VictorJuiz/thesis huggingface dataset:
Impact of Policy Changes on Utilization of Community Medication Review Services in Ontario among People Living with Diabetes

Since 2007, the Ontario government has funded pharmacy medication review services (MedsCheck Annual [MCA]) for residents taking 3+ chronic medications. In 2010, MedsCheck was broadened to include patients with diabetes (MCD). In 2016, a policy change added several components to Medscheck services, including diabetes-specific training for pharmacists and diabetes-specific education/goal-setting with patients. The objective of this thesis was to examine the impact of the 2010 and 2016 policy changes on the monthly rate of MedsCheck service delivery among adults living with diabetes. Using interrupted time-series analysis, our study demonstrated that the 2010 policy change slightly increased delivery of MedsCheck services, whereas the 2016 policy change resulted in a dramatic decline in the use of MedsCheck services; with evidence of possible displacement from MCD to MCA. Future research is needed to better understand the impact of the policy changes on access and effectiveness of MedsCheck services, and barriers/facilitators of MedsCheck implementation.

Keywords: Community pharmacy services
Health policy
Interrupted time series analysis
Medication reconciliation
Advisor: Cadarette, Suzanne M
Role of Peroxisome Proliferator-activated Receptor γ (PPARγ), Pulmonary Blood Flow and Oxygen Delivery in the Regulation of Surfactant Maturation in the Fetal Lung

At birth, the fetal lung must be mature enough for the fetus to survive the transition to an air-breathing environment. This requires reduction of surface tension at the air-liquid interface to prevent alveolar collapse, achieved by production of surfactant. One factor regulating surfactant production is peroxisome proliferator-activated receptor-γ (PPARγ). This thesis examines the effect of intrafetal rosiglitazone (RGZ; a PPARγ agonist) and leptin administration on surfactant maturation in sheep. In addition, the effect of maternal late gestation undernutrition (LGUN) on surfactant maturation, pulmonary blood flow (PBF) and oxygen delivery (DO2) is investigated. Our findings suggest that there is no effect of RGZ or LGUN on PPARγ signaling or surfactant maturation, whereas leptin infusion increases PPARγ and decreases surfactant protein (SFTP)-B expression in the fetal lung. An additional novel finding is the negative correlation between PBF and DO2 with SFTP-B mRNA expression in late gestation.

Advisor: Seed, Mike
Morrison, Janna L.
Maternal BMI, Breastfeeding and Perinatal Factors that Influence Early Childhood Growth Trajectories

Obesity among children is a global concern. Fetal programming and early life nutrition have been implicated in both childhood and adult obesity. Perinatal interventions aimed at reducing the risk of child obesity may be important for prevention. It was hypothesized that anthropometric and genetic analysis can identify a priority population that would benefit from an exclusive breastfeeding intervention. To test this hypothesis, a scoping review was conducted, and ALSPAC cohort data was analyzed. The scoping review results show early life risk factors were multi-factorial, they were also socially patterned and accumulative. These data suggest children with overweight and obese mothers, who were low income and from an ethnic minority group were at higher risk for obesity and could be targeted for preventive intervention. The results from the ALSPAC study show maternal BMI and the genetic risk score are the strongest independent predictors of obesity at 17 years of age.

Keywords: Breastfeeding
Childhood obesity
Maternal and infant health
Maternal BMI
R programming
Scoping review
Advisor: Lye, Stephen J
Dennis, Cindy-Lee
Characterization of Matrin-3 Mutations Associated with Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal disease that is characterized by progressive motor neuron degeneration. Matrin-3 (MATR3) is an RNA-binding protein that is involved in alternative splicing regulation. S85C and F115C are dominantly inherited MATR3 mutations that are linked to familial ALS. I investigated the role of MATR3 mutations in ALS pathogenesis using two models: 1) transgenic flies expressing human wild-type or mutant MATR3 in the motor neurons and 2) MATR3 S85C knock-in mice. I found that mutant MATR3 expression in the motor neurons is more toxic to flies than wildtype MATR3. In addition, MATR3 S85C knock-in mice show features reminiscent of ALS including severe motor impairments associated with degeneration of the Purkinje cells and α-motor neurons. Interestingly, a striking loss of MATR3 expression was observed in the affected neuronal populations. These fly and mouse models will be useful for future studies on the mechanism underlying MATR3-related ALS pathogenesis.

Keywords: ALS
disease model
drosophila
MATR3
mouse
neurodegeneration
Advisor: Park, Jeehye
Body Mass Index Trajectories, Concurrent Body Mass Index, and Cardiometabolic Risk in Young Children

Background: Little is known about the relationship between rapid BMI gain trajectories and increased cardiometabolic risk (CMR) in early childhood. Objectives: To identify age and sex standardized body mass index (zBMI) trajectories in children 0-60 months. To examine the association zBMI trajectories and CMR. To determine the role of concurrent zBMI in this association. Methods: Latent Class Mixed Models were used to identify zBMI trajectories. Linear regression was performed to determine the association between zBMI trajectories and CMR. Mediation analyses were performed to determine the role of concurrent zBMI. Results: Children in the rapidly BMI gain trajectory had higher total CMR score and waist circumference score compared to the stable low group. Concurrent zBMI mediated the associations. Conclusions: Monitoring zBMI trajectories and weight status in early childhood may be helpful for clinicians to identify children at increased risk of cardiometabolic disease.

Keywords: cardiometabolic risk
cohort
Growth
obesity
Advisor: Birken, Catherine S
Investigating the Impact of Running-specific Prostheses Use for Children and Youth with Lower Limb Absence

For children and youth with lower limb absence, the functionality of their prostheses plays an important role in sport participation. The limited functionality of daily-use prostheses (DUPs) necessitates the use of specialized devices such as running-specific prostheses (RSPs); however, much remains unknown regarding their use in paediatric populations. The thesis objective is to investigate the impact of RSP use for children and youth. First, a systematic literature review about running biomechanics using RSPs was conducted which explored the compensatory strategies used by amputees. Second, a study protocol for the evaluation of paediatric RSP running biomechanics is proposed and the intrasession reliability of the start-stop task was assessed in typically developing children. Third, a qualitative analysis through semi-structured interviews was conducted to understand children’s experiences using RSPs. In conclusion, RSPs have positively contributed to children’s participation in sports; however, design improvements can still be made to better suit children’s needs.

Keywords: biomechanics
lower limb absence
paediatrics
running-specific prostheses
sport participation
Advisor: Andrysek, Jan
An Affect-aware Socially Assistive Robot for Exercise Facilitation

Older adults generally engage in less physical activities than other age groups, which can increase the risk of developing diseases associated with aging. It is increasingly difficult for caregivers to support older adults due to the global decline in the old-age support ratio. Socially assistive robots have shown success in supporting older adults and extending the capability of healthcare workers. This thesis aims to develop: 1) an affect elicitation and detection methodology using a social robot to directly elicit user affect that occurred during human-robot interactions (HRIs) to train affect detection models; 2) an autonomous socially assistive robot to facilitate upper body exercises. Exploratory experiments with both younger and older adults were conducted to validate the robot’s ability to elicit user affect and facilitate exercises. The results showed that the robot successfully elicited and detected user affect as well as facilitated exercising, and that the participants also reported high acceptance of the robot.

Keywords: Affective Computing
Assistive and Social Robotics
Human-Robot Interaction
Advisor: Nejat, Goldie
Benhabib, Beno
The Role of Inflammatory Cytokines in the Palmitate-mediated Dysregulation of NPY in Hypothalamic Neurons

A contributing factor to the development of obesity is the consumption of saturated fats. Saturated fatty acids such as palmitate dysregulate energy homeostasis by inducing neuroinflammation and orexigenic Npy mRNA in the hypothalamus. Inflammatory analysis identified cytokines that may mediate the induction of Npy mRNA by palmitate: NAMPT/visfatin, MIF, IL-17F and IL-6. With the exception of NAMPT/visfatin, treatment of the NPY/AgRP-expressing mHypoE-46 cell line with the aforementioned cytokines nor conditioned media from palmitate-treated cells were able to directly induce Npy mRNA suggesting a minimal role for cytokines. The monounsaturated fatty acid oleate successfully blunted palmitate-mediate increases in Npy and inflammation in mHypoE-46 cells through mechanisms involving PKA but not SIRT1. This study demonstrates that inflammation and Npy are distinct processes that are induced in a specific population of NPY/AgRP neurons and suggest that differential mechanisms mediate the dysregulatory effects of palmitate in a population-specific manner.

Keywords: Cytokine
Hypothalamus
Neuron
Obesity
Oleate
Palmitate
Advisor: Belsham, Denise D
First Generation Molybdenum-Nitride-graphite Supercapacitor Electrodes Produced from Solution Precursor Plasma Spray

First-generation molybdenum-nitride-graphite electrodes were fabricated and studied as a low-cost alternative to ruthenium oxide electrodes. They were fabricated using solution precursor plasma spray, and thereafter, heat treated using an ammonia temperature programmed reaction. Initially, a proof of concept study was conducted, successfully demonstrating that graphite could be added to the molybdenum nitride electrodes. The proof of concept revealed that graphite could withstand the high temperatures of the plasma plume and the subsequent heat treatment without decomposing into one of its gaseous products. Subsequently, an optimization study was carried out to identify the spray conditions that would produce the highest capacitance electrodes. By using a solution containing 91 g/L of graphite at a standoff distance of 80 mm and a gas composition of 50% argon and 50% nitrogen, an electrode with a capacitance of 180 mF/cm2 was fabricated – outperforming previously developed molybdenum nitride electrodes at the CACT by 188%.

Keywords: Cyclic Voltammetry
Molybdenum-nitride-graphite Electrodes
Solution Precursor Plasma Spray
Supercapacitor Electrodes
Advisor: Coyle, Thomas W.
Characterization of MATR3 Drosophila and Human Cell Models to Identify Genetic Modifiers of MATR3 Toxicity

Multisystem proteinopathy (MSP) is a degenerative disorder combining amyotrophic lateral sclerosis, frontotemporal dementia, inclusion body myopathy and Paget’s disease of bone. Many MSP genes including Matrin3 (MATR3) encode RNA binding proteins, highlighting the role of RNA metabolism in MSP. Over a dozen mutations in MATR3 have been identified, but the mechanisms of MATR3 pathogenesis remain unknown. To investigate MATR3-associated MSP, we developed a Drosophila model expressing wildtype or mutant MATR3 in indirect flight muscles, which exhibits an abnormal wing position and muscle degeneration. We simultaneously developed human neuronal cell lines stably expressing MATR3. In both fly and human cell models, wildtype and mutant MATR3 are localized in the nucleus. However, MATR3 S85C and F115C are less soluble than wildtype MATR3. A candidate genetic screen identified enhancers of mutant MATR3 toxicity and implicated cytoskeletal dysfunction in MATR3 pathogenesis. Together, this work may shed light on the mechanisms underlying MATR3-associated MSP.

Keywords: Amyotrophic Lateral Sclerosis
genetic screen
Matrin 3
Multisystem Proteinopathy
RNA binding protein
Advisor: Park, Jeehye
Direct Nerve Electrical Stimulation and Local FK506 Drug Delivery to Enhance Axon Regeneration in Nerve Gap Reconstruction

Functional recovery after peripheral nerve injuries is rarely complete, particularly with severe nerve injuries resulting in gap defects. Although nerve autografts are the gold standard for nerve gap reconstruction, they have inherent disadvantages such as limited quantity, donor site morbidity, and variable outcomes. Strategies to improve axon regeneration through nerve autografts or nerve substitutes have important implications for patients with devastating nerve gap defect injuries. In this thesis, we investigate two emerging bioengineering strategies. In Experiment 1, we demonstrate that low frequency, direct nerve electrical stimulation at the time of nerve gap reconstruction improves axon regeneration through nerve autografts. In Experiment 2, we demonstrate that a local FK506 (tacrolimus) drug delivery system enhances axon regeneration through fresh nerve allografts, a nerve substitute. Our results suggest that both electrical stimulation and local FK506 drug delivery may be clinically translatable strategies to improve peripheral nerve regeneration for patients with nerve gap defects.

Keywords: Electrical stimulation
FK506
Local drug delivery
Nerve graft
Nerve regeneration
Tacrolimus
Advisor: Borschel, Gregory
Diabetes-Induced Impairments in Robo Signalling Augment Glomerular Angiogenesis

Diabetic glomerular angiogenesis represents an early form of diabetic kidney injury driven by VEGF. Robo1 and Robo4 are cell surface receptors that can regulate VEGF-mediated endothelial angiogenic activity. We have shown previously that glomerular endothelial Robo4 expression is downregulated with high glucose exposure, whereas Robo1 expression is unchanged and that Robo1 is essential for VEGF-induced angiogenic activity. In this thesis I aim to determine whether alterations in Robo2 and Robo4 levels regulate VEGF-induced glomerular angiogenesis in high glucose and diabetes. Robo4 deficiency was associated with augmented migration in vitro while Robo2 did not change with high glucose or diabetes exposure. Robo4 KO mice exhibited increased PECAM-1 density, glomerular capillary length, and creatinine clearance after 5 weeks of STZ-induced diabetes. Our observations suggest that diabetic glomerular angiogenesis is driven by enhanced glomerular endothelial VEGF responsiveness promoted by a shift in Robo signalling, favouring more pro-angiogenic Robo1, and less anti-angiogenic Robo4 activity.

Keywords: Diabetes
Diabetic Nephropathy
Robo Signaling
Vascular Biology
VEGF
Advisor: Yuen, Darren
Adverse Event Detection in Laparoscopic Videos

Human errors are one of the main causes of surgical adverse events. These events are reported by physicians which is an error-prone process. An automatic surgical adverse event detection system can reduce biases in the reports, provide quick feedback to surgeons, and help guide postoperative care. Few studies have developed such a system for laparoscopic procedures -- a major type of minimally-invasive procedure that has 15 million cases each year. We developed a deep learning system that can automatically detect two major surgical adverse events: bleeding and thermal injury. The system consists of a module that reduces camera motion in a scene, a module that extracts spatial-temporal features from videos, and a final module that takes into account the full temporal resolution of a procedure and makes predictions. This system significantly outperforms the prior state-of-the-art architectures developed for action recognition and adverse event detection in laparoscopic videos.

Keywords: bleeding detection
deep learning
laparoscopy
surgical adverse event detection
thermal injury detection
Advisor: Taati, Babak
Grantcharov, Teodor
The Investigation of ABA Transport in Arabidopsis thaliana and Brassica napus

Abscisic acid (ABA) is a phytohormone that plays a major role in plant responses to biotic and abiotic stresses. Increases in ABA levels have been reported in conditions such as drought, high salinity, and low temperature. Although the movement of ABA within plants has been documented, its migration pattern is still debatable. Recent application of Positron Emission Tomography (PET) on plants using radioactive tracers has provided a potential new method of studying ABA migration within plants. In order to study the localization pattern of 3’-18F-ABA in planta, I performed histochemical analyses of β-glucuronidase (GUS) expression in GUS reporter lines, and report that the radioactive tracer, 3’-F-ABA, has similar bioactivity to ABA. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) -based phytochemical analyses of 3’-F-ABA- or ABA-treated Arabidopsis thaliana and Brassica napus plants also showed a bi-directional distribution towards the reproductive organs and to the roots, suggesting a phloem mediated transport of ABA under non-stressed conditions.

Keywords: ABA transport
Abscisic acid
Arabidopsis thaliana
Brassica napus
Positron emission tomography
Advisor: Nambara, Eiji
Selectively Filled HC-PCF Microfluidic Raman Sensor and Its Biomedical Applications

In this thesis, selectively filled HC-PCF microfluidic chip was developed to be a low-cost Raman sensor with high sensitivities for biomedical applications. During the development, a new selective filling technique and a corresponding model were proposed to solve the signal decrease problem, caused by the liquid sample flowing into the air cladding of the HC-PCF. Two biomedical applications are utilized to validate the performance of the developed HC-PCF chips. The HC1060 chips working with 632.8 nm laser were applied to measure the glucose concentrations in the range of 0-10 mg/mL in prepared tear-like solutions. Results show that the developed HC1060 chips achieved two orders higher Raman sensitivity and a better quality of obtained spectra than the conventional TCT. The HC800 chips, working with 785.0 nm laser, were applied to measure the CO2 concentrations (400, 600, 800, 1000 ppm) in the medical air, showing potential on quantitative analysis of gas.

Advisor: Helmy, Amr
Skipping a Beat: Development and Characterization of a 3D in vitro Model of Human Cardiac Arrhythmia

Introduction: Cardiac arrhythmias impact ≥350,000 Canadians result in ≥40,000 deaths annually. High-fat diets promote heart failure and arrhythmias. Studying arrhythmias in living patients and animals has practical ethical constraints. Furthermore, 2D in vitro models do not recapitulate the human heart environment. A 3D in vitro model would address these limitations. Aim: Develop characterize a robust 3D acquired arrhythmia model. Methods: Three-dimensional microtissues consisted of hiPSC-derived cardiomyocytes and fibroblasts. Arrhythmia was induced by high fatty acid supplemented media. Electrophysiology, contractile force, beating frequency, pharmacological electrical cardioversion, and differential gene expression were assessed. Results: Arrhythmias developed within 5 days; more complex electrophysiological phenotypes were observed towards day 5. Arrhythmogenesis significantly reduced contractile force and elevated beating frequency and pathogenic gene expression was evident. Pharmacological and electrical interventions effectively cardioverted arrhythmic tissues. Conclusion: This robust 3D in vitro arrhythmia model can serve as a fundamental investigative tool for understanding arrhythmias developing novel therapies.

Keywords: 3D Model
Arrhythmia
Cardiac lipotoxicity
Heart-on-a-chip
Human Cardiac Stem Cells
Metabolic Dysfunction
Advisor: Nunes de Vasconcelos, Sara S
Effect of Maternal Vitamin D Supplementation on Nasal Pneumococcal Carriage in Infants in Dhaka, Bangladesh

Nasopharyngeal carriage of Streptococcus pneumoniae (pneumococcus) is a necessary antecedent to invasive pneumococcal disease. In vitro studies have shown that vitamin D (VD) is an immunomodulator that promotes specific responses against pneumococcus. This study investigated whether these in-vitro effects translate into the public health context by examining whether VD supplementation during pregnancy and lactation, versus placebo, had an effect on the risk of pneumococcal acquisition, dynamics and density (pneumococcal carriage) in infants in Dhaka, Bangladesh. In this sub-study of the Maternal Vitamin D Supplementation for Infant Growth Trial, we found no significant effect of VD supplementation on pneumococcal carriage. However, parental education, season and number of siblings in the household were associated with carriage. Contrary to our hypothesis, there was no protective effect of prenatal and postpartum VD supplementation against infant pneumococcal carriage and therefore cannot be recommended at this time for the prevention of pneumococcal carriage in early infancy.

Keywords: Bangladesh
Carriage
Infants
Pneumoccocus
Vitamin D
Advisor: Roth, Daniel E
Investigating the Colorimetric Response of Surfactant Capped Gold Nanoparticles

Gold nanoparticles are popular colorimetric agents. The colour of a gold nanoparticle solution is dependent on the nanoparticle size, shape, etc. The colorimetric response of gold nanoparticles stems from their aggregation in different conditions and exposure to analyte(s) they have been programmed to react to. This work uses surfactants/polymers as nanoparticle capping agents for two distinctly different types of nanoparticles. Each surfactant/polymer might be used as a capping agent for one or both type of nanoparticles under investigation. The nanoparticles display a number of different colours, colour intensities, and timed responses to particular testing media. The behaviour of each differently capped nanoparticle sample is investigated separately, two-surfactant systems are explored in terms of enhanced stability, and a few nanoparticle mixtures are examined for the development of a wearable time sensing device.

Keywords: Colorimetric
Gold Nanoparticles
Nanoparticles
Surfactant
Advisor: Gu, Frank
Investigating the Role of Inositol Polyphosphate 4-Phosphatase Type II (INPP4B) in Pancreatic Cancer

Pancreatic cancer is one of the deadliest malignancies, with 5-year survival rates of less than 5%. Survival analyses of pancreatic cancer patient databases revealed that high expression of Inositol Polyphosphate 4-Phosphatase Type II (INPP4B) was associated with poor survival. Thus, we hypothesized that INPP4B promotes pancreatic cancer aggressiveness. Herein, the functional role of INPP4B on pancreatic cancer cell biology was explored in vitro. Analyses of independent patient databases revealed that INPP4B is frequently upregulated in pancreatic tumours compared to normal cells. Exogenous INPP4B expression in vitro enhanced proliferation, anchorage-independent growth, clonogenic potential, migration, invasion, and resistance to gemcitabine, a standard of care agent in pancreatic cancer therapy. Conversely, INPP4B knockdown attenuated these phenotypes. The underlying perturbations in signalling mechanisms associated with INPP4B remain unclear, however these findings support a tumour promoting function for INPP4B in pancreatic cancer, with implications for the development of novel therapy targeting INPP4B.

Advisor: Salmena, Leonardo