VictorJuiz/thesis huggingface dataset:
Predictors of Muscle Function in Hemodialysis Patients
Keywords: Exercise
Physiology
Nutrition
Dialysis
Hemodialysis
Chronic Kidney Disease
Kidney
Physical Activity
Physical Function
Muscle
Handgrip
Dynamometer
Accelerometer
Food Record
Nutrition Analysis
Vitamin D
Strength
25-OHD

Decreased skeletal muscle function (MF) is ubiquitous in hemodialysis (HD) patients and linked to functional decline. Serum vitamin D (25-OHD) and habitual physical activity (PA) are decreased in HD and linked to reduced MF in other populations. The associations between 25-OHD, PA, and MF were investigated in 81 stable HD patients. PA intensity was quantified using accelerometery, MF using handgrip strength dynamometery, 25-OHD via serum measures, and dietary and supplementation of vitamin D intake via three-day food records. MF correlated with PA (r =0.411, p = 0.003) when controlled for body mass (BM) and with 25-OHD (r =0.298, p = 0.023) when controlled for BM, age, and sex. Both MF (r=0.285, p=0.025) and 25-OHD (r=0.314, p=0.005) correlated with vitamin D supplementation. MF remained correlated with supplementation after controlling for 25-OHD (r=0.269, p=0.037). These findings should be further explored in interventional studies to assess how their manipulation influences MF in HD.
Neuropsychological Outcome following Cranio-spinal Radiation in Medulloblastoma Patients: A Longitudinal Analysis of Predictors
Keywords: Medulloblastoma
Neuropsychology
Pediatric

Medulloblastoma is the most common malignant central nervous system (CNS) tumor in childhood. The cranio-spinal radiation (CSR) required to treat this disease results in long-term cognitive and neurologic impairments. Medulloblastoma was recently categorized into four genetic subgroups (WNT, SHH, Group 3, and Group 4). This study examined neuropsychological and intellectual functioning in 91 medulloblastoma patients (41 Group 4; 20 Group 3; 18 SHH; 12 WNT) following treatment, and examined the impact of several medical, treatment and demographic factors on functioning over time. Longitudinal growth curve analyses revealed hydrocephalus most clearly predisposes to poor neuropsychological functioning. Results also indicate medulloblastoma subgroups have heterogeneous intellectual outcomes following treatment. All subgroups experience intellectual declines following treatment; however, comparing between subgroups revealed Group 4 performs most poorly, and Group 3 has the best overall intellectual outcome. Lastly, qualitative analyses suggest treatment with a larger CSR dose may contribute to poor intellectual functioning.
Publicly Funded Dental Care in Ontario: Rationing Principles and Rules
Keywords: rationing health care
publicly funded dental care

Objective: To identify principles and rules used by stakeholders in making limit-setting decisions for publicly funded dental care. Methods: A purposive sample, including administrators, academics, funders, clinicians and community representatives was surveyed using a 28-item questionnaire, in the first round of a proposed three-round modified Delphi study. Using open and closed-ended questions participants made and explained decisions on prioritizing populations and services. Open-ended text was analyzed with a thematic qualitative approach using open and axial coding. Results: Consensus emerged on two rationing principles; achieving equity and providing essential care. Rules for eligibility were defined as the inability to pay and/or assume full personal responsibility for securing dental care. Inclusion/exclusion of treatment categories rested on relieving pain/infection, preventing disease and maintaining/restoring function. Conclusions: Stakeholders presented principles and rules that suggest extending the distribution of publicly funded dental care to include, at a minimum, essential services for those unable to afford care.
Hypoglycemic Seizures in Juvenile Rats: Acute Mortality is Associated with Severe Seizures in Diabetic and Non-diabetic Subjects
Keywords: Hypoglycemic seizure
juvenile diabetes
EEG

Iatrogenic hypoglycemia is a limiting factor for managing diabetes mellitus and can have severe outcomes such as seizures and coma. Although several studies have investigated the central nervous system consequences of hypoglycemia, the effects of seizures, as well as possible treatment strategies, have yet to be elucidated in juvenile animals. The objective of this thesis was to establish an in vivo model of severe hypoglycemia and seizures in juvenile diabetic and non-diabetic rats. In both groups there existed a similar blood glucose threshold for seizures, and mortality only occurred following severe seizures, particularly with repeated seizures that were unresponsive to treatment. While the administration of anticonvulsants temporarily mitigated seizures, glucose administration was required to prevent mortality. Abnormalities in the hippocampal and brainstem electroencephalograms (EEG) were observed in hypoglycemic animals without a clear correlate to convulsive activity.
Active Hedgehog Signaling Regulates Renal Capsule Morphogenesis
Keywords: developmental biology
kidney development
renal capsule
stroma

The renal capsule is a flattened layer of cells which surround the kidney. Expression of the transcription factor Foxd1 is required for normal development of the capsule. Furthermore, current evidence suggests that during development the capsule progenitors are in a state of active hedgehog signaling. We hypothesize that hedgehog plays a role in modulating capsule morphogenesis in the embryonic kidney. To test the hypothesis hedgehog signaling was inhibited in the capsule via Foxd1Cre mediated deletion of Smoothened (Smo), the activator of the pathway. Mutant kidneys were approximately 48% smaller in volume and had a 42% decrease in nephron number. Furthermore, mutants displayed abnormal patterning of the capsule where regions on the surface of the kidney had no capsule cells. The discontinuous capsule phenotype was observed only after E13.5. Additionally, capsule cells progressively lost expression of known markers Foxd1 and Raldh2 and their proliferative capacity was decreased by 54% at E13.5.
Effects of a Feedback-reward System on Speeding and Tailgating Behaviours
Keywords: Driving behaviour
Feedback
Speeding
Tailgating
Headway
Speedlimit
Reward
Incentive
Driving

This thesis investigates the effect of a feedback-reward system on speeding and tailgating behaviours. Data utilized in this study were collected from 37 participants through a field trial commissioned by Transport Canada. In this trial, a feedback-reward system was investigated, which provided feedback and rewards to the drivers based on speed limit compliance and safe headway maintenance. The trial consisted of three phases: baseline, intervention, and post-intervention. During the intervention phase, real-time feedback was provided on an in-vehicle display. Participants also accumulated reward points and could view related information on a website. Results indicate that the intervention resulted in a significant increase in speed limit compliance, and this positive effect, although dampened, was still apparent after system removal. Similarly, results on headway compliance rate indicate a positive intervention effect, however, this effect did not sustain after system removal. These findings have implications for developing better aids to improve driving behaviour.
Wastewater Contaminant Sorption and Dissolved Organic Matter Characterization
Keywords: organic contaminants
dissolved organic matter
sorption
organic geochemistry
soil
soil organic matter

Irrigation using reclaimed wastewater can introduce organic contaminants and dissolved organic matter (DOM) to soils. Sorption of three common organic wastewater contaminants to five soils of diverse organic matter composition was studied both before and after the removal of soil carbohydrate and peptide components using acid hydrolysis. Results suggest that these polar components may block organic contaminants from accessing higher affinity sorption sites in soil organic matter. The sorptive fractionation of DOM by three mineral soils was studied to assess the terrestrial fate of this complex environmental matrix. Carboxyl- and aromatic-containing moieties appear to preferentially and reversibly sorb to mineral soils. Conversely, carbohydrate and peptide components of DOM preferentially remain in the aqueous phase while aliphatic moieties were selectively retained only by a soil with high surface area. This thesis illustrates that reclaimed wastewater should be applied to soils cautiously as it may degrade soil and groundwater quality.
The Expression and Regulation of CYP2D in a Monkey Model of Ethanol and Nicotine Exposure
Keywords: CYP2D6
Nicotine
Ethanol
African green monkey
Induction
Brain
Liver
Smokers
Alcoholics
Parkinson's disease
Personality
Brain drug metabolism

CYP2D6 metabolizes a range of centrally acting drugs, neurotoxins, and endogenous neurochemicals. Higher levels of brain, but not liver, CYP2D6 have been identified in alcoholics and smokers, suggesting exposure to ethanol and/or nicotine may induce brain CYP2D6. We investigated the independent and combined effects of chronic ethanol self-administration and nicotine treatment on CYP2D expression. METHODS: Monkeys were randomized into 4 groups of 10/group consisting of a control group, ethanol-only group, nicotine-only group, and a combined ethanol and nicotine group; treatments occurred for 64 days. RESULTS: Exposure to chronic ethanol and nicotine induced CYP2D across various brain regions and cell types, particularly when both drugs were given in combination. No changes in protein levels were observed in liver or in CYP2D mRNA levels in liver and brain. CONCLUSIONS: Ethanol and nicotine increase brain CYP2D levels, which may affect CNS drug response, neurodegeneration and personality among those exposed to alcohol and/or nicotine.
Characterization of the Minimalist Hybrid Protein Inhibitor ME47 as a Potential Anti-tumour Agent Designed to Target Myc Activity in Cancer
Keywords: Myc
Omomyc
Max-E47
Cancer

Effective therapeutics are urgently needed to improve the treatment and survival of cancer patients and we believe that targeting the MYC oncogene would fill this gap. Our strategy to achieve this goal involves the design of minimalist hybrid protein inhibitors (MHP) - 25-75 amino acid proteins composed of subdomains of known transcription factor families to generate hybrids that act as structural competitive inhibitors of the Myc/Max:DNA E-box interaction. We have established cell systems, reagents and assays using our prototype MHP, ME47 to evaluate the biological effectiveness of this putative inhibitor as well as subsequently designed MHPs using cell-based proliferation and transformation assays. Omomyc was included as a proof-of-concept control to optimize our systems and gauge the performance of ME47. This research demonstrates for the first time that ME47 exerts desirable biological effects in human cells lines and provides support for the validity of our MHP strategy thus warranting further investigation.
A Look at Model Uncertainty in the Evaluation of Commodity Contingent Claims: A Practitioner's Guide
Keywords: uncertainty
commodity

Model uncertainty in financial markets is prevalent by the very nature of how models are constructed and used by financial practitioners. As such, a proper characterization of model uncertainty should be paramount in the eyes of every practitioner, and furthermore, a proper framework for implementing such a characterization towards financial activities should be implicit. While model uncertainty is acknowledged by practitioners, a cohesive and robust framework for determining a model uncertainty risk measure that is broadly accepted by practitioners is missing. We acknowledge this deficiency and provide a practitioner's guide for evaluating a modern characterization of model uncertainty, specifically that of Li and Kwon, as applied to a subset of derivative related calculations, with the goal of promoting its implementation by practitioners. We promote its implementation by demonstrating the utility and flexibility of such a characterization relative to another modern model uncertainty risk measure, specifically that of Cont.
Analysis of District Heating Potential in Toronto Using Geographical Information Systems
Keywords: district heating
toronto
energy efficiency
GIS
geographical information systems
sustainability

New district heating systems in Toronto have the potential for significant financial and environmental gains. Through the use of Geographical Information Systems (GIS) and the data required to estimate heating loads, heat maps were generated on a building-by-building basis for over 4400 buildings at nine different intersections in Toronto. School locations and planned construction maps were used to enhance the data and demonstrate the benefit of considering factors beyond finance and the environment. Out of the intersections studied, Yonge and Eglinton; Yonge and Sheppard; and Yonge and Empress held the largest heating loads. Individual building data allowed for plant locations to be suggested based on their proportional distance to the highest loads. GIS allowed for the visualization of the vast quantity of data. The opportunities for improvement include increasing the availability of location-based data and the application of the methodology to other areas of infrastructure planning and decision making.
An Economic Evaluation of Conception Strategies for Heterosexual Serodiscordant Couples with HIV-positive Male Partners
Keywords: cost-effectiveness analysis
cost-utility analysis
markov model
HIV
conception

An economic evaluation of the three interventions to conceive without the sexual transmission of HIV between heterosexual, HIV-discordant couples with positive male partners can inform policy decisions to subsidize pregnancy planning in this setting, as there is currently no coverage as such in Ontario. A decision tree and Markov model were designed to determine the short and long-term outcomes of unprotected intercourse restricted to timed ovulation (UIRTO), sperm washing with intrauterine insemination (SWIUI), and unprotected intercourse restricted to timed ovulation with pre-exposure prophylaxis (UIRTO-PrEP). In the short-term, UIRTO was the most cost-effective strategy. In the long-term, cases of negligible HIV transmission risk determined UIRTO-PrEP as the preferred option, while SWIUI was the choice method when this risk was high. There remains a viable risk of HIV transmission between discordant couples during attempts to conceive that require the concurrent and subsidized use of UIRTO-PrEP or SWIUI to protect against HIV infection.
The Association between Metformin Therapy and Mortality Following Breast Cancer: A Population-based Study
Keywords: General 0566

Metformin has been associated with a reduction in breast cancer incidence, however its effect on mortality following cancer has not been adequately examined. The purpose of this study was to evaluate the impact of metformin therapy on mortality in women with breast cancer. Using Ontario health databases, this retrospective cohort examined the impact of metformin on mortality among women aged 66 years or older with diabetes and breast cancer. After a mean follow-up of 4.5 years, there was no association between cumulative metformin use and either all-cause or breast cancer-specific mortality (HR 0.97, 95% CI 0.92-1.07; HR 0.91, 95% CI 0.81-1.03 respectively per additional year of cumulative metformin use). Though metformin was not associated with a reduction in mortality in our study of older women with breast cancer, there is still a need to examine whether metformin has an effect on mortality in other breast cancer populations.
Sources of Spatial Variation in Herbivory and Performance of an Invasive Non-native Plant, Common Burdock (Arctium minus)
Keywords: Herbivory
Invasive Species
Species Ranges

The herbivory experienced by non-native invasive plants may depend on their local environments, such as herbivore abundance. In this study, I performed a common garden experiment with plants sampled from 11 populations of Arctium minus, from southern Ontario to near its northern range limit. I also compared performance and herbivory of burdock in open and understory habitats. Finally, I conducted freezing tolerance experiments with the lepidopteran seed predator Metzneria lapella, and palatability tests with plants from different populations. Results suggested that the previously described latitudinal trends in herbivore damage among populations are due to environmental differences rather than genotypic differences among populations. At a local scale, plants of open habitat were less damaged and had better performance than understory plants. Burdock has not escaped damage by herbivores in its invaded range; instead variation among sites in herbivore populations and impacts may significantly affect the invasiveness of this species.
The Genetic Basis of Fecundity Variation in Caenorhabditis briggsae
Keywords: quantitative genetics
fecundity
Caenorhabditis briggsae

Identifying the genetic basis for phenotypic variation is a central question in evolutionary biology and can be studied in detail using model organisms. Fecundity variation in different isolates of C. briggsae has been observed previously, but the genetic causes of this variation are unclear. Crosses between C. briggsae advanced-intercross recombinant inbred lines (AI-RILs) and parental strains yield near isogenic line (NIL) strains, which I created to provide a powerful genetic resource to fine-map the basis for fecundity and other trait differences. Phenotypic analysis of the NILs shows the complexities of possible epistatic interactions on phenotypic expression. These NIL strains contribute a valuable genetic resource toward the long-term goal of identifying the genes responsible for differences in fecundity in this species. The elucidation of the basis for this trait variation will also contribute further into the mechanisms for how genotype and phenotype and environment all interact.
Functional Plasmonic Mesh Architectures
Keywords: Plasmonic Slot Waveguides

The aim of this thesis is to establish a platform for implementing nanoscale plasmonic slot waveguide (PSW) devices that can interface with dielectric technology for hybrid silicon-plasmonic interconnect applications. For waveguide excitation, an orthogonal junction coupler that operates based on momentum matching is analyzed and then experimentally demonstrated to have coupling efficiency of 50 +/- 2 % between 450 nm wide silicon waveguide and 50 nm wide PSW across a 200 nm bandwidth. Next, for designing scalable optical components with multiple-input multiple-output capability and high fabrication tolerance, two dimensional PSW mesh structure that utilizes simultaneous power distribution and interference within a network of intersecting PSW junctions is introduced. Finally, a closed-form model for PSW mesh structures is derived by incorporating the characteristic impedance model into the scattering matrix formalism. The model can handle arbitrary combination of junctions and has less than 5 % discrepancy when compared to Finite-Difference Time-Domain results.
A Call For Autonomy And Compassion
Keywords: Euthanasia
Assisted suicide
Assisted death
Belgium Law
Compassion
Patient Autonomy

The current blanket prohibition of assisted death in Canada continues to be the subject of much debate. This thesis examines the shortcomings and strengths of the Belgium Law on Euthanasia of 2002 and discusses whether similar legislation could be implemented in Canada. More particularly, the thesis looks at the spirit and intent of the law, the conditions under which assisted death is permitted, and the control mechanism present in the Belgian law. The analysis of Belgium’s ten years of experience with assisted death allows us to argue that the risks inherent in assisted death regime can be controlled in a system where an exception is made for competent people in a situation of unbearable suffering. Important safeguards to prevent abuse and protect people from vulnerable groups are identified in the Belgian statute. This thesis recommends in its conclusion to regulate assisted death as an expression of compassion for suffering patients, in line with Canada’s longstanding commitment to respect for patient autonomy.
Six4/5 Family Transcription Factor UNC-39 Controls the Development of RID Neuron in Caenorhabditis elegans
Keywords: C. elegans
neuronal development
RID
Six4/5
Six5
unc-39
genetics
cell fate
transcription factor
homeobox
homeodomain

Members of the Six4/5 family of homeobox transcription factors have been implicated in multiple human disorders, including type I mytonic dystrophy, branchio-oto-renal syndrome, and holoprosencephaly, suggesting a role for these factors in the nervous system development. Using a forward genetics approach, we identified unc-39, a C. elegans homologue of the human SIX5 gene, as a novel regulator of the development of a specific neuron, called RID. Our data support the role of unc-39 early in C. elegans development and suggest a possibility of complete absence of RID neuron in unc-39 mutants. unc-39 mutant has a similar locomotion phenotype to the RID-ablated animals, which provides further support to the hypothesis that the absence of RID contributes to the locomotion phenotype observed in the mutant. We show that unc-39 functions at multiple points in the lineage that gives rise to the RID neuron, and that its function is context-dependent.
Development and Validation of a Novel Quantitative Assay for Cell surface Expression of GPCRs using a Receptor β-lactamase fusion Protein and the Colourometric Substrate Nitrocefin
Keywords: GPCR
Assay
β-lactamase
Nitrocefin
Surface Expression
ELISA
Internalization
Pharmacological Chaperone
Molecular Chaperone

Trafficking of GPCRs is a dynamic process that is tightly regulated and sometimes defective in human diseases. Therefore it is important to develop new methods to allow simple and quantitative measurement of surface expression of membrane proteins. Here we describe the development and validation of a new assay for quantification of cell surface expression of GPCRs using β-lactamase as a reporter. For this assay we N-terminally fused β-lactamase (βlac) to the β2-adrenergic receptor (β2AR) and GABA b R1 (GBR1). The results obtained by the βlac assay are quantitatively and qualitatively similar to well established ELISA when measuring agonist induced internalization of β2AR. We also show that measurement of GBR1 surface expression with GBR2 co-expression is quantitatively identical between the βlac and ELISA. In conclusion, our results show that our newly developed βlac assay is quantitatively similar while being less expensive, more robust and higher throughput compared to an ELISA.
Somatostatin Receptor Type 2 Antagonism Improves Glucagon Counter-regulation in Biobreeding Diabetes-prone Rats
Keywords: Type1 diabetes
Somatostatin receptor type 2 anatgonist
Glucagon
counterregulation

Impaired counterregulation during hypoglycemia in type 1 diabetes (T1D) is partly due to inadequate pancreatic islet alpha-cell glucagon secretion. We hypothesized that hypoglycemia can be prevented in autoimmune T1D by selective somatostatin receptor type 2 (SSTR2) antagonism of alpha cells to relieve SSTR2 inhibition, thereby increasing glucagon secretion. Diabetic biobreeding diabetes prone (BBDP) rats (D) vs non-diabetic BBDP (N) rats, underwent infusion of vehicle or SSTR2 antagonist (SSTR2a) during insulin-induced hypoglycaemia. D rats, treated with SSTR2a, needed little or no glucose to maintain hypoglycemia. To monitor real-time glucagon secretory response directly, we developed the technique of thin slices of the pancreas from D and N rats as well as normal human pancreas, subjected to perifusion with vehicle vs SSTR2a. SSTR2a treatment enhanced glucagon secretion in N and D rats and human pancreas. We conclude that SSTR2 antagonism can enhance hypoglycemia-stimulated glucagon release sufficient to achieve normoglycemic control.