title: REWARD LEARNING CAPACITY IN A COMMUNITY SAMPLE OF INDIVIDUALS WHO USE CANNABIS

contributor:
Balodis, Iris
Neuroscience

subject:
cannabis
reward learning
reinforcement learning
Probabilistic Reward Task

abstract:
Rationale: Cannabis use has been related to poor psychosocial and socioeconomic outcomes, which may be due, in part, to impairments in forming non-drug reward associations. However, few studies have objectively evaluated reward learning in cannabis use populations.
Purpose: To investigate reward learning capacity in a community sample of individuals who use recreational cannabis, using the Probabilistic Reward Task (PRT), and to evaluate performance in relation to cannabis use characteristics.
Methods: Thirty-eight individuals who use cannabis and 34 control participants completed the PRT, in which reward learning was evidenced by the development of a response bias toward the more frequently rewarded stimulus. Relationships between response bias and cannabis use characteristics were explored (e.g., frequency, chronicity, potency) along with comorbid psychiatric symptoms (i.e., depression).
Results: Both cannabis and control groups developed a response bias across 3 blocks of the PRT. No group differences in response bias emerged, however, in the cannabis group, there was a trend for lower response bias in relation to greater chronicity and self-reported potency.
Conclusion: The results suggest that a community sample characterized by a range of cannabis use patterns, are not impaired in the ability to form non-drug related reward associations, although deficits may emerge with greater severity of use. These findings are important in supporting therapeutic approaches where forming reward associations outside of cannabis use are imperative, as well as informing public awareness and policy around cannabis use patterns.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Cannabis use has been related to impairments in reward processing. An important element of reward processing is reward learning, which means to form an association between a behaviour and a positive outcome. This study evaluated if individuals who use cannabis recreationally can learn reward associations unrelated to the substance, and if reward learning is affected by greater cannabis use. In this study, 38 participants who use cannabis and 34 control comparisons completed a reward learning task, and cannabis participants completed questionnaires about their use. The results showed that cannabis and control groups performed equally well on the task, but longer duration of cannabis use and higher potency was related to poorer performance. This suggests that individuals who use cannabis can learn non-drug reward associations, however, reward learning impairments may arise with greater severity of use. The findings are important in improving our understanding of the potential consequences of cannabis use.


title: Effects of self-control training and brain endurance training on endurance performance and ratings of perceived exertion

contributor:
Bray, Steven
Kinesiology

subject:
Self-Control Training
Brain Endurance Training
Ego Depletion
Ratings of Perceived Exertion
Isometric Endurance Performance

abstract: Self-Control Training (SCT) and Brain Endurance Training (BET) are novel training modalities designed to enhance physical endurance by building fatigue resiliency. Despite their similarities, it has yet to be examined whether combining SCT and BET provides an additive or redundant/overlapping effect on endurance exercise performance. This study investigated the effects of SCT and combined SCT+BET on performance of a maximal exertion isometric resistance endurance task (high plank) and ratings of perceived exertion (RPE). Participants (N = 33) were randomized to engage in 4 weeks (18 training sessions) of SCT (isometric handgrip; n = 13), SCT+BET (10-minute cognitively demanding task, followed by SCT; n = 10), or no-training/control (n = 10). Isometric endurance performance trials were completed at pre-, mid-, and post-training. One-way analysis of covariance (ANCOVA) models were computed for each of the mid- and post-training trials (controlling for pre-training high-plank performance) to assess effects on performance.  Results showed no significant effects of training on high plank performance between groups at mid-training; however, a large and significant effect for SCT compared to control was observed at post-training (p = .044, d = .961). No significant main effects or interaction effects were found for changes in RPE over time (p’s > .05). Findings support the use of SCT as an effective training method for physical endurance performance and suggest that BET may not offer additional performance benefit compared to SCT under the training and testing conditions used in this protocol. Future research should explore potential dose-response effects of SCT on performance and moderators such as trait self-control.

abstract: Thesis

abstract: Master of Science (MSc)


title: An Assessment of Movement Behaviours and Inflammation in Children with a Chronic Inflammatory Disease

contributor:
Obeid, Joyce
Medical Sciences

subject: Inflammation, Physical Activity, Paediatric, Chronic Disease

abstract:
Children with chronic inflammatory disease (CID) are at an increased risk for health complications including mental health issues, cancer, and cardiovascular disease. These complications have been linked to elevated levels of pro-inflammatory cytokines and lifestyle behaviours including low physical activity, and high sedentary time. Physical activity may represent a simple and effective strategy to modulate inflammation and subsequently improve health outcomes. However, the link between cytokines and movement behaviours in children with a CID remains poorly understood. Indeed, no studies to date have examined the link between a broad complement of inflammatory markers and patterns of movement behaviours in children with a CID. Therefore, the objectives of this study were to: (1) examine movement behaviours and inflammation in children with either cystic fibrosis (CF), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), and type 1 diabetes (T1DM), (2) examine movement behaviours and inflammation in children with a CID compared with healthy controls and (3) examine the association between movement behaviours and inflammation profiles in children with a CID. We hypothesized that (1) children with a CID will have comparable movement profiles and inflammation, (2) children with a CID will have lower physical activity levels and higher levels of pro-inflammatory cytokines relative to healthy counterparts, and (3) children with a CID who are more physically active and engage in less sedentary time will have less inflammation. Boys and girls with a CID and controls wore an ActiGraph GT3X accelerometer around the waist during waking hours for 7 days. Outcomes of interest included, sedentary time, time spent in light physical activity (LPA), moderate-to-vigorous PA (MVPA), and total PA (TPA), determined using Evenson cut-points. After one week a fasted blood sample was collected to determine serum cytokines (TNFα, IL-23, IL-1β, IL-12, IL-6, IL-
17, TGFβ, IL-10) by multiplex assays and C-reactive protein by enzyme linked immunosorbent assay. A total of 132 participants (47% girls; age: 13.3±2.8 years), including JIA (N=27), IBD (N=21), CF (N=14), T1DM (N=18) and healthy controls (N=52), completed the study. Physical activity and inflammatory profiles were comparable between CF, JIA, IBD and T1DM groups. Children with a CID participated in 13.3 fewer mins/day [95% confidence interval 6.9, 101.2] (MVPA (F(1,113)=11.015, p=0.001) of MVPA relative to healthy controls and had comparable cytokine profiles. Physical activity did not predict inflammation in children with a CID. However, we know that physical activity has many beneficial cardiorespiratory and mental health effects. As such, it is still of interest to uncover any potential effects movement behaviours may have on our immune system.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The purpose of this study was to assess how physical activity, sedentary time, and inflammation are associated. Inflammation is an important part of our immune system that protects us from infection and disease; however, when inflammation goes unchecked, it can cause serious chronic inflammatory disease. We were interested in understanding if children with a chronic inflammatory disease had different levels of physical activity and sedentary time, or different levels of inflammation than healthy children with no medical conditions. We were also interested in understanding if physical activity or sedentary time were related to levels of inflammation in children with a chronic disease. We asked boys and girls between 7 and 17 years old to visit our lab twice. Some of our participants had a medical condition, including chronic kidney disease, cystic fibrosis, juvenile idiopathic arthritis, or inflammatory bowel disease and type 1 diabetes. We also invited a group of children who had no medical condition to participate. During their first visit, we measured their weight, height, pubertal status and gave them a physical activity monitor to wear for 7 days before coming back for their second visit. At their second visit we took a small blood sample that we used to measure immune proteins called cytokines, these proteins act like messengers to tell the immune system what to do. Some of them make inflammation worse, and others help to bring down levels of inflammation. We found that children who had a chronic inflammatory disease participated in less physical activity but had similar levels of sedentary time compared with healthy children. We also found that there were no differences in inflammation between children with a chronic disease and healthy children. Lastly, we found that physical activity and sedentary time were not related to inflammation levels. Although we did not find a relationship between physical activity and inflammation, we know that physical activity has many beneficial cardiorespiratory and mental health effects. As such, it is still of interest to uncover any potential effects movement behaviours may have on health outcomes.


title: The Place of the Jewish Court Tales in Early Jewish Literature: Form, Development, and Function

contributor:
Machiela, Daniel
Religious Studies

subject:
court tales
Aramaic
Greek
Dead Sea Scrolls
Hebrew
Early Judaism
Hebrew Bible
Old Testament
Ancient Near East
apocalyptic
apocalypse
Jewish literature
Jewish language

abstract:
Literary tales about the lives and vicissitudes of officials serving in the courts of powerful kings are attested throughout the writings of the ancient Near East. Such ‘court tales’ were a popular literary form during the Jewish Second Temple period (515 BCE-70 CE). With the discovery of the Dead Sea Scrolls, a collection of previously unknown ancient Jewish court tales was discovered, along with others preserved in their original languages. The discovery of these texts has expanded our corpus of extant Jewish court tales. Research on these texts has yet to be systematically integrated into broader analyses of the Jewish court tales. This dissertation addresses this desideratum and integrates the court tale evidence from the Dead Sea Scrolls into research on the already extant Jewish court tales, with a focus on the themes of punishment, exile, and restoration.
Chapter One outlines the history of scholarship on the Jewish court tales. Chapter Two examines the literary themes and concerns of other ancient Near Eastern and Mediterranean court tale traditions. Chapters Three and Four analyze the themes of punishment, exile, and restoration within the Jewish court tales, and highlight their uniqueness to the Jewish tales. Chapter Five discusses the development and decline of the Jewish court tales. In doing this, I demonstrate that a major purpose of the Jewish adoption of the court tale tradition was to upend earlier convictions that exilic life was solely a form of punishment, with the purpose of demonstrating the benefits of exilic life and God’s sovereignty over foreign political actors. My examination of the court tales contributes to discussions about the origins of Jewish apocalyptic literature, with the court tales employing eschatological terminology to address the theme of restoration.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Ultrafast Lasers in Additive Manufacturing

contributor:
Fang, Qiyin
Engineering Physics

subject:
ultrafast laser
additive manufacturing
ablation
fiber laser
Ti-6Al-4V
selective laser melting

abstract:
Ultrafast lasers are valuable research and manufacturing tools. The ultrashort pulse duration is comparable to electron-lattice relaxation times, yielding unique interactions with matter, particularly nonlinear absorption, melting, and ablation. The field of ultrafast laser manufacturing is rapidly evolving with advances in related laser technologies. The applications of ultrashort pulse lasers in additive manufacturing aim to fill gaps left by conventional techniques especially on the nano- and micro-scale. Concurrently, uptake of ultrafast fiber lasers for micromachining has increased, and may replace the Ti:Sapphire laser as the ultrafast laser of choice. Both additive and subtractive manufacturing are accomplished with ultrafast lasers which presents the possibility of hybrid, all-in-one devices using a single laser source. As one such combination of laser techniques, ultrashort pulse surface modification of additively manufactured metals is an area of limited investigation.
This thesis aims to address the ever-changing landscape of ultrafast laser manufacturing by 1) reviewing ultrafast laser additive manufacturing techniques and recent advancements 2) comparing the design, operation, and micromachining potential of a commercial ultrafast Ti:Sapphire and ultrafast fiber laser, and 3) investigating femtosecond ablation of as-printed additively manufactured Ti-6Al-4V at a range of parameters to test the feasibility of surface feature control. Ultrafast laser additive manufacturing is still in its infancy with mostly niche applications. The ultrafast fiber laser architecture is found to deliver a platform that is easier to operate and maintain and has superior micromachining throughput relative to Ti:Sapphire lasers. In our experimental work, five main surface morphologies are obtained by femtosecond ablation of a rough Ti-6Al-4V surface: laser-induced periodic surface structures (LIPSS), undulating grooves, micro-ripples, grooves, and micro-cavities. Transitions between ablation regimes and evolutions of the surface under increasing pulse energy and number of pulses are observed. These patterns allow for control over the surface geometry without the need for post-printing polishing.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Ultrafast pulsed lasers of <10 picoseconds pulse duration are commonly used to modify, melt, or ablate materials. As an important research and manufacturing tool, ultrafast lasers and techniques have seen great change in the past two decades. Additive manufacturing has emerged as an area in which ultrafast lasers are becoming increasingly prevalent. To make sense of this continuously evolving landscape, this thesis 1) reviews ultrafast laser additive manufacturing techniques, applications, and advances towards industrial use and commercialisation, 2) compares the setup, operability, and characteristics for two ultrafast laser designs, and 3) investigates the surfaces produced by ultrafast laser irradiation of an additively manufactured titanium alloy part. The surface morphologies that are produced are categorised into five main patterns: laser-induced periodic surface structures, undulating grooves, micro-ripples, grooves, and micro-cavities. Each is a distinct pattern that may allow for tuning of the surface properties with respect to the wettability and biocompatibility.


title: Explorations in Padic Model Theory

contributor:
Haskell, Deirdre
Mathematics

subject: Model Theory, Formal Verification, p-adics

abstract:
This thesis explores various aspects of the model theory of p-adic fields. It is divided
into two distinct parts. The first part pertains to the theory of P -minimal structures.
The main focus is exploring a class of P -minimal structures which display a certain
tameness property with respect to the approximation of definable functions by their
Taylor polynomials, and builds to a proof of a theorem for passing from local ap-
proximations by Taylor polynomials to global (piecewise-definable) approximations
of functions by their Taylor polynomials in such structures. The final chapter of this
part discusses some aspects of classifying the scope of the class of structures that this
theorem applies to. The second part of the thesis describes a formally verified proof
of Macintyre’s quantifier elimination theorem for p-adic fields in the Isabelle proof
assistant. The algebraic formalisations to required state and prove this theorem are
outlined, including constructions of the p-adic integers and fields, as well as a formally
verified proof of Hensel’s Lemma.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract:
This thesis explores theoretical and computational aspects of the p-adic numbers,
which are fundamental objects of study in number theory. The thesis approaches
these problems using techniques from model theory, which is a branch of mathemat-
ical logic which is particularly effective at analyzing algebraic structures. The thesis
has two parts. The first is purely theoretical and focuses on the proof of a theorem
about p-adic functions which can be defined in certain logical languages. The second
part takes a computational approach and focuses on developing theoretical results
about p-adic numbers using a special software system called a proof assistant (the
particular proof assistant is called Isabelle). By developing theory of p-adics in Is-
abelle, we can use software to automatically verify the correctness of proofs of results
and coherence of definitions. The resulting libraries can then be imported and used
in future developments of machine-verified mathematical theory for more complex
results.


title: Cardiovascular risk in individuals with and without osteoarthritis using the Canadian Longitudinal Study on Aging

title: Osteoarthritis and Cardiovascular Disease Risk

contributor:
Al-Khazraji, Baraa
Kinesiology

subject:
Osteoarthritis
Cardiovascular disease
Cardiovascular disease risk
Menopause
Women's health
Aging

abstract:
Osteoarthritis (OA) is a prevalent and progressive musculoskeletal condition characterized by the degradation of the cartilage and bone and is often comorbid with cardiovascular disease (CVD), with both disease prevalence’s increasing with age. Several factors, such as the site of OA and the menopause transition, are known to independently influence both conditions. OA and CVD share overlapping risk factors and proposed mechanisms, though it is not well understood how these mechanisms influence the risk of comorbidity. This thesis examines the relationship of CVD risk factors, sites of OA, and menopausal variables on CVD risk in individuals with OA.
The first aim of this thesis was to examine preclinical markers of CVD risk, namely the carotid intima-media thickness (cIMT) and cardiovascular risk scores, the Framingham risk score (FRS) and the InterHeart risk score (IHRS), in individuals with and without OA to examine differences in CVD risk profiles. Additional considerations were given to the site of OA, as well as non-specific CVD risk factors (such as social disadvantage and frailty). Risk factors were compared between age- and sex-matched individuals with and without OA and between weight-bearing and non-weight bearing OA. Individuals with OA had significantly greater cIMT, FRS, and IHRS, though no differences were found when comparing the site of OA. Unadjusted and multivariate adjusted odds ratios (OR) calculated odds of CVD at 3-year follow-up in the same cohorts. There was a significantly unadjusted (p<0.001, OR:1.70) and adjusted (p<0.001, OR ranging from 1.67-1.70) influence of OA diagnosis on odds of CVD at 3-year follow-up. There was no significant unadjusted or adjusted difference in odds of CVD at 3-year follow-up when comparing different sites of OA (p ranging from 0.24-0.75, OR ranging from 0.69-0.71).
The second aim of this thesis was to study CVD risk in post-menopausal women. CVD risk factors and the IHRS were used to calculate differences between age-matched post-menopausal women. Unadjusted and multivariable adjusted ORs calculated odds of CVD at 3-year follow-up. There was a significant unadjusted influence of OA diagnosis (p=0.03, OR:1.34) on CVD outcomes, though the effect of OA diagnosis became non-significant after adjusting for the IHRS (p=0.25, OR:1.36) and the IHRS with menopausal variables (p=0.22, OR:1.40).
Although OA is a multifaceted condition, it has often been viewed as a joint-centric disease. The elevated risk of CVD individuals with OA suggests that additional aspects of the OA pathology, such as inflammation and frailty, may drive the increase in risk of CVD independent of age, sex, or menopausal status.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Osteoarthritis (OA) and cardiovascular disease (CVD) are two of the most prevalent comorbidities that affect the aging population. Surrogate measures of CVD, such as CVD risk scores and carotid intima-media thickness, have rarely been examined in individuals with OA despite studies showing elevated CVD risk in individuals with OA. We used baseline and 3-year follow-up data collected by the Canadian Longitudinal Study on Aging to study CVD risk factors in older individuals with and without OA, with considerations given to the site of OA and to menopause, which are additional non-modifiable factors known to influence vascular outcomes. We hypothesized that individuals with OA have greater CVD risk and odds of developing CVD compared to individuals without OA. We found that individuals with OA have greater CVD risk and odds of developing CVD at 3-year follow-up, with no influence of OA site on CVD outcomes, and post-menopausal women with OA have greater odds of developing CVD than post-menopausal women without OA. Our findings suggests that aspects of the OA pathology play a role in increasing CVD risk, which are partially explained through shared risk factors and etiology.


title: Energy Management Strategies for Hybrid Electric Vehicles with Hybrid Powertrain Specific Engines

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

subject:
Energy Management Strategy
Hybrid Electric Vehicle
Hybrid Powertrain Specific Engine
Adaptive ECMS
Reinforcement Learning
Dynamic ECMS

abstract:
Energy-efficient powertrain components and advanced vehicle control strategies are two effective methods to promote the potential of hybrid electric vehicles (HEVs). Aiming at hybrid system efficiency improvement, this thesis presents a comprehensive review of energy-efficient hybrid powertrain specific engines and proposes three improved energy management strategies (EMSs), from a basic non-adaptive real-time approach to a state-of-the-art learning-based intelligent approach.
To evaluate the potential of energy-efficient powertrain components in HEV efficiency improvement, a detailed discussion of hybrid powertrain specific engines is presented. Four technological solutions, i.e., over-expansion cycle, low temperature combustion mode, alternative fuels, and waste heat recovery techniques, are reviewed thoroughly and explicitly. Benefits and challenges of each application are identified, followed by specific recommendations for future work. Opportunities to simplify hybrid-optimized engines based on cost-effective trade-offs are also investigated.
To improve the practicality of HEV EMS, a real-time equivalent consumption minimization strategy (ECMS)-based HEV control scheme is proposed by incorporating powertrain inertial dynamics. Compared to the baseline ECMS without such considerations, the proposed control strategy improves the vehicle drivability and provides a more accurate prediction of fuel economy. As an improvement of the baseline ECMS, the proposed dynamic ECMS offers a more convincing and better optimal solution for practical HEV control.
To address the online implementation difficulty faced by ECMS due to the equivalence factor (EF) tuning, a predictive adaptive ECMS (A-ECMS) with online EF calculation and instantaneous power distribution is proposed. With a real-time self-updating EF profile, control dependency on drive cycles is reduced, and the requirement for manual tuning is also eliminated. The proposed A-ECMS exhibits great charge sustaining capabilities on all studied drive cycles with only slight increases in fuel consumption compared to the basic non-adaptive ECMS, presenting great improvement in real-time applicability and adaptability.
To take advantage of machine learning techniques for HEV EMS improvement, a deep reinforcement learning (DRL)-based intelligent EMS featuring the state-of-the-art asynchronous advantage actor-critic (A3C) algorithm is proposed. After introducing the fundamentals of reinforcement learning, formulation of the A3C-based EMS is explained in detail. The proposed algorithm is trained successfully with reasonable convergence. Training results indicate the great learning ability of the proposed strategy with excellent charge sustenance and good fuel optimality. A generalization test is also conducted to test its adaptability, and results are compared with an A-ECMS. By showing better charge sustaining performance and fuel economy, the proposed A3C-based EMS proves its potential in real-time HEV control.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Characterization of the bone marrow niche in Acute Myeloid Leukemia patients

contributor:
Bhatia, Mick
Biochemistry and Biomedical Sciences

subject:
acute myeloid leukemia
mesenchymal stem cells
bone marrow niche

abstract: The bone marrow (BM) microenvironment (the niche) plays a critical role in regulating normal hematopoietic process and is dysregulated in bone and marrow-related malignancies such as Acute Myeloid Leukemia (AML). AML is an aggressive blood cancer affecting the myeloid lineage of the hematopoietic hierarchy, and occurs in mostly individuals of older age. The goal in recent years has been to prolong the survival of these elderly patients, who show morbidity and early induction mortality in the face of intensive treatments. Disease relapse also poses a major hurdle to overcome following the supposed eradication of the leukemic disease, as current disease monitoring strategies used to detect minimal residual disease (MRD) are insufficient and may vary between patients. Many turn to look at the hematopoietic niche for the development of non-cell autonomous AML therapies in the hopes of more targeted and tolerable therapies; however, these strategies focus solely on the elimination of leukemic cells, and remain ignorant to the deterioration of the niche stemming from the disease. As yet, studies on niche cells, including mesenchymal stem cells and their progenies, are riddled with discrepancies and remain challenging to perform as methods used in the field to investigate mesenchymal populations rely primarily on ex vivo assays which are subject to extraneous factors that can lead to biased interpretation. Here, we used an in vitro mesenchymal CFU assay to interrogate the BM niche of AML patients and identify aberrations to the diseased niche throughout progression of the leukemic disease. Our experimental findings showed that while BM adipocyte and osteoblast populations appeared to be equally impaired in AML patients, the reduction in adipogenesis capacity of BM mesenchymal cells seemed to be unique in relapsed patients. We further identified a novel adipogenesis-inducing molecule, Isoginkgetin, that can successfully correct this deficiency in AML BM-MSCs and promote BM adipogenesis in vivo.

abstract: Thesis

abstract: Master of Health Sciences (MSc)


title: BARRIERS AND FACILITATORS TO ACCESSING MENTAL HEALTH CARE BY ARABIC-SPEAKING NEWCOMER CHILDREN AND YOUTH IN HAMILTON, ONTARIO

contributor:
Georgiades, Kathy
Global Health

abstract:
Background: Evidence suggests that refugee and immigrant children and youth are less likely to access needed mental health care. In most cases, settlement service providers may assist by connecting individuals with local resources to help with the transition and providing non-clinical mental health and wellbeing assistance. Few studies have examined the access to mental health care by newcomer children and youth, creating a knowledge gap in addressing the barriers and facilitators for accessing mental health services. This study aimed to explore the service providers’ perceptions of the barriers and facilitators to accessing mental health services for Arabic-speaking newcomer children and youth in Hamilton, Ontario.
Methods: Data was collected using semi-structured key informant interviews with service providers (n=7) representing a variety of sectors. Data were analyzed using thematic analysis.
Results: Six themes identified the data's most significant and pertinent aspects relative to my research question. The attitudes of Arabic-speaking newcomers toward mental health and mental well-being, the stigma around mental health, and trust-related issues were identified as three distinct individual factors that can function as barriers to seeking mental health care. Another theme emphasized the importance of the cultural competency and diversity of service providers. Lastly, two themes addressed health system-related variables that highlighted the gaps and challenges in the existing mental health care system for newcomers and the detrimental effects of the COVID-19 pandemic.

Conclusion: Enhancing and enabling access to mental health care for all newcomer children and youth is essential for their current and future mental health and wellbeing. This study suggests a few recommendations and future directions for service providers, researchers, and decision-makers to promote newcomers’ access to mental health care.

abstract: Thesis

abstract: Master of Science (MSc)


title: Deriving induced pluripotent stem cells from acute myeloid leukemia patients towards applications of autologous therapies and disease modeling

contributor:
Bhatia, Mickie
Biochemistry and Biomedical Sciences

subject:
Acute Myeloid Leukemia
induced pluripotent stem cells
disease modeling
autologous therapies
Hematopoietic stem cells
Cancer
reprogramming

abstract: Acute myeloid leukemia (AML) is a highly heterogeneous cancer with a poor prognosis. Clinical presentation is characterized by the abundant non-functional immature hematopoietic cells (blasts) in the bone marrow (BM) and peripheral blood (PB) of patients. Untreated, the rapid proliferation of these blasts contributes to hematopoietic system failure within months, leading to death. Although the standard chemotherapy regimen has remained relatively unchanged for decades and has proven to be effective at achieving initial remission induction, most patients succumb to relapse forming the basis of poor long-term survival. Incomplete mechanistic understandings of disease initiation, progression and maintenance of AML have impeded advances in therapy required for the improvement of long-term patient survival rates. This suggests that innovative and new model systems are required to understand the earliest initiation processes of AML disease towards more effective targeted therapy development. The ability to generate induced pluripotent stem cells (iPSCs) from human somatic cells provided a breakthrough in biomedicine to ‘capture’ diseased cells and their genome in a self-renewing state. Patient-derived human induced pluripotent stem cells (hiPSCs) have the theoretical ability to develop patient-specific (autologous) cell-based therapies and/or produce an endless number of specialized disease-associated cells, allowing replication of pathological characteristics of human disease in vitro. Despite the technical challenge of reprogramming human cancer cells due to the high inefficiency of the process compared to healthy samples, whereby iPSCs are often skewed in favor of residual normal cells over cells of the premalignant or malignant clone, I propose to develop a library of AML patient-derived iPSCs. Moreover, I hypothesize that pluripotent reprogramming can provide a unique alternative approach to dissect heterogeneity and molecular basis of AML that cannot be captured and studied in existing in vitro or in vivo patient-derived xenograft models. Additionally, I seek to investigate the ability of human iPSCs in the derivation of HSCs as a proof of concept for autologous cell-based therapies.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: A diagnosis of Acute Myeloid Leukemia (AML) varies from patient to patient, as there are many different subtypes of this cancer. This is referred to as ‘patient cancer heterogeneity’. AML represents one of the most heterogeneous types of cancers, and unfortunately, only 20% of AML patients survive past five years from diagnosis. AML is a cancer of the blood system that causes the bone marrow to fill up with immature cells that are unable to develop into functional blood cells. The ability to reprogram AML patient cells into induced pluripotent stem cells (iPSCs), which can give rise to any cell in a dish, provides an opportunity to study this disease. Our research proposal is to develop a diverse library of AML patient-derived iPSCs providing a unique alternative approach to interrogate the therapeutic potential, heterogeneity, and molecular basis of AML that “drive” the disease to continue which cannot be captured and studied in existing in vitro or animal models of the disease.


title: Memory for temporally nonadjacent tonal centers mediated by musically salient features

contributor:
Woolhouse, Matthew
Psychology

subject:
memory
music
nonadjacent key relationship
surface features
harmony
time decay

abstract:
Research on memory often describes the remarkable longevity of music. However, memory for music is not uniform. Cook (1987) found that participants were not able to tell apart excerpts that modulated from those that did not when the excerpt was longer than 1 minute in length. This suggests that participants were no longer able to remember, and compare, musical keys after a relatively short period of time. Farbood (2016) and Woolhouse et al. (2016) further explored the limitations of memory for tonal structures finding that, in fact, harmonic memory only lasts up to 21 seconds after modulation. However, this research was done using homophonic stimuli—arpeggios or quarter-note chords—that may not be representative of the music participants would be listening to regularly. The focus of this project was to explore how the addition of certain musical features, such as melodic or rhythmic figurations, may influence harmonic memory. Observing these possible influences may provide us with insight into the processes responsible for auditory memory and how it differs from other domains, such as speech or vision. Chapter 1 explores prominent memory literature and music cognition experiments that support, or address concerns with, common memory models. Here, I introduce a cognitive system which reconciles music research with models by memory specialists such as Baddeley and Snyder. Chapter 2 presents a detailed account of background empirical literature, including Farbood (2016) and Woolhouse et al. (2016). Though fundamental to the exploration of temporally nonadjacent harmonic memory, this research is potentially limited in its generalizability due to the homophonic nature of the stimuli. Chapter 3 explores this limitation by testing the effects of adding surface features—melodic and rhythmic components often used for elaboration in composition—on memory for large-scale tonal structures. Results found that harmonic memory is, indeed, enhanced and prolonged by these elaborative components, lasting up to 33 seconds, well past the limit found in previous research. Farbood (2016) further claimed that harmonic memory is significantly interrupted by new, highly harmonic excerpts. However, results from Woolhouse et al. (2016), Spyra et al. (2021) and those from Chapter 3 all question this claim as they employed stimuli that was highly harmonic. Chapter 4 investigates the contradiction by testing whether functional diatonic, functional chromatic, or random sequences degraded harmonic memory for an original key. Functional diatonic intervening information resulted in increased harmonic memory, directly contradicting Farbood’s original findings. In Chapter 5, these results are explored in terms of prominent memory models in the field of cognition, supporting standard models of memory such as that by Baddeley and Hitch (1974) or Atkinson and Shiffrin (1968), as well as my proposed cognitive system. This is further  elaborated by discussing the process of undergoing a musical judgement task from perception through to decision-making. In summary, this project suggests that more generalizable stimuli containing realistic musical features produce a significant boost in harmonic memory. Furthermore, this arguably calls into question standard practices in analysis that categorize surface features as hierarchically less important than ’deeper’ harmonic events, and thus, potentially less important from a cognitive perspective. Which is to say, this evidence suggests that these features may play a vital role in remembering nonadjacent harmonic
structures.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract:
Memory for music is often celebrated for its longevity. Music is a complex stimulus, however, and not all of its characteristics are remembered equally well. Past research has found that participants were not able to remember musical keys after a surprisingly short period of time: Farbood (2016) and Woolhouse et al. (2016) found that harmonic memory—i.e., memory for a key—lasts up to 21 seconds after a key change. Compared to nursery rhymes remembered from childhood bedtimes, this is remarkably limited. Yet this research did not fully explore which musical characteristics affect harmonic memory as it was done using simple musical stimuli: compositions made of blocks of chords. Whereas a string of chords might sound pleasant, it may not be representative of the type of music that people listen to regularly (with complex melodies and instrumentation). The focus of this project was to explore musical factors, such as melodies or rhythms, and measure how they interact with musical memory. Observing specific aspects of the stimulus gives us a window into the complexities of human memory, particularly that of the auditory domain.
Chapter 1 provides an overview of memory literature with a focus on common memory models and the musical research that supports them or contributes to their development. Here, I propose a cognitive system which integrates prominent models that otherwise describe different stages of processing complex auditory stimuli. Chapter 2 presents a detailed account of background empirical literature. This provides a basis for a series of experiments outlined in Chapters 3 and 4. These experiments investigate how components of music influence harmonic memory. Components include Surface Features, or ornamentations in music such as melodies or rhythms, and Harmony, the structure of the key itself which can make an excerpt sound more, or less, familiar. Results suggest that memory is significantly enhanced and prolonged by the addition of surface features. Furthermore, harmony that most resembles culturally familiar compositional practices also provides a memory boost when compared to random or somewhat ambiguous sequences. In Chapter 5, the implications of these results are explored with regards to the general memory models discussed in Chapter 1. Results support standard models of memory and my proposed cognitive system, as demonstrated by following the processing of my experimental musical stimuli from sound to executive function. This project suggests that more complex and musically realistic stimuli produce a significant memory boost. This puts into question traditional practices in music analysis which separate surface features into hierarchically less important positions when, in fact, the musical surface may be vital to our processing of auditory stimuli.


title: Genetic Contribution to Cannabis Use and Opioid Use Disorder Treatment Outcomes

title: GENETIC CONTRIBUTION TO CANNABIS USE AND OPIOID TREATMENT

contributor:
Samaan, Zainab
Neuroscience

subject:
cannabis
genetics
methadone
opioid use disorder
genome-wide
polygenic risk score
systematic review

abstract:
Background: Canada continues to face an opioid epidemic with 5,368 opioid apparent related deaths occurring between January and September of 2021. Methadone Maintenance Treatment (MMT), a form of Medication Assisted Treatment used to treat Opioid Use Disorder (OUD), has been reported to decrease opioid cravings and opioid use, however, individual differences exist in the effective dose of methadone. Further, individuals living with an OUD have higher rates of substance use including cannabis. A genetic component has been suggested to exist for both cannabis use and MMT outcomes, however inconsistent findings have been reported.

Methods: Knowledge synthesis and primary genetic association studies were conducted. A protocol was prepared for the planning of a systematic review for Genome-Wide Association Studies (GWASs) of cannabis use. The full systematic review was then conducted, providing an assessment of the literature and a description of studies quality. A GWAS and Polygenic Risk Score (PRS) was then conducted for cannabis use and MMT outcomes, separately, in Europeans only. The top Single Nucleotide Polymorphisms (SNPs) were then analyzed separately by sex and sex interactions were conducted.

Results: The systematic review included 6 studies, identifying 96 genetic variants associated with cannabis use. The GWASs for both cannabis use and MMT outcomes did not identify any significant results. A significant PRS was found for regular cannabis use and methadone dose. No sex-specific results were identified.

Discussion: This thesis summarised the evidence on the genetics of cannabis use as well as employed GWASs and PRSs to investigate cannabis use and MMT outcomes within a European population. We were able to highlight gaps within the genetic literature of cannabis and MMT outcomes as well as identify areas of interest for future research.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: Cannabis use rates in Canada are increasing, with Opioid Use Disorder (OUD) patients having high rates of cannabis use despite inconsistent findings on the impacts. To combat the opioid crisis, Methadone Maintenance Treatment (MMT) is utilized to reduce opioid cravings and use. However, individuals on MMT are likely to use other substances, including cannabis. This thesis explores the genetic literature on cannabis use and conducts a Genome-Wide Association Study (GWAS) and a Polygenetic Risk Score (PRS). The GWAS investigates genetic variants throughout the whole genome associated with a trait, while the PRS creates a genetic weight risk score. GWAS and PRS methods were used to investigate cannabis use and MMT outcomes within Europeans with OUD. While no significant GWAS results were found, a statistically significant PRS was found for regular cannabis use and methadone dose, suggesting each respective score can estimate an individual’s risk of that trait.


title: THE ROLE OF NEAR-INFRARED GUIDED ANATOMIC SEGMENTAL RESECTION FOR EARLY-STAGE NON-SMALL CELL LUNG CANCER

contributor: Clinical Health Sciences (Health Research Methodology)

subject:
Lung Cancer
Robotic Surgery
Early-Stage NSCLC
Segmentectomy
Learning Curve

abstract:
Robotic-assisted segmentectomy is a pulmonary resection procedure that is emerging as an alternative to lobectomy for the treatment of early-stage lung cancer tumours less than 2 cm in  maximal diameter. Segmentectomy offers better lung function after surgery by only removing a few segments of the lobe that contain the tumour, and sparing remaining healthy lung tissue. As tumours are being more frequently detected in their early-stages, segmentectomy has gained considerable attention for its potential as a primary treatment option for suspected nodules less than 3 cm in maximal diameter. However, there is a reluctance in adopting segmentectomy due to technical challenges while performing the operation, and the lack of high-quality prospective data compared to lobectomy, which is the current standard of care.
From a technical standpoint, segmentectomy is difficult to perform because the pulmonary lines that separate segments, or intersegmental planes, are invisible. This poses a challenge for the operating surgeon in determining where to resect the lung tissue to obtain adequate margin distance from the tumour. Near-infrared mapping (NIF) with indocyanine green dye (ICG) is a recent advancement in robotic-assisted segmentectomy that provides a complete delineation of the intersegmental plane. Previous work at our center has also shown that this technique was associated with an increase in the oncological margin distance compared to the surgeons’ initially estimated resection line. Given that segmentectomy is associated with a learning curve, we evaluated whether this was observed due to our early experience in robotic-assisted segmentectomy, and hypothesized that the added benefit of ICG would diminish as more cases were performed. In Chapter 2, we used a temporal analysis to monitor surgeon experience over time, and found that the clinical utility of NIF mapping diminished after approximately 42 cases with ICG, and the surgeon began to identify the location of the intersegmental plane more accurately and consistently without ICG injection since.
The second barrier in the adoption of segmentectomy is the lack of high quality-prospective data. Current evidence pertaining to the effectiveness of segmentectomy in terms of cancer-related outcomes is inconclusive and difficult to generalize to the current lung cancer population. In Chapter 3, we performed a secondary analysis of a prospectively collected database of participants who underwent robotic-assisted segmentectomy or lobectomy for tumours less than 3 cm. The oncological efficacy of segmentectomy can be evaluated by the measuring the number of lymph node stations sampled intraoperatively and rates of nodal upstaging, and comparing these outcomes to pulmonary lobectomy. These are important surrogate outcomes that can be readily evaluated, and have been shown to predict overall survival after lung resection. We observed that these outcomes, including overall survival, were similar between patients who underwent segmentectomy and lobectomy for tumours less than 3 cm. While these findings were consistent for patients that underwent segmentectomy for tumours between 2 and 3 cm, recurrence-free survival was found to be significantly lower after segmentectomy compared to lobectomy.
In conclusion, the clinical utility of near-infrared mapping diminishes over time, which is indicative of an improved ability to perform robotic-assisted segmentectomy as more cases were attempted. Second, adequate lymph node evaluation can be expected after segmentectomy, reducing the likelihood of missing positive lymph nodes. Although patients who underwent segmentectomy for tumours greater than 2 cm may be at a greater risk of experiencing recurrence compared to lobectomy, this population did not experience any reductions in overall survival.

abstract: Thesis

abstract: Master of Health Sciences (MSc)


title: Postnatal Development of NMDA Receptors in an Immature Inhibitory Circuit

contributor:
Gillespie, Deda
Neuroscience

subject:
NMDA
Plasticity
Auditory Brainstem
Glutamate
Refinement
Superior Olivary Complex
Inhibitory Circuit
Development

abstract:
For optimal function, neural circuits require precise connectivity. Neural circuits
achieve this precision through developmental refinement that typically takes place in
early postnatal life. N-methyl-D-aspartate receptors (NMDARs) are known mediators of
developmental refinement in many glutamatergic circuits and are hypothesized to
mediate refinement in glutamate-releasing immature inhibitory circuits of the superior
olivary complex (SOC). Physiological studies in the SOC have shown that NMDAR activity
is high at birth, occurs primarily through NMDARs that contain the GluN2B subunit, and
decreases rapidly over the first two postnatal weeks. These studies did not distinguish
whether the decrease in GluN2B-mediated NMDAR activity could be due to a subunit
substitution or an overall reduction in NMDAR expression. Using fluorescent in
situ hybridization and immunohistochemistry, I assessed the expression of NMDAR
subunits during early postnatal development in the rat SOC’s primary and periolivary
nuclei: the lateral superior olive, the medial superior olive, the medial nucleus of the
trapezoid body, the ventral nucleus of the trapezoid body, the lateral nucleus of the
trapezoid body, and the superior periolivary nucleus. I found that all NMDAR subunit
transcripts decreased between postnatal days 0 and 28 in all nuclei. All subunits in the
GluN2 subunit family – GluN2A, GluN2B, GluN2C, and GluN2D – showed varying
expression patterns, which are consistent with a subunit substitution. These results
suggest the involvement of different NMDAR subtypes during circuit refinement in
glutamate-releasing immature inhibitory circuits and a decline in NMDARs when the
circuit reaches its mature state. The developmental profile of NMDARs might suggest
the events taking place during refinement.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
To precisely locate a sound in space, the brain compares intensity and timing
differences in sound between both ears. Interconnected structures in the brainstem
perform this task, and the connections between these structures must be precise to
accurately attend to sound. The process of developing this precision is called
refinement, and it occurs early in the development of the brain after birth. To
understand refinement and how to fix it when it goes awry, we need to understand the
mechanisms available to the brain during this period. In this study, I looked at the
development of NMDA receptors, which are implicated in refinement. I found that the
number and composition of NMDA receptors in these structures change throughout
refinement, suggesting that there are different types of NMDA receptors involved during
refinement.


title: SYNTHESIS OF ANTIFOULING, BIOFUNCTIONAL “ROMANTIC” POLYMER COATINGS

contributor:
Wylie, Ryan
Chemical Biology

subject: Biomaterials, polymers, antifouling, biosensors, LSPR, elastomers,

abstract:
Materials in contact with the biological milieu (biomaterials) spontaneously and nonspecifically adsorb constituent proteins which may lead to unwanted cell adhesion and responses or hinder device performance. These interactions and their related phenomena lead to complications in ~3% of implant surgeries. Thus, resistance to these nonspecific interactions is critical to the performance of many implanted biomaterials and biosensing surfaces. Further, these interactions have widespread importance to industrial materials in contact with biological environments such as food packaging, and agricultural and nautical surfaces.
Thin film coatings of antifouling polymers are one of the leading methods for reducing nonspecific interactions. Both polymer composition (chemical composition and molecular weight) and polymer grafting density are the principal determinants of coating performance. For applications requiring specific bioactivity, such as selective ligand-analyte interactions for sensors, the polymer coating must remain antifouling and be amenable to functionalization with capture ligands. Tethered polymer coatings can be made by surface initiated polymerization (“graft-from”) which results in higher density coatings, but complex fabrication limits commercialization and capacity of functionalization with capture ligands. Simpler “graft-to” procedures, where pre synthesized polymers are immobilized to a surface, are more amenable to translation but suffer from inferior antifouling properties due to lower density coatings. New fabrication methods are therefore required to improve both graft-to and graft-from coatings.
Herein, the effects of polymer density on material performance are explored and leveraged to produce novel functional surfaces using two classes of polymers, namely amphiphilic and thermoresponsive poly(oligo(ethylene glycol)) methyl ether methacrylate, and zwitterionic, functionalizable poly(carboxybetaine methacrylamide) (pCB), as well as copolymers thereof. Specifically, polymer grafting techniques which exploit grafting density effects on surfaces were developed, leading to surfaces: 1) that are both high-loading and antifouling due to two different grafting densities within bimodal architectures, and (2) with enhanced anti-fouling properties despite being prepared via a “grafting-to” method using shrinkable or expandable substrates. Interestingly, shrinking substrates with antifouling polymers resulted in a novel LSPR biosensor with high translation potential.
Chapter 2 describes the pH controlled, one-pot production of two-layer brushes composed of an antifouling dense layer and a high-loading lower density layer where capture ligand immobilization was improved by 6 times compared to a single high density layer. Towards improving fouling and bioactivity of graft-to surfaces, Chapter 3 describes the first demonstration of Graft-then-Shrink where a stretched polystyrene (PS) substrate coated in a thin gold layer modified with thiol-terminated pCB was thermo-shrunk to one sixth in footprint to increase polymer surface coating content for enhanced antifouling properties and the production of micro/nano gold wrinkles to generate a localized surface plasmon resonance (LSPR) active surface. The low-cost sensors can
vi
detect biomolecular interactions by tracking changes in absorbance in the visible spectrum using ubiquitous plate readers. In Chapter 4, Graft-then-Shrink was extended to elastomeric materials, where thiol terminated polymers were grafted onto solvent swollen silicone via thiol-maleimide click chemistry, producing strongly antifouling materials.
Taken together, these developments represent significant advances in the preparation and application of antifouling polymer coatings towards the improvement of antifouling surface properties of medical devices and resulted in the development of a novel, low-cost LSPR sensor without the need for specialized equipment.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
When a material, such as a medical implant or sensor, is placed in contact with tissues and biological fluids, biomolecules stick to the exposed surfaces through nonspecific interactions. It is important to minimize nonspecific interactions because they can lead to bacterial infections, inflammation, implant failure and loss of device performance. Coatings to minimize nonspecific interactions therefore remain an active area of research. In this thesis, we explored new methods to create biomolecule and cell repellent coatings of long, chainlike molecules known as polymers grafted onto surfaces. Specific types of polymers, known as antifouling, were particularly effective at reducing these interactions.
Although it is important to block nonspecific interactions, many devices require bioactive surfaces through selective interactions. For example, sensors for analysis of blood products require the selective binding of the target ligand with minimal binding of non-target agents. To this end, functionalizable antifouling polymers are often modified with a capture or binding agent corresponding to the target ligand. Polymer coatings which are both antifouling and functionalizable for specific interactions, are called “romantic” because of their selective love of a single interaction. To synthesize these romantic polymer coatings, two main methods have been reported: 1) “grafting-from” where the polymer is grown from the surface, producing a very dense coating, and 2) “grafting-to” where the polymer is synthesized in solution, and then immobilized onto the material surface, which produces coatings of lower density. For antifouling polymer coatings to be as effective as possible, polymers should be tethered densely on the material surface, but to maximize the loading of capture agents, polymer density must be lower to allow for grafting within the layer. Further, the grafting-from method is typically more synthetically challenging hindering commercialization.
To improve the selective bioactivity of graft-to and graft-from coatings as well as antifouling properties of graft-to coatings, we present two methods to improve the specific bioactivity of anti-fouling polymer coatings and the first description of Graft-then-Shrink, a method to enhance the antifouling properties of graft-to coatings for medical implants and label-free in vitro sensors. For graft-from coatings, we produced a hierarchical romantic surface that consists of two polymer layers, the lower of which is dense and antifouling, and the upper of which is low-density and can accommodate high-levels of bioactive agents, resulting in a best of both worlds; the density of the layers is controlled by a novel pH controlled polymerization procedure. A method to improve the less labor intensive “grafting-to” strategy was then devised, called “Graft-then-Shrink” where the antifouling polymers are grafted onto a shrinkable material, and then the material is shrunk, leading to an increase in grafted polymer content over grafting-to alone. This method was successfully applied to a heat shrinkable material and an elastomeric silicone material, a common material for medical devices, for improved antifouling properties. Finally, a method for combining the Graft-then-Shrink technique
iv
with a novel localized surface plasmon resonance (LSPR) biosensor was found, that provides a simple route to access romantic surfaces on high-sensitivity, easy to fabricate LSPR biosensors. Together, these fabrication methods will simplify and expedite the translation of antifouling and romantic surfaces for medical devices and sensors.


title: CHARACTERIZING THE HUMAN INTESTINAL MICROBIOTA IN HEALTHY INDIVIDUALS AND PATIENTS WITH ULCERATIVE COLITIS USING CULTURE-DEPENDENT AND -INDEPENDENT APPROACHES

title: CHARACTERIZING THE HUMAN INTESTINAL MICROBIOME

contributor:
Surette, Michael G
Biochemistry and Biomedical Sciences

subject:
Gut microbiome
Intestinal Microbiota
Microbiota
ulcerative colitis

abstract:
The collection of microbes that inhabits the human gastrointestinal tract is known as
intestinal microbiota, and an enormous body of work has shown that their activities
contribute to health and disease. Ulcerative colitis (UC), which is a type of inflammatory
bowel disease, is considered to arise due to a disruption in the balance between the
immune system and microbiota. However, there is little consensus on the mechanism
of action and microbes involved in the disease manifestation. In this work, I applied
culture-enriched metagenomics (CEMG) to characterize the dynamics of gut microbiota
in healthy individuals and UC patients. I showed that CEMG provides a higher resolution
to study these microbial communities, and we used this approach to understand
microbial colonization after fecal microbiota transplantation (FMT) therapy in UC patient.
I showed that sequencing approaches alone did not reveal consistent engraftment
across FMT responders. Using CEMG and a collection of bacterial whole-genome sequences,
I showed patient-specific microbial strain transfer and a signature of commonly
engrafted genes only in patients who responded to FMT. In this work, I also investigated
the dynamics of a highly abundant bacteriophage, crAssphage, in an FMT donor
and implemented a new method to detect bacteriophage engraftment post-FMT using
SNP analysis. Finally, it has been suggested that antibiotic treatment before FMT may
increase the efficacy of FMT. However, in this work, I show that while antibiotics alter
the microbiome, there was no difference in the composition of the microbiome of antibiotic
vs placebo group post-FMT. This is consistent with the randomized controlled trial
results that shows pretreatment with antibiotics does not improve FMT outcome. Together,
this work demonstrate the importance of in-depth microbiome analysis applied
to culture-dependent and -independent sequencing to characterize microbial changes
post-FMT.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract:
Many bacteria reside in the human gut, and they are essential in our health and in
disease. It is evident that these bacteria are associated with inflammatory bowel disease,
but we do not yet know how and what bacteria are involved in this disease. In this
work, I describe a method to study these bacteria from stool that relies on growing
them and investigating their DNA. I showed that our approach helped us recover a
greater diversity of these bacteria and their genetic content in healthy individuals and
patients with inflammatory bowel disease compared to methods that use only DNA
based approaches. Using this method, we could better understand why some patients
responded to a treatment consisting of transferring stool content from healthy donor to
patient. I also investigated a group of viruses that infect bacteria and implemented a new
computational method based on DNA sequencing to test whether these viruses transfer
to the patient after receiving the fecal therapy. We also found that antibiotic treatment
before fecal therapy in patients with inflammatory bowel disease does not improve the
patient’s recovery.


title: REFUGEE HEALTH PROMOTION IN CANADA: A SYSTEMATIC REVIEW OF THE EVIDENCE ON THE IMPLEMENTATION OF THE IHR IN CANADA REGARDING REFUGEE HEALTH PROMOTION WITHIN THE CONTEXT OF A PHEIC

contributor:
Kapiriri, Lydia
Global Health

subject:
refugee health
International Health Regulations
PHEIC
health promotion
Canada
PHAC
health security
Public Health Canada
systematic review

abstract: Refugees remain the most vulnerable members of society and face several health risks for adaptation to a host country. These include an increased risk of developing communicable diseases that are exacerbated during a PHEIC . The purpose of this systematic review is to evaluate the reported implementation of the IHR in Canada, specifically in refugee health promotion, during PHEICs. The chosen method is a systematic review which locates and synthesizes evidence from as many relevant studies as possible. 9 electronic databases were searched and screening was conducted on Covidence. Articles that were included contained IHR policies on PHEICs, quantitative and/or qualitative methodologies of analysis, systematic reviews, published in English, provided a Canadian context, involved at least 1 of the refugee health outcomes from the following: access to health services and quality health care provision, improved health security, improved health literacy and published between 2005 and 2022 Risk of Bias was assessed using the ROBIS tool. Thematic Synthesis was used to code textual data on MAXQDA to extract descriptive themes and analytical themes. 19 studies were selected for the systematic review. 10 descriptive themes were found and analyzed to determine 2 analytical themes. Findings exhibit lack of effective policy/legislation translation as well as inappropriate applications of public health restrictions and safety protocols as barriers to promoting positive refugee health outcomes during a PHEIC. The findings may also reflect a lack of consistency in implementing some of the IHR core capacities and PHAC core competencies for refugee health promotion in Canada. Thus, it is essential that future research focus on appropriate needs-assessment tools, the use of legal frameworks that can inform the capacity- building of health systems for refugee populations as well as ongoing consultation amongst governing entities, health care administration, health care providers and refugee populations for strengthening Canada’s implementation of the IHR for refugee health promotion.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Refugee populations are at increased risk for developing poor mental health outcomes and infectious diseases, that are exacerbated during Public Health Emergencies of International Concern (PHEICs). The purpose of this systematic review is to evaluate the reported implementation of the IHR in Canada, specifically in promoting the health of refugee populations, during PHEICs. Nine electronic databases were searched and thematic synthesis methodology was used to analyze the results. Findings demonstrate lack of effective policy/legislation translation as well as inappropriate applications of public health restrictions and safety protocols as barriers to promoting positive refugee health outcomes during a PHEIC. A lack of consistency in implementing some of the IHR core capacities and PHAC core competencies for refugee health promotion in Canada, was also observed. Future research should focus on improving needs-based assessment and applying equity-based frameworks for implementing the IHR in Canada for refugee health promotion during a PHEIC.


title: Evolution of Security in Automated Migration Processes

contributor:
Paige, Richard
Computing and Software

subject:
Software Security
Software Obsolescence
Software Migration
Automated Migration

abstract: As users’ requirements change in today’s fast-paced business market, computer software has to adapt to new hardware, technologies and requirements to keep up with the trend. Therefore, to avoid depreciation and obsolescence, which can have detrimental effects on a product, software needs to be constantly maintained and, when passed a certain point in its lifecycle, needs to be migrated or re-developed from scratch. Automated migration enables software vendors to decrease the cost of the migration process by source code generation. However, as security is a crucial requirement in any system, it is not guaranteed that the previously satisfied security requirements are satisfied in the migrated software. Therefore, it is critical to study the evolution of security throughout the automated migration process to predict where new security vulnerabilities may emerge and to understand the scale on which the security is affected.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Defining the Self as Axiological Organization: An Enactive Approach to the Metaphysics of Personal Identity

contributor:
Klein, Alex
Philosophy

subject:
Self
Personal Identity
Enactivism

abstract:
Enactivism builds on the “embodied turn” in cognitive science to firmly establish the close connection between mind and life, exemplified in the work of Evan Thompson. The more recent “interactive turn” emphasizes that individuals’ mental and cognitive processes are shaped by social interactions with other cognitive agents. Regarding personal identity, Miriam Kyselo argues that it remains unclear how and to what extent the self is individuated by these processes, and whether or not social relations are necessary for self-persistence. Further, it remains unclear how the self of simple biological organisms is continuous with the much more complicated personal identity of human beings, who are subject not only to the forces of the natural world, but also to forces that arise only in their uniquely symbolic and sociocultural milieu.
I contend that we can come to understand how evaluations dependent on the individual’s needs and desires, what Charles Taylor refers to as “weak evaluations,” are continuous with “strong evaluations,” whose validity are independent of the individual’s needs and desires, by recognizing that some organisms not only create value, but respond to values already present in their environment. The general notion of selfhood that results is one of axiological organization. I argue that what we are really referring to with the term “self” is the organization of evaluations that organisms make in regard to environmental affordances, a system which, over time, comes to take on definitive traits and characteristics. The self, regardless of the particular context in which it is situated, becomes individuated by the evaluations it makes, and is experienced as persistent because evaluative activity is an on-going process, ending only in death. The self is further experienced as persistent because these evaluations are made in accordance with a critical standard which itself rarely, and the overall axiological organization retains a high degree of stability.

abstract: Thesis

abstract: Master of Philosophy (MA)

abstract: The aim of this thesis is to provide a conception of selfhood and personal identity capable of accounting for the both the “embodied turn” and the “interactive turn” in cognitive science. It seeks to explain the persistence and individuation of selves both biologically, as living systems, and socially, as members that participate in or distinguish themselves from social groups. The first chapter explores selfhood from the perspective of Evan Thompson’s work on the definition of living systems as self-producing and self-organizing. Chapter two introduces Charles Taylor’s work on the necessity of moral frameworks for personal identity, a view which initially appears difficult to reconcile with the approach outlined in the first chapter. The third chapter attempts to combine these approaches by demonstrating that selfhood is best conceived of as axiological organization – the way living beings evaluate and prioritize possible actions in their environment.


title: NETWORK META-ANALYSIS: STRATEGIES TO IMPROVE INTERPRETATION

contributor: Clinical Epidemiology/Clinical Epidemiology & Biostatistics

abstract: Network meta-analysis (NMA) is a relatively new methodology that allows for the comparison of multiple interventions, with particular benefit in allowing for the indirect comparison of interventions that have never been compared directly within randomized trials. There lacks a consensus with regard to many NMA methodology considerations, often leading to inadequately conducted NMAs. This provides an opportunity for novel research initiatives to develop and promote improved NMA methodologies; which will translate to improved information provided to clinicians for evidence-based decision making. This thesis highlights the need for better standards in NMA methodology and reporting, developed and user-tested a novel tool for effectively presenting NMA results to clinicians and key stakeholders, and utilized this tool within an NMA of surgical treatment options for displaced femoral neck fractures – an area of great interest for orthopaedic clinicians and researchers due to the numerous available treatment options and considerable equipoise that exists in this area. The NMA methods landscape will continue to evolve, and the components of this thesis provide the groundwork to solidify and advance the implementation of NMA results into clinical practice.

abstract: Thesis

abstract: Doctor of Science  (PhD)


title: Evaluation of metabolic enzymes as predictive biomarkers of risk for prostate cancer progression

contributor:
Tsakiridis, Theos
Health Sciences

subject: Prostate Cancer, Metabolic Enzymes, ACLY, ACC, GLUT1, PSMA, AMACR, Active Surveillance

abstract:
Currently, many patients with early-stage localized prostate cancer (PrCa) (D’Amico: low
risk or low-intermediate risk) do not receive immediate therapy but are monitored within
systematic AS programs. Prospective trials showed rates of stage reclassification and
progression to the treatment of 20–40% over 2–5 years. However, in certain patients, PrCa
progresses rapidly to an advanced stage that requires combined modality therapies, which
carry increased risk for toxicity and poor outcomes. There is a need to identify biomarkers
that can predict the risk for disease progression in this population. Research showed that
dysregulation of metabolism is an important hallmark of cancer progression. Here, we
pursued a pilot investigation of enzymes of de novo lipogenesis [ATP-citrate lyase
(ACLY), Acetyl-CoA Carboxylase (ACC)], lipid oxidation [a-Methylacyl-CoA Racemase
(AMACR)], glucose uptake [facilitative glucose transporter 1 (GLUT1)], and folate –
glutamate metabolism (PSMA: prostate-specific membrane antigen) as potential
biomarkers of PrCa progression in AS patients. With ethics approval from the Hamilton
Integrated Research Ethics Board (HiREB), 40 AS patients were accrued prospectively
from the Niagara Health System PrCa diagnostic program clinics and were asked to donate
their biopsy tissue. 28 patients progressed on repeat biopsies at 12 or 24 months after initial
diagnosis and were included in the “Progressed” group, and 12 did not who were included
in the “Non-Progressed” group. Baseline diagnostic prostate core biopsy tissues of both
groups were evaluated with H&E and immunohistochemistry (IHC) staining for ACLY,
ACC, GLUT1, AMACR and PSMA expression (quantified by H-score). H-scores were
evaluated in benign and malignant components (epithelial cells) and were compared
between the two groups of patients. We observed statistically significant increased GLUT1
expression in malignant epithelial cells of the progressed group compared to the non-progressed group. Also, we found statistically significant increased PSMA expression in
the benign epithelial cells of the progressed group compared to the non-progressed group.
Further, our results demonstrated a statistically significant increase in ACLY and ACC
expression in malignant epithelial cells compared to benign epithelial cells in the
progressed group, while AMACR was detected solely in the malignant component.
Overall, the results of this pilot study are consistent with the notion of induction of
glycolytic metabolism, de novo lipogenesis and increased PSMA expression associated
with the risk for PrCa progression. The levels of expression of PSMA within benign
epithelial cells and GLUT1 within malignant epithelial cells may have value as predictive
markers of risk for PrCa progression in AS patients. Future studies should investigate this
concept systematically in larger AS cohorts.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
Currently, many patients with localized prostate cancer do not receive immediate therapy
and are monitored within systematic active surveillance (AS) programs. The main aim of
AS management is to prevent overtreatment and treatment-related complications in
patients who would otherwise have a good quality of life despite dealing with prostate
cancer. However, many of these patients, especially those with low intermediate-risk
prostate cancer have a significant risk for disease progression and metastasis.
Additionally, there is a lack of promising tissue biomarkers to predict the risk for
progression in AS patients at the time of initial diagnosis. Research showed that
metabolism dysregulation is an essential hallmark of cancer progression, including
prostate cancer. In this pilot study, we examined whether the expression of enzymes
involved in lipid, glucose and protein metabolism could have value as biomarkers of risk
for prostate cancer progression in patients managed with AS. The expression of five
metabolic enzymes (ACLY, ACC, GLUT1, AMACR and PSMA) was examined in tumor
and benign regions of diagnostic biopsies of the prostate obtained from men managed
with AS. Our early results suggest that the expression of enzymes of protein (PSMA) and
glucose (GLUT1) metabolism may have value as biomarkers of risk for prostate cancer
progression and should be investigated further in systematic studies.


title: SPEECH IN NOISE: EFFECTS OF NOISE ON SPEECH PERCEPTION AND SPOKEN WORD COMPREHENSION

contributor:
Stroińska, Magda
Cognitive Science of Language

subject: speech in noise, energetic masking, informational masking, speech perception, spoken word comprehension

abstract: The study investigated the effects of noise, one of the major environmental stressors, on speech perception and spoken word comprehension. Three tasks were employed – listening span, listening comprehension, and shadowing – in order to find out to what extent different types of background noise affected speech perception and encoding into working verbal memory, as well as spoken word comprehension. Six types of maskers were used – (1) single babble masker in English, (2) single babble masker in Mandarin, (3) multi babble masker in Greek and (4) construction site noise, (5) narrow-band speech signal emulating phone effect and (6) reverberated speech signal. These could be categorized as energetic (2, 3, and 4), informational (1) and signal degradation (6 and 7) noise maskers. The study found that general speech perception and specific word comprehension are not equally affected by the different noise maskers – if shadowing is considered primarily a task relying on speech perception, with the other two tasks considered to rely on working memory, word comprehension and semantic inference. The results indicate that informational masking is most detrimental to speech perception, while energetic masking and sound degradation are most detrimental to spoken word comprehension. The results imply that masking categories must be used with caution, since not all maskers belonging to one category had the same effect on performance. Finally, introducing a noise component to any memory task, particularly to speech perception and spoken word recognition tasks, adds another cognitively stimulating real-life dimension to them. This could be beneficial to students training to become interpreters helping them to get accustomed to working in a noisy environment, an inevitable part of this profession. A final study explored the effects of noise on automatic speech recognition. The same types of noise as in the human studies were tested on two automatic speech recognition programs: Otter and Ava. This technology was originally developed as an aid for the deaf and hard of hearing. However, their application has since been extended to a broad range of fields, including education, healthcare and finance. The analysis of the transcripts created by the two programs found speech to text technology to be fairly resilient to the degradation of the speech signal, while mechanical background noise still presented a serious challenge to this technology.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: The study investigated the effects of noise, one of the major environmental stressors, on speech perception and spoken word comprehension. Throughout three different tasks (listening span task, in which participants were asked to recall a certain number of items from a list; listening comprehension task, in which listeners needed to demonstrate understanding of the incoming speech; and shadowing, in which listeners were required to listen and simultaneously repeat aloud the incoming speech), various types of background noise were presented in order to find out which ones would cause more disruptions to the two cognitive processes. The study found that general speech perception and specific word comprehension are not equally affected by the different noise maskers – provided that shadowing is considered primarily a task relying on speech perception, with the other two tasks considered to rely on working memory, word comprehension and semantic inference, or the way the listener combines and synthesizes information from different parts of a text (or speech) in order to establish its meaning. The results indicate that understandable background speech is most detrimental to speech perception, while any type of noise, if loud enough, as well as degraded target speech signal are most detrimental to spoken word comprehension. Finally, introducing a noise component to these tasks, adds another cognitively stimulating real-life dimension, which could potentially be beneficial to students of interpreting by getting them accustomed to working in a noisy environment, an inevitable part of this profession. Another field of application is the optimization of speech recognition software. In the last study, the same types of noise as used in the first studies were tested on two automatic speech recognition programs. This technology was originally developed as an aid for the deaf and hard of hearing. However, its application has since been extended to a broad range of fields including education, healthcare and finance. The analysis of the transcripts created by the two programs found speech to text technology to be fairly resilient to a degraded speech signal, while mechanical background noise still presented a serious challenge to this technology.


title: LANDLORDS, TENANTS, AND THE INFORMALITY OF THE PRIVATE PROVISION OF LOW-COST RENTAL UNITS: A CASE STUDY OF HAMILTON, ONTARIO

contributor:
Harris, Richard
Newbold, Bruce
Dunn, James
School of Geography and Geology

subject: housing, mobility, displacement, gentrification, informality, rental market, qualitative

abstract: Housing affordability is an enduring issue globally. Disproportionately affected by this trend are renters: those households who do not own their primary dwelling. Rather than being a transitionary phase – a stepping stone to homeownership – as in decades past; renting is becoming a permanent, and often financially draining, state for many households. Housing affordability is significant to the lives of renters, as renters overwhelmingly spend more of their income, as a proportion, on housing than homeowners do. In Canada, renters are not eligible for many wealth subsidies that homeowners enjoy (i.e., the exclusion of capital gains tax on the sale of primary residence), have less autonomy over their living space, and less security of tenure. These concerns, combined with aging multi-unit rental stock, disinvestment of governments from social housing funding, and a funneling of private funds towards condominium developments, has left those in the rental market with increasingly fewer housing options. This dissertation seeks to explore how households renting in the low-cost segment of the housing market gain access to housing and why they move. Special emphasis is placed on the nom-purpose built market, and a tool for better enumerating otherwise undocumented housing units is proposed. Findings suggest that previously undocumented, secondary units play a significant role in local housing markets, particularly within dense 19th century neighbourhoods with good access to amenities and transit. The dissertation also suggests that the social milieu of participants’ lives, including relationships with landlords and property managers, highly influences decisions to move. Lastly, the research finds that informal agreements, as well as units, characterizes entry and habitation of many units within the low-cost segment of the housing market. This dissertation contributes to the field of knowledge on residential mobility and housing geographies by exploring two primarily unexamined areas of local housing markets: informal units and informal agreements.

abstract: Thesis

abstract: Candidate in Philosophy

abstract: This dissertation examines the role of the private sector in housing individuals living in the low-cost segment of the rental market. Emphasis is placed on non-purpose built rentals and how they contribute to the larger function of local housing provision. Hamilton, Ontario is used as a case-study in all three papers that comprise the thesis. Findings are largely derived from a novel field enumeration technique and qualitative interviews with tenants. Taken together, results from the three papers indicate that the non-purpose built market plays a non-negligible role in providing affordable housing options to tenant households. The presented findings also suggest that amateur landlords and informal rental arrangements highly influence the form and function of low-cost rental units. Lastly, the papers suggest that highly mobile tenant populations are considerably affected by social milieu in the selection of housing units and intra-urban mobility decisions.


title: The Biological Correlates of Emotion Dysregulation in Adolescents

contributor:
Boylan, Khrista
Neuroscience

subject:
Emotion dysregulation
Adolescence
Depression
EEG Asymmetry

abstract:
Background: Emotion regulation is the ability to modulate behavioural responses to emotion-inducing stimuli in a goal directed manner. When emotion regulation processes become maladaptive, it results in emotion dysregulation (ED). ED is present in 25-45% of children with psychiatric disorders and strongly predicts poor clinical outcomes. ED presents as elevations in comorbid internalizing and externalizing symptoms. The relative contributions of these heterotypic comorbidities to ED in a particular patient is unclear. Clinicians must prioritize treatment of either domain of symptoms without empirical evidence. Objective measures of ED would assist in guiding treatment decisions. This thesis aimed to explore the biological correlates of ED with a focus on associations between ED and electroencephalographic (EEG) asymmetry. A secondary aim was to explore whether these relationships differed in populations with mood versus behavioural disorders.
Methods: A systematic review was conducted to qualitatively evaluate present literature on ED and its biological correlates. The relationship between frontal and parietal EEG asymmetry and ED, measured by the child behaviour checklist – dysregulation profile, was assessed in a secondary analysis of the D-Psypher dataset with a transdiagnostic sample of 88 adolescents with varying severity of psychopathology and risk for ED. Relationships were assessed in the whole sample, and according to the following groups: depression only, depression comorbid with a behavioural disorder, and controls.
Results: The systematic review included 12 studies and found ED-related differences in neural, cardiac, and genetic measures. The second study found associations between right parietal EEG asymmetry and ED in the whole sample and in youth with depression only. In youth with comorbid depression, ED was associated with left frontal asymmetry.
Conclusion: This thesis outlines several findings related to the biological correlates of ED in adolescents. Understanding how these correlates differ in various disorder categories has important implications for the measurement and treatment of ED.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Emotion dysregulation (ED) is a transdiagnostic feature of psychopathology that presents as elevations in comorbid internalizing and externalizing symptoms and/or disorders; however, it is unknown whether ED may manifest more prominently from externalizing versus internalizing brain process. A neural measure of ED would help differentiate between these processes. Thus, the first study in this thesis synthesized the available literature on biological correlates of ED and found evidence for differences in neural correlates involved in mood versus behavioural disorders. The second study explored correlations between frontal and parietal electroencephalographic asymmetry and ED in a transdiagnostic sample of youth and compared youth with major depressive disorder (MDD) only to youth with MDD comorbid with oppositional defiant disorder (ODD) or disruptive mood dysregulation disorder (DMDD) and controls. Findings of this thesis suggest differences in neural processes underlying ED in different disorder categories, which has important implications for the measurement and treatment of ED.


title: From Extreme Behaviour to Closures Models - An Assemblage of Optimization Problems in 2D Turbulence

contributor:
Protas, Bartosz
Mathematics and Statistics

subject:
Navier–Stokes equation
2D Turbulence
PDE-constrained optimization
Adjoint-Analysis

abstract:
Turbulent flows occur in various fields and are a central, yet an extremely complex, topic in fluid dynamics. Understanding the behaviour of fluids is vital for multiple research areas including, but not limited to: biological models, weather prediction, and engineering design models for automobiles and aircraft. In this thesis, we study a number of fundamental problems that arise in 2D turbulent flows, using the 2D Navier-Stokes system. Introducing optimization techniques for systems described by partial differential equations (PDE), we frame these problems such that they can be solved using computational methods. We utilize adjoint calculus to build the computational framework to be implemented in an iterative gradient flow procedure, using the "optimize-then-discretize" approach. Pseudospectral methods are employed for solving PDEs in a numerically efficient manner. The use of optimization methods together with computational mathematics in this work provides an illuminating perspective on fluid mechanics.

We first apply these techniques to better understand enstrophy dissipation in 2D Navier-Stokes flows, in the limit of vanishing viscosity. By defining an optimization problem to determine optimal initial conditions, multiple branches of local maximizers were obtained each corresponding to a different mechanism producing maximum enstrophy dissipation. Viewing this quantity as a function of viscosity revealed quantitative agreement with an analytic bound, demonstrating the sharpness of this bound. We also introduce an extension of this problem, where enstrophy dissipation is maximized in the context of kinetic theory using the Boltzmann equation.

Secondly, these PDE-constrained optimization techniques were used to probe the fundamental limitations on the performance of the Leith eddy-viscosity closure model for 2D Large-Eddy Simulations of the Navier-Stokes system. Obtained by solving an optimization problem with a non-standard structure, the results demonstrate the optimal eddy viscosities do not converge to a well-defined limit as regularization and discretization parameters are refined, hence the problem of determining an optimal eddy viscosity is ill-posed.

Further extending the problem of finding optimal eddy-viscosity closures, we consider imposing an additional nonlinear constraint on the control variable in the problem, in the form of requiring the time-averaged enstrophy be preserved. To address this problem in a novel way, we employ adjoint calculus to characterize a subspace tangent to the constraint manifold, which allows one to approximately enforce the constraint. Not only do we demonstrate that this produces better results when compared to the case without constraints, but this also provides a flexible computational framework for approximate enforcement of general nonlinear constraints. Lastly in this thesis, we introduce an optimization problem to study the Kolmogorov-Richardson energy cascade, where a pathway towards solutions is outlined.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Investigating Resting State Functional Connectivity in Cannabis Use Disorder Individuals Using Human Connectome Project Data

subject:
resting state
cannabis
CUD
cannabis use disorder
fMRI
functional connectivity
triple-network

abstract:
PURPOSE: The triple-network model of psychopathology theorizes psychological disorders
manifest from aberrant functional connectivity in three major brain networks, the central
executive network, default mode network, and salience network. To date, no research has used
this framework to investigate resting-state functional connectivity in cannabis users using fMRI
technology. Since attentional deficits have been associated with cannabis use, the dorsal attention
network was an additional network of interest.
METHODS: Using Human Connectome Project Young Adults (HCP-YA) data, 34 CUD
individuals were matched to 34 controls using propensity score matching, resulting in 68
participants with brain data (Mage: 27.2, 17.6% female). Functional connectivity was assessed
using CONN, a MATLAB-based extension package for Statistical Parameter Mapping 12
(SPM12) dedicated to assessing and displaying functional connectivity using fMRI technology.
A seed-to-voxel technique was used, with a priori regions of interest (ROI) derived from
CONN’s library of ROI. Significant clusters exceeded a voxel threshold of p < .0001 FDR-
correction, and p < .001 cluster threshold.
RESULTS: CUD individuals had aberrant functional connectivity across the default mode
network, salience network, and dorsal attention network. A consistent finding across networks
was weaker anti-correlation with the occipital cortex. Both the default mode network and dorsal
attention network exhibited weaker positive connectivity with surrounding areas and pre-/post-
central gyrus. The salience network in CUD individuals uniquely exhibited greater connectivity,
with greater positive connectivity between the right supramarginal gyrus and left inferior frontal
gyrus / precentral gyrus / central opercular cortex, and greater anti-correlation between the left
insula and right postcentral gyrus.
CONCLUSION: The triple-network approach to CUD revealed systemic differences across
networks; but may not be the best model for understanding CUD biomarkers. The results
highlight functional brain connectivity with problematic cannabis usage.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Cannabis Use Disorder (CUD) is the recent Diagnostic and Statistical Manual diagnosis for problematic cannabis use. Cannabis is known to impact both cognition and the structure of the brain, but the underpinnings of CUD are unknown. One historically successful approach to investigating psychological disorders is evaluating patterns of associations at rest in three distinct brain networks: the task positive, default mode, and salience networks. These networks are integral to cognitive control and function. Using Human Connectome Project Young Adult (HCP-YA) data, these brain networks were analysed in CUD individuals and healthy controls. Differences in brain activity were found across all three networks. The three brain networks in CUD individuals exhibited a regression to random activity within the occipital lobe, an area of the brain associated with vision. Additionally, the task-positive and default mode network in CUD individuals exhibited decreased brain activity within the respective networks.


title: Changes in Experiences of Accessing Healthcare: Perspectives of Sri Lankan Tamil Canadians

contributor:
Kapiriri, Lydia
Sim, Amanda
Global Health

subject:
Sri Lankan Tamil Canadian
Access to Healthcare
Healthcare Experiences
Refugees and Immigrant Health
Qualitative Research

abstract: Background: Currently, there is limited research on the importance and need for access to healthcare amongst refugee and immigrant populations in Canada. Amongst such populations are the Sri Lankan Tamils in Canada, who arrived in Canada as either refugees or immigrants due to the ongoing war in Sri Lanka in the late 1980s. Although Canada is home to the majority of Sri Lankan Tamils, there is minimal research showcasing the need and access to better healthcare for such individuals who have fled from a crisis, the civil war in Sri Lanka. As such, this study aims to assess and understand the experiences of the Canadian Sri Lankan Tamils in accessing healthcare upon their initial arrival to Canada and how these experiences have changed overtime. Methods: An Interpretative Phenomenological Analysis approach was used to conduct semi-structured interviews in English and Tamil with 8 Sri Lankan Tamil Canadians who arrived in Canada during the late 1980s and are currently between the ages of 55-75 years, residing in the Greater Toronto Areas. Interviews were transcribed and analyzed using the IPA to elicit themes. Results: The interviews revealed facilitators and challenges to access care within the past and present experiences of Sri Lankan Tamil Canadians. Past experiences revealed facilitators to access care, such as the influences of personal factors, the significance of social support systems and structural facilitators. The impacts of immigration status and acculturation in Canada were identified as barriers to access to care in the past. As for present experiences in accessing care, the degradation of the Canadian healthcare system revealed itself as a barrier to care, whereas settling down as a gradual process came up as a facilitator to accessing healthcare services. Conclusion: While Sri Lankan Tamil Canadian’s perspectives suggested facilitators in accessing care, their experiences still reveal many areas for improvement in the healthcare system for future newcomer populations in Canada. As such, these findings may have implications for policymakers who focus on refugee and immigrant health and service providers working with these populations.

abstract: Thesis

abstract: Master of Science (MSc)