title: Weightlifting Training: Effects on Circulatory Responses During Weightlifting and Activities of Daily Living in Older Men

contributor:
McCartney, Neil
Human Biodynamics

subject:
weightlifting training
weightlifting
activities of daily living
ADLs
circulatory responses
older men
human biodynamics
circulatory response

abstract:
Recent studies have demonstrated that increases in dynamic strength after weight-training in healthy subjects
were associated with reductions in heart rate (HR) and arterial blood pressure (ABP) during formal lifting of
identical absolute loads (McCartney et al., 1989; Sale et al., 1990). This study investigated whether the effect
could be transferred to strength-related activities of daily living in healthy older men. The effects of 10 weeks (30
sessions) of progressive dynamic weightlifting training on HR and ABP in 10 weight-trained (wttrain) subjects were
compared with 5 control subjects. Before and after training intra-brachial artery pressure and HR were monitored
continuously during: 10 repetitions of single-arm curl (SAC) and single-arm military press (SAMP) at 70 % of initial 1
repetition maximum (1 RM); 12 repetitions of single- (SLP) and double-leg press (DLP) exercise at 80% of initial 1 RM; 10 mins treadmill walking at 2.5 mph, carrying 20 and 30 pound loads between mins 4-6 and 8-10 respectively (T-10); 4 mins of treadmill walking at 3.0 mph up an incline of 8% (T-4); 12 flights of stairclimbing at 60 steps/min on a Stairmaster 6000 Ergometer (STR). In the wttrain group the 1 RM in SAC, SAMP, SLP and DLP increased overall by 61 (p < 0.007), 30 (p < 0.001), 27 (p<0.001) and 27 per cent (p < 0.001), respectively. After training the mean maximal systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), and rate-pressure product (RPP; 10^3) values in all 4 weightlifting exercises were lower. The decreases were only significant however, for the DBP in the SAC (144.0 ± 14.9 to 110.0 ± 5.2 Torr; p < 0.001), SAMP (151.0 ± 5.9 to 144.0 ± 5.4 Torr; p < 0.007), the MAP for the DLP ( 154.0 ± 5.0 to 147.0 ±5.0 Torr; p < 0.021) and RPP for the SAC (22.7 ± 2.2 to 19.1 ± 1.4; p < 0.041). The same respective measurements in the control group were either unchanged or higher. After training, there were overall reductions in the SBP (p < 0.05, mins 8-10), DBP , MAP and RPP (P < 0.05, mins 1-4) responses during T-10 with consistently higher values found in the control group. Similar, but nonsignificant patterns emerged for T-4. In contrast, there was little or no reduction in any of the measured parameters during stairclimbing. It was concluded that improved strength in older subjects results in an attenuated HR and ABP response during weightlifting, and there is a modest transfer of this effect to certain activities of daily living which involve the trained muscles.

abstract: Thesis

abstract: Master of Science (MSc)


title: Some Aspects of the Fusarium Wilt of Muskmelon and Watermelon in Southwestern Ontario

contributor:
Miller, J. J.
Botany

subject:
fusarium
muskmelon
fusarium wilt
watermelon
southwestern ontario

abstract: Distribution of Fusarium wilt of muskmelon and watermelon in southwestern Ontario was studied. Particular attention was paid to morphological and physiological variations of the isolates obtained. Morphological variations were based on comparison in culture with a selected standard. Physiological variations were detected by pathogenicity experiments, and a study of assimilation of various carbon and nitrogen compounds. Some further aspects of the biology of the organisms were investigated. An experiment was carried out, employing several muskmelons and watermelon varieties, to compare their resistance under field conditions.

abstract: Thesis

abstract: Master of Science (MS)


title: Attributable Risk Estimation in Matched Case-Control Studies

contributor:
Walter, Stephen
Statistics

subject:
risk estimation
attributable risk estimation
attributable risk
matched case-control studies
case-control
case-control studies
statistics

abstract:
This project discusses some of the methodologies developed over the years to estimate attributable risk among exposed persons and the attributable risk in the entire population (also called Etiologic Fraction). It provides a general framework for estimating attributable risk among the exposed (denoted lambda_e). By making use of the recent observation that the two measures of attributable risk can be linked through the prevalence of the risk factor among the cases (denoted V_x), an estimate of population attributable risk (denoted lambda) for matched case-control studies is determined. Using the methodology developed recently by Kuritz and Landis (1987), this project provides explicit formulas for estimating the attributable risk among the exposed and the population attributable risk, and their large sample variances. This has been done both in situations where exactly R controls have been matched to a case and for a variable number of controls per case. The methodologies are illustrated with data from some case-control studies reported in the literature. Asymptotic relative efficiencies of different
matching designs computed in terms of the costs of gathering cases and controls, are presented, together with some recommendations on what design is considered optimal.

abstract: Thesis

abstract: Master of Science (MSc)


title: Mean-Variance Utility Functions and the Investment Behaviour of Canadian Life Insurance Companies

contributor:
Aivazian, V. A.
Callen, J. L.
Robb, A. L.
Economics

subject:
investment behaviour
canadian life insurance
canada
life insurance
mean-variance approach

abstract: In recent years, considerable effort has been directed toward establishing the nature of the investment behaviour of life insurance companies. In this dissertation an extended portfolio analysis model was developed for the simultaneous determination of the efficient composition of insurance and investment activities of a life insurance company. This was done within a model that takes advantage of the existing finance foundations and the concepts and techniques of modern demand system analysis. Unlike current models which used quadratic programming techniques and are interested in the construction of efficient sets, we have used a utility maximization approach. A two parameter portfolio model was constructed utilizing elements of utility theory and of the theory of insurance. The model provided us with the proportion of assets held in the balance sheet as well as which liabilities are used to raise the necessary capital. The model developed has sufficient empirical content to yield hypotheses about life insurance portfolio behaviour and thus was tested using appropriate econometric techniques. A comparative static analysis yielded elasticities of substitution between financial assets and liabilities. The estimation of these elasticities in the context of a flexible functional form model, forms a central part of this dissertation. More specifically, by utilizing a mean-variance portfolio framework and a general Box-Cox utility function we were able to model the demand for assets and liabilities. by an insurance company. On empirical grounds we found that, in general, the square root quadratic utility function best fits the data. We also tried to evaluate the square root quadratic approximation by showing that, broadly speaking, it yields signs for elasticities of substitution which are consistant with the theory. A by-product of the model developed is the ability to compare stock and mutual life insurance companies. The common belief that mutual companies follow a riskier path in the way they conduct their business was supported by the results in this study. The results obtained from the study are-of significant importance since life insurance companies have substantial obligations to millions of households in the economy. Furthermore, despite the extraordinary decline in the importance of the life insurance industry in the bond and mortgage markets during the sixties and the seventies, the industry is still a major supplier of funds to those markets.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Mutagenesis and functional analysis of dveli, the Drosophila ortholog of C. elegans lin-7

contributor:
Jacobs, J. Roger
Biology

subject:
mutagenesis
functional analysis
dveli
Drosophila
Drosophila ortholog
C. elegans lin-7
Drosophila ortholog of C. elegans lin-7
biology

abstract: Proper assembly and localization of receptors and the associated signal transduction protein complex is important for normal cell function. Scaffolding proteins have been implicated in organizing the assembly of protein complex and localization of receptors. PDZ domain containing proteins are one major type of scaffolding protein. One well characterized system is the C. elegans LIN-2/LIN-7/LIN-10 PDZ protein complex. In C. elegans, this protein complex acts as a scaffold for the proper localization of LET-23, the ortholog of EGFR, to the epithelial basolateral membrane. The Drosophila orthologs, cmg, dveli and dmint/dX11L, have been identified. The sequence homologies and expression patterns suggest that these genes may have similar functions as their mammalian orthologs. The possible functions include cell-cell junction formation, receptor localization, ion channel localization and neurotransmitter vesicle trafficking. The main objectives of this thesis work are the mutagenesis and functional analysis of dveli. Potential mutants were generated by P element insertional mutagenesis, however, further analysis is required to identify the affected genes. A systemic RNAi experiment was performed. The delivery mechanism used was the RNAi soaking technique adapted from Dr. Davis’s laboratory protocol. Primary results from RNAi experiments show that loss of dveli function results in a reduction in larval locomotion speed. This slower locomotion phenotype along with the post-synaptic expression of dVELI at larval neuromuscular junction suggest a synaptic role of dVELI, perhaps aiding in synapse formation or proper localization of neurotransmitter receptors.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Evaporation of an Iron - 5 Percent and an Iron - 25 Percent Chromium Alloy in the Temperature Range 900°C to 1080°C

title: The Evaporation of an Iron - 5 and 25 Percent Chromium Alloy

contributor:
Smeltzer, W.W.
Metallurgy

subject:
evaporation
iron 5 percent chromium alloy
iron 25 percent chromium alloy
iron - 5 percent chromium alloy
iron - 25 percent chromium alloy
chromium alloy
metallurgy
900°C to 1080°C
temperature range 900°C to 1080°C
temperature range of 900°C to 1080°C

abstract:
In this thesis, the theory of metal crystal evaporation and of vapour pressure determinations are
presented, followed by a literature survey on the evaporation characteristics of iron, chromium and alloys of iron - chromium. Results are presented for an investigation carried out on the free evaporation kinetics of iron base alloys containing 5 percent and 25 percent chromium for the
temperature range 900°C to 1080°C. Also, a complete description of the surface topographies of evaporated specimens is presented using normal, hot stage and interferometric microscopic techniques. These results are correlated in terms of the evaporation theory and pertinent experimental data reported for other metallic systems.

abstract: Thesis

abstract: Master of Science (MSc)


title: A Geochemical Study of Sillimanite, Andalusite and Kyanite

subject: geochemical sillimanite andalusite kyanite

abstract:
Thesis
Master of Science (MS)


title: The Gospel of Mark within Judaism: Reading the Second Gospel in Its Ethnic Landscape

contributor:
Runesson, Anders
Thiessen, Matthew
Religious Studies

subject:
Gospel of Mark
Ethnicity
Judaism

abstract:
This thesis argues that the Gospel of Mark reflects a social location within the social boundaries of the Jewish ethnos and outlines relevant features of Mark’s configuration of Jewishness. It is divided into two parts. Part one provides a flexible definition of Jewishness in antiquity in order to assess what it meant to be Jewish and what characterized the boundaries between Jews and non-Jews. It makes an independent contribution to the study of Jewishness in antiquity by using a recent sociological model that explains how and why ethnicity matters in certain societies and contexts to map changes and features of Jewishness during the Hasmonean and Early Roman periods (129 BCE–132 CE) in the Southern Levant. It also addresses the relevant methodological issues for locating texts in relation to a social category such as “Jewish.”
Part two addresses the Gospel of Mark through the same methodological lens and in light of the re-conceptualization of Jewishness. It both argues that Mark should be read as a Jewish text and addresses how Mark configures Jewishness. It shows that the categorical boundaries in the text reflect a common Jewish way of categorizing and ranking people. In particular, Mark’s narrative assumes a hierarchical relation between the Jews and other people groups (i.e., “gentiles” or “the nations”) in which Jews are to the nations as children are to dogs. In addition, Mark’s narrative employs the concept of the kingdom of God to remake the boundary system of Roman Judea in two ways. First, Mark attempts to overturn the hierarchical Roman/Jew boundary by presenting the kingdom of God as imminent, earthly, and entailing the end of Roman power. Second, Mark subdivides the Jewish ethnos by limiting kingdom membership to “righteous” members of the Jewish ethnos, a strategy shared with the majority of Jewish texts examined in part one. The concluding section addresses the configuration of Jewishness in Mark’s narrative in terms of six common features of ethnic identity.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: This thesis argues that the Gospel of Mark should be read as Jewish literature and examines how Mark configures Jewishness. Part one provides a flexible definition of Jewishness in the Southern Levant during the Hasmonean and Early Roman periods (129 BCE–132 CE). Part two shows that the categorical boundaries in the Gospel of Mark reflect a common Jewish way of categorizing and ranking people groups. It then examines how Mark uses the concepts of the kingdom of God and Torah observance to overturn the hierarchical Roman/Jew boundary and limit kingdom membership to the righteous ones among the Jewish people. While Mark may assume that non-Jews participate in the expected kingdom, the absence of direct evidence highlights the Jewish-centric perspective of Mark’s Gospel.


title: Data Analysis for a Clinical Trial of the Management of Urinary Tract Infections in Residential Long-Term Care Facilities

title: Data Analysis for a Clinical Trial

contributor:
Walter, S. D.
Statistics

subject:
data analysis
clinical trial
urinary tract infection
residential long-term care facility

abstract: The main object of the research is to analyze the effect of the clinical intervention algorithms proposed for reducing antibiotic use for older adults in long-term care facilities (LTCFs) by managing urinary tract infections (UTIs). 20 paired nursing homes were enrolled in the 12-month study. Within each pair, one was randomized to use of the intervention algorithms and the other to use of regular management. Cluster-level paired t-tests (unweighted and weighted) and regression analyses (unweighted and weighted) were used in the analysis of the data. Paired t-tests show that the algorithms did not significantly reduce the antibiotic use, the number of urine cultures or the antibiotic use for urinary infections in most months. However, they did reduce the proportion of antibiotic use for urinary infections significantly in most months. Regression analysis indicates that the difference between the control group and intervention group has no significant increasing or decreasing trend with time (month). And the algorithms significantly reduced the antibiotic use for urinary infections, number of cultures and the proportions through the 12-month study. The analyses reached a similar conclusion using nonparametric methods and weighted analysis.

abstract: Thesis

abstract: Master of Science (MS)


title: Optimal Mobile Computation Offloading With Hard Task Deadlines

contributor:
Todd, Terence D.
Karakostas, George
Electrical and Computer Engineering

subject:
Mobile Cloud Computing
Computation Offloading

abstract: This thesis considers mobile computation offloading where task completion times are subject to hard deadline constraints. Hard deadlines are difficult to meet in conventional computation offloading due to the stochastic nature of the wireless channels involved. Rather than using binary offload decisions, we permit concurrent remote and local job execution when it is needed to ensure task completion deadlines. The thesis addresses this problem for homogeneous Markovian wireless channels. Two online energy-optimal computation offloading algorithms, OnOpt and MultiOpt, are proposed. OnOpt uploads the job to the server continuously and MultiOpt uploads the job in separate parts, each of which requires a separate offload initiation decision. The energy optimality of the algorithms is shown by constructing a time-dilated absorbing Markov process and applying dynamic programming. Closed form results are derived for general Markovian channels. The Gilbert-Elliott channel model is used to show how a particular Markov chain structure can be exploited to compute optimal offload initiation times more efficiently. The performance of the proposed algorithms is compared to three others, namely, Immediate Offloading, Channel Threshold, and Local Execution. Performance results show that the proposed algorithms can significantly improve mobile device energy consumption compared to the other approaches while guaranteeing hard task execution deadlines.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Anomaly Detection for Water Quality Data

contributor:
Sekerinski, Emil
Copp, John
Computing and Software

subject:
Anomaly Detection
Water Quality
Machine Learning
Local Outlier Factor
Isolation Forest
Random Cut Forest
S-H-ESD
EMA
Statistic Learning

abstract:
Real-time water quality monitoring using automated systems with sensors is becoming increasingly common, which enables and demands timely identification of unexpected values. Technical issues create anomalies, which at the rate of incoming data can prevent the manual detection of problematic data.
This thesis deals with the problem of anomaly detection for water quality data using machine learning and statistic learning approaches. Anomalies in data can cause serious problems in posterior analysis and lead to poor decisions or incorrect conclusions. Five time series anomaly detection techniques: local outlier factor (machine learning), isolation forest (machine learning), robust random cut forest (machine learning), seasonal hybrid extreme studentized deviate (statistic learning approach), and exponential moving average (statistic learning approach) have been analyzed. Extensive experimental analysis of those techniques have been performed on data sets collected from sensors deployed in a wastewater treatment plant.
The results are very promising. In the experiments, three approaches successfully detected anomalies in the ammonia data set. With the temperature data set, the local outlier factor successfully detected all twenty-six outliers whereas the seasonal hybrid extreme studentized deviate only detected one anomaly point. The exponential moving average identified ten time ranges with anomalies. Eight of them cover a total of fourteen anomalies. The reproducible experiments demonstrate that local outlier factor is a feasible approach for detecting anomalies in water quality data. Isolation forest and robust random cut forest also rate high anomaly scores for the anomalies. The result of the primary experiment confirms that local outlier factor is much faster than isolation forest, robust random cut forest, seasonal hybrid extreme studentized deviate and exponential moving average.

abstract: Thesis

abstract: Master of Computer Science (MCS)


title: Muscle Morphology, Function and Bone Mineralization in Girls with Turner's Syndrome

title: Musculoskeletal System in Turner's Syndrome

contributor:
Blimkie, Cameron
Human Biodynamics

subject:
muscle morphology
bone mineralization
turner's syndrome

abstract: The purposes of this research were i) to compare skeletal muscle development, function and bone mineralization in girls with Turner's syndrome (TS) (n=7) and healthy control girls (n=13), and ii) to examine the effects of growth hormone (GH) and estrogen (E2) therapy on musculoskeletal variables using a case study approach in two TS girls and one healthy control. Anthropometric measurements included: height, body mass, percent fat, and muscle and bone cross-sectional areas and muscle density from computed axial tomography. Evoked peak twitch torque (TT), maximal voluntary strength (MVC), contractile properties and motor unit activation (MUA) were determined for the elbow flexors (EF), plantar flexors (PF) and the knee extensors (KE). Total body and segmental bone mineral content (BMC) and density (BMD) were measured with dual photon absorptiometry. Dietary intake and participation in physical activity were assessed from questionnaires. Absolute strength (TT and MVC) for the TS patients was lower than that of the control girls' for EF, PF and KE and could not be accounted for by differences in muscle density, contractile properties, MUA, diet or level of physical activity. There were no significant differences in evoked and voluntary strength corrected for muscle area and lever length between the TS and control girls. Total body, leg and trunk BMC were lower in the TS girls compared to the controls; however, when normalized for body mass and bone width, total body BMC (g/kg) and BMD respectively were comparable between the TS and control girls. Growth hormone therapy increased height and lean mass, and reduced adiposity. All measures of arm strength increased but leg strength (PF & KE) was reduced. These may reflect the lack of GH effects on the leg muscle or possibly a detraining effect from the subject's withdraw! from a skating program. Growth hormone therapy resulted in increased leg BMC which may reflect a lag time between bone growth and subsequent mineralization. Estrogen therapy resulted in increased muscle area, fat mass and strength at all 3 muscle groups. The latter may be due to the laying down of muscle proteins as a result of estrogen therapy. The lack of major changes in BMC or BMD probably reflects the short duration of the follow-up period. Further studies are required with larger numbers for longer treatment periods in order to make conclusive statements about the effects of hormonal therapy on muscle function and bone mineralization in Turner's patients.

abstract: Thesis

abstract: Master of Science (MS)


title: The Effect of Hydrotherapy on Recovery and Performance During High Intensity Exercise

contributor:
Gibala, Martin
Human Biodynamics

subject:
hydrotherapy
recovery
high intensity exercise
exercise
performance

abstract: Athletes use a wide range of interventions to promote recovery from strenuous exercise, but few data are available regarding the efficacy of such practices. OBJECTIVE: To examine the effectiveness of commonly used interventions [Rest, light exercise (AR), contrast therapy (CT) and cryotherapy (CR)] during recovery between bouts of intense exercise. We tested the hypothesis that hydrotherapy interventions (CT and CR) would induce favorable physiological and/or psychological alterations such that performance would be improved versus AR and Rest. METHODS: In Study I, 12 active men (25-35 yrs; VO2peak = 46±3 ml·kg-1·min-1; mean±SD) performed 5 consecutive days of HI exercise (4-6 bouts x 30 sec 'all out' Wingate Tests, with 4-min recovery, each day). After each training session, subjects either rested for 20 min (CON, n=6) or completed a CT protocol (n=6) that consisted of alternating cold (10°C) and hot (40°C) tubs using a 4x2:3 min ratio. Performance measures [Peak (Wmax) and mean (Wmean) power, VO2peak, and a 250 kJ Time Trial (TT)] were assessed before and after the HIT. In Study II, 9 active men (29±6 yr, VO2peak = 44±8 ml·kg-1·min-1) performed 3 exercise trials separated by 1 wk. Each trial consisted of 3 x 50 KJ time trials(~100-120%VO2peak) with a different 20-min recovery period [CON, AR (cycling@ SOW) or CR (cold tub@ 10°C)] between rides each week. Venous blood samples were obtained after each recovery period, and analyzed for lactate, interleukin-6, neutrophils, and lymphocytes. Questionnaires designed to assess exercise preparedness were also completed daily in both studies. RESULTS: In Study I, Wmax and TT performance improved after 5 d of HI exercise (time effect, P<0.05), but there were no differences between groups (Wmax-CT: Post: 1310±45 vs Pre: 1215±86; CON: Post: 1343±54 vs Pre: 1220±74 W: TT-CT: Post: 15.8±0.6 vs Pre: 16.7±0.7; Rest: Post: 18.1±1.0 vs Pre: 18.8±1.2 min, means±SEM). In Study II, TT performance averaged 118±10 sec for bout 1 and was 8% and 14% slower during bouts 2 (128±11 sec) and 3 (134±11 sec), respectively, with no difference between treatments (Time effect, P≤0.05). Blood lactate was lower after AR compared to CR and Rest, and neutrophils and lymphocytes were higher and lower respectively (P≤0.05), after CR (8.7±1.3 and 1.4±0.2 x 109cells/L) versus AR (7.1±1.0 and 1.6±0.1) and Rest (6.7±0.7 and 1.6±0.1). With respect to the psychological measurements, the CT and CR groups in both studies reported feeling more revitalized after each treatment session and greater preparedness for subsequent exercise (Treatment effect, P≤.05). CONCLUSIONS: Exercise performance during repeated bouts of intense cycling was not influenced by the type of recovery intervention employed, either during a single session or over the course of a 5 d training session. CR caused greater perturbations in blood immune markers and most notably, hydrotherapy interventions created the perception that subjects were better prepared for subsequent exercise.

abstract: Thesis

abstract: Master of Science (MS)


title: Multi-Platform Genomic Data Fusion with Integrative Deep Learning

contributor:
Qiao, Sanzheng
Computational Engineering and Science

subject:
deep learning
information fusion
cancer detection
dimensionality reduction

abstract: The abundance of next-generation sequencing (NGS) data has encouraged the adoption of machine learning methods to aid in the diagnosis and treatment of human disease. In particular, the last decade has shown the extensive use of predictive analytics in cancer research due to the prevalence of rich cellular descriptions of genetic and transcriptomic profiles of cancer cells. Despite the availability of wide-ranging forms of genomic data, few predictive models are designed to leverage multidimensional data sources. In this paper, we introduce a deep learning approach using neural network based information fusion to facilitate the integration of multi-platform genomic data, and the prediction of cancer cell sub-class. We propose the dGMU (deep gated multimodal unit), a series of multiplicative gates that can learn intermediate representations between multi-platform genomic data and improve cancer cell stratification. We also provide a framework for interpretable dimensionality reduction and assess several methods that visualize and explain the decisions of the underlying model. Experimental results on nine cancer types and four forms of NGS data (copy number variation, simple nucleotide variation, RNA expression, and miRNA expression) showed that the dGMU model improved the classification agreement of unimodal approaches and outperformed other fusion strategies in class accuracy. The results indicate that deep learning architectures based on multiplicative gates have the potential to expedite representation learning and knowledge integration in the study of cancer pathogenesis.

abstract: Thesis

abstract: Master of Science (MSc)


title: Modeling Virus Transmission and Evolution in Mixed Communities

contributor:
Bolker, Benjamin
Biology

subject: Ecology Evolution Epidemiology

abstract: In the early 1980s Anderson and May showed that parasite virulence (host mortality rate when infected) and parasite transmission are positively correlated because of their joint dependence on host exploitation (e.g. replication rate). This correlation often results in maximum parasite fitness at intermediate virulence, which has important implications for both parasite evolution and transmission. Anderson and May's observation has led to nearly four decades of work on the ecology and evolution of host-parasite interactions, which focuses on making either general predictions for a range of simplified host-parasite systems or detailed predictions for a single host-parasite system. Yet, despite decades of research, we know comparatively little about parasite evolution and transmission in heterogeneous and/or small host populations. Additionally, much previous work has distanced itself from empirical data, either by outpacing the collection of data or under-utilizing available data. My work focuses on the evolution and transmission of parasites in heterogeneous host populations; I rely on tradeoff theory, but adopt a case-study approach to maximize the use of empirical data. Using West Nile virus infections of birds I show that a continent-wide strain displacement event cannot be explained by current data (Chapter 2), and that transmission in heterogeneous host communities can be estimated using data from citizen scientists, laboratory experiments, and phylogenetic comparative analysis (Chapter 3). Using Myxoma virus infection of European rabbits, I show that tradeoff theory can help us to understand parasite evolution in host populations with heterogeneous secondary infection burden (Chapter 4). In Chapter 5 I show that poorly evolved parasites invading new host populations experience transient evolution away from optimal virulence. In addition to my biological focus, I emphasize clarity and rigor in statistical analyses, including the importance of appropriate uncertainty propagation, as well as reproducible science.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: In their work in the late 1970s and early 1980s, Anderson and May demonstrated that pathogen induced host harm and pathogen transmission ability are intimately linked. This work clearly showed that pathogens maximize their reproductive potential by causing some harm their hosts, contrary to the established belief that pathogens shouldn't harm their hosts at all. I extend this work to study pathogen evolution and transmission in heterogeneous host populations, using two model host-pathogen systems: birds infected with West Nile virus, and European rabbits infected with the myxoma virus, as well as a general model for the evolution of poorly adapted pathogens in small host populations. I show that pathogen transmission in heterogeneous host populations can be estimated using citizen science data, that pathogen transmission is lower in heterogeneous populations, and that pathogens invading naive host populations may experience short-term evolution to higher-than-optimal virulence, increasing infection burden.


title: The environmental toxin, chlorpyrifos disrupts mitochondrial function in brown adipose tissue and promotes the development of obesity and metabolic dysfunction in mice

contributor:
Steinberg, Gregory
Medical Sciences

abstract: Chlorpyrifos, one of the most utilized organophosphate pesticides worldwide, is commonly found on many fruits and vegetables, and has been associated with the development of obesity. Brown adipose tissue (BAT) has an abundance of multilocular lipid droplets and mitochondria that express uncoupling protein-1, a protein which generates a futile cycle that contributes to resting energy expenditure in rodents and humans. Reductions in BAT activity are associated with the development of obesity and related metabolic comorbidities including insulin resistance and non-alcoholic fatty liver disease (NAFLD). In this thesis, chlorpyrifos, at a dose which mimics non-occupational exposure, was fed to mice in combination with a control low fat or a high-fat diet and mice were maintained at either room temperature or at thermoneutrality. On a control diet chlorpyrifos had minimal effects on obesity and glucose homeostasis but when combined with a high-fat diet it was found to promote obesity, non-alcoholic liver disease and insulin resistance; effect was more prominent at thermoneutrality. This effect of chlorpyrifos in high-fat diet fed mice was associated with reduced expression of uncoupling protein-1, and disruption of mitochondrial homeostasis within brown adipose tissue, an effect associated with reductions in AMPK and markers of mitophagy. These data suggest that chlorpyrifos may promote obesity and metabolic dysfunction by suppressing brown adipose tissue mitochondrial function.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Role of Gut-Brain Signalling in Functional Responses to Chronic Social Stress

contributor:
Bienenstock, John
Forsythe, Paul
Medical Sciences (Neurosciences)

subject:
Neuroscience
Stress
Gut-brain signalling
Microbiota
Central nervous system
Vagus nerve
Fos proteins
Depression

abstract: Chronic stress has a cumulative physiological impact, causing dysregulation of multiple systems due to allostatic overload. There is growing evidence that one such system, the microbiota, is engaged in persistent bidirectional interplay with the brain—a phenomenon that influences neural function and behaviour.  However, the functional role of the microbiota in stress-associated changes and the underlying pathways of communication are unknown. Using a murine model of depression, we demonstrate that chronic stress has top-down effects on the structure of the microbiota community, reducing its richness and diversity, altering its profile, and causing differential abundance of various bacterial genera. These structural changes have functional consequences, including in metabolic pathways responsible for the synthesis of short chain fatty acids, tryptophan, and tyrosine. Using a physiologically active bacteria, Lactobacillus rhamnosus (JB-1), we probed for bottom-up signalling in chronic stress. JB-1 attenuated deficits in anxiety-like and social behaviours, and induced systemic immunoregulatory effects, independent of affecting stress-induced changes in the microbiota. In examining possible mechanisms of gut-brain brain signalling, we observed that in unstressed mice, a single dose of JB-1 causes rapid expression of c-Fos—a marker of neuronal activation—in distributed areas of the brain within 165 minutes, absent behavioural changes. No such effects were observed with heat-killed JB-1, despite that both live and heat-killed preparations facilitated vagal activity. Sub-diaphragmatic vagotomy prevented neuronal activation in most but not all brain regions, suggesting that vagal signalling is critical but indicating the presence of additional independent pathways. Finally, only chronic JB-1 treatment increased ΔFosB expression in the brain, which is indicative of long-term neuronal adaptations, in association with behavioural changes. These studies demonstrate a role for bidirectional gut-brain signalling in chronic stress, and highlight the signalling pathways and brain regions through which gut bacteria exert their influence on host behaviour.

abstract: Thesis

abstract: Candidate in Philosophy

abstract:
Stress, which is a leading risk factor for mental illnesses such as depression,
drastically affects the microbiota—the community of intestinal bacteria. However, this
influence is bidirectional as gut bacteria can also influence the brain. Thus, we sought to
understand the role of the microbiota in the negative effects of stress and how these
microorganisms interact with the brain. We observed that behavioural changes in mice
after chronic stress were associated with inflammation and community-wide changes in
the microbiota. Treatment with a bacterial strain, Lactobacillus rhamnosus (JB-1),
attenuated changes in behaviour and inflammation, but had no effect on the microbiota
composition. We observed that the brain rapidly responded to JB-1 via the vagus nerve,
and that chronic treatment caused long-term changes in brain regions. This work will
allow us to discover novel pathways that can be targeted with greater specificity in
clinical settings, providing an innovative approach to treatment of psychiatric conditions.


title: Fault-Tolerant Supervisory Control

contributor:
Leduc, Ryan
Computer Science

subject:
Discrete-Event Systems
Supervisory Control
Fault tolerant

abstract:
In this thesis, we investigate the problem of fault tolerance in the framework of discrete-event systems (DES). We introduce our setting, and then provide a set of fault-tolerant definitions designed to capture different types of fault scenarios and to ensure that our system remains controllable and nonblocking in each scenario.
This is a passive approach that relies upon inherent redundancy in the system being controlled, and focuses on the intermittent occurrence of faults.
Our approach provides an easy method for users to add fault events to a system model and is based on user designed supervisors and verification. As synthesis algorithms have higher complexity than verification algorithms, our approach should be applicable to larger systems than existing active fault-recovery methods that are synthesis based. Also, modular supervisors are typically easier to understand and
implement than the results of synthesis.
Finally, our approach does not require expensive (in terms of algorithm complexity) fault diagnosers to work. Diagnosers are, however, required by existing methods to know when to switch to a recovery supervisor. As a result, the response time of diagnosers is not an issue for us. Our supervisors are designed to handle the original and the faulted system.
In this thesis, we next present algorithms to verify these properties followed by complexity analyses and correctness proofs of the algorithms. Finally, examples are provided to illustrate our approach.
In the above framework, permanent faults can be modelled, but the current method was onerous. To address this, we then introduce a new modeling approach for permanent faults that is easy to use, as well as a set of new permanent fault-tolerant definitions. These definitions are designed to capture several types of permanent fault scenarios and to ensure that our system remains controllable and nonblocking in each scenario. New definitions and scenarios were required as the previous ones were incompatible with the new permanent fault modeling approach.
We then present algorithms to verify these properties followed by complexity analyses and correctness proofs of the algorithms. An example is then provided to illustrate our approach.
Finally, we extend the above intermittent and permanent fault-tolerant approach to the timed DES setting. As before, we introduced new fault-tolerant properties and algorithms. We then provide complexity analyses and correctness proofs for the algorithms. An example is then provided to illustrate our approach.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: The Use of Digital Storytelling for Impression Management by City Cultural Organizations

contributor:
Detlor, Brian
Business

subject:
Digital Storytelling
City Cultural Organizations
Impression Management
Cultural Heritage
Effective Use
Outcomes of Use
Narrative Transportation
Everyday Life Information Seeking
Information Behaviour
Leisure Learning

abstract:
This dissertation provides a context-specific theory to understand how city cultural organizations can best use digital stories and impression management to create a desired image or enhance public perceptions. The generated model describes how a digital storytelling information system can affect user impressions of a city and the outcomes of using such a system. The study responds to a growing interest among cultural organizations regarding how to use emerging information technologies in the communication of cultural content.
An interpretive case study was conducted on the “Love Your City, Share Your Stories” digital storytelling initiative in Hamilton, Canada. Data collection included 95 one-on-one interviews with the general public, the gathering of documents, and the researcher’s personal observations of participants during the data collection process. A systematic approach of data analysis was utilized to capture participant opinions and visualize this information in a data structure. Theories from the literature on information systems, organizational impression management, and narrative transportation ground the study.
Findings suggest that a digital storytelling information system can be a viable tool to share city cultural heritage information and positively affect people’s perceptions of a city. The overall outcome of creating/maintaining a positive favorable impression is shaped through a layered experience of benefits by the users. Users are first personally engaged and informed about a city’s cultural heritage (primary benefits), and then they are influenced and inspired positively towards the city (secondary benefits). Findings show that technology characteristics (i.e., media quality and story quality) are critical factors affecting outcomes of use, and that user characteristics and context of use both moderate this relationship.
This research provides theoretical insights and practical recommendations for researchers and city cultural organizations wishing to explore the utilization of newer information technologies, such as digital storytelling, for impression management.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
This dissertation aims to understand how city cultural organizations can best use digital stories and impression management to enhance public perceptions. The generated model describes how a digital storytelling information system can affect user impressions of a city. The study responds to a growing interest among cultural organizations regarding how to use emerging information technologies in the communication of cultural content.
Findings suggest that a digital storytelling information system can be a viable tool to share city cultural heritage information and positively affect people’s perceptions of a city. Findings show that technology characteristics (i.e., media quality and story quality) are critical factors affecting outcomes of use and that user characteristics and context of use both moderate this relationship.
Theoretical insights and practical recommendations are provided for researchers and city cultural organizations wishing to explore the utilization of newer information technologies, such as digital storytelling, for impression management.


title: Planning for Inclusion? An Assessment of Ontario's Emergency Preparedness Guide for Disabled Persons

contributor:
Wilton, Robert
Geography and Earth Sciences

subject:
Disability
Emergency Preparedness
disaster
Inclusion
inclusive emergency planning
diversity of disabilities

abstract: The opinions and expertise of disabled people are often absent from emergency preparedness planning. As a result, when emergencies occur disabled people’s needs may go unmet. While there have been recent efforts to acknowledge the need for disability inclusive planning processes (in, for example, the development of a Disability Inclusive Disaster Risk Reduction framework), more research is needed to understand how efforts to include the perspectives and experiences of disabled people work (or do not work) in practice.  In this research, I examine the development of a disability-inclusive emergency preparedness plan in Ontario, Canada. I use semi-structured interviews with key informants from the provincial government and disability organizations to unpack the planning and consultation process. The analysis indicates that while the plan represents an important attempt to include disabled people in emergency preparedness planning, it falls short in a number of ways not least because it rests on a narrow conception of disability as physical limitation. In particular, people with intellectual disabilities are absent from the planning process and final plan, a fact that reflects their broader marginalization within society. I draw on interviews with a small sample of self-advocates living with intellectual disabilities to identify how the plan could be revised to recognize the views and experiences of this population.

abstract: Thesis

abstract: Master of Arts (MA)


title: A CHIMERIC ANTIGEN CONSISTING OF TYPE III SECRETION PROTEINS AS A CHLAMYDIA VACCINE CANDIDATE

contributor:
Mahony, James
Medical Sciences

subject:
Chlamydia
Vaccine
Type III Secretion

abstract: Chlamydia is the most prevalent sexually transmitted bacterial infection in many developed countries, including Canada. Untreated infections in women can lead to a number of complications including pelvic inflammatory disease, tubal factor infertility, and ectopic pregnancy. Public health programs, including screening for at-risk individuals, partner identification, and antibiotic treatment, have had limited success in controlling the rising incidence of chlamydial infections over the past two decades. A chlamydia vaccine that prevents infection and its pathological sequelae is the next essential step to control this persistent public health problem. Chlamydia spp. utilize the highly conserved type III secretion (T3S) system as an essential virulence factor for infection and intracellular replication. Here, we evaluated a novel chimeric antigen (BD584) consisting of three T3S proteins from C. trachomatis (CopB, CopD, and CT584) as a potential chlamydia vaccine candidate. Intranasal immunization with BD584 elicited strong humoral responses that neutralized infection in vitro. Following intravaginal challenge with C. muridarum, immunized mice had a 95% reduction in chlamydial shedding and a 87.5% reduction in incidence of upper genital tract pathology compared to control mice. BD584 immunization generated strong cell-mediated and mucosal antibody responses in mice with different genetic backgrounds, and conferred protection against an intravaginal C. trachomatis infection in two out of three strains of mice. BD584 formulated with NE01, a mucosal adjuvant known to be safe and effective in humans, was shown to be highly immunogenic and efficacious against C. trachomatis infection in mice. These results suggest that BD584 may represent a promising antigen for use in a chlamydia vaccine.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Chlamydia is the most common sexually transmitted bacterial infection in the world. The goal of this thesis is to evaluate a novel chlamydia vaccine in a mouse model of genital chlamydia infection. We engineered a fusion protein, BD584, made up of three highly conserved type III secretion (T3S) proteins CopB, CopD, and CT584. We show that vaccination with BD584 generated strong immune responses and protected mice from chlamydia infection and the associated reproductive tract disease. Interestingly, the level of protection afforded by BD584 vaccination is dependent upon the genetic background of the animal. Furthermore, we have identified particular antibody subtypes directed against BD584 as markers of BD584-mediated protective immunity. Lastly, we show that vaccination with BD584 formulated with a clinically safe and effective mucosal adjuvant generates robust immune responses and confers protection against chlamydia in mice. Together, these results provide support for the use of T3S proteins in a chlamydia vaccine.


title: Mapping the Protein Interactome of ASD-associated Genes by using BioID2

contributor:
Doble, Bradley
Singh, Karun
Biochemistry and Biomedical Sciences

abstract: Autism spectrum disorder (ASD) is an array of neurodevelopmental disorders that vary in the severity of symptoms presented by affected individuals. In Canada, ASD is estimated to affect 1 in 66 children1. Though severity can vary, the clinical diagnostic criteria define deficits in social interaction, presence of repetitive behaviors and restricted interests, as characteristic manifestations2. The disorder not only reduces the quality of life for those affected, but also places an immense emotional and financial burden on their families and an economic burden on society. ASD is a heterogeneous disorder, with hundreds of implicated loci and genes. However, only a small number of implicated genes have well-defined neurobiological functions. Defining the pathogenesis and etiology of ASD in genetic and molecular terms is essential for expanding our understanding of the disorder, uncovering protein biomarkers for diagnosis, and identifying targets for therapeutic development. My project used a chemico-genetic proximity labeling approach, termed BioID2, to map the protein interactome of ASD-associated gene products. I employed the genome editing CRISPR-Cas9 technique to engineer mouse embryonic stem cells with a BioID2 expression cassette linked to an ASD-associated gene of interest. A mouse model will be generated from the edited mouse embryonic stem cells.  This approach will permit the tracking of protein-protein interactions on an endogenous level, which provides a more accurate representation of the interacting partners. I also initiated a second approach in which lentiviral constructs harboring BioID2-tagged ASD-associated genes of interest will be used to overexpress resultant BioID2 fusion proteins in primary cortical neurons. This method will allow us to propose protein networks for our genes of interest and to dissect the molecular function of these genes. Studying protein-protein interactions of candidate ASD gene products is critical for understanding the molecular etiology of ASD. The elucidation of ASD-associated protein networks will be indispensable to the development of novel therapeutic agents, by informing target selection. This project will expand our current understanding of ASD, identify novel protein markers, and contribute to development of therapies. It can also serve as proof-of-concept that can be adapted for various other neurological disorders.

abstract: Thesis

abstract: Master of Health Sciences (MSc)


title: City, Town and Village: An Intra and Inter Site Analysis of Long Bone and Rib Fractures at Five Settlements in the Western Roman Empire

contributor:
Brickley, Megan
Anthropology

subject:
fractures
social identity
Roman

abstract:
Fractures indicate how an individual has moved through the world. Yet, how an individual navigates their world is also dependent on variables such as age and gender, and the intersection of such variables. This was never more true than during the Roman period, where how one lived was contingent on a number of variables such as class, gender, and age.
The current project analyzed data from 1121 individuals to examine whether one’s age, gender, burial treatment and the confluence of these variables related to one’s fractures. To capture the diversity of the Roman Empire, the project examined three large settlements: Winchester, UK; Lisieux Michelet, France; and Barcelona, Spain, as well as two smaller settlements: Godmanchester, UK; and Vagnari, Italy. Temporally, the settlements span from the 1st-8th c. CE, the height of the Roman Empire to the Merovingian period.
The results of the current study found that when variables are treated in isolation, there were distinct gendered lifeways at most settlements, with males having more fractures. When the variables are considered together, fractures reflect more complex dynamics of temporal stress, age, and labour within burial communities at the three larger settlements. When settlements were compared to one another, the absence of differences in fracture prevalence between settlements suggest than rather than simple urban/rural divides, settlements are shaped by their economies and lifeways. Further, odds ratios suggest that fracture risk differed for men and women, young and old.
The current study represents the first study to examine multiple large and small settlements outside of Roman Britain, as well as the first to consider fractures in relation to burial treatment. By cross cutting variables, this study expands the current understanding of small, complex communities within cemeteries, and contributes to the discussion on the confluence of identities in the Roman and Merovingian periods.

abstract: Thesis

abstract: Master of Arts (MA)


title: Frustrated magnetism studies in NaCaNi$_2$F$_7$, Er$_3$Ga$_5$O$_{12}$ and ErMgGaO$_4$

contributor:
Luke, Graeme
Physics and Astronomy

subject: Frustrated magnetism

abstract:
This dissertation details studies of three different frustrated magnet families: NaCaNi$_2$F$_7$, Er$_3$Ga$_5$O$_{12}$, and ErMgGaO$_4$, using a variety of techniques, including magnetization, specific heat, neutron scattering and muon spin rotation/relaxation ($\mu$SR).

NaCaNi$_2$F$_7$ belongs to the fluoride pyrochlores family. In this thesis, we study the effect of the randomness on the A site on the magnetic property of B site. This chemical disorder randomness was caused by the mixture of two different elements from Group 1 and 2 (Na and Ca). DFT calculation and computation simulations indicates a possible non-centred $F-\mu -F$ muon stopping site. Zero field (ZF) and longitudinal field (LF) $\mu$SR shows that the $Ni^{2+}$ spins undergo spin freezing into a disordered ground state below 4K, with persistent spin dynamics to our lowest temperature 75 mK.

We obtained high quality single crystal of Er$_3$Ga$_5$O$_{12}$ by utilizing the optical floating-zone (OFZ) technique. We performed inelastic neutron scattering measurements to determine the crystalline electric field (CEF) Hamiltonian, eigenvalues and eigenvectors, indicating an Ising-like anisotropy ground state which is also consistent with our specific heat experiment with entropy approaching $Rln(2)$. All seven crystalline electric field excitations from the ground state Kramers doublet were identified. In addition, Rietveld refinement of neutron powder diffraction data reveal that Er$_3$Ga$_5$O$_{12}$ orders into the $\Gamma_3$ magnetic structure, with ordered magnetic moment $\mu_{ord} = 5.24(4)~\mu_{B}$, in agreement with $\mu_{Ising}$ = 5.61 $\mu_{B}$ from our deduced CEF Hamiltonian. Our $\mu$SR measurements also reveals the presence of fluctuating local fields on the muon timescale, indicating exotic slow spin dynamics in the ground state.

The objective of the work on ErMgGaO$_4$ was to identify a new quantum spin liquid candidate. Single crystals of ErMgGaO$_4$ were obtained through (OFZ) technique as well, and the structure was refined and confirmed by powder X-ray diffraction and Laue diffraction after a repeated refinement of our synthesis process. Susceptibility measurements reveal no evidence of a magnetic transition down to 0.5 K, in agreement with specific heat measurement which exhibit no anomalies which would have been evidence of an ordering transition. ZF-$\mu$SR measurements reveal no sign of coherent long range order or spin freezing down to 25 mK, while LF-$\mu$SR measurements shows persistent spin dynamics at 25 mK. Our observations provides evidence for a quantum spin liquid ground state in this compound.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Multiplexed Separations for New Advances in Biomarker Discovery and Tissue Metabolomic Studies

contributor:
Britz-McKibbin, Philip
Chemistry and Chemical Biology

subject:
Capillary Electrophoresis
Mass Spectrometry
Biomarker Discovery
Tissue Metabolomics
Chronic disease prevention
Supplementation and Exercise
Sex adaptations in gestation

abstract: PhD Thesis

abstract: Metabolomics offers a systemic approach to discover clinical biomarkers for early detection of chronic diseases while also revealing underlying mechanisms relevant to human disorders of complex aetiology. Metabolomic studies in support of chronic disease prevention have focused primarily on surrogate biofluids (e.g., serum, plasma) for analysis due to their routine and less invasive sample collection in a clinical setting. However, biofluids are non-organ specific and thus are reflective of confounding biochemical processes within the body that are often difficult to interpret. As a result, it is necessary to assess metabolite changes localized within tissues since they are the direct site of pathogenic processes, in order to obtain more robust and specific biomarkers. This thesis aims to contribute to new advances in biomarker discovery and tissue metabolomic studies using multiplexed separations together with innovative data workflows based on multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). Chapter II introduces a high throughput yet targeted screening method for accurate quantification of serum γ‐glutamyl dipeptides from a cohort of overweight Japanese non-alcoholic steatohepatitis (NASH) patients that may allow for better risk assessment of long-term survivorship complementary to histopathology. Chapter III introduces a non-targeted metabolite profiling strategy for fasting plasma samples from prediabetic, older adults undergoing short-term step reduction (<1000 steps/day) in order to identify adaptive metabolic responses to abrupt changes in physical inactivity for early detection of sarcopenia in high-risk older persons. Chapter IV describes the first metabolomics study to characterize the human skeletal muscle metabolome from mass-restricted tissue biopsies together with matching plasma samples, which identified novel metabolic signatures associated with strenuous interval exercise, as well as treatment effects from high-dose bicarbonate pretreatment that delays the onset of muscle fatigue. Lastly, in Chapter V, metabolite coverage was expanded to include fatty acids for comprehensive characterization of murine placental tissue metabolome, which revealed sex-specific metabolic adaptations during gestation from maternal dams fed a standardized diet. In summary, this thesis contributes to new innovations in metabolomics for the discovery of novel biomarkers from blood and/or tissue specimens as required for early detection of chronic diseases relevant to population health, which were also used to validate the efficacy of therapeutic interventions based on physical activity to support healthy ageing.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Exploring the Association between Mental Health and Goal Attainment for Individuals Enrolled in a Healthy Lifestyles Program

contributor:
Alvarez, Elizabeth
Health Research Methodology

abstract:
Background:
Rates of mental illness have been rising in Canada. Lifestyle changes (e.g., increasing physical activity) can decrease symptoms of mental illness. Setting goals as part of a lifestyle program is integral in changing behavior, though previous literature surrounding the association between goal achievement and mental health is unclear. This study examined the relationship between mental health and goal achievement for individuals enrolled in a person-centered and holistic program, the healthy lifestyles program (HLP), which is rooted in principles of cognitive behavioral therapy and theories of health behavior.

Methods:
A mixed methods pilot pragmatic trial was conducted to test the feasibility and effectiveness of the HLP. Participants in the intervention arm (N=15) met weekly for education and peer-support sessions and every month individually with members of the healthcare team in order to develop personalized healthcare goals and an action plan. Participants in the control arm (N=15) met every three months to set goals and an action plan with a research assistant trained in theories of health behavior. Participants in both arms completed validated health scales every 3 months. Generalized estimating equations were used to model the data.

Results:
There were significant reductions in depression, insomnia, and loneliness scores between baseline and 9-months in the intervention group. Depression (β = -.331, 95% CI [-.458, -.204], p < .001), insomnia (β = -.168, 95% CI [-.325, -.010], p = .037), and loneliness (β = -.260, 95% CI [-.456, -.064], p = .009), significantly predicted mean goal attainment. Partaking in the HLP improves the likelihood that participants meet their health goals (β = 2.359, 95% CI [.943, 3.778], p = .001).

Conclusion:
This study aims to discern the relationship between lifestyle interventions, goal achievement and mental health. Partaking in an HLP can reduce risk for mental illness and improve quality of life.

abstract: Thesis

abstract: Master of Public Health (MPH)

abstract: Rates of mental illness are increasing in Canada. Lifestyle changes and setting goals can help improve symptoms of mental illness. This study examined the relationship between mental health and goal achievement for individuals enrolled in a person-centered and holistic program, the healthy lifestyles program. Fifteen participants in the intervention group met weekly for education and peer-support sessions and every month individually with members of the healthcare team in order to develop personalized health goals and an action plan. Fifteen participants in the control arm met every three months to set goals and an action plan with a research assistant. There were reductions in depression, insomnia, and loneliness symptoms between baseline and 9-months in the intervention group. Participants with higher depression, insomnia, and loneliness scores were less likely to meet their goals. Participants in the intervention group were more likely to meet their health goals.


title: Segmentation of Breast Cancer Ultrasound Images

contributor:
Nedialkov, Ned
Computational Engineering and Science

abstract:
Breast cancer is the most common cancer occurring in women. Breast-conserving surgery is a desirable choice for an early-stage breast cancer. An intra-operative margin assessment of excised breast lesion tissue can help avoid additional surgeries. An essential problem in intra-operative margin assessment is how to extract an accurate boundary of the excised lesion automatically and quickly. To solve this problem, we segment breast cancer ultrasound (US) images and then generate boundaries based on the segmentation results.

In this research, we propose a new convolutional neural network model, named IU-Net, to segment breast cancer US images. IU-Net combines inception blocks and the well-known U-Net model. We train IU-Net with US images and corresponding manually segmented images provided by Dr. Jeffery Carson and his research group of the Lawson Health Research Institute, London, Ontario, Canada. We also apply an autoencoder in training IU-Net. The experimental results show that IU-Net achieves slightly more accurate results than U-Net and uses 3.8x fewer parameters than U-Net.

abstract: Thesis

abstract: Master of Science (MSc)


title: Understanding Moral Empathy: A Phenomenological Exploration

contributor:
Grierson, Lawrence
Health Science Education

subject:
empathy
motivation
phenomenology
verbatim theatre
medical education

abstract:
Background: Empathy is essential to forming strong patient-physician relationships that enable physicians to provide better healthcare. In the medical education literature, empathy consists of cognitive, affective, behavioural, and moral domains. Studies have measured declines in empathy during medical training. Researchers speculate that factors within formal, informal, and hidden curricula contribute to empathic decline. Several frameworks suggest that empathy in the moral domain (i.e., the inner motivation to accept patients unconditionally, commit to understanding patients, and help patients achieve their needs) is the most fundamental to the empathic response. Studying the factors that influence moral empathy during training is important to developing insights into the reasons for the demonstrated declines in resident empathy.
Methods: Descriptive phenomenology was used to address the research objective. Medical residents from various specialties participated in lightly structured interviews concerning their experiences. Interview transcripts were inductively and collaboratively analyzed to construct a preliminary set of factors that influence moral empathy. These factors informed the creation of a script for a verbatim theatre play that was performed for an audience of residents, educators, learners, researchers, and scholars. Following the play, audience participants completed a survey that served as a member-check of the factors that contributed to the final construction of factors.
Results: The results were constructed as three categories under which seven factors are nested. These categories are: Innate Capacity, Previous Personal Encounters, and Specific Patient Encounters. With the exception of a few, most factors do not directly influence residents’ moral empathy but rather challenge their ability to act on their moral empathy.
Discussion: These results offer unique insights into the declines in empathy that have been previously reported in the medical education literature, while also highlighting a moral-behavioural tension that has implications for competency-based medical education, the four-factor model of empathy, and the assessment of empathy in medical education. Future work may build on the results of this study to develop an assessment tool for moral empathy and to elucidate the relationships between the domains of empathy in order to arrive at a more refined conceptualization of the construct.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Empathy—the ability to comprehend the experiences of others—is an important tool that enables physicians to build relationships with patients, which helps them provide better healthcare. Studies have shown that empathy declines during medical training due to a variety of factors. Frameworks describing the empathic response suggest that one’s inner motivation to accept patients unconditionally, commit to understanding patients, and help patients achieve their needs may be fundamental to providing clinical care with empathy. As such, the goal of this study was to explore the factors that influence these inner motivations of residents in order to gain insights about the evidence that purports residents to demonstrate less empathy as they progress in their training. To address this objective, 10 medical residents from various specialties were interviewed about their experiences, the data were analyzed by way of a descriptive phenomenological methodology, and the initial findings were presented as a verbatim theatre play as a means of member-checking the proposed results. After viewing the play, an audience of medical residents, educators, learners, researchers, and scholars provided feedback through a survey that contributed to the final conclusions of the study. In this regard, the study shows that, apart from a few factors, residents’ inner motivations to be empathic are not significantly influenced during medical training. Rather, certain factors associated with residency affect their ability to deliver on their inner motivations. This study offers insights into the role of motivation in empathic decline, assessment of empathy during medical training, and potential significance of a tension between one’s motivation to be empathic and the opportunities that they are afforded to be empathic during residency.


title: Towards All-Printed Lateral Flow Biosensors

contributor:
Pelton, Robert
Chemical Engineering

subject:
Lateral flow biosensor
Inkjet printing
nanoparticle
calcium carbonate

abstract:
Lateral flow biosensors are analytical devices that detect biomaterials with physicochemical signals, such as optical signals. Unlike other biosensors, lateral flow biosensors are based on porous membranes, which use capillary force to transport biomaterials spontaneously. However, lateral flow biosensors are fabricated in batch mode, which means that membranes need to be cut from the rolls, pretreated, and assembled using a step-by-step process. Thus, there is a need for a more efficient manufacturing process. This thesis aims to accelerate the fabrication process by developing a method wherein the whole device is printed directly, including the printable substrates, as well as by developing a clog-free process for depositing expensive reagents.
These novel printable porous media were developed using printing inks that contained various pigments and polymer binders. To this end, candidate formulations were screened from nine hundred inks formulations via wicking experiments. The results of these tests showed that the most promising formulations were based on calcium carbonates and latex polymers. This formulation was then used to develop printable porous media that can easily be printed into complex patterns, with changeable wicking speeds within each pattern. In addition, a bio- colorimetric assay of alkaline phosphates conducted on these porous media showed strong color signals that were comparable to the traditional membrane-based lateral flow strips.
Clog-free printing processes were investigated by using a piezoelectric inkjet printer to print silica sols and six nanoparticle inks. The results of these tests showed that the vibration of the piezoelectric layer and the deposition of particles on the printhead surfaces induced clogging issues. Over time, the silica sols formed multilayer deposits on the print head surface, which subsequently detached due to the vibration of the piezoelectric layer. Consequently, these large sheets of silica clogged the nozzles during printing. This clogging issue was eliminated by adjusting the pH value of the silica sol inks to 3.1. The hydrophobic cationic polystyrene nanoparticles form a sub-monolayer on the printhead surface, which causes air entrainment and promotes air bubble adhesion into the interior of the print head surface when the piezoelectric layer deforms. Thus, alternate surface chemistries for the print head and ink particle surfaces may be required in order to print hydrophobic ink materials. Overall, this enhanced understanding of these clogging mechanisms helps to explain why printer performance varies when different particles are used.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Many devices in our day-to-day lives incorporate lateral flow biosensors, for example, home pregnancy test kits. These tests allow users to obtain results within 30 minutes by simply applying a few droplets of urine onto a test strip. However, these biosensors are largely manufactured using manual processes: workers cut strips (also called substrates) from sheets, deposit reagents onto the strips, and then assemble the pretreated strips into devices. As such, these processes are time consuming and less productive. To accelerate the manufacturing process, we developed printable porous substrates and a clog-free printing process for depositing expensive reagents onto the substrates.
Novel porous media can be flexibly printed into complex patterns using pigment- based inks. Moreover, the use of different pigments within the designed patterns enables these porous media to control wicking velocity. In addition to printable porous substrates, the research in this thesis shows that the manufacturing process can be improved by using piezoelectric inkjet printers. The use of these printers not only allows the expensive reagents to be precisely deposited onto the substrates, but it also offers a more cost-effective method of doing so. Finally, in order to ensure the printing process remained clog-free, we systematically investigated clogging mechanisms by printing with different polymers and nanoparticles.


title: Employing metagenomics to capture the dynamics and the diversity of freshwater bacteria and viruses

title: Assessing the diversity of freshwater bacteria and viruses

contributor:
Schellhorn, Herb
Biology

abstract: Microbial water communities are a complex consortium of bacteria, viruses and protozoa. These complex microbial and viral communities may contain pathogens that cannot be detected by conventional methods. Next-generation sequencing (NGS) offers the potential to exhaustively characterize all microbial and viral components of a given water sample and facilitates the identification and quantification of pathogens of interest. The goals of this thesis were to assess the dynamics and the diversity of freshwater bacterial and viral communities of the lower Great Lakes region and identify pathogenic bacterial and viral species. We first assessed the diversity of viral communities in six different beaches of Lake Ontario and Lake Erie, two of the largest freshwater reservoirs in North America. We employed a robust and routinely applicable approach that can provide a comprehensive analysis of bacterial and viral community composition. Our analysis suggests that the viral communities of the lower Great Lakes region are dominated by bacteriophages but also contained viruses of plants and animals. Exhaustive characterization of bacterial communities indicates that the bacterial community composition is highly diverse, and the diversity differs between recreational waters and beach sands. In addition, we identified sequences of pathogens that are not currently included in traditional water monitoring schemes in both recreational water and beach sand. To investigate the impact of spatiotemporal and environmental factors on the distribution of bacterial species, we employed a computational approach and our analysis suggests that dissolved oxygen (DO) level is strongly associated with bacterial community diversity. Using a computational approach, we have also identified habitat-specific bacterial species and a possible link between inter-connected habitats.  The findings of this thesis aid in our understanding of bacterial and viral community diversity in recreational waters and provide useful information to water quality decision makers.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Electron and Ion Beam Imaging of Human Bone Structure Across the Nano- and Mesoscale

contributor:
Grandfield, Kathryn
Materials Science and Engineering

subject:
Human bone
Transmission electron microscopy
Plasma focused ion beam
Hierarchical structure
Mineral
Collagen
Osteocyte network

abstract:
Human bone tissue has an inherent hierarchical structure, which is integral to its material properties. It is primarily composed of a collagen fiber matrix that is mineralized with hydroxyapatite. A comprehensive understanding of bone and the linkages between structural and cellular organization is imperative to developing fundamental knowledge that can be applied to better our understanding of bone disease manifestations and its interaction with implant devices. Herein, this thesis investigated non-traditional methods for evaluating bone structure across the nano- and meso-length scales.
Firstly, due to the inhomogeneous organization of collagen fibrils and mineral platelets of bone ultrastructure, a suitable methodology for the investigation of both phases needed to be generated. In this work, focused ion beam (FIB) microscopy was employed to create site-specific scanning transmission electron microscopy (STEM) lift-outs of human osteonal bone that could be visualized with correlatively with STEM and small angle X-ray scattering (SAXS). Samples were successfully characterized using both techniques, and minimal visual damage was induced during data acquisition.  This work is the first to demonstrate the potential for bone to be investigated correlatively using both STEM and SAXS.
Secondly, this work is the first to employ a dual-beam plasma FIB (PFIB) equipped with a scanning electron microscope (SEM), to investigate bone tissue across the mesoscale. This equipment enables large volume three-dimensional (3D) imaging at nanoscale resolution across larger mesoscale volumes. This thesis aimed to reduce ion beam-based artifacts, which presents as curtain-like features by adjusting the composition of protective capping layers. Subsequently, large volume tomograms of bone tissue were acquired, demonstrating the effectiveness of the PFIB to reveal mesoscale features including the cellular network of bone tissue.
Overall, this thesis has developed methods that allow for the application of advanced microscopy techniques to enhance the understanding of bone tissue across the nanoscale and mesoscale.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Bone tissue has a unique structure that perplexes both biologists and materials scientists. The hierarchical structure of bone has garnered the interest of materials scientists since the body’s skeletal strength and toughness are governed by the nanoscale (millionth of centimetres) to macroscale (centimeters) organization of bone. In this work, the intricate organization of bone is investigated using advanced electron and ion beam microscopy techniques, which achieve high-resolution imaging of bone structure. Firstly, this work developed a sample preparation workflow to correlate electron and X-ray imaging of the same bone tissue. Secondly, this work was the first to apply serial-sectioning plasma focused ion beam tomography to human bone tissue to investigate its structure at high resolution across micron-sized volumes. Here, previously unexplored methodologies to image bone are demonstrated with the hopes of applying such techniques to investigate healthy and pathological bone tissue in the future.


title: BCG-Induced Trained Innate Immunity in Alveolar Macrophages and Their Role in Early Protection Against Tuberculosis

contributor:
Xing, Zhou
Medical Sciences

subject:
Mycobacterium tuberculosis
Pulmonary
BCG
Innate immune response
Trained innate immunity
Vaccine
Alveolar macrophage
Macrophage memory

abstract: Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) is the leading cause of infectious disease-related death worldwide. The critical role of adaptive immunity in anti-TB host defence has been firmly established; thus, current efforts in developing novel vaccination strategies against TB are primarily focused on generating protective adaptive immunity at the infection site, the lungs. Innate immunity has not been a target for vaccination strategies against TB due to the belief that innate immune cells cannot exhibit memory-like characteristics which are known to be central to the long-lasting immunity created by vaccines. Also, the importance of innate immunity in anti-TB immunity has been overlooked. However, over 25% of individuals that are heavily exposed to M.tb clear infection without any detectable conventional T cell immune responses, suggesting a crucial role for innate immune cells in bacterial clearance. Interestingly, the early protection in these individuals is associated with their Bacillus Calmette-Guerin (BCG) vaccination status. Epidemiological studies have shown that BCG is capable of providing protection against numerous infections unrelated to TB in an innate-immune dependent manner. Such observations suggest that the innate immune system exhibits memory-like characteristics, capable of remembering the exposure to the vaccine and thereby responding in an augmented manner to future systemic infections. Nonetheless, it still remains unknown whether parenteral BCG immunization modulates the innate immune cells in the lung and airways, and if so, what role the trained innate immune cells play in early protection against pulmonary TB. Using a subcutaneous BCG immunization and pulmonary TB challenge murine model, we show that early protection against M.tb is independent of adaptive responses in the BCG immunized host. Our data suggest that enhanced early protection is mediated by the BCG-trained memory alveolar macrophages that we have shown to be functionally, phenotypically, metabolically, and transcriptionally altered following immunization. These novel findings suggest a significant anti-TB immune role for the innate immune memory established in the lung following parenteral BCG immunization and have important implications for the development of novel vaccination strategies against TB.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Pulmonary tuberculosis (TB) is a disease of the lung and is now one of the leading causes of human mortality worldwide. For more than eight decades, parenterally administered Bacillus Calmette–Guérin (BCG) vaccine has been globally used as the only approved vaccine against TB. Recently, it has also been observed that BCG vaccination provides protection against other diseases unrelated to TB and reduces childhood mortality in many developing countries where it is routinely administered to children shortly after birth. The mechanisms underlying the off-target protective effects of BCG vaccine remains largely under-investigated. In this project, we investigated how BCG vaccination enhances the immune system responses against TB and other unrelated infectious diseases. A better understanding of how the BCG vaccination modulates our immune system will provide us with the knowledge that will be useful in the development of more effective vaccination strategies against infectious diseases.


title: DEVELOPING EDUCATOR CAPACITY USING JOB–EMBEDDED COACHING: A COLLECTIVE CASE STUDY

contributor:
Richardson, Julie
Rehabilitation Science

subject: Job-embedded coaching, Professional Development, Inclusion, Inclusive Education, Disability, Case Study

abstract: Job–embedded coaching, whereby an expert in a particular knowledge domain such as childhood disability, teaching, or special education actively works and collaborates with educators long–term, has been demonstrated to be a successful approach to developing educator knowledge and practice. In consultative models educators may consult colleagues within the school, such as health care professionals and fellow educators, or they may attend professional workshops. However, consultative do not efficiently address how educators can better support students’ learning challenges in daily teaching practice and this knowledge is difficult to attain through traditional short–term professional development. The learning, social, and behavioural needs experienced by children and youth with disabilities frequently stem from underlying complex health care needs and are oftentimes too challenging for educators alone to address. Using a realist evaluation framework––which examines what works for whom and how in a given setting–– this multiple case comparison critically analyzed two separate cases that used job-embedded coaching in Ontario schools to build educator capacity about teaching children with diverse needs within the general classroom. One case was grounded in the rehabilitation model of service delivery whereby the coach was an occupational therapist, and the other case was grounded in education and employed a teacher with training in special education in the coach role. Examining context revealed that factors beyond coaching were responsible for its success. The contexts to which the implementing leaders belonged informed project driver mechanisms (e.g., professional training, designation, perspectives and experiences, model of service delivery) important for service delivery, teacher, coach, and student outcomes. Community mechanisms associated with the environment in which coaching was implemented (e.g., community culture as well as school ethos and school priorities) also were important for all outcomes. The alignment of project driver mechanisms with community mechanisms was important for the way in which service delivery was adopted. Job–embedded coaching is an effective method of professional development and its success is greater when a congruency in beliefs, priorities and culture exists in collaborative partnerships.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: As research about childhood disability increases, teachers are becoming more aware that the difficulties students experience at school may be part of an underlying health–related or developmental problem. Teachers attend professional development workshops to learn new skills; yet applying those skills in the classroom is an ongoing challenge. Daily practice and long-term training are more effective ways to develop teaching skills. One way of achieving this is through job-embedded coaching. Job–embedded coaching involves an expert (in this case an expert on disability) who coaches the teacher in the classroom during classroom time about different teaching techniques that will include and benefit all students. This research describes how two separate Ontario research teams (one health-based and one education-based) used job–embedded coaching to improve teachers’ abilities to teach students with a variety of learning needs. In one project, an occupational therapist acted as the job–embedded coach, while in the other project, the coach was a teacher with training in special education. This research compared both projects to learn more about what made coaching work, for whom it worked for, how it worked, and why it worked. The findings of this research showed that reasons beyond coaching alone were responsible for its success. The approach, perspectives, and culture coaches brought to the schools were important and were influenced by the environments to which the research teams belonged. The alignment between coaches’ approaches and culture and the school’s culture and vision was important to the success of coaching as well as to teacher, coach, and student outcomes. Job–embedded coaching as a form of professional development does work and can be improved in the school settings with a shared understanding about students with complex learning needs.


title: THREE ESSAYS ON PARTISAN POLITICS AND STOCK RETURNS

contributor:
Balvers, Ronald
Business Administration

abstract:
This dissertation contains three essays on partisan politics and its effect on the time series and cross-section of stock returns. The first essay investigates the presidential puzzle (Santa-Clara and Valkanov, 2003) -- the fact that the equity premium is 10% higher in years with Democratic governments than in years with Republican governments. I find the existence of a negative price reaction after Democratic victories in presidential elections. I also establish that the difference in the equity premium is significant only in the first year of the presidential cycle and that there is a negative equity premium in the fourth year of the cycle when the incumbent Republican loses the election. Moreover, the market reaction to changes in the likelihood of a candidate winning the election is significantly different for Republican and Democratic candidates. The evidence is consistent with a risk explanation and policy uncertainty. Finally, I explore several specifications for a presidential factor (P-factor) that improves on the CAPM and Fama-French 3-factor model for different test assets.
	The second essay considers the effect of different measures of corporate taxes on stock returns. The results support the partisan politics cycle effect on equity returns. A high minus low (Hi-Lo) portfolio sorted by (Total Corporate Taxes/Total Assets) has an annual return of +3.8% during Republican presidential terms and -6.3% for Democratic terms. Similarly, a high minus low portfolio sorted by (Marginal Tax Rate) has an annual return of +12.7% during Republican presidential terms and -6.4% for Democratic terms. Investors partially anticipate these results during the election period, i.e., increases in the probability of the Democratic candidate being elected are associated with negative returns for the (Hi-Lo) portfolio, which are significant for the 2016 election. The evidence is consistent with a cash-flow based explanation, in contrast with a risk-based explanation.
	The third essay studies the effect of partisan politics on stock returns in Latin America. The results are partially consistent with previous literature. There is a negative market reaction when left-wing parties win presidential elections. In contrast, the observed democratic premium in the U.S. is not observed in the sample of Latin American countries. Firms have higher returns during periods when the president is from a Centrist party. Moreover, the Christian-Secular dimension is analyzed, firms have significantly higher returns during periods when the president is from a Christian party and the market reaction is higher the day after the candidate from the Christian party wins. Results are consistent with Christian party led governments providing a low-risk and high profitability environment and stock market underreaction.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: INVESTIGATION OF THE CONTRIBUTION OF GENETIC VARIANTS ON THE DEVELOPMENT OF OBESITY AND METABOLIC COMPLICATIONS IN A MULTI-ETHNIC CONTEXT

contributor:
Meyre, David
Medical Sciences

abstract:
Obesity is a complex, multifactorial disease associated with several metabolic complications including type 2 diabetes (T2D) and cardiovascular disease. Obesity is also characterized by a state of chronic low-grade inflammation due to dysregulated adipokine secretion and macrophage infiltration, which is believed to be the pathophysiological link between obesity and other metabolic complications. It is currently unclear if inflammation is a cause of obesity and metabolic complications, or merely a consequence of it. Moreover, some ethnic groups are disproportionately affected by obesity and its metabolic complications, suggesting underlying genetic differences in the susceptibility to obesity.
This thesis aims to (1) to provide a comprehensive discussion of the ethnic differences in the genetic architecture of obesity, including a meta-analysis of heritability estimates of body mass index (BMI) from various ethnic groups, (2) examine the effects of the PPARγ Pro12Ala polymorphism on T2D-related traits, (3) investigate the contribution of genetic variants in inflammation-related genes on metabolic traits, and (4) determine the effects of genetic variation in the insulin sensitizing adipokine adiponectin and cardio-metabolic traits, aims (2), (3) and (4) being investigated in a high-risk population of Mexican children.
The major findings are (1) there is no difference between heritability estimates for BMI among African, admixed American and Asian populations, relative to Europeans, and in Mexican children: (2) circulating lipids can interact with PPARγ Pro12Ala to modulate markers of insulin resistance, (3) there is no association between inflammation-related genes and metabolic traits, and (4) circulating adiponectin concentration is strongly associated with metabolic traits.
Together this thesis provides insight into the biological mechanisms involved in obesity and its metabolic complications. With a better understanding of the molecular mechanisms involved, more effective prediction of high-risk individuals, preventions and treatments and can be developed.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: A Comparison of Beam Induced Damage from Xenon and Gallium Focused Ion Beams

contributor:
Bassim, Nabil
Materials Science and Engineering

subject:
FIB
Ion beam
lithography
nanofabrication

abstract:
Focused ion beam/scanning electron microscopy (FIB/SEM) is a tool commonly used for applications including preparation of site-specific transmission electron microscopy (TEM) samples, nanotomography, and electronic circuit edit. Another potential application is optical device prototyping; however, the ion beam itself has been shown to cause damage fatal to device operation. This thesis first includes several examples of FIB-fabricated optical devices that had limited functionality compared to simulation. Second, the underlying causes of ion beam-induced optical damage from gallium and xenon ion sources is characterized.
	Monte Carlo simulations of ion-solid interactions were confirmed using TEM analysis to measure the thickness of the damaged layer. For crystalline samples such as silicon, Raman response can be used as a measure of lattice damage. Using these techniques, it was found that optical damage from a gallium beam is more severe than from a xenon beam, and occurs in the form of lattice amorphization and implantation of beam ions. This damage hinders optical coupling by altering the physical and electronic structure of the sample. Consequently, the xenon PFIB is a better choice for optical device prototyping.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The second half of the 20th century saw the advent of nanotechnology, both in the context of understanding the structure of the natural world beyond the limit of light microscopy, as well as manipulating materials to create useful microscopic devices, including the computers ubiquitous in today’s life. One technology that has contributed to today’s nano-centric paradigm is the focused ion beam/scanning electron microscope (FIB/SEM). The FIB/SEM is used to machine materials with extreme precision for many diverse applications such as modifying microcircuits, three-dimensional (3D) nanotomography, or to prepare samples for other microscopy techniques. For some applications, however, damage to the sample from the ion beam can be fatal. New ion sources have become available in the past ten years that may cause less damage to samples, and thus open up new applications for FIB. This thesis includes first a description of a series of optical devices prototyped using FIB. This is followed by a comparison of the damage induced by the conventional liquid gallium ion source and new xenon plasma ion sources, and a discussion of the relative merits of the ion sources for optical device fabrication.


title: MACROPHAGE IRON CONTENT AND EXACERBATIONS OF COPD

contributor:
Nair, Parameswaran
Medical Sciences

subject:
COPD
Macrophage
Iron Overload

abstract:
Background: Many COPD patients have recurrent exacerbations due to infection, but there are no valid predictors of this phenotype. Previously an observational study showed that higher iron content in sputum macrophages was associated with infectious exacerbations.
Objectives: The thesis aimed to assess the mechanisms of pulmonary macrophage iron sequestration, test the effect of macrophage iron-loading on bacterial uptake and killing, and prospectively determine if sputum hemosiderin index can predict infectious exacerbations of COPD.
Methods: Intracellular iron was measured directly and indirectly in cell-line-derived and isolated sputum macrophages after treatment with exogenous IL-6, hepcidin or heat-inactivated H.influenzae. Bacterial uptake and killing were compared in both types of macrophages, in the presence or absence of iron-loading. A prospective cohort of COPD patients had their sputum hemosiderin index measured at baseline and were monitored for 1-year for infectious exacerbations requiring admission to hospital.
Results: For pulmonary iron sequestration, IL-6 appears important, but the role of hepcidin is not clear. Iron-loading reduced the uptake of COPD-relevant organisms by almost one-third in cell-line-derived macrophage, and there was a near-significant linear relationship between sputum hemosiderin index and killing of H.influenzae (p=0.075). In terms of infective exacerbations, FEV1 had predictive utility (beta=-0.051, p=0.017) while a positive trend for sputum hemosiderin index (beta=0.035, p=0.051) suggests that this biomarker has clinical promise.
Conclusion: Through in vitro experiments and cohort data, we have established a framework suggesting that excess iron in pulmonary macrophage may contribute to recurrent bacterial airway infection in COPD. IL-6 appears to contribute to sputum macrophage iron sequestration, which subsequently may lead to immune cell dysfunction and ultimately result in an increased frequency of infective exacerbation.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: COPD patients often require hospitalization due to respiratory infections (bacterial or viral) that result in worsening of their breathing. It is difficult to predict who is at high risk for this to occur, which makes it harder to prevent. Many species of bacteria depend on iron as a nutrient. We wanted to see if iron being present in certain immune cells (macrophages) in the sputum could predict these flares by: testing how iron enters these cells, seeing if bacterial growth is altered by putting iron into these cells, and following a group of COPD patients and seeing if those with higher iron in their sputum had higher risk of infectious flares. Though more testing is needed, we found that a protein often present with chronic inflammation may be associated with higher sputum macrophage iron, and that there is evidence that killing of bacteria in COPD sputum macrophages is lower with high iron, and that patients with higher sputum iron are at greater risk of having infectious flares.