title: INVESTIGATING SOURCES OF PERIPHERAL SEROTONIN SYNTHESIS: IMPLICATIONS FOR REGULATING METABOLISM

contributor:
Steinberg, Gregory
Medical Sciences

subject:
Obesity
Type 2 Diabetes
Non-alcoholic Fatty Liver Disease
Serotonin
Thermogenic Adipose Tissue
Mast Cells
Metabolism
Immunometabolism

abstract: PhD Dissertation

abstract: Obesity is a major risk factor for type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD), and is attributed to excess energy intake in comparison to energy expenditure. Therapeutics that reduce energy intake in obesity have limited efficacy, with weight loss typically reaching  less than 10% of initial body mass, leading to efforts to uncover new therapies that may increase energy expenditure. Unlike lipid-storing white adipose tissue, brown and beige adipose tissues undergo futile cycling, oxidizing lipids and carbohydrates thereby increasing energy expenditure. With obesity, the metabolic activity of brown and beige adipose tissue is reduced, suggesting that restoring adipose tissue thermogenesis may represent a new means to enhance energy expenditure. Previous studies in mice have shown that peripheral serotonin synthesis by the enzyme tryptophan hydroxylase 1 (Tph1) inhibits adipose tissue thermogenesis and contributes to the development of obesity, insulin resistance and NAFLD. However, the primary Tph1 expressing tissue(s) inhibiting adipose tissue futile cycling is not known. In this thesis, we genetically removed Tph1 in mast cells of mice and discovered that this elevated beige adipose tissue activity protecting mice from developing high-fat diet induced obesity, insulin resistance and NAFLD. In contrast to these findings, genetic deletion of Tph1 in adipocytes did not result in protection from obesity, suggesting that mast cells are the primary source of serotonin that inhibits white adipose tissue thermogenesis. Lastly, to determine the importance of adipose tissue thermogenesis in mediating the beneficial metabolic effects of reduced Tph1, mice were housed at thermoneutrality, blocking the requirement for adipose tissue thermogenesis. Under these conditions, mice lacking Tph1 had comparable brown and beige adipose tissue metabolic activity, energy expenditure and adiposity, however, surprisingly, were still protected from insulin resistance and NAFLD. The studies in this dissertation have discovered that mast cell Tph1 is critical for inhibiting adipose tissue thermogenesis and that serotonin plays an important role in promoting NAFLD, independently of its inhibitory effects on adipose tissue thermogenesis. Collectively, these findings further define the roles of serotonin in regulating whole-body energy metabolism, providing critical clues and mechanistic insights for potential therapies to mitigate metabolic diseases.

abstract: Dissertation

abstract: Doctor of Philosophy (Medical Science)

abstract: Obesity, type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) can develop when caloric intake exceeds expenditure. In contrast to lipid-storing white fat, brown and beige fat burn calories. Serotonin is a hormone that reduces the burning of calories in fat, therefore finding ways to inhibit its effects on fat tissue without altering serotonin in the brain may lead to new therapies for obesity and other related diseases. In this thesis, we examined potential sources of serotonin that might inhibit the burning of calories in adipose tissue of mice. By reducing the synthesis of serotonin in a white blood cell called mast cells, but not fat cells, mice were protected from obesity, pre-diabetes and NAFLD due to increased activity of beige fat. Moreover, when we kept mice in a warm environment, thus reducing the need for mice to burn calories in brown and beige fat, this eliminated the effects of serotonin to promote obesity, but not pre-diabetes and NAFLD. These studies have identified how serotonin generated from mast cells inhibits the burning of calories in adipose tissue, a finding that may lead to new therapies for obesity, T2D and NAFLD.


title: HOUSEHOLD CHAOS, MATERNAL DISTRESS AND PARENTING: ASSOCIATIONS WITH CHILD FUNCTION ACROSS MULTIPLE DOMAINS

contributor:
Gonzalez, Andrea
Neuroscience

subject:
Household chaos
Child executive functions
Maternal distress
Parenting

abstract: Proximal risk factors including household chaos, parenting and maternal distress can have a broad impact on multiple domains of child development and functioning. Using multiple methodologies including a meta-analysis and structural equation modeling with an empirical, cross-sectional design from a larger longitudinal research study; in this dissertation, I examine the impact of household chaos on child executive functioning, socioemotional and physiological stress outcomes, the role that parenting plays in this association, and how maternal distress predicts chaos in the home. In study 1, I conduct a meta-analysis examining the direct association between household chaos and child executive functioning, as well as multiple potential moderators (e.g. child age, sex and race/ethnicity). It incorporates 26 studies, with 27 independent effect sizes with a total sample of 8,944 children. Overall, I found a significant  effect of r = .22 between household chaos and child executive function. Among the moderators assessed, only measurement approach of executive functions (informant-completed questionnaire versus direct assessment) was significant, with informant-completed questionnaires yielding an effect of r = .27 compared to direct assessment, r = .16.  I conducted a series of separate moderation analyses for questionnaire and direct assessment effects. No significant moderators emerged from the questionnaire analyses, despite heterogeneous effect sizes. Direct assessment analyses revealed that both household chaos dimensions (disorganization and instability) were significantly related to child executive functions, however instability was a stronger correlate (r = .21) than disorganization (r = .09). Composition of the sample was also a significant moderator with effects increased with the proportion of minorities, and with parents with lower levels of education. Building on this work, in studies 2 and 3, I used cross-sectional empirical data from a sample of 137 mothers and their school-aged (5-year old) children. During home visits, mothers completed questionnaires assessing their mood, stressful experiences, the home environment and their child’s socioemotional functioning. Mothers also completed a video tour of the home. Mother-child interactions were videotaped and later coded for parenting.  Both mothers and children independently completed behavioural assessments of executive function. Also, hair samples were collected from mothers and children from which the stress hormone, cortisol, was extracted as a biomarker of chronic stress. In order to empirically test the findings from the meta-analysis, in my second study, I used structural equation modeling to examine the indirect effect of household chaos on child executive functioning via parenting. I found that household chaos was directly and indirectly (via maternal cognitive sensitivity and emotional availability) associated with a latent variable of child executive functioning. Furthermore, instability, but not disorganization, significantly predicted child executive functioning directly and indirectly via parenting. Finally, sex-based analyses indicated that the effect of chaos on child executive functioning was significant through indirect effects only for boys. In the third study, in order to elucidate potential contributing factors to household chaos, I used a structural equation model to examine the indirect effects of a linear regression-weighted composite variable of maternal distress (depression, negative affect and physiological stress) on child hair cortisol levels and externalizing and internalizing behaviour problems via household chaos. I found that maternal distress had both direct and indirect effects (via household chaos) on child hair cortisol levels; however, only indirect effects were significant for externalizing and internalizing behaviour problems. Also, the indirect effect was only significant for household disorganization, but not instability, for child hair cortisol and externalizing and internalizing behaviour problems. Taken together, the findings from my dissertation demonstrate that: 1) household chaos has a direct, negative effect on child executive functioning and an indirect effect via parenting; and 2) maternal distress plays an important role in predicting the levels of chaos within the home which has implications for child chronic stress levels and behavioural problems. Collectively, these findings highlight the need to take a multi-method approach to measuring executive functioning in children and further, to develop and evaluate interventions that aim to support mothers, improve parenting and promote order and stability within the home in order to foster healthy developmental trajectories for children.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: Children exposed to household chaos may experience adverse outcomes across multiple domains. Parenting can also be negatively affected by household chaos which may impact the quality of parent-child interactions. Further, the physical and psychological health of the mother may regulate the levels of chaos in the home which has implications for child outcomes as well. This dissertation seeks to examine the influence of household chaos on child executive functioning, stress levels and socioemotional functioning, and the roles that parenting and maternal distress play.  I address three primary objectives: 1) using meta-analytic techniques, I examine the magnitude of effect of household chaos on child executive functioning based on existing literature as well as potential factors that may modulate the strength of the linkage between household chaos and child executive functioning; and using cross-sectional data, I examine 2) how household chaos impacts parenting and subsequently, how parenting impacts child executive functioning; and 3) how maternal distress influences the level of chaos in the home and how this chaos impacts child stress levels and socioemotional functioning. Collectively, the results from this dissertation indicate that household chaos has a broad negative impact on child outcomes, and both parenting and maternal distress play important roles in understanding this impact. Further, it demonstrates the need for intervention research aimed at supporting the physical and psychological health of mothers, improving parenting and creating order and stability in homes for children.


title: Oral Anticoagulation Persistence in Atrial Fibrillation

title: Evaluating Oral Anticoagulation Persistence in Patients with Atrial Fibrillation

contributor:
Nieuwlaat, Robby
Health Sciences

subject: Persistence Anticoagulation

abstract: PhD Thesis

abstract:
Long-term persistence with oral anticoagulants (OAC) in atrial fibrillation (AF) is associated with improved outcomes. However, 1-year discontinuation of vitamin K antagonists (VKA) is as high as 50%. Persistence to non-VKA oral anticoagulants (NOAC) show some signal of improvement but the estimates are variable.
This thesis includes a prospective evaluation of newly diagnosed AF patients in 44 countries using physician reported start and stop dates of anticoagulation. One-year persistence to dabigatran was 75.6% and 69.2% at 2 years. Approximately half of discontinuers switched to another OAC, increasing estimates of general overall 2-year OAC persistence to 84.1%. Probability of discontinuation was highest in the first 6 month period (83.7%, 95% confidence interval [CI] 82.7-84.8%) and lower in successive periods. Patients persistent with dabigatran at 1 year had >90% probability of remaining persistent at 2 years. Patients with symptomatic AF, and prior bleeding had higher discontinuation, those with prior stroke, lower discontinuation. Standardized stroke incidence rates post-discontinuation were (95% CI) 1.76 (0.89 to 2.76) in non-switchers, and 1.02 (0.43 to 1.76) in those who switched, consistent with the expected benefit of remaining on treatment.
Supplemental patient education may be one mechanism to improve persistence to treatment and improve patient outcomes. A systematic review of the impact of education on outcomes in 9 randomized clinical trials showed low to very low certainty of evidence for benefit of education over usual care. Sufficiently powered trials or different approaches are required to further assess the impact of education on patient outcomes.
Finally, important considerations for interpreting available research in OAC persistence, including differences in study methodology, setting, and timing are examined, and patient factors associated with higher or lower persistence reported. A framework for assessing persistence studies is presented to assist researchers and clinicians in evaluating current research and to support planning of future studies.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract:
Oral anticoagulants (OAC) are approved for stroke prevention in atrial fibrillation (AF) patients, however discontinuation rates are high and associated with poor patient outcomes. Prior to the last decade, medications to reduce blood clotting by reducing vitamin K action [vitamin K antagonists (VKA)] were primarily used. However, up to 50% of patients discontinue VKA within one year. The introduction of non-VKA (NOAC) anticoagulants that do not require continuous monitoring or dose adjustments, show some promise of improvement in persistence.
This thesis examines and reports on long-term persistence over 2 years to the first NOAC available, dabigatran. Reasons, clinical predictors, and periods of risk for discontinuation as well as outcomes following discontinuation are prospectively examined. A systematic review of educational interventions examines existing evidence for improving outcomes with structured education. Finally, important considerations for interpreting OAC persistence research as well as recommendations for future research in this area are discussed.


title: Analysis of Three-Way Data and Other Topics in Clustering and Classification

contributor:
McNicholas, Paul David
Mathematics and Statistics

subject: clustering, classification, mixture models, matrix variate distributions

abstract: Clustering and classification is the process of finding underlying group structure in heterogenous data. With the rise of the “big data” phenomenon, more complex data structures have made it so traditional clustering methods are oftentimes not advisable or feasible. This thesis presents methodology for analyzing three different examples of these more complex data types. The first is three-way (matrix variate) data, or data that come in the form of matrices. A large emphasis is placed on clustering skewed three-way data, and high dimensional three-way data. The second is click- stream data, which considers a user’s internet search patterns. Finally, co-clustering methodology is discussed for very high-dimensional two-way (multivariate) data. Parameter estimation for all these methods is based on the expectation maximization (EM) algorithm. Both simulated and real data are used for illustration.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: The role of multimerin 1 (MMRN1) in platelet adhesion and characterization of its interactions with fibrillar collagens

contributor: Medical Sciences (Blood and Cardiovascular)

subject:
multimerin 1
collagen
platelets
thrombosis
hemostasis
platelet adhesion

abstract:
Multimerin 1 (human: MMRN1, mouse: Mmrn1) is a large homopolymeric
glycoprotein that is synthesized and stored by platelets and endothelial cells until
activation-induced release. MMRN1 is able to support platelet adhesion through
mechanisms involving von Willebrand factor (VWF) and glycoprotein (GP)Ibα, and β3
integrins on activated platelets, and it enhances platelet adhesion to fibrillar collagen,
potentially by binding to putative MMRN1-specific GPAGPOGPX (where O is
hydroxyproline and X is valine or glutamine) motifs in fibrillar collagens. Using mice
with and without selective Mmrn1 deficiency, the goals of this thesis were: 1) further
characterize the ability of Mmrn1 to enhance platelet adhesion to collagen, 2) explore the role of fluid shear stress in the ability of Mmrn1 to enhance platelet adhesion, and 3) test the specificity of the GPAGPOGPX motif for Mmrn1 and the ability of GPAGPOGPX to support or enhance platelet adhesion. Mmrn1-deficient (Mmrn1-/-) mouse platelets showed impaired aggregate formation on fibrillar collagen surfaces under high (1500 s-1) and low (300 s-1) shear flow compared to wild-type (Mmrn1+/+) mouse platelets, which was due to reduced initial adhesion and a slower rate of platelet accumulation onto collagen surfaces. Similarly, Mmrn1-/- platelets formed smaller aggregates on immobilized recombinant (r)Vwf surfaces compared to wild-type platelets, and Mmrn1-/- platelets had impaired adhesion and aggregate formation on immobilized murine fibrinogen, but not fibrin, when platelets were pre-activated to release Mmrn1. Type I fibrillar collagen was found to contain a variant of the GPAGPOGPX motif (GPAGPOGPI), and GPAGPOGPX motifs supported adhesion of wild-type, but not Mmrn1-/-, platelets. When presented with the VWF-binding GPRGQOGVMGFO motif and the integrin α2β1-binding GFOGER motif present in fibrillar collagens, the GPAGPOGPX motifs synergistically enhanced platelet adhesion. These findings expand upon the known adhesive functions of platelet multimerin 1 and update knowledge of the motifs that support platelet adhesion to fibrillar collagens.

abstract: Dissertation

abstract: Doctor of Philosophy (Medical Science)


title: Changes in fitness with long-term cardiac rehabilitation

contributor:
Tang, Ada
Rehabilitation Science

subject:
cardiac rehabilitation
cardiorespiratory fitness
cardiovascular disease
exercise
mixed model analysis
heart disease
muscle strength
fitness
long-term cardiac rehabilitation

abstract: Despite known associations between fitness and recurrent cardiovascular events, changes in cardiorespiratory fitness (CRF) and muscle strength with long-term cardiac rehabilitation (CR) have not been extensively examined in men, and data in women is absent in the literature. The purpose of this thesis was to estimate changes in CRF and muscle strength associated with long-term CR program enrollment in men and women, and to examine the influence of baseline fitness and age on these fitness trajectories in men.  Our methods and interpretations of the findings are discussed in the thesis, but in brief, using mixed model analyses we observed important fitness benefits over long-term CR enrollment in men and women and influences of baseline fitness and age on the trajectories in men.  Our data provide new evidence of improved fitness trajectories in men and women after long-term CR enrollment and highlight the importance of long-term exercise-based CR after the completion of short-term programs.  Larger prospective cohort studies are warranted to confirm the observations, and to identify potential mechanisms underlying these findings.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: EVALUATION OF THE IMPLEMENTATION OF A REAL TIME ELECTRONIC TRIAGE DECISION-SUPPORT TOOL (eCTAS) IN ONTARIO EMERGENCY DEPARTMENTS

contributor:
Guyatt, Gordon
Health Research Methodology

abstract:
Triage is a fundamental process for the safe and efficient management of patients where health care demands exceed available emergency department (ED) resources. The Canadian Triage and Acuity Scale (CTAS) is the standard used in all Canadian and many international EDs to aid in safely determining the priority by which patients should be assessed. The scale delineates 5 levels of acuity: level 1 (resuscitation), level 2 (emergent), level 3 (urgent), level 4 (less urgent) and level 5 (non-urgent).

Many provincial governments use CTAS as an administrative metric to estimate patient care requirements, compare ED performance, and estimate ED physician staffing needs. Despite its clinical and administrative importance, the process by which CTAS scores are derived is highly variable. eCTAS is a real-time electronic decision-support tool designed to standardize the application CTAS guidelines.

This dissertation includes three scientific papers that describe the evaluation of the provincial implementation of eCTAS in hospital EDs across Ontario. This thesis first describes the results from a prospective, observational study of nearly 1,500 triage encounters from sevens EDs that found that a standardized, electronic approach to performing triage assessments improves both interrater agreement and data accuracy compared to each hospital’s previous triage process, without substantially increasing triage time.

We then present our findings from a study exploring the consistency of CTAS score distributions across 35 hospital EDs pre and post-eCTAS implementation for 16 high-volume presenting complaints, and describe the association between use of eCTAS clinical modifiers and triage consistency. We found that compared to the previous triage process, eCTAS increased triage consistency across many, but not all, high-volume presenting complaints. Modifier use was associated with increased triage consistency, particularly for non-specific complaints such as fever and general weakness.

The third paper includes data from 354,176 triage encounters from 31 EDs and describes a change in the distribution of triage scores (from higher to lower acuity) that is likely due to eCTAS implementation. It also explores the possible impact of eCTAS implementation on the ED metrics of hospital admission, left without being seen, and time from triage to physician initial assessment, finding low quality evidence of minimal if any impact of eCTAS on these outcomes. Finally, this thesis concludes with suggestions for future research in this area.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Toward Transition State Analysis of DAHP Synthase

contributor:
Berti, Paul
Biochemistry and Biomedical Sciences

abstract: Antibiotic resistance is a major threat to the global health. The overuse and misuse of antibiotics have accelerated the process of antibiotic resistance and the emergence of multiple drug resistant bacteria. Therefore, it is urgent to develop new antibiotics. 3 Deoxy-D-arabinoheptulosonate-7-phosphate (DAHP) synthase is a promising target due to its vital role in shikimate pathway in bacteria, and the lack of mammalian counterpart. It catalyzes the aldol-like reaction between erythrose 4-phosphate and phosphoenolpyruvate, the first step in shikimate pathway. Inhibiting DAHPS will disrupt the shikimate pathway, leading to bacteria death. However, no clinical available DAHPS inhibitor makes it important to fully understand DAHPS catalytic mechanism. A tetrahedral intermediate (THI) is formed and broken during the reaction. Two possible mechanisms regarding THI breakdown generate the opposite charge distribution on the transition state (TS). The TS is an ideal target for inhibitor design. Due to the low concentration and short lifetimes, kinetic isotope effects (KIEs) are the only means to determine TS structures in detail. Competitive KIEs measurement involves measurement of the ratio of isotopologues in the same reaction. In this study, we have developed a method for accurate measurement of isotope ratios by quantitative NMR that involves using a less time-consuming pulse program that only flips the magnetization to an ‘Ernst angle’, and processing the NMR peaks with Voigt deconvolution fitting model which considers both the natural line shapes and the contributions from the spectrometer.

abstract: Thesis

abstract: Master of Science (MSc)


title: Diagnostic exposure of ionizing radiation and its long-term effects

contributor:
Wilson, Joanna
Biology

subject:
Ionizing Radiation
Respiratory System
X-rays
Fetal Programming

abstract: Medical radiation is vital in acquiring a patient diagnosis, but some clinicians are concerned with the perceived risks associated with ionizing radiation. This risk is heightened when incorporating in utero exposures due to the risk to the developing foetus. Although other organ systems have been studied, there is a paucity of data on the effects to the respiratory system from in utero exposures. The aim of this thesis was to understand the long-term effects on the respiratory system from in utero exposures, but as a first step, it was important to determine what levels patients receive whilst admitted to hospital. Two polar populations were chosen based on their predicted exposure levels during hospitalisation; one with high levels, intensive care unit (ICU) patients, and one with low levels, pregnant patients. Most patients cumulatively received < 1mSv with median exposures of 0.99 mSv (ICU patients) and 0.02 mSv (pregnant patients). However, both cohorts had patients that surpassed 10 mSv. To assess the effects from in utero exposures on the respiratory system, two animal models were conducted both exposed during late gestation, one healthy model and one acute lung injury model. In the health animal model, cardiovascular outcomes were also measured, however, ionizing radiation (50, 300, 1000 mGy) did not appear to influence these two organ systems from the outcomes measured. In the acute lung injury model, lipopolysaccharide (3mg/Kg) stimulated an acute lung inflammatory response, however, there was also no overt effect of radiation from the outcomes measured (10, 100, 1000 mGy). In both models, ionizing radiation did cause growth restriction up to 16 weeks of age, but this was only observed from doses above 100 mGy. Overall, the levels of ionizing radiation patients receive is low and from diagnostic exposures during pregnancy, there does not appear to be any strong effects on the developing foetus.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Radiation is necessary in medicine to observe the internal structures of the body, but it can sometimes cause unwanted biological changes within the body. This risk is heightened when considering exposure to developing baby because of the dynamic changing it is naturally going through and possible lifetime left to experience effects. This thesis aimed to understand what levels of radiation patients receive in hospital, observing one population predicted to receive high levels (Intensive care patients) and one predicted to receive low levels (pregnant patients). Overall, the majority of patients in the two cohorts received less than the recommended yearly public limit of 1 millisievert (mSv). The second aim was to observe the effects on the growth, lungs and hearts of the babies in an animal model when they are exposed during pregnancy. Radiation had no overall effect on the lungs or heart but can reduce body weight at moderate (100 milligrays (mGy) and high (1000 mGy) exposures.


title: Investigating the role of cellular bioenergetics in genetic neurodegenerative disorders

contributor:
Truant, Ray
Biochemistry and Biomedical Sciences

subject:
Neurodegeneration
Huntington's disease
Spinocerebellar ataxia
Cellular stress
Trinucleotide repeat disorder

abstract: Neurodegenerative disorders are among the most devastating human illnesses. They present a significant source of morbidity and mortality, and given an aging population, an impending public health crisis. Disease-modifying treatments remain sparse, with most current therapies focused on reducing symptom burden. The cellular stress response is intimately linked to energy management and has frequently been posited as playing a central role in neurodegeneration. Using two distinct neurodegenerative diseases as ‘case studies’, aberrant cellular stress and energy management are demonstrated as potential pathways contributing to neurodegeneration. First, the Huntington’s disease protein, huntingtin, is observed to rapidly localize to early endosomes, where it is associated with arrest in early-to-late and early-to-recycling endocytic trafficking. Given the energy-dependent nature of vesicular trafficking, this arrest is postulated to free substantial energy within the cell, which may subsequently be diverted to pathways that are critical for the initiation of longer-duration stress responses, such as the unfolded protein response. In the context of Huntington’s disease, impaired recovery from this stress response is observed, suggesting deficits in intracellular vesicular trafficking and energy regulation exist in disease states. In the second ‘case study’, a novel spinocerebellar ataxia variant is characterized, occurring as a result of point mutations within two genes: ATXN7 and TOP1MT, which encode ataxin-7 and the type I mitochondrial topoisomerase (top1mt), respectively. Ataxin-7 has previously been implicated in spinocerebellar ataxia type 7, which occurs as a result of a polyglutamine expansion in the first exon of the protein. Patient cells are noted to have substantially lower mitochondrial respiratory function in comparison to healthy controls and decreased levels of mitochondrial DNA, and ataxin-7 subcellular localization is observed to be abnormal. This suggests that there is important interplay between the mitochondria and proteins implicated in neurodegeneration and provides further support for aberrant cellular bioenergetics as a unifying pathway to neurodegeneration. In the concluding chapters, the nuclear localization signal of ataxin-7 is characterized, and there is analysis comparing conical ‘atraumatic’ lumbar puncture needles with bevel-tipped ‘conventional’ needles. Atraumatic needles are noted to be associated with significantly less patient complications and require fewer return visits to hospital. Moreover, atraumatic needles are demonstrated to have similar rates of success and failure when controlling for important variables like clinician specialty, dispelling common misconceptions surrounding their ease-of-use. As lumbar puncture is ubiquitous within the clinical neurosciences and is important for diagnosis, monitoring, and treatment of disease, as well as clinical trials, this work has far-reaching implications for patient care and future research.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Functional outcomes and management for distal biceps tendon rupture

contributor:
MacDermid, Joy
Rehabilitation Science

subject: Distal biceps, surgery, rehabilitation, exercise, physiotherapy, physical therapy,

subject: Distal biceps rupture, rehab, surgical tendon repair

abstract:
Although rare, distal biceps tears are common in middle-aged men in their 4th and 5th decades of life. The evidence surrounding prognosis, complications and rehabilitation interventions for distal biceps ruptures are of poor quality and therefore, many questions remain to be answered. This thesis includes four manuscripts describing studies that aim to improve our understanding of the rehabilitation of surgical and non-surgical management of distal biceps tendon rupture, prognostic factors associated with surgical repair and the outcomes for non-surgical management.
	The first manuscript is a scoping review of rehabilitation procedures described in the literature for the management of distal biceps ruptures. Overall, rehabilitation descriptions for distal biceps ruptures are poor for both post-surgical and non-surgical management. The findings suggest heterogeneity, both on the reporting and the content of rehabilitation delivered as a stand-alone intervention or post-operatively.
	The second manuscript is a cross-sectional study evaluating potential factors associated with reduced function post double incision surgical repair. The findings suggest that having a smoking history and weaker biceps flexion strength are associated with a poor prognosis and accounted for 50.4% of the variability in functional scores. These findings support existing studies that indicate a smoking history is associated with less favourable pain, function and disability outcomes follow distal biceps repair.
	The third manuscript is a prospective study evaluating prognostic factors associated with reduced function for those undergoing double incision surgical repair. These findings suggest that the majority of persons undergoing a distal biceps repair using a two-incision approach have minimal complications and good functional outcomes. In addition, having surgery on the non-dominant hand and having a weaker grip strength at baseline accounted for 43.4% of the variability of functional scores.
	The fourth manuscript describes two cases of non-surgical management of a complete distal biceps rupture. Despite the common belief that surgical repair for biceps rupture results in superior elbow flexion and supination strength, these cases demonstrated that full recover of strength and function is possible through rehabilitation alone. This study contributes to the evidence-base by questioning the need for surgical repair for all cases of distal biceps ruptures.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: The biceps tendon is prone to rupture where it inserts into the elbow. While not a common injury, it does occur more often in middle aged men following a forceful movement. Most of the research regarding the prognosis and management of distal biceps ruptures is of poor quality and imprecise due to small sample sizes. This thesis examined management in a set of studies. A scoping review indicated that rehabilitation descriptions for distal bicep ruptures were of very poor quality for both surgical and non-surgical management for this condition. A cross-sectional analysis of 60 patients revealed that having a smoking history and weaker flexion strength was associated with poor outcomes after distal biceps repairs. A prospective cohort study of 34 patients found that having surgery on the non-dominant arm and weaker grip strength was associated with poor outcomes 6-12 months after surgical repair. Given the excellent outcomes after surgery and presumption of the need for surgery as standard practice, there has been little attention to the role of conservative management. We evaluated two cases where patients refused surgery and were able to recover full strength and functional abilities using a comprehensive rehabilitation program. This thesis confirms that excellent outcomes occur after this injury and raises the need for future trials comparing surgery and rehabilitation as treatment options. The fact that this injury often occurs in healthy men may partially explain the excellent outcomes with surgery or rehabilitation.


title: ROADSkills: Developing an evidence-based and user-informed approach to refreshing older adults' driving skills

title: Refreshing older adults' driving skills

contributor:
Vrkljan, Brenda
Rehabilitation Science

subject:
Older Adults
Driver Training
Driver Education
Refresher Program
Older Driver
Feedback
Systematic Review
Randomized controlled trial

abstract:
Driving is the preferred mode of transportation among community-dwelling older Canadians. Unfortunately, drivers aged 70+ have a high risk of being injured or killed in a collision. Many collisions are caused by poor driving habits, which could be avoided by improving their behind-the-wheel behaviours. The manuscripts in this thesis describe the development of an evidence-based and user-informed driver training program aimed at refreshing older adults’ driving skills.
First, a systematic review of older driver training programs was undertaken to examine evidence specific to the impact of this training on improving road safety knowledge, self-perceived driving abilities, and on-road performance. Results highlighted the breadth of approaches used to train older drivers. Interventions were most effective when feedback was tailored to the specific needs of an aging driver.
The second manuscript outlines a qualitative descriptive analysis exploring older adults’ motivations to participate in driver training with key stakeholders (i.e., older drivers and service delivery providers). Findings indicated having insight into one’s driving abilities, experiencing a near-miss or crash, as well as an openness to improving behind-the-wheel skills were factors that could influence seeking out and participating in such training. Stakeholders also emphasized considerations for educating older drivers.
The final manuscript describes the design and evaluation of a driver training program. In this randomized controlled trial, older drivers watched either a video of tailored feedback on their driving or a generic video on aging-in-place. When the on-road performance was compared between treatment groups, those who received tailored feedback significantly reduced the number of errors they made behind-the-wheel.
Ensuring driver training programs are designed to consider the specific needs and preferences of older adults is critical, which can lead to innovations that help maintain driving ability and community mobility in later life.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Being able to drive is important to many older Canadians. Unfortunately, drivers aged 70+ have a high risk of being injured or killed in a car crash. Many crashes could be avoided by improving their driving skills. This thesis describes the development of an older driver training program. The first study examined research evidence on such programs where tailoring feedback was key to improving on-road performance. In the second study, older adults and other stakeholders identified what was important when designing training for aging drivers. They felt the focus should be on areas of improvement as well as strengths when behind-the-wheel. In the final study, older drivers underwent training where they watched either a video with feedback on their driving or a generic video on aging-in-place. Those who received feedback made fewer mistakes behind-the-wheel. Findings emphasize the importance of including older adults’ needs and preferences when designing driver training programs.


title: STUDIES ON THE PATHOPHYSIOLOGY OF CANCER-INDUCED BONE PAIN

contributor:
Singh, Gurmit
Health Sciences

subject:
Pain
Cancer
Cancer Pain
Cancer-Induced Bone Pain
System xC-
xCT
SLC7A11
Progesterone
Pregabalin
Electrophysiology
RNA-Seq
Neuroprotection

abstract: Metastatic bone cancers cause severe symptoms including pain that compromises patient functional status, quality of life, and survival. Current treatment strategies have limited efficacy and dose-limiting side effects. Cancer-induced bone pain (CIBP) is a unique pain state that shares features with but is distinct from the pathology of neuropathic and inflammatory pain. This dissertation investigates how CIBP is generated and maintained by the direct effects of cancer cells on their metastatic microenvironment and the peripheral nervous system, including unique signaling properties and gene expression changes. In particular, we found that genetic knockdown of the functional subunit xCT of the system xC- cystine/glutamate antiporter can reduce CIBP, further elucidating this as a therapeutic of interest. We found that the neuroprotective voltage-gated calcium channel inhibitors progesterone and pregabalin markedly reduce mechanical hypersensitivity and excitability in sensory neurons of the dorsal root ganglion (DRG) in male rat models of neuropathic pain, but that these effects and less pronounced in females. In cancer pain, these sex differences are reversed, with females but not males demonstrating a delay in time-to-onset of mechanical hypersensitivity. We also analyzed gene expression at the DRG by RNA-Sequencing of rat models of CIBP. Our findings uncovered differential gene expression between CIBP and sham controls and between ipsilateral and contralateral DRGs in CIBP model rats. These studies have identified several promising avenues for therapeutic research for CIBP.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: The tools we have right now to manage severe and chronic pain are insufficient. Patients with advanced cancers including bone cancer can suffer from very severe pain. This pain is generated in a number of ways including by the tumour itself releasing chemicals that activate pain-sensing nerves, by the destruction of the bone in and around the tumour, and by the sensitization of the nervous system, which can make pain worse and longer lasting. We have taken three approaches to researching cancer pain and to investigating new treatments. We have found that by reducing the amount of glutamate that cancer cells can release into their environment, we can reduce cancer pain in mice. We also found that treating rats with pregabalin and progesterone can change nerve signaling and reduce neuropathic pain, but that this effect is most pronounced in male rats with neuopathic pain and smaller in female rats with neuropathic pain, and even smaller in rats with cancer pain. We also analyzed expression of all the protein-coding genes in dorsal root ganglia from rats with cancer pain and found that there are many differences from rats without pain. Some of these differences may be promising new research targets. Going forward this research has provided important evidence necessary for next steps to develop new therapies and research strategies for cancer pain.


title: SYNERGISTIC HEMOLYSIS IN “NON-HEMOLYTIC” BACTEROIDES SPECIES

subject: Bacteroides Hemolysis

abstract:
Bacteroides is a genus of anaerobic bacteria that are often found in high abundance in the human colon. They have a complex relationship with their human host, conferring health benefits as members of the gut microbiota but also acting as opportunistic pathogens. Though many of the virulence factors in Bacteroides have been characterized, it is currently classified as nonhemolytic. Work with Bacteroides isolates led to the observation, by happenstance, of unexpected hemolytic activity in multiple species. After incubation on blood agar plates, we observed that some isolates were clearly hemolytic, but only when plated in close proximity to certain, ‘activating’ isolates. We performed a systematic screen for hemolytic activity on a library of 94 Bacteroides isolates and identified one which was able to activate hemolysis in 30% of the collection.
Using timelapse photography, we show this zone of hemolysis begins between the two colonies and proceeds in a retrograde fashion towards the ‘activated’ colony. The asymmetrical patterns of hemolysis are unlike any bacterial synergy reported to date. To investigate the mechanism behind this pattern, we combined a comparative genomics and mutagenesis approach to narrow down the genetic basis of this phenotype. Here, we characterize a unique synergistic hemolysis phenotype in Bacteroides, a genus of bacteria currently classified as nonhemolytic. This novel phenotype may provide further insight into Bacteroides as an opportunistic pathogen and may have uncovered a new mechanism by which they interact.

abstract: Thesis

abstract: Master of Science (MSc)


title: Gone to the War Dogs: An Analysis of Human-Canine Relationality in Twenty-First Century Conflict and War

contributor:
O'Brien, Susie
English and Cultural Studies

subject:
cultural theory
human-animal studies
dogs
critical war studies

abstract:
This dissertation approaches both being and knowledge as functionally no different than storytelling, with stories themselves given life by the various theoretical and narrative frameworks and strategies through which they are shaped and made credible. Storytelling is the foundational methodology of this work, and the work itself takes imagination as central to complicating and disrupting the normative terms (i.e., the stories) of both being and knowledge. Its particular agenda is in making space for imagining futures without both war and the figure of the human, especially the human as Man, as a way through the interminable conflict characteristic of the contemporary historical moment.
Situated in the field of human-animal studies, the analysis takes up military working dogs, which I argue are made to sustain the disimagination processes inherent to militarization. The innate dehumanization of war requires narratives that recover the human, and dogs, as companion species and creatures of the home, are especially well positioned for this task. Drawing on Black feminist thought, and anti-colonial insights from Indigenous thinkers, this work also shows how such dogs are used strategically within assemblages of whiteness to reify certain forms of sovereignty at the expense of both racialized people and dogs. Finally, I argue that imagining futures without conflict and war requires asking seemingly unimaginable questions, such as why sacrificing dogs in combat seems an unassailable truth given the alternatives. By asking such questions, I seek to engage a kind of radical imagination unconstrained by the limits of Man as the locus of ethics, especially during times of conflict, and to bring about an appreciation of dogs, whether in combat or otherwise, as beings for whom our responsibility to, and ethical relation with, runs far deeper than most humans willingly acknowledge.

abstract: Dissertation

abstract: Candidate in Philosophy

abstract: This project looks at weaponized and military working dogs within the context of war and conflict to examine the stories we tell about them, and what these stories do. I ask, how do these stories work and who are they for? To answer these questions, I traverse an expansive archive that includes, among other things, popular media representations, military memoir, mainstream journalism, and documentary film. I am especially interested in the ways stories about dogs inform how we understand war, militarization, and race, and how they impact the operation of power and sovereignty. I argue that dogs have been used to teach us who is and isn’t human, but that our obligation and responsibility to the gift that dogs bring is to undo the oppressive story of Man, which institutes untold amounts of suffering and oppression across species, and to tell new stories in its place.


title: Being, Negotiating, Mending: Experiences of Care in Neoliberal Times

contributor:
Chouinard, Vera
Geography and Earth Sciences

subject: healthcare, care, lived experience, neoliberalism, ethnography, autoethnography, austerity

abstract: The purpose of this study is to explore care in Ontario, Canada from the perspective of patients. I took on the roles of both a patient and a researcher, exploring the current state of care as a patient who has navigated the health system and as a researcher with background in disability studies and social geography. I use feminist auto/ethnographic methods, including observation and fieldnotes, journaling, memory, and notes in my patient records as data. I also conducted semi-structured in-depth interviews with seven individuals who underwent hip or knee replacement surgery and two family members who provided informal care to individuals post-operatively. I have organized data using three storylines: being patient, negotiating care, and mending fault lines. There are two layers of my analysis: our individual encounters with carers alongside our changing embodiment and the broader care relations of the system, increasingly influenced by neoliberalism. Care is increasingly informalized and commodified as austerity measures cut public financing for care and services are de-listed. Neoliberalism produces poor and precarious working conditions for nurses and personal support workers and this translates into insufficient care for patients and support for families. With care increasingly being shifted to the home and community, individuals and families are taking on more responsibility in terms of caring for family members.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: In this study I explore care in Ontario, Canada both as a patient and as a researcher with background in disability studies and social geography. I observed care and recorded fieldnotes as a patient researcher over thirty-two months and interviewed a total of nine people who underwent hip or knee replacement surgery about their experiences of care pre and post-operatively. Two daughters of participants also took part in interviews. I explore our individual stories of care and how the broader health system helps to shape our encounters with health care workers. Government reductions in funding for care and the de-listing of services translates into poor working conditions for health care workers and insufficient care for patients. The responsibility for care is increasingly being shifted from the state to individuals. My research reveals how patients manage within this fragmented system made up of formal, informal, and private care arrangements.


title: SYSTEM-LEVEL SEISMIC PERFORMANCE OF CONCENTRICALLY BRACED FRAMES WITH REPLACEABLE BRACE MODULES

contributor:
Wiebe, Lydell
Civil Engineering

subject:
Earthquake engineering
Steel structures
Concentrically braced frames
Replaceable brace modules
Collapse fragility
Inelastic behaviour
Seismic design
Column demand
Large-scale tests
Seismic performance

abstract: Concentrically braced frames with replaceable brace modules (RBMs) have the potential of improving the constructability of braced frames, mitigating the structural damage during earthquakes, and minimizing the time of post-earthquake repairs. To fill the gaps between the component-level performance of RBMs and system-level behaviour of SCBFs with RBMs, this thesis focused on the overall system-level seismic performance of SCBFs with RBMs in three steps. Firstly, the effects of beam-column connection fixity on the behaviour of three SCBFs were investigated to determine what level of fixity, if any, is required to ensure adequate collapse capacity of an SCBF. Secondly, the effects of column design parameters on braced frame seismic performance were investigated, where two different brace-to-frame connections were considered: 1) conventional gusset plate connection and 2) the newly proposed connection detail with RBMs. Detailed numerical modelling was undertaken to develop improved provisions for designing columns in SCBFs. Finally, a large-scale experimental program was conducted to evaluate the seismic performance of braced frames with initial and replaced RBMs where realistic boundary conditions were provided. Three different beam-column connections that can be used in SCBFs with RBMs were designed and tested. Based on the current work, the recently proposed concept of replaceable brace modules, accompanied by the recommended methods for designing columns and detailing beam-column connections, appears to be a promising approach. The fabrication and installation are simpler, the seismic performance is similar to that of SCBFs with currently accepted connection detailing, and the approach can increase the post-earthquake reparability of steel concentrically braced frames.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Human Stem Cell Models Identify Targets of Healthy and Malignant Hematopoietic Regulation

contributor:
Bhatia, Mick
Biochemistry and Biomedical Sciences

subject:
hematopoiesis
pluripotent stem cells
chronic lymphocytic leukemia
chemotherapy-induced myelosuppression
patient derived xenograft model
trisomy 12

abstract: Hematopoiesis is the highly regenerative process of producing billions of blood cells each day, including white blood cells, red blood cells, and platelets. Given the relatively short life span of these mature cells, hematopoiesis is dependent on stem and progenitor cells to generate renewed progeny, which represents a tightly regulated process. This includes cell intrinsic and external factors, and where dysregulation can lead to anemia and cancer. As such, the hematopoietic hierarchy has been intensely studied for nearly a century and represents a gold standard model of cell fate and developmental biology, in research and clinical applications. Cellular models, such as in vitro culture and human-mouse xenografts in vivo, have been developed to explain complex phenomena pertaining to hematopoiesis and also interrogate processes which are too invasive to study in humans. Hematopoietic generation is required beyond sustaining homeostasis, and progenitors can be damaged through cytotoxic injuries such as radiation and standard chemotherapy, and also undergo leukemic transformation. There are two main treatment modalities for leukemia patients (a) receiving a stem cell transplant, and (b) drug or radiation-based therapy. In the former, shortages of donors and stem cells has remained an unmet clinical need for decades. In the latter, selective targeting of genetic mutations has become a successful standard-of-care in leukemias such as chronic myelogenous leukemia and acute promyelocytic leukemia. However, in the most common adult hematologic malignancy, chronic lymphocytic leukemia (CLL), similar targeting therapies have not been developed. Altogether, shortages of stem cells from healthy donors, chemotherapy-induced immune dysfunction, and a lack of targeted therapies, all reinforce the immediate need for innovative cellular models to address these clinical problems. To generate additional sources of human hematopoietic progenitors for laboratory study, human PSCs have been used. Unlike hematopoietic progenitor cells collected from healthy and leukemic donors, human pluripotent stem cells (PSC) can be easily propagated and expanded in vitro. PSCs can generate hematopoietic progenitor cells, but they remain poorly understood and have not been robustly applied to solve the aforementioned deficiencies related to patient treatment. Importantly, the biological regulation of both hematopoiesis and PSCs has been experimentally confirmed to significantly deviate between humans and other animals, such as mice, further reinforcing the importance of human-specific cell models of hematopoiesis. Therefore, I hypothesized that human stem cell models provide a focused approach to interrogate the regulation of hematopoiesis from the apex of the hierarchy, which can be used to understand the promotion of healthy hematopoiesis and understand malignant transformation. Collectively, the data presented within this thesis offer a deeper conceptualization of human stem cell models and the deconvolution of several complex components of hematopoietic regulation. This work has revealed novel, clinically relevant, and actionable targets to ultimately enable the promotion of healthy hematopoiesis on multiple fronts.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: This thesis presents research on novel molecular and genetic regulatory pathways of self-renewal and differentiation in models of healthy and malignant human hematopoiesis. The origin of healthy hematopoietic regulation stems from a large body of work spanning decades and encompasses many efforts by others to derive hematopoietic stem cells from human pluripotent cells. The development of a genetic model for the malignant regulation of CLL was truly serendipitous, was propelled through robust and intriguing results that begged for further exploration, and filled a clinical gap in identifying actionable targets in CLL. Lastly, these two projects, along with my supportive roles in other published works throughout my graduate studies, instructed me to develop a human-mouse transplant model to uncover the biology of regenerating healthy hematopoiesis during injury.


title: Design of Time-Gated CMOS SPADs Towards High-Performance Imagers

title: Design of CMOS SPADs Towards High-Performance Imagers

contributor:
Deen, Jamal
Electrical and Computer Engineering

abstract:
SPAD (Single-Photon Avalanche Diode) sensors, capable of detecting down to the single photon level for ultimate sensitivity, have shown great promise as the photodetector of choice for next-generation devices used in positron emission tomography, fluorescence lifetime imaging, light detection and ranging, and more. SPAD fabrication has shifted recently towards custom technologies, 3D stacked designs, and post-processing steps (micro-lenses) to improve performance at the expense of increased cost and complexity. This thesis explores time-gating and multi-junction techniques to improve SPAD performance in standard planar CMOS (Complementary Metal-Oxide-Semiconductor) processes to take advantage of their potential for monolithic integration with other mixed-signal circuitry for simple, low-cost, high-performance imaging solutions.
An unbuffered triple-junction SPAD was fabricated to investigate the potential for wavelength distinction, however the top two junctions (n+/p-well and p-well/deep n-well) showed excessive noise, and the deepest junction exhibited a similar spectral response to the top junction, potentially due to a large influence from the process layers over the active area. A time-gated SPAD pixel based on the top junction was also designed and fabricated in the TSMC standard 65 nm CMOS process with a fill-factor of 28.6%. At an excess voltage of 300 mV, it achieved a peak photon detection efficiency of ~3.5% at 440 nm, <1% afterpulsing probability for hold-off times >22ns, and <200 ps timing jitter.
Lastly, the potential for high-performance CMOS imaging systems was demonstrated through the development of a prototype open-source, low-cost, highspeed camera built with standard commodity hardware. It achieved 211 frames per second (fps) at its maximum resolution of 1280x1024, and up to 2329 fps at a 256x256 resolution, with a cost well under $1000 USD. It was found to be very competitive to current low-cost, commercial highspeed cameras using a new figure-of-merit comparison and was tested for biological microscopy applications involving C. elegans worms.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: The CMOS (Complementary Metal-Oxide-Semiconductor) technology process has made accessible the development of highspeed digital circuitry and sophisticated image sensor arrays. SPADs (Single-Photon Avalanche Diodes) capable of detecting single photons for ultimate sensitivity can be fabricated in a standard CMOS process and paves the way for low-cost, next-generation, high-performance, and miniature imaging solutions. In this thesis, a time-gated SPAD implemented in a smaller CMOS technology node not typically investigated in the literature was tested and showed strong overall performance despite suffering from increased noise. A multi-junction SPAD capable of increased photon detecting capabilities was also explored and a time-gated, dual-junction solution was designed and simulated to take advantage of both structures while overcoming the difficulties of integrating them. Finally, a low-cost, highspeed camera is built with standard commodity hardware and a CMOS image sensor to demonstrate the capabilities and ease of developing high-performance imagers comparable to or better than commercial solutions.


title: THERMOMECHANICAL PROCESSING OF MICROALLOYED STEELS: EXPERIMENTS AND MODELLING

contributor:
Zurob, Hatem
Materials Science and Engineering

subject:
Thermomechanical Processing
Microalloyed Steels
Experiments
Modelling

abstract:
Recovery, recrystallization, grain growth and precipitation constitute the fundamentals of thermomechanical controlled processing (TMCP) of microalloyed steels.  In-depth understanding of these phenomena is indeed needed.  In this work, the individual components and some of the potential mutual interactions have been investigated deliberately.
The effect of alloying elements of Mn, Si, and Al on recovery and recrystallization has been systematically studied by conducting the stress relaxation tests on binary Fe-0.1%C and ternary Fe-0.1%C-X alloys.  The effect of temperature on recovery kinetics was also investigated.  The effects were considered by fitting the recovery model through the activation volume term.  Higher temperature or lower solute content will accelerate the recovery process and then facilitate the onset of recrystallization.
NbC precipitation behavior has been investigated using a nickel-based model alloy, having samples deformed at both room temperature and elevated temperature and subjected to annealing at 700℃ for different times, in order to elucidate the stages of nucleation, growth and coarsening for precipitation.  The microstructures preserved by water quenching were examined using transmission electron microscopy (with both metal foil and carbon replica specimens).  Results from mechanical response and microstructural evolution are linked and discussed.  The precipitate number density and size evolution show good agreements with predictions from a classical strain-induced precipitation model.
The in-situ laser-ultrasonics measurement of C-Mn steels provides a unique way to evaluate grain size evolution during TMCP, for different strains of 0.15, 0.25 and 0.35, at 950℃ and 1050℃.  Effects of temperature and strain on recovery, recrystallization and grain growth have been covered and elucidated.  Higher strains facilitate the onset of recrystallization and grain size refinement.  However, higher temperatures only shorten the onset of recrystallization but lead to larger grain size.  The effect of microalloying element of Nb on softening kinetics was also investigated by comparing C-Mn/C-Mn-Nb steels at the same conditions.  The solute drag effect of Nb can be seen by the onset-delays of recrystallization and larger grain sizes.  The laser-ultrasonics results can match well with stress relaxation measurements.  The in-situ grain size evolution data has given the possibility to develop robust thermomechanical processing (TMP) models combining deformation, recovery, precipitation, recrystallization and grain growth. The application and validation of the TMP models have been attempted and remain ongoing.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Psychiatry Educators' Perception of Communication Development in Psychiatry Trainees: Developing a Competence Framework

contributor:
Sherbino, Jonathan
Health Science Education

subject:
psychiatry
medical education
competency-based
communication

abstract:
Introduction: In medical education, communication is recognized as a core competency for physicians. In Canada, medical students are taught core communication abilities. The importance of communication in postgraduate training is recognized in the CanMEDS competency framework. Although robust literature exists on teaching communication abilities to medical students, research in communication abilities for psychiatry residents is lacking, despite the fact that the clinical interview is frequently the only diagnostic tool available and often a key part of patient treatment. Given the transition to competency-based education in Canadian postgraduate medical education, it is critical that the psychiatric profession gains an improved understanding of the progression of communication abilities in psychiatry training. This study seeks to understand the progression of communication skills development in psychiatry.
Methods: This study used a constructivist grounded theory approach. This study used purposive sampling and conducted semi-structured interviews with 14 faculty educators who regularly supervise psychiatry residents at two sites affiliated with one university-based residency program. Constant comparative analysis occurred concurrently with iterative data collection until thematic sufficiency was reached and all relationships between themes were determined.
Results: Five themes outlining the progressive development of communication abilities were identified. Three themes identified three foundational sets of abilities, including refining pre-existing relational abilities, developing a repertoire of specific psychiatric communication abilities, and learning to reflect upon and manage one’s own internal reactions. These competencies served as foundational pillars for the final two themes, in which residents develop the personalized art of flexible psychiatric interviewing, which then allows them to skillfully partner with their patients in co-creating care plans.
Conclusion: This research represents a first step in defining a communication competency framework for psychiatry residents. It includes defining the core abilities required for progression to unsupervised practice. Future research should explore generalizability, test the framework, and determine teaching and assessment methods.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: In contemporary medical education, the ability to communicate well with patients is a fundamental competency. This set of abilities is taught in medical schools and reflected in residency training competence frameworks, such as the CanMEDS framework. In psychiatry residency training, communication is fundamental as the clinical interview is typically the only diagnostic tool available and frequently part of the treatment of psychiatric illness (e.g., psychotherapy). However, the development of psychiatric communication competency remains understudied. With the shift to competency-based education across Canadian psychiatry postgraduate residency education, understanding the development of patient communication abilities in psychiatry residents is critical for teaching and assessment. This research examines psychiatry educators’ perceptions of the developmental model of psychiatry resident competence in communication. The results of this study highlight five clear themes that emerge to explain how residents achieve the abilities to communicate with their patients at a level of competence that is compatible with independent practice. This framework brings clarity to the unique set of abilities that psychiatrists use to communicate with and help their patients. It will also serve as a foundation for developing teaching and assessment methods in psychiatry residency education and will serve as a basis for further research on the development of communication abilities in psychiatry residents.


title: Molecular simulation for physicochemical properties of liquid mixtures with industrial applications

contributor:
Xi, Li
Chemical Engineering

subject:
Molecular Dynamics
Polymer
Thermodynamics
Azeotrope
Plasticizer
Design Parameters

abstract:
Liquid mixture is everywhere in the chemical industry and widely studied by researchers.
An accurate prediction of its physicochemical property is of vital importance in developing efficient process optimization. However, measurements from experiment are usually time consuming and inefficient. Furthermore, clear understanding of many of fundamental physicochemical phenomena hasn't been obtained, which restricts the development of novel products. Molecular simulation techniques have become an impressive tool to deal with these challenges during past decades. This thesis mainly applied molecular simulation to predict the physicochemical properties of industrially relevant mixtures and investigate the molecular mechanism behind observed phenomena. Among various properties, cohesive energy is the central focus, which reveals intermolecular interactions between molecules of different types. Mixture systems of two different areas of application were studied.

The first is amorphous polymer-plasticizer mixtures, which, with varying composition, correspond to plastic products of different grades for application in different areas. The most important class of plasticizers are phthalate diesters, in which di (2-ethylhexyl) phthalate (DEHP) is the most frequently used compound. However, phthalates are prone to migration loss from the host poly(vinyl chloride) (PVC), which results in the contamination of surrounding environment, gradual deterioration of plastics performance, and potential harm to human health. It has thus prompted tightening governmental regulation on their usage. With this background, we aim to address three challenges: (I) model plasticized PVC to predict its physicochemical property, (II) obtain molecular insight into plasticization and plasticizer diffusion pattern inside PVC, (III) correlate plasticizer performance -- compatibility, efficacy, and mobility --  with its molecular structure. Cohesive energy plays a central role especially in understanding plasiticzer compatibility and migration tendency.
Our modeling and simulation protocol is firstly tested on phthalates, where the simulated plasticization efficacy and thermodynamic compatibility with the host polymer agree well with all known experimental observations. Furthermore, through simulation of plasticizer diffusion pattern, we found relaxation of the alkyl side chains is a key factor in plasticizer migration. Next, we expand our simulation to a wider group of plasticizers including adipates, trimellitates, and citrates. The computed mixing enthalpy and Young's modulus again show an excellent agreement with available experimental data. Dependance of plasticizer performance on seven molecular design parameters are evaluated. The obtained relationship clearly tells us decreasing leg length or increasing branching on the leg will raise plasticizer compatibility with PVC, changing the torso group from benzene ring to alkane chain will highly improve plasticizer efficacy, and attaching three legs on the torso will decrease plasticizer mobility. As a side outcome, we also report a nontrivial chain-length dependence of the cohesive energy and solubility parameter of long-chain polymers, which is an important consideration in the calculation of these quantities using molecular simulation.

The second area is azeotropes, the separation of which in chemical processes is usually very difficult due to the same composition in vapor and liquid phases at the azeotropic point. So far, a fundamental understanding of azeotrope formation is still missing. In this thesis, we aim to address two fundamental questions: (I) the mechanism for ethanol/benzene azeotrope formation, (II) classification of different polar-polar positive azeotropes.
First, Gibbs ensemble Monte Carlo (GEMC) simulation is performed to predict the vapor-liquid equilibrium (VLE) phase diagram of ethanol/benzene, including an azeotrope point. The results match well with experiments. Free energy and cohesive energy profiles analyses are then performed. From a thorough liquid structure analysis, we conclude a three-stage mechanism for azeotrope formation: 1) formation of small ethanol clusters at low composition, 2) microscopic phase separation between ethanol and benzene, 3) isolation of benzene. This approach is then extended to four additional polar-polar mixtures (ethyl acetate/methanol, ethyl acetate/ethanol, ethanol/water, and 1-propanol/water) to obtain their VLE diagrams, which again match well with experiments. Free energy and cohesive energy analyses indicate that there are two types of mechanisms, a three-stage mechanism with weak cross-interactions (for the first two mixtures) and a three-stage mechanism with strong cross-interactions (for the last two mixtures). So far, our analyses on mixture liquid micro-structure can partially prove the existence and classification of those mechanisms.

Overall, the successful prediction in physicochemical properties of two liquid mixtures with very different molecular scales proves the robustness of our study strategy, which could be used to study any liquid mixtures and understand their related physicochemical phenomena.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: PLANNING AND SCHEDULING OF CONTINUOUS PROCESSES VIA INVENTORY PINCH DECOMPOSITION AND GLOBAL OPTIMIZATION ALGORITHMS

title: INVENTORY PINCH DECOMPOSITION AND GLOBAL OPTIMIZATION METHODS

contributor:
Mahalec, Vladimir
Chemical Engineering

subject: planning and scheduling

subject: inventory pinch

subject: global optimization

subject: normalized multiparametric disaggregation

subject: gasoline blend scheduling

subject: refinery planning

abstract: Ph. D. Thesis

abstract:
In order to compute more realistic production plans and schedules, techniques using nonlinear programming (NLP) and mixed-integer nonlinear programming (MINLP) have gathered a lot of attention from the industry and academy. Efficient solution of these problems to a proven ε-global optimality remains a challenge due to their combinatorial, nonconvex, and large dimensionality attributes.
The key contributions of this work are: 1) the generalization of the inventory pinch decomposition method to scheduling problems, and 2) the development of a deterministic global optimization method.
An inventory pinch is a point at which the cumulative total demand touches its corresponding concave envelope. The inventory pinch points delineate time intervals where a single fixed set of operating conditions is most likely to be feasible and close to the optimum. The inventory pinch method decomposes the original problem in three different levels. The first one deals with the nonlinearities, while subsequent levels involve only linear terms by fixing part of the solution from previous levels. In this heuristic method, infeasibilities (detected via positive value of slack variables) are eliminated by adding at the first level new period boundaries at the point in time where infeasibilities are detected.
The global optimization algorithm presented in this work utilizes both piecewise McCormick (PMCR) and Normalized Multiparametric Disaggregation (NMDT), and employs a dynamic partitioning strategy to refine the estimates of the global optimum. Another key element is the parallelized bound tightening procedure.
Case studies include gasoline blend planning and scheduling, and refinery planning. Both inventory pinch method and the global optimization algorithm show promising results and their performance is either better or on par with other published techniques and commercial solvers, as exhibited in a number of test cases solved during the course of this work.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Optimal planning and scheduling of production systems are two very important tasks in industrial practice. Their objective is to ensure optimal utilization of raw materials and equipment to reduce production costs. In order to compute realistic production plans and schedules, it is often necessary to replace simplified linear models with nonlinear ones including discrete decisions (e.g., “yes/no”, “on/off”). To compute a global optimal solution for this type of problems in reasonable time is a challenge due to their intrinsic nonlinear and combinatorial nature.
The main goal of this thesis is the development of efficient algorithms to solve large-scale planning and scheduling problems. The key contributions of this work are the development of: i) a heuristic technique to compute near-optimal solutions rapidly, and ii) a deterministic global optimization algorithm. Both approaches showed results and performances better or equal to those obtained by commercial software and previously published methods.


title: Link-focused prediction of bike share trip volume using GPS data: A GIS based approach

contributor:
Scott, Darren
Geography

subject:
Bike share
Cycling
Active travel
Eigenvector Spatial Filtering
Network Analysis
Geographic Information Systems

abstract: Modern bike share systems (BSSs) allow users to rent from a fleet of bicycles at hubs across the designated service area. With clear evidence of cycling being a health-positive form of active transport, furthering our understanding of the underlying processes that affect BSS ridership is essential to continue further adoption. Using 286,587 global positioning system (GPS) trajectories over a 12-month period between January 1st, 2018 and December 31st, 2018 from a BSS called SoBi (Social Bicycles) Hamilton, the number of trips on every traveled link in the service area are predicted. A GIS-based map-matching toolkit is used to generate cyclists’ routes along the cycling network of Hamilton, Ontario to determine the number of observed unique trips on every road segment (link) in the study area. To predict trips, several variables were created at the individual link level including accessibility measures, distances to important locations in the city, proximity to active travel infrastructure (SoBi hubs, bus stops), and bike infrastructure. Linear regression models were used to estimate trips. Eigenvector spatial filtering (ESF) was used to explicitly model spatial autocorrelation. The results suggest the largest positive predictors of cycling traffic in terms of cycling infrastructure are those that are physically separated from the automobile network (e.g., designated bike lanes). Additionally, hub-trip distance accessibility, a novel measure, was found to be the most significant variable in predicting trips. A demonstration of how the model can be used for strategic planning of road network upgrades is also presented.

abstract: Thesis

abstract: Master of Science (MSc)


title: Applications of Stochastic Control Theory in The Trading of Stocks and Futures

contributor:
Pirvu, Traian
Mathematics and Statistics

abstract:
In this thesis, we apply stochastic control methodology to analyze the trading of stocks and futures dynamically. The trader's quest for profits is formulated as an optimal control problem with finite horizon, where the objective is to maximize the expected utility of wealth at the end of the horizon, and the optimized trading strategy is given by the optimal control. Based on various well-established stochastic models of these financial securities, we derive the stochastic differential equations that describe the price dynamics in each model, formulate the utility maximization problems, analyze the associated Hamilton-Jacobi-Bellman (HJB) equations, and solve for the trading strategies in closed form. Numerical examples based on securities traded in the US markets are presented for all models.

Specifically, we investigate pairs trading with cointegrated stock pairs under the Duan-Pliska model, and with volatility index futures where the spot index is modeled as a Central Tendency Ornstein-Uhlenbeck process. We also study optimal trading of commodity futures under the two-factor Schwartz model, and under a more general $n$-factor Cortazar and Naranjo model. Given the closed-form expressions for the optimal strategies, the value functions, and the wealth processes, we see directly the dependence of the optimal positions on different model parameters, and therefore we can quantify the impact of varying parameter and coefficient values. Qualitatively, we will see, in line with intuition, that the optimal positions in general decrease in magnitude as the volatilities in the underlying factors increase. In all cases we find that the magnitudes of the optimal positions are inversely proportional to the degree of risk aversion, as expected.

In the pairs trading cases where two stocks or two futures contracts are traded, the optimal positions are of opposite signs, corresponding to a long and a short position, where the quantities are given explicitly by the closed-form formulae. Based on parameters calibrated from VIX futures historical data, we find that traders should take bigger positions in the long end of the futures curve. In the WTI oil futures trading example, we see that the optimal positions are insensitive to time to maturity. We also find that the certainty equivalent for trading two contracts simultaneously is significantly greater than that derived from trading only a single contract, regardless of the maturity of either of the single contract. Analogous result holds for the more general $n$-factor model as well.

abstract: Dissertation

abstract: Doctor of Science  (PhD)


title: Optimal Design and Operation of  Community Energy Systems

subject:
Community energy system
Optimal design and operation
Uncertainty
Life cycle GHG emissions
borehole thermal energy storage

abstract:
Energy demand for buildings has been rising during recent years. Increasing building energy consumption has caused many energy-related problems and environmental issues. The on-site community energy system application is a promising way of providing energy for buildings. Community energy system usage reduces the primary energy consumption and environmental effects of greenhouse gas (GHG) emissions compared to the implementation of the stand-alone energy systems. Furthermore, due to the increase in electricity price and shortage of fossil fuel resources, renewable energies and energy storage technologies could be great alternative solutions to solve energy-related problems. Generally, the energy system might include various technologies such as internal combustion engine, heat recovery system, boiler, thermal storage tank, battery, absorption chiller, ground source heat pump, heating coil, electric chiller, solar photovoltaics (PV) and solar thermal collectors, and seasonal thermal energy storage.
The economic, technical and environmental impacts of energy systems depend on the system design and operational strategy. The focus of this thesis is to propose unified frameworks, including the mathematical formulation of all of the components to determine the optimal energy system configuration, the optimal size of each component, and optimal operating strategy. The proposed methodologies address the problems related to the optimal design of the energy system for both deterministic and stochastic cases. By the use of the proposed frameworks, the design of the energy system is investigated for different specified levels of GHG emissions ratio, and the purpose is to minimize the annual total cost.
To account for uncertainties and to reduce the computational times and maintain accuracy, a novel strategy is developed to produce scenarios for the stochastic problem. System design is carried out to minimize the annual total cost and conditional value at risk (CVaR) of emissions for the confidence level of 95%. The results demonstrate how the system size changes due to uncertainty and as a function of the operational GHG emissions ratio. It is shown that with the present-day technology (without solar technologies and seasonal storage), the lowest amount of GHG emissions ratio is 37%. This indicates the need for significant technological development to overcome that ratio to be 10% of stand-alone systems.
This thesis introduces novel performance curves (NPC) for determining the optimal operation of the energy system. By the use of this approach, it is possible to identify the optimal operation of the energy system without solving complex optimization procedures. The application of the proposed NPC strategy is investigated for various case studies in different locations. The usage of the proposed strategy leads to the best-operating cost-saving and operational GHG savings when compared to other published approaches. It has shown that other strategies are special (not always optimal) cases of the NPC strategy.
Based on the extensive literature review, it is found that it is exceptionally complicated to apply the previously proposed models of seasonal thermal energy storage in optimization software. Besides, the high computational time is required to obtain an optimum size and operation of storage from an optimization software. This thesis also proposes a new flexible semi-analytical, semi-numerical methodology to model the heat transfer process of the borehole thermal energy storage to solve the above challenges. The model increases the flexibility of the storage operation since the model can control the process of the storage by also deciding the appropriate storage zone for charging and discharging.

abstract: Thesis

abstract: Doctor of Engineering (DEng)


title: GaN Based Cycloconverter-Type Dual-Active Bridge Converter: Control, Design, Analysis, and Experimental Verification

contributor:
Emadi, Ali
Electrical and Computer Engineering

abstract:
In recent years, there has been a greater push to reduce green house gas emissions
due to the looming threat of climate change. This has resulted in a shift towards
more electrified transportation and as a result, reliance on renewable energy such as
solar or wind and a decreased reliance on fossil fuels. Battery energy storage systems
(BESS) have been one of the prevailing methods for storing electrical energy from
intermittent energy sources due to their performance, cost and size. However, in order
to interface BESS with the AC power grid, power electronics are a necessity. With
this paradigm shift from fossil fuels to renewable energy, power electronics and their
components have been a large focus of research in the scientific community. There has
been a trend for continuous improvement of power electronic converter performance
which has led to the desire for advances in semiconductor switches. Switches with
lower power loss would allow power electronic systems to achieve higher efficiency and
higher power density. Due to the continuous desire for improvement, researchers have
begun to adopt Wide-bandgap (WBG) switching devices since silicon (Si) has been
reaching its material limit and WBG devices offer improved performance. Silicon
carbide (SiC) and gallium nitride (GaN) offer improved performance over Si, GaN in
particular offers the fastest switching speeds and based on the device rating is well
suited for medium power levels in BESS. Although the potential of GaN is known, it
is a fairly new technology and therefore a full analysis of its loss behaviour is required
in order to model the device. In addition, GaN requires advanced measurement
technologies to analyze them due to the high frequency operation and tiny device
parasitics. Before GaN can reach widespread adoption in power electronic converters,
the detailed analysis of the theoretical loss breakdown of a GaN-based power electronic
system and measurement is required.
The incorporation of GaN into isolated DC/AC converters necessary for interfacing
the AC grid with the DC battery has the potential to increase the power density
and efficiency. However, incorporating GaN alone can not fix all the current problems
in the conventional design approach of two-stage cascaded Dual-active bridge (DAB)
and inverters. Typically, the DAB and inverter are connected through an intermediate
DC bus which requires large and unreliable electrolytic capacitors to filter the
ripple power, these capacitors reduce the life-time of the converter significantly.
This thesis proposes a GaN based single-stage DC/AC converter which does not
require the large electrolytic capacitors or additional devices to filter the ripple power.
In order to control the converter, a combined duty and phase shift control method
is used. The operating condition for each discretized voltage output is derived based
on the calculation for the lowest power loss conditions.
To further investigate the proposed control and use of GaN, a greater focus on
gate driver and PCB design is needed to take advantage of the new WBG switching
devices such as GaN HEMTs. As switching frequencies are continuously pushed
higher and higher to improve the power density of converters, there is a need for
extremely fast turn on and turn off times for FETs in order to minimize losses and
maximize efficiency. However, large slew rates have a negative impact on the circuit
because the small parasitics present in the device packaging and PCB traces are no
longer negligible and can result in severe oscillations and voltage spikes that can lead
to increased losses or even device failure. Analysis of gate driver design and potential
issues for designing with GaN are presented before the prototype is presented and
analysed.
A single-stage isolated DC/AC converter using GaN is shown to provide superior
performance compared with the traditional two-stage approach. Simulation comparisons
of both converters reveal that the proposed topology greatly improves efficiency
while also removing the intermediate DC bus which is known to cause reliability issues.
The efficiency improvement is achieved through a proposed control scheme that
determines the duty and phase shift for each discretized output voltage based on a
weighting equation for minimum losses. The control scheme and converter behaviour
are both validated through the use of a experimental prototype.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Design and Fabrication of InGaAsP Quantum-Well Semiconductor Optical Amplifiers for Integration with Silicon Photonics

contributor:
Knights, Andrew
LaPierre, Ray
Engineering Physics

subject:
laser diode
silicon photonics
III-V
semiconductor optical amplifier
fabrication

abstract:
Silicon photonics provides an environmentally sustainable pathway to a more robust data infrastructure. To compensate for optical power losses, methods of amplification are required; specifically, amplifiers that can fit in a small footprint for applications in data centres. Semiconductor optical amplifiers (SOA) provide such a solution, and can be fabricated using III-V ternary or quaternary materials to enhance optical signals through a device on the scale of most CMOS components.
	This research sought to fabricate an InGaAsP multiple quantum well semiconductor optical amplifier using the facilities in McMaster University’s Centre for Emerging Device Technologies (CEDT). A ridge waveguide laser diode was first fabricated and validated, then altered by applying an anti-reflective coating to the waveguide facets to suppress reflections in the Fabry-Perot cavity in an attempt to create an SOA. The design process and fabrication methodology are explained, including an analysis of failed methodologies. Characterization measurement techniques are then detailed for the fabricated devices. Finally, the performance of the devices is presented, and future steps are suggested for improving the fabrication process to enhance device characteristics. The fabricated laser diodes produced an output power in excess of 20 mW at a peak wavelength near 1580 nm. The subsequently coated devices proved difficult to measure, displaying a maximum of 0 dB or 1 dB gain when checked for amplification, with suspicions that output loss (and therefore gain) was higher than measured. The coated devices exhibited gain saturation between -10 and 0 dBm of input power. Owing to the shapes of their characteristic curves, it was determined that SOA devices were successfully created.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Examining abiotic and biotic factors influencing bacterial and host interactions in the female reproductive tract

contributor:
Kaushic, Charu
Medical Sciences

subject: Vaginal microbiota

abstract: Currently, the leading route of new HIV-1 infection is via heterosexual transmission, in which women are disproportionately burdened. One key factor associated with a fourfold increased risk of HIV-1 acquisition is a dysbiotic vaginal microbiota (VMB). A dysbiotic VMB is characterized by a diverse mix of anaerobic species without any appreciable amounts of beneficial Lactobacillus species. Our understanding of the species-specific manner by which vaginal bacteria interact with one another and with the host to induce susceptibility remains incompletely understood.  With this, this study was designed to elucidate the interactions between common vaginal bacteria and host vaginal epithelial cells. The phenotypic and metabolic characteristics of these bacteria were also examined to provide a deeper understanding about the conditions in which each species may be able to survive and thrive. Common vaginal bacteria analyzed included dysbiosis associated species Gardnerella vaginalis and Prevotella bivia, as well as Lactobacillus species L. crispatus and L. iners. The presence of P. bivia, G. vaginalis and L. iners cocultured with vaginal epithelial cells in vitro resulted in reduced viability of vaginal epithelial cells, reduced barrier integrity and the production of pro-inflammatory cytokines. Conversely, the presence of L. crispatus did not, and was able to negate these adverse effects when placed in a dual species coculture with either of the other species. Additionally, we found that L. crispatus was the only one of these four species to produce hydrogen peroxide, and its supernatant was capable of inhibiting the growth of G. vaginalis and P. bivia. While we found that all four vaginal species could use glycogen for their growth, L. crispatus was able to use the widest range of carbohydrates tested. This translated to L. crispatus significantly outcompeting the other three bacterial species when cocultured in bacterial broth media with various carbohydrates tested. Our data provides insight into the species-specific nature by which common vaginal bacteria may interact with vaginal epithelial cells to increase host susceptibility to infection through cytotoxicity, decreased barrier function, and inflammation. We importantly observed the ability of L. crispatus to largely mitigate these effects and our phenotypic characterization place L. crispatus as the species most adept to provide protection in the FRT. Together, this work contributes to a better understanding of the interactions that govern the dynamics of the VMB and can be built upon to develop more rationale therapeutic or prophylactic interventions to improve the reproductive health of many vulnerable women.

abstract: Thesis

abstract: Master of Science (MSc)


title: Controlled Release from Agricultural Spray Deposits

contributor:
Pelton, Robert H.
Chemical Engineering

subject:
Copper Chlorophyllin (CuChl)
Colloidal and Adsorption Properties
Quartz Crystal Microbalance
Rainfastness
Agricultural Spray
Suspoemulsions

abstract:
Copper chlorophyllin (CuChl) is an antioxidant from renewable sources, which has shown as a potential active ingredient in agricultural crop sprays. The major objectives of this thesis are to understand the colloidal and interfacial behaviors of CuChl, and to develop strategies for improving its effectiveness in field applications. In this project, the following three areas are examined and analyzed.

In practice, CuChl-based formulations are sprayed directly onto a plant’s foliage. As such, there is a need to understand how CuChl interacts with relevant plant surfaces. To this end, quartz crystal microbalance with dissipation (QCM-D) was used to quantify the adsorption of CuChl aqueous solutions onto four model surfaces: polystyrene, cellulose, pullulan, and silica. The results showed that cellulose adsorbed the highest amount of CuChl, followed by polystyrene and pullulan. In addition, the results also showed that the surfactants, SDS or DTAB, could alter the binding of CuChl to cellulose when used in concentrations above the critical micelle concentration.

CuChl is composed of water-soluble and dispersed components, therefore it is not intrinsically rainfast, which limits its field application. To immobilize CuChl on leaves, a polymer combination of CMC (carboxymethyl cellulose) and PAE (polyamidoamine-epichlorohydrin) was designed for use as a spray adjuvant. The release behaviors of CuChl from dried spray deposits were investigated using varied polymer compositions and concentrations and compared with those of a water-soluble dye, brilliant sulfaflavine (BSF). The results indicated that a small amount of CuChl was immediately released upon exposure to water whereas BSF’s release behavior was dependent on the square root of time. The unusual behavior of CuChl was attributed to the presence of particles in the solution. These nanoparticles were coated with CMC:PAE complex, with the result of being immobilized on parafilm.

Suspoemulsion is the most complex agricultural formulation that is composed of both dispersed particles and emulsion droplets. The objective of this work is to understand the relationship between the solution properties of suspoemulsions and the resulting dried deposits on hydrophobic surfaces. The results showed that the distribution of polychlorinated Cu (II) phthalocyanine (PG7) particles in dried deposits was related to the extent to which PG7 particles were adsorbed on or entrained in oil droplets. The PG7 particles that mainly ended up in the center (dome) area after drying were bound to the oil/water interface in the suspoemulsion, whereas individually dispersed particles ended up in the annulus.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Agricultural formulations have been developed and widely applied to crops in an effort to maximize yields to keep up with the food demands of the world’s ever-growing population. However, there are still many challenges associated with the application of these formulations, such as huge losses due to spray drift, wash-off, and degradation during spraying. These issues can reduce the formulation’s overall efficacy and pose serious risks to the environment and human health.

The primary objective of this thesis is to explore the agricultural application of a new environmentally-friendly active ingredient, copper chlorophyllin (CuChl). To this end, this work begins by determining CuChl’s colloidal and adsorption behaviors, with a particular focus on its binding tendencies for relevant plant surfaces. Next, a polymer combination was designed as a spray adjuvant to enhance CuChl’s rainfastness performance and CuChl’s release from dried deposits was characterized. Finally, the distribution of dispersed particles in dried suspoemulsion deposits was determined.