk of infection. Recovery of immunoglobulins occurred in 64 percent of acquired hypogammaglobulinemia over four years. Conclusion: The majority of acquired hypogammaglobulinemia in adults with SLE is transient. Only low acquired IgA increases the risk of infection among adult patients with SLE. Mechanism of this association requires further investigation.

Keywords: Cohort
Immunoglobulins
Infection
Lupus erythematosus
Observational
Advisor: Urowitz, Murray B
Gladman, Dafna D
“We're sisters now”: Reciprocal Learning in a Canadian/Chinese Cross-cultural Educational Collaboration

My thesis presents the findings from a research study that examined the cross-cultural teacher collaboration between two elementary school teachers from Toronto and Shanghai within the context of the ‘Reciprocal Learning in Teacher Education and School Education Between Canada and China SSHRC Partnership Grant Project’. The theoretical framework that I use to analyze the research data draws on theories of multiliteracies, plurilingualism and cosmopolitanism. This exploratory narrative case study aims to answer the broad research question: What does reciprocal learning look like in a cross-cultural collaboration? The collaboration between the two teachers resulted in a digital ABC book and a series of video-taped Read Alouds by the students. Reciprocal learning in the classroom involved participants teaching and learning from each other, using multimodal literacy practices, recognizing and including cultural and linguistic diversity, focusing on relationship building, and co-constructing teaching and learning practices together.

Advisor: Cummins, Jim
Gagne, Antoinette
Childhood Disability and School Travel

There has been little research on children living with disabilities that use school boards’ accessible bus services, and no attention has been paid to their differences in excess travel compared to their non-disabled peers. This thesis explores the literature on childhood disability and school travel in order to identify current knowledge gaps and provide potential future research recommendations. In addition to, examining whether or not children with disabilities experience greater excess travel than their non-disabled peers when using accessible school buses and why? The results indicate that children with disabilities are experiencing significant inequalities in their school trips due to the much higher amounts of wasteful travel they encounter than non-disabled children. The findings also suggest there are numerous issues of ableism and disablism within educational settings that may have substantial influence on education access and school mobility for disabled children with potential long-term impacts.

Keywords: access
accessible busing
disability
education
excess travel
school travel
Advisor: Buliung, Ronald
Intervention for Arch Obstruction After Norwood: Prevalence, Associated Factors, and Practice Variability

Aortic arch obstruction after Norwood is common and causes mortality. We analyzed arch reinterventions after Norwood to determine associated factors and association with mortality. From 2005-2017, 593 neonates underwent a Norwood procedure. Multivariable parametric models, including a modulated renewal analysis, were performed. There were 218 arch reinterventions in 146 patients (25%) at median age 4.3 months. Factors associated with reduced risk for arch reintervention included: interdigitation of the distal aortic anastomosis and prior surgical arch reintervention. Factors associated with increased risk for arch reintervention included: development of tricuspid valve regurgitation and right ventricular dysfunction and transcatheter reintervention. Non-significant variables included: shunt type, coarctectomy, and pre-Norwood aortic measurements. Reintervention was not associated with increased mortality. There was wide institutional variation in arch reintervention practices. Serial surveillance for arch obstruction, including changes in right ventricular function and tricuspid valve regurgitation, is recommended after Norwood to enable prompt treatment of post-Norwood arch obstruction.

Keywords: arch intervention
complications
congenital cardiac surgery
Norwood procedure
parametric hazard analysis
survival
Advisor: McCrindle, Brian W
Anchorage of Single Leg Stirrups in Reinforced Concrete Slabs and Walls

According to CSA A23.3-14, stirrups shall be anchored by standard hooks or by heads of headed bars. In almost all applications, standard stirrup hooks require a bend of at least 135°. However, single leg stirrups with 135° hooks on both ends can be difficult to place in rebar cages. The purpose of this research was to compare the anchorage of single leg stirrups with 90° hooks, 135° hooks, 180° hooks, and T-headed bars. Four beams were made to test varying combinations of each kind of stirrup anchor. It was observed that stirrups with one 90° hook and one 135° hook were significantly weaker than stirrups with two 135° hooks. Stirrups with one 180° hook and one T-head were observed to be slightly weaker, but within 10% of the strength of stirrups with two 135° hooks. The results also indicated potential issues with the current CSA provisions for 15M stirrup anchorage.

Keywords: anchorage
concrete
hook
rebar
single leg
stirrup
Advisor: Collins, Michael P
Bentz, Evan C
Full-scale Monitoring of a Tall, Slender Building with Coupling Viscoelastic Dampers

Tall, slender buildings are sensitive to dynamic vibrations caused by wind, and the design of the building may be governed by occupant motion perception. A method to control dynamic vibrations is to increase the damping of the structure, which may be accomplished by the addition of a supplemental damping system. A novel system, the Viscoelastic Coupling Damper (VCD), was implemented for the first time in a tall, slender building which was under construction during the completion of this thesis. This building was the subject of a year-long plus monitoring program where output-only system identification algorithms were applied to track the development of the dynamic properties through the construction of the building. Additionally, several large amplitude wind events occurred during the program allowing for the tracking of amplitude-dependent phenomenon. The role of the VCD system was evaluated, and numerical finite-element models were constructed with reference to the experimental results

Keywords: Damping
Monitoring
Structural Dynamics
Structural Engineering
Tall Buildings
Viscoelastic Coupling Damper
Advisor: Christopoulos, Constantin
Development of an In Vitro Outer Annulus Fibrosus-cartilage Endplate Model and its Response to Dynamic Mechanical Loading

Tissue-engineering research to date has neglected to address the annulus fibrosus (AF)-cartilage endplate (CEP) interface of the intervertebral disc. It was hypothesized that in vitro-formed outer AF and cartilage tissues will integrate in co-culture to form an interface containing ECM that resembles the native interface, and that can be mechanically and compositionally enhanced through dynamic loading. 2-week old in vitro OAF tissues integrated with 3-day old in vitro cartilage by 1 week of co-culture, and resembled the distributions of collagen type I, collagen type II, and aggrecan seen in the native interface. The apparent tensile strength of the in vitro interface increased between 2 and 4 weeks of co-culture. Dynamic mechanical loading did not enhance the mechanical strength, appearance, or composition of the interfacial matrix. This study demonstrated the ability to engineer a biological AF-CEP interface model, and will assist in defining how future tissue-engineered disc replacements should be developed.

Keywords: Annulus Fibrosus
Biomaterials
Cartilage Endplate
Intervertebral disc
Tissue engineering
Advisor: Kandel, Rita
Santerre, Paul
Column-parallel 7um-pitch 2nd-order Delta-Sigma ADCs for Computational Image Sensors

This thesis presents a methodical way to integrate the full digital readout chain on-chip for computational image sensors to help lower the system complexity. A review of conventional readout architectures for image sensors is done. Next, the choice of a column-parallel 2nd-order incremental delta-sigma ADC followed by a serializer is argued for. System-level performance verification of the ADC is done in MATLAB. Circuit implementation of blocks such as integrators and quantizer are then described. Simulation results for these circuits are presented. The entire readout chain was implemented in 110 nm CMOS and characterized. An ENOB of 11.65 bits is obtained at the modulator output. The modulator consumes 475.6 uW while operating at 250 kSps. A FoMSchrier of 156 dB is achieved. Finally, a novel hardware-efficient way to integrate programmable gain within the delta-sigma modulator is also proposed, and simulation results are discussed.

Advisor: Genov, Roman
Combined Multimodal Cerebral Monitoring and Serial Hemodynamic Assessments at the Bedside in the First 72 Hours after Birth in Extremely Low Gestational Age Preterm Infants

Previous research on intraventricular hemorrhage in preterm infants has shown that characteristic patterns of cerebral monitoring or echocardiography parameters measured during the transitional period after birth are associated with, and may precede its occurrence. Clinical application of combined cerebral and hemodynamic monitoring in preterm infants has not been previously studied. In a cohort of 50 preterm infants born at gestational ages between 23+0 and 27+6 weeks, we prospectively demonstrated the feasibility and safety of using a combination of cerebral near infrared spectroscopy, amplitude integrated electroencephalography, sequential head ultrasound and echocardiography, in the first 72 hours after birth. Application of multimodal monitoring was feasible in 49 (98%) of infants. We characterized the patterns of measurements in infants with and without intraventricular hemorrhage. Our work lays foundation for future research on brain and heart monitoring for early identification of preterm infants at risk of developing brain injury.

Keywords: amplitude integrated EEG
cerebral saturation
echocardiography
Intraventricular Hemorrhage
neuro-monitoring
preterm
Advisor: Guerguerian, Anne-Marie
Examining the Use of Wireless Physical Activity Monitors Among Adults Living with HIV

Background: Wireless physical activity monitors (WPAMs) are used to measure physical activity among healthy and chronic illness populations, however their use and measurement properties in the context of HIV are unclear. Methods: I conducted a Scoping Review using the Arksey and O’Malley framework and a cross-sectional measurement study to assess criterion and construct validity of the Fitbit Zip® to measure physical activity among adults living with HIV. Results: Twenty-five articles were included in the scoping review. WPAMs were used primarily as a measure of physical activity, and to a lesser extent a motivational tool to enhance physical activity. The cross-sectional measurement study provided evidence of criterion validity of the Fitbit Zip® to measure steps taken but not distance walked (m) and did not establish construct validity for measuring physical activity. Conclusion: Results provide directions for future research including, physical activity promotion using WPAMs and assessing measurement properties of other WPAMs.

Keywords: HIV
Measurement
Physical Activity
Wireless Physical Activity Monitor
Advisor: O'Brien, Kelly K
Substrate Dependent Galvanotaxis of Directly Reprogrammed Human Neural Precursor Cells

Adult neural precursor cells (NPC) show great promise for the repair of central nervous system tissue following injury or disease, however, their activation is not sufficient for neurorepair. Enhancing NPC mediated repair is a goal of regenerative medicine. Here, we examined the electric field (EF) induced migration of a clinically relevant human NPC population and the role of the extracellular matrix. Human NPCs were found to migrate in a substrate dependent manner, where the direction of migration differed according to substrate. We explored the responsiveness of EF induced human NPC migration to extracellular matrix (ECM) components, secreted factors of neighboring cells, extracellular pH, and substrate stiffness. Interestingly we found human NPCs migrate anodally on softer substrates (matrigel/cell monolayer) and cathodally on stiffer substrates(fibronectin). This study aims to provide a better understanding of human NPC migration to direct future in vivo studies focused on enhancing NPC migration to promote neural repair.

Advisor: Morshead, Cindi M
Popovic, Milos R
Building Clinically Relevant Thermal Simulation Tools for High Intensity Focused Ultrasound Therapy in Soft Tissue

Magnetic Resonance guided High Intensity Focused Ultrasound (MRgFUS) therapy is a non-invasive thermotherapy, with a range of potential applications, including paediatric soft tissue tumours. The aim of this project is to create a clinically-relevant, modular MRgFUS simulation tool. The tool was developed using Python, open-source python libraries, and CUDA, a library for parallel computing. Validation of the simulator was achieved through the comparison of simulated and experimental sonications of ex vivo agar-sealed porcine kidney (n=4) and liver (n=4) tissue samples. The tool was analyzed using four metrics: peak temperature difference, cool down rate, ablation ratio, and spatial accuracy. This generalized software simulation tool will help to bring MRgFUS therapy one-step closer to being the clinical standard across a wide range of complex conditions.

Keywords: Acoustics
Bioheat
Computational Modelling
Focused Ultrasound
Parallel Programming
Wave Propogation
Advisor: Drake, James
Waspe, Adam
Early Cardiac Remodeling in Women with Breast Cancer, Receiving Sequential Therapy with Anthracycline and Trastuzumab – Cardiac MRI Study

Background: Cardiotoxicity is an adverse prognostic marker in women with early-stage breast cancer. Understanding cardiac changes using cardiac-MRI will provide the opportunity to establish predictive models for early detection of cardiotoxicity. Methods: Eighty-three patients had cardiac MRI pre-anthracycline, within three weeks post-anthracycline, and at five months (~three months into trastuzumab therapy) on a 1.5T scanner; along with thirty volunteers scanned at matched time points. Results: Temporal and inter-observer test-retest variability, repeatability, and reproducibly of left and right ventricular volumetric parameters in healthy volunteers were statistically small. Ten patients (12.1%) developed LV-cardiotoxicity, 1 (10%) at 2 months and 9 (90%) at 5 months. LV-cardiotoxicity was associated with a significant increase in LVESV in 91% of the patients. Conclusions: Ventricular remodeling occurs during cancer therapy. The primary mechanism of cardiotoxicity is likely a reduction in contractility. Change in LVESV at 2 months is an early predictor of cardiotoxicity by 5 months.

Keywords: Breast Cancer
Cardiac MRI
Cardiotoxicity
Healthy Volunteers
Postprocessing
Temporal Variability
Advisor: Connelly, Kim A
Thavendiranathan, Paaladinesh
Accelerating 3D Monte Carlo Photonic Simulations on Tightly Coupled CPU-FPGA Systems

Many medical applications use light for diagnostics and treatment purposes, and they require modeling of light propagation in heterogeneous biological tissues. To model the light transfer accurately, researchers generally use Monte-Carlo simulations which are computationally expensive and accelerating these simulations would be benecial to many medical applications. In this thesis, we explore methods of accelerating the light propagation simulation on Field-Programmable Gate Arrays (FPGAs). We introduce a hardware-accelerated light transfer simulator with a 3D voxel-based tissue representation designed using High-Level-Synthesis. Our experimental results show a 3x speedup against the fastest software simulator published to date (FullMonte [1]). Additionally, we enhance the fastest existing hardware-accelerated 3D tetrahedron-based simulator to-date (FullMonteHW [2]) by adding features such as various light emitters. We demonstrate how this tightly-coupled CPU-FPGA simulator can enable the full functionality of the software version of FullMonte, while maintaining the expected performance gain of 16X via FPGA acceleration.

Advisor: Betz, Vaughn
Arabidopsis thaliana Meiosis: HOP2 Interactions with Proteins and Chromatin

Homologous Pairing 2 protein (HOP2) is believed to play a crucial role in meiosis by promoting pairing of homologous chromosomes in anticipation of recombination. The loss of HOP2 causes a multitude of meiotic aberrations leading to sterility in yeast, mice, and plants. My research focuses on the Arabidopsis thaliana HOP2 homolog and its interactions with proteins and chromatin. In this study, using co-immunoprecipitation and chromatin immunoprecipitation assays, I set out to confirm existing and identify novel protein-protein interactions involving HOP2. Moreover, I attempt to elucidate the manner in which HOP2 interacts with chromatin. I demonstrate the in vivo interaction of HOP2 with Meiotic Nuclear Division 1 protein (MND1) and the preferential interaction of HOP2 with euchromatin which follows crossover occurrence patterns in Arabidopsis thaliana. My research corroborates previous findings regarding HOP2-protein interactions and provides a basis for HOP2 studies involving chromatin interactions.

Keywords: Chromatin interaction
Homologous recombination
HOP2
Meiosis
Protein interaction
Advisor: Riggs, Dan
CD22 is Indispensable for Galectin-9-mediated Inhibition of B Cell Signaling

B-cells are an important component of the adaptive immune system, producing antibodies and conferring long-term immunity. B-cell activation is initiated by recognition of foreign particles (antigens) by B-cell receptors (BCR). Previous research in our lab found that the lectin, Galectin-9 (Gal9), regulates B-cell activation; however, the mechanism remains unclear. In this study, we demonstrate using super-resolution microscopy that Gal9 regulates the organization of a lattice of inhibitory and stimulatory receptors to inhibit B-cell signaling. We found that the inhibitory receptor CD22 is crucial for this Gal9-mediated mechanism. Furthermore, we demonstrate that CD22 N-linked glycosylation is required for Gal9-mediated inhibition of signaling. To our knowledge, our study is the first to highlight the importance of galectins in regulating CD22 organization, as well as define N-glycans in CD22 as imperative in regulating B-cell signaling. Our findings may have important implications for the therapeutic application of Gal9 to alleviate B-cell mediated autoimmune diseases.

Keywords: B cell
Galectin
Immune
Immunology
Microscopy
Signaling
Advisor: Treanor, Bebhinn