title: Effects of COVID-19 drugs chloroquine, hydroxychloroquine, azithromycin and remdesivir on hERG expression and function

contributor:
Zhang, Shetuan
Biomedical and Molecular Sciences

subject: hERG, COVID-19, chloroquine, hydroxychloroquine, azithromycin, remdeisivir, potassium channels, LQTS

abstract:
A prolongation of the cardiac action potential may present itself as long QT syndrome (LQTS).
LQTS can occur as a side effect of a wide variety of medications. A common cause of drug induced
LQTS is through drug interactions with the human ether-á-go-go related gene (hERG) potassium channel
or the KCNQ1+KCNE1 potassium channel. These channels produce the rapidly and slowly activating
delayed rectifier currents in the human heart, IKr and IKs, respectively. IKr and IKs are repolarizing currents
of the ventricular action potential and are key determinants of QT interval length. The COVID-19
pandemic caused by the severe acute respiratory syndrome coronavirus 2 has led to unprecedented
healthcare challenges. In the treatment of COVID-19 there have been investigations into repurposing
existing medications and using them to treat the disease in “off-label” use. Drug safety concerns have
arisen from reports of QT prolongation in patients receiving certain off-label COVID-19 drugs. In my
study, I investigated the effects of chloroquine, hydroxychloroquine, azithromycin and remdesivir on
hERG and KCNQ1+KCNE1 channel function. My results show that chloroquine and hydroxychloroquine
acutely blocked IhERG with an IC50 of 3 µM, and 23.4 µM respectively. Azithromycin and remdesivir did
not acutely effect IhERG. When these drugs were added to the cell culture medium at 10 µM for 24 hours,
remdesivir increased IhERGas well as hERG mature channel protein expression by 2-fold. The other 3
drugs tested had no chronic effect on hERG. Results from real time qPCR indicate that the increase in
mature hERG protein expression is through an increase in hERG mRNA through an unknown mechanism
of action. None of the four drugs tested had either acute or chronic effects on KNCQ1+KCNE1 at 10 µM.
These results provide insight into reports of QT prolongation from the use of off label COVID-19 drugs,
as well as show discovery of an unknown mechanism by which IhERG and hERG mature protein
expression is increased by remdesivir treatment.

abstract: M.Sc.


title: Changing accommodations in transition: Students with disabilities and their experiences at university

contributor:
McColl, Mary Ann
Rehabilitation Science

rights: Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada

rights: ProQuest PhD and Master's Theses International Dissemination Agreement

rights: Intellectual Property Guidelines at Queen's University

rights: This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.

subject:
transition
students with disabilities
accommodation
university

abstract: The transition from high school to university is one of the most significant that students with disabilities undergo in their academic career. Helping students make this transition successfully includes preparing them for accessing accommodations at university. While noting how the approval process differs, research to date has not detailed how student accommodations change as they transition from high school to university, or how these changes impact on their academic performance and experience at university. This doctoral thesis sought to address this gap. A retrospective cohort design was used to collect quantitative accommodation and academic data from 71 participants and qualitative data from a subset of 6 participants. To ensure precise comparison of high school and university academic accommodations, an Academic Accommodation Comparator Tool was created. Key findings of the thesis include: (a) disability labels and academic accommodations changed for students with disabilities as they transition from high school to university, (b) students received fewer accommodations and they were more likely to lose human assistance-type and modification-type accommodations at university, (d) despite being matched on key variables (i.e., admission average and gender), students with disabilities had a lower GPA and were more likely to fail a course in first year compared with non-disabled students, (e) some accommodations at university were associated with poorer academic performance, (f) the more accommodations students lost, the worse their academic performance at university, (g) despite these negative associations, students with disabilities were largely satisfied with the accommodation approval process and the accommodations they received at university. The thesis highlights practice implications for high schools and universities seeking to support the transition of students with disabilities and their success at university.

abstract: PhD


title: Attentional Orientation and Vocabulary Size

contributor:
Kuhlmeier, Valerie
Fitneva, Stanka
Psychology

rights: Attribution-NonCommercial-NoDerivs 3.0 United States

subject:
Disambiguation
Word learning
Gaze shifting
Vocabulary

abstract:
Quickly looking to a plausible referent of a word is both an indicator of effective lexical processing and an opportunity to learn new words. Beginning in infancy, faster attentional orientation during recognition and disambiguation is associated with superior vocabulary ability (Bion et al., 2013; Fernald et al., 2006). Yet, existing research on attentional orientation during word learning is limited. The present study examined whether the speed of attentional orientation during novel word learning is associated with word learning and vocabulary ability in adults.
The speed of attentional orientation likely depends on strengthening consistent associations and pruning spurious ones. In this study, exposure to word-object pairs in a familiarization phase affected individuals’ expectations. In each trial of the subsequent Cross-Situational Word Learning phase, individuals saw two referents and heard two words. The first word remained consistent from the familiarization phase to the learning phase. The second word was inconsistent from the familiarization to the learning phase. Adults used relative certainty to disambiguate the referents of inconsistent words in the first block of the learning phase, despite having seen these words co-occur with different objects earlier. Adults who oriented more quickly following consistent and inconsistent words learned those words better. Faster attentional orientation following the inconsistent word was associated with more developed productive and receptive vocabulary abilities.
These findings suggest that attentional orientation, measured in a context that does not draw on previous experiences with the words and objects, is still associated with vocabulary and word learning in adulthood. Additionally, the relationships between attentional orientation, word learning, and vocabulary ability are not specific to infancy. Adults who attend to the most likely referent of a novel word faster have better vocabulary abilities.

abstract: M.Sc.


title: Prognostic Features of Non-Muscle-Invasive Bladder Cancer: Grade, Molecular Subtype and Tumour Immune Microenvironment

contributor:
Berman, David
Pathology and Molecular Medicine

subject:
Non-Muscle-Invasive Bladder Cancer
Immunohistochemistry
Tissue Microarrays
Molecular Subtypes
Immunology
Immune Microenvironment
Prognostic Biomarkers

abstract: Intrinsic molecular subtypes with luminal or basal features have been identified in both breast and bladder cancer as promising areas for biomarker development. These intrinsic molecular subtypes may explain marked variation in prognosis and response to therapy. However, complex testing algorithms and little attention to more prevalent, early stage, non-muscle-invasive bladder cancers (NMIBCs) have hindered implementation of subtyping in routine clinical practice. Furthermore, the current grading classification for NMIBC includes a low-risk category known as PUNLMP and has been understudied with respect to molecular subtypes that could clarify its diagnostic distinction from other low-grade and high-grade NMIBCs. It is unclear whether subtype-specific clinical behaviors arise from tumour-intrinsic genomic features or signals from the surrounding benign tissue (stroma). We propose that profiling tumour and stromal immune cell populations across NMIBC samples may identify features contributing to the variability in prognoses and sensitivities to intravesical BCG immunotherapy. Current research suggests that clinical outcomes may be attributed to differences in the tumour immune microenvironment (TIME) of NMIBC patients, including immune cell populations such as CD3+/CD8+ T-cells, M2 macrophages and B-cells in the tumour and stromal compartments. However, simultaneous profiling of the TIME coupled with patient outcomes have not yet been described in NMIBC. To address these issues, we have developed a simpler, more robust method for molecular subtyping of NMIBC. We identified protein assays routinely used in surgical pathology laboratories that represent cardinal features of luminal and basal subtypes. Here, we validate the diagnostic and prognostic significance of molecular subtypes in PUNLMP and NMIBC cohorts using a simplified three-antibody algorithm. Furthermore, we used multiplex IHC methods to comprehensively profile both immune cell populations and immune checkpoints using three separate IHC panels for T-cells (CD3, CD8, Ki67, FOXP3), B-cell/Macrophage markers (CD103, CD163, CD79a) and PD1/PD-L1 (PD1, PD-L1, IDO1, CK5). Applying these profiling methods to NMIBC, we explore the differences in tumour and stromal immune microenvironments and their associations with prognosis. This work examines the prognostic associations between molecular subtypes across NMIBC tumour grades in conjunction with their immune microenvironment, and in doing so, reveals key biological and clinical differences amongst NMIBC tumours.

abstract: PhD


title: Frequency Analysis of the QRS Complex for Implantable Cardioverter Defibrillator Patients for Risk Stratification

contributor:
Redfearn, Damian
Translational Medicine

subject:
Sudden Cardiac Death
Risk Stratification
Signal Analysis

abstract:
Background: Sudden cardiac death (SCD) is one of the leading causes of cardiovascular death in North America. A metric called Layered Symbolic Decomposition frequency (LSDf) has been found to independently predict risk of SCD by stratifying patients into high risk or low risk groups based on a threshold determined from a derivation patient cohort. Here, we aimed to 1) validate the LSDf threshold to associate with event outcomes, 2) determine the predictive potential of the threshold, and 3) investigate the underlying physiological relationship of LSDf with SCD.
Methods & Results: Signal Averaged ECG recordings were completed for all patients recruited into our studies. Event outcomes were defined as surrogates for SCD including sustained ventricular arrhythmias (>30sec), appropriate ICD shock or anti-tachycardia pacing, new onset of heart failure, or cardiac mortality. For aim 1, a cross-sectional cohort of 172 patients with previous cardiac defibrillator devices (ICD and CRT-D) were stratified by the pre-determined LSDf threshold of 13.25%. The rate of events was significantly higher for patients with an LSDf ≤13.25%, with a relative risk of 1.43 times higher for experiencing an event than LSDf >13.25% (RR: 1.43 [1.22 – 1.67], p<0.01). The odds of experiencing an event for LSDf ≤13.25% patients were 6.05 times greater than LSDf>13.25% patients. For aim 2, two prospective studies involving a CABG cohort and ICD cohort comprised of 172 and 61 patients respectively were stratified as high or low risk for events prior to the cardiac intervention. The overall accuracy of correctly identifying patients as high risk or low risk was 81.4% [74.8 – 86.9%] for CABG patients and 50.8 [37.7 – 63.9%] for ICD patients. For aim 3, LSDf was found to change significantly following VT ablation (1.76 ± 1.24%, p<0.01) in 13 patients, whereas there was no significant change in LSDf following procainamide infusion (0.705 ± 1.89%, p=0.295) in 12 patients.
Conclusions: LSDf is a promising metric to facilitate the identification for patients at risk of SCD and provide a novel method for patient screening that is both non-invasive and relatively inexpensive to implement into clinical settings.

abstract: M.Sc.


title: A Refined Spatiotemporal Analysis of Extracellular Waveforms From Neurons Within the Lateral Intraparietal Area of the Macaque Posterior Parietal Cortex

contributor:
Paré, Martin
Neuroscience Studies

subject:
Neuroscience
Monkey
Action Potential
Spike Width
Lateral Intraparietal Area
Posterior Parietal Cortex
Electrophysiology
Extracellular Recording
Pyramidal Neuron
Interneuron

abstract:
Extracellular spike waveforms recorded from neurons are known to reflect the intracellular process of action potential generation through the activation and inactivation of ion channels. The variability between the shape of spike waveforms is thought to be a direct result of the differential ion channel expression between these subtypes. In cerebral cortex, spike waveforms recorded from pyramidal neurons are known to be ‘broader’ than the ‘narrow’ spike waveforms exhibited by interneurons. To capture this temporal variability in primarily biphasic waveforms, where a negative deflection occurs before a positive deflection, researchers have used the spike width—the time between the trough and peak of the waveform. However, numerous accounts have shown that this approach is too simplistic, failing to robustly discriminate putative pyramidal neurons from interneurons, as well as account for further nuanced classes of neurons. Continuing efforts are therefore being made to refine classifications with firing statistics and other parameters of the spike waveform shape.

In this thesis, I report on the defining characteristics of neurons recorded from the lateral intraparietal area, for which there exists only three other studies, within the posterior parietal cortex of one rhesus monkey. I significantly refined the standard approach to calculating the template mean waveform, which I used to extract previously reported spatiotemporal parameters as well as several new parameters.  Using unsupervised classification, I derived a three-class provisional model comprised of one narrow-spike class robustly separated from two broad-spike classes. Consolidating this classification, I identified a phenomenon observed exclusively in all broad-spike neurons, a knee-like change in the voltage close to the waveform peak. In addition, narrow-spike neurons were characterized by high firing rates, more irregular firing, and generally lacking bursting. While displaying converse firing statistics from narrow-spike neurons, there was no identifiable difference in the discharge properties between the two identified broad-spike classes. Nevertheless, several waveform features involving the knee-like change were highly discriminating between these two classes. Moreover, the class with the broader spikes exhibited more highly unusual troughs, which has been associated with multiple Na+ influxes thanks to larger dendritic tree arborization. Hence, I speculate that this phenomenon is predominant in pyramidal neurons within infra-granular layers. My detailed analysis provides a fresh perspective and new tools to help identify distinct spatiotemporal and functional signatures of three different types of cortical neurons.

abstract: M.Sc.


title: Diagnosing Witchery: Early Modern Medical Discourses, Public Health, and the Gendered Body in the Seventeenth Century English Witch-Panics

contributor:
Collins, Jeffrey
History

subject:
Witchcraft
Early Modern Europe
Early Modern England
Gender
History of Medicine
Early Modern Medicine
Body
Witch Panics
Heresy
Seventeenth Century
Public Health

abstract: This research examines the nexus of witchcraft and early modern healthcare. It draws on witchcraft studies and history of medicine to frame witchcraft as a public health crisis originating in, and investigated through, misogynistic medical ideologies. This research began primarily as an attempt to answer lingering questions of gender discrepancy in predominance of female executions. By examining the witch-panics of the 1640s through early modern medical discourses, this thesis contributes to understanding the physiological origins of witchcraft. Its findings provide the intersection of medical history and the gendered body as a cohesive framework for the dominant discourses in early modern English witchcraft scholarship. It engages with traditional historiographical narratives of witchcraft largely dominated by socio-economic and gender dynamics of daily life in a tumultuous period of English history. It utilizes sources from medical literature, witchcraft treatises, pamphlet testimony records, statistical data, as well as the diaries and reports of early modern contemporaries. The study demonstrates the witch-panics possessed an emphatically environmental dimension. This consisted of century-long concerns over public health instigated by humanity’s sins: worsening mortality crises, rampant endemic diseases, violent religious conflicts, and crop failures. These disasters implicated human sin at the root of these catastrophes. By interrogating the physiological weaknesses characterizing the female body, this work situates witches as covert carriers of sin and harbingers of illness. This understanding shaped all levels of English witchcraft investigation within notions of public health and disease. Witchcraft is examined vis-à-vis burgeoning English public health discourses, the medicalized misogyny informing the witch-figure in popular European culture, and the investigative and protective roles of the body in East Anglian witch investigations.

abstract: M.A.


title: An examination of the lived experiences of older people in Ghana

contributor:
Rosenberg, Mark
Geography and Planning

subject:
Older adults
Aging
Lived experiences
Food security
Sharing circles
Migration

abstract:
The number and proportion of older people (people aged 60 and over) in Ghana has grown steadily over the past few decades. Parallel to a growing older population in Ghana are changing social, economic, and environmental systems. Yet issues pertaining to older people have received less attention. There is limited understanding of the lived experiences of older people in Ghana, which has critical implications for knowledge and practice especially given the heavy reliance of older people on family members and the limited formal support systems. The overarching goal of this dissertation is to examine how the social and physical environments of older people in Ghana shape their lived experiences.
The findings generally suggest that older people in Ghana face numerous challenges which adversely affect their health and wellbeing. These challenges relate to insufficient social support, decline in functional and health status, decline in social status, inadequate access to water and sanitation facilities, food insecurity, economic insecurity, and caregiving burden. In contrast some older people receive adequate support and have positive experiences because of their perceived social status and authority. Based on this finding, it can be concluded that aging realities in Ghana are complex and (re)produced by the interaction between individual, contextual, and structural factors. This research makes important theoretical, methodological, and practical contributions. Theoretically, the research advances ecological systems theory and a geography of aging perspective by demonstrating how experiences of older people can be influenced by the different but interconnecting levels of the human environment. The research also highlights the complex and multiple experiences of older people in Ghana. Methodologically, the research provides an effective example of the usefulness of multiple data collection techniques, particularly, interviews and sharing circles in exploring the experiences and perceptions of a vulnerable population group in a low-income context. With regards to practice, the research demonstrates the need for a multi-pronged approach that considers the different levels of the environment in addressing the needs of older people.

abstract: PhD


title: Effects of Phosphodiesterase Variants on Angiogenic Functions of Vascular Endothelial Cells

contributor:
Maurice, Donald
Translational Medicine

subject:
angiogenesis
phosphodiesterase splice variant
cAMP
endothelial cells

abstract:
Angiogenesis, the biological process of new vessel growth from already existing vasculature, occurs
physiologically and pathologically. Previous studies have linked insufficient angiogenic activity to
ischemic disease and excessive angiogenesis to cancer. These disease states have a massive global
burden. During angiogenic sprouting, a select few endothelial cells (ECs) develop a tip cell phenotype
and function to guide cell migration towards angiogenic factors to form the new growth. While
angiogenesis is a highly regulated process, the precise molecular mechanisms dictating individual EC
functions like migration are not fully identified. The cAMP second messenger is involved in regulating
EC angiogenic activity. Macromolecular complexes containing unique combinations of cAMP effectors
and individual phosphodiesterase isoforms, provide signal specificity by allowing control of local pools
of cAMP to mediate distinct functions. A PDE3B/ protein kinase A (PKA) signalling complex regulating
angiogenesis has previously been defined and more recently, it has been shown that impairment of
PDE4D signalling induces a hyper-migratory EC phenotype. The studies presented in this thesis
investigated the individual PDE4D splice variant responsible for regulating EC migration in telomerase-immortalized
ECs. We identified that PDE4D5, not pan-PDE4D or PDE4D7, silencing impedes EC
migration. We further identified unique sequences in the N-terminal region of PDE3B and PDE4D
isoforms that can be targeted using CRISPR-Cas9 to create stable variant selective knockout cell lines;
though due to time constraints, we opted to use other strategies to elucidate individual splice variant
function. We additionally found that the creation of a cell line stably expressing a dominant negative
PDE4D5 is possible, while PDE4D7 is not. Overall, this work supports the concept that individual PDE
isoforms regulate distinct functional pools of cAMP activity and indicates that translation would lead to
increased efficacy and decreased side effect profiles of therapeutics targeting dysregulated PDE
signalling.

abstract: M.Sc.


title: EXPERIMENTAL ASSESSMENT OF FRP-CONFINED CONCRETE COLUMNS WITH DAMAGED JACKETS

contributor:
Fam, Amir
Civil Engineering

subject:
FRP-concrete
CFFT
Angle-ply
Cross-ply
Damage
Axial
Cut
Residual strength
Column
Confinement

abstract:
Axial compressive strength of circular concrete-filled fibre-reinforced polymer (FRP) tubes (CFFTs) benefits greatly from significant concrete confinement by the tubes. Accidentally or deliberately induced damage to the tube would undermine the CFFT strength. In this study, 33 CFFT short columns of 144-168 mm outer diameter and 420-460 mm height were tested under concentric loading to failure. Tube damage was artificially induced in the form of through-thickness linear cuts at mid-height. The cut length and orientation angle with respect to the longitudinal axis were varied. Two types of Glass-FRP (GFRP) tubes were studied, namely a nominal [±55o] angle-ply tube with diameter-to-thickness ratio (D/t)=35 and a [86o/-12o] near cross-ply with D/t=48, to investigate two commonly available but distinctly different tubes. The effect of cuts in the two tubes studied was very similar. Vertical and diagonal cuts significantly affected strength, whereas horizontal cuts had insignificant effect on strength. A nonlinear descending trend can be seen in axial strength ratio, relative to the intact CFFT strength, as vertical cut length increase. Initially, a rapid descent occurs up to a 40% reduction of strength, at cut lengths of 20% of the height, followed by a lower rate decline. Strain measurements revealed stress concentrations at the tip of the cut, where crack propagations occurred in the tube.
A design-oriented simple model is presented to capture the strength reduction of the damaged CFFT column. Concepts of models for partially confined columns were adapted to the conditions of CFFTs with linear damage. Different assumed conditions regarding the FRP volume and idealized parabola on the concrete at the level of the cut were assessed to establish the expressions that best predict the reduced strength of damaged CFFTs. By idealizing the cut length projection on the longitudinal axis as the gap between two bands of FRP with the same properties as the intact jacket, the strength of damaged CFFT columns can be calculated using this method based on the model proposed by Wang et al. (2018).

abstract: M.A.Sc.


title: SPATIAL AND TEMPORAL TRENDS IN RANGE-USE BY THE BATHURST CARIBOU DURING A POPULATION DECLINE, 1997-2019

contributor:
Danby, Ryan
Geography and Planning

subject: Spatial Analysis , Residence Time, Barren-Ground Caribou, Brownian Bridge Mapping

abstract: The Bathurst barren-ground caribou herd of Northwest Territories and Nunavut declined by 98% between 1986 and 2019; from an estimated population of 470,000 animals to just 8,200. Although caribou herds are known to fluctuate greatly between high and low populations, the recent population low has raised fears that this herd may go extinct. There are many factors which influence herd health, and disentangling how each contributes to decline is difficult. Our research goal was to examine broad scale spatial-temporal trends in range-use of the Bathurst herd from 1997-2019, in order to better speculate on how these caribou may be responding to external factors. We conducted a Residence Time movement analysis on animal collar data to determine specific timing of seasonal range-use. We used this timing information to create Brownian Bridge maps that capture seasonal ranges unique to herd behavior each year, as well as mapping their annual ranges. We applied linear regression models to our annual and seasonal range maps to explore temporal trends of habitat-use across space. We found significant decreases in the size of annual (90%) and seasonal (35 - 91%) ranges that mirrored the herd’s population decline. The duration of the herd’s spring migration significantly decreased, with caribou reaching their calving ground eight days earlier over the study period; potentially in response to an earlier onset of vegetation green-up. The time spent on the post-calving range increased over the monitoring period by thirteen days, suggesting that caribou have become more active; potentially as a mechanism to deal with insect harassment. Geographical analyses of the calving range showed that, unlike other ranges, there was little change in size and range-use. The consistent nature of this range may indicate that resources there are disproportionately important to caribou, relative to the other ranges. These temporal and geographic changes are not consistent with changes observed in other declining herds; a discrepancy that may indicate the Bathurst caribou are responding specifically to unique regional changes, such as timing in snowmelt, vegetative phenology, changes in insect activity, and industrial activity.

abstract: M.Sc.


title: EFFECT OF WETTING AND DRYING CYCLES ON THE PERFORMANCE OF MODIFIED AND NON-MODIFIED GCLS USED IN COVER AND BASE SYSTEMS AND UNDER HIGH HYDRAULIC GRADIENT

contributor:
Rowe, R. Kerry
Civil Engineering

subject:
GCLs
Wet and dry cycles
Hydraulic conductivity
Polymer enhanced bentonite

abstract: The effect of prolonged exposure to wet and dry cycles on the hydraulic performance of five different GCLs was studied. Three GCLs had polymer-modified bentonite and two GCLs had standard sodium bentonite. The GCLs were placed on a 3H:1V slope and subjected to three different modes of wet and dry cycles. The wetting cycles of the three modes lasted for eight hours, while the drying cycles varied between 16h for the W/D: 8h/16h mode, seven days for the W/D: 8h/7d mode, and 14d for the W/D: 8h/14d mode. Tap water was used for the wetting cycles and the drying cycles were conducted at room temperature. After one year of wet-dry aging, the hydraulic conductivity of the GCLs was examined by adopting conditions simulating the GCLs were used (i) alone or under a thin layer of cover soil and exposed to rainfall in cover systems, (ii) under a geomembrane’s wrinkle with a hole in a landfill base system. The k of the standard bentonite GCLs increased by one to two orders of magnitude and the polymer-modified bentonite GCLs increased by three to four orders of magnitude when permeated with tap water. When permeated with two strong synthetic leachates, the k was affected by the RMD of the permeant as the higher RMD of the solution, the lower k of the GCL. However, the GCLs directly under the GMB’s wrinkle had the poorer k. Four GCLs (two GCLs with polymer amended bentonite) were subjected to a high hydraulic gradient (i ~ 2000) of tap water infiltrating through the GCL for around one year. The k of the modified bentonite GCLs was lower than the standard bentonite GCLs when permeated with tap water, and higher than the standard bentonite GCLs when permeated with strong synthetic leachates. The effect of the number and the size of the needle punching bundles, the carrier geotextile type, the bundles’ thermal treatment, and the length of the drying cycles are discussed.

abstract: M.A.Sc.


title: Characterizing the association between regional cerebral oxygen saturation and neurological impairment after cardiac surgery

contributor:
Boyd, J. Gordon
Neuroscience Studies

subject:
post-operative cognitive dysfunction
cardiac surgery
delirium
robotic technology
cerebral oximetry

abstract:
It is well-known that patients undergoing cardiac surgery are at risk of developing acute, fluctuating (i.e. delirium), and/or long-term post-operative neurological complications. Incidence of neurological impairment can be as high as 60%, and has been associated with increased length of hospital stay, mortality, and severe cognitive impairment. While the exact etiology is unknown, it has been postulated that cerebral hypoperfusion may be associated with neurological deficits after cardiac surgery. Near-infrared spectroscopy (NIRS) is a commonly used, non-invasive technique that measures regional cerebral oxygen saturation (rSO2) during cardiac surgery, acting as a surrogate marker for cerebral perfusion. However, research has demonstrated inconsistent results regarding the relationship between NIRS-derived rSO2 and post-operative neurological impairment in cardiac surgical patients.

The primary objective of this thesis is to investigate whether low rSO2 levels are associated with post-operative neurological impairment in patients undergoing cardiac surgery. A systematic review was undertaken to evaluate sources of variability present in this body of research. This research project also assessed the feasibility of using robotic technology to quantify neurological functioning before and after surgery. Following an analysis of 40 patients undergoing coronary artery bypass grafting surgery, it was determined that subtle pre-existing impairment, detected by robotic technology, was a stronger indicator of post-operative dysfunction than intraoperative rSO2. Subsequent chapters describe the expansion of the study to include post-operative delirium and other cardiac surgeries, as well as relating rSO2 with other hemodynamic variables such as mean arterial pressure to quantify the degree of disturbed cerebral autoregulation. Preliminary findings also suggest that patients who experienced delirium may perform worse on the robotic tasks prior to surgery, suggesting that subtly impaired performance may be a reflection of poor cognitive reserve. In addition, I performed a pilot study that quantified
neurological impairment in higher risk patients undergoing non-invasive valve replacement.

The findings presented in this thesis provide evidence for the inclusion of perioperative neurological assessment as part of the standard of care for cardiac surgical patients. As well, it provides a strong framework for determining the benefits of measuring and monitoring rSO2 during cardiac surgery. Future research will include the role of delirium and pre-existing functioning to determine whether low rSO2 and/or disturbed cerebral autoregulation is associated with post-operative neurological impairment.

abstract: PhD


title: Development of P(TMC)-Based Polymers for Sustained Delivery of  Acid-Sensitive Drugs

contributor:
Amsden, Brian
Chemical Engineering

subject:
octreotide
drug delivery
trimethylene carbonate
peptide
acid-sensitive
sustained release
PTMC

abstract: Peptides are a quickly growing drug class, which continue to garner attention in pharmaceutical research due to their applications in the treatment of a variety of diseases. The major challenge when working with these drugs is their rapid degradation in vivo and poor membrane-permeability. This makes simple administration via oral routes infeasible and necessitates the use of a localized drug delivery system. One example of such a system is to load the peptide into a biodegradable polymer which is then injected close to the drug’s site of action. The polymer provides extended drug release, before degrading and being removed by the body. This is done commercially by a polymer called poly(lactide-co-glycolide), or PLG. However, PLG breaks down to form highly acidic by-products, which react with the peptide and alter the drug’s chemistry. Depending on the peptide, this can lead to reduced effectiveness or inactivation. In this work, a P(TMC)-based polymer was synthesized and assessed as a delivery vehicle for acid-sensitive drugs. P(TMC-HTMC-BtTMC) copolymers with varying compositions and molecular weights were examined. Ultimately, a low molecular weight viscous liquid formulation was the most feasible delivery option, and its degradation was characterized. Release of a representative peptide drug, octreotide, from the polymer was also studied. Increasing the HTMC content resulted in increased degradation, but complete degradation of the polymers was not achieved after 8 weeks, with degradation slowing considerably as HTMC content approached 15%. Modification of the octreotide was reduced in comparison to studies done using PLG.

abstract: M.A.Sc.


title: Physical Testing and Numerical Modeling to Develop Design Equations for Corrugated Steel Culverts under Live Loading

contributor:
Hoult, Neil
Moore, Ian
Civil Engineering

subject:
Physical testing
Three-dimensional numerical modeling
Corrugated steel culverts
New design equations
Live loading

abstract: This thesis investigates the structural behavior of corrugated steel culverts under live loading, through the use of field experiments and finite element modeling with the goal of developing design equations. An in-service corrugated steel arch culvert was monitored under static loading. Total station, digital image correlation, and LiDAR were found to be appropriate tools for field monitoring of culverts. Fiber optic strain sensors were also used to capture strain distributions around the culvert circumference. The experimental results revealed that bending moments could be as important as thrusts for shallow buried culverts. Another in-service arch culvert was tested under both static and dynamic loading. The distributed measurements showed that the front axle induced higher thrusts and moments than the rear axles. The asphalt pavement reduced moments by up to 38% but only reduced thrusts by 10% for this structure. To develop finite element models of corrugated steel culverts suitable for parametric studies, equivalent orthotropic properties of corrugated sheets were derived analytically. The developed expressions showed a significant improvement over those previously used in corrugated pipe finite element analysis, and guidelines for their use were then provided. Three-dimensional finite element analyses were calibrated with the experimental data from existing laboratory tests and the new field tests. The impact of various modeling choices and experimental uncertainties was studied using sensitivity analyses. The most appropriate model for circular and ellipse culverts was recommended, and used orthotropic shell elements, elastic soil properties with elastic moduli varying with depth, and tie constraints between the soil and the culvert. Finally, new design equations for thrust and moment under live loading were developed from the results of 1596 finite element analyses. The proposed thrust equations considered the relative stiffnesses between the soil and the corrugated steel culvert for the first time. Evaluations against the experimental and numerical data suggested that the new moment equations could potentially replace the current code design equations. The proposed equations were able to provide a conservative estimate of the ultimate load measured in a failure test with a 15% error while accounting for the flexural failure mechanism.

abstract: PhD


title: Theory and Computation of Intrinsic Propagation Losses and Disorder-Induced Modes in Topological Photonic Crystal Waveguides Using Mode Expansion Techniques

contributor: Physics, Engineering Physics and Astronomy

subject:
Topological photonics
Intrinsic losses
Disorder
Guided mode expansion
Bloch mode expansion
Photonic crystal
Slab waveguide

abstract: Photonic crystal (PC) slabs are promising optical systems for manipulating the flow of light on the nanoscale as a result of their combined in-plane lattice structure and slab waveguide properties. By introducing a line defect to the two-dimensional lattice, an efficient waveguide is formed that yields regions of fast and slow light.  Although conventional PC waveguides are relatively well understood and have been partly optimized in terms of their intrinsic losses, they are prone to significant disorder-induced backscattering and propagation losses. Topological PC slab waveguides have been proposed as a means to help mitigate disorder-induced backscattering and offer additional control of light-matter interactions.  However, many topological structures in optics are not yet well understood, due to being relatively new in the field of nanophotonics. In this thesis, we first investigate the intrinsic losses of topological PC slab waveguides using the semianalytical guided mode expansion method for perfectly periodic structures. We show that certain topological structures proposed in the literature are in fact intrinsically very lossy, while other, more recent “valley Hall” structures are able to achieve lossless propagation modes with good bandwidth. Second, we study the role of structural disorder using a Bloch mode expansion technique, which conveniently uses the solutions from the guided mode expansion as input. We find that the disorder-induced modes and impact on the photonic density of states for a topological structure is actually similar or worse than the W1 waveguide, and forms cavity-like modes with very small mode volumes. Future work is required to investigate how to mitigate the potential problems of disorder on these waveguides, and to assess which structures are more robust when coupling to resonators and spin-charged quantum emitters, where the topological waveguides show good promise.

abstract: M.A.Sc.


title: COMBINING ELECTROENCEPHALOGRAPHY AND FUNCTIONAL NEAR INFRARED SPECTROSCOPY TO IMPROVE ACCURACIES IN INTERPRETING INTENT DURING MOTOR IMAGERY TASKS FOR USE IN BRAIN COMPUTER INTERFACES

contributor:
Davies, T. Claire
Mechanical and Materials Engineering

subject:
brain computer interface
electroencephalography
functional near infrared spectroscopy
motor imagery

abstract: A Brain Computer Interface (BCI) system can bypass impaired systems in the brain, nervous system, and muscles to enable alternate function and allow the user to reconnect with the outside environment. Measurements for these systems usually include the collection of brain signal activity from sensors mounted on the surface of the scalp. Electroencephalography (EEG) and functional near infrared spectroscopy (fNIRS) are two commonly used non-invasive brain imaging modalities in BCI systems. EEG records the electrical activity produced by neuronal activations whereas fNIRS measures the concentration changes of oxy- (HbO) and deoxyhemoglobin (HbR) molecules in the brain cortex. In this thesis, both EEG and fNIRS data collected during a bilateral right- and left-hand motor imagery task were used to detect brain signals that suggest intent to move. Feature extraction and classification are two important components of a BCI in which discriminant features are extracted from the brain signals and then decoded to interpret the user’s intent. Using the fNIRS data in the first part of this thesis, different features were extracted (mean, peak, minimum, skewness, and kurtosis) and classification algorithms (linear (LDA) and quadratic discriminant analysis (QDA), support vector machine (SVM), Logistic Regression, and Naïve Bayes) were compared to find the set of features and classifiers with the highest accuracy. The mean, peak, and minimum of HbO, as well as the mean of HbR and mean of difference between HbO and HbR produced the highest accuracies among features, whereas skewness and kurtosis of HbO resulted in the lowest accuracies. Furthermore, QDA and SVM with polynomial and Gaussian kernel functions resulted in the highest accuracies compared to other classifiers. Using QDA and SVM, this study assessed a channel selection algorithm to reduce the number of sensors in the BCI examining a strategy to use fNIRS results to target the placement of EEG electrodes. Lastly, the feasibility of hybrid EEG and fNIRS system was investigated by comparing corresponding classification accuracies to EEG and fNIRS alone. The combined EEG and fNIRS system resulted in significant improvements in classification accuracies compared to EEG or fNIRS alone.

abstract: PhD


title: MODELLING COASTAL PROCESSES DRIVEN BY WINDS AND TIDES ACROSS A RANGE OF SPATIAL SCALES IN A MACROTIDAL BAY

contributor:
Mulligan, Ryan
Law, Brent
Civil Engineering

subject:
storm surge
waves
coastal wetland
hurricane winds
Bay of Fundy
Gulf of Maine
Delft3D
currents
intertidal marsh
morphology
bed shear stress

abstract: The Bay of Fundy system in the Atlantic Ocean is a highly dynamic environment characterized by the highest tidal range in the world. The area contains a wide range of coastal environments and structures including salt marshes and protective dyke systems. These systems are at risk of being altered due to future climate change, with likely increases in mean sea level and storm intensity, and proposed installation of in-stream tidal power extraction devices. To assess the vulnerability of the Bay of Fundy to hazards, large-scale and small-scale investigations are completed using available field observations and the hydrodynamic model Delft3D. The large-scale investigation composed of examining the effects of hurricane induced storm surge in the Gulf of Maine and Bay of Fundy using a depth-averaged model and two connected model grids. Hurricane Arthur (2014) is used as a test storm to validate the model before varying input conditions were used including modelling the Saxby Gale of 1869, a devastating storm that impacted the Bay of Fundy. Model results suggest that the combined effects of wind driven waves and storm surge could overtop dyke systems in the Minas Basin if the storm coincides with the high tide of a perigean spring tide. The small-scale investigation is focused on Kingsport Marsh, Nova Scotia, an intertidal salt marsh in the Minas Basin, using a three-dimensional model and four connected model grids with increasing resolution. The goal of this study is to gain insight to the hydrodynamics and morphology of the marsh channels and mudflats. Observational results over a 7-year time period suggest that the bed is slowly accreting in the marsh and that the networks of creek channels are migrating. Model results are validated at the two instrument sites and the model is used to spatially analyze the intertidal hydrodynamics. Spatial model results display a dynamic environment during the flood and ebb tides with bed shear stresses sufficient to initiate sediment resuspension. Overall, this research contributed to a better understanding of the coastal processes in a highly dynamic macrotidal environment, by aiding in the understanding of the complexity of tidal marsh environments as well as assessing the risk involved in storm surge interactions to local dyke systems, needed to accurately predict future responses to storms, climate change and proposed infrastructure development.

abstract: M.A.Sc.


title: On Cinema and Revolutions: Tricontinental Militancy and the Cinema of the Palestinian Revolution

contributor:
Naaman, Dorit
Cultural Studies

subject:
Palestinian Revolution
Third Cinema
Cinema of the Palestinian Revolution
Tri-Continantalism
Culture of Solidarity

abstract:
This thesis explores and analyses the Cinema of the Palestinian Revolution as an expression of Third Cinema, a political and aesthetic project created and sustained by filmmakers throughout Africa, Asia, and Latin America during the 1970s. The research is an attempt to place the Cinema of the Palestinian Revolution in the political and the historical context in which it emerged, in particular, the Palestinian revolution (1967-1982), the Lebanese Civil War (1975-1990), and the tri-continental connections of solidarity and cultural exchange of the 1970s.  In doing so, the thesis explains how furthering knowledge of Third Cinema’s politics and aesthetics, can illuminate not only our understanding of the past but also of our present.
The thesis constitutes a documented reflection on the politics, international solidarity, emancipatory aspirations, and revolutionary aesthetics at play in Third Cinema and the Cinema of the Palestinian Revolution, and their effect on the contemporary cultural and political space. The research also focuses on 21st century scholarly and cinematic work about the Cinema of the Palestinian Revolution. These new films and books are a testimony of the revival of the interest in the political and aesthetic alternatives offered by Third Cinema and the Cinema of the Palestinian Revolution. This research helps us to make connections, parallels and comparisons showing that similar forms of subjugation -- which Third Cinema and the Cinema of the Palestinian Revolution contested and fought against -- are still being imposed today and highlight how the forms of resistance that they produced, can inspire cultural spaces of political action today.

abstract: M.A.


title: Tracking the Temporal Dynamics of Distraction in a Continuous Performance Task

contributor:
Wilson, Daryl
Psychology

subject:
Attentional capture
Irrelevant distraction
Perceptual load

abstract: Many daily life tasks require sustained attention (e.g., studying) and are impacted by distractions that are irrelevant to the current task (e.g., friends talking). However, distraction paradigms typically fail to capture the continuous aspect of tasks, and commonly use distractors that are not actually irrelevant to current task goals. Hence, the aim of the present thesis was to provide a measure of distraction that better reflects daily life inattention. In Experiment 1, I tested my novel distraction task, referred to as the Continuous Classification Task, to determine whether previous findings of distraction replicate. Participants proceeded clockwise through a 12-item circular array making forced-choice responses as to whether the identity of each item was a letter or a digit. On thirty percent of the trials, a colorful cartoon character was presented in the center of the display. As predicted, there was significant distractor interference for the first response following distractor presentation. In Experiment 2, using an online version of the Continuous Classification Task, I tested its validity by correlating performance with scores on the Childhood and Current ADHD symptoms scales and the Cognitive Failures Questionnaire. As with Experiment 1, I found significant interference, however, here the interference was present for multiple items following distractor presentation. Furthermore, individuals who scored higher on measures of inattention also experienced greater distraction in my task supporting the external validity of the Continuous Classification Task. Finally, with Experiment 3, I examined the impact of perceptual load on distraction within my task. In a low-load condition, participants discriminated between visibly distinct items (i.e., c and o vs. i and l), whereas in a high-load condition, participants discriminated between visibly similar items (i.e., d and b vs. q and p). As with Experiment 2, I found distraction for multiple items following distractor presentation. However, inconsistent with Load Theory (Lavie & Tsal, 1994), increasing perceptual load increased distraction, suggesting that perceptual load may impact distraction differently in the continuous tasks that are typical of daily life. Together, these findings support the use of my Continuous Classification Task for investigating inattention in daily life.

abstract: M.Sc.


title: STEALING THUNDER: THE INFLUENCE OF SPECIFICITY,  ELABORATION, AND ARGUMENT QUALITY

contributor:
Fabrigar, Leandre
Psychology

subject:
stealing thunder
impression management
confessions
social influence

abstract:
Stealing Thunder is a phenomenon where transgressors reveal potentially damaging information
about their transgressions before its details can be revealed by a third party. Much research has
been done on the Stealing Thunder phenomenon, with the majority having been focused on
establishing the existence of the effect and the potential moderating factors that influence the
efficacy of the tactic. A review of the literature reveals it to be somewhat lacking in several
regards. First, the breadth and depth of research on the moderators and features of stealing
thunder have been quite limited. Second, the interpretability of existing research is often difficult
because of methodological ambiguities. The present document describes two programs of
research designed to address some of the breadth and methodological issues present in the
existing literature. The first program of research investigated the potential influence of a
previously unexamined feature of stealing thunder, confession specificity. Across four studies,
results showed that stealing thunder confessions were more effective when they contained
specific details regarding the transgression than when they contained comparatively vague
details. Additionally, the evidence suggests that previously-assumed interchangeable dependent
variables should not be used interchangeably, and stealing thunder exerts a stronger effect on
measures of honesty than on measures of global evaluation because honesty is a more proximal
outcome of stealing thunder than is global evaluation. The second program of research
investigated the influence of elaboration on stealing thunder across two studies. However,
because not all manipulations in this second program of research were effective, it was not
possible to fully evaluate the critical hypotheses. Nonetheless, this second set of studies might
provide building blocks towards improved studies that might provide a more satisfying answer to
the research question. Overall, results across two programs of research not only extended the iii
stealing thunder literature, but also contributed to a broader understanding of stealing thunder
mechanisms as well as the comparative effectiveness of stealing thunder on shaping judgments
of different dimensions of person perception.

abstract: PhD


title: Object Detection and Pattern of Life Analysis from Remotely Piloted Aircraft System Acquired Full Motion Video

contributor: Geological Sciences and Geological Engineering

subject:
Object detection
Pattern of life
Remotely Piloted Aircraft System
Full Motion Video
drone
object tracking
virtual reality
four-dimensional visualization
YOLOv3
unsupervised
artificial intelligence
machine learning
computer vision
flight parameters
survey design
unmanned aerial vehicle
uninhabited aircraft
photogrammetry
3D model
feature engineering
exploratory data analysis
data visualization
clustering
human machine interface
game engine
unity
oculus rift
geospatial

abstract: Remotely piloted aircraft systems (RPAS) have introduced a new ability to quickly deploy low-cost, fully or partially autonomous aerial sensor platforms which has created new intelligence, surveillance, and reconnaissance capabilities in various domains using cameras which are ubiquitous in most RPAS. Despite the utility of these aerial sensor systems, the full motion video (FMV) they acquire presents a big data challenge for operators as they generate large volumes of data that are impractical to analyze using current workflows due to excessive time requirements, computational resources, cost, or the availability of human analysts. Additionally, moving the camera rather than having a static network of stationary cameras, complicates the data processing steps required to generate valuable outputs. In order to address this big data challenge, various artificial intelligence (AI) based algorithms and data analytic workflows that can extract useful insights and knowledge from large amounts of complex and ambiguous FMV data streams from airborne sensors are developed and assessed. A data acquisition campaign was launched resulting in a dataset consisting of 33 flights recording approximately eight and a half hours of RPAS acquired FMV to assess the suite of AI-based algorithmic tools. Some of the tools useful for analyzing aerial FMV include object detection, and tracking namely to conduct pattern of life (POL) analysis for which aerial sensors mounted on RPAS are well suited for as they capture spatiotemporal information crucial to understanding the context of a scenario. Analysis and interpretation of the acquired dataset revealed that state of the art performance was achieved using the AI-based tools when the RPAS was deployed under an altitude of 30 m, at a velocity of under 7 m/s, and at pitch angles ranging from 25° to 65° while acquiring FMV at a resolution of 4.16 MP. The POL analysis conducted on two flights proved the two developed feature engineering based workflows to be robust behavioral anomaly detection tools for the staged pedestrian traffic and high value target assailant scenarios. The acquired data was also visualized in virtual reality within an immersive four-dimensional scene as a novel enhanced dissemination tool to aid in the POL interpretation and decision making. The acquisition, processing, analysis, and dissemination of the data from the 33 flights has indicated that RPAS acquired FMV combined with AI-based algorithmic tools could serve as an effective and reliable platform for creating and handling the big data for a variety of different applications such as peace support, public safety, and aerial monitoring to name a few.

abstract: M.A.Sc.


title: Assessing individual response to exercise training: Statistical considerations, analytical approaches, and moderators of response

contributor:
Gurd, Brendon
Kinesiology and Health Studies

subject:
Exercise
Individual response
Fitness

abstract: A growing body of research has classified “responders” or “non-responders” to exercise training and has assessed whether individuals respond differently to exercise training. In recent years, biostatisticians have raised concerns regarding the statistical rigour required to classify individual responses and determine whether interindividual variability can be attributed to differences in exercise trainability per se. This dissertation attempts to advance our understanding of these concerns by describing, critically evaluating, and demonstrating how to implement statistical approaches when classifying individual responses and estimating interindividual differences in trainability. The literature review first overviews the statistical principles relevant for examining individual responses to exercise training, and then reviews the purported biological mechanisms that explain why individuals respond differently to exercise training. The literature review also contains a systematic review with two novel analyses that: i) demonstrate the importance of considering error and meaningful thresholds when classifying individual responses, and ii) present evidence questioning the existence of interindividual differences in trainability. The following two chapters showcase and discuss the limitations with ignoring error and meaningful thresholds when classifying individual responses, and also demonstrate a new method for calculating response estimates – individual monoexponential regressions – that improves the accuracy in classifying individual VO2max responses. We then provide evidence supporting the hypothesis that higher response rates – the proportion of participants classified as “responders” – are explained by larger mean changes and not reduced interindividual variability. The remaining chapters focus on investigating the existence of interindividual differences in trainability by: i) critically evaluating the SDIR method, ii) presenting mixed evidence of interindividual differences in trainability across a range of morphological and molecular skeletal muscle outcomes following aerobic exercise training, and iii) revealing a lack of interindividual differences in trainability from an individual participant data meta-analyses that included over 1,500 participants from 8 RCTs. Collectively, this dissertation highlights the importance of adopting statistical methods when examining individual responses to exercise training.

abstract: PhD


title: Rocks and Stars, Earth and Mars: a Deluge of Distinct Dark Sector Detectors

subject:
dark matter
high energy physics
phenomenology

abstract: The nature of dark matter remains among the most confounding conundra in modern physics. This thesis studies the potential consequences of the existence of relatively high-mass, strongly-interacting dark matter. In particular, it details this type of dark matter's potential impact on billion-year-old objects, such as the Earth, the Sun, Mars, and minerals buried within the Earth. The existence of some of the dark matter models considered would have had consequences that have not come to pass, such as the destruction of the Earth and Sun, and thus these models can be excluded. Other models studied have consequences that could potentially be detected by future experiments, and thus the work presented in this thesis also points out new methods and phenomena applicable to future dark matter searches.

abstract: M.A.Sc.


title: Understanding Educator Perspectives of French Language Instruction in Play-Based Kindergarten

contributor:
Timmons, Kristy
Education

subject:
Kindergarten
French Immersion
Play-Based Learning
Additional Language Acquisition

abstract: This study examined issues related to additional language acquisition in French Immersion play-based kindergarten contexts, from the perspective of educators. Little is currently known about the impacts of play-based kindergarten on children in French Immersion programs in Ontario; the Kindergarten Curriculum does not address specific considerations with regards to Immersion students. The overarching research question for the study (RQ1) asks: How do play-based kindergarten programs impact student acquisition of French language skills, as perceived by French Immersion educators?  Two additional sub-questions, (RQ2 and RQ3), guide this study. RQ2 asks: How do French Immersion kindergarten teachers and ECEs plan for and deliver meaningful French language instruction within a play-based setting? RQ3 asks: Which specific French language outcomes do educators expect kindergarten children to have achieved by the end of kindergarten?  This study followed a basic qualitative design, using an online qualitative questionnaire to collect data. Participants included a purposeful sample of French Immersion kindergarten teachers (10) and early childhood educators (3) from one board in eastern Ontario. General inductive analysis was used to analyse responses. Findings indicate that educators are purposeful and intentional in teaching the French language, and there is a fine balance between direct instruction and play-based learning. A wide variety of approaches to play-based learning and additional language acquisition were described by participants, suggesting a need for consistent, clear expectations for educators. Ongoing professional learning for educators is needed. Future research is recommended to study an ideal entry point for early immersion programs.

abstract: M.Ed.


title: Volunteering the Valley: Designing Technology for the Common Good in the San Francisco Bay Area

contributor:
Möllers, Norma
Sociology

subject:
civic technology
capitalism
labor
volunteering
silicon valley
digital technology

abstract: How can digital technologies be designed for good rather than harm? Dozens of civic organizations under the “tech for good” banner have emerged in recent years to address exactly this question. Although these organizations have commendable goals, many scholars have criticized them for naively believing that technologies can solve complex social problems. However, we do not yet have empirical data on how they are, in practice, working to address local social problems. This study investigates one particular effort to design digital technologies for the common good: civic technology. Civic technology organizations are made up of technologists—employed or seeking employment in the high-tech industry—who volunteer in their spare time to build digital technologies to be used by municipal employees and local residents. Drawing on participant observation and interviews with civic technologists in the San Francisco Bay Area, I argue that civic technologists’ efforts end up being less about serving local residents and more about proving that, despite current critiques, the Big Tech industry can still ‘save the world.’ To capture the complex dynamics which lead volunteers to repair their investment in the Big Tech industry even as they critique it, I develop the concept of the “spirit of civic technology,” which is an ethos comprised of value judgments about what makes a ‘good’ technology, technologist, project, and organization, and which are exported from high-tech workplaces into civic organizations. I conclude the spirit of civic technology leads volunteers to inadvertently reinforce the epistemic, economic, and cultural power of Big Tech firms.

abstract: PhD


title: LAW ENFORCEMENT PERCEPTIONS OF YOUTH DIVERSION: A CASE STUDY OF THE DURHAM REGIONAL POLICE SERVICE

contributor:
Sytsma, Victoria
Sociology

subject:
Youth Diversion
Policing
Ontario
YCJA
Police Perceptions

abstract: Enacted in 2003, the Youth Criminal Justice Act (YCJA) began the transition into a new era of youth justice in Canada (Bala 2015). As a result, the CJS saw a drastic increase in the use of extrajudicial measures and decrease in the use of courts and custodial sentences for minor offences (Bala 2003). The YCJA’s emphasis on the use of alternative measures has produced many favourable outcomes for youth offenders, the legal system, and society (Bala 2015). Despite favourable outcomes, when police officers—the gatekeepers of the CJS—hold unfavourable attitudes towards diversion, diversionary measures are applied in an inconsistent manner (Schulenberg 2015; Marinos and Innocente 2008; Prenzler and Hayes 2000; Maclure Campbell and Dufresne 2003; Lurigio and Skogan 1994; Skogan 2008; Lumb and Brezeale 2003). Considering that the overall success of pre-charge diversion programs is limited to a police officer’s willingness to apply diversionary measures, this study explores the perception and attitudes of Durham Regional Police Service (DRPS) officers around the DRPS Youth Diversion Program (YDP). An original 41-item anonymous online survey was administered to 36 DRPS officers. Findings from the survey suggest that officers generally hold favourable views of the YDP and are willing to engage with the YDP. Officers are knowledgeable of the YDP and believe that their diversion-related training is sufficient. That said, findings also indicate that officers require additional training in order for the YDP to be implemented as it was intended by the YCJA.

abstract: M.A.


title: The path to Antioch: an analysis of the Norman and Greek relationships of Bohemond of Taranto

contributor:
Greenfield, Richard
History

subject:
Bohemond of Taranto
Antioch
Alexios I Komnenos
Normans
First Crusade
Tancred
Robert Guiscard
Count Raymond of Toulouse
Sichelgaita
Roger Borsa
Count Roger I of Sicily

abstract:
Bohemond of Taranto has been painted by modern scholars as an opportunistic knight who embarked for the east from Sicily with the Latin armies of the First Crusade in order to acquire a significant lordship for himself. However, the details of his early life and other factors which influenced his decision to abandon his holdings in Italy and journey to the east have not received adequate examination. Scholars simply mention Bohemond’s early context in passing but do not investigate the important relationships with his family and other Norman leaders that forced him to depart. These include his father, Robert Guiscard de Hauteville, half-brother, Roger Borsa, stepmother, Sichelgaita, and uncle, Count Roger I of Sicily.

In addition, his subsequent relationship with the Byzantine emperor Alexios I Komnenos has, for the most part, been presented negatively as one in which both individuals distrusted each other and were unwilling participants in their alliance. While this interpretation may hold some credibility, it has become too influenced by the hindsight of knowing that Bohemond would eventually take control of the city of Antioch instead of returning it to the emperor. As a result, scholars have tended to disregard the mutual benefit they offered one another. Bohemond’s desire to receive an estate in the east would profit from a powerful patron to sponsor his aims, while Alexios required an able military leader to manage his eastern borders, as had been his common practice, and defend against the encroaching Seljuk Turks. In this thesis I thus argue that the element of mutual benefit suggests their early relationship was not tense or distrustful at the outset, despite their past history, but rather cordial. I suggest this relationship only changed, once Bohemond realized the opportunity to hold Antioch for himself had become too great to ignore.

abstract: M.A.


title: The Use of Carotid Artery Ultrasound for the Assessment of Coronary Artery Disease and Cardiovascular Risk

contributor:
Johri, Amer
Biomedical and Molecular Sciences

subject: Ultrasound Cardiovascular Imaging Contrast Carotid

abstract:
Background: It is well known that the majority of cardiovascular (CV) events are caused by atherosclerotic plaque. However, it has recently been shown that it is not the quantity of plaque, but rather its vulnerability to rupture that increases cardiovascular risk. Coronary angiography remains the clinical standard for the diagnosis of coronary artery disease (CAD), or atherosclerosis of the coronary arteries, though it is not recommended for initial screening. Thus, the development of safe, effective and accessible screening tools for CAD is essential. It has been previously shown that quantifying plaque in the carotid artery serves as a prediction method of significant CAD. Thus, the central theme of this PhD project was to evaluate the correlation between carotid plaque characteristics, significant angiographic CAD, and CV outcomes.
Methods: In a cohort of intermediate risk patients referred for coronary angiography, basic and advanced ultrasound modalities were carried out in order to assess both plaque quantity and features that contribute to plaque vulnerability.
Results: We demonstrated that hand-held and conventional ultrasound devices could equally quantify carotid plaque. Beyond quantification, we showed that the vulnerability characteristics of neovascularization and ulceration were able to independently predict CAD and 30-day cardiovascular outcomes. Moreover, we demonstrated for the first time that there is a direct link between intraplaque neovascularization and plaque composition in the carotid plaque lesions of patients with acute coronary syndrome.
Conclusions: Overall, the data presented in this thesis support the use of carotid plaque characteristics detected using novel ultrasound methods as imaging biomarkers for cardiovascular risk.

abstract: PhD


title: A Machine Learning Framework for Oncological Margin Detection

contributor:
Fichtinger, Gabor
Mousavi, Parvin
Computing

subject:
Machine Learning
Breast Cancer
Margin Detection
Self-supervised Learning
Autoencoder
Multi-Instance Learning
weak labels
Basal Cell Carcinoma
iKnife
Mass Spectrometry

abstract:
Cancer is the cause of one in four deaths in North America. A common phase of early-stage oncological treatment is the surgical resection of cancerous tissue. The presence of cancer cells on the resection margin, referred to as positive margin, is correlated with the recurrence of cancer and demands re-operation. The iKnife is a mass spectrometry modality that produces real time margin information based on the signatures of metabolites in surgical smoke. Using this modality and real-time tissue classification, surgeons could remove all the cancerous tissue during the initial surgery, improving patient survival, mental health, and cosmetic outcomes. An obstacle in developing iKnife cancer recognition models is the destructive, time consuming and sensitive nature of the data collection that limits the size and quality of the datasets.
We propose to use machine learning techniques to create robust and generalizable cancer recognition models for the iKnife. To do so, we first perform a feasibility study using an easily accessible cancer type, basal cell carcinoma (BCC). This high incidence, low metastases cancer allows us to capture a larger dataset. We follow this work by implementing an attention based multi-instance learning model (MIL), which can better compensate for our small dataset by training on groups of samples given one collective label (e.g. cancer or benign) to learn the signatures of BCC. Finally, we propose to address the target dataset of breast cancer by building a self-supervised learning model from limited, weakly-labeled data. This model also explores the applications of domain transfer by first, learning to contextualize the general features of iKnife data using the BCC dataset. Following this pretraining, the model is then applied to our target breast cancer classification task.
Through extensive experiments, we show the benefits of using machine learning frameworks for the development of iKnife oncological recognition models. Throughout our studies, we also focus on exploring the biochemical significance of the data by uncovering patterns and investigating biochemical attentions that support current literature. In the future, this work can be extended to other tissue types and translated to intraoperative use for real-time prediction of tissue signatures at the tumor margin.

abstract: M.Sc.


title: Characterization of pyrene films for background rejection in liquid argon dark matter experiments

subject:
Dark Matter
Liquid Argon
Wavelength Shifters
Background Rejection
Pyrene
TPB

abstract:
About a hundred years after the first references to dark matter, the mystery around the nature of that elusive type of matter has still not been solved. Direct detection dark matter experiments are getting more and more sensitive but still face a lot of various backgrounds. We focus here on DEAP-3600, a liquid argon (LAr) target WIMP detector for which pulse shape discrimination (PSD) techniques are particularly efficient to distinguish nuclear recoils (NR), events characteristic of WIMP-argon interaction, from electronic recoil (ER) background events. However, α-events occurring in the neck of the DEAP-3600 detector lead to shadowed nuclear recoil-like events which mimic WIMP low energy scintillation pulse shape. Applying a wavelength shifter coating with high light yield and slow decay in the neck of the detector is expected to lead to a discrimination power of O(10^5) assuming a 100% signal acceptance. This thesis investigates the fluorescence properties of the favoured coating candidate, a pyrene-polystyrene thin film that could alter the pulse shape of these α-events in order to take them out of the WIMP region of interest.

Emission spectra, fluorescence yield and fluorescence time constants were studied at 18 temperatures between 4 K and 300 K, including room temperature and LAr temperature (87 K), for several pyrene-polystyrene samples with varied pyrene concentrations (12% and 15%) and purities (98%, 99% and 99.9%). The highest pyrene concentration (15% pyrene) and the highest pyrene purity (99.9%) were found to have the highest light yield at all temperatures. At LAr temperature, the light yield of the 99.9% purity 15% pyrene sample relative to 1,1,4,4-tetraphenyl- 1,3-butadiene (TPB), a wavelength shifter commonly used in dark matter detectors, was found to be 45%. The highest pyrene purity samples (99.9% purity) also showed the slowest decay. The fluorescence profiles were modelled first using an adhoc model with a bi-exponential decay. The majority of the light at LAr temperature for both 12% and 15% concentration samples (99.9% purity) was found to be dominated by a decay with time constant higher than 250 ns. Overall, the 15% pyrene (99.9% purity) sample showed the highest potential for discrimination of DEAP-3600 neck α-events. For this sample, pyrene monomer and excimer fluorescence profiles were separated and modelled separately. At LAr temperature, the decay was dominated by the monomer fluorescence profile, a 293 ± 7 ns decay.

abstract: M.Sc.


title: The Impact of Primary Care Practice Models on Indicators of Unplanned Health Care Utilization for Ontario Adults Newly Diagnosed with Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study

contributor:
Tranmer, Joan
Godfrey, Christina
Nursing

subject:
chronic obstructive pulmonary disease
health care utilization
hospitalizations
emergency department use
primary care

abstract:
Background: Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic disease among Ontario’s general population. Most of the care for this population occurs within the primary care setting; however, the extent to which different primary care practice models influence the care and outcomes of patients with COPD is largely unknown.
Objective: The overall aim of this study was to compare and explore the impact of different primary care practice models on indicators of unplanned health care utilization among adults newly diagnosed with COPD.
Methods: We conducted a retrospective cohort study using health administrative datasets housed within the Institute for Clinical Evaluative Sciences (ICES). Our cohort consisted of Ontario individuals 35 years and older with physician-diagnosed COPD between January 1, 2014 and December 31, 2019. Individuals were assigned to the following cohorts: team-based (FHT), traditional (CCM, FHO, FHN, FHG), and no enrolment (walk-in clinics). The primary outcomes were indicators of unplanned health care utilization as defined by emergency department (ED) visits and hospitalizations. Adjusted logistic regression models were used to analyze the association between the different practice models and unplanned health care utilization while controlling for confounders.
Results: In total, 57,145 individuals met the inclusion criteria and 55,994 were included in the regression analysis. 62.8% of patients were in the traditional group, 30.3% in the team-based group, and 6.9% in the no enrolment group. Between 2014-2019, 70.7% of the cohort had at least one all-cause ED visit without hospitalization. In the adjusted logistic regression models, patients in the traditional model had a lower risk of ED visit without hospitalization, regardless of cause [all-cause (AOR = 0.89; 95% CI = 0.85-0.94) or COPD-related (AOR = 0.90; 95% CI = 0.84-0.97)] in comparison to patients enrolled in team-based models.
Conclusion: Amongst patients newly diagnosed with COPD, patients in team-based primary care models were more likely to have an ED visit without hospitalization when compared to patients in traditional primary care models. Primary care models are complex, with influence from remuneration and organizational structures, reinforcing the importance of continuing research efforts in this area to broaden the understanding of primary care reforms.

abstract: MNSc.


title: Quasinormal-mode theory and design of elastic Purcell factors, mechanical cavity modes and Fano resonances in optomechanical beams

subject:
Mechanics
quasinormal
quasinormal mode
mechanical quasinormal modes
elastic quasinormal modes
elastic Purcell factor
mechanical Purcell factor
optomechanics
mode theory
leaky modes
mechanical leaky modes
complex eigenfrequencies
lossy mechanical cavities
mode dissipation

abstract: In optomechanical systems, the radiation forces exerted by photons are exploited to manipulate and measure mechanical motion, finding applications is optics, nanophotonics, mechanics, and gravitational wave detection. To understand and design such structures, the optical and mechanical mode behavior must be well understood and characterized. For example, one should have a good idea of how the design parameters of a system affect the underlying modes, how the modes interact with their surroundings (dissipation), and how the modes interact with each other. The recent development of quasinormal-mode (QNM) theory in cavity optics, which allows for a quantitatively accurate model of realistic cavities subject to energy losses and interference, has proven to be very powerful in nanophotonics design and simulations. In this thesis, we introduce a QNM theory of mechanical open-cavity modes, and use it to study the elastic mode behavior of optomechanical resonators subject to intrinsic loss and mode coupling, including a quantitative description of the elastic Purcell effect. In addition, we present controllable designs of exceptionally high quality-factor mechanical modes for coupled optomechanical cavities. Our semi-analytical theory is exemplified and confirmed by full three-dimensional numerical calculations on optomechanical beams, and the general findings apply to a wide range of mechanical cavity modes. This QNM formalism, when also coupled with a QNM theory of optical cavities, offers a unified framework for describing a wide range of optomechanical structures where dissipation is an inherent part of the resonator modes.

abstract: M.A.Sc.


title: COMBINING BCG IMMUNOTHERAPY WITH STING PATHWAY ACTIVATION TO INDUCE TERTIARY LYMPHOID STRUCTURES IN THE TREATMENT OF NON-MUSCLE-INVASIVE BLADDER CANCER

contributor:
Koti, Madhuri
Biomedical and Molecular Sciences

subject: Bacillus Calmette Guerin (BCG)

subject: Stimulator of Interferon Genes (STING)

subject: Tertiary Lymphoid Structures (TLS)

subject: Non-Muscle-Invasive Bladder Cancer (NMIBC)

subject: Combination Immunotherapy

abstract:
Following surgical resection, high-risk non-muscle invasive bladder cancer (NMIBC) is best
treated with intravesical Bacillus Calmette-Guérin (BCG) immunotherapy. BCG is the live-attenuated
form of Mycobacterium bovis and is utilized in an adjuvant setting to recruit immune cells and potentiate
anti-tumor immunity. Like other mucosal sites, the bladder has the potential to harbor immune outposts
known as tertiary lymphoid structures (TLSs). These ectopic structures resemble the germinal centers of
secondary lymphoid organs and are highly organized aggregates of various immune cell populations,
including T cells, B cells, and follicular dendritic cells. TLS induction is a type 1 interferon (IFN1)-
dependent response to chronic inflammation and has been associated with positive prognosis in multiple
cancer types. However, the attenuation of Mycobacterium bovis for clinical use as BCG removes the
ability of the mycobacteria to trigger the Stimulator of Interferon Genes (STING) pathway. This pathway
plays a crucial role in producing a potent IFN-1 response, and its removal hinders the induction of TLS
formation. Therefore, we hypothesized that combining BCG with exogenous STING pathway activation
has the potential to induce TLS formation in the bladder mucosa, which could potentially improve
outcomes for patients with NMIBC. We have previously demonstrated the potential of this combination
to synergistically upregulate IFN1-associated genes and promote the release of chemokines in vitro.
Therefore, our current objective is to determine if simultaneous administration of STING pathway agonist
(SA) and BCG immunotherapy will induce TLS formation in the bladder mucosa. Here we show that the
combination of BCG and SA induces MB49 murine bladder cancer cell death in vitro. Furthermore, we
demonstrate that this combination leads to the upregulation of TLS-associated genes, recruitment of
immune cells, and production of pro-inflammatory cytokines in the MB49 orthotopic murine model of
bladder cancer. Finally, we characterize the organization and developmental stages of pre-existing, tumor-associated lymphoid aggregates present in tumors from patients with NMIBC. Overall, this work has the
potential to improve the treatment of NMIBC by providing rationale for the utilization of synergistic
immunotherapy consisting of BCG and STING pathway activation.

abstract: M.Sc.


title: In the lie of this Multicultural Land: An Analysis of Barbados-Canada Relations, 1966 -1990.

contributor:
Walker, Barrington
History

subject: Black, Barbados, Barbadian, Canada, Canadian, anti-black, racism, migrant, emigrant, immigration, island, relationship, benefits, Commonwealth, Caribbean, multicultural.

abstract:
Barbados-Canada relations spanned many decades, from November 30, 1966, those relations entered a new dimension, since Barbados now an independent state, was no longer ruled by Britain. This new relationship witnessed new political, social, and economic ties being established between the two nations.  Approximately one year later, in 1967, Canada implemented a points system which further transformed its discriminatory immigration policy, thus making it somewhat easier for Black Barbadians and other Black people to enter the country. Despite these new post-independence changes, Barbadians found that racial profiling and anti-black discrimination undergirded their relationship with Canada, whether in policymaking, social and cultural diplomacy, economic activities, or emigration. And webbed in that reality, was the standard narrative of Canada being a helper of underdeveloped Barbados, by way of development assistance and other economic benefits.
	This dissertation challenges the perception that historically Canada has primarily rendered assistance to Barbados – a recipient of Canadian generosity without reciprocation. Utilizing archival research at the Library and Archives Canada (LAC), and the oral testimonies of some Black Barbadian emigrants, this dissertation argues that Barbados was not just a passive beneficiary of Canadian assistance. But in fact, the island provided Canada with more benefits, particularly, social benefits in return, which made the relationship more beneficial to Canada in the 1966 to 1990 era. This argument challenges Ralph Paragg’s portrayal of Barbados and the Caribbean as merely recipients of Canadian beneficence, by showing that Barbados gave back to Canada more than it received.

abstract: PhD


title: A Morphological Awareness-based Intervention for Struggling Readers

contributor:
Kirby, John
Education

subject: Morphological Awareness, Decoding and Analysis

subject: Literacy Development

subject: Dyslexia

subject: Word Reading

subject: Spelling

abstract:
Morphological awareness is the awareness of and ability to manipulate the smallest units of meaning in words, and it enables children to identify meaningful units in words. Studies have shown morphological awareness predicts and affects word reading (Kirby et al., 2012), reading comprehension (Deacon, Tong, & Francis, 2017; Carlisle & Fleming, 2003), vocabulary (McBride-Chang et al., 2005), and spelling (Deacon & Bryant, 2006; Deacon, et al., 2009). Recent meta-analyses have found that morphological awareness intervention benefits at-risk and struggling readers, leading to gains in phonological awareness and morphological awareness, as well as gains in word reading, spelling, and reading comprehension (Bowers, Kirby, & Deacon, 2010; Carlisle, 2010; Goodwin & Ahn, 2010; 2013; Reed, 2008), with larger effects when in conjunction with other types of literacy intervention (phonological awareness, letter knowledge, and vocabulary). This study assesses the effects of a morphological awareness-based intervention for students with dyslexia to improve word reading and spelling. This study employed a wait-list control group design and assessed all 24 students before and after the intervention which consisted of direct instruction on morphological awareness and its application to reading, spelling and vocabulary.
Data were analyzed with t-tests, repeated measures ANOVAS and ANCOVA. The results showed that the sample met the criteria for a learning disability in reading, and that the experimental group showed larger gains than the control group on the following outcome measures: Word Analogy, Sentence Completion Derivation, Morphological Decoding, Morphological Analysis, and Morphological Spelling. There were no significant effects on word reading (fluency and accuracy), or on standardized spelling. Gains in morphological processing, particularly in decoding and analysis, strengthen the foundation for literacy gains and are encouraging in that they lend themselves to predictions that, with more instructional time, results might have shown medium to far transfer of knowledge.
These findings align with the perspective that morphology is a binding agent among orthography, semantics, and phonology, and offers many direct and indirect pathways to literacy development (Levesque et al., 2020).

abstract: M.Ed.


title: The study of time representations for chemical production scheduling models

contributor:
Li, Xiang
Chemical Engineering

subject: Scheduling MILP

abstract:
Optimal scheduling has been extensively investigated in the Process Systems Engineering (PSE) community. Most of the existing mathematical programming models for scheduling can be classified into two categories in terms of the time representation: continuous-time (CT) and discrete-time (DT). The CT and DT approaches have their own strengths and weaknesses, and are suitable for different types of scheduling problems. In order to accommodate more production problems and address the issue of computational complexity, a mixed-time (MT) representation has also been studied in the literature, which integrates the DT and the CT representations. This thesis compares the different time representations for scheduling of continuous and batch processes. The thesis also establishes a new and more general MT modeling framework that uses discrete time grids and continuous time variables to describe time. The main research contents of this thesis are as follows:

1. For the scheduling of a continuous process with the goal of minimizing energy consumption, a CT mixed-integer linear programming(MILP) formulation is proposed. The model describes various operating constraints, including three delivery modes, as well as sequence-dependent transition, processing time constraints, and boundary constraints. The CT formulation is compared with an existing DT formulation in terms of model scale and solution accuracy.

2. A new MT presentation based model is proposed for the continuous process scheduling problem. In this model, a discrete time grid is adopted as a reference and the event points are not restricted to the fixed grid points. In addition, continuous time variables are introduced to represent the deviation of event points to the discrete time grid. The MT model is more precise in modeling time and often includes fewer integer variables than the CT model.

3. The MT representation is also applied to the scheduling of a batch process, which has multiple tasks with fixed processing times. The MILP model includes unit allocation and capacity constraints, time balance constraints, and an objective to minimize the total cost. The computational results demonstrate the advantage of the MT model over the DT model for the batch process.

abstract: M.A.Sc.


title: Vascular Function in Women and Children Following a Pregnancy Complicated by Preeclampsia

contributor:
Smith, Graeme
Biomedical and Molecular Sciences

subject: preeclampsia pregnancy postpartum vascular endothelium

abstract:
Preeclampsia is a severe hypertensive complication of pregnancy that poses significant maternal and fetal risk. Evidence suggests that preeclampsia is linked to later-life cardiovascular disease development in both mother and offspring. However, the mechanisms responsible for this phenomenon have not been determined, nor how they can be ameliorated. Non-invasive vascular assessment allows for the evaluation of subclinical indicators of cardiovascular risk.
Herein we describe a series of studies which were undertaken to measure postpartum and offspring vascular functional alterations associated with preeclampsia in pregnancy and to improve the accuracy and clinical applicability of laser perfusion imaging. Our studies of postpartum women reveal that those with prior severe preeclampsia display heightened microvascular endothelium-dependent and -independent vasodilation and exhibit higher carotid stiffness compared to women with mild or no disease. In a small trial of offspring born to preeclamptic pregnancies, microvascular function does not appear to differ from uncomplicated counterparts, though recovery of perfusion after occlusion appears to occur faster. Finally, we describe the novel application of a computer vision modality to enable frame-by-frame segmentation of participant movement during a trial. Importantly, we demonstrate that a computer vision modality makes similar predictions to an experienced human rater in a fraction of the time.
In short, the present data add to the growing understanding of postpartum mechanisms associated with preeclampsia which may predispose women to future disease, and the broad applications of perfusion imaging as a tool for measurement and disease surveillance.

abstract: PhD


title: Exploring the relationship between quality and quantity of participation in an online community-based exercise program

contributor:
Tomasone, Jennifer
Kinesiology and Health Studies

subject:
Quality Participation
Physical Disability
Community-based exercise program
Sequential Explanatory Design

abstract: The Quality Participation Framework conceptualizes how to promote full and effective participation in exercise programs for individuals with disabilities. Prior to this investigation, it was believed that repeated quality experiences would foster continued quality participation in the sport and exercise setting. Preliminary studies have investigated a potential relationship between quality and quantity of participation in an exercise setting; however it is unknown how these factors may interact. The main objective of this study was to explore the relationship between quality and quantity of participation in an exercise setting. Individuals (n=17) with a physical disability engaged in 10 weeks of Revved Up @ Home, an online community-based exercise program designed to foster quality participation. Using a mixed-methods sequential explanatory design, participants completed global questionnaires at baseline and 10-weeks, and acute questionnaires following each exercise session evaluating their subjective experience of quality participation. At 10 weeks, graphs of survey results derived from the acute questionnaires were shown to participants in a semi-structured interview (i.e., graphic elicitation) and participants were asked about their quality and quantity of participation during the program. Correlations were computed to quantify the relationship between quality and quantity of participation, and situated within critical realism, thematic analysis facilitated an exploration of the contextual relationship between quality and quantity of participation. Qualitative and quantitative findings were integrated, highlighting important relationships between meaning and quantity of participation, as well as between challenge and mastery. The quantitative data highlighted relationships that may exist between different aspects of quality participation, while the qualitative data demonstrated potential links between the aspects of quality participation and quantity of participation. Findings from this investigation provide preliminary evidence that repeated quality experiences lead to quality participation and contributes to our growing knowledge of the Quality Participation Framework by detailing a contextual understanding of the relationships between the aspects of quality participation. This study also serves to help program providers understand links within the Quality Participation Framework, to enhance community-based exercise programs’ ability to bolster quality participation and attendance among individuals with physical disabilities.

abstract: M.Sc.


title: Downregulation of the unfolded protein response by metformin may confer antineoplastic effects in colorectal cancer

contributor:
Davey, Dr. Scott
Pathology and Molecular Medicine

subject:
Unfolded Protein Response
Metformin
Type 2 Diabetes
Colorectal Cancer

abstract:
In 2020, there were 1.93 million cases of colorectal cancer (CRC) diagnosed and 935 thousand CRC-related deaths (1–3). Approximately 50 percent of patients are diagnosed with stage III or IV disease, limiting the efficacy of available treatments (4). Type 2 diabetes mellitus (T2D) is a risk factor for CRC development and progression. Nonetheless, metformin-treated diabetic CRC patients tend to have better clinical outcomes than diabetic CRC patients not exposed to metformin. Thus, we sought to investigate the molecular underpinnings of metformin’s protective effects to determine whether its mechanism could be exploited to improve patient outcomes.

We performed a targeted transcriptomic analysis of primary CRC tissue samples (N = 272). Next, a supervised learning algorithm was used to pinpoint features discriminating between metformin-treated and diet-controlled diabetic CRC samples, as well as those discriminating between non-diabetic samples based on their five-year survival status; these features were used to generate corresponding classification models. Finally, we analyzed the differential gene expression patterns in diabetic treatment groups and non-diabetic survival categories to identify expression profiles suggesting that a gene and/or pathway may be linked to metformin’s antineoplastic effects.

Our results show downregulation of TMEM132 in metformin-treated samples (p = 0.053) and non-diabetics with good clinical outcomes (p = 0.053) relative to diet-controlled and non-diabetics with poor survival, respectively; SCNN1A was upregulated in metformin-treated samples (p = 0.044) and non-diabetics with good clinical outcomes (p = 0.011) relative to diet-controlled samples and those with poor clinical outcomes, respectively; FN1 was downregulated in metformin-treated samples relative to diet-controlled samples (p = 0.121). These findings suggest a role for the unfolded protein response (UPR) in mediating metformin-related CRC protective effects, by enhancing apoptosis. We also show that sFas, an antiapoptotic protein, is downregulated in metformin-treated samples relative to diet-controlled samples (p = 0.005). Therefore, metformin may synergistically enhance apoptosis through the regulation of Fas alternative splicing, inhibiting CRC development and progression. Taken together, we outline two key cellular processes that may be implicated in metformin’s antineoplastic action and provide justification for further investigation of these pathways to determine if they may be targets for novel CRC therapies.

abstract: M.Sc.


title: The role of ErbB inhibitors in promoting nerve regeneration in a mouse model of nerve injury

contributor:
Hendry, Michael
Kawaja, Michael
Neuroscience Studies

subject:
nerve regeneration
nerve injury
ErbB inhibitors
lapatinib
gefitinib

abstract: Nerve injury is a common clinical challenge that has a considerable impact on an individual’s quality of life and function. Despite multiple surgical strategies, functional outcomes following nerve injury remain poor. Increasing the rate at which axons regenerate could profoundly improve the success of recovery. The goal of this thesis was to investigate whether the dual ErbB1-ErbB2 inhibitor lapatinib or the ErbB1 inhibitor gefitinib could promote nerve regeneration in both in vivo and in vitro models. Using a mouse transection and repair sciatic nerve injury model, lapatinib was found to increase the number of regenerated myelinated axons at 28 days following nerve repair. For elucidation of the molecular pathway that could be promoting nerve regeneration, in vivo neurite growth assays interestingly demonstrated that gefitinib, more than lapatinib rescued the inhibitory effects by chondroitin sulfate proteoglycan on neurite growth. Furthermore, a mouse forelimb model of nerve injury was characterized which can be used to study the cellular and molecular effects of ErbB inhibitors in transgenic mice. The repurposing of ErbB inhibitors to enhance nerve regeneration requires further study to determine whether this therapy could be translated to improve functional recovery in people with nerve injury.

abstract: M.Sc.