title: Carrier Lifetime and Diffusion Measurement using Free-carrier Absorption Imaging

contributor:
Kleiman, Rafael
Engineering Physics

subject:
lifetime spectroscopy
recombination lifetime
pump/probe
silicon

abstract: At the moment, when energy and environmental issues are of concerned in our society, photovoltaic technology has received tremendous development and demand. Because carrier lifetime and diffusion coefficient are the important indicators to determine the recombination level, which influences the efficiency of solar cells to a large extent, they are regarded as key in choosing solar cell materials.  A technique for effective lifetime measurement, modulated free-carrier absorption (FCA), can extract lifetime and diffusion coefficient simultaneously, which is supported by a general mathematical model that predicts the experimental signal accounting for the 3-dimensional (3D) charge-carrier transport and recombination within the semiconductor. A single mode 1064 nm laser modulated by an EO modulator is used as the pump and a 2050 nm modulated LED is used as probe in this experiment as the pump/probe parts. An IR camera detects the frequency-domain diffusion image from the tested silicon sample at the tested frequency range between 1 kHz to 200 kHz and the lifetime can be extracted by frequency-domain free-carrier concentration equation, which is a Lorentzian model. By simulating the diffusion data from the camera with the 3D free-carrier absorption model, we can extract lifetime and diffusion coefficient simultaneously. The fitted lifetime from frequency-domain free-carrier absorption equation is 33.5 ± 1.3 μs, and the fitted lifetime from this 3D FCA model is 32.8 ± 1.5 μs, which match to within the error bars. The fitted diffusion coefficient from this 3D FCA model is 15.6 ± 0.7 cm2/s, which agrees with the theoretical value of 16 cm2/s for silicon. Good quantitative agreement is found among the model, experimental data, and theory.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Mental Health, Violence, and Corrections Canada: A Critical Discourse Analysis of 2 Reports Published by CSC on Mental Health in Federal Corrections

contributor:
Joseph, Ameil
Social Work

subject:
mental health
federal corrections
violence
critical discourse analysis

abstract: This critical discourse analysis aims to explore the construction of discourses on mental health inside of Canadian federal corrections through analysis of two reports published by the Correctional Service of Canada (CSC). Simultaneously utilizing Mad and Critical Disability studies as a theoretical framework, I engage with the material to examine the ways that individuals with mental health concerns are constructed in the texts. Results indicate that CSC relies on medical and individual understandings of mental health and (re)produce discourses of violence and risk as well as individual deficiency or otherness within their texts. Ways in which CSC operationalizes these discourses are explored and include violent treatments for those with mental health concerns such as segregation, forced medication, labelling, and restraint or use of force. An analysis of the ways in which CSC maintains their power and domination over discourse regarding mental health concerns in Canadian corrections is examined, including critiques of the ways they ensure erasure and silencing of mental health consumers as well as their lack of attention to historical, political and social implications in their texts. This research reveals how CSC uses negative discourses, namely discourses of violence or risk and medical or individual deficiency, to authorize various violences on those with mental health concerns within federal corrections.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Investigating Biological Rhythms Disruptions Across the Menstrual Cycle in Women with Comorbid Bipolar Disorder and Premenstrual Dysphoric Disorder

contributor:
Frey, Benicio
Neuroscience

subject:
Bipolar Disorder
Premenstrual Dysphoric Disorder
Biological Rhythms
Menstrual Cycle

abstract:
Introduction: Sleep and biological rhythms have not been investigated in women with comorbid Bipolar and Premenstrual Dysphoric Disorder in the context of the menstrual cycle. We explored whether menstrual cycle phase causes increased disturbances in sleep, biological rhythms and mood symptoms. Additionally, we explored whether these women have worse illness outcome than women diagnosed with either Bipolar or Premenstrual Dysphoric Disorder, and healthy women.
Methods: In this post-hoc analysis, participants were split into four groups: those with a Bipolar and comorbid Premenstrual Dysphoric Disorder diagnosis (n = 17, BDPMDD), those with a Bipolar Disorder diagnosis (n = 16, BD), those with a Premenstrual Dysphoric Disorder diagnosis (n = 19, PMDD), and women with no history of psychiatric diagnosis (n = 25, HC). The primary outcome variable was biological rhythm disruption as measured by the Biological Rhythms Interview and Assessment in Neuropsychiatry (BRIAN). The secondary outcome variables were depressive symptoms (Montgomery-Asberg Depression Scale, MADRS; Hamilton Depression Rating Scale, HAMD), manic symptoms (Young Mania Rating Scale, YMRS), and sleep quality (Pittsburgh Sleep Quality Index, PSQI). All variables were collected at both mid-follicular and late-luteal stages of the menstrual cycle.
Results: The BDPMDD group did not have significantly higher disruptions in biological rhythms than the BD or PMDD groups at the luteal phase; however, there were significant disruptions and mood symptoms in comparison to the HC group, especially at the follicular stage, which point to markedly higher disruptions in these areas that seem to persist beyond the symptomatic luteal phase.
Conclusion and Future Directions: Women diagnosed with a BD and PMDD comorbidity experience a higher illness burden then women diagnosed with either BD or PMDD. A relatively small sample size, not excluding for participants who were taking medications that affect sleep and relying solely on subjective measures of biological rhythms may explain some of the null results. Future studies should employ objective measures of sleep such as actigraphy to complement subjective measures like the BRIAN, as well as recruit a larger sample of participants. More importantly, more studies surrounding this topic must be done in order to create a robust body of evidence that can be used to compare results across studies and identify specific biological rhythms domains that can be targets for treatment.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Sleep disruptions are common in women diagnosed with Bipolar Disorder and in those diagnosed with Premenstrual Dysphoric Disorder. Illness burden has been shown to be greater in women diagnosed with a comorbidity of the above disorders in terms of clinical variables such as number of comorbidities, episode relapse, rapid cycling and mixed mood states. This thesis aims to investigate whether women diagnosed with Bipolar and comorbid Premenstrual Dysphoric Disorder have greater biological rhythms disruptions than women diagnosed with either disorder. Biological rhythms will be evaluated at both the follicular and late-luteal stages. The overall goal of this work is to add to the currently scant literature on the clinical presentation of a Bipolar and Premenstrual Dysphoric Disorder comorbidity.


title: Development of novel approaches to support the decision-making process of guideline panels

title: Novel approaches to support decisions by guideline panels

contributor:
Schünemann, Holger J.
Health Research Methodology

subject: health research methods, evidence-based medicine, clinical practice guidelines

abstract: Trustworthy clinical practice guidelines assist health care professionals in selecting the management options that optimize patient health outcomes. The development of trustworthy guidelines requires the consideration of many aspects and the involvement of multiple contributors, often working in groups. The guideline panel plays the key role in the development process as it is responsible for prioritizing topics that should be covered as part of the guideline effort, formulating questions, reviewing the evidence, developing and agreeing on the recommendations, and endorsing the final guideline document.  Ensuring transparency throughout the process by appropriately organizing and documenting panel activities is an essential standard that is used to assess the credibility of a developed guideline and its resulting recommendations. The adoption of conceptual frameworks that systematically guides panel members in their decision-making process (e.g. the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) frameworks) can aid in the formulation of methodologically sound recommendations.  In this dissertation, I used the example of a guideline on diagnosis and treatment of autism spectrum disorders to describe how rigorous research methods can support guideline panels in the development process from early stages to the formulation of recommendations. In another prominent guideline development effort with the American Society of Hematology, I have identified two steps in the process where panel members may benefit from further support and addressed these gaps by conceptualizing and developing novel approaches. The first approach comprises modelling baseline risk estimates for patient-important outcomes when only surrogate data is available. The second approach proposes a method to estimate decision thresholds for judgments on health benefits and harms using the GRADE EtD framework. While these approaches are tailored to address specific guideline panel needs, guideline methodologists could use the underlying concepts to find solutions to aid guideline panels in other steps of the development process.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Clinical practice guidelines assist health care professionals in selecting management options that can best improve the health outcomes of their patients. The development of trustworthy guidelines is a complex process that requires the contribution of several entities. The guideline panel, which typically comprises different experts (clinicians, patient representatives, experts in research methodologies) plays the key role in this process as it is responsible for selecting the most important questions to address in the guideline, reviewing the evidence supporting an option, agreeing on the recommendations, and endorsing the final guideline document. To ensure that the process of developing guidelines is transparent and that the recommendations are credible, it is important that panel activities are well documented and follow rigorous methods. Structured frameworks, such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) approach, have been developed to systematically guide the panel members and to minimize the error that could be introduced while making decisions. In this thesis, I describe the development of an approach and its application for comprehensive guideline development by the Italian National Health Institute, to describe rigorous guideline development and propose two novel approaches to further assist panel members in enhancing their guideline development. The first of these two enhancements to guideline development describes how to derive a modelled estimate of the risk of having certain health conditions when this data is not directly available in the medical literature. The second of the two enhancements is a method to support guideline panels in judging how substantial the desirable and undesirable effects of health interventions are. Both approaches were tailored to fit specific needs but can be adapted to inform the improvement of other steps in the guideline development process.


title: Population Genetic Investigation of the White-Nose Syndrome pathogen, Pseudogymonascus destructans, in North America

contributor:
Xu, Jianping
Biology

subject:
clonal expansion
fungal pathogen
adaptation
colony size
pigmentation
pigment diffusion
spore germination
genome sequencing

abstract: Fungal infections of animals have become an increasingly important global issue. White-Nose Syndrome is an ongoing fungal epizootic of North American hibernating bats, caused by epidermal infections of the fungus, Pseudogymnoascus destructans. Infections emerged early in 2006 in New York State and have since spread to 35 US States and seven Canadian Provinces, with rates of mortality exceeding 90% in some bat colonies. As an emerging outbreak in North America, the transmission of P. destructans is assumed to occur in a radial fashion outwards from the point of origin. In addition, the factors that may influence P. destructans transmission have been postulated, but not tested before. Lastly, as reproduction is assumed to be strictly clonal in North America, invasive populations should have low genetic diversity, and may even accumulate deleterious mutations over time. The aim of my PhD research is to test these assumptions regarding the spread, evolution, and adaptation of P. destructans using  combination of genotyping methods. My results showed how P. destructans isolates have shifted in terms of phenotypes and physiological capabilities since being introduced. In addition, I describe patterns of connectivity across the landscape, which are more consist with the level of anthropogenic activity than variation in climate. The mutations common to all invasive strains of P. destructans are associated with adaptations that have occurred since being introduced from Europe, some with relevant metabolic functions that fit their pathogenic lifestyle. Together, my results revealed significant phenotypic and genotypic changes during the spread of P. destructans in North America. The factors identified here that influence the phenotypic and genotypic changes should help developing better management strategies against the White-Nose Syndrome pathogen.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Effects of Inhibition of DNA Methyltransferase by 5-Azacytidine on MANF and CDNF Expression

contributor: Medical Sciences (Division of Physiology/Pharmacology)

abstract: The role of neurotrophic factors (NTFs) in neuronal development, differentiation, neuroprotection, and maintenance is well documented. The novel family of mesencephalic astrocyte-derived neurotrophic factor (MANF) and cerebral dopamine neurotrophic factor (CDNF) have been found to protect dopaminergic neurons, providing a potential therapeutic avenue for neurodegenerative diseases. Our group has previously shown an induction of NTFs including MANF and CDNF, following treatment with valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, in both cultured cells and rat brain. Furthermore, increased histone H3 acetylation was observed, indicating that epigenetic mechanisms may play a role in the modulation of MANF and CDNF. The interaction between HDAC inhibitors and DNA demethylation prompted us to investigate if DNA demethylation plays a role in the regulation of these NTFs. Treatment with 5-azacytidine (AZA; 1 – 25 µM), a potent DNA demethylating agent, for 24 hours, resulted in a significant increase in CDNF mRNA expression in rat C6 glioma cells. In the same time period, treatment with AZA resulted in a significant decrease in MANF mRNA expression. Furthermore, AZA decreased DNA methyltransferase 1 (DNMT1) mRNA and protein levels, suggesting a decrease in DNMT1 activity. Consistent with these findings, global DNA methylation was decreased following treatment with AZA. In view of the foregoing, the significant changes seen with CDNF and MANF mRNA expression following treatment with AZA, indicate that DNA demethylation may play a role in the regulation of these NTFs. These results may provide novel therapeutic approaches for neurological or related disorders and help to elucidate the mechanisms underlying the regulation of NTFs.

abstract: Thesis

abstract: Master of Science (MSc)


title: Teaching for transfer: A retrieval-based intervention, and a putative tool to gauge learning outcomes

contributor:
Monteiro, Sandra
Psychology

subject: Transfer, Learning, Retrieval-practice, Student perceptions

abstract:
The phenomenon of transfer—our ability to perform novel tasks by generalizing from past experiences—has long captivated theorists and practitioners. As educators it is essential for us to understand what types of learning best promote transfer and to structure our curricula accordingly. With that goal in mind, this dissertation outlines two lines of research.
       For the first line of research I adopted an experimental approach in the domain of problem solving, examining a training technique whereby the learner solves practice problems for the same principle in dissimilar contexts as opposed to highly similar contexts. The key finding was that contextual variability improved transfer outcomes when a set of training problems were solved spaced in time (akin to a closed-book test), but not when prior training problems and their solutions remained visible throughout training (akin to an open-book test). This finding suggests that contextual variability during training can be beneficial because it forces the learner to more effortfully recall what they have learned in the past.
       For the second line of research I then adopted a correlational approach, investigating a ubiquitous self-report inventory, the Study Process Questionnaire (SPQ), which is meant to quantify student learning approaches to predict educational outcomes. However, the SPQ’s predictive validity has recently been challenged because deep learning and its corresponding outcomes remain poorly defined. To tackle this measurement issue, my colleagues and I operationally defined outcome measures in real university courses to tap more precisely into transfer of learning. Across several studies we found limited evidence for the SPQ’s ability to predict transfer outcomes, leading us to suggest that educators and researchers should be more cautious about using this self-report inventory to characterize student learning.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: A central goal of education is to equip students with ‘flexible’ knowledge, enabling them to transfer the far-reaching principles they have learned to solve new, real-world problems. But what conditions of training are most conducive to transfer? One understudied technique involves being tested on the same principle in dissimilar contexts. The experiments reported in Chapter 2 provide evidence for this training technique in the domain of problem solving. Aside from direct interventions, another approach has been to measure individual differences among students to predict how much they engage in “deep learning”—a process closely associated with transfer. However, four correlational studies in Chapters 3 and 4 revealed little support for this approach, highlighting the difficulty of characterizing learning strategies using self-reports. In sum, this shows promise for interventions involving repeated testing in dissimilar contexts, but little promise for a self-report inventory meant to capture individual differences in student learning.


title: The Epistemic Validity Of Empathic Knowledge Claims

title: The Epistemic Validity Of Empathy

contributor:
Doubleday, Nancy
Philosophy

subject:
Empathy
Bias
Stereotype
Knowledge
Theory of Knowledge
Pragmatic
Law
Cognitive Empathy
Affective Empathy
Emotional Empathy
Justified True Belief
Causation
Epistemology
Empathic Concern

abstract: This paper is written in special acknowledgement and recognition of oppressed minority groups including, but not limited to, those of Black, Indigenous, and Asian persons. All lives do not matter until Black, Red, and Yellow lives matter.

abstract:
Obama once spoke of his desire to see empathetic individuals appointed to the position of Supreme Court Justice of the United States. His desire was met by many with resistance as people voiced concerns regarding the unreliability of beliefs founded on empathy and possible negative consequences that may come about. Concerns regarding unreliability are the product of our inability to access the ‘privileged information’ or the actual thoughts and perspectives of those we intend to empathize with. Attempts to form empathic beliefs, in the absence of this information, could lead to various harms to the very groups we intend to empathize with. Stereotyping, bias, and claims of sincerely ‘knowing’ the unique circumstances of those very different from ourselves can all lead to the justification of actions with harmful consequences.
 In my thesis I wish to address these concerns by acknowledging that most practical sources of knowledge (those we make use of and depend on regularly), such as those predicated on notions of cause and effect, have similar risks associated with them. Theories such as gravity and evolution remain theories and yet via the establishment of best practices and diligent communities, we are able to minimize the dissemination of false knowledge claims and their respective harms. In my paper I acknowledge this and explain how empathy can be dealt with in a similar fashion, while also reducing potential harms to others and allowing us to take advantage of the many benefits empathic knowledge has to offer. In the same way that we still continue to make use of our understanding of gravity to improve our lives and society by building aircrafts, we can make use of empathy to improve the ability of individual social and moral agents, as well as society as a whole. Under this pragmatic approach even the legal system can reap the benefits of empathic knowledge claims, so long as we, moving forward, work to collectively discern how to best ensure the validity of empathic knowledge claims.

abstract: Thesis

abstract: Master of Philosophy (MA)

abstract: Obama once spoke of his desire to see empathetic individuals appointed to the position of Supreme Court Justices of the United States. His desire was met by many with resistance as people voiced concerns regarding the unreliability of beliefs founded on empathy and possible negative consequences that may come about. In my thesis I wish to address these concerns by acknowledging that most useful sources of knowledge have similar risks associated with them, and yet via the establishment of best practices and diligent communities we are able to minimize the dissemination of false knowledge claims and their respective harms. In my paper I acknowledge this and explain how empathy can be dealt with in a similar fashion, while also reducing potential harms to others and allowing us to take advantage of the many benefits empathic knowledge has to offer.


title: Exploring The Experiences of Violence against Women living with HIV in the Context of HIV Non-Disclosure Criminalization in Canada

contributor:
Greene, Saara
Social Work

subject:
HIV
Women
Violence against Women
Structural Violence
Criminalization
Disclosure
Canada
Arts-Based Research
Body Mapping
Intersectional Feminism

abstract: An extensive body of knowledge points to the intersection of violence against women and HIV as it is well-established that violence is ubiquitous in the lives of women living with HIV. Experiences of violence exist within a socio-legal context that criminalizes HIV non-disclosure. In Canada, the federal law requires people living with HIV to disclose their HIV positive status before a sexual encounter with a partner that may pose, according to the Supreme Court of Canada, a “realistic possibility of transmission.” The criminalization of HIV non-disclosure carries particularly negative consequences for women living with HIV. This thesis includes an analysis of data from the Women, ART, and the Criminalization of HIV (WATCH) Study, a qualitative, arts-based research study on the impact of the HIV non-disclosure law on women living with HIV in Canada. Grounded in an intersectional feminist framework, this thesis presents findings from the narrative and visual data collected from the three Ontario workshops in the WATCH study. This thesis explores how women living with HIV visually and narratively express and describe their experiences of violence in the context of the criminalization of HIV non-disclosure. The stories and artwork shared by participants demonstrate how the law used to criminalize HIV non-disclosure creates and exacerbates experiences of interpersonal and structural violence and surveillance in the lives of women living with HIV. This thesis offers important insights for reconceptualising violence against women living with HIV from a structural lens. This project demonstrates how violence stems from legal institutions that do not respond to the needs of women, and instead, further exacerbate marginalization, violence, and surveillance in the lives of women living with HIV.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: PNIPAAM Immobilized Nanoparticles for Posterior Ocular Delivery

contributor:
Sheardown, Heather
Chaudhary, Varun
Biomedical Engineering

subject: Ophthalmic materials, PLGA Nanoparticles, Drug Delivery, PNIPAAm,

subject: Biomaterials

abstract: Ocular drug delivery to the posterior segment of the eye is extremely challenging. The delivery of the pharmaceuticals is made difficult by the numerous barriers that are present in the eye, as well as the isolated nature of the eye. The eye also consists of efficient drainage routes that eliminate the drug that has entered the eye successfully. Because of these reasons, drug delivery to the posterior segment of the eye is challenging and complicated. As a result, conventional eye drops are an inefficient way to deliver the pharmaceuticals to the eye as <5% of the administered dose is delivered to the anterior segment of the eye, and a negligible amount is delivered to the posterior tissues. The work presented in this thesis focuses on the design, synthesis, and characterization of the PLGA nanoparticles as a drug delivery vehicle to treat diseases associated with the posterior segment of the eye. The slow-release formulation was developed using PLGA nanoparticles and synthesized by the Double Emulsion Method (W1-O-W2). The PLGA nanoparticles were optimized by following various protocols and formulations to obtain the highest encapsulation efficacy and desired particle size range by changing the intensity of sonication, speed of ultracentrifugation, composition, and amount of the stabilizer and PLGA nanoparticles. The nanoparticles showed a 97% encapsulation efficiency with Bovine Serum Albumin (BSA) and a particle size of 201 nm. The slow-release formulation was further developed by immobilization of the particles in a thermogelling PNIPAAM scaffold. In vitro drug release results suggest that PNIPAAM containing PLGA nanoparticles produced in this work has the potential to be further developed and used as a drug delivery vehicle for the posterior segment of the eye.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Propulsion System Integration of a Parallel Through The Road Hybrid Electric Vehicle

contributor:
Emadi, Ali
Mechanical Engineering

subject:
EcoCAR
Hybrid
Electric Vehicle
Through The Road

abstract:
This thesis outlines the mechanical design and integration of a P0/P4 Parallel Through-the-Road Hybrid Electric Vehicle. The vehicle is McMaster University’s entrant into the EcoCAR Mobility Challenge, the current offering of the long running Advanced Vehicle Technology Competition series. The competition challenges students to electrify a 2019 Chevrolet Blazer, while meeting the needs of a car sharing platform.

The design of the McMaster vehicle will be explored, starting with a walkthrough of the architecture selection process performed in the first year of competition. The design process of both powertrains will be examined, starting with component selection and working up to assembly integration. Particular attention will be paid to the rear electrified powertrain, which has been designed from the ground up for this purpose, including custom single speed gear reduction.

The current integration status of the vehicle will be shown. Timeline delays due to the COVID-19 pandemic will be discussed, as well as next steps to move towards complete vehicle integration. A vehicle testing plan will be put forward, using the cutting edge systems available at the McMaster Automotive Resource Center.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract:
As Hybrid Electric Vehicles continue to grow in market share, the Advanced Vehicle Technology Competition series seeks to challenge and train students in this booming industry. The current competition in this series is the EcoCAR Mobility Challenge, where students must re-engineer a 2019 Chevrolet Blazer into a hybrid vehicle over four years. The vehicle is to incorporate new autonomous technologies, as well as be targeted at a car sharing application. The McMaster University Engineering EcoCAR team has entered into this competition.

This thesis describes the detailed mechanical design of the new vehicle. This begins by examining the selected hybrid layout, or architecture. Then the design process of individual systems is shown, with emphasis on how each system meets the McMaster team goals. Then the current state of the vehicle is shown, and delays due to COVID-19 are discussed. Finally, a testing plan is proposed, to ensure all systems can meet their design goals.


title: Three Essays on Stochastic Volatility with Volatility Measures

contributor:
CHAMBERLAIN, TREVOR
Business

subject:
Stochastic Volatility
Realized Volatility
Bayesian MCMC
Implied Volatility
Volatility forecasting
Overnight Volatility

abstract: This thesis studies realized volatility (RV), implied volatility (IV) and their applications in stochastic volatility models. The first essay uses both daytime and overnight high-frequency price data for equity index futures to estimate the RV of the S\&P500 and NASDAQ 100 indexes. Empirical results reveal strong inter-correlation between the regular-trading-time and after-hour RVs, as well as a significant predictive power of overnight RV on daytime RV and vice versa. We propose a new day-night realized stochastic volatility (DN-SV-RV) model, where the daytime and overnight returns are jointly modeled with their RVs, and their latent volatilities are correlated. The newly proposed DN-SV-RV model has the best out-of-sample return distribution forecasts among the models considered.  The second essay extends the realized stochastic volatility model by jointly estimating return, RV and IV. We examine how RV and IV enhance the estimation of the latent volatility process for both the S\&P500 index and individual stocks. The third essay re-examines asymmetric stochastic volatility (ASV) models with different return-volatility correlation structures given RV and IV. We show by simulation that estimating the ASV models with return series alone may infer erroneous estimations of the correlation coefficients. The incorporation of volatility measures helps identify the true return-volatility correlation within the ASV framework. Empirical evidence on global equity market indices verifies that ASV models with additional volatility measures not only obtain significantly different estimations of the correlations compared to the benchmark ASV models, but also improve out-of-sample return forecasts.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Computational Modeling of RNA Replication in an RNA World

contributor:
Higgs, Paul
Biochemistry

subject:
RNA World
Origin of life

abstract: The biology of modern life predicts the existence of an ancient RNA world. A phase of evolution in which organisms utilized RNA as a genetic material and a catalyst. However, the existence of an RNA organism necessitates RNA’s ability to self-replicate, which has yet to be proven. In this thesis, we utilize computational modeling to address some of the problems facing RNA replication. In chapter 2, we consider a polymerase ribozyme replicating by the Qβ bacteriophage mechanism. When bound to a surface, limited diffusion allows for survival so long as the termination error rate is below an error threshold. In Chapter 3, we consider the replication of short oligomers through an abiotic mechanism proposed in prebiotic experiments. When limited by substrate availability, competition results in the emergence of uniform RNA polymers from a messy prebiotic soup containing nucleotides of different chirality and sugars. In chapter 4, we consider the possibility of an RNA world lacking cytosine. Without cytosine, the ability of RNA to fold to complex secondary structures is limited. Furthermore, G-U wobble base pairing hinders the transfer of information during replication. Nevertheless, we conclude that an RNA world lacking cytosine may be possible, but more difficult for the initial emergence of life. In chapter 5, we analyze abiotic and viral mechanisms of RNA replication using known kinetic and thermodynamic data. While most mechanisms fail under non-enzymatic conditions, rolling-circle replication appears possible. In chapter 6, we extend our analysis of the rolling-circle mechanism to consider the fidelity of replication. Due to the thermodynamic penalty of incorporating an error, rolling-circle replication appears to undergo error correction. This results in highly accurate replication and circumvents Eigen’s paradox. Rolling-circle replication therefore presents an appealing option for the emergence of RNA replication in an RNA world.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Analysis and Modelling of Soil CO2 Emissions Within Temperate Coniferous and Deciduous Forests

contributor:
Arain, Altaf
Earth and Environmental Sciences

subject:
Soil Respiration
Neural Network
Modeling
Coherence Analysis
Turkey Point
TPD and TP74

abstract:
Climate change and extreme weather events have impacted global forest
ecosystems’ ability to sequester atmospheric carbon dioxide. In this study, the
temporal and spatial dynamics of soil CO2 efflux or soil respiration (Rs) was
measured in a temperate coniferous (TP74) and a deciduous forest (TPD) over a
six-year period (2014 to 2019). Analysis of Rs trends showed a strong positive
correlation with soil temperature (Ts) and soil moisture (SM) at TPD and TP74
causing large pulses of Rs. The average annual temperature sensitivity (Q10) was
found to be 2.06 for TPD and 1.87 for TP74. Coherence analysis for both sites from
2017 to 2019 showed that in extreme weather events, TP74’s carbon pool was less
stable than that of TPD. Dynamics of Rs at both forest sites was further analyzed
using thirteen different Rs models (e.g. Ts only, SM only, Ts and SM models,
neural network) to evaluate their performance in simulating observed patterns of
soil CO2 effluxes. As compared to other models, the Gaussian – Gamma model
consistently reproduced observed dynamics of Rs where on average 70% of
variability in Rs was explained.
This study showed that Ts and SM are key determinants of Rs in both forests.
Models that incorporate the influence of SM on Rs and were able to better simulate
Rs dynamics as compared to Ts only models. Results also suggest that coherence
analysis can be utilized to understand temporal variations in Rs. The knowledge of
environmental drivers of Rs can be used to determine the impact of climate change
and extreme weather events on Rs and assist in developing ecosystem models.

abstract: Thesis

abstract: Master of Science (MSc)


title: Organizational- and Provider-Level Factors Impacting Parental Engagement in Child and Youth Mental Health Services

contributor:
La Rose, Tara
Social Work

subject:
Child and Youth Mental Health
Parental Engagement
Neoliberalism
New Public Management
Constructivist Grounded Theory

abstract:
The literature indicates that engaging parents in child/youth mental health services is crucial for achieving positive outcomes. Yet, little research exists on how providers and organizations might hinder or facilitate parental engagement. This study aims to address this gap in literature by answering three research questions: (1) how do service providers working in child and youth mental health services define parental engagement? (2) Why does engaging parents in treatment remain a challenge for service providers? (3) What organizational- and provider-level factors contribute to this challenge?
To facilitate this aim, semi-structured interviews were conducted with four service providers, including those working in community-based or outpatient child and youth mental health services. Participants were recruited using a snowball sampling recruitment method. Interviews were audio-recorded, transcribed and analyzed following principles of Constructivist Grounded Theory.
Study results highlighted system- (e.g., access), organizational- (e.g., expectations and constraints), provider- (e.g., stance) and parental-level (e.g., shame) factors impacting parental engagement in services. These findings coincide with the documented impacts of neoliberalism and New Public Management on shaping mental health services. This study thus challenges traditional conceptualizations of engagement and underscores the interplay of complex factors that occur between service-levels. An expanded definition of parental engagement is therefore warranted if providers and organizations intend on holistically engaging parents in their child/youth’s care.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: CCL11 and GDF11 Levels in Drug-Naive Young Adults with Bipolar Disorder

contributor:
Kapczinski, Flavio
Health Sciences

subject: CCL11; GDF11; bipolar disorder

abstract: Bipolar disorder (BD) is a chronic and often progressive illness that has a significant impact on quality of life and functioning. Pharmacological treatments are not effective for all patients, emphasizing the need to better understand the pathophysiology of the disorder. It is well known that patients with BD present with increased levels of inflammatory markers during mood episodes and often exhibit chronic low grade inflammation, implicating the immune system in the etiology of the disorder. Furthermore, patients with BD show deficits in neurotrophic factors suggesting that alterations in neurogenesis may precipitate clinical features. Recent evidence indicates that accelerated aging processes may underlie the pathophysiological changes observed in BD, implicating biomarkers related to aging. The chemokine C-C motif chemokine 11 (CCL11) and the cytokine growth differentiation factor 11 (GDF11) have been identified as proteins that increase and decrease with age, respectively. As such, this thesis presents research examining serum levels of these proteins in drug-naive young adults with BD and a matched healthy control group. We analyzed serum levels of CCL11 and GDF11 using enzyme linked immunosorbent assay (ELISA). Our results indicate that serum levels of CCL11 and GDF11 do not differ between the BD group and the healthy control group, however CCL11 levels were elevated in males and in individuals with tobacco abuse/dependence when considering the entire sample. Our results suggest that serum levels of these proteins do not differ between drug-naive young adults with BD and healthy controls, but that alterations may be due to demographic and lifestyle factors. Small sample size and low power should be considered when interpreting these results.

abstract: Thesis

abstract: Master of Science (MSc)


title: ANALYSIS OF MACHINE LEARNING MODELS ON INFANT MOVEMENT DATA

contributor:
Reilly, James P.
Galea, Victoria
Electrical and Computer Engineering

abstract: This thesis presents a study of feature engineering and supervised models on infant general movements. General movements are purposeless movements produced by infants that can be used by clinicians to evaluate an infant’s developmental health. Given a database of healthy infant movement recordings, we train both supervised models and clustering algorithms to gain clinical insight into the data. First, a large set of time domain and frequency domain features are calculated to extract clinically meaningful features from the raw movement data. The infants’ data were split into different age groups based on the range of age, with the age group being used as the training label. Then various supervised models were trained on age group labels to predict the age group of an infant given their movement features. Using appropriate validation schemes, the supervised models attained good sensitivity and specificity on out-of-sample subjects, but also reflected large physiological variance by showing overlap between the age groups. Finally various future directions are presented most important of which is applying clustering algorithms with some preliminary results showing interesting clusters of infants. Overall these results show how healthy infants in the early months of life move, and are conducive to further studies that can quantify at-risk infant development relative to healthy infants.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Surface Modification of Model pHEMA Contact Lenses with Aptamers for Controlled Drug Release

contributor:
Sheardown, Heather
Chemical Engineering

subject:
Contact lenses
Aptamers
Drug delivery
Poly(hydroxyethyl) methacrylate

abstract:
An efficient delivery system and patient compliance are two of the most important factors for any drug delivery system design to be successful. The current standard, particularly to the ocular anterior segment, are topical applications including eye drops. However, due to ocular physical barriers including blinking, the varying tear film layers, and the structure of the corneal epithelium, less that 5% of drug reach the target tissue from a single eye drop dose. While most treatment regiments combat this with increased frequency of dosage and higher than needed concentrations, the need for a more efficient and controlled system has been recognized to reduce the risk of possible side effects. Contact lenses (CL) have been a widely discussed potential drug delivery device given their accepted use in the population, their ability to hold drug, as well as their placement on the ocular surface.
	The current work focuses on testing a novel delivery system using CLs with the incorporation of drug specific oligonucleotide chains known as aptamers on the surface of the lenses. This application of contact lenses is aimed at capitalizing on the strong affinity of aptamers to hold drug on the surface of the lenses until they are applied to the eyes. The aptamers were covalently attached to the surface via the activation of the hydroxyl groups on pHEMA as a model lens material using 1’1-carbonyldiimidazone CDI chemistry and subsequent reaction with the amine group on the 5' end of the aptamer. The presence of aptamers was confirmed using 6-carbofluorescein (6-FAM) fluorescence detection and x-ray photoelectron spectroscopy (XPS). The release of kanamycin B in comparison to regular pHEMA gels using a soaking uptake method was assessed.
	In this work, aptamers were confirmed through fluorescence to have been successfully reacted onto the surface, however XPS was not able to confirm a consistent reading. This may have been due to low initial amounts of aptamer or uneven distributions along the surface. The efficiency of the aptamer reaction was not tested and would need to be further investigated. The contact angle had a significant change with increased hydrophilicity at 60.7 ± 1.55° compared to 66.6 ± 0.67°, however physically it should not affect wettability. The lower aptamer amounts resulted in no significant difference during drug release. Kanamycin B was detected using liquid chromatography mass spectroscopy (LCMS) with a reverse phase method using a C18 column however quite a few errors in the methodology led to the conclusion that this method of drug release requires further investigation. It is recommended an aptamer-surface reaction efficiency be determined with the use of a much larger starting aptamer amount, as well as a follow up drug release.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: The Diabetes Drug Canagliflozin Enhances the Response of Prostate Cancer to Radiotherapy

contributor:
Tsakiridis, Theodoros
Health Sciences

subject:
Prostate Cancer
Radiation
Canagliflozin
Metabolism

abstract: Canagliflozin (CANA) is a sodium-glucose co-transporter 2 (SGLT2) inhibitor used for the treatment of type II diabetes. There is recent evidence suggesting that Canagliflozin has antiproliferative effects against malignant tumours. Canagliflozin is able to inhibit cell growth and cancer progression by inhibiting mitochondrial complex I leading to a reduction in cellular ATP levels. This alteration in the energy status of the cell leads to AMP-activated kinase (AMPK) activation, which in turn downregulates protein synthesis, lipogenesis and induces cell cycle arrest. The aim of this thesis is to explore whether Canagliflozin can be combined with radiation to enhance the outcome of radiation therapy in the treatment of prostate cancer and to further our knowledge on the cellular pathways impacted by Canagliflozin. Proliferation and clonogenic survival assays were used to establish the antiproliferative effect of Canagliflozin in vitro alone and when combined with radiation. Prostate cancer cell lines with different mutation profiles were used to assess the effectiveness of the drug under different radiation doses. A xenograft model was then used to test Canagliflozin’s effects in vivo. PC-3 cells were injected in the flank of balb/c nude mice. Mice were treated with Canagliflozin, radiation or a combined treatment and tumour growth was monitored. Furthermore, a western blot analysis of cells treated with Canagliflozin and radiation was performed to deepen our understanding of the cellular pathways affected by Canagliflozin. Our results show that Canagliflozin has an additive effect when combined with radiation. Canagliflozin was able to effectively downregulate the mTOR pathway, blocking mitosis and leading to cell cycle arrest. These findings provide evidence that Canagliflozin could be used as an adjunct to radiation therapy in clinical settings.

abstract: Thesis

abstract: Master of Science in Medical Sciences (MSMS)

abstract: Radiation therapy is a key therapy for prostate cancer. Although it is very effective at treating early stages of prostate cancer, prostate cancer cells develop resistance to radiation therapy rendering it less effective. One way to overcome this obstacle is by delivering higher doses of radiotherapy. However, this leads to increased side effects caused by radiation on normal tissues surrounding the prostate. An additional potential solution to this problem is administering a drug that can make cancer cells more sensitive to radiotherapy. This way we can deliver lower doses of radiation to avoid side effects while treating the disease. This study focuses on using a drug called Canagliflozin in combination with radiation in order to improve the outcomes of radiotherapy in prostate cancer.


title: The Structure and Processing of Persian Compound Words in the Mental Lexicon: Experimental Studies on Compound Word Processing in Persian

creator: Ahmadi-Torshizi, Narges (Torshizi, Narcisse)

contributor:
Service, Maarit Elisabet
Cognitive Science of Language

abstract:
This thesis examines the processing of N-N compound words in Persian. The main research question is whether and how the order of their functional components, modifier and head, affects their processing. Persian is an Indo-European language with subject object verb (SOV) word order. Persian allows for different head-modifier orders in compounds and, therefore, opens an opportunity for researchers to investigate if the processing effort is different for head-final (right-headed or RH) versus head-initial (left-headed or LH) compounds. In a series of three experiments, this thesis (i) presents a novel database of familiarity, imageability, and age of acquisition (AOA) ratings for Persian compounds, (ii) investigates effects of constituent order and syntactic structure of compound words on their recall from working memory, and (iii) explores the effectivity of different constituents of compounds to activate the whole-word representation for naming.
Chapter 2 introduces a database of AOA, familiarity, and imageability ratings as lexical variables that affect compound word processing. The database also includes information on the right and left constituents of these compounds, their headedness, meaning in English, length in letters and in phonemes, and Google frequencies. Correlational analysis indicated that familiarity, imageability, and AOA are highly inter-correlated in both right-headed and left-headed compounds.
Chapter 3 presents data on compound word maintenance in short-term memory. The results revealed better recall of commonly occurring RH compounds compared to common LH ones. This supports the view that right headedness is the default form of compound words in Persian. The results also indicated that processing of an irregular or marked structure could negatively affect short term memory span in Persian, and confirmed a syntax-based decomposition approach for the mental lexicon in Persian.
Chapter 4 reports the results of a cross-modal primed naming time experiment. The results demonstrated that RH compounds have shorter reaction times than LH compounds. Importantly, there was an interaction between headedness (RH vs. LH) and whether the first or the second constituent was used as prime, suggesting that priming effects are different for the two types of compounds. The results of this chapter provide additional evidence on the role of certain syntactic structures of compounds in the processing and organization of these words in the mental lexicon.
Overall, the experimental data suggest that the head position of compound words can affect their processing in the mental lexicon. The three experiments are the first to provide such evidence for Persian. The findings also provide more proof for the decompositional routes of processing in the mental lexicon. The findings are in line with data from other languages, pointing to negative effects of marked structures on complex word access and maintenance. Another major contribution of this thesis is to provide evidence on the importance of the Ezafe construction on the processing of complex words in Persian.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: CELL SURFACE GRP78 IS REQUIRED FOR THE UPREGULATION OF TSP-1 BY HIGH GLUCOSE IN KIDNEY MESANGIAL CELLS

contributor:
Krepinsky, Joan
Medical Sciences

subject:
diabetic nephropathy
GRP78
nephrology
TSP

abstract: Diabetic nephropathy (DN) is a complication associated with diabetes and is characterized by proteinuria and a progressive loss of kidney function. The disease morphologically manifests as an increase in the extracellular matrix (ECM) produced by kidney cells including specialized mesangial cells found in the kidney glomeruli. The mesangial cells undergo increased proliferation and hypertrophy, produce ECM components at an elevated rate and in turn the ECM itself is broken down at a reduced rate. This leads to fibrosis, or the scarring of the glomeruli. The process of fibrosis is known to be promoted by pro-fibrotic factors such as transforming growth factor beta-1 (TGF-β1), which is activated by various proteins including thrombospondin-1 (TSP-1). Both of these proteins are known to have an increased rate of expression and activation in a high glucose environment and in the kidneys of diabetic patients. Glucose-regulate protein 78 (GRP78) is another protein altered by high glucose, as it is translocated to cell surface in DN (cell surface GRP78, csGRP78). In this study, we investigate the role csGRP78 has in the regulation of TSP-1 and downstream signaling by high glucose, using primary rat mesangial cell cultures. Our results confirm that TSP-1 protein levels are increased in the cell lysate and in the ECM of cells treated with high glucose. We further show that inhibitors of csGRP78 and downstream PI3K/Akt reduce the high glucose-induced increase in TSP1 at both protein and transcript levels, and attenuate TGF-β1 signaling.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Diabetic nephropathy is a condition that is associated with a gradual loss of kidney function as well as the presence of protein in the urine. As the name implies, diabetic nephropathy occurs as a result of diabetes mellitus. The disease causes the mesangial cells in the kidney to produce excess extracellular matrix leading to scarring in the kidney, a process called fibrosis. One of the key fibrotic proteins is called transforming growth factor beta-1 (TGF-β1), stored in a latent form. A major activator of TGF-β1 is thrombospondin-1 (TSP-1). Our results demonstrate that the cell surface localization of glucose regulated protein 78 (GRP78) is required for the upregulation of TSP-1 in a high glucose environment, leading to activation of profibrotic pathways that are well known to perpetuate the fibrotic phenotype seen in diabetic nephropathy.


title: A Fault-aware Sensor Fusion System for Autonomous Vehicles

contributor:
Wassyng, Alan
Lawford, Mark
Computing and Software

subject:
Autonomous
Safety
Sensor Fusion
STPA
Accidents
Autopilot
Design
Hazard Analysis
Tesla
Uber

abstract:
There have been several accidents involving autonomous vehicles on public
roadways under scenarios that are normally avoidable by competent human
drivers. This thesis contains a review of these accidents and their causes as
a result of inadequate hazard mitigation. As a solution to this problem, a
novel design pattern is proposed. This design pattern was developed from a
hazard analysis using Systems Theoretic Process Analysis ( STPA ) methodologies
that analyzed the circumstances common to several of these accidents. To
demonstrate the effectiveness of the novel design pattern, an example system is
constructed and tested in simulation against several accident scenarios similar to
the ones studied. The results are then explained to demonstrate the effectiveness
of the proposed design pattern.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Caring Ahead: Development and Evaluation of a Questionnaire to Measure Preparedness for End-of-Life in Caregivers of Persons with Dementia

contributor:
Kaasalainen, Sharon
Health Sciences

subject:
mixed methods
dementia
caregivers
preparedness
palliative
questionnaire

abstract: Family/friend caregivers of persons with dementia often do not feel prepared for end-of-life, which contributes to high rates of complicated grief, depression and anxiety in bereavement. This mixed methods study used an exploratory sequential design to explore the core concepts and indicators of preparedness, develop and evaluate a multidimensional questionnaire aimed at measuring caregiver preparedness for end-of-life for persons with dementia. In Phase 1, a qualitative study with an interpretive descriptive design was used to explore the core concepts and indicators of preparedness with 16 bereaved family caregivers recruited from six long-term care homes located in Ontario, Canada. In Phase 2, a quantitative, cross-sectional Delphi-survey was conducted with 5 caregivers and 12 diverse professional experts to select preparedness indicators/items and develop the Caring Ahead questionnaire. Lastly in Phase 3, the self-report, paper format questionnaire was evaluated for evidence of validity and reliability using a quantitative cross-sectional design. In this final phase, the questionnaire was completed through the postal mail by 134 caregivers from over 50 long-term care homes/residential care facilities, primarily in Ontario, Canada. Evidence for internal structure and concurrent validity was generated along with reliability coefficients suggesting internal consistency and stability in a test-retest. Findings from this study contributed to the conceptualization and operationalization of preparedness and produced the new, multidimensional questionnaire titled Caring Ahead: Preparing for End-of-Life with Dementia with preliminary evidence for validity and reliability. This questionnaire aims to fill an existing gap expressed by researchers who aim to design and evaluate interventions promoting preparedness through a palliative approach. In addition, policy-makers should benefit from introduction of the Caring Ahead questionnaire as an outcome measure to monitor and evaluate the effectiveness of policies surrounding a palliative approach.

abstract: Thesis

abstract: Candidate in Philosophy

abstract: Providing care to a family member or friend with dementia can be very challenging and different than caring for persons with other disorders. Healthcare providers should provide a palliative approach to care which focuses on quality-of-life and helping family caregivers prepare for end-of-life. However, many family caregivers do not feel prepared for death and this can lead to serious mental health problems in bereavement. This thesis explores what feeling prepared for death means and describes the development and testing of a questionnaire to assess how prepared family caregivers feel for the end-of-life of someone with dementia. Through interviews and surveys with caregivers and professional experts, we developed and tested the Caring Ahead: Preparing for End-of-Life with Dementia questionnaire. Use of the new Caring Ahead questionnaire aims to help us understand how prepared family caregivers are feeling for end-of-life and what supports are needed.


title: The Female Gaze: Reclaiming and Redefining Black Femininity and Sexuality in Sexual Health Discourse and Education

subject: social work, sexual education, critical race theory, black feminism, hip-hop feminism

subject: sex education, black sexuality, black femininity, race relations, race studies

subject: sexual health politics, public health, sexual statistics, hip hop culture, black literature

subject: policy, critical theories, social welfare, community, focus group, qualitative studies

abstract:
Sex-education in Canada has predominantly been informed by an abstinence-based content, leaving the sexual literacy of adolescents hanging in the balance. As public health statistics indicate, sexually transmitted infection, early and unwanted pregnancy, and rates of HIV/ AIDS are staggeringly high. At the center of these statistics is the young Black female, as they are disproportionately over-represented in negative public health statistics. Many factors have been theorized to be the cause; from socioeconomic factors to educational limitations, it has been historically concluded that the individual failings and class issues of Black women are the root cause of sexual decision making that causes negative health implications. However, adopting a critical perspective may lead to a different conclusion.
This qualitative study sought to explore if the lack of comprehensive, racially attentive, and reflective sex-education as well as the influential societal discourse that shapes Black women and their sexuality in stereotypical lights, may have an impact on the sexual decision making of Black women. Through centering and highlighting the lived experiences, perspectives, and insights of a diverse pool of Black women, the stereotypes and scripts of Black femininity and sexuality, their root causes, and the impacts on young Black girl’s sexual decision making were captured to collaboratively redefine and reclaim Black femininity and sexuality while capturing what would be helpful to include in sex-education, specific to Black girls and women.
This study’s theoretical underpinnings are Black Feminist Theory, Critical Race Theory, and Hip-Hop Feminism, which has been coined by me as “the trifecta”. A focus group with Black female-identified participants was conducted and facilitated through open-ended question and discussion based processes. Thematic analysis was adopted to explore themes, meanings and to gain a better understanding of the participant’s collective perspectives regarding sex-education and Black femininity and sexuality. The main finding of this study, based in the lived experiences and insights of the participants, were that harmful societal scripts and stereotypes about Black femininity and sexuality historically and as they are presented in popular media, coupled with inconsistent and bare sex education, has the ability to affect the sexual decision making of young Black girls in a way that feeds participation in unsafe sexual practices.
This study fills gaps in literature because it contributes to the limited critical body of research that paramount the voices and insight of Black women in regards to sexual practice. This study also fills gaps by extending the conversation of Black women and sexual decision making, by suggesting tangible solutions of how the participant’s insights can be injected into larger policy and practice as well as social work research. The information supplied by the participants of this study will help social workers, policy makers, and educators create racially attentive, comprehensive, and accessible sex-education.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Understanding Oral Anticoagulation Across Clinical Settings

contributor: Clinical Health Sciences (Health Research Methodology)

abstract:
Oral anticoagulation (OAC) remains the cornerstone of stroke prevention in patients with atrial fibrillation (AF). Some areas of OAC management are well supported, while other areas require further research to inform clinical practise and support guidelines. My thesis focuses on generating knowledge about OAC use in 2 understudied settings: a) the emergency department (ED), and b) after cardiac surgery.
Chapter 1 is a preface that provides the rationale for conducting each of the following three chapters. In the ED, physicians are in a unique position to initiate OAC; however, prescription remains low. In the early period after open-heart surgery, initiating OAC is not the main issue, but rather, what class of OAC is the most safe and efficacious.
Chapter 2 uses a global registry dataset to explore the clinical patterns that lead to initiating OAC in the ED, along with the factors associated with patients’ long-term use of OAC.
Chapter 3 reviews the current literature around the safety and efficacy of direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) in the early period after cardiac surgery.
Subsequently, chapter 4 provides the rationale and design for the Direct Oral Anticoagulation versus Warfarin after Cardiac Surgery (DANCE) noninferiority, open-label vanguard trial.
In chapter 5, I present the main conclusions of this thesis and areas for further research.

abstract: Thesis

abstract: Master of Science (MSc)


title: Astrocytic Deficits in Maintaining Oxidative Homeostasis in the Fragile X Syndrome Cortex

contributor:
Scott, Angela
Biology

subject:
Fragile X Syndrome
Astrocyte
Mouse model
Oxidative stress
Mitochondrial respiration
Reactive species
Antioxidants
Physiological hypoxia

abstract: Fragile X Syndrome (FXS) is caused by the instability of a CGG-repeated tract at the 5’ end of the Fmr1 transcript. This instability causes silencing of the gene coding for FMRP. Higher levels of reactive oxygen species, lipid peroxidation, and protein oxidation within brain tissue have been found to be associated with the disease. These imbalances, along with altered levels of components of the glutathione system, provide evidence for increased oxidative stress. Astrocytes, glial cells within the brain, have many functions within neurodevelopment. Specifically, they regulate growth and synaptic contacts of neurons, regulate the level of excitability of synapses, and protect neurons at high levels of activity. To protect neurons from oxidative stress, astrocytes maintain oxidative homeostasis through their mitochondrial electron transport and antioxidant systems. This study examines the relationship between oxidative stress and FXS by assessing mitochondrial function and the antioxidant system of astrocytes. Using the Fmr1 knockout (KO) mouse model, mitochondrial respiration, and reactive oxygen species (ROS) production was analyzed in cultured cortical astrocytes. Astrocytes collected from male and female mice were analyzed under both normoxic and hypoxic conditions. In addition, western blots were conducted on both cortical tissue and cultured cortical astrocytes to determine potential differences in enzyme expression. Results indicate elevations of leak state respiration and ROS production in Fmr1 KO cultured cortical astrocytes alongside alterations in antioxidant and NADPH-oxidase expression. Characterization of mitochondrial function and the antioxidant system of astrocytes will be highly valuable to the understanding of glial roles during brain development and could provide future insight to direct clinically relevant studies of FXS and other neurodevelopment disorders.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Fragile X Syndrome (FXS) is the most common genetic cause of intellectual disability. It is characterized by the loss of FMRP, an important protein in brain development. Within the FXS brain there is evidence of oxidative stress. The cells that maintain oxidative homeostasis in the brain are astrocytes. Astrocytes are glial cells important for brain development. This thesis evaluated astrocytes' ability to maintain oxidative homeostasis in the FXS cortex. The findings of this thesis provide important insights into our understanding of FXS pathology and will help direct clinically relevant studies of FXS and other neurodevelopmental disorders.


title: INTERSECTIONALITY AND THE ROLE OF SERVICE PROVIDERS: A STEP TOWARDS IMPROVING THE EMPLOYMENT OUTCOMES OF IMMIGRANT WOMEN

contributor:
Ion, Allyson
Social Work

subject:
Social Work
Immigrant Women
Intersectionality
Employment
Unemployment
Barriers and Facilitators
Service Providers
Employment Services
Employment Outcomes
Economic Integration
Critical ethnography
Settlement Services
Greater Toronto Area
Labour Market

abstract: Examining service providers’ perspectives of barriers and facilitators for immigrant women seeking employment

abstract:
There are multi-faceted barriers that shape the employment trajectories and
economic outcomes of immigrant women in the Canadian labour market. In response to
the barriers that immigrant women experience, the Federal government, Immigration,
Refugee, and Citizenship Canada (IRCC), have initiated funding towards employment
programs for immigrant women. This critical ethnographic study examines the
perspectives of ten service providers in the Greater Toronto Area (GTA), in order to
identify the barriers and facilitators immigrant women experience within employment
services when trying to obtain secure well-paid employment. The data analysis revealed
three major themes: the role of funding for employment programs and settlement
services, the categorization of immigrant women by skills; and the application of
individualized services to meet the needs of immigrant women. Using an intersectional
lens, my research highlights that immigrant women experience various challenges to
finding, obtaining, and maintaining employment due to the intersection of their social
location (e.g. race, gender, immigration status, language, culture, and religion). Service
providers mitigate some of these barriers to secure well-paying employment by providing
individualized services to meet differential needs of immigrant women. While this
approach has led to success in matching some immigrant women to jobs that align with
their field of expertise and career goals, service providers are restricted in their ability to
meet the full needs of immigrant women due to underfunding and structural barriers. My
research reveals that employment services, immigration processes, and labour market
practices can (re)produce and maintain the marginalization of immigrant women in the
labour market. This paper concludes with some policy recommendations for immigrant-serving employment services and social work practice.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Superbubble Feedback in RAMSES

contributor:
Wadsley, James
Physics and Astronomy

subject: Astrophysics Simulation Galaxies Feedback

abstract: We present a new model for stellar feedback in the hydrodynamics code RAMSES. This model, called the superbubble model, represents many temporally and spatially-clustered supernova events combining to form a single large bubble. It avoids the overcooling problem by splitting the gas into two distinct phases with their own temperatures and densities. It features conduction and a sub-grid implementation of evaporation in order to facilitate mass-loading of the bubble's interior. We find that this model produces bubbles 40% larger, and preserves four times as much of the supernovae energy, compared to the default RAMSES case. These results are similar to those obtained in earlier work in the Gasoline code by Keller et al (2014), and demonstrate that the superbubble model is an effective way of generating the feedback necessary to simulate galaxies without relying on any free parameters or ad hoc adjustments.

abstract: Thesis

abstract: Master of Science (MSc)


title: Intersection Simulation and Path Estimation

subject:
Path Planning
Autonomous Vehicles
Navigation
Functional Safety
Intersections
Vehicle to Vehicle Communication
Simulation
Mathworks

abstract: As autonomous vehicles begin to move towards full autonomy, the controllers and software within them are becoming incredibly more complex to deal with any plausible scenario. Automotive manufacturers must balance the need for safety with the customers' desire for performance and features. A robust set of tools is a necessity to develop vehicle control protocols and navigation strategies. Vehicle to everything communication protocols and path planning are two aspects of autonomous vehicles that need a large amount of development effort. The MathWorks has put a great amount of effort in developing a robust simulation tool for autonomous vehicles. However, it currently lacks a method to develop V2X communication and path routing. In this thesis, I developed an extension for the Mathworks Simulink autonomous driving toolbox to incorporate graph-based path planning and vehicle to vehicle communication.  The navigation system models each road using standard civil engineering techniques, to calculate the intersection points and bounding areas for regions of interest. Based on these regions, a directed graph is created to aid in calculating the shortest path. The navigation system also provides a redundant method for path planning for poorly marked areas and intersections. The vehicle to vehicle communication system emulates the 802.11p protocol and deals with practical challenges such as latency to provide developers with a realistic environment in which to develop vehicle communication protocols.  The final result is a simulation where multiple vehicles drive safely and efficiently throughout a city network, sending messages at regions of interest and follow computed paths to their desired destinations.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Vehicle to Everything communication protocols and path planning are two aspects of autonomous vehicles that need a robust framework to aid in their development. I developed an extension for the Mathworks Simulink autonomous driving toolbox to incorporate graph-based path planning and vehicle to vehicle communication.  The navigation system models each road using standard civil engineering techniques, to calculate the intersection points and bounding areas for regions of interest. Based on these regions, a directed graph is created to aid in calculating the shortest path. The navigation system also provides a redundant method for path planning for poorly marked areas and intersections. The vehicle to vehicle communication system emulates the 802.11p protocol and realistic effects such as latency to provide developers with a realistic environment to develop vehicle communication protocols.  The final result is a simulation where multiple vehicles drive throughout a city network, sending messages at regions of interest and follow a computed path to their desired destination.


title: Engineering Hybrid Polymer Materials for Enhanced Biosensing

abstract:
Biosensors, as a potential diagnostic tool contributing to next-generation medicine, have been continuously researched and optimized to achieve improved performance with lower cost. Among them, electrochemical sensors coupled with multi-functional polymers have attracted particular attention because of their ability to provide real-time, quantitative, and highly-sensitive analysis. For example, appropriate polymers can enhance the bioavailability of an immobilized biomolecule or recognition elements and/or facilitate lower limits-of-detection when used as a coating.

In this thesis, magnetic microgel beads and ion-conductive polymers were fabricated to serve as anti-fouling bioactive immobilization platforms. Magnetic microgel beads are routinely used in biosensing and bioseparation applications given their high surface area for immobilization (and thus high capacity to capture biomolecules) coupled with their facile separation from suspension using a magnetic field. However, current magnetic beads are typically based on silica or polystyrene and thus have relatively poor protein-repellent properties, leading to enhanced binding of non-target molecules and thus reduced signal:noise ratios. In response, magnetic microgel beads based on the highly protein-repellent polymer poly(oligo(ethylene glycol) methacrylate (POEGMA) were fabricated using a semi-batch inverse emulsion polymerization. The resulting microgel beads have a narrow size distribution centred around ~5 μm, a low level of aggregation, and high colloidal stability, all at a low cost. Effective magnetic separation can be achieved within five minutes, while the inherent protein-repellent properties of POEGMA significantly reduce non-specific protein adsorption. Upon using carbodiimide chemistry to tether a methylene blue-linked DNAzyme to the microgel bead that is selectively cleaved in the presence of E. coli, a 6.3-fold higher signal was measured upon exposure to E. coli in buffer and a 97-fold higher signal retention was achieved in clinical urine (based on the electrochemical detection of released methylene blue from capture probes) relative to that achieved with Dynabeads®, a leading commercial magnetic bead.

To reduce non-specific adsorption on gold electrodes without compromising the conductivity and thus signal:noise of the electrochemical device, three types of water-soluble polymers were synthesized and tested for their anti-fouling performance and conductivity when coated on gold electrodes. POEGMA polymer functionalized with (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) failed to show sufficient conductivity, while POEGMA polymer functionalized with thiol groups that bound directly to the gold electrode maintained sufficient ion conductivity but reduced the DNA signal at the desired voltage (as generated by hybridization between cleaved probes from DNAzyme and capture probes grafted on electrodes).  The possible explanation is that the capture probes were not immobilized on polymer efficiently because of the reversibility of imine bonds formed between amine labelled probes and aldehyde groups from polymer. Zwitterionic polymer poly[2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide] (PDMAPS) functionalized with thiol groups enhanced the conductivity of the electrode (showing a lower resistance to ion conductivity even compared to the bare electrode), although further optimization is still required to realize higher DNA signals for clinical applications.
Overall, both magnetic beads microgels and conducting non-fouling polymers enabled significantly improved performance of electrochemical biosensors for E.coli detection. Magnetic microgel beads show potential for commercialization in the future.

abstract: Thesis

abstract: Master of Science in Biomedical Engineering

abstract:
Electrochemical biosensors are analytical devices that convert the signal of a biological reaction into an electrochemical signal and are used in a range of clinical, pharmaceutical, agricultural, and food applications. Since their first development, scientists have put many efforts into designing smaller, more accurate, and more automated biosensors.  One approach for achieving these goals is through the integration of various types of polymers. Magnetic microgels, crosslinked three-dimensional polymer networks containing entrapped magnetic materials, are demonstrated to help achieve these goals by carrying higher quantities of biological components relative to two-dimensional surfaces while being separable easily with a magnet after the sensing reaction is complete. To satisfy the end-use, magnetic microgels with optimal size, stability, magnetization properties, and functionality were designed in this project.
Another general focus in the area of biosensors is to achieve detection of targets without the need to pre-process the source sample (e.g. blood, urine, saliva, etc.) prior to analysis. However, most in-field biosensors have to work with untreated clinical samples and thus generate noisy or low-resolution signals. Polymer can play an important role in reducing this interfering signal by preventing the interfering molecules from approaching the detector. While coating the detector with a highly water-loving polymer can minimize such interference, such polymers are typically non-conductive and as such also block the desired signal from target binding. Therefore, thin layer polymer coatings were designed and optimized to repel interfering molecules without influencing the detection of targets.


title: Single molecule fluorescence microscopy image analysis for the study of the 2D motion of cellulases and Bcl-2 family proteins

contributor:
Fradin, Cecile
Moran-Mirabal, Jose
Physics and Astronomy

subject: Single Particle Tracking

subject: Fluorescence Microscopy

subject: TIRF

subject: line-scanning FCS

subject: Hidden Markov Model

subject: Bcl-2 Family Proteins

subject: Mitochondria-like supported lipid bilayer

subject: Cellulases

abstract:
Biological systems carry inherent complexity, which pose difficulties observing behavioural properties, such as diffusion coefficients, kinetic constants and state switching occurrences. With constantly improving computing power and microscopy technologies, single molecule methods have become a viable alternative when probing the behaviour of proteins, enzymes, lipids and other molecules. Processed microscopy images and videos provide information such as particle intensities and trajectories, avoiding ensemble averaging and therefore allowing for a detailed breakdown of particle mobility and interactions.

A single particle tracking (SPT) algorithm was developed which implements detection, localization and position linking on image stacks. Sub-pixel precise detection is done via either centroid determination, Gaussian fit, or radial symmetry centres, while tracking makes use of distance based global cost optimization. The detection algorithm is also used for single particle spectroscopy, where intensity information is used to determine the size of oligomers, as well as their interaction with other molecules through channel intensity cross-correlation. The algorithm underwent benchmarking with simulated videos and was applied to three different biological systems with comparison to other established methods of analysis.

The first system studied was the diffusion of the fluorescent lipophilic dye DiD in a five-component mitochondria-like solid-supported lipid bilayer. Comparing line-scanning fluorescence correlation spectroscopy (FCS) and single particle tracking, the measured diffusion coefficients were found to be statistically different, with DFCS = 3 μm2s-1 and DSPT = 2 μm2s-1, indicating different operational ranges for the two methods. FCS outperforms SPT when the diffusion coefficient exceeds 1 μm2s-1, making it ideal for lipid diffusion in fluid membranes and proteins in solution with weak membrane interaction. SPT is best suited for mobile and immobile membrane inserted proteins, as well as lipid diffusion in viscous membranes.

The second system studied was the interaction between the two proteins Bax and Bid when inserted in a membrane. Bax and Bid are both members of the Bcl-2 family of proteins, which plays a vital role in the apoptosis mechanism, by inducing mitochondrial outer membrane permeabilization. To study this system with single particle spectroscopy, fluorescently labelled Bax and truncated Bid (tBid) were imaged when interacting with a mitochondria-like supported lipid bilayer with confocal microscopy. Immobile and mobile particles were detected and distinguished based on the eccentricity of the observed fluorescence spot. The intensity of the particle signal was used to determine oligomer type (homo-oligomerization) while the interaction with the particles' counterpart (hetero-oligomerization) was determined by channel cross-correlation. This allowed the measurement of the 2D-KD values for mobile (0.6 μm-2) and immobile (0.08 μm-2) Bax/tBid complexes, showing that the degree of insertion of the proteins in the membrane greatly affect their affinity for each other.

The third and final system studied was the motion of cellulases on cellulose fibers. Enzymatic hydrolysis of crystalline cellulose is a costly step in the generation of fermentable sugars for biofuel production. Due to the complex structure and many possible interaction states of the enzymes with cellulose, single particle tracking is a well-adapted technique to the gathering of information on the enzyme dynamics, which is essential for process optimization. The movement of cellulases on cellulose substrate was observed via labelled Thermobifidia fusca Cel5A, Cel6B and Cel9A on bacterial micro-crystalline cellulose substrate. The detected trajectories were analyzed using multiple diffusion models. A simple one-state diffusion model was insufficient to describe the observed radial displacement distributions and so a two-state model was introduced and confronted with the data using conventional least-squares fits , as well as a hidden Markov approach. The diffusion coefficients of the two states are found to be on the order of Dfast = 10-3 μm2s-1 and Dslow = 10-4 μm2s-1, with the slow state being more stable and therefore more likely to occur.

Single particle tracking can give us better insight into complex interactions, such as synergistic binding of proteins existing in several different states and processive enzymatic behaviour, where ensemble averaging techniques can fall short. The uses of single molecule methods are plentiful and with the current rise of machine learning, higher levels of abstraction will provide us with more detailed insights into biological processes, driving promising developments in the medical field, as well as new technologies in many sectors of industry.

abstract: Thesis

abstract: Doctor of Science  (PhD)

abstract:
Proteins are the motors that drive most cellular processes, for example steering a cell’s life
cycle, or decomposing sources of nutrients. Being able to observe the motion of individual
proteins is key to understanding their behaviour. In this work a single particle tracking
(SPT) program was developed to extract protein trajectories from fluorescence microscopy
experiments. With this tool-set we investigated the following two systems.
The first system of interest is the Bcl-2 protein family, which is vital during the pro-
grammed cell death at the end of each cell’s life span. The failure of a controlled cell death
can have dire consequences, such as necrosis and cancer. The Bcl-2 family proteins Bid
and Bax are active on the outer membrane of the mitochondria, where they initiate the
process of terminating the cell’s functions by forming pores. For our experiments we ar-
tificially mimicked the outer membrane of the mitochondria, introduced Bid and Bax and
observed their preferential groupings on the membrane surface. This provided indications
of the mechanisms involved during binding and pore formation.
The motivation behind the investigation of the second system is the improvement of
biofuel generation from a renewable source: plant-based biomass. Cellulases are enzymes
from bacteria or fungi that break down cellulose – one of the main building blocks of all
plant cell walls – into fermentable sugars. In fluorescence microscopy experiments a purified
cellulose substrate was used to monitor the motion of three types of cellulases. The insight
which we gained into the cellulase behaviour may allow the optimization of the process of
cellulose decomposition.


title: On the Concept of the Reconfigurable Multi-Source Inverter for Electrified Vehicle Powertrains with a Hybrid Energy Storage System

contributor:
Emadi, Ali
Electrical and Computer Engineering

subject:
power electronics
inverters
hybrid vehicles
hybrid energy storage system

abstract: This thesis focuses on the concept, design, and simulation of the Reconfigurable Multi-Source Inverter for EV applications and its effectiveness when combined with a HESS. The current trends in the automotive market, including different vehicle types, and the adoption of electrified vehicles by the public are discussed. The benefits and logistics of different vehicle architectures are analyzed and compared. Hybrid vehicles will be essential in helping transition society from conventional internal combustion engine vehicles to purely electric vehicles. The individual components of these electrified vehicles are reviewed, and common topologies are discussed with the benefits of each system compared. The batteries required for these electric vehicles are costly and require many individual cells in order to operate efficiently. Many hybrids vehicles make use of expensive power electronics, such as DC/DC converters to help boost the operating voltage of the battery pack without adding additional cells. A Reconfigurable Multi-Source Inverter in introduced and its switching structure is explained in depth. Its’ ability to make use of multiple DC sources to create four different voltage levels is outlined and possible modulation techniques are presented. This thesis aims to introduce a novel Reconfigurable Multi-Source Inverter using a Space Vector Pulse Width Modulation (SVPWM) scheme and is further investigated through simulations and with plans for experimental validation on an R-L load.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: One of the main factors affecting the cost of electrified vehicles is the expense of building a high voltage battery pack. Motor’s used in electric vehicle applications typically operate at higher voltages and therefore require large battery pack or costly power electronics to step the voltage of the pack up to a suitable operating level. A Reconfigurable Multi-Source Inverter uses a combination of two sources to create different voltage levels. This novel inverter can be used to maximize the voltage of smaller packs to help reduce the overall cost of vehicle electrification.


title: Building a Network: Black Women's Visions for Online Peer Support and Advocacy in Health Care

title: Black Women's Visions

contributor:
Greene, Saara
Social Work

subject:
Black women
health care
primary care
advocacy
social media
online platforms
peer support
online support
twitter
#Blackwomentwitter
Black feminist thought
Black feminism
intersectionality
community

abstract: Black women have long traditions of peer support and self-advocacy that has been advanced by the current digital age. Social media and online platforms have become spaces where Black women share and connect with other Black women, and campaign for their own needs regarding health care access and navigation. Drawing on the findings emerging from a focus group discussion between six Black women that explored their experiences in Ontario based health care settings, this paper describes women’s suggestions for increasing access to Black and women-centered virtual health-related support and advocacy. Findings reveal that despite being young, Canadian-born and university educated, anti-Black racism and sexism permeates the health care encounters of all Black women; that Black women engage in emotionally taxing labour to have their health care needs met; and that Black women’s positive and challenging experiences inform their suggestions for support and advocacy online with other Black women. The women’s visions for health care support and advocacy expose an urgency for race and gender-specific online health care support and health care reform that acknowledges the legacies of Black patients and goes beyond structural competency.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: What is Mental Health and Why?

contributor:
Barry, Allen
Philosophy

subject:
mental health
philosophy of psychiatry
psychiatry
philosophy of medicine
mental disorder
mental illness
well-being
wellness
philosophy of science
philosophy of mental health
philosophy of well-being
philosophy of mental disorder

abstract:
The term “mental health” is everywhere, from government agendas, to educational reforms, to daily discourse. This is for good reason—hundreds of millions of people suffer from significant mental health concerns with a diagnosable mental disorder, let alone the fact that nearly all individuals have struggled with their mental health. The importance of mental health is uncontroversial, but the same cannot be said about its nature. Every practice related to mental health—which involves some of the most vulnerable people in the world—is committed to a conceptualization of mental health regardless of whether that practice is cognizant of this fact. Therefore, it is imperative to develop better answers to the questions of “what is mental health and why?” because conceptualizations of mental health systematically guide research, intervention, policy, and even how individuals strive to live their lives.
I argue that the answer to the question of “what is mental health?” is that mental health is a causal nexus of positive facts. That is, mental health is to be identified with a cluster of positive facts that regularly co-occur such as resilience, hedonistic mental states like joy, high cognitive functioning like concentration, and productivity. The answer to the question “why is mental health what it is?” is that the positive facts regularly appear together due to the causal relations between them, rather than arbitrarily. For instance, resilience causes high cognitive functioning, which in turn causes resilience, which causes productivity, which causes high cognitive functioning and joy, and so forth. This explains why mental health is what it is because the causal relations between positive facts “glue” them together, causing them to regularly co-occur, thereby making them a stable category of existence that factors into epistemic practices such as induction and prediction. However, given the state of our knowledge, further empirical evidence is needed to elucidate the exact positive facts that constitute the mental health causal nexus and thus answer what mental health is. I provide a novel methodology—the anchoring analysis—that involves studying the mechanisms of causal interactions between potential positive facts to determine which are the most causally important and thus should be considered constitutive facts of mental health. Elucidating the homeostatic mechanism of the kind mental health is a daunting task; however, we only complicate matters for ourselves if we simplify the complexity of mental health.

abstract: Thesis

abstract: Candidate in Philosophy


title: Characterizing the development of neuroimmune proteins in the human primary visual cortex

contributor:
Murphy, Kathryn M.
Neuroscience

subject:
Visual cortex
Human brain development
Neuroimmune proteins

abstract: Neuroimmune proteins are involved in a wide array of biological functions throughout brain development. Importantly, these molecular mechanisms regulate the activity-dependent sculpting of neural circuits during the critical period. Abnormal expression of these molecular mechanisms, especially in early development, is linked to the emergence of neurodevelopmental disorders. Despite having central roles in both normal and pathological conditions, very little is known about the lifespan expression of neuroimmune proteins in the human cortex. As studies exploring the relationship between inflammation and disease tend to rely on animal models, unpacking immune lifespan trajectories in the human brain will be essential for translational research. Furthermore, it will aid the development of timely and effective therapeutic interventions for neurodevelopmental disorders.  In my thesis, I characterize the development of 72 neuroimmune proteins in 30 postmortem tissue samples of the human primary visual cortex. These samples cover the lifespan from 20 days to 79 years. I compare the developmental profiles of these immune markers to those of well-studied classic neural proteins including glutamatergic, GABAergic and other synaptic plasticity-related markers. Using a data-driven approach, I found that the 72 neuroimmune proteins share approximately eight developmental patterns, most of which undulate across the lifespan. Furthermore, I used unsupervised hierarchical clustering to show that the development of neuroimmune proteins in the human visual cortex varies from that of classic neural proteins. These findings facilitate a deeper understanding of human cortical development through two classes of proteins involved in brain development and plasticity.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The human brain develops across the lifespan. This ability of the brain to change and adapt to the environment is called plasticity and it is essential for normal brain functions, such as processing visual information. Immune proteins play important roles in the visual cortex- the brain region responsible for visual information processing. They help establish brain circuits in early development and regulate ongoing neural processes important to brain plasticity. In my thesis, I measure the expression of neuroimmune proteins to unpack their developmental patterns in the human visual cortex. I found that these proteins have fluctuating levels across development, with many displaying heightened expression levels in early childhood. Additionally, I found eight common trajectory patterns that were shared between the proteins. These findings enable a better understanding of how regulators of human brain development mature.


title: Pain Observation, Empathy, and the Sensorimotor System: Behavioural and Neurophysiological Explorations

contributor:
Obhi, Sukhvinder
Psychology

subject:
Empathy
Pain Observation
Sensorimotor System
Reaction Time
Transcranial Magnetic Stimulation
Electroencephalography

abstract: Previous research has established that observing another in pain activates both affective and sensorimotor cortical activity that is also present during the first-hand experience of pain. Some researchers have taken this “mirroring” response as indicative of empathic processing. However, very little work has explored the downstream behavioral effects of empathic pain observation. The aim of this dissertation is to begin to fill this gap in the literature by exploring the relationship between empathic pain observation, overt motor behaviours, and sensorimotor activity. In chapters 2-4, I provide robust evidence that observing pain inflicted on another person leads to faster reaction time responses. This effect is shown to be temporally extended (by at least 500ms after pain observation), effector-general (affecting both finger and foot responses), influenced by top-down (i.e., instructions to explicitly empathize) but not bottom-up (i.e., the perceived level of pain) factors, and is not influenced by adaptive (approach/withdraw) behaviours. In chapter 5, I show that sensorimotor activity, measured via TMS-induced Motor Evoked Potentials, increases while observing another in pain regardless whether the observer is preparing to make an action vs. passively observing the stimuli. These results run counter to the literature, and I provide several explanations for why these results were found. Lastly, in chapter 6, I show that sensorimotor activity, measured via Mu and Beta suppression, also increases while observing another in pain regardless whether the observer is preparing to make an action vs. passively observing the stimuli. Interestingly, I do not find significant correlations between sensorimotor activity during pain observation and faster reaction times after pain observation. I embed these findings in relation to the wider social neuroscience of empathy literature and discuss several limitations and challenges in empirically measuring “empathy” as a psychological construct. Overall, this dissertation furthers our understanding of empathy for pain by highlighting the behavioural consequences of pain observation and its connection (or rather, lack thereof) to sensorimotor activity during pain observation.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Past research suggests that overlapping brain activity during the first-hand experience of pain and pain observation may be indicative of empathy. However, very little work has been done to explore how pain observation influences overt behaviours. This thesis investigates this issue by having participants complete a reaction time task while watching videos of needles stabbing a person’s hand. The findings reported in this thesis suggests that observing another in pain facilitates motor behaviours (i.e., faster reaction times); this facilitation extends 500ms after pain observation, affects both the hand and feet, is accentuated by instructing participants to explicitly empathize, and is not influenced by approach vs. withdraw movements. Brain activity in the motor system was also found to increase during pain observation. Overall, this thesis begins the discussion of how empathic pain observation influences explicit motor behaviours, and how such behaviours may be related to brain activity.