title: formation and evolution of inclusions in calcium-treated liquid steel

contributor:
Dogan, Neslihan
Sun, Stanley
Materials Science and Engineering

subject:
calcium treatment
steelmaking
inclusions
steel
ladle metallurgy
pyrometallurgy

abstract:
The cleanliness of steel impacts the success of steel production and the physical and chemical properties of the final product. Improving the cleanliness of steel, therefore, becomes a necessity in the present time, with an ever-increasing demand for high-quality steel products. The cleanliness can be improved by removing the harmful inclusions through flotation or by modifying their composition and morphology to less detrimental forms. The present study focuses on better understanding the second approach, a specific modification method commonly known as the calcium (Ca) treatment in advanced high strength steel (AHSS) production.
The chemical and morphological evolutions of Al2O3 inclusions under experimental and industrial conditions, as well as the formation of CaS and MnS inclusions, were studied in this work. Six laboratory experiments with different combinations of calcium and sulfur contents of liquid steel were conducted. Samples were taken at different time durations after calcium addition. The inclusions on the sample cross-sections were analyzed using an automated SEM-EDS system to obtain their chemical, size distribution, population, and morphological information. Similar steps were taken in the analysis of industrial samples. The findings obtained based on the automated SEM-EDS analyses were further supported and validated against other analysis results such as manual SEM analysis, thermodynamics, and kinetics calculations.
The modification mechanism for Al2O3 inclusions was established in the first part of the study. After adding 10 ppm, 20 ppm, and 35 ppm Ca, small-sized calcium aluminates CAx (C and A denote CaO and Al2O3, respectively) inclusions become the primary oxygen bearer instead of Al2O3 inclusions. The modification extent of the CAx inclusions depends on the Ca content. CaS inclusions also form at the early stage of calcium treatment. In the later stage, CaS inclusions act as the Ca source to modify the remaining Al2O3 inclusions to CAx inclusions and simultaneously modify the existing CAx inclusions until equilibrium is reached. CaO inclusions only form in steel containing 20 ppm S and 35 ppm Ca; the primary oxygen bearer will change from Al2O3 to CaO, followed by a transformation from CaO to CaS. In other S and Ca contents, CaO inclusions do not form. This finding clarified that modification of Al2O3 inclusions is mainly driven by dissolved Ca and CaS inclusions, with CaO showing a minor direct impact. Moreover, the experimental studies showed that total area fractions of liquid and semi-liquid inclusions, which are inclusions that are partially liquid and partially solid, are correlated with the thermodynamic stability of CaS inclusions. The fraction of liquid inclusions decreases after the area fraction of CaS inclusions drastically increases when steel chemistries allow stable CaS inclusions to precipitate.
The correlation between the steel chemistries and inclusions was improved by
iv
incorporating more data from industrial heats. Three modification indexes were proposed to estimate the control of CAx, CaS, and MnS inclusions. The fraction of CAx inclusions with more than 50 pct liquid, and the area fraction of CaS and MnS inclusions in tundish samples were correlated with the Ca, Al, Mn, and S contents of liquid steel. Later, these modification indexes were incorporated to evaluate the effectiveness of calcium treatment quantitatively. This makes the present study the first to discuss the correlations between Ca, Al, Mn, and S contents and the number of inclusions in the open literature. The correlations were validated against industrial data, they may be used in industry to determine the optimum Ca content for inclusion control and modification.
Based on the experimental and industrial data, the coarsening of CaS inclusions was initially governed by mass transport, then shifted to collision-related mechanisms. When agitation is absent, Brownian motion shows the most significant impact on the growth of CaS inclusions, while turbulent flow is the critical cause of collision and coagulation when the melt is stirred, such as in industrial conditions. It has been found that CAx inclusion growth mainly occurs in the early stage after Ca addition. The potential reason is that the lack of attraction prevents coagulation after CAx inclusions are modified to liquid and semi-liquid.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: The shared signaling pathways of autism-risk genes and their disruption by genetic variants

title: INVESTIGATING THE CONVERGENT DISEASE-RELEVANT MECHANISMS IN AUTISM SPECTRUM DISORDER

contributor:
Singh, Karun
Biochemistry and Biomedical Sciences

subject:
Neurodevelopmental Disorder
BioID
Autism spectrum disorder

abstract: Autism spectrum disorder (ASD) encompasses a broad range of neurodevelopmental disorders, with two core symptoms: deficits in social communication, and restrictive interests and repetitive behaviors. Genetics is thought to play a large role in ASD and currently there are hundreds of associated genes. We first studied the thousand and one amino acid kinase gene (TAOK2), which plays an important role in neurodevelopment. We found that loss of TAOK2 causes deficits in neuron development and activity, leading to morphological changes in various mouse brain regions and ASD-related behaviors. We studied the impact of de novo mutations identified in TAOK2, which caused aberrant neuron dendritic arborization and formation of synapses. To elucidate how TAOK2 regulates neuron development we used a proximity-labeling proteomics technique (BioID) to identify its protein-protein interaction (PPI) network. We applied this same methodology to a total of 41 ASD-risk genes and observed multiple convergent biological processes, including the less-studied mitochondrial and metabolic pathways. ASD-risk genes, including TAOK2, associated with mitochondrial proteins were found to have altered cellular respiration. The shared ASD-risk gene PPI network enriched for other ASD-risk genes and was used to group genes based on their shared PPI networks. These gene groups showed correlation between the clinical behavior scores of individuals that had mutations within the distinct gene groups. Lastly, we identified changes in the PPI networks of multiple ASD-risk genes through BioID, which we validated with various functional assays. In summary, we developed a proximity-labeling proteomics method that identified multiple convergent biological pathways associated with ASD. Studying the function of TAOK2 revealed multiple disease-relevant pathologies associated with the disorder, however proximity labeling has the potential to categorize multiple ASD-risk genes and elucidate their shared signaling pathways, which together, can advance the development of robust treatments for ASD.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Autism spectrum disorder (ASD) is a group of brain disorders that affect more than 1% of children. Genetic variants are thought to cause ASD pathology, however there are currently hundreds of genes that have not been studied. We studied how disruption of one of those genes, TAOK2, alters brain development in mice and identified TAOK2 variants in multiple children with ASD. We then used BioID to find the shared disease-related mechanisms between multiple ASD-risk genes, and found that mitochondrial function and activity were connected to many of these genes. We showed that BioID can be used to study the effect of mutations in multiple ASD-risk genes simultaneously. Last, we could group children with ASD with similar behavior test scores based on the shared mechanisms of ASD-risk genes.  Together our findings could be used to advance the development of robust treatments or new diagnostic tools for ASD.


title: FACTORS AFFECTING RECRUITMENT TO SURGICAL ONCOLOGY CLINICAL TRIALS AND OPPORTUNITIES TO IMPROVE ACCRUAL

contributor:
Bhandari, Mohit
Health Research Methodology

abstract:
Surgical trials involve patients undergoing a surgical intervention. Poor recruitment is the
most important issue that can lead to study failure.
Chapter 1 provides the conceptual framework of recruitment issues that can arise when
conducting a surgical trial. Different methodological challenges that lead to poor
recruitment are discussed based on the different steps of a trial. It provides a rationale for
conducting the included studies.
Chapter 2 describes a double blind, placebo controlled randomized clinical trial; a pilot
feasibility trial evaluating the use of perioperative nutritional supplements versus placebo
for patients undergoing gastrointestinal cancer surgery. This chapter expands on issues
related to recruitment to surgical trials in this setting (i.e., surgical trials that compare a
medical intervention or drug among patients undergoing surgery) and explores potential
opportunities to improve accrual.
Chapter 3 presents a single arm, multi-institutional, pilot trial, evaluating the feasibility of
enrolling patients to a trial involving an innovative surgical intervention. This chapter
evaluates recruitment issues to surgical trials that investigate surgical interventions and
explores potential solutions to these challenges.
Chapter 4 reports on a prospective study that was performed alongside the trial presented
in Chapter 3 that evaluated the use of population-based electronic databases as a possible
opportunity to improve accrual.
Chapter 5 describes a protocol for a randomized controlled trial comparing simultaneous
versus staged resection for synchronous colorectal cancer liver metastases. It uses the
results gathered from previous trials for its design and proposes the use of population-based
databases as a recruitment strategy.
Chapter 6 discusses the lessons learned from the two different trials and the one prospective
cohort study as a form of conclusion, examining possible opportunities to improve
recruitment, based on the challenges described in this PhD thesis. This chapter also
discusses limitations as well as future research planned based on this thesis work.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
The most common factor that leads to trial failure is poor recruitment. A trial is a
prospective study of an intervention (either with a comparator or not). This thesis discusses
issues with recruitment and ways to improve recruitment. It uses a series of trials. The first
trial investigated nutritional supplements before surgery. Problems with recruitment were
related to the short time interval before surgery and the opportunity for improvement is to
approach participants during their first appointment with surgeons.
The second trial investigated the feasibility of performing a surgical intervention in patients
with colon cancer and liver metastases, in which the liver and colon are removed at the
same time. A method of using provincial databases to identify potential participants is
proposed.
Next, the thesis proposes a surgical trial of a surgical technique using the methods from the
previous studies and ends with the lessons learned from the thesis.


title: CARDIOVASCULAR COMPLICATIONS FOLLOWING TRANSCATHETER AORTIC VALVE REPLACEMENT: QUANTIFICATION AND SYSTEMATIC DIFFERENTIATION USING CLINICAL MEASUREMENTS AND IMAGE-BASED PATIENT-SPECIFIC IN SILICO MODELING

contributor:
Keshavarz-Motamed, Zahra
Emadi, Ali
Mechanical Engineering

subject:
Transcatheter aortic valve replacement
Left ventricle hemodynamics
Lumped parameter modeling
Fluid-structure interaction

abstract:
The success of TAVR procedure hinges on quantifications of the global hemodynamics (heart function metrics and workload), and the local hemodynamics (3-dimensional flow dynamics in left ventricle, aortic root, and coronary arteries). In this study, we developed an image-based framework that can quantify local and global hemodynamics for TAVR assessment. The proposed framework uses fluid-structure interaction method and lumped-parameter modeling that only needs routine non-invasive clinical patient data. The computational framework was validated against clinical cardiac catheterization data and Doppler echocardiographic measurements.
One of the challenging aspects of TAVR is its common association with complex valvular, ventricular, and vascular diseases (C3VD). Treatment strategies for these patients are quite uncertain and, on a case-by-case basis. In order to examine long term risk factors and create guidelines for intervention aimed at minimizing the progression of cardiovascular disease, the impact of C3VD on ventricle fluid dynamics in patients who underwent TAVR was investigated in this thesis. Our results showed that interactions of C3VD with TAVR fluid dynamics may amplify adverse hemodynamic effects that limit the benefits of TAVR and might contribute to speed up disease progression. The results suggest that some other interventions in addition to TAVR, such as mitral valve intervention and percutaneous coronary intervention, might be required as regularly chosen current surgical techniques might not be optimal for patients with C3VD who undergo TAVR.
Post-TAVR complications including paravalvular leakage, thrombosis and coronary obstruction remain as the main Achilles heels of TAVR. While coronary artery disease (CAD) is present in approximately half of TAVR candidates, correlation of post-TAVR complications such as paravalvular leakage (PVL) or misalignment with CAD are not fully understood. To effectively evaluate risk status and create guidelines for intervention, precise quantification of aortic root and coronary artery hemodynamics is required. We used a patient-specific multiscale computational-mechanics framework in both pre and post TAVR states to investigate the effect of TAVR complications such as PVL and misalignments on the coronary arteries and aortic root hemodynamics. The proposed framework could provide a platform for testing the intervention scenarios and evaluating their influences on the hemodynamics.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Transcatheter aortic valve replacement is an emerging less invasive intervention for patients with aortic stenosis. Although hemodynamics quantification is critical for accurate and early diagnosis of aortic stenosis, proper diagnostic methods for these diseases are still lacking because fluid-dynamics methods, that can be used as engines of new diagnostic tools, are not well developed yet. We developed an image-based patient-specific computational framework that can quantify hemodynamics in patients with aortic stenosis who received transcatheter aortic valve replacement. We also used its diagnostic abilities by providing novel analyses and interpretations of clinical data to answer clinical questions.


title: HIV in Mexico: A 10-Year Population-Based Analysis to Evaluate Policy Changes in Diagnosis, Treatment, and Early Mortality on PLWH 2008-2017

contributor:
Tarride, Jean-Eric
Health Policy

subject: HIV Evaluation policies Mexico

abstract:
The last twenty years have been dynamic and relevant for the HIV/AIDS epidemic worldwide. Compared to the beginning of the HIV epidemic, People Living with HIV (PLWH) are living longer and better lives because of increased understanding of the disease, awareness, access to treatments and better quality of health care. In Mexico, since 2007 there was a major initiative that provided universal access to antiretroviral treatment and care for all PLWH, regardless their insurance status. The last two major health policy changes were implemented in 2013, and 2014. First expanding actions to increase early diagnosis and treatment. Second, modifying clinical guidelines (in 2014) to expand universal antiretroviral treatment access, irrespective of their baseline CD4 cell count and symptoms.
This dissertation examined the relationship of the two HIV policy changes in Mexico on diagnosis, treatment, and early mortality of people living with HIV using data from Mexican individuals receiving antiretroviral treatment from 2008 to 2017. The three original papers also identify the key determinants for the same three indicators. Results from the first study indicated that actions implemented in 2013 decreased the proportion of individuals with a late HIV diagnosis. The second article highlighted the importance of removing clinical indicators for treatment initiation, as this increases the number of PLWH initiating antiretroviral treatment and reduces the number of PLWH who develop virological failure. The last article showed that that being male, being older, showing worse biomarker levels at the time of diagnosis, and being diagnosed in a region other than Mexico City were factors associated with early mortality. While the descriptive data showed that the proportion of individuals experiencing early mortality decreased after the HIV policy changes implemented in Mexico in 2014. The entire work tells a complete story for understanding the HIV epidemic in Mexico, based on three main indicators.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: Health policies are designed, implemented, or changed to improve the population healthcare. Specifically, for the context of the HIV, policies also target to contain the global epidemic. Identify socio-economic determinants of People Living with HIV and the relationship with policy success is key to control and end with this public health concern. This doctoral thesis evaluates recent changes in HIV health policies in Mexico and identifies determinants of the three major HIV outcomes these policies affect: diagnosis, treatment, and early mortality in People Living with HIV.


title: Hierarchical Omniphobic Surfaces for Pathogen Repellency and Biosensing

contributor:
Didar, Tohid
Soleymani, Leyla
Biomedical Engineering

subject:
omniphobic surfaces
hierarchical surfaces
bacteria repellent
anti coagulant
biosensing
liquid infused surfaces
electrochemical biosensor
non-specific binding

abstract: Development of repellent surfaces which can supress bacteria adhesion, blood contamination and thrombosis, and non-specific adhesion on diagnostic devices has been a topic of intense research as these characteristics are in high demand. This thesis focused on design and development of omniphobic surfaces based on hierarchical structures and their application for preventing pathogenic contamination and biosensing. First, a flexible hierarchical heat-shrinkable wrap featuring micro and nanostructures, was developed with straightforward scalable methods which can be applied to existing surfaces. These surfaces reduced biofilm formation of World Health Organization-designated priority pathogens as well as minimized risk of spreading contamination from intermediate surfaces. This is due to the broad liquid repellency and the presence of reduced anchor points for bacterial adhesion on the hierarchical surfaces. Next, the developed surfaces were applied to minimize blood contamination and clot formation as well as facile integration of hydrophilic patterns. This led to droplet compartmentalization and was utilized for detection of Interleukin 6 in a rapid dip-based assay. Furthermore, in a review article the need for anti-viral or virus repellent surfaces and future perspectives were discussed as the global COVID-19 pandemic surged and attracted interest toward innovative technologies for suppressing the spread of pathogens. To address the pressing issue of non-specific adhesion in diagnostics devices, an omniphobic liquid infused electrochemical biosensor was developed. This was achieved by electroplating gold nanostructures on fluorosilanized gold electrodes. These electrodes demonstrated rapid and specific detection of Escherichia coli within an hour in complex biological liquids (blood, urine, etc.) without dilutions or amplification steps from clinical patient samples which are major bottle necks when rapid detection systems are sought for at the point of care.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Repellent surfaces have a variety of applications in healthcare, for coating medical devices (e.g. indwelling implants, stethoscopes, and other external devices.), coating hospital surfaces for blood and pathogen repellency, and for developing anti-fouling diagnostic devices. Furthermore, they can be applied in the food sector for limiting contaminations, and in public areas on high-touch surfaces to eliminate the spread of infection. Therefore, there is a need for repellent surface which can be easily applied to surfaces with various form factors while having an easy fabrication method. Featuring hierarchical structures on a heat-shrinkable material, a repellent wrap was designed to be integrated on existing surfaces and repel pathogens and suppress the spread of infection as an intermediate surface. Similar concept was used for designing blood repellent surfaces which were patterned with hydrophilic regions for a rapid dip-based biosensing platform. Finally, surface textures on conductive materials with liquid infused repellent coatings were investigated for electrochemical biosensing in complex biological liquids.


title: Preparedness for Clinical Trials in Medical Oncology Subspecialty Training in Canada - A National, Bi-Lingual Questionnaire

contributor:
Pond, Gregory
Health Research Methodology

subject:
Education
CBME
Medical Education
Medicine
Residency
Medical Oncology

abstract:
Background: There is no standardized approach to clinical trial education for Canadian medical oncology subspecialty training. Canadian medical oncology subspecialty training programs have transitioned to a competency by design (CBD) educational framework. This study aims to determine whether current education practices in medical oncology subspecialty training programs in Canada prepare medical oncology trainees for participating in clinical trials as an investigator.

Methods: A national, online, bi-lingual questionnaire to understand exposure to clinical trials and general research in training, self-perceived competence, preparedness, and willingness to participate in clinical trials was conducted. Participants included medical oncology resident trainees and fellow trainees and new-to-practice physicians who have practiced in medical oncology for less than 5 years. All participants had to complete a medical oncology subspecialty training program in Canada. Data were collected from November 2021 to February 2022. Results are presented using descriptive statistics.

Results: Out of the 41 respondents (response rate: 15%), most were new physicians (41%), from Ontario (61%). 73% did not have formal training on how to participate in clinical trials as an investigator. 65% rated their competence in clinical trials as fair/poor and 74% rated their preparedness for clinical trials as fair/poor after training. 79% were willing to participate as an investigator in clinical trials after training. A correlation analysis revealed structured or in-clinic teaching in clinical trials trended towards improved self-evaluations of competence, preparedness, and willingness to participate in clinical trials (p > 0.05). Most respondents (56%) sought additional clinical trial education after training.

Conclusion: Training in clinical trials is highly variable. After training, most trainees do not feel competent or prepared to participate in clinical trials as an investigator, but they have a willingness to pursue clinical trials. Further assessment into how to produce competent medical oncology clinical trial investigators is warranted.

abstract: Thesis

abstract: Master of Health Sciences (MSc)

abstract: Clinical trials are pivotal in the field of medical oncology, leading to the changing diagnostic and treatment landscape in medical oncology. Knowledge of how to participate in clinical trials as an investigator is becoming increasingly important in the field of medical oncology. Early integration of clinical trial experiences can increase early-career physician participation. This study assessed current teaching practices related to clinical trial education in medical oncology subspecialty training programs in Canada. Self-assessments of competence and preparedness to participate in clinical trials after training were low, while self-assessment of willingness to participate was high. In-clinic training trended towards improved self-assessments of competence and preparedness. An approach to medical education that increases in-clinic exposure to clinical trials in the subspecialty curriculum is needed to improve preparedness and competence in clinical trials after medical oncology subspecialty training.


title: Impact of Hemodynamic Parameters on a Stenotic Aortic Valve: An in Vitro Study

contributor:
Keshavarz Motamed, Zahra
Mechanical Engineering

abstract:
Aortic Stenosis (AS) is a common valve disease, defined as the narrowing of the aortic valve. AS usually occurs together with other vascular and ventricular diseases; leads to insufficient blood supply to the body and adds stress on the heart. This study aims to investigate the impact of hemodynamic parameters on a stenotic aortic valve. Experiments were carried out in a cardiovascular simulator to replicate different physiological conditions. One aortic valve geometry was developed using computed tomography images, with four hypotheticals thicknesses: 0.3, 0.6, 0.8, and 1.0 mm. A physiological (non patient -specific) left ventricle volume waveform was applied as the input, and the valves were tested in different physiological conditions to investigate the impact of different parameters on the aortic stenosis.
The effect of artery constriction on AS was evaluated by measuring pressure and flow rate and calculating Effective Orifice Area (EOA) and left ventricle (LV) workload. It was observed that a 49% increase in the Systemic Vascular Resistance (SVR) brings about a 27% reduction in EOA and a 79% increase in left ventricle workload. The coexistence of AS and left ventricle disorder in providing sufficient stroke volume reduces the valve opening area. Experimental results show a 30.5% (0.36–0.25 cm2) reduction in EOA when the stroke volume decreases by 50% (60-30 ml). A thicker valve with a higher resistance in turn decreased the EOA and increased the left ventricle workload. The results depict that the LV workload considerably increased with the leaflet thickness (34%). EOA, on the other hand, significantly decreased with the thickness (46.3%). This study highlights that hemodynamic parameters may exacerbate the aortic valve function in patients with AS. Moreover, to investigate the underlying logics of AS, other coexisting disorders need to be considered.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Solving the Extremely High Dead Time During Ultra-High-rate Gamma-ray Spectrometry Using a LaBr3(Ce) Detector

contributor: Radiation Sciences (Medical Physics/Radiation Biology)

subject:
LaBr3 detector
Gamma-ray Spectrometry

abstract: One of the main challenges during the ultra-high count rate gamma-ray spectrometry is the large dead time. Using a LaBr3(Ce) detector (TRT 0.3 µs, TFT 0.5 µs), with an input count rate of 4.8×10E5 cps, the dead time could be as high as 87%. Such high dead time could significantly reduce the quality of the data collected as a considerable number of counts would be lost. Thus, this project aimed to reduce the dead time by modifying the detector system. Based on the setup used by previous research, the new system has its preamp, which is normally used for signal processing, removed. Experiments were made with calibration sources to optimize the new system. The calibration sources (Cs-137 and Co-60), Cs-137 resin sources, and Shephard Cs-137 sources were used to create different count rates, with the highest being 1.22×10E6 cps, for measurements. Side-by-side measurements were performed with the setup with preamp and the one without preamp at various count rates. The analysis, which focused on the dead time and resolution, shows the setup without preamp would have much lower dead time, especially during ultra-high count rate measurements. The method was proved to be successful, for, at 4.8×10E5 cps, the dead time decreased from 87% to 54%.

abstract: Thesis

abstract: Master of Science (MSc)


title: Numerical Simulations of Planetesimal Formation

contributor:
Wadsley, James
Physics and Astronomy

subject:
protoplanetary disc
hydrodynamics
instabilities
planet formation
planetesimals

abstract: A long-standing question in planet formation is the origin of planetesimals, the kilometre-sized precursors to protoplanets. Asteroids and distant Kuiper Belt objects are believed to be remnant planetesimals from the beginnings of our Solar system. A leading mechanism for explaining the formation of these bodies directly from centimetre-sized dust pebbles is the streaming instability (SI). Using high resolution numerical simulations of protoplanetary discs, we probe the behavior of the non-linear SI and planetesimal formation in previously unexplored configurations. Small variations in initial state of the disc can lead to different macroscopic outcomes such as the total mass converted to planetesimals, or the distribution of planetesimal masses. These properties can vary considerably within large simulations, or across smaller simulations re-run with different initial perturbations. However, there is a similar spread in outcomes between multiple smaller simulations and between smaller sub-regions in larger simulations. In small simulations, filaments preferentially form rings while in larger simulations they are truncated. Larger domains permit dynamics on length scales inaccessible to the smaller domains. However, the overall mass concentrated in filaments across various length scales is consistent in all simulations. Small simulations in our suite struggle to resolve dynamics at the natural filament separation length scale, which restricts the possible filament configurations in these simulations. We also model discs with multiple grain species, sampling a size distribution predicted from theories of grain coagulation and fragmentation. The smallest grains do not participate in the formation of planetesimals or filaments, even while they co-exist with dust that readily forms such dense features. For both single-grain and multiple-grain models, we show that the clumping of dust into dense features results in saturated thermal emission, requiring an observational mass correction factor that can be as large as 20-80\%. Finally, we present preliminary work showing that the critical dust-to-gas mass ratio required to trigger the SI can vary between 3D and 2D simulations.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Investigating High-Efficiency Thermoelectric Materials: Chalcogenide GeTe and Skutterudite Co4Ge6Te6

subject: Thermoelectrics

abstract:
The focus of this research is to explore high-efficiency thermoelectric materials, which can be put into daily application to mitigate the energy crisis. Some fundamentals and modern characterization techniques are briefly discussed.
Due to their ability to convert waste heat into electricity, thermoelectric materials have drawn significant attention in the past two decades. The most widely used thermoelectric materials nowadays are still composed of Pb and Te. Due to the toxic nature of Pb, extensive work has been done on the GeTe system, an environmentally friendly replacement for PbTe. Unfortunately, the pristine GeTe suffers from a high carrier concentration originating from the low formation energy of Ge vacancies. Herein, the introduction of ZnO nanoparticles into the GeTe matrix to form ZnTe nanophase resulted in the suppression of carrier concentration. This simultaneously increased the average Seebeck coefficient by 40% and achieved a substantial reduction (33%) in electrical thermal conductivity below 600K when compared to a pure GeTe. As a result, the peak zT reached 1.44 at 690K in the 1.5wt.% ZnO sample, and an average zT value was increased by 23% to 0.79 in the 323-733K range.
By adopting partial substitution of Fe at the Co site in the Co4Ge6Te6 ternary skutterudites, Co4-xFexGe6Te6 (x=0.04 and 0.12) was successfully tuned from an n-type material into a p-type one as proven by the positive Seebeck coefficient. An enhanced electrical conductivity was achieved by increasing the carrier concentration.

abstract: Thesis

abstract: Master of Science (MSc)


title: Finite Element Modelling Investigation of Transverse Cracking During Continuous Casting of Steel

title: FEM Investigation of Cracking During Continuous Casting

contributor:
Phillion, Andre
Materials Engineering

subject:
Transverse Cracking
Steel Slab
3D Finite Element
Finite Element Analysis
Thermal Modelling
Segregation Modelling
Mechanical Modelling
Stress

abstract: Continuous casting represents 96% of all steel products made worldwide. To cast new alloys, optimal process parameters must be determined that reduce quality issues. Traditionally, this is a time-consuming and expensive process due to the need to run multiple casting trials. Alternatively, numerical models can be used to help guide development of optimal process parameters. In this thesis, a 3D thermal-solute-mechanical finite element model has been created using the THERCAST software to simulate the casting process of a new advanced high strength steel grade at Stelco’s Lake Erie Works facility. The model represents the caster from mould to exit, and takes into account heat transfer from the mould, sprays, rolls, and ambient air. The model has been extensively validated using plant measurements from steel shim trials and pyrometer data. The model is used to investigate the evolution of temperature and shell thickness along the cast length, and the effect of spray cooling and casting speed on the surface temperature at unbending to predict transverse cracking during secondary cooling. It was found that the susceptibility to cracking increased with lower casting speed and increased water spray cooling. Increasing the casting speed had a negligible effect, and it was found to decrease with decreasing water spray cooling. This decreased water spray cooling is also accompanied by an increase in metallurgical length, so further work is required to determine appropriate safety factors to ensure the steel is completely solidified. However, preliminary results of solute and mechanical models are also presented. Further work is required to improve the predictions made by these simulations.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Developing an ERP Paradigm to Assess Conceptual Processing in Doc Patients: A Proof of Principle Study

contributor:
Connolly, John
Health Sciences

subject: EEG, ERP, Neuroimaging, Coma, Disorders of Consciousness, DOC

abstract: Severe acquired brain damage can sometimes result in a set of conditions resulting in altered states of consciousness, called Disorders of Consciousness (DOC). Event-related potentials (ERPs) extracted from electroencephalography (EEG) have proven to be a reliable neuroimaging method to accurately diagnose and predict the outcome of patients with DOC. The N400 component indicates higher order cognitive activity associated with processing, including language, music, and environmental sounds. An increased N400 amplitude has mainly been observed in response to sentence and word priming paradigms, mostly from healthy and native speakers of the language. Stimuli like sentences can tax working memory, which can cause misinterpretation of a patient’s condition as reflecting a language dysfunction when, in fact, the problem is about memory. Environmental sounds, or sounds related to common events, encode conceptual meanings similar to language and could be easier for such patients to comprehend. This study introduces a unimodal auditory priming paradigm with environmental sounds and spoken words to investigate if significant N400 activity could be elicited in a sample of 18 healthy participants and one DOC patient. ERP components (N400, N100 and P200) were extracted and averaged across 18 participants, as well as collected individually from each participant and one patient. The environmental sounds were paired with conceptually congruent and incongruent words. Comparisons of amplitude and latency were made between congruent and incongruent conditions. Statistical analysis indicated that the N400 amplitude peak in response to incongruent sound-word pairs was significantly higher than the responses to the congruent sound-word pairs across the grand average of 18 participants and for each individual participant as well. Significant differences for the amplitude and latency of N100 and P200, components that indicate auditory processing were seen across the average of 18 participants. The DOC patient showed a possible N400 effect upon visual inspection. Further testing of this paradigm with more non-communicative patients with neurological dysfunction is required to determine the utility of this priming paradigm in clinical protocol for diagnostic and prognostic purposes.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Severe brain damage can sometimes result in a set of neurological conditions called Disorders of Consciousness (DOC). These patients are often misdiagnosed due to clinical protocols relying on observation of visible signs of brain function and awareness. A brain imaging technique called electroencephalography (EEG) records electrical brain activity using metal discs or electrodes attached to the scalp. This can provide information about various kinds of cognitive and sensory activity. This study aims to investigate whether spoken words and environmental sounds can induce brain activity related to understanding meaning in healthy participants, and ultimately, in DOC patients.


title: A CRITICAL EXPLORATION OF DEI LEADERSHIP PRACTICES IN ONTARIO’S CHILD WELFARE

title: A Critical Exploration of DEI Leadership Practices

contributor:
Saara, Greene
Social Work

subject:
African
Caribbean
Black
Africentric
diversity
equity
inclusion
child welfare

abstract: The primary goal of my research is to understand how practices of diversity, equity, and inclusion (DEI) are used to mitigate the elevated numbers of children of African heritage in child welfare.  The disproportionate state-sanctioned child welfare apprehensions of Black children present as policing our most vulnerable members from communities of African heritage – our children.  The anti-Black state violence in Ontario has been “acknowledged” by child welfare agencies who are now required to address the racial disparities within child welfare agencies.  This thesis attempts to understand the histories, complexities, and current measures aimed at mitigating disparities of African, Caribbean, and Black children involved in child protective services from the perspective of child welfare service providers of African heritage.  Diversity, Equity, and Inclusion (DEI) are incorporated into hegemonic child welfare institutions while the provincial government has failed to publicly critique the current measures implemented to address the disparities for communities of African heritage.  Five participants were recruited from the Greater Toronto Hamilton area to participate in one-to-one interviews

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Getting Exclusionary Reasons Right

contributor:
Sciaraffa, Stefan
Philosophy

subject:
exclusion
normativity
obligations
reason-responsiveness
practical reason

abstract: Getting Exclusionary Reasons Right offers a defense of exclusionary reasons as originally conceptualised by Joseph Raz. Exclusionary reasons are second-order reasons to refrain from acting for some reasons and are used to explain the ordered nature of practical normativity, and the various normative concepts that are said to follow from it, i.e. mandatory rules, rule-following, authority, and promises to name just a few. Exclusionary reasons differ from other kinds of defeaters in that they exclude valid reasons, i.e. reasons that still justify or make eligible the actions they count for. According to Raz, this is because excluded reasons are defeated not qua reasons, but as reasons we can act for, or that motivate, which explains why exclusionary reasons are reasons to refrain from acting for a reason. However, the coherence and distinctiveness of the idea of an exclusionary reason—understood in this way—has faced serious challenges. I take up these challenges in what follows. Chapter one presents a coherent account of exclusionary reasons as reasons to refrain from acting for a reason, or to ‘not-φ-for-p’. It both clarifies the sense in which exclusionary reasons concern motivations and motivating reasons, and rejects alternative accounts according to which exclusionary reasons have as their object other normative reasons. It is argued that when they are understood as excluding some considerations as reasons that can rationally motivate, exclusionary reasons confer value on or point to an agent’s not acting for otherwise valid reasons. That is, they justify our not being responsive to certain values on some occasions. Chapter two vindicates the notion of acting-for-a-reason on which Raz’s account relies. It considers objections which claim that not acting for otherwise valid reasons presupposes a level of control over our reasons and motivations that is incompatible with the rational constraints on attitudes (beliefs, intentions, etc.), and shows how exclusionary reasons, as they are restated in chapter one, avoids them. Perhaps surprisingly, it is argued that instances where exclusionary reasons are relevant, when properly understood, are not instances where reasoning about what we ought to do involves choice. Getting Exclusionary Reasons Right concludes by considering the implications the account offered herein has for rationalist approaches to obligations and authority. Namely, it makes clear how fully rational agents can ever be moved to act for, or out of an awareness of their obligations.

abstract: Thesis

abstract: Master of Arts (MA)

abstract:
Getting Exclusionary Reasons Right investigates the distinctiveness and coherence of the idea of an exclusionary reason—a reason to not act for other reasons (i.e. promises, rules, commands, etc.). It first defends exclusionary reasons as reasons to ‘refrain from acting for some reason(s)’. Understood in this way, exclusionary reasons are relevant where it matters not just what we choose to do, but how we choose to do it. Promises, rules, commands, etc. are features of the world that make it valuable to or justify our not acting for otherwise good reasons when they apply. It then considers what ‘refraining from acting for some reason(s)’ consists in. While exclusionary reasons are thought to be reasons to have motivations of certain kinds, they are not reasons to choose to be motivated in some way. They are instead, reasons that determine for us the reasons we ought to act for. It is argued that while there are some instances where determining what we have reason to do is up to us, exclusion is not one of them.
Getting Exclusionary Reasons Right concludes by considering the implications the account offered herein has for rationalist approaches to obligations and authority.


title: Characterization of Astrocyte and Oxytocin Neuron Activity Dynamics in the Paraventricular Nucleus of the Hypothalamus

contributor:
Choe, Katrina
Neuroscience

subject:
Oxytocin
Stress
Astrocyte
Paraventricular Nucleus
Hypothalamus
Social
Fiber Photometry
Behaviour

abstract:
The paraventricular nucleus of the hypothalamus (PVN) is at the axis of stress
and social responses. During stress, PVN corticotropin-releasing hormone (CRH)
neurons become active and release arginine vasopressin (AVP) and CRH onto
downstream targets. While CRH and AVP initiate the release of glucocorticoids into the
blood stream, AVP also binds to receptors on PVN astrocytes to induce calcium waves.
Previous studies have found that PVN astrocyte activity is important for
modulating CRH neuron activity. It has been shown that oxytocin (OXT), the social
hormone, is also released in the PVN during stress to provide anxiolytic effects. We
hypothesize that stress-induced OXT release in the PVN acts on PVN astrocyte
receptors to provide the anxiolytic effects seen in previous studies. We sought to
explore this hypothesis by using fiber-photometry on C57Bl/6 mice during a social odour
preference test, freely behaving social tests, the looming shadow stress task, and the
tail lift procedure. We found that PVN OXT neurons are active while a mouse sniffs
another mouse and decrease in activity while a mouse sniffs an appetitive odour. We
also found that PVN astrocytes are active during stressful tasks and are active moments
before a mouse interacts with a non-familiar mouse. We did not see any interactions
between these two cell types during our experiments. An experimental technique with a
higher temporal resolution may be needed in the future to better identify if and how
these two cell types interact to modulate PVN CRH neuron activity.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
The goals of this thesis are to identify how two key cell types of the
paraventricular nucleus of the hypothalamus (PVN), namely oxytocin (OXT) neurons,
and astrocytes interact with each other during stress and social situations. We
employed fiber photometry in mice to investigate the interactions between PVN
astrocytes and OXT neurons during social and stress experiments. We found that PVN
astrocytes are strongly activated during the stress response and immediately prior to
sniffing a non-familiar mouse. On the other hand, we found that PVN OXT neurons did
not elicit a response in our stress tests but did increase in activity during social sniffs.
Interestingly, we also found that PVN OXT neurons reduce in activity while a mouse
sniffs an almond odour. These results suggest that PVN astrocytes are active during
stressful stimuli while PVN OXT neurons are active during periods of socialization and
decrease in activity while sniffing an appetitive odour.


title: Data-driven building energy models for design and control of community energy systems

contributor:
Cotton, James
Lightstone, Marilyn
Mechanical Engineering

subject:
community energy systems
building energy models
energy use disaggregation
cooling dominant buildings

abstract:
Building energy models are used to forecast building energy use to design and control efficient building energy systems.  Building energy use can generally be decomposed into heating, ventilation and air conditioning, refrigeration, appliance and lighting loads.  These loads will depend on multiple factors such as outdoor weather conditions, occupants, building type, controls and scheduling.  Data-driven models have become more popular with the increase in smart meter data available that can be used to train and fit the models.  Additionally, buildings with high refrigeration loads have greater heat harvesting potential, however, few data-driven models have been developed for buildings such as supermarkets and ice rinks.
In this work, linear regression models are used to predict the disaggregated space cooling, heating, baseload and refrigeration components of building energy use.  In most cases, measured aggregate electricity use is available, however individual appliances or component loads require submetering equipment which can be expensive. Therefore the proposed models use time-based and weather features to separate the thermal and baseload portions of the electrical load.  A generalized approach is also used to predict new buildings with data from existing buildings.  Furthermore, a simplified model is used to predict hourly space heating from monthly natural gas measurements and hourly weather measurements.  The models were evaluated on real data from buildings in Ontario and the disaggregated loads were verified with synthetic data.  The results found that aggregate use was predicted reasonably well using linear regression methods, with most building types having a median normalized root mean squared error between 0.2 and 0.3, depending on the forecasting period.  The model is flexible as it does not require detailed information related to the building such as lighting or setpoint schedules, however, it can be adapted in the future to include additional information and improve predictive capability.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Integrating Software Issue Tracking and Traceability Models

contributor:
Pantelic, Vera
Paige, Richard
Computing and Software

abstract: Awareness of the importance of systems and software traceability and tool support for traceability have improved over the years. However, an effective traceability solution must align with an organization's engineering processes. Specifically, the phases of the traceability process model (traceability strategy, creation, use and maintenance of traceability) must be aligned with the organization's engineering processes. Previous research has discussed the benefits of integrating traceability into the configuration management process. This research proposes a process based on Model-Driven Engineering (MDE) where traceability is integrated into Change Request (CR) management. In this process, traceability is managed with the status of the CR; for example, traceability is used to report the progress of the implementation of a CR. The proof of concept of the integrated process is demonstrated with a tool, Traceability Centric Issue Tracking System (TraceITS), based on Eclipse Modelling Tools and Epsilon model management framework. A preliminary evaluation of TraceITS indicates several advantages over regular ITS.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Primary care-based interventions to address patients' unmet economic needs

title: Primary care-based interventions to address unmet economic needs

contributor:
Dunn, James R
Health and Aging

subject:
Social determinants of health
Poverty
Primary care
economic needs
scoping review
qualitative research
case study
income inequality
health impact of poverty
high-income countries
intervention
primary care responsiveness to poverty

abstract: Poverty is acknowledged as the largest single social determinant of health in many high-income countries. Research into income interventions in primary care settings to address the health impact of poverty is a nascent and evolving field, with many gaps in knowledge. This thesis sets out to fill three related knowledge gaps in three separate papers. The first is a scoping review of the literature, which examines existing interventions currently in use in high-income countries. This review provides a unique overview of income interventions across different primary care settings, gleaned from over 200 papers, focusing on interventions targeting economic needs, and investigating interventions in the primary care setting across the whole spectrum, from screening patients, and collecting and managing the data generated in the process, to referring patients to external services, and directly intervening to address patients’ needs. The second is a case study of an income security health promotion service in a family practice in Toronto, Ontario, Canada. The study is the first to gather perspectives of key informants involved in this service, and to understand its origins, context and functioning. The study explores the external forces and contextual factors that have shaped the origin and development of the service, and offers important insights into how to create and sustain such a programme in other primary care settings. The third paper looks at an environment with extremely high rates of poverty–Hong Kong–where there are no such interventions in place. Through interviews with family physicians, the study explores the multiple barriers to primary care responsiveness to poverty, as well as potential facilitators and avenues for change. In doing so, the paper offers pointers for the introduction of such interventions not only in Hong Kong, but also in other high-income settings with high levels of inequality.

abstract: Thesis

abstract: Candidate in Philosophy

abstract: People’s health is affected by the conditions of daily life. In many high-income countries, poverty is known to adversely affect people’s health. Some primary care practices try to help patients who are experiencing poverty with non-medical measures, such as increasing their income or reducing their expenses. This study comprises three parts. The first part is a review of such interventions in high-income countries. This gives a broad overview of what kinds of interventions there are—from screening patients to referring them for help. The second part is a case study of a primary care practice in Toronto, Canada, that has a dedicated team to help patients who do not have enough money to meet their daily needs. The third part is a study of the barriers to doing so in Hong Kong, where there are high levels of poverty, but no such interventions.


title: A HUMAN IN VITRO INVESTIGATION OF THE AUTISM SPECTRUM DISORDER RISK GENE SCN2A

contributor:
Singh, Karun
Biochemistry and Biomedical Sciences

subject:
Autism Spectrum Disorder
Stem cells
Neurodevelopmental Disorders
Electrophysiology
SCN2A

abstract: Autism spectrum disorder (ASD) encompasses a group of heterogeneous disorders that affect approximately 1% of children worldwide. ASD is characterized by two core symptoms, the first being deficits in social communication and interaction, and the second being restrictive and repetitive behaviours. Although environmental and genetic factors are known to contribute to the development of ASD, the etiology remains unknown. Genetic sequencing studies have implicated over 1000 genes with risk variants that are ASD-associated. Recent sequencing studies have highlighted that SCN2A, a gene that encodes the Voltage-Gated Sodium Channel Type II Alpha Subunit habours a large proportion of genetic risk variants for ASD. An emphasis was put on this gene because many of the top genes regulate transcription and cytoskeletal dynamics and not sodium flux aiding in regulating neuron excitability. Initial investigations of complete loss of Scn2a in mice led to perinatal lethality where heterozygous loss exhibited many behavioural phenotypes associated with ASD. Through our collaboration with Dr. Stephen Scherer (Hospital for Sick Children, Toronto) we identified two de novo truncating point variants in SCN2A. In our study, we focused on using human iPSC-derived neurons for disease modelling. We found these two variants caused a reduction in synapses suggesting that neuronal communication may be altered. Furthermore, electrophysiological characterization of the neurons harbouring the differing SCN2A variants showcased that loss-of-function (LoF) variants can produce differential phenotypes based on their location. Beyond the initial ion channel characterization, we wanted to probe whether cellular pathways were altered directly or indirectly by atypical neuronal activity. Proteomics of neurons expressing the more severe variant, p.R607*, found differentially expressed proteins (DEP)s that were upregulated and downregulated. Moreover, these DEPs were enriched and clustered into cellular pathways that were altered, with one of these clusters representing mitochondrial function. We functionally validated these findings in the same neurons and found corroboration between the molecular and cellular data of impaired mitochondria. Lastly, we used Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene editing to generate an isogenic model to validate our findings of the less severe p.G1744* variant. Together, this will aid in the discovery of new variant categorizations and targeted treatments for rescues of atypical neural connectivity or pathways that are altered downstream.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Investigation of the potential effects of bone turnover on x-ray fluorescence measurements of bone lead in young women

subject:
XRF
Cortical porosity
Bone turnover
3d printing
MCNP
radiation
young women
Lead

abstract: The potential effect of bone turnover on bone lead k X-Ray Fluorescence (XRF) measurements in young women were examined in this thesis. Published data has shown that men and women do not release lead back into blood from bone stores at the same rate until after menopause. Recently our laboratory re-investigated this phenomenon, and currently unpublished data showed that the release rate for young women may be better modelled through a non-linear function. One possible explanation is sex differences in cortical porosity. However, it was unknown whether cortical porosity could create a measurement artifact. Using 3D printing techniques, a phantom design was created that emulates cortical porosity at structural sizes of 300 microns. A calibration set of lead-doped cortical porosity phantoms were created and compared with past bone lead phantoms, there was no statistically significant differences observed. In phantoms with homogenous distributions of lead, cortical porosity does not appear to affect phantom measurements. Monte-Carlo simulations were performed using MCNP to verify and expand upon these results. Findings agreed with experimental results, and it was also shown that heterogenous distribution of lead did not affect K-XRF measurements until the distributions were extreme. Cortical porosity does not appear to result in XRF measurement artifacts, and the non-linearity in the relationship between blood and bone levels observed in young women appears to be real. Published analysis of in vivo data sets of young women found measurements in morbidly obese women were inaccurate. The effect of soft tissue overlay on bone lead measurements was therefore examined using MCNP. Results showed as soft tissue overlay thickness increases, the average measured bone lead value decreases. MCNP further showed that while the measured bone lead level in an individual is reduced, an increase in measurement uncertainty measurement masked the reduction. This may explain why the phenomenon has not been clearly observed and understood until now.

abstract: Thesis

abstract: Master of Science (MSc)


title: Investigating the Potential Effects of Platelet Inhibition and Aging on Coronary Artery Disease Development in Mice

contributor:
Trigatti, Bernardo
Biochemistry and Biomedical Sciences

subject:
Atherosclerosis
Coronary Artery Disease
Platelets
Mouse Models
Cardiovascular
Myocardial Infarction
Aging

abstract: Coronary artery disease (CAD) is one of the leading causes of mortality worldwide, and is driven by atherosclerosis development that can lead to occlusive thrombus formation and myocardial infarction. Platelets are known to contribute to atherosclerosis development and thrombosis. Scavenger receptor class B type 1 (SR-B1) deficiency in apolipoprotein E (ApoE) knockout or low-density lipoprotein receptor (LDLR) knockout mice results in occlusive coronary artery atherosclerosis, platelet accumulation in atherosclerotic coronary arteries, and myocardial fibrosis. In this thesis, we examine the effects of genetically inactivating neurobeachin-like 2 (NBEAL2), which has a prominent role in platelet function, on CAD development in SR-B1/ApoE double knockout mice. NBEAL2 deficiency in SR-B1/ApoE double knockout mice reduced aortic sinus and coronary artery atherosclerosis and platelet accumulation in atherosclerotic coronary arteries, but increased myocardial fibrosis levels and reduced survival. NBEAL2 deficiency in SR-B1/ApoE double knockout mice reduced neutrophil granularity and the proportion of myeloperoxidase-positive neutrophils in the myocardium, which may in part contribute to the increased myocardial fibrosis levels.	Protease-activated receptor 4 (PAR4) also has a prominent role in platelet function. By using a novel pepducin (RAG8), we examine the effects of pharmacological inhibition of PAR4 on CAD development in high-fat, high-cholesterol, cholate (HFCC) diet-fed SR-B1/LDLR double knockout mice. RAG8 treatment did not alter aortic sinus atherosclerosis levels, but reduced coronary artery atherosclerosis, platelet accumulation in atherosclerotic coronary arteries, and myocardial fibrosis. These protective effects are not dependent on changes in circulating lipids, cytokines, and immune cells, but may be due to reduced vascular cell adhesion 1 (VCAM-1) protein expression in coronary arteries. We also examine the effects of aging on CAD development in HFCC diet-fed SR-B1 single KO mice. Older age in SR-B1 single KO mice did not alter susceptibility to HFCC diet-induced aortic sinus atherosclerosis, but increased susceptibility to HFCC diet-induced coronary artery atherosclerosis, platelet accumulation in atherosclerotic coronary arteries, and myocardial fibrosis. Older-aged SR-B1 KO mice exhibited reduced survival when fed the HFCC diet. These age-dependent changes are not driven by changes in plasma lipids, but likely driven by a combination of increased VCAM-1 protein levels in coronary arteries and circulating cytokines and neutrophils. This thesis demonstrates the potential effects of platelet inhibition and aging on CAD development in mice, and demonstrates that SR-B1 single KO mice may be a versatile and useful diet-inducible mouse model for atherosclerosis studies. Moreover, this thesis highlights the importance of analyzing atherosclerosis at multiple sites and utilizing mice that develop CAD and myocardial fibrosis when investigating the effects of interventions on atherosclerosis and/or CAD development.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Tracking Neurophysiological Markers of Auditory Change Detection and Consciousness for Clinical Assessment in Coma

contributor:
Connolly, John F.
Neuroscience

subject:
coma
EEG
Event-related potentials

abstract: The present dissertation expands the utility of EEG-based tools for the clinical assessment of coma. First, auditory mismatch negativity (MMN) responses were recorded in healthy controls and in a case series of comatose patients (over 12 and 24 hours, respectively). The  results (Chapter 2) showed that the MMN elicited by deviant sounds, particularly for duration stimuli, is extremely robust in full conscious state over the course of several hours at both the group and single-subject levels. However, preliminary results in three comatose patients provide further evidence that the MMN is present but fluctuates in detectability in coma. These findings highlight that repeated assessments and proper stimuli selection are essential when assessing this ERP component as neurophysiological predictor of coma emergence. Then, a follow-up study (Chapter 3) demonstrated the feasibility of multivariate pattern analysis in our sample as an automatic tool able to discriminate accurately between single-trials responses at single-subject level, providing further evidence of changes in auditory discrimination over time in coma patients. Additionally, a phase-based measure of functional connectivity in response to auditory stimuli and resting state was computed for the first time at both the sensor (electrode) and source levels in a dying comatose patient. This report provided a ML procedure able to discriminate (with perfomance accuracies above 90%) single-trial functional connectivity elicited by deviant sounds between a comatose patient and healthy controls; and showed at least a period of increased synchronized activity during resting state before the end of life in the coma patient. Taken together, our findings showed that the EEG/ERP responses here studied, are highly transient in acute coma over hours and days, suggesting that repeated assessments are crucial for their objective detection and the methods of analyses should be sensitive enough to capture such changes. Overall, this work illustrates the utility of EEG along with machine learning to individualized neurophysiological assessment of comatose patients.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Single point mutations in type IV pilus fiber proteins restore twitching in ΔpilU mutants

contributor:
Burrows, Lori
Biochemistry and Biomedical Sciences

subject:
Type IV Pili
PilU
Twitching Motility
PilA
Pseudomonas aeruginosa
Microbiology

abstract: Type IV pili (T4P) are long adhesive surface filaments produced by bacteria and are a key virulence factor for many pathogens. T4P are produced by a dynamic intracellular nanomachine that facilitates the assembly (extension) and disassembly (retraction) of pili. Pilus dynamics are enabled by the motor subcomplex of the nanomachine, where cytoplasmic ATPases power pilus assembly (PilB) and disassembly (PilT and PilU). In many, but not all, T4P expressing bacteria – including our model organism Pseudomonas aeruginosa – two retraction ATPases are required for functional retraction, which can be assessed by measuring twitching motility. Deletion of pilT results in loss of twitching and phage susceptibility (another hallmark of pilus function) while deletion of pilU results in loss of twitching but retention of phage susceptibility, indicating pili can still be retracted. We hypothesized that PilU adds to the force of pilus retraction, facilitating disassembly when the fiber is under tension. We mutated ΔpilU and pilU::Tn5 strains with ethyl methanesulfonate and screened for gain-of-twitching mutants. Whole genome sequencing revealed multiple point mutations in the major pilin protein PilA or the pilus adhesin, PilY1. These point mutations were recapitulated in a ΔpilU strain and restored twitching to varying degrees. Complementation of pilA point mutants with pilU in trans influenced the twitching zone of only one mutant, and in trans expression of wild-type pilA resulted in a significant reduction in twitching in most. The contribution of PilU to the force of pilus retraction was further investigated by a polyacrylamide micropillar assay, where no pulling events could be detected for either ΔpilT or ΔpilU mutants. Exopolysaccharide production, a proxy for surface sensing, was uncoupled from twitching motility in the pilA point mutants. These results are a significant step forward to understanding what PilU does and, provides insight to the dynamics of the pilus fiber.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Pseudomonas aeruginosa is a bacterium that causes serious infections. P. aeruginosa uses adhesive, “grappling hook” filaments called Type IV pili (T4P) to stick to its hosts. T4P can be repeatedly extended and retracted, allowing the bacteria to crawl on surfaces (twitching) but making them susceptible to bacteriophages, viruses that attach to pili then kill the bacterial cells. The motor proteins PilT and PilU are required for twitching, but only PilT is essential for phage killing, implying that pili are retracted even when PilU is missing. Here we hypothesized that PilU is important for twitching because it helps generate force for retraction when pili are under tension. We isolated multiple mutations in pilus components that restored twitching in the absence of PilU, and propose that these mutations allow for easier retraction of pili. This information helps us understand how T4P help the bacteria to spread during infection.


title: IMPACT OF PERIPHERAL IMMUNE CELLS AND SIGNALS ON BRAIN AND BEHAVIOUR OUTCOMES

contributor:
Foster, Jane
Neuroscience

subject:
immune-brain communication
T cell
behaviour
microglia

abstract:
Immune-brain communication is a critical component of the microbiome-gut-brain axis, and an important topic for today’s neuroscientists. Recent behavioural studies revealed that mice lacking the b and d chains of the T cell receptor (TCRb-/-d-/-) – which are functionally deficient in T cells – showed reduced anxiety-like behaviour on approach/avoidance tests. Therefore, in order to contribute to the knowledge of how the adaptive immune system participates in neurodevelopment, this thesis examines adaptive immune influence on the brain and behaviour: the impact of T cell deletion on microglia, myeloid cells in the blood, and behaviour, and of microbiota manipulation on neuroanatomy. The first study examined microglia number and density in adult TCRb-/- d-/- mice and showed increased numbers of microglia in the basolateral amygdala, and evidence of regional reductions in microglial density in TCRb-/-d-/- mice. Mice completely lacking microbiomes (Germ free - GF), are generally recognized to be deficient in mature lymphocytes. To determine how the microbiome impacts brain development, structural brain imaging was used to identify volume changes in neuroanatomy both globally, and regionally in stress circuitry. GF mice had smaller total brain volumes, and larger cortex but smaller hippocampus volumes, relative to total brain volume. Two models of recolonization indicate roles for the microbiome in postnatal brain volume development and contributed to identifying regional volumes that remain susceptible to postnatal microbiota influence. To understand how T cell deletion impacts peripheral immunophenotype, the final study investigated circulating myeloid cell numbers before and after puberty, alongside approach-avoidance behaviour tasks. Results indicate that TCRb-/-d-/- mice have higher monocyte and lower neutrophil
v
numbers compared to controls, and lack typical maturation of population heterogeneity and monocyte subtype observed in controls. Overall, this thesis demonstrates that the adaptive immune system is essential for typical neurodevelopment and contributes to efforts to identify the potential neuroimmune basis of neurodevelopmental disorders.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: The immune system has been linked to mental health, therefore understanding how it interacts with the brain is critical. T cells do not normally enter brain tissue but affect brain structure. Examining microglia – the brain’s immune cell – in mice without T cells revealed number and density differences in stress-associated brain areas. Research on gut bacteria-brain communication uses germ free (GF) mice, which live in sterile conditions. GF mice behave differently than controls, so neuroanatomy was mapped to identify regions most reactive to bacteria, and a timeline for microbe- associated neurodevelopmental changes was made. Mice without T cells seem less anxious than normal mice. Different immune cell varieties were collected from T cell deficient mice across puberty to identify immune-brain connections that might become compromised in neurodevelopmental disorders. Identifying changes in immune cells surrounding adolescence and linking to behaviour may reveal how immune-brain communication contributes to the onset of mental health disorders.


title: Assessing hydrologic impact of climate change in the Kou Basin

contributor:
Coulibaly, Paulin
Earth and Environmental Sciences

subject:
Kou Basin
SAWT+
MODFLOW
Climate change

abstract:
One of the key areas of climate change impacts is the water resources. Surface water has been compromised by climate change, and so has groundwater. Sub-Saharan Africa has been one of the major sufferers of climate change since the early 70s. The limitations of current global climate models in the prediction of the future climate over the continent have been a source of research challenges in the last decade. Over the decades, West Africa and the Sahel region have been subjected to major droughts and recurrent dry spells. While most studies in the region have tackled climate change effects on surface water and agriculture, a few have highlighted its effects on groundwater. This study investigates climate change impacts on both surface and groundwater in the Kou basin in Burkina Faso. The Kou River and its tributaries have experienced depletion over the last decades. Therefore, it has become necessary to investigate the deficit of the river flow and how the groundwater that forms the springs that feed the rivers is affected by climate change. The study resorts to integrated hydrologic modelling approach using the SWAT surface model and the MODFLOW groundwater model to assess the impact of climate change. Simulations from selected Regional Climate Models (RCMs) are used.
Investigations from the RCMs show that the study area is expected to be drier with less precipitation and higher temperatures. Furthermore, the SWAT model results show that as rainfall reduces, future stream flows also significantly decrease. Results from the MODFLOW model also follow the trend of the SWAT model. Groundwater levels are declining whatever the RCM outputs used. Overall, all the models predicted a severely decreasing trend in surface and groundwater in the Kou basin. The study results will be particularly useful for water resources managers in the Kou River basin.

abstract: Thesis

abstract: Master of Science (MSc)


title: Contaminants and nutrients in fish from the Wolastoq | Saint John River (New Brunswick): Spatial and species variability

contributor:
Kidd, Karen
Biology

abstract:
Fish provide a rich source of nutrients, like the omega-3 fatty acids (FAs) eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA), but can also accumulate harmful contaminants such as
mercury (Hg), organochlorine contaminants and trace elements. In rivers, dams can alter the
distribution and biogeochemical cycling of contaminants and nutrients, which can sometimes
increase their availability to and uptake in fish. However, it is unclear whether FAs covary with
contaminants within and among species along dammed systems. This study examined the spatial and species differences in contaminants and nutrients in fish from the Wolastoq | Saint John River (New Brunswick), which has a large hydroelectric dam and supports the subsistence
fishing of six First Nation communities. In 2020 and 2021, Smallmouth Bass, Yellow Perch,
American Eel and Striped Bass were collected from locations upstream and downstream of the
dam and analyzed for Hg, FAs, organochlorine pesticides (OCPs), polychlorinated biphenyls
(PCBs), trace elements and stable isotope ratios of nitrogen (δ15N) and carbon (δ13C), to
determine the trophic position and basal carbon source of the fish, respectively. Contaminants
varied by species where the lipid-rich American Eel were highest in lipophilic contaminants
(OCPs and PCBs) and the top predator Striped Bass was highest in biomagnifying elements like
Hg and selenium. Furthermore, EPA was highest in Yellow Perch while greater DHA
concentrations were observed in higher-trophic-level fish, both within and among species. Fish
from the dam’s reservoir were highest in the elements sulfur and phosphorus, and Hg for Yellow
Perch. The dam also appeared to alter food web dynamics as fish from the reservoir and just
below the dam had higher trophic positions, and reservoir fish were depleted in δ13C. Preliminary risk-benefit analyses indicated that the fish do not provide optimal EPA + DHA intake if they are consumed at levels that are considered safe for contaminants like Hg. Overall, this study suggests that dams can alter food web dynamics and the uptake of contaminants and nutrients by fish, and that location and species are important factors to include in risk-benefit analyses for fish consumption.

abstract: Thesis

abstract: Master of Science (MSc)


title: Wildfire Refugia Within a Boreal Shield Peatland and Rock Barrens Landscape: Identification, Drivers, and Ecohydrological Indicators

contributor:
Waddington, James Michael
Earth and Environmental Sciences

subject: Wildfire Refugia Peatlands Ecohydrology Peat Fire

abstract:
Fire refugia, defined as unburned, functionally intact patches of habitat within a fire footprint, play an important role in post-fire recovery and landscape resilience to fires. Increased fire activity in the Canadian boreal forest due to climate change highlights the need to properly identify and manage wildfire refugia to protect the natural resilience of boreal ecosystems. While previous fire refugia research has focused on western Canada, we present the first characterization of fire refugia, with a focus on peatland fire refugia, in Ontario. We use remotely sensed multispectral imagery and stereo-derived DEM data from the 2018 Parry Sound 33 wildfire in the Ontario Boreal Shield to determine the primary drivers of fire refugia formation on this landscape, and to develop a model to predict the occurrence of potential fire refugia based on these drivers. We found that the Normalized Difference Moisture Index (NDMI) and the Topographic Position Index (TPI, 200m radius neighbourhood) had the strongest control on wildfire refugia probability in the model, with a combined relative influence of 63.8%. Additionally, wildfire refugia tended to form in peat-filled depressions, valleys, and forested areas within the study area, whereas drier, open rock barrens were most susceptible to fire. Overall, the model had a high predictive accuracy, with a cross-validated AUC of 0.88, and a sensitivity of 81.2%. We conclude that local scale topography and simple flow accumulation models can act as a powerful tool in predicting fire refugia occurrence in this landscape.
In the second part of this study, we examined the in-situ indicators of peatland fire refugia occurrence. We conducted vegetation surveys at eight peatland fire refugia and eight reference sites representative of the range of wetland types found on this landscape. We found that the peatland fire refugia had a significantly different understorey vegetation composition when compared to the reference sites. Environmental factors within the peatland fire refugia which significantly influenced this separation included median peat depth, pH, and specific conductance (SpC); where peatland fire refugia were deeper and had a lower pH and SpC when compared to the reference sites. While no vascular indicator species were identified within the peatland fire refugia, there were two bryophyte indicator species: Sphagnum rubellum and Sphagnum magellanicum which were significantly associated with the peatland fire refugia. We conclude that understorey vegetation composition, indicator species presence, peat depth, pH and SpC could be useful when distinguishing peatlands with a high refugia probability, however, further research is needed to understand how this may vary geographically and in response to top-down controls, such as fire weather. Overall, the preliminary characterization of fire refugia in the Ontario Boreal Shield will provide a basis for the identification and mapping of fire refugia within this ecozone for applications in conservation, restoration, and fire and land management.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Areas which remain unburned, or burn at a low severity during a wildfire, are referred to as fire refugia by scientists and conservationists for their role in providing habitat to plants and animals following a fire and promoting the regeneration of the burned landscape. Here, we use modelling and field survey methods to examine the biological and physical controls of fire refugia occurrence in an Ontario Boreal Shield landscape. We find that large, deep peatlands and wetlands in bedrock depressions on this landscape are more likely to act as fire refugia, and that confirmed peatland fire refugia have distinct vegetation communities and more stable water tables when compared to other peatlands and wetlands on this landscape. These insights into fire refugia occurrence in the Ontario Boreal Shield will assist in the detection of potential refugia for the targeting of conservation and management strategies to help protect these ecologically important areas.


title: Tri-Level Mixed-Integer Linear Programming Problems: Solution Approaches and Applications

contributor:
Hassini, Elkafi
El-Dakhakhni, Wael
Business Administration

subject:
Tri-level Programming
Multi-level Optimization
Bi-level Programs
Branch and Bound
Decomposition Algorithms
Heuristics
Defending Critical Infrastructure
Protecting Electrical Networks

abstract:
Multi-level programming has been suggested as a suitable methodology for modelling the interactions between the different levels of decisions in organizations that follow a hierarchical structure. It has been applied in different fields such as revenue  and energy management. Due to the rise of decentralized decision-making and the need for efficient algorithms, the overarching motivation of this thesis is to develop algorithms suitable for solving multi-level programming problems and testing them on practical applications.
First, we conduct a bibliometric analysis of the literature to categorize the major topics of study and solution methodologies. In addition, we identify research gaps and future research directions. Second, we direct our focus to developing efficient algorithms for solving specific classes of linear tri-level programs. In Chapter 3, we propose three heuristic-based approaches; each heuristic type offers a trade-off between solution quality and computational time. To illustrate our solution approaches, we present an application for defending critical infrastructure to improve its resilience against intentional attacks.  In Chapter 4 we study bi-level mixed-integer linear problems and a general class of tri-level programs by proposing a general-purpose algorithm capable of handling mixed-integer variables in both levels of a bi-level linear program and solving a general class of tri-level mixed-integer programs with a convex optimization problem being at the most lower-level.  In chapter 5, we examine a  three-level non-cooperative game with perfect information that can have a min-max-min or a max-min-max structure. We propose a heuristically-enhanced exact algorithm. We demonstrate the proposed algorithm on two applications: defending critical infrastructure and the capacitated lot-sizing problem with the capability of interdiction and fortification.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract:
Multi-level programming has been suggested as a suitable methodology for modelling the interaction between the different levels of decisions in organizations that follow a hierarchical structure. It has been used in practical contexts such as in determining pricing strategies, and energy management. Due to the rise of decentralized decision-making and the need for efficient algorithms, the overarching motivation of this thesis is to develop algorithms suitable for solving multi-level programming problems. We develop solution strategies for solving different classes of multi-level problems including novel heuristics, general-purpose solvers, and exact algorithms. We address different classes of multi-level problems and apply the proposed solution approach(es) on relevant applications.
Although the developed techniques are inspired by specific practical applications, they can be applied in many other domains. We show numerically that our proposed solution approaches lead to better solution quality and are computationally more efficient. Furthermore, our proposals form a cornerstone for interesting theoretical and algorithmic developments in  this area of research.


title: Investigating the evolution of menopause through computational simulation

contributor:
Stone, Jonathon
Biology

subject:
menopause
evolution
elephants
aneuploidy
computer simulation
computational modeling
post-reproductive lifespan
senescence
humans
life history

abstract: Menopause is characterized by prolonged lifespan beyond the point of reproductive cessation. Defined so that at least 25% of adulthood is nonreproductive, humans and some toothed whale species are the only groups that have been found to exhibit menopause. Menopause is a puzzling trait that seems to contradict classical evolutionary theory that equates selection operating on reproduction to selection operating on survival. I created two computational models to gain better understanding of the evolution of menopause. The first model explored why menopause is not observed in elephants despite their being characterized by key features in common with menopausal species, specifically offspring care from older females and longevity. Simulations allowed testing the effects of varying age at reproductive cessation and levels of offspring care, modeled by decreases in interbirth intervals. I found that hypothetical populations with greatest post-reproductive lifespans, characterized by longer interbirth intervals and earlier reproductive cessation, were most likely to be out-competed by contemporary elephants. Conversely, hypothetical populations that were most reproductively competitive, those with shorter interbirth intervals and older ages of reproductive cessation, returned post-reproductive lifespans that failed to meet the 25% post-reproductive lifespan criterion for menopause. I identified a small region in the parameter space where populations that were both menopausal and reproductively competitive evolved, but the majority of that region corresponds to biologically unrealistic scenarios. The scenario that is most feasible involves an interbirth interval of 4 years and an age at reproductive cessation of 40 years. The second model studied how menopause might have evolved in humans through a behavioural strategy of ending reproduction early to avoid risk of aneuploidy later in life and diverting resources toward extant kin. I found that populations that ceased reproduction earlier and exhibited greater post-reproductive lifespan returned lower reproductive success. The model also demonstrated that the aneuploidy avoidance behaviour is most successful when reproduction ends at approximately age 50. These concepts have never been explored computationally before, so these experiments contribute a novel simulation-based perspective to the growing body of knowledge surrounding the origin and evolution of menopause.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Menopause can be defined generally for a group as a life history characterized by prolonged post-reproductive lifespan. Defined specifically so that at least 25% of adulthood is nonreproductive, menopause has been recorded in only humans and some species of toothed whales. This trait presents an evolutionary puzzle, as it appears to contradict classical evolutionary theory, which suggests that reproduction should continue until the end of life. In this thesis, I use computational modeling to explore why elephants have not evolved menopause despite sharing key features with menopausal species and how aneuploidy might have contributed to the evolution of menopause in humans.


title: Thermally tuned TeO2-Si Microdisk Resonators

contributor:
Bradley, Jonathan
Engineering Physics

subject: Silicon Photonics

abstract: In this research, we design and characterize thermally tuned hybrid tellurium ox- ide coated silicon (TeO2-Si) microdisk resonators for the development of tunable on chip lasers. Several heater designs are proposed that are compatible with stan- dard silicon photonics foundry processes and the requirement to deposit TeO2 onto the fabricated chips in post-processing. The devices are designed using simulation software packages such as Lumerical MODE and HEAT to simulate the mode profiles and thermo-optic coefficients of the microdisk resonators and the heating profiles of the various heater designs. The devices are laid out using the Luceda IPKISS Photonics Design Platform and fabricated at the AMF silicon photonics foundry. TeO2 is then deposited onto the fabricated chips at McMaster University in a single post-processing step via reactive radio frequency magnetron sputter- ing. Passive optical transmission measurements are performed to characterize the intrinsic Q-factors, loss and FSR of the microdisks. This is followed by resonance tuning measurements to characterize the tuning efficiencies of each of the heater designs presented in this thesis. The performances of each of the heater designs are then discussed and compared.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Rules of Customary Behaviour in the Mūlasarvāstivāda-vinaya

contributor:
Clarke, Shayne
Religious Studies

subject: buddhism; vinaya; monasticism

abstract:
This dissertation is a study of the rules of customary behaviour (āsamudācārika-dharmas) found in a North Indian Buddhist monastic law code, the Mūlasarvāstivāda-vinaya. Other than Gregory Schopen, few scholars have noted the significance of these rules. Schopen points out that according to this vinaya, adherence to rules of customary behaviour is foundational for achieving nirvāṇa. Yet, these rules have been practically ignored in contemporary scholarship. Building on Schopen’s work, I approach this material with two main questions: 1) What are rules of customary behaviour? and 2) How do rules of customary behaviour function in the Mūlasarvāstivāda-vinaya?
	In an attempt to answer these questions, I explore passages from the Mūlasarvāstivāda-vinaya in which the Buddha prescribes rules of customary behaviour for specific monastics in response to a variety of narrative situations. I organize this material into three thematic chapters. First, I discuss rules of customary behaviour related to the administration of the monastic community (saṃgha). Next, I explore rules of customary behaviour relevant only in specific environments. Finally, I investigate rules of customary behaviour prescribed in response to illnesses in the saṃgha.
	Through the above exploration, I demonstrate three main points:

	1) that there are three ways that rules of customary behaviour appear in the    			   Mūlasarvāstivāda-vinaya;
	2) the adoption of rules of customary behaviour prescribed in narratives in the 			   Mūlasarvāstivāda-vinaya does not necessarily signal the creation of a new 			   monastic office or official duty; and
	3) In the vast majority of cases, these rules seem to be designed to protect the   			   integrity of the saṃgha and accommodate monks or nuns who are experiencing 			   temporary challenges to their ecclesiastical status.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Exploring Clients’ Expectations of the Physical and Procedural Aspects of Sex Workers’ Services and the Resulting Impact on Sex Workers

contributor:
Elmi, Arij
Social Work

abstract:
Background: Currently in Canada, sex work is criminalized under Bill C-36. Since sex work is not considered legal work, it has been underresearched as a form of labour. Researching sex work as a form of labour would further the understanding sex workers’ work environments and needs within a labour context.

Aims: The aim of this study was to uncover what clients’ expectations of the physical and procedural aspects of sex workers’ services are, how these expectations are formed, and how these expectations impact sex workers.

Methods: Data was collected from an online discussion/review board called TERB (Toronto Escort Review Board) and was analyzed using the qualitative thematic analysis method.

Results: The findings suggested that clients and sex workers tended to have conflicting expectations of the physical and procedural aspects of sex workers’ services and that clients in the TERB community often relied on client reviews to form their expectations. Clients also formed their expectations based on the expectations they had of other non-sex work services, their own desires, and their knowledge of the law. Client expectations tended to have various negative impacts on sex workers and this highlighted the importance of having formal established rules, boundaries, and procedures in place in order to manage these expectations.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Effects of mental fatigue, exercise type, and exercise duration on the relative reinforcing value of exercise

contributor:
Bray, Steven
Kinesiology

abstract: People’s decisions to engage in exercise depend on the reinforcing value of exercise relative to competing sedentary alternatives, which may differ based on the type and duration of exercise. Mental fatigue is a commonly cited barrier to exercise and biases people’s choices towards sedentary behaviour versus exercise. However, the effects of mental fatigue on the relative reinforcing value (RRV) of exercise has not yet been examined. This study investigated the effects of mental fatigue, exercise type, and exercise duration on the RRV of exercise. In addition, this study compared ratings of liking and enjoyment for two common types of exercise, high intensity interval training (HIIT) and moderate intensity training (MIT), and assessed whether exercise enjoyment and mental fatigue predict the RRV of exercise. Participants (N = 48, Mage = 19.73  2.50 years) sampled a 6-min HIIT task as well as a 6-min MIT task and completed ratings of liking and enjoyment. Participants were then randomly assigned to engage in either a high cognitive demand (HCD) task, intended to increase levels of mental fatigue, or a low cognitive demand (LCD) task, intended to maintain levels of mental fatigue. The RRV of exercise was then assessed using a questionnaire that asked participants to make a series of choices between gaining access to a type of exercise (i.e., HIIT or MIT) versus a sedentary behaviour for a duration of time (i.e., 10, 20, or 30 min), with each option associated with a work requirement in the form of computer keyboard button presses. The questionnaire was repeated to calculate an RRV for each exercise type and duration combination. Results of the 2 (group; LCD, HCD) X 2 (type; HIIT, MIT) X 3 (duration; 10, 20, 30) mixed ANCOVA revealed a significant main effect of duration on the RRV of exercise (p < .001), indicating that people are less willing to work for access to longer durations of exercise compared to shorter durations. No other significant main effects or interactions were observed (ps > .13). Separate paired samples t-tests revealed that participants reported significantly greater ratings of both liking (p = .007) and enjoyment (p = .01) for the HIIT task compared to the MIT task. Further, results of hierarchical linear regression analyses revealed that HIIT enjoyment scores predicted the RRV for 10 min of HIIT (p = .03), with higher enjoyment predicting a greater RRV. No other predictors were significant (ps > .07). Overall, findings provide support for the promotion of shorter, intermittent bouts of exercise rather than longer continuous bouts. Given more positive affective responses to HIIT, individuals may be more likely to adopt and maintain exercise programs involving HIIT rather than MIT. Findings also suggest that increasing exercise enjoyment may be important for increasing the RRV of exercise, which in turn, may help support long-term exercise participation.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Fecal Metabolome of Irritable Bowel Syndrome

title: Fecal metabolomic analysis of irritable bowel syndrome using multisegment injection-capillary electrophoresis-mass spectrometry

contributor:
Britz-McKibbin, Philip
Chemistry and Chemical Biology

subject:
IBS
Irritable Bowel Syndrome
Stool
Metabolomics
Capillary Electrophoresis
CE

abstract: Irritable bowel syndrome (IBS) is increasingly common in Canada, effecting upwards of 18% of the population. The cause of functional gut disorders is not well understood, and new tools are urgently needed to help understand these complex chronic diseases and more accurately diagnose patients. Comprehensive metabolite profiling is a promising strategy to derive new insights into microbiome activity, but a clear set of guidelines for the handling and storage of human fecal specimens has yet to be thoroughly developed. The objective of this thesis is to create standardized sample handling procedures to enable reliable untargeted metabolite analysis of stool samples from IBS patients for biomarker discovery and differential diagnosis. Our results indicated that lyophilization prior to sample extraction not only increased the extraction efficiency on average by 28.5% compared to crude extraction, but also provided good long-term stability with less then 50% of metabolites showing altered responses after long-term storage while frozen up to 21 weeks. Additionally, lyophilization increased study repeatability, by simplifying the weighing and extraction process, reducing variability due to inconsistent stool water content as metabolite concentrations can be normalized to dried weight. This approach was subsequently applied in a pilot metabolomics study involving a cohort of IBS patients (n = 60) and healthy non-IBS controls (n = 20), where lyophilized stool extracts were analyzed by multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) with stringent quality control. The study included a differential stool metabolome analysis of diarrhoea and constipation predominate IBS subgroups (IBS-D; IBS-C), while also classifying IBS patients during contrasting periods of active or dormant symptoms based on their self-reported symptom severity and Bristol stool scale scores. Untargeted and targeted metabolite profiling of stool extracts by MSI-CE-MS under full-scam data acquisition in positive and negative ion modes revealed several promising biomarkers unique to IBS subtypes and symptomology, while also identifying novel metabolic signatures underlying IBS pathophysiology. Stool metabolomic studies aim to better decipher the underlying mechanisms of debilitating digestive disorders having complex aetiologies, which may also improve diagnostic testing and therapeutic treatments optimal for individual patients.

abstract: Thesis

abstract: Master of Science (MSc)