title: Exploring the role of physical activity for health, behaviour, and cognition in children with autism spectrum disorder

contributor:
Cairney, John
Kinesiology

abstract: Children with autism spectrum disorder (ASD) experience difficulties with social communication and social interactions, in addition to the presence of a restricted or repetitive range of behaviours and interests. On top of these core symptoms, children with ASD experience numerous health deficits, as well as impairments in executive functioning. It is possible that physical activity may be an effective intervention to collectively address these deficits and behavioural challenges. Yet, to-date, literature in this area has been limited. Therefore, this dissertation explored the role of physical activity and its relationship to pertinent health, behavioural, and cognitive variables in children with ASD. The first study in this dissertation demonstrated the feasibility and test-retest reliability of select fitness assessments in 7-12 year old children with ASD. Study two demonstrated the association between motor competence and adaptive behaviour. The third study built on this work by showing that motor competence and fitness are positively associated and that adaptive behaviour moderates this relationship. However, significant associations were not present between physical activity and health or behavioural variables. Lastly, study four demonstrated that an acute bout of exercise improves executive functions in children with ASD, with a circuit-based workout eliciting larger effects than aerobic exercise. Collectively, this dissertation provides a comprehensive examination of the role of physical activity for children with ASD. Specifically, these studies highlight the important relationships between motor competence and behaviour, irrespective of physical activity levels, while also highlighting the acute effect of physical activity on executive functions. These findings provide important foundational knowledge that can be built upon to improve the health and behavioural well-being of children with ASD through physical activity-based programs and interventions.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Children with autism spectrum disorder (ASD) experience a range of behavioural and physical health difficulties. Participation in physical activity may address these difficulties. However, there is limited evidence regarding the utility of physical activity for children with ASD. This dissertation explored the role of physical activity for this population through a set of studies designed to fill multiple gaps in the literature. First, the ability to use common fitness assessments for children with ASD was established. Next, this dissertation explored the importance of adaptive behaviour for the physical health of children with ASD, finding a positive relationship between motor competence and adaptive behaviour and that adaptive behaviour influences the relationship between motor competence and fitness. Lastly, this dissertation provided preliminary support for improved cognitive abilities following 20-minutes of exercise. Together, these findings highlight the role of physical activity in the health, behaviour, and cognitive functioning of children with ASD.


title: SYNTHESIS AND PROCESSING TECHNIQUES OF ADVANCED ELECTRODE MATERIALS FOR SUPERCAPACITOR APPLICATIONS

contributor:
Zhitomirsky, Igor
Materials Science and Engineering

subject: Supercapacitors, Energy Storage

abstract:
In a world that relies heavily on electricity and portable energy, the development of high performing energy storage devices is crucial. The ongoing push for energy storage devices such as batteries and supercapacitors to store more energy and charge/discharge faster has become exponentially stronger over the past decade. In order to meet the high demands, new materials and processing techniques must be developed.
A particle extraction through the liquid-liquid interface (PELLI) technique was used with a versatile extracting molecule, Octyl Gallate (OG). It was found that OG was able to extract a variety of materials including oxides, oxyhydroxides, and pure silver. The advantage of PELLI is that it circumvents the drying stage that occurs in many electrode synthesis techniques where metal oxides are synthesized in aqueous then dried and mixed with conductive additives dispersed in organic solvent. This drying stage causes a practically irreversible agglomeration which hinders mixing with conductive additives as well as reduces the surface area of the material, limiting its electrochemical performance. Using hydroxamates such as octanohydroxamic acid and bufexamac, a novel PELLI technique was developed based on the use of OHA as an extracting agent as well as a capping agent.
In addition, a preliminary investigation was started on advanced negative electrode material for supercapacitors. FeOOH-based electrodes exhibit high capacitance but low cyclic stability. Zn2+ ions were introduced during synthesis forming a doped Zn/FeOOH electrode which showed a significant increase in cyclic stability.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Graduate Mental Health and Wellness at McMaster University

contributor:
Robson, Karen
Sociology

subject:
mental health
graduate students
psychological distress
help seeking
stigma
mental health services
informal supports

abstract: Overview: Most of the mental health literature on students focuses on the experiences of undergraduates. In nearly all instances when graduate students are examined, their experiences are typically combined with those of undergraduates, despite graduate students representing a different group of students. Research questions: I asked what are correlates of psychological distress for graduate students? Which services or supports were students accessing? What were the characteristics of students who accessed help? Methods: This study used an online survey conducted during the spring and summer of 2018 that examined the mental health experiences of 389 graduate students at McMaster University. Results: I found that there was no consistent pattern for which groups of graduate students experienced distress markers: year of study did not predict which students would experience distress, and white and non-white students were equally likely to seek help. Students were more likely to seek a combination of formal and informal supports than select one type over the other. Finally, students who experienced stigma were equally likely to seek help as those who did not experience it. Contributions to literature: This thesis has highlighted some important findings about the graduate student population at McMaster University. By providing this information, I have helped extend the mental health literature to the graduate student group that is so often underrepresented or misrepresented.

abstract: Thesis

abstract: Master of Arts (MA)

abstract: This project investigated the mental health experiences of graduate students (i.e. Master’s degree or Ph.D. students) at McMaster University through an online survey. This survey was designed with the goal of determining the following: whether students were experiencing distress; what kinds of mental health services McMaster students use; and what some of the characteristics were for the students who seek help. I found that numerous students experienced overwhelming depression and overwhelming anxiety. A person’s racial background did not strongly influence whether they accessed services. Students were more likely to access a combination of supports between talking to a professional and talking to family, friends, or partners about mental health issues. Stereotypes or prejudices around mental health did not strongly influence which students accessed services. This thesis offers some important insights into the mental health experiences of graduate students, a topic which is often ignored in academia.


title: Bi-directional vulnerability of brain tumors to Wnt signaling

contributor:
Singh, Sheila K
Biochemistry and Biomedical Sciences

subject:
glioblastoma
medulloblastoma
Wnt
beta-catenin
CD133
Bmi1
brain tumor-initiating cell
cancer stem cell

abstract: Brain tumors represent a leading cause of cancer mortality, of which medulloblastoma (MB) and glioblastoma (GBM) represent the most frequent malignant pediatric and adult brain tumors, respectively. The identification of a rare clonal population of cells, termed cancer stem cells (CSCs) or brain tumor-initiating cells (BTICs), as having the ability to initiate, proliferate, and maintain tumor growth has offered a developmental framework for studying MB and GBM. Evidence in support of cell signaling programs carried forward from brain development into oncogenesis have provided opportunities for BTIC-directed therapies targeting the key BTIC property of self-renewal. Given that neural stem cells (NSCs) must maintain a relative balance between self-renewal and differentiation, brain tumorigenesis may be conceptualized as a disease of unregulated BTIC self-renewal. In this work, I aim to demonstrate the re-emergence of self-renewal genes that regulate NSCs in BTICs, use the Wnt pathway as a model by which these genes may be regulated in a context-specific manner, and identify clinically tractable therapies directed at the overall BTIC self-renewal signaling machinery. Specifically, in Chapter 2, I describe the presence of a shared signaling program between NSCs and MB BTICs consisting of Bmi1 and FoxG1. In Chapter 3, I provide evidence in support of a context-specific tumor suppressive function for activated Wnt/β-catenin signaling in MB. Lastly, in Chapter 4, I demonstrate a CD133-AKT-Wnt signaling axis in which CD133 functions as a putative cell surface receptor for AKT-dependent Wnt activation in GBM. Overall, the body of this thesis offers a mechanistic model by which BTICs may be regulated and targeted to impair tumor growth and improve overall survivorship in childhood MB and adult GBM.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Three Essays on Voluntary Disclosure of Performance Metrics in Marketing Channels

contributor:
Kacker, Manish
Business Administration

subject:
Marketing Channels
Signaling
Retailing
Panel Data
Financial Performance Representations
Voluntary Information Disclosure
Screening
Franchising
Information Asymmetry
B2B Contractual Relationship

abstract:
Research on Voluntary Information Disclosure (VID) has been of interest in several disciplines including, but not limited to, entrepreneurship, accounting, finance, law, and marketing. Although there has been extensive research on VID aimed at financial market investors, scant research in marketing exists on VID targeted at prospective business partners that can influence firm future performance significantly. Financial and marketing disclosures have been advocated for by investors and public policymakers as they mitigate the adverse selection problems between the firm and its stakeholders (e.g., investors, customers, and prospective channel partners). Managers are, however somewhat skeptical about its outcomes because of the cost of disclosures (i.e., ex-ante costs of collecting, processing and disseminating the information, ex-post costs of conflicts and litigations, competitive position and proprietary costs). My dissertation consists of three essays on voluntary disclosure of performance metrics in marketing channels and aims to enhance our understanding of the antecedents and consequences of such VIDs.
The first essay examines the antecedents of ex-ante VID for standardized contracts in marketing channels. Prior literature in accounting, entrepreneurship, and marketing has investigated drivers of information disclosures to analysts, investors, and customers. Nonetheless, this study bridges the gap in examining why some firms disclose information to prospective channel partners when it cost them to do so and makes the firms vulnerable to competitors. If the disclosure is a signal of quality, we are also interested in knowing whether it is a substitute for other signals of quality or a complement. I draw on signaling and institutional theories to develop a theoretical framework and empirically test it through econometric analyses of multi-sector panel data for the U.S. franchising industry. The results suggest that firms (e.g., franchisors) make such disclosures to prospective business partners (e.g., franchisees) in order to signal profitability of partnering, to attract financial and managerial resources, and develop their entrepreneurial networks. This study contributes to signaling theory literature by investigating organizational quality signaling, providing empirical evidence for drivers of multiple signaling and shedding light on the conflicting views on substitutability or complementarity of multiple quality signals. The study has implications for managers who wish to attract potential business partners through signaling profitability of their business. Furthermore, there are some insights for regulators on the debate on making voluntary disclosures mandatory.
The second essay examines the performance consequences of i) signaling through ex-ante voluntary disclosure of performance metrics and ii) screening through selection standards, in the formation stage of new partnerships in marketing channels. It is essential for many entrepreneurial business networks to expand their channel by attracting business partners while still preventing low-quality partners from joining the network. However, information asymmetry between the two parties introduces a double-sided adverse selection problem to the relationship. In other words, the heterogeneous quality - the ability to perform the job - of each party (i.e., the focal firm or the prospective partner) is unknown to the other party. To date, most of the empirical studies have addressed the issue from only one side, either from the perspective of the buyer or the supplier, and have assumed that the other side is open to the relationship. However, in a selective inter-firm relationship that both parties have the option to select the other party, adverse selection problems should be resolved for both of them to enhance the performance of the partnership. To bridge this gap in the literature (i.e., to mitigate double-sided adverse selection problems), I propose a novel framework based on signaling and transaction cost theories. This study suggests and empirically examines a complementary effect of the simultaneous use of signaling and screening on the firm performance. I integrate secondary data from various sources to shape a unique multi-sector panel data set that allows for assessment of the effects of these predictors on firm performance over time through a rigorous econometric model. Contrary to some claims in the extant literature, the results demonstrate that rigorous screening process hurts the firm performance unless it is combined with a proper quality signaling mechanism.  This study contributes to the B2B marketing literature and provides implications for practitioners by shedding light on the performance implications of channel governance mechanisms such as signaling and screening. Further, it provides empirical support for the effects of B2B marketing strategies on firm sales revenue growth.
The third essay looks closely into the voluntary disclosure of performance metrics. In the previous studies, the decision to disclose is operationalized as a binary variable of whether a firm discloses or not. In the absence of comprehensive regulation, disclosure strategies are subject to significant variation amongst firms, but can also vary over time within an individual firm. Through a content analysis of disclosure documents and scrutiny of the different components that comprise them, I explore the impact of disclosure content on firm performance. This study attempts to reconcile conflicting views of managers, investors, analysts, and regulators. On the one hand, VID should positively impact firm performance through mitigating information asymmetry. On the other hand, skeptical managers make the argument that VID negatively impacts a firm’s performance through costs of preparation, dissemination, potential litigation, and competition. Using a sample of publicly traded restaurant chains in the U.S., I empirically assess firm performance as a function of the disclosure strategy and its interactions with the firm’s characteristics and governance mechanisms. I collect independent variables from the firms’ disclosures through content analysis of public documents and obtain performance metrics of the firms in the stock market from Compustat. This study provides a novel context within which to investigate whether and how financial markets look at the firm’s disclosure behavior in dealing with its prospective channel partners, and it contributes to marketing-finance interface literature.
My dissertation is positioned in the marketing strategy-entrepreneurship interface domain and is a multi-faceted study that looks at the phenomenon of VID from different angles and provides implications for several stakeholders.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Distribution channel strategy has a long-term effect on firm performance, is associated with considerable irreversible costs, and can constitute a sustainable asset and competitive advantage for firms. Information asymmetry among the distribution channel members has been known as the basis of opportunistic actions in such exchange relationships. My dissertation research investigates drivers and consequences of information disclosure strategies and is focused on the firms’ voluntary disclosure of performance metrics at the inter-firm relationship formation stage of developing marketing channels.
This dissertation consists of three inter-related essays. In the first one, I study drivers of voluntary information disclosures to prospective channel partners. Then, I investigate the performance consequences of such disclosures and their interactions with channel governance mechanisms such as screening, in the second study. Since firms are heterogeneous in the content of their disclosures, in the third study, I conduct a content analysis of the firm’s disclosures to understand its influence on firm performance.
Based on Organizational Economics theories and Institutional Theory, I develop my theoretical frameworks and test them empirically using archival data. The empirical context for my work is the franchising industry because it is the most common type of partner-based retail system and is a significant component of the US economy as well as other developed countries and emerging economies.
The research findings offer both theoretical and practical implications for researchers and practitioners and contribute to the literatures on signaling and transaction cost theories as well as information disclosure and franchising.


title: Cobalt Germanide Contacts: Growth Reaction, Phases, and Electrical Properties

title: Cobalt Germanide Contacts

contributor:
Haddara, Yaser
Electrical and Computer Engineering

subject: cobalt germanide, germanium, electric contact, cobalt germanide phases, fermi level pinning, Schottky barrier height

abstract: This thesis is a sandwich thesis composed of three papers that are published in refereed journals or conferences. The first paper is a systematic experimental study conducted to identify the first phase to form during cobalt germanidation. Hexagonal β-Co5Ge3 was the first phase to form at temperatures as low as 227°C followed by monoclinic CoGe as the second phase at the same temperature. We also report for the first time that both phases that formed were highly ordered partial epitaxial crystal orientations suggesting that both of those low-temperature phases could potentially serve as high quality contacts for germanium based devices with a very low thermal budget which is advantageous for the process design. Those results contributed to a better understanding of cobalt germanidation leading to the first multiphase technology computer aided design model presented in the second paper. This kinetic model for cobalt germanide growth can predict the resulting phase based on anneal time, temperature, and ambient. The model has been calibrated to experimental results. This predictive model can help in the design of cobalt germanide contacts with low resistance and can serve as a general modeling framework for multiphase solid state reaction binary systems. A comprehensive survey of the experimental results for formation of cobalt germanides is discussed and the data are reconciled in the third paper. Factors affecting the resulting phases and their quality are identified and some optimum choices for the experimental parameters are pointed based on the survey. The role of germanium crystal orientation in ohmic and Schottky properties of the contact is analyzed. Fermi level pinning plays a role mainly on metal/(100) n-type Ge interfaces and its role is minimal on p-type Ge and other crystalline orientations. Schottky Barrier Heights for cobalt germanide contacts reported in the literature are surveyed. Crystalline cobalt germanides, forming when Co is deposited at high temperatures, are expected to have lower interface resistivities compared to those reported. The work is important because contact resistance has become one of the most important factors in advanced complementary metal oxide semiconductor (CMOS) technology and advanced devices already include germanium (Ge) in the source/drain regions of devices. It is also important because heating at the interface due to contact resistance is one of the key challenges in power devices and cobalt germanide can be used both for Si and Ge based devices as well as for gallium nitride (GaN) devices. The latter application is possible because cobalt germanide is lattice-matched to GaN.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: The main goal of this thesis is to create predictive empirical, mathematical, and physical models to help the designer of the semiconductor process technology to design high quality electric contacts, namely cobalt germanides, to their semiconductor devices, germanium based. The choice of cobalt germanides is motivated by their expected superior quality given the possibility of growing them in crystalline form. We settled a theoretical and experimental controversy regarding the first phase to form by conducting experiments demonstrating that low-temperature forming cobalt germanide phases are highly ordered and could serve as high quality contacts. A predictive physical based mathematical model was developed to assist the designer in obtaining the desired cobalt germanide phase for its needed electrical properties by design. Factors affecting the quality of the germanide were identified based on an extensive survey and the optimum choices for the parameters to obtain high quality contact were pointed.


title: Optical Spectroscopy and Visual Assessment for Grading Erythema

contributor: Radiation Sciences (Medical Physics/Radiation Biology)

subject: Erythema, optical spectroscopy, radiation therapy, skin assessment, hyperspectral imaging, diffuse reflectance

abstract:
ABSTRACT
Erythema is a well-documented early indicator of tissue injury resulting from exposure to high doses of ionizing radiation. Close monitoring of radiation-induced injury to the skin can help identify opportunities for early interventions that may prevent or reduce more severe reactions. The gold standard for monitoring erythema is visual assessment (VA) by a trained clinician. This method has been criticized for being subjective and designed with very broad categorical descriptors.
This work introduces a newly developed VA scale called the clinician erythema assessment for radiation therapy (CEA-RT).The reliability and accuracy of the CEA-RT scale was tested among 20 radiation therapists who trained to use the scale on digital images of radiation induced erythema. CEA-RT demonstrated to be highly reliable when therapist’s grades were compared to themselves, but moderately accurate when therapist’s grades were compared to each. A follow-up study with real patients and fewer but more extensively trained raters was proposed to demonstrate the grading accuracy of the CEA-RT scale.
As an alternatively to VA, spectroscopy has the ability to monitor erythema by measuring the change in concentration of hemoglobin (Hb) within the vessels of the skin. These changes in Hb concentration are linked to the degree of erythema. This thesis also investigated the use of hyperspectral imaging (HSI) and diffuse reflectance spectroscopy (DRS) as potential technological alternatives for evaluating erythema.
In a second study, Erythema was artificially induced in 3 volunteers who participated in a pilot study designed to assess the ability of an experimental HSI camera to detect skin changes.  The data extracted from the hyperspectral images was found to effectively yield spectral profiles and Dawson’s erythema indices (EI) in agreement with the erythema grades assigned by the gold standard therefore showing HSI to be a viable alternative of assessing erythema.
Finally, a third study compared DRS measurements to VA using the CEA-RT scale. The DRS system was previously used to measure in vivo erythema but did not compare spectral measurements to an accepted standard. Ten patient volunteers received daily DRS and VA evaluations for a period of 2 to 4 weeks. The results demonstrated that the Dawson’s EI calculated from the spectral data correlated well with the gold standard (VA grades) and that DRS is able to detect changes in the skin throughout the course of radiation treatments.

abstract: Thesis

abstract: Master of Science (MSc)


title: Assessing Health Risk Areas and Activity-Travel Behaviour of Carer-Employees

contributor:
Williams, Allison
Geography and Earth Sciences

subject:
carer-employees
mixed-methods
assisted-transport
mobility dependence
care-recipients

abstract:
Carer-employees are defined as individuals who provide unpaid care to a disabled / ill dependent person(s) while working full-time in the paid labour force. In Canada, there are 6.1 million carer-employees, many of which are experiencing work-life balance struggles, which may result in ill-health. To minimize negative impacts, there is interest in developing caregiver-friendly workplace policies (CFWPs) as an intervention strategy to improve CEs’ work-life balance. However, the effectiveness of CFWPs are still in their infancy and often only focus on the work dimension.
One of the most critical dimensions that have not yet been assessed is the activity-travel behaviour of carer-employees, which is largely impacted by the assisted-transport demands of their care-recipient. To contribute to filling in this gap, this dissertation addresses the following objectives: 1) develop an activity-travel behaviour profile of carer-employees using sociodemographic and caregiving characteristics; 2) identify spatial locations with potentially high assisted-transport demand while suggesting new areas to improve mobility independence of care-recipients, and; 3) create and apply a mixed-methods framework that classifies the actual activity-travel behaviour of carer-employees. The purposes of all three objectives are to: contribute to closing the literature gap; visually inform decision-makers and health planners, and; efficiently develop caregiver-friendly transport policies (CFTPs).
Highlighted findings show that carer-employees conducting assisted-transport have lower income and are more likely to be tired and overwhelmed than those not performing the transport task (Objective 1). In Hamilton metropolitan area, 38% of the older adult population are not within immediate reach to a vital service, and another 15% are located in potentially high
assisted-transport demand areas. Suggested areas for service implementation would improve access for older adults by 18% (Objective 2). Lastly, the framework has classified and ranked three types of activity-travel behaviours (Objective 3). All of these findings have led to the discussion of a multi-pronged implementation strategy for uptake of CFTPs.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Identifying Novel Regulatory Inputs Governing Salmonella Enterica Niche-Specific Gene Expression

title: Niche Specific Gene Regulation in Salmonella Enterica

contributor:
Coombes, Brian
Biochemistry and Biomedical Sciences

subject:
Salmonella
Regulatory Evolution
Bacterial pathogenesis
SsrA-SsrB

abstract: Salmonella enterica is an enteric pathogen with a broad host tropism that can cause disease ranging from self-limited gastroenteritis to enteric fever. The evolution of S. enterica as a pathogen is driven by the horizontal acquisition of genes that promote virulence and survival within host immune cells, as well as the coordinated regulation of these and ancestral genes by two-component systems (TCS). TCS integrate environmental cues with the transcriptional reprogramming of bacteria, and in the case of Salmonella, result in niche-specific gene expression in response to anti-bacterial cues produced by the host. The TCS SsrA-SsrB in S. enterica is considered the master regulator for intracellular virulence, where SsrA is a sensor kinase that triggers the activation of the DNA binding protein SsrB. The full suite of genes regulated by SsrB in S. enterica, as well as the cues that activate this TCS, have not been fully characterized. Here, we demonstrated that horizontally acquired and ancestral genes in the S. enterica genome have evolved to be regulated by SsrB, and the repression of a set of ancestral genes involved in flagellar motility promotes evasion of the host immune system. Additionally, we identified the production of reactive oxygen species (ROS) by host immune cells as a signal that can activate a cluster of genes regulated by the SsrA-SsrB TCS, likely mediated by SsrA sensing of these ROS. Together, these results expand our understanding of the complex interplay between the pathogen S. enterica and the host that results in bacterial infections.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Salmonella enterica (S. enterica) is a species of bacteria that can cause food poisoning in various animals, including humans, through consumption of contaminated food and water. During an infection, host cells activate numerous defense mechanisms to prevent disease. S. enterica has evolved to turn specific genes on or off in response, resulting in modifications to bacterial and host cell behaviour that promote infection. The timing of these genetic changes is controlled by proteins that can sense specific environmental signals and adjust gene expression accordingly. The specific signals sensed by S. enterica that allow for adaptive gene expression within the host, and the types of genes that are regulated to promote survival, have not been fully identified. Here, we show that S. enterica evolved to repress genes involved in flagellar motility to hide from the host immune response. We further demonstrate that S. enterica can sense anti-bacterial molecules produced by the host, called reactive oxygen species, to trigger specific changes in gene expression. Together, this work reveals novel aspects for the molecular basis of Salmonella enterica pathogenesis.


title: Using machine learning to predict long non-coding RNAs and exploring their evolutionary patterns and prevalence in plant transcriptomes

contributor:
Weretilnyk, Elizabeth
Golding, Brian
Biology

subject:
lncRNA
machine learning
phylogenetic signal
transcriptomes
extremophile
Eutrema salsugineum
plants

abstract:
Long non-protein coding RNAs (lncRNAs) represent a diverse and enigmatic classification of RNA. With roles associated with development and stress responses, these non-coding gene regulators are essential, and yet remain understudied in plants. Thus far, of just over 430 experimentally validated lncRNAs, only 13 are derived from plant systems and many of which do not meet the classic criteria of the RNA class. Without a solid definition of what makes a lncRNA, and few empirically validated transcripts, methods currently available for prediction fall short. To address this deficiency in lncRNA research, we constructed and applied a machine learning-based lncRNA prediction protocol that does not impose predefined rules, and utilises only experimentally confirmed lncRNAs in its training datasets.
Through model evaluation, we found that our novel lncRNA prediction tool had an estimated accuracy of over 96%. In a study that predicted lncRNAs from transcriptomes of evolutionary diverse plant species, we determined that molecular features of lncRNAs display different phylogenetic signal patterns compared to protein-coding genes. Additionally, our analyses suggested that stress-resistant species express fewer lncRNAs than more stress sensitive species. To expand on these results, we used the prediction tool in concert with a transcriptomic study of two natural accessions of the drought tolerant species Eutrema salsugineum. Previously reported to show little physiological differences in a first drought, but differ significantly in a second, we instead demonstrated that the two ecotypes displayed vastly different transcriptomic responses, including the expression of lncRNAs, to a first and second drought treatment. In conclusion, the prediction tool can be applied to studies to further our knowledge of lncRNA evolution and as an additional tool in classic transcriptomic studies. The suggested importance of lncRNAs in drought resistance, and evidence of expression in two natural E. salsugineum accessions, merits further studies on the molecular and evolutionary mechanisms of these putatively regulatory transcripts.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Managing Assurance Cases in Model Based Software Systems

contributor:
Maibaum, Tom
Chechik, Marsha
Computing and Software

subject:
Safety Assurance
Model Based Systems
Software
Model Driven Engineering
Automotive Safety

abstract:
Software has emerged as a significant part of many domains, including financial service platforms, social networks, medical devices and vehicle control. In critical domains, standards organizations have responded to this by creating regulations to address issues such as safety, security and privacy. In this context, compliance of software with standards has emerged as a key issue. For companies, compliance is a complex and costly goal to achieve and is often accomplished by producing so-called assurance cases, which demonstrate that the system indeed satisfies the property imposed by a standard (e.g., safety, security, privacy) by linking evidence to support claims made about the system. However, as systems undergo evolution for a variety of reasons, including fixing bugs, adding functionality or improving system quality, maintaining assurance cases multiplies the effort. Increasingly, models and model-driven engineering are being used as a means to facilitate communication and collaboration between the stakeholders in the compliance value chain and, further, to introduce automation into regulatory compliance tasks. A complexity problem also exists with the proliferation of software models in model-based software development, and the field of Model Management has emerged to address this challenge. Model Management focuses on a high-level view in which entire models and their relationships (i.e., mappings between models) can be manipulated using specialized operators to achieve useful outcomes. In this thesis, we exploit this connection
between model driven engineering and regulatory compliance, and explore how to use Model Management techniques to address software compliance management issues, focusing on assurance case change impact assessment, evolution and reuse. We support the presented approach with tooling and a case study. Although the main contributions of this thesis are not domain specific, for validation, we ground our approaches in the automotive domain and the ISO 26262 standard for functional safety of road vehicles.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Noise and Robustness downstream of a morphogen gradient: Quantitative approach by imaging transcription dynamics in living embryos

contributor:
Fradin, Cecile
Dostatni, Nathalie
Biochemistry

subject:
embryonic development
bicoid
drosphila melanogaster
hunchback
gene networks
quantitative live imaging

abstract: This thesis was done in collaboration with Sorbonne University as part of a double degree Cotutelle.

abstract:
During development, cell differentiation frequently occurs upon signaling from concentration or activity gradients of molecules called morphogens. These molecules control in a dose-dependent manner the expression of sets of target genes that determine cell identity. A simple paradigm to study morphogens is the Bicoid gradient, which determines antero-posterior patterning in fruit fly embryos. The Bicoid transcription factor allows the rapid step-like expression of its major target gene hunchback, expressed only in the anterior half of the embryo. The general goal of my thesis was to understand how the information contained in the Bicoid morphogen gradient is rapidly interpreted to provide the precise expression pattern of its target.
Using the MS2 system to fluorescently tag specific RNA in living embryos, we were able to show that the ongoing transcription process at the hunchback promoter is bursty and likely functions according to a two-state model. At each nuclear interphase, transcription is first observed in the anterior and it rapidly spreads towards the posterior, as expected for a Bicoid dose-dependent activation process. Surprisingly, it takes only 3 minutes from the first hints of transcription at the anterior to reach steady state with the setting of a sharp expression border in the middle of the embryo. Using modeling taking into account this very fast dynamics, we show that the presence of only 6 Bicoid binding sites (known number of sites in the hunchback promoter) in the promoter, is not sufficient to explain the establishment of a sharp expression border in such a short time. Thus, either more Bicoid binding sites or inputs from other transcription factors could help reconcile the model to the data. To better understand the role of transcription factors other than Bicoid in this process, I used a two-pronged strategy involving synthetic MS2 reporters combined with the analysis of the hunchback MS2 reporter in various mutant backgrounds. I show that the pioneer factor Zelda and the Hunchback protein itself are also critical for hunchback expression, maternal Hunchback acting at nuclear cycle 11-12, while zygotic Hunchback is acting later at nuclear cycle 13-14. The synthetic reporter approach indicate that in contrast to Hunchback and Caudal, Bicoid is able to activate transcription on its own when bound to the promoter. However, the presence of 6 Bicoid binding sites only leads to stochastic activation of the target loci. Interestingly, the binding of Hunchback to the Bicoid-dependent promoter reduces this stochasticity while Caudal might act as a posterior repressor gradient. Confronting these experimental data to theoretical models is ongoing and should allow to better understand the role of transcription factors, other than Bicoid, in hunchback expression at the mechanistic level.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Have you ever wondered how a single cell can become a full grown organism? Well it starts when an egg and sperm fuse together. As time passes this single cell divides over and over again until an organism is formed. During this developmental process, somehow the cells know exactly where they are and what they need to become so that they form the organism. However, we don’t fully understand this process and this is what we hope to answer with our research: How do the cells know where they are and what they need to become during development?
We study this process in the fruit fly. Although fruit flies might not look a lot like us, during early embryonic development we are quite similar, so we can try to answer these questions in fruit flies and what we find might be relevant to other organisms like us.
During development, the first element that an embryo needs to know is the orientation of its body, where the head and tail, the left and right and the back and front of the body will be. We concentrate on studying how the head to tail axis, which we call the anterior-posterior axis, is formed.
To know where the head is going to be, the embryo releases proteins called morphogens that broadcast instructions to other genes so that cells know where they are and what they should become. We study a morphogen called Bicoid. Its concentration is high in the anterior, the region that will become the head of the embryo, and lower as you move towards the posterior where the tail will form. Bicoid activates a gene called hunchback, which ends up dividing the embryo in two large parts, the top and the bottom. However, Bicoid’s message fades away during each cell division and needs to be read again at the beginning of each new nuclear cycle. So how is the message read and how long does this process take?  This last question is particularly critical during the period of very fast cell division.
My thesis tries to answer this question. We found out that it takes 3 minutes for a nuclei to read the Bicoid concentration, activate hunchback and express it correctly. However, in contrast to what was believed before, or namely, that only Bicoid was involved in this process, we found out that other players are involved in helping relay this message. This way hunchback can accurately divide the body in two parts exactly in the middle and without mistake in such a short period of time.


title: On the Use of Light-Emitting Freewheeling/Blocking Diodes for Optical Wireless Communications

contributor:
Hranilovic, Steve
Narimani, Mehdi
Electrical and Computer Engineering

subject: VLC, OWC, visible, light, communications, optical, wireless, switched-mode, power, supply, SMPS, LED, Light-Emitting, Diode, IoT, Internet of Things, LEFD, LEBD, lighting

abstract: Integration of optical wireless communications (OWC) within switched-mode power supplies (SMPS)

abstract:
Although visible light communication(VLC) systems can provide high density links
for use with IoT devices, an energy efficient, high rate method of designing a VLC
transmitter is still unclear. Present designs for transmitters such as the bias-T, designs
with switch manipulation, and interleaved converters are not commercially viable due
to costly and complex designs that sacrifice energy efficiency for data rate. A design
allowing for efficient, high rate communications, while maintaining a low cost would
allow for widespread adoption of this technology.
In this thesis, a novel approach of integrating power converters and VLC systems is
explored by replacing commutating diodes with LEDs. By leveraging switched-mode
power supply(SMPS) structures, the power dissipated within the converter may be
harnessed and used for communications. The result is a simple and energy efficient
solution capable of high rate links.
Simulation and experimental results demonstrate buck and boost SMPS topologies
that simultaneously increase energy efficiency and provide communications at SMPS
switching rate without increasing component count.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Assessing Remote Sensing Approaches to Map Invasive Phragmites australis at Multiple Spatial Scales

contributor:
Chow-Fraser, Patricia
Biology

subject:
remote sensing
Phragmites
wetlands
ecology
Great Lakes
GIS

abstract:
Phragmites australis (Cav.) Trin. ex Steud., the invasive common reed, is a perennial grass with a cosmopolitan distribution. Unlike the native subspecies (Phragmites australis subsp. americanus) in North America, this invasive haplotype is an aggressive competitor and has firmly established itself throughout the Great Lakes basin by dominating wetlands and wet habitat, forcing out native plants and creating monocultures of little use to native fauna. Growing clonally and from seed, invasive Phragmites can quickly dominate wet areas throughout North America. It has also become a prominent feature in roadside habitats, where native plants are subject to increased disturbance under which invasive Phragmites will thrive competitively. In order to effectively manage this aggressive invader, we must be able to accurately map its distribution at multiple spatial scales, understand its invasion ecology, and determine efficacy of current removal efforts.
	In this thesis, I evaluated multiple remote sensing methods to determine the extent of invasive Phragmites.  The basin-wide wetland mapping project based on satellite image data was a collaborative effort between U.S. and Canadian scientists to document the current and potential distribution of invasive Phragmites throughout 10-km of the shoreline of the Great Lakes, including all coastal marshes.  To elucidate its distribution through road networks, I used provincial orthophotography databases to map changes in the distribution of Phragmites in road corridors between 2006 and 2010. Based on these data, I created a conceptual model to show the relationships among the main factors that govern the establishment of invasive Phragmites in roadsides within Ontario.  These factors included habitat quality, habitat availability, and propagule dispersal.  I also showed how unmanned aerial vehicles can be used with very high accuracy to map the distribution of very small stands of Phragmites at the beginning of an invasion, and to determine short-term changes in habitat availability in smaller wetlands.  Using various remote sensing approaches, I was able to determine the efficacy of treatment programs implemented by provincial agencies on roadway corridors at the scale of the entire southwestern, southcentral and central regions of Ontario.  This is the first quantitative evidence of invasive Phragmites removal along roads and one of the largest spatial and temporal time scales used to evaluate these processes. Finally, I synthesized the capabilities and limitations of these remote sensing methods to create an evaluative framework that outlines how to best map invasive Phragmites across varying landscapes. This research integrates geography and biology to create novel mapping techniques for invasive Phragmites and has furthered our understanding of this aggressive plant and how its invasion can be controlled.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Invasive common reed, Phragmites australis subsp. australis, is one of the most aggressive and problematic invasive species in North America. This species rapidly expanded in the late 1900s and now occupies large patches of our critical wetland habitats as monocultures, especially in the northeastern states and the Great Lakes basin. My thesis presents new methods to identify where invasive common reed is present at a landscape level so that it can be targeted for large-scale control and removal. With colleagues in Michigan we created the first basin-wide map of invasive common reed for the Great Lakes region using satellite image data. Within Ontario, I used imagery from satellites and planes to determine the extent of invasive common reed along our road networks. At a site-specific scale, I used drones or unmanned aerial vehicles to map a protected wetland with high precision and accuracy. I used many of these approaches in combination to determine how effective current invasive common reed removal efforts are along roadway corridors. I compare all of these mapping processes and techniques to showcase the strengths and weaknesses of each approach and to help managers decide which approach is most suitable for their unique case. With all of these data, I have created new mapping techniques that can show the rapid spread of invasive common reed and how effective current management plans have been in combatting this aggressive invader.


title: PARTIES AT THE WATER’S EDGE: CANADA’S POLITICAL PARTIES AND THE FOREIGN POLICY DOMAIN

contributor:
Flynn, Greg
Political Science

subject:
foreign policy
issue ownership
campaign promises
election manifestos

abstract: Foreign policy is the nexus between domestic and international political systems. Studies in Canada have so far produced mixed findings related to the role of political parties in foreign policy. Drawing from campaign promise, issue ownership and foreign policy decision-making literature, this dissertation investigates whether there is a foreign policy domain consistently dominated by a particular political party in the Canadian context. Part I uses data from the Comparative Manifesto Project (CMP) combined with manually coded foreign policy promises to determine the content and scope of foreign policy-related election promises in Canada. Part II follows the well-established pledge approach to measure promise fulfilment of foreign policy promises of Canadian governing parties following elections. This dissertation not only seeks to determine whether parties matter in the context of foreign policy, but also whether one party consistently “owns” the foreign policy domain or specific foreign policy issues. Findings from this research will fill an existing gap in the literature related to policy-specific promise fulfillment in Canada and will bridge existing theoretical assumptions related to political party behaviour and foreign policy decision-making.

abstract: Thesis

abstract: Master of Arts (MA)


title: Microstructural Evolution and Mechanical Properties of a Medium Manganese Transformation Induced Plasticity Third Generation Advanced High Strength Steel

contributor:
McDermid, Joseph
Materials Engineering

abstract:
Third-generation advanced high strength steels (3G AHSS) are being developed to facilitate vehicle lightweighting in order to improve their fuel efficiency without compromising passenger safety. This thesis will examine the development of microstructure and mechanical properties of a prototype medium Mn TRansformation- and TWinning-Induced Plasticity (TRIP/TWIP) 3G-AHSS with a composition of 0.15C-6Mn-1Si-1Al. Heat treatments consisting of intercritical annealing and overageing stages compatible with the continuous galvanizing process were investigated in terms of their effects on the microstructure and the mechanical properties from the as-received, tempered martensite (TM) microstructure and a fully martensitic (M) starting microstructure. Samples intercritically annealed from the M starting microstructure exhibited a lamellar morphology of retained austenite/martensite laths and faster austenite reversion kinetics. Samples intercritically annealed from the TM starting microstructure exhibited a globular/equiaxed morphology and slower austenite reversion kinetics. Though they had high (~0.3 volume fraction) initial amounts of retained austenite, samples intercritically annealed from the TM starting microstructure did not meet the 3G-AHSS mechanical property envelope due to insufficient mechanical stability of retained austenite and its resulting transformation to α’-martensite at low strains. These samples did, however, show impressive UTS values (up to 1600 MPa), despite lower tensile elongation values. Despite having lower fractions of retained austenite in the as-annealed microstructure, the samples intercritically annealed from the M starting microstructure achieved combinations of strength and tensile elongations that met the 3G-AHSS mechanical property envelope. In particular, the M-690-120 sample nearly met the specific U.S. DOE mechanical property target of 1200 MPa UTS and 30% TE exhibiting 1150 MPa UTS and 29% TE. TEM results from strained and fractured tensile samples showed that samples intercritically annealed from the TM and M starting microstructures both exhibited deformation twinning in the retained austenite, which suggests that the combination of the TRIP and TWIP effect resulted in an excellent combination of strength and tensile elongation.
	Based on experimental results, this work demonstrates that medium Mn TRIP/TWIP alloys are capable of achieving the target 3G-AHSS mechanical properties employing heat treatments compatible with the continuous galvanizing process.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Development of A Microfluidic-Based Artificial Placenta Type Neonatal Lung Assist Device for Preterm Neonates

contributor:
Selvaganapathy, P. Ravi
Biomedical Engineering

subject:
Artificial Lung
Artificial Placenta
Microfluidic
Oxygenator

abstract: Among all organs, lungs are the last ones to grow and develop fully. As a result, extreme premature neonates may suffer from respiratory failure due to their immature lungs and will require respiratory support in the form of mechanical ventilation or extracorporeal membrane oxygenation (ECMO). In addition, extreme prematurity is recognized as the primary cause of neonatal morbidity and mortality. The conventional standard of care for respiratory support of preterm neonates with respiratory failure are invasive and may lead to long-term morbidities and complications. Hence, a non-invasive respiratory support technique named “Artificial Placenta” has been developed to address the issues and challenges associated with the current technologies. An artificial placenta type device is one designed to provide required oxygenation in room air via non-invasive access to the umbilical vessels without the need of any external pump. In this thesis, microfluidic and microfabrication technologies have been employed in the development of a pumpless neonatal lung assist device (LAD) for preterm neonates in two approaches: 1) design and develop novel microfabrication techniques to fabricate advanced microfluidic blood oxygenators with high gas exchange capacity and reduced form factor and 2) design and construct several modular LADs based on the oxygenators that were developed to fulfill the required gas transfer needs for these babies. The new microfluidic blood oxygenators with double-sided gas transfer channels were found to enhance oxygenation up to 343 % in room air and be easily scaled-up to achieve higher gas exchange capacities without a noticeable increase in priming volume. Furthermore, this microfabrication method has been utilized to make the largest all PDMS ultra-thin double-sided blood oxygenator with higher gas exchange capabilities. Also, a novel composite material made of PDMS and PTFE was introduced that conferred high flexibility to the oxygenator to decrease the form factor of such devices. This device was one of the first microfluidic blood oxygenators with enough flexibility to be deformed, bent, or rolled without limitation and losing its functionality. In order to satisfy the gas transfer need of these preterm neonates, few microfluidic-based modular LADs were constructed to support different birth weights up to 2 kg. The main design criteria for such a LAD in this research was low pressure drops (capable of being operated by a baby’s heart), an oxygen transfer of 1.3 – 1.9 mL min-1 kg-1 of body weight (or an increase in oxygen saturation level from ~ 75 % to ~ 100 % and ideally in room air), and low priming volume (less than 10 % of the total blood volume of a baby). These LADs first were evaluated in vitro to measure their gas exchange capacities and those which could meet needed oxygenation would be tested in vivo. For the first time, it was shown that a pumpless microfluidic-based LAD could support a newborn piglet and provide adequate oxygenation in room air or the oxygen-rich environment. The application of these microfluidic blood oxygenators was not only limited to preterm neonates but also can be used to develop LADs for adult patients.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Slope Stability Analysis Using the Kinematic Element Method

contributor:
Stolle, Dieter
Civil Engineering

subject:
Kinematic Element Method
Slope Stability
Slope Stability Analysis
Numerical Modelling
Geotechnical Engineering
Geotechnical
Limit Equilibrium Method
LEM
KEM

abstract: Thesis regarding the application of the Kinematic Element Method to slope stability analysis in geotechnical engineering.

abstract: In this thesis, the effectiveness of the Kinematic Element Method (KEM), developed by Dr. Gussmann at the University of Stuttgart, was evaluated by comparing the solutions with the Limit Equilibrium Method (LEM), specifically the Morgenstern-Price method. The KEM was evaluated using a variety of problems, ranging from homogeneous slopes to retaining walls. The KEM was shown to predict similar potential failure mechanisms and values for the factor of safety (FS) as the Morgenstern-Price method. The FS were generally within the ±6% which is the range of variance for rigorous limit equilibrium methods. A simplified version of KEM (KEMv) was developed based on limit equilibrium formulations. In KEMv, an alternate iterative scheme to determine the FS is proposed, in which boundaries between elements are vertical. The KEMv provided similar values for the factor of safety and interelement forces as Gussmann’s KEM for vertical interelement boundaries given similar element locations. The KEM was assumed by Gussmann to be an upper bound solution. However, given the similarities in the solutions between KEM and KEMv, it may be a limit equilibrium method. The interelement forces from the KEM and KEMv were found to be sensitive to the location of the elements. Elements in the upper part of the slope often had small normal forces relative to shear forces, possibly being negative as well. Sensitivity analysis regarding the number of elements showed that a 5-element solution predicts the appropriate failure mechanism and provides a reasonably accurate FS. In a parametric study, slope geometry and soil properties were varied and comparisons were made between KEM and the Morgenstern-Price method. The KEMv displayed similar trends in factor of safety as the Morgenstern-Price method but predicted slightly larger values. The change in KEM critical slip surfaces with soil properties was consistent with trends predicted by Janbu’s dimensionless parameter.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: The stability of slopes is a challenging subject in geotechnical engineering. Geotechnical engineers are often interested in the factor of safety (FS), which is a quantitative measure of the stability of a slope. In this thesis, the effectiveness of the Kinematic Element Method (KEM) is evaluated by comparing its solutions to the Limit Equilibrium Method (LEM). The KEM was shown to predict similar potential failure mechanisms and values for the factor of safety. A simplified version of the KEM (KEMv) was developed based on LEM formulations. In KEMv, an alternate iterative scheme to determine the FS is proposed, in which the boundaries between elements are vertical. The KEMv provided similar values for the factor of safety and element forces as Gussmann’s KEM for vertical interelement boundaries. In a parametric study, KEM displayed similar trends in the change in FS and critical slip surface as the LEM.


title: THE POTENTIAL FOR MACHINE LEARNING IN MENTAL HEALTH POLICING: PREDICTING OUTCOMES OF MENTAL HEALTH RELATED CALLS FOR SERVICE

contributor:
Costa, Andrew
eHealth

subject: Police, Mental, Random Forests

abstract:
My objective was to predict outcomes following police interactions with PMIs, and compare the predictive accuracy of logistic regression models and Random Forests learning algorithms. Additionally I evaluated if predictive accuracy of Random Forests changed when applied to merged versus region-specific data. I conducted a retrospective cohort study of reports completed by police in 13 communities between 2015 and 2018. 13,058 reports were analyzed. Random Forests learning algorithms were compared against logistic regression models for predictive accuracy in a merged dataset (13 communities) and 3 regional datasets. Outcomes for prediction were high risk of harm to self, risk of harm to others, and risk of failure to care for self within 24 and 72 hours following police contact. Random Forests learning algorithms were trained on merged and regional datasets, and compared against merged and regional holdout datasets. Performance was compared by area under the curve. For Random Forests learning algorithms, confusion matrix statistics were calculated for each outcome and predictive utility was examined by calculating conditional probabilities.
Prediction accuracy was modest across all methods. Random Forests achieved better predictive accuracy than logistic regression. Random Forests accuracy varied between merged and regional holdout data. Sensitivity of Random Forests learning algorithms were moderate (74% average, 6 outcomes, merged holdout set). Specificity was low (53% average, 6 outcomes, merged holdout set). Conditional probabilities were modestly improved by the use of the Random Forests learning algorithm. The rareness of the target outcomes created a situation where even predictions with moderate likelihood ratios had only modest predictive value. Though the Random Forests learning algorithms did outperform the logistic regression learning algorithms, the clinical significance of those benefits were limited when conditional probabilities were calculated. These findings are limited to the outcomes considered, and may not apply to more common outcomes.

abstract: Thesis

abstract: Master of Health Sciences (MSc)

abstract: The study goal was to predict outcomes following police interactions with persons with mental illness (PMIs). Additionally we compare the predictive validity of logistic regression and Random Forests learning algorithms. Classification approaches were applied to outcomes following police interactions with PMIs, including: high risk of harm to self, high risk of harm to others, and high risk of failure to care for self within 24 hours and 72 hours of initial police contact. The study also sought to determine if the predictive accuracy of Random Forests was sensitive to the police service community. Variation in predictive accuracy was assessed between a merged data set (13 communities) and 3 community-specific data. The study found that the predictive accuracy of the classification approaches on outcomes was modest. Random Forests exhibited greater predictive validity than logistic regression. The performance of the Random Forests suggested that performance was not sensitive to police service context.


title: Differences in Urban Residential Property Maintenance by Tenure Type

contributor:
Harris, Richard
Geography and Earth Sciences

subject:
housing
absentee landlord
resident landlord
residential
Rochester
property maintenance
landlord
tenure
code violations
residential code
tenure type
Buffalo
Syracuse
residential property
slumlord
rental housing
tenant-landlord
urban housing
urban
neighbourhood
neighborhood
homeownership
homeowner
single family home

abstract: One of the key determinants of the “quality” of a neighbourhood is the extent to which owners maintain their properties. Much has been written about the impact of neighbourhood blight or the physically rejuvenating impact of gentrification. To better understand why some neighbourhoods are thriving, and others not, a critical variable that has seen little exploration is the type of tenure. This thesis, focused mostly on data from the City of Rochester NY, comparing absentee landlords, resident landlords and owner-occupiers, looking for differences in the level of maintenance of residential properties. Using a procedure developed by the author, every house in Rochester, Buffalo, and Syracuse containing 1-6 units was assessed, creating a quantitative analysis that is both more current, and on a much larger scale than previous work. Findings mostly confirmed observations and theories in the literature, but there were a number of significant differences. The key observation within Rochester was that, regardless of geographic scale, absentee owners consistently took the worst care of their properties, followed by resident landlords and then owner-occupiers. Further, size and type of absentee landlord mattered. Tenure was found to be the driving force in predicting maintenance outcomes, compounded by variables such as property values and race. Evidence from Buffalo and Syracuse indicated that findings may be generalizable, at least for declining industrial cities.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Synthesis & Characterization Of “Plum Pudding” Poly (Oligoethylene Glycol Methyl Methacrylate) Hydrogels Using Starch Nanoparticles

contributor:
Hoare, Todd
Chemical Engineering

subject: Hydrogels, composites, starch, nanoparticles, tissue engineering, drug delivery

abstract:
Hydrogels are defined as swellable polymer networks with the mechanical, interfacial, and physical properties similar to native tissues in the body. Nanocomposite hydrogels, defined as hydrogels that either entirely consist of or have embedded nanoparticle phases, have been shown to further expand the range of properties achievable with hydrogels and be suitable in many applications such as building tissue scaffolds. In particular, nanocomposite phases that can be eroded offer interesting potential to construct nanoscale voids that can be made in the gel that may be highly beneficial for applications in drug delivery, bioseparations, and tissue engineering.
In this thesis, two methods of incorporating starch nanoparticles (SNPs) into a ultraviolet (UV)-cured poly(ethylene glycol methacrylate) (POEGMA) matrix are described. In the first method, the SNPs were physically entrapped during the curing of the gels. An investigation of the effect of fabrication parameters such as monomer ratios, crosslinker amounts, and entrapped SNP concentration on swelling and shear storage modulus (G’) was performed. Enzymatic degradation of the nanophase was also observed to be possible upon amylase treatment, and the resulting internal morphology was confirmed to have increased internal porosity based on a methylene blue uptake experiment. In the second method, chemically functionalized SNPs were used as the exclusive crosslinker to create the POEGMA network. The swelling and mechanical performance of the SNP-crosslinked hydrogels were investigated and compared to the entrapped SNP gels. A preliminary study of the consequences of degradation of a naturally occurring crosslinker to the enzyme α-amylase was also performed. The combination of cytocompatible components and potential for internal porosity control make gels an interesting platform for tissue scaffolding and bioseparation applications.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Investigation of SAR-associated small molecules as inducers of resistance in cucumber and biofilm formation by Pseudomonas syringae pv. tomato in Arabidopsis

contributor:
Cameron, Robin K.
Biology

subject:
Pseudomonas syringae
Biofilm
Cucumber
Arabidopsis
Systemic Acquired Resistance
PAMP-triggered immunity

abstract:
Greenhouse environments often promote bacterial and fungal infections in important crop plants. Exogenous application of chemical inducers could help reduce the severity of infection, or even prevent infection. Small molecules such as glycerol, azelaic acid and pipecolic acid have been implicated as being important signaling molecules during Systemic Acquired Resistance (SAR). To examine if these small molecules could be used to induce resistance in crop plants, exogenous treatment assays were developed in cucumber. Glycerol spray and azelaic acid infiltration induced modest resistance at locally treated leaves. Pipecolic acid soil treatment induced modest resistance in aerial tissue of cucumber plants, and strong resistance when plants were treated weekly. This knowledge may be useful in promoting the commercialization of SAR-associated compounds to protect important crop plants against disease.

Plants possess multiple defense pathways that include an SA signaling component to initiate resistance to microbial pathogens. However, during Age-Related Resistance (ARR) in Arabidopsis, a number of studies support that SA acts as an anti-microbial and anti-biofilm agent against Pseudomonas syringae pv. tomato (Pst) in the plant intercellular space. Little is known about the role of Pst biofilm formation during infection of young plants or if other defense responses act to suppress bacterial biofilm formation. Therefore Pst biofilm formation and the effect of PAMP Triggered Immunity (PTI) on bacterial biofilm formation was examined. PTI was induced with flg22 in wild-type Col-0, fls2, bak1-3 (PTI mutants) and sid2-2 (SA biosynthesis mutant). In vivo bacterial biofilm-like aggregate formation was monitored using Pst DC3000 PDSK-GFPuv and epifluorescence microscopy. Pst aggregate occurrence and size were positively correlated with bacterial success in susceptible plants (wild-type Col-0, fls2, bak1-3, sid2-2), while fewer and smaller bacterial aggregates were observed in Col-0 undergoing PTI. To determine if the extracellular polysaccharide, alginate was a major contributor to biofilm formation, in vivo bacterial aggregate formation was monitored using alginate deficient Pst-GFP. Alginate deficient Pst-GFP and wild-type Pst grew to similar levels in wild-type plants suggesting that the ability to produce alginate was not necessary for Pst pathogenicity and success in planta. Fewer alginate-deficient Pst aggregates were observed compared to wild-type Pst in inoculated plants, suggesting that the ability to produce alginate was modestly important for aggregate formation. These data provide novel insights into how biofilms form in planta, the association between pathogen virulence and biofilm formation, and how plant defense responses such as PTI not only reduce bacterial growth, but also target biofilms.

abstract: Thesis

abstract: Master of Science (MSc)


title: A STUDY OF THE EFFECT OF A SURFACE TREATMENT ON THE PERFORMANCE OF CEMENTED CARBIDE INSERTS

contributor:
Veldhuis, Stephen
Mechanical Engineering

subject:
Cemented Carbide inserts
Shot peening
WPC
Surface treatment

abstract:
The main objective of this research is to investigate the effect of wide peening and cleaning (WPC) also known as fine particle peening on the surface properties and cutting performance of cemented carbide inserts. In WPC, the surface of the material is bombarded with millions of high-velocity fine shot generating a uniform layer of plastic deformation near the surface. The plastically deformed layer will have higher compressive residual stress levels, higher surface hardness, experience changes in surface morphology and changes in microstructure.  Selecting suitable peening parameters is crucial for achieving proper results.  In this study, tools are treated under different pressures varying between 0.2 to 0.4 MPa, and for different peening durations of 2.5 to 10 s.
The cutting performance of uncoated tools treated with WPC was examined while turning ductile cast iron and AISI 4140. To have a better understanding, the surface morphology, microstructure, surface roughness, cutting edge radius, residual stresses, and surface hardness were measured and discussed. The results are also compared with untreated tools. The compressive residual stresses were significantly higher after WPC. In addition, uncoated tools treated with WPC resulted in a 12-30% higher tool life over untreated tools.
Based on the findings outlined in this thesis, WPC can be recommended as a surface treatment on uncoated cemented carbide inserts for increasing tool life. Also, this study shows significant potential for using WPC as a pre-coating treatment for improving coating adhesion on cemented carbide cutting inserts.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: DEVELOPMENT OF DATA-DRIVEN MODELS FOR INFLUENT PREDICTION AT WASTEWATER TREATMENT PLANTS

contributor:
Zoe, Li
Civil Engineering

subject: Civil Engineering

abstract: Influent flow rate is essential to the operation and management of wastewater treatment plants (WWTPs). To support safe operation and effective management of WWTPs, a number of process-driven models were previously built for predicting the influent flow rate. However, in order to capture the complex nonlinear relationships in wastewater systems, these process-driven models require large-scale monitoring and complicated parameter tuning. In this research, to address those drawbacks, data-driven models are investigated for influent flow rate prediction. Three data-driven models, including multilayer perceptron (MLP), long short-term memory (LSTM) network, and random forest (RF), are introduced and developed. The developed models are applied to three WWTPs in Canada for influent flow rate prediction to demonstrate their applicability. Influent flow rate prediction with two temporal resolutions (i.e., daily and hourly) are provided. The results show that the proposed models have an overall good performance, especially the RF model. For both temporal resolutions, the performance of RF models is stable and satisfactory. In addition, an uncertainty analysis approach for the RF model is developed to provide more robust predictions. To the author’s knowledge, this is the first Canadian study of wastewater influent flow rate prediction based on advanced data-driven techniques. The high temporal resolution prediction and the probabilistic prediction approach proposed in this research represent a unique contribution to methodologies related to wastewater modeling. This research can provide valuable support for WWTPs to improve operational efficiency and management effectiveness.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Examining applications of Neural Networks in predicting polygenic traits

contributor:
Canty, Angelo
Statistics

subject:
Deep Learning
Neural Networks
Polygenic Risk Score
Machine Learning
Statistics
Genetics

abstract:
Polygenic risk scores are scores used in precision medicine in order to assess an individual's
risk of having a certain quantitative trait based on his or her genetics. Previous works have
shown that machine learning, namely Gradient Boosted Regression Trees, can be successfully
applied to calibrate the weights of the risk score to improve its predictive power in a target
population. Neural networks are a very powerful class of machine learning algorithms that have
demonstrated success in various  elds of genetics, and in this work, we examined the predictive
power of a polygenic risk score that uses neural networks to perform the weight calibration.
Using a single neural network, we were able to obtain prediction R2 of 0.234 and 0.074 for height and BMI, respectively. We further experimented with changing the dimension of the input
features, using ensembled models, and varying the number of splits used to train the models
in order to obtain a  nal prediction R2 of 0.242 for height and 0.0804 for BMI, achieving
a relative improvement of 1.26% in prediction R2 for height. Furthermore, we performed
extensive analysis of the behaviour of the neural network-calibrated weights. In our analysis,
we highlighted several potential drawbacks of using neural networks, as well as machine learning algorithms in general when performing the weight calibration, and o er several suggestions for improving the consistency and performance of machine learning-calibrated weights for future research.

abstract: Thesis

abstract: Master of Science (MSc)


title: 3D Surface Reconstruction and 2D Segmentation of Scanning Electron Microscopy Images

contributor:
Christopher Anand, Nabil Bassim
Computer Science

abstract:
Scanning Electron Microscopy (SEM) used in a wide range of industrial and research applications. SEM produces greyscale images of a specimen by bombarding it with high-energy electrons, causing secondary and backscattered electrons and x-ray photons to be produced by several different mechanisms. Images obtained from SEM have information about the topography and composition of the sample. Because the electron beam must scan the sample in a serial, rostered fashion, SEM imaging is time consuming and expensive. In this thesis we give two methods of using mathematical optimization to extract extra information from SEM images.
In the first part, we reconstruct three-dimensional images from two-dimensional SEM images acquired with different types of electron contrasts and in different orientations, reducing the need for costly Atomic Force Microscopy (AFM) probes or other 3-D metrology tools. In the second part, we accelerate the SEM process of imaging by reconstructing full images from images with only a fraction of the rows scanned, and apply this to the problem of segmenting images used in circuit analysis for reverse engineering. In the example images, we show that by simultaneously acquiring two images from different types of electron detectors, and skipping three out of four scan lines, we can segment the example images with partial images acquired in one quarter of the time. To use two sparse, simultaneously-acquired images to build the segmentation model, we construct a second optimization problem which optimally combines the two images taking into account the different signal and noise characteristics of the two images.

abstract: Thesis

abstract: Master of Science (MSc)


title: Point cloud scan selection for indoor floor plan generation

contributor:
Rong, Zheng
Computing and Software

subject: floor plan, lidar, indoor

abstract:
Building Information Models (BIM) are becoming a standard in the construction indus- try for storing information about buildings and assets. Automatically creating BIMs has attracted a lot of attention, as it has great potential to improve efficient resource man- agement. A detailed description of the building can decrease the cost of management, heating and cooling, and restoration. For pre-existing structures design documents are typically outdated or unavailable, making BIMs challenging to acquire.
The field of indoor floor plan creation has grown in recent years due to advancements in LIDAR technology. However, LIDARs create millions of points per scan, making it computationally expensive to process all of them. In order to properly create a floor it is imperative to acquire a sufficient number of scans to visualize the whole building, while simultaneously minimizing the number of scans for computational reasons. We propose a method for selecting a subset of the scans, as well as a method for clustering points into lines to be used for floor plan extraction. Our method works by clustering nearby points, creating a convex hull around them, and selecting scans based on the most area covered by the union of the hulls. The point clustering splits the pointcloud into potential lines by projecting each point along its surface normal, clustering points from the same line together. Those improvements allow for the efficient generation of floor plans for large buildings.

abstract: Thesis

abstract: Master of Science (MSc)


title: EMOTIONAL LABOR FROM AN OCCUPATIONAL LENS

title: CONSEQUENCES, RESOURCES AND THE STATUS SHIELD AMONG EMOTIONAL LABORERS

contributor:
Glavin, Paul
Sociology

subject: Emotional Labor; Emotions; Health; Stress; Gender

abstract: The management and display of emotions has become a pervasive occupational role requirement for many workers in the service industry. Service workers’ interactions with clients or customers exposes them to occupational requirements where they must effectively display certain emotions, while at the same time internally suppressing other felt emotions—a type of work activity referred to by Arlie Hochschild (1983) as emotional labor. Despite a vast literature on the subject, there remain a number of knowledge gaps regarding the consequences of emotional labor. My dissertation addresses this issue by merging occupational-level data with a national survey dataset of American workers to examine a variety of consequences of emotional labor using a multidimensional approach. I reveal that emotional labor poses the greatest threat to well-being in resource deprived work contexts, and that occupations that have little job control are mostly occupied by minority women. I also find that high control beliefs serve as an important psychological resource for men that can buffer the strain that leads to customer/client conflict in emotional labor intensive occupations.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Demographic patterns in Medieval London inferred from wills probated in the Court of Husting, 1259-1688

contributor:
Earn, David
Mathematics and Statistics

abstract:
The Calendar of Wills Proved and Enrolled in the Court of Husting, London, 1258--1688 (Husting wills) is exploited (i) to characterize, using statistics, the social and demographic characteristics of Medieval London and (ii) to analyze the temporal patterns of the four plague epidemics that occurred in London between 1348 and 1376.

The Husting wills were digitized by British History Online (BHO) in 2017. We created an R package that uses the BHO version of the Husting wills and provides tools for analysis of these wills.

Statistical analyses performed on the 4110 Husting wills reveal that 10.9% of testators were women. There is no clear evidence of bias of writing wills on particular weekdays. However, wills were least and most commonly written on Thursdays (11.72%) and Saturdays (16.18%), respectively.  51.2% of wills mention the career of the testator. By categorizing careers into one of four classes (business, church, city or nobility), we were able to determine that most testators were in the business category (80.2%). Among these individuals, the five most common occupations were fishmonger, merchant, goldsmith, draper and skinner.

Further analyses of the Husting wills strongly suggest that the temporal patterns of plague epidemics can be estimated more accurately from the dates wills were written rather than the dates they were probated.  We identify two probable factors that make probate dates harder to interpret: First, the Court of Husting probated wills only on Mondays.  Second, highly varying lags between the writing and probating of wills adds noise to statistics based on probate dates. The observed lags for the Husting wills are well approximated by a lognormal distribution.

abstract: Thesis

abstract: Bachelor of Science (BSc)


title: Measuring and modelling thermal and moisture regimes in seasonally frozen soils, Wolf Creek, Yukon Territory

contributor:
Carey, Sean
Earth and Environmental Sciences

subject:
hydrology
modelling
cold regions
soils
frozen soils

abstract: Frozen ground is an important consideration in cold regions hydrology because pore ice can impede the ability of water to infiltrate into and migrate within soils, thereby altering water flow paths and increasing surface runoff. High latitude regions are particularly susceptible to changes in climate, where increases in temperature and changing precipitation trends can alter soil freeze/thaw dynamics. However, there has been limited research on infiltration processes in subarctic alpine environments due to sparse historic data and difficulties with gathering direct measurements. In addition, few hydrological models consider the complexity of frozen soils in such environments. The objectives of this thesis are to assess the ability of the GeoStudio finite element modelling suite to simulate observed soil temperature and moisture data and to evaluate the sensitivity of the models to changing climate scenarios. GeoStudio’s Multiphysics model integrates several models that allow it to simulate concurrent water flow and temperature dynamics in variably saturated environments experiencing soil freezing and thawing. Field data for this study are obtained from Wolf Creek Research Basin (WCRB) in southern Yukon, Canada. Data for quantifying snowmelt, soil moisture, soil temperature, and soil composition were collected at three sites in WCRB from April 2015 to August 2016, adding to the available historical data. Results of the GeoStudio models illustrate the dominance of snow in controlling freeze/thaw dynamics and simulate the study environment to reasonable accuracy with some discrepancies in timing and variability. In addition, GeoStudio is particularly sensitive to surface conditions affecting both coupled heat and water flow processes compared to independent changes of air temperature and precipitation, suggesting future climatic scenarios may have a notable impact on frozen soils. This research helps elucidate the complex heat transfer and water movement processes that control infiltration in northern environments and provides a quantitative assessment of their sensitivity to future climate warming.

abstract: Thesis

abstract: Master of Science (MSc)


title: X-RAY FLUORESCENCE MEASUREMENT OF SKIN IRON CONCENTRATIONS AS A SURROGATE MARKER FOR LIVER IRON CONCENTRATIONS IN CADAVERS

contributor: Radiation Sciences (Medical Physics/Radiation Biology)

subject:
X-Ray Fluorescence
Liver
Skin
Iron Concentrations

abstract: This thesis explores the use of skin iron concentration, assessed using a portable x- ray fluorescence (PXRF) analyzer, as an indicator of liver iron concentration. Ultrasound images were acquired from four sites on human cadavers: thenar eminence (TE), between the metacarpophalangeal joint 1 and 2 (MJ), patella (P), and plantar arch (PA). Skin thickness was subsequently measured using boundary detection software applied to the ultrasound images. Skin iron concentrations, from the same sites, were obtained directly from 13 cadavers using a PXRF analyzer. As the iron concentrations determined using PXRF may have been impacted due to beam attenuation through the skin, these iron concentrations were subsequently corrected using the Beer-Lambert Law accounting for the skin thickness at each site. Huber XRF is a bulk tissue measurement system that was used to measure iron concentrations from the extracted samples of the four sites. The skin iron concentrations determined using both PXRF and Huber XRF were compared to evaluate the agreement between the two methods. As such, samples from the four sites were extracted and the iron concentrations of the extracted samples were measured using a Huber X-Ray Fluorescence (XRF) analyzer as the control. A statistically significant relationship with a p-value of <0.01 and a strong correlation with a R2 value of 0.87 was seen between the corrected skin iron concentrations determined using PXRF and the skin iron concentrations determined using Huber XRF analysis of the extracted samples. Thus, the skin iron concentrations obtained using PXRF are representative of the skin iron concentrations collected by Huber XRF. For further validation, liver samples were obtained from 6 of the 13 cadavers and the liver iron concentrations were assessed using Huber XRF. The non- corrected PXRF, corrected PXRF and the Huber XRF skin iron concentrations were then compared with the liver iron concentrations. The relationships between iron concentrations measured at the PA site and in the liver were found to be statistically significant with strong correlations (R2 = 0.94 for Huber XRF, R2 = 0.87 for non-corrected PXRF, and R2 = 0.95 for corrected PXRF). Therefore, the skin iron concentrations at the PA site determined by PXRF and determined by Huber XRF analysis of skin samples could be used in the future as a surrogate marker for the liver iron concentrations in humans.

abstract: Thesis

abstract: Master of Science (MSc)


title: Runoff Reduction Benefits of Retrofitted Enhanced or Extended-Depressed Tree Pits of the Beasley and Landsdale Neighbourhoods in Hamilton, Ontario

contributor:
Guo, Yiping
Civil Engineering

subject:
Extended Tree Pits
Enhanced Tree Pits
Climate Change
Sustainable Stormwater Management
Natural Infrastructure
Nature-Based Engineering
Sustainable Development Goals
Low Impact Development
Resilient Infrastructure

abstract: This research explores the potential of retrofitting enhanced or extended-depressed tree pits (ETPs/EDTPs) around existing street trees to bolster pre-development hydrological processes in two Hamiltonian neighbourhoods to help satisfy their social, economic, and environmental needs and work toward the Sustainable Development Goals (SDGs). Using QGIS and openly available data to create catchment areas, establish the feasibility of a 20:1 catchment to pit area ratio, and investigate the performance of five available structured soil cells, the innovative Analytical Probabilistic Model (APM) for Bioretention systems was adapted to conduct a parametric sensitivity analysis and subsequently compute the Road Runoff Reduction Efficiency (RRRE) of the designs under different climatic scenarios. The catchment to pit area ratio, design storage depth, and final infiltration rate were found to have a significant impact on the RRRE while the average evapotranspiration rate did not. Based on a 75% efficiency cut-off, and assuming a 20:1 catchment to pit area ratio, the shallowest two depths were deemed ineffective in all final infiltration rate scenarios while the largest depth provided efficiencies greater than 75% runoff reduction even when faced with the lowest rate of 6 mm hr-1. Comparing the RRRE during current climatic conditions to a simulated 2050s winter suggests that the RRRE of the deepest implementation is impacted only half as much as the shallowest; larger systems are more resilient. This research has reinforced the versatility and efficiency of the Analytical Probabilistic Model for modeling system performance of LIDs and ETPs, supports the prominent findings of the efficacy of enhanced tree pits to significantly contribute to urban stormwater management and re-establish more natural and sustainable hydrologic processes, and promotes them as a key to reaching the SDGs in Hamilton, Ontario.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: The Sustainable Development Goals call for action from every member of society. This research explores the potential Stormwater Management Engineers have to do so by retrofitting street trees with Enhanced or Extended-Depressed Tree Pits, increasing rooting volume and offering the tree more water from the adjacent road to simultaneously meet the natural needs of the tree and reduce urban runoff.


title: EVALUATING THE CREDIBILITY OF EFFECT MODIFICATION CLAIMS  IN RANDOMIZED CONTROLLED TRIALS AND META-ANALYSES

contributor:
Guyatt, Gordon
Health Research Methodology

subject:
randomized controlled trial
meta-analysis
effect modification
subgroup analysis

abstract:
Background: Many randomized controlled trials (RCTs) and meta-analyses include analyses of effect modification (also known as subgroup, interaction, or moderation analyses). Methodologists have widely acknowledged the challenges in deciding whether an apparent effect modification is credible or likely the result of chance or bias. Various sets of credibility criteria are available (Chapter 2 provides an example) but are inconsistent, vague in wording, lack guidance for deciding on overall credibility, and have not been systematically tested.

Objective: To systematically develop a formal instrument to assess the credibility of effect modification analyses (ICEMAN) in RCTs and meta-analyses of RCTs.

Methods: Key steps in the development process included 1) a systematic survey of the literature to identify available criteria, rationales, and previous instruments, 2) a formal consensus study among 10 leading experts, and 3) a formal user-testing study to refine the instrument based on interviews with trial investigators, systematic reviewer authors, and journal editors who applied drafts of the instrument to published claims of effect modification.

Results: The systematic survey identified 150 relevant publications, 36 candidate credibility criteria with associated rationales, and 30 existing checklists (Chapter 3). The consensus study consisted of two main video conferences and multiple rounds of written discussion. The user-testing involved 17 users (including systematic review authors, trial investigators, and journal editors) who suggested substantial improvements based on detailed interviews. The final instrument provides separate versions for RCTs (five core questions) and meta-analyses (eight core questions) with explicit response options, and an overall credibility rating ranging from very low to high credibility. A detailed manual provides rationales, supporting references, examples from the literature, and suggestions for use in combination with other quality appraisal tools and reporting (Chapter 4).

Discussion: ICEMAN is a rigorously developed instrument to evaluate claims of effect modification and addresses the main limitations of previous approaches.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Randomized controlled trials and meta-analyses provide the best available evidence to evaluate whether effects of a therapy vary among individual patients. Efforts to decide whether treatment effects differ across patients are important and frequently done but difficult to interpret. The fundamental challenge is to decide whether apparent differences in effect are real or due to chance. To aid this decision, experts have suggested various sets of credibility criteria, all with important limitations. This thesis documents how we systematically addressed the limitations of previous approaches. Key steps were a systematic survey of the available credibility criteria, a consensus study among leading methodologists, and a formal user-testing study. The result is a new instrument for assessing the credibility of effect modification analyses (ICEMAN).


title: DRUG DELIVERY SOLUTIONS FOR THE  POTENTIAL TREATMENT OF CHILDHOOD OCULAR CONDITIONS

contributor:
Sheardown, Heather
Chemical Engineering

subject:
drug delivery
ocular
retinoblastoma
myopia

abstract:
Ocular drug delivery remains a challenge due to the anatomical and physiological barriers of the eye. Topical drops have poor penetration and side effects, and injections are highly invasive; an alternative approach is transscleral delivery. Sustained drug release systems utilizing this delivery pathway are non-invasive yet provide extended treatment periods with single doses. Specifically, such systems would be beneficial for treating pediatric populations for diseases such as retinoblastoma and myopia. A chemo-preventative treatment for retinoblastoma, a childhood ocular cancer, has been proposed utilizing CdK inhibitors such as roscovitine and R547. Myopia, a more common, chronic condition in children, can be treated with atropine, though the dosing must be tightly controlled. Three novel delivery systems have been developed in this work to deliver these drugs, generating potential treatment platforms for these conditions.
Contact lenses have been investigated previously to deliver various therapeutics, as they act as a slow, equilibrating reservoir, and the prolonged corneal residence time improves bioavailability. Silicone lenses, with their ability for continuous wear, have been explored looking at various material compositions and drug loading levels and techniques to confirm the feasibility of this system for these conditions (Chapter 2). This work has been extended to include covalent tethers for roscovitine, ensuring that it is able to survive a more commercially-relevant synthesis and providing additional ways to tailor the drug release profiles (Chapter 3).
Alternatively, amphiphiles, which can self-assemble in the presence of excess water, have been explored for their drug delivery potential. Novel materials consisting of oleoylethanolamide and linoleoylethanolamide were developed to exhibit cubic phase transitions at physiologically relevant conditions, and their subsequent drug release characteristics were explored (Chapter 4). Silicone-based materials have broad usages as biomaterials, and a novel approach of incorporating PEG into the material without the use of metal catalysts were explored (Chapter 5). These exhibited a significant reduction in protein fouling, and material compositions were further iterated on, and their subsequent drug delivery capabilities were examined (Chapter 6). Overall, these three approaches have been able to successfully delivery roscovitine, R547 and atropine in non-invasive manners that have the potential to be an appropriate treatment for the childhood conditions they are intended to treat.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract:
Sustained ocular drug delivery is critical to minimize side effects, maximize compliance and improve the clinical outcomes experienced by the patient. This is particularly true in pediatric applications, such as retinoblastoma and myopia. The objective of this thesis is to create drug delivery systems that could be used to treat these childhood conditions, with a focus on non-invasive delivery technologies.
In this project, contact lenses are explored as drug delivery vehicles for two drugs which can be used to treat retinoblastoma and myopia. Multiple materials and drug loading are explored to create a sustained drug delivery system that meets the needs of these conditions. This is then expanded into examining systems that fit within current commercial manufacturing practices, creating a delivery system that meets the demands of the disease and industry.
Alternative delivery systems that could be utilized as inserts are also explored. A lipid based system, whose materials are native to the body, are explored as a unique system capable of delivering drugs in a controlled fashion under specific hydration and temperature conditions. Alternatively, a silicone-based system is explored, whose unique chemistry eliminates many of the prohibitive biological side effects seen with these materials, allowing for a sustained drug delivery system for these ocular conditions.