title: Roles of clinical practice guidelines outside the clinical encounter

contributor: Clinical Health Sciences (Health Research Methodology)

subject:
guidelines
quality improvement
coverage decisions
drug reimbursement
evidence-based medicine
medical education
research prioritization
research gaps
medical litigation
judicial decisions
maintenance of certification
accreditation

abstract:
Clinical practice guidelines (CPGs) are statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options. CPGs’ recommendations have traditionally focused on informing clinicians and patients on the best options, i.e., supporting decisions that occur at the clinical encounter level. Considering all their advantages (a systematic and comprehensive review of the evidence, a multidisciplinary team assessing the evidence and balancing benefits and harms, and the additional considerations such as patients’ preferences, implementability and feasibility of interventions and their costs) CPGs have also become powerful tools to inform decisions and activities outside the clinical encounter. This, because the clinical encounter cannot be completely separated from other decisions that indirectly affect that level, such as those related to quality improvement activities and economic decisions in healthcare. Moreover, activities that are not directly related to the clinical encounter can benefit from CPGs, like education and licensing activities and research prioritization processes, or judicial decisions. The role of CPGs in all these activities has been neglected in the literature.
In this study, I performed a critical interpretive synthesis of the literature to summarize the different roles CPGs play outside the clinical encounter and to understand how, and under what conditions CPGs are used in these roles. I also conducted an international survey to describe how frequent these roles exist, from the CPGs developers' perspectives. Lastly, I conducted a multiple case study to understand how and under what conditions CPGs play one of the main roles outside the clinical encounter (drug funding decisions), in two different settings (Colombia and Canada/Ontario).
Based on the results, I developed a framework to describe and categorize the roles of CPGs outside the clinical encounter and to determine how and under what conditions CPGs are used in these roles. I highlighted the key areas that require additional methodological research and categorize the roles in main, secondary and unanticipated roles. I also described how international developers reported that CPGs play these roles and how these roles are part of their CPGs final aims in the second study. Lastly, in the case study, I revealed that CPGs were instrumentally used to inform one of the main roles, drug funding decisions, in the Colombian case, and they had a minor conceptual use in the case of Canada/Ontario.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Applying Machine Learning to Explore Nutrients Predictive of Cardiovascular Disease Using Canadian Linked Population-Based Data

title: Machine Learning to Predict Cardiovascular Disease with Nutrition

contributor: Clinical Epidemiology/Clinical Epidemiology & Biostatistics

subject:
machine learning
nutritional epidemiology
public health
artificial intelligence
conditional inference forest
interpretable machine learning
population health survey
data linkage
cardiovascular disease
nutrition
prediction
predictive modeling

abstract:
McMaster University MASTER OF PUBLIC HEALTH (2020) Hamilton, Ontario (Health Research Methods, Evidence, and Impact)

TITLE: Applying Machine Learning to Determine Nutrients Predictive of Cardiovascular Disease Using Canadian Linked Population-Based Data AUTHOR: Jason D. Morgenstern, B.Sc. (University of Guelph), M.D. (Western University) SUPERVISOR: Professor L.N. Anderson, NUMBER OF PAGES: xv, 121

abstract: The use of big data and machine learning may help to address some challenges in nutritional epidemiology. The first objective of this thesis was to explore the use of machine learning prediction models in a hypothesis-generating approach to evaluate how detailed dietary features contribute to CVD risk prediction. The second objective was to assess the predictive performance of the models. A population-based retrospective cohort study was conducted using linked Canadian data from 2004 – 2018. Study participants were adults age 20 and older  (n=12 130 ) who completed the 2004 Canadian Community Health Survey, Cycle 2.2, Nutrition (CCHS 2.2). Statistics Canada has linked the CCHS 2.2 data to the Discharge Abstracts Database and the Canadian Vital Statistics Death database, which were used to determine cardiovascular outcomes (stroke or ischemic heart disease events or deaths). Conditional inference forests were used to develop models. Then, permutation feature importance (PFI) and accumulated local effects (ALEs) were calculated to explore contributions of nutrients to predicted disease. Supplement-use (median PFI (M)=4.09 x 10-4, IQR=8.25 x 10-7 – 1.11 x 10-3) and caffeine (M=2.79 x 10-4, IQR= -9.11 x 10-5 – 5.86 x 10-4) had the highest median PFIs for nutrition-related features. Supplement-use was associated with decreased predicted risk of CVD (accumulated local effects range (ALER)= -3.02 x 10-4 – 2.76 x 10-4) and caffeine was associated with increased predicted risk (ALER= -9.96 x 10-4 – 0.035). The best-performing model had a logarithmic loss of 0.248. Overall, many non-linear relationships were observed, including threshold, j-shaped, and u-shaped. The results of this exploratory study suggest that applying machine learning to the nutritional epidemiology of CVD, particularly using big datasets, may help elucidate risks and improve predictive models. Given the limited application thus far, work such as this could lead to improvements in public health recommendations and policy related to dietary behaviours.

abstract: Thesis

abstract: Master of Public Health (MPH)

abstract: This work explores the potential for machine learning to improve the study of diet and disease. In chapter 2, opportunities are identified for big data to make diet easier to measure. Also, we highlight how machine learning could find new, complex relationships between diet and disease. In chapter 3, we apply a machine learning algorithm, called conditional inference forests, to a unique Canadian dataset to predict whether people developed strokes or heart attacks. This dataset included responses to a health survey conducted in 2004, where participants’ responses have been linked to administrative databases that record when people go to hospital or die up until 2017. Using these techniques, we identified aspects of nutrition that predicted disease, including caffeine, alcohol, and supplement-use. This work suggests that machine learning may be helpful in our attempts to understand the relationships between diet and health.


title: Hot Tearing Susceptibility of Single-Phase Al-3.8 wt%Zn-1 wt%Mg Alloy Using the Constrained Rod Solidification Experiment: Influence of 1.2 wt%Fe Addition and Grain Refinement

contributor:
Shankar, Sumanth
Mechanical Engineering

subject:
Hot Tearing
Aluminium Alloys
high pressure die casting
structural alloys
CT scan

abstract: The increasing global demand for a substantial lightweighting of automobiles to enable a reduction in the greenhouse gas (GHG) emissions and fuel consumption has led to the adaptation of the high strength Al wrought alloys such as the 2xxx and 7xxx series in near net-shaped manufacturing using the high pressure die casting (HPDC) process.  However, the obstacle for this adaptation is the high susceptibility to hot tearing during the solidification of these alloys. A new structural Al alloy for high pressure die casting application was developed from the single-phase Al-Zn-Mg family; a high strength and ductile alloy that could be adapted to manufacturing automotive structural components using HPDC and help with a significant reduction in the overall curb-weight of an automobile and thereby increasing the vehicle fuel efficiency. The objective of this study was to enable a better understanding of the hot tearing phenomenon during solidification of the Al-3.8 wt%Zn-1 wt%Mg alloy, the effect of adding 1.2 wt% Fe to the alloy to improve the castability in HPDC process and the effect of adding Ti as a grain refiner of the primary Al phase during solidification of the alloy using Al-5 wt%Ti-1 wt%B master alloy.  The constrained rod solidification (CRS) experiments were carried out to measure transient stress, transient strain, and transient temperature during solidification of the alloy. Improvements to the CRS experiments were also developed to obtain a repeatability of the acquired data. The computerized Tomography (CT) imaging was used to visually characterize the hot tearing. Hypothesis on the factors promoting the hot tearing tendencies in single-phase alloys solidified using net-shaped casting processes has been presented with evidence-based on transient stress-strain and thermal data curves obtained during the solidification experiments.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Development and application of µXRF-CS Cl as a proxy for Holocene drought and hurricane conditions in the Yucatan Aquifer, Mexico

contributor:
Reinhardt, Eduard
Earth and Environmental Sciences

subject: yucatan peninsula, cave systems, sedimentology, paleoclimatology, paleosalinity,

abstract:
The highly porous karst limestone of the Yucatan Peninsula promotes infiltration of rainwater into the subsurface, where it becomes part of the Yucatan Aquifer.  The combination of high subsurface porosity, high evapotranspiration, and seasonal droughts results in relative scarcity of lakes or drinkable water at the surface. The majority of past and present people living on the Yucatan Peninsula have depended on groundwater resources for domestic purposes. Whereas coastal karst aquifers such as the one in the Yucatan Peninsula are important water resources, they are highly vulnerable to climate-related changes such as sea level (SL) rise, increased hurricane intensity and extended droughts. With ongoing development along the eastern coast of the Yucatan Peninsula (Quintana Roo), predicted increases in storm intensity, and rising population and potential pollutant output, it has become imperative to study the seasonal and long-term effects of climate and human activity on the Yucatan Aquifer.
Like many coastal karst aquifers, the Yucatan Aquifer is stratified according to density, with the Meteoric Water Mass (MeWM) flowing towards the coast on top, and the Marine Water Mass (MaWM) flowing inland on the bottom. The current basis of our knowledge about how the two water masses interact has been from short-term instrumental monitoring and numerical modelling, which is useful for understanding straightforward relationships between salinity, precipitation and temperature across the two water masses and have paved the way for more complex analyses to be completed using the simple principles to guide geochemical studies of sediment within the systems. Generally, sediment cores have been analysed discretely using various methods including grain size analysis, micropaleontology, WD-XRF, and others, however the recent rise of µXRF Core Scanning provides a quicker, more cost effective and higher-resolution method for studying climate-related patterns in sediment cores.
This thesis outlines and provides robust evidence for three new methods of using µXRF-CS to determine past and present climatological changes and their relationship to sediment elemental counts. We provide the first outline of the seasonal and spatial controls of geochemical changes in sedimentation in a coastal cave system (Yax Chen), using four years of in situ sediment collection.  We then provide the first calibrated record of past salinity based on Cl counts within sediment cores taken from shallow lakes. Although instrumental monitoring has provided evidence that the aquifer is impacted by modern wet and dry periods, the effect of past climate on the aquifer has not been investigated. We provide the first record of water-column mixing at three locations within coastal Quintana Roo. This demonstrates that there has been a long-term climate impacts to coastal Yucatan Peninsula groundwater, which may be scaled to other karst islands and provides evidence that increased hurricane frequency and/or magnitude could change the baseline salinity of the fresh MeWM.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: The porous limestone (karst) geology of the Yucatan Peninsula results in percolation of rainwater down into the subsurface where it is held in the vast Yucatan Aquifer that past and present people have depended on for water resources. Such aquifers are highly vulnerable to human activity and also climate change via increased sea level rise, hurricane intensity and droughts. The Yucatan Aquifer is made up of two separate water masses that have different salinities, and can interact physically and chemically due to changes in climate and weather.  Sediment cores can be used to look at subannual geochemical changes which reflect long term behaviour of the aquifer, but first the relationship between sediment change and climate must be established.  This thesis uses an iTRAX X-Ray Fluorescence Core Scanner (XRF-CS) to investigate changes in surface water and groundwater over the past 6000 years, and provides the first record of rainfall-induced mixing in a coastal karst aquifer. We also provide evidence of rapid salinity change in shallow lakes associated with intense dry periods, and reveal relationships between cave sedimentation and surface vegetation coverage.


title: Exploring Perception and Action Response to Multisensory Incompatibility Effects

contributor:
Lyons, Jim
Kinesiology

abstract:
It has been suggested that both visual (e.g., Ward et al., 2002) and auditory (e.g., Sinnett & Kingstone, 2010; Cañal-Bruland, 2018) stimuli can influence anticipatory judgements. The following studies address the nature of the perceptuomotor mechanisms underlying these judgments by contrasting two well-established theoretical frameworks that differentially explain the linkage of perception and action (i.e., a perception-action dissociation model, Milner & Goodale, 2006; a planning-control model, Glover & Dixon, 2001). Specifically, this thesis explores how, when two sources of sensory information (audition and vision) are put into conflict, motor actions may mediate simple perceptual judgements. With reference to the theoretical models noted above, perception-action dissociation theory would predict that incompatible sensory information would have no influence on action. Conversely, the planning-control model would predict incompatible sensory information to significantly influence action. In the three studies comprising this thesis, participants completed two tasks under two distinct response conditions: Perception only; and perception combined with a goal-directed aiming action.

In Studies 1 and 3, participants (n=16) predicted when a visual stimulus travelling at either a fast (224 mm/s) or slow (113 mm/s) velocity in a straight-line trajectory would enter a specified target zone. In Study 1, this was accomplished by simply pushing a button whereas in Study 3, participants moved a stylus controlling an on-screen cursor to the predicted interception point. In both experiments, either a loud (70dB), soft (50db), and no (0db) burst of white noise was presented for 150 ms at the initiation of visual stimulus movement. On each trial, the stimulus would disappear after either 33% or 66% of distance traveled.  Results of Study 1 suggest that when the loud sound accompanied the 33% vision stimulus, overshoot bias was significantly reduced. Conversely, when the loud sound accompanied the 66% vision stimulus, overshoot bias increased (and vice versa) suggesting that in situations where visual information is less reliable, robust auditory information may serve as a useful substitute. When, however, more vision is available, that same robust auditory information may interfere with perceptual judgements. In Study 2, no differences were observed in participants’ accuracy and directional bias when the auditory stimulus originated from a different hemifield than the origin of the visual stimulus. Lastly, in Study 3, participants were less accurate overall in predicting the point of interception. In addition, results from the kinematic markers associated with participants moving the stylus (e.g., Movement Time, Peak Velocities and Acceleration, etc.)  suggest that differing combinations of auditory and visual stimulus information affect how motor actions are generated and executed in these types of multisensory anticipatory interception tasks.

abstract: Thesis

abstract: Master of Science in Kinesiology


title: The Under-Representation of Women in Randomized Controlled Trials of Heart Failure

contributor:
Van Spall, Harriette
Health Research Methodology

subject:
Heart Failure
Randomized Controlled Trials

abstract: Women are thought to be under-represented as clinical trial participants and as clinical trialists in heart failure. We reviewed randomized controlled trials of heart failure published in high impact medical journals and examined the representation of women as both participants and authors. Furthermore, we explored clinical trial characteristics independently associated with women as clinical trial participants and as lead authors. Our analysis demonstrated that women are under-represented as both clinical trial participants and leaders, with no change in temporal trends over time. Addressing clinical trial characteristics associated with under-representation and developing strategies to overcome barriers may be a strategic way to improve the representation of women in heart failure research.

abstract: Thesis

abstract: Master of Science (MSc)


title: Perinatal Determinants of Mental Disorders Identifying Risk Factors and Testing the Effectiveness of Early Interventions on Infant and Child Emotion Regulation

contributor:
Van Lieshout, Ryan
Neuroscience

subject: Developmental origins of health and disease

subject: emotion regulation

subject: infancy

subject: psychopathology

subject: prenatal diet

subject: postpartum depression

subject: childhood

abstract:
Objectives: To investigate the preventive potential of the Developmental Origins of Health and Disease (DOHaD) hypothesis as it pertains to emotion dysregulation and psychopathology by: i) elucidating the impact of modifiable perinatal risk factors, and ii) examining whether a postnatal intervention can improve infant emotion regulation.
Methods: Studies 1 and 2 used data from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort and the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort to examine if modifiable perinatal risk factors (including prenatal diet quality) confounded the link between prenatal metabolic complications and offspring psychopathology. Study 3 used MIREC data to examine if prenatal diet quality was linked to a biomarker of emotion regulation in infants (autonomic nervous system (ANS) function). Studies 4 and 5 used data from 40 infants of mothers diagnosed with postpartum depression (PPD) and 40 healthy control infants matched on infant age sex and socioeconomic status. These studies examined if infant emotion regulation (Study 4) and mother-infant physiological synchrony (a marker of dyadic emotion regulation-Study 5) improved following maternal cognitive behavioral therapy (CBT) for PPD.
Results: In Studies 1 and 2, prenatal diet quality accounted for significant variance in the links between prenatal metabolic complications and offspring psychopathology. In Study 3, poor prenatal diet quality was associated with adverse ANS development in offspring. In Studies 4 and 5, infants exhibited more adaptive emotion regulation and mother-infant synchrony improved following maternal receipt of CBT for PPD.
v
Conclusions: Elucidating the impact of modifiable perinatal risk factors on offspring psychopathology provides meaningful targets for intervention, and postnatal interventions may improve offspring emotion regulation and could reduce the risk of psychopathology. This work highlights the importance of the perinatal period as a time during which modifiable risk factors can be identified and intervened upon to reduce mental disorder risk across the lifespan.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: Healthy brain development is important for health and success in life. However, risk factors such as the mother’s poor physical and mental health during pregnancy and in the first postnatal year can increase the risk of emotion and behaviour problems in offspring. Therefore, the objectives of this thesis were to i) identify links between modifiable pre and postnatal risk factors and poorer offspring brain development and ii) determine if intervening on one of these risk factors might improve offspring brain development. Results from this thesis show that an unhealthy maternal diet in pregnancy was linked to more offspring emotion, behaviour, and brain development problems and that treating postpartum depression in mothers may improve offspring brain development. This work suggests that identifying and intervening on modifiable risk factors is important to improve early brain development and may prevent the development of mental disorders later in life.


title: Post-Synthetic Modification of Polymeric Structures using the Strain-Promoted Azide-Alkyne Cycloaddition

contributor:
Adronov, Alex
Chemistry and Chemical Biology

abstract:
The discovery of functional materials and compounds is a goal shared across multiple fields of chemistry. This can be achieved by preparing multiple derivatives from independent syntheses, or by the post-synthetic modification (PSM) of a reactive material. This distinction is important in the realm of polymer chemistry, as it significantly reduces the synthetic workload, while maintaining a constant degree of polymerization (DP) between the derivatized series. The criteria for a suitable reaction are complicated by the need for efficient and quantitative chemistry. In the world of small molecule synthesis, impure products can be easily removed from the target substrate. However, for a polymer to undergo a successful PSM, every reactive unit must be converted without fail, as defects are covalently bound to the scaffold. This issue is further amplified by the low solubility (and at times, insolubility) of polymeric materials in a narrow selection of solvents. In my Thesis, I address this issue by introducing a reactive dibenzocyclooctyne (DIBO) repeat unit into polymeric and macromolecule structures, such as linear conjugated polymers and covalent organic frameworks (COFs). The strained-alkyne present in DIBO undergoes the strain-promoted azide-alkyne cycloaddition (SPAAC) to readily produce triazoles with a variety of organic azides.
I initially explore the utility of the SPAAC reaction to produce a library of conjugated polymers, differing only in their side-chain in Chapter 2. By using PSM to accomplish this, the DP of all the polymers remained identical. This is vital, as the objective of this polymer library was to reveal the effect of varying the side-chain on the supramolecular complexes formed between the produced conjugated polymers, and single-walled carbon nanotubes (SWNTs). We showed that the polymers retained the same DP among the series and established a new understanding of polymer-SWNT interactions. Although we had a viable scaffold for PSM with SPAAC, the imine-backbone of the polymer compromised the long-term stability of the structure. Imines are prone to hydrolysis and are especially unstable in acidic environments. A compromised polymer backbone would diminish the importance of a uniform DP among our polymer library. To remedy this, in Chapter 3, I prepared a novel bisaldehyde DIBO monomer, and polymerized it with Wittig chemistry. I show that this new polymer system possessed the same reactivity with azides, with the benefit of long-term stability, and interesting photophysical properties that the previous polymer lacked. To demonstrate this, the new polymer was ultimately cross-linked to form a photoluminescent hydrogel.
Lastly in Chapter 4, I attempt  the synthesis of a COF bearing a DIBO repeat unit. COFs are a fascinating class of polymer materials, and the PSM and exfoliation of these materials are of scientific interest. I demonstrate the synthesis, and thoroughly characterize a DIBO bearing COF. The COF undergoes PSM with SPAAC, and I leverage this reactivity to prepare a stable colloidal dispersion of the 2D polymeric sheets.

abstract: Thesis

abstract: Doctor of Science  (PhD)


title: Development of an In-Situ Alloyed Microstructure in Laser Additive Manufacturing

contributor:
Phillion, André Bernard
Zurob, Hatem S.
Materials Science and Engineering

subject:
Additive Manufacturing
Selective Laser Melting
Titanium
Laser Powder-Bed Fusion
3D Printing
Beta-Ti Alloys
In-Situ Alloying
Synchrotron
X-Ray Diffraction

abstract: Additive Manufacturing (AM) processes are gaining prominence in industry as they can build parts to near-net-shape with minimal postprocessing.  Metal laser AM techniques, such as Selective Laser Melting (SLM), offer rapid cooling rates on the order of 10^5-10^6 K/s. This is due to a highly-focused laser heating a microscopic volume in an otherwise lower-temperature environment. Hence, metal laser AM can manufacture novel, out-of-equilibrium microstructures that cannot be produced in near-net-shapes with other processes. It is desirable to optimize feedstocks for metal AM processes to leverage their advantages. One option of optimizing feedstocks is through in-situ alloying, or by using elemental powders. Elemental powders homogenize over the course of multiple laser passes, or intrinsic heat treatments. However, rapid cooling rates prevent the homogenization of a layer when first printed. To investigate the homogenization process, this thesis used synchrotron X-ray Diffraction (sXRD) to track the phase transformations during the SLM of a 14-layer single wall (single-hatch, multilayered) of Ti-1Al-8V-5Fe (Ti-185) from elemental Ti, Fe and an alloyed AlV powders, capturing frames at 250 Hz. Infrared imaging was performed simultaneously on the surface at 1603.5 Hz to observe the temperature changes at the surface. Post-mortem electron microscopy was performed on cross-sections of the wall perpendicular to the scanning direction to observe the changes in the microstructure with respect to the build direction. Specifically, Electron Dispersive X-Ray Spectroscopy and Electron Backscatter Diffraction were performed to observe the alloying elemental distribution and microstructure of the wall with respect to the build direction. The research performed found that in the melted zone, phase transformation times below 50 ms yielded a partially-alloyed microstructure, with regions concentrated and dilute in alloying elements. Partial mixing was diffusion-induced by laser beam heat and the exothermic heat of mixing of Ti-185 from its constituent elements. Further diffusion during reheating cycles yielded an alloyed microstructure.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Relational Data Curation by Deduplication, Anonymization, and Diversification

contributor:
Chiang, Fei
Computing and Software

subject:
data quality
data cleaning
data privacy

abstract:
Enterprises acquire large amounts of data from a variety of sources with the goal of extracting valuable insights and enabling informed analysis.  Unfortunately, organizations continue to be hindered by poor data quality as they wrangle with their data to extract value since most real datasets are rarely error-free. Poor data quality is a pervasive problem that spans across all industries causing unreliable data analysis, and costing billions of dollars. The large body of datasets, the pace of data acquisition, and the heterogeneity of data sources pose challenges towards achieving high-quality data. These challenges are further exacerbated with data privacy and data diversity requirements. In this thesis, we study and propose solutions to address data duplication, managing the trade-off between data cleaning and data privacy, and computing diverse data instances.

In the first part of this thesis, we address the data duplication problem. We propose a duplication detection framework, which combines word-embeddings with constraints among attributes to improve the accuracy of deduplication. We propose a set of constraint-based statistical features to capture the semantic relationship among attributes. We showed that our techniques achieve comparative accuracy on real datasets. In the second part of this thesis, we study the problem of data privacy and data cleaning, and we present a Privacy-Aware data Cleaning-As-a-Service (PACAS) framework to protect privacy during the cleaning process. Our evaluation shows that PACAS safeguards semantically related sensitive values, and provides lower repair errors compared to existing privacy-aware cleaning techniques. In the third part of this thesis, we study the problem of finding a diverse anonymized data instance where diversity is measured via a set of diversity constraints, and propose an algorithm to seek a k-anonymous relation with value suppression as well as satisfying given diversity constraints. We conduct extensive experiments using real and synthetic data showing the effectiveness of our techniques, and improvement over existing baselines.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Peripheral Monocytes and Intestinal Macrophages during Chronic Inflammation

contributor: Medical Sciences (Molecular Virology and Immunology Program)

abstract: Inflammation is a complex biological response required to maintain homeostasis, but chronic inflammation increases risk of morbidity and mortality. Monocytes and macrophages often contribute to pathology in chronic inflammatory disorders. We hypothesized that chronic inflammation alters peripheral monocyte and intestinal macrophage prevalence, phenotype, and functions. We predicted these effects are modulated by different biological conditions, and they can be mediated by TNF and the intestinal microbiota. In Chapter 3, we investigated peripheral blood immune cell quantities (immunophenotype) under conditions of homeostasis. We observed that the female reproductive cycle did not have a significant effect on immunophenotype, though there were sex differences. In Chapter 4, we examined the relationships between adiposity, chronic inflammation, circulating monocytes, hyperglycemia, and hyperinsulinemia, in male mice. We found that increased circulating Ly6Chigh monocytes correlated with insulin resistance, and that this was mediated by TNF. In Chapter 5, we observed in non-pregnant female mice that there were temporal effects of obesity on peripheral blood immunophenotype, with an increase in Ly6Chigh monocytes. Pregravid obesity altered immunophenotype at mid-pregnancy. In late pregnancy, removal of TNF did not prevent obesity-associated changes to immunophenotype. Excess gestational weight gain also influenced peripheral immunophenotype in lactation. In Chapter 6, we found that obesity altered ileum and colon CD4-TIM4-, CD4+, and CD4+TIM4+ macrophage numbers, phenotype, and cytokine production, in a temporal and tissue-specific manner. Neither peripheral nor intestinal effects of obesity in non-pregnant female mice were mediated by TNF. We identified that there were microbiota-associated and age-associated effects that contributed to changes in colon macrophages between young and old mice. Obesity, excess gestational weight gain, and biological aging had different effects on intestinal macrophage populations. This research provides a better understanding of how peripheral monocytes and intestinal macrophages change in response to inflammation under different biological conditions across the life course.

abstract: Thesis

abstract: Doctor of Philosophy (Medical Science)

abstract: High levels of inflammation in the absence of infection or injury, as occurs in obesity, can increase an individual’s susceptibility to developing chronic disease (e.g. diabetes, heart disease). Inflammation changes numbers and functions of immune cells like monocytes and macrophages. Inflammation is influenced by biological sex, and increases naturally in pregnancy and with age. The goal of this thesis was to characterize how inflammation affects monocyte and macrophage numbers and functions within the blood and the gut, which may contribute to risk of chronic disease. We identified that obesity alters monocytes within the blood of young individuals and in pregnancy, but reduction of inflammation in obesity had distinct effects in males and females. We also found that obesity, pregnancy, and aging cause different changes to macrophages in the gut. These findings suggest that monocytes and macrophages have altered numbers and functions under different biological conditions associated with inflammation.


title: Nietzsche's Standard of Value: Degrees of Strength

contributor:
Allen, Barry
Philosophy

subject:
Nietzsche
degrees of strength
strength
power
will to power
value

abstract:
The aim of this study is to identify and explicate Nietzsche’s standard of value, that is, the basis upon which he approves of some human phenomena (e.g., moralities, philosophies, artistic and political movements, etc.) and disapproves of others. I argue that this standard is best captured by the concept of “degrees of strength.”

Part I undertakes a detailed examination of Nietzsche’s philosophical methodology, which must be understood in order to understand his conception of degrees of strength. I argue that the central tenet of his methodology is his commitment to “historical philosophy,” that is, to the view that absolutely opposite phenomena like soul and body, good and evil, and so on, do not exist as opposites, and that their opposition is only relative. I here engage with what is perhaps the most prominent reading of Nietzsche’s methodology in the Anglophone world today, namely that it is a form of “naturalism,” understood as a commitment to some kind of continuity with the empirical sciences. I show that this reading relies on a definition of “nature” that Nietzsche never gives, and commits him to an ontology that he explicitly rejects, without doing anything to clarify his methodology that is not done by the concept of historical philosophy.

Part II examines Nietzsche’s attempt to formulate a “proper physio-psychology” based on historical philosophy, which requires him to conceive of human beings as communities of willing subjects that he calls “drives.” I argue that Nietzsche adopts the notion of the human being as a multiplicity from physiology, and attempts to combine it with the notion of the willing subject that arises from introspective psychology. He believes that the human belief in causality is a result of the psychological experience of willing, and that physiology cannot explain the causal relations among events in the body without appealing to a concept of will. I then show how he extends this insight beyond the body to the world as a whole, arguing that we cannot comprehend causality at all except by means of the concept of “will to power.” This, I claim, is Nietzsche’s main reason for asserting that the world is “will to power and nothing else.”

Part III introduces Nietzsche’s concept of the “problem of value,” the solution of which amounts to what he calls “the determination of the order of rank among values,” that is, of which human values contribute most to the enhancement of the power of humanity, and which frustrate such enhancement. I argue that the standard by which Nietzsche determines this is a symptomatology based on the concept of degrees of strength: those “ways of thinking and valuing” that are symptomatic of higher degrees of physio-psychological strength are more valuable for the enhancement of the overall power of humanity, while those that are symptomatic of weakness are less valuable, or even disvaluable, for that end. While the main focus of Part III is to explicate the concepts of physio-psychological strength and weakness, I conclude with an examination of what Nietzsche calls the “great economy of the whole,” according to which even weakness often has value for enhancing the power of humanity, so long as it is kept in its proper place and not valued more highly than strength.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: The Intersection of Food Insecurity, Gestational Diabetes, and Mental Health Conditions: Examining Pregnancy From a Biocultural Perspective

contributor:
Moffat, Tina
Anthropology

subject:
biocultural approach
food insecurity
gestational diabetes
mental health
pregnancy health
syndemic risk

abstract:
Pregnancy brings numerous physiological and psychosocial changes and conditions, which can include gestational diabetes mellitus (GDM), and mental health conditions, including anxiety, and mood disorders such as depression. Food insecurity, or not having access to a diet that meets needs and preferences, may make management of pregnancy complications more challenging. I examined whether or not food insecurity was associated with a greater prevalence of mental health conditions, or GDM during pregnancy. I used the biocultural and syndemics approaches to the investigate the relationships among these conditions and to understand their interactions with the larger environment.
The main questions are: (1) Does pregnancy increase the risk of developing or worsening food insecurity? (2) Are there positive associations between food insecurity during pregnancy and GDM as well as mental health conditions? (3) How does food insecurity impact the management of above-mentioned issues? (4) What are the experiences of individuals who have had GDM during pregnancy? To answer these questions, I undertook a mixed methods approach that involved quantitative analysis of the Canadian Community Health Survey, as well as a survey administered to pregnant people in the city of Hamilton. I also quantitatively analyzed pre-existing focus group transcripts and conducted one-on-one interviews with pregnant and postpartum people in Hamilton.
This study found that there is a syndemic interaction between food insecurity, GDM, and mental health conditions in Canada. Analysis of focus group and interview transcripts provided further insight into the complex environments that shape risk for developing one, or more of these conditions during pregnancy. These results indicate how the pregnancy experience is impacted by a multitude of factors, which can lead to increasing complication risk.

abstract: Thesis

abstract: Master of Arts (MA)


title: Midwifery Students and Obstetrical Residents Learning, Understanding and Application of Shared Decision Making

contributor:
Darling, Liz
Health Science Education

subject:
Shared Decision Making
Midwifery
Obstetrics
Residents

abstract:
Introduction:

Childbirth is an important time in a client and patient’s life. The pregnant client seeks to obtain as much control over their circumstance as possible. The more perceived control in childbirth by the client, the better the outcomes are for the client-newborn dyad. One way that clients obtain control during childbirth is by participating in clinical decision making with their healthcare providers. This research intended to study the ways in which OB residents and midwifery students engaged in the understanding, learning and application of shared decision making with clients and patients.

Methodology:

This study utilised a constructivist grounded theory approach to obtain data and formulate a theory using semi-structured interviews with five senior obstetrical residents and five senior midwifery students from Ontario.

Results:

Qualitative data revealed four themes and eight sub-themes. Our theory describes the way residents and students absorb, mirror, and perform shared decision making through an informal process of observation and experience throughout their training. Our theory further describes how support for students and residents creates the foundation for learning shared decision making. Support includes how the mentor minimizes the impacts of the hierarchy of power in medical and midwifery education, as well as increasing psychological safety for the learner.

Conclusion:

The study results support the exploration of future methods for the teaching of shared decision making to obstetrical residents and midwifery students. Participants of this study agreed that more training is needed for shared decision making, as well as training for the mentor to ensure learners are optimizing their experience. More training needs to be available for mentors to help reduce the negative impacts of the hierarchy of power, and to increase psychological safety for the learner.

abstract: Thesis

abstract: Master of Health Sciences (MSc)

abstract: This thesis examines the ways in which obstetrical residents and senior midwifery students learn, understand and apply shared decision making in their training. Shared decision making is a way in which health care providers can work collaboratively with their patients or clients to make decisions that are best for their health. Both obstetrical residents and midwifery students were asked about how they understood shared decision making, and the process by which they learn and perform shared decision making. Childbirth is full of uncertainty and fear. Shared decision making may be one way that the pregnant patient or client navigates through the fear by having some control over their decision making. Our study intends to help understand how obstetrical residents and midwifery students gather the skills they need to do shared decision making and how best to support learners with this skill set in the future.


contributor:
Emerson, Claudia
Philosophy

subject: crowdfunding ethics

abstract:
McMaster University MASTER OF ARTS (2020) Hamilton, Ontario (Philosophy)

TITLE: Funding the future? Ethical considerations for the use of research-focused crowdfunding platforms

AUTHOR: Rachel Katz, B.A. (McMaster University)

SUPERVISOR: Dr. Claudia Emerson

NUMBER OF PAGES: xi, 106

abstract:
Crowdfunding is an online fundraising tool that allows individuals or groups to collect donations from individuals both in and beyond their immediate networks, usually facilitated by social media. While many crowdfunding platforms support a panoply of projects, there are others that cater specifically to researchers. In this thesis, I evaluate a number of ethical and social issues related to the growth in popularity of these platforms. I discuss the issues of governance, accountability and trust, and transparency. I argue that currently, these platforms cannot be said to operate in a manner that indicates strong governance, and add that crowdfunding lacks the built-in accountability mechanisms of more traditional funding avenues such as grant-based funding. As a result, crowdfunding requires the building of trust between researchers, donors, and the platforms themselves. I conclude this section by arguing that better transparency may provide a way for crowdfunding to become a more trustworthy style of funding.
I also critique the claims that crowdfunding can resolve a number of social inequalities related to income, experience, and global development. I dedicate a chapter to this critique and argue that despite claims that crowdfunding is currently democratizing research, there are still a number of issues that demonstrate that crowdfunding is not currently the “great equalizer” many claim it to be.
This project marks one of the first long-form efforts to critically evaluate the conduct of crowdfunding platforms that specialize in funding for research, and I present and defend the view that while potentially beneficial for individuals and institutions, crowdfunding for research cannot continue to exist as a “Wild West”.

abstract: Thesis

abstract: Master of Arts (MA)

abstract: Crowdfunding is an online fundraising tool that allows organizations to collect funds from a broad range of individuals. While many crowdfunding platforms support a panoply of projects, there are others that cater specifically to researchers. Due to the novelty of crowdfunding as a financial resource for researchers, a number of important, complex issues surrounding its use have yet to be addressed and a number of ethical questions have yet to be answered. This project marks one of the first efforts to evaluate the ethical concerns associated with the use of crowdfunding platforms to support the production of research. I highlight ethical issues that pertain to governance, trust and accountability, and transparency, along with a number of other pressing issues related to social inequalities. Crowdfunding has the potential to revolutionize how research is produced and funded, but it cannot be allowed to persist as an online space with so few rules.


title: Lyapunov-based Control of Nonlinear Processes Systems: Handling Input Constraints and Stochastic Uncertainty

contributor:
Mhaskar, Prashant
Chemical Engineering

subject: Nonlinear Control, Input Constraints, Lyapunov Control, Stochastic Uncertainty

abstract:
This thesis develops Lyapunov-based control techniques for nonlinear process systems subject to input constraints and stochastic uncertainty. The problems considered include those which focus on the null-controllable region (NCR) for unstable systems. The NCR is the set of states in the state-space from where controllability to desired equilibrium point is possible. For unstable systems, the presence of input constraints induces bounds on the NCR and thereby limits the ability of any controller to steer the system at will. Common approaches for applying control to such systems utilize Control Lyapunov Functions (CLFs) . Such functions can be used for both designing controllers and also preforming closed--loop stability analysis. Existing CLF-based controllers result in closed--loop stability regions that are subsets of the NCR and do not guarantee closed--loop stability from the entire NCR. In effort to mitigate this shortcoming, we introduce a special type of CLF known as a Constrained Control Lyapunov Function (CCLF) which accounts for the presence of input constraints in its definition. CCLFs result in closed--loop stability regions which correspond to the NCR. We demonstrate how CCLFs can be constructed using a function defined by the NCR boundary trajectories for varying values of the available control capacity. We first consider linear systems and utilize available explicit characterization of the NCR to construct CCLFs. We then develop a Model Predictive Control (MPC) design which utilizes this CCLF to achieve stability from the entire NCR for linear anti-stable systems. We then consider the problem of nonlinear systems where explicit characterizations of the NCR boundary are not available. To do so, the problem of boundary construction is considered and an algorithm which is computationally tractable is developed and results in the construction of the boundary trajectories. This algorithm utilizes properties of the boundary pertaining to control equilibrium points to initialize the controllability minimum principle. We then turn to the problem of closed--loop stabilization from the entire NCR for nonlinear systems. Following a similar development as the CCLF construction for linear systems, we establish the validity of the use of the NCR as a CCLF for nonlinear systems. This development involves relaxing the conditions which define a classical CLF and results in CCLF-based control achieving stability to an to an equilibrium manifold. To achieve stabilization from the entire NCR, the CCLF-based control design is coupled with a classical CLF-based controller in a hybrid control framework.
In the final part of this thesis, we consider nonlinear systems subject to stochastic uncertainty. Here we design a Lyapunov-based model predictive controller (LMPC) which provides an explicitly characterized region from where stability can be probabilistically obtained. The design exploits the constraint-handling ability of model predictive controllers in order to inherent the stabilization in probability characterization of a Lyapunov-based feedback controller. All the proposed control designs along with the NCR boundary computation are illustrated using simulation results.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: The neural correlates of perinatal OCD: An exploratory investigation into serotonin risk genes and cortical morphology

contributor:
Steiner, Meir
Hall, Geoffrey
Neuroscience

subject:
obsessive-compulsive disorder
perinatal period
sex differences
genetic association
serotonin transporter
serotonin receptor 2A
structural imaging
cortical morphology

abstract:
Introduction: Obsessive-compulsive disorder (OCD) is a complex disorder that is associated with significantly impaired functioning. The current prevailing model of OCD implicates dysfunction of the serotonergic neurotransmitter system and fronto-striatal neural networks, but challenges in replicating findings within OCD samples are often attributed to clinical heterogeneity. OCD symptoms that develop or worsen within the perinatal period appears to reflect a distinct subtype of the disorder, but the genetic and neurobiological factors that contributes to its presentation in women is poorly understood. In this dissertation, we aimed to review the literature on the genetic architecture of OCD, identify potential gene candidates for perinatal OCD and analyze one serotonin system gene according to OCD and possible subtypes using meta-analytic techniques. Based on these findings, we then tested the association of serotonergic candidate gene polymorphisms with the presence of infant-related obsessive-compulsive symptoms (OCS). Lastly, we investigated the cortical morphological features associated with perinatal OCD and OCS symptom severity in postpartum mothers.
Results: From prior reports in the literature and our own meta-analytic investigation, polymorphic variants in genes coding for the serotonergic transporter and serotonin 2A receptor subtype (SLC6A4 and HTR2A, respectively) appear to be candidates for perinatal OCD due to their association in female samples. However, upon investigation in our perinatal sample (n=107), we found no evidence to support the association of the 5-HTTLPR polymorphism of SLC6A4 with perinatal-related OCS, but larger samples are needed to confirm this finding. Due to technical challenges, the HTR2A polymorphism remains to be tested. Our novel whole-brain explorations revealed distinct cortical morphology associated with symptom worsening across the perinatal period, irrespective of diagnosis. Cortical parameters were not able to differentiate mothers with and without OCD; however, OCD mothers displayed positive correlations between cortical surface area and symptom severity in widespread regions, including the frontal, parietal, temporal and occipital cortex.
Conclusions: Overall, this body of work aimed to fill the gap in the literature by exploring the possible genetic and cortical correlates of perinatal-related OCS and OCD. While 5-HTTLPR or HTR2A are candidates for perinatal OCD, it is not yet clear whether they increase susceptibility for the development of infant-related OCS in the perinatal period. Distinct cortical alterations in surface area appeared alongside OCS exacerbation in the postpartum period in regions that extend beyond the frontoparietal network. This suggests that additional neural networks may be contributing to symptom severity and that the cortical plasticity that occurs across the perinatal period may predispose women for risk of OCD. Future studies should continue to use a multiple perspective approach, that utilizes genetic and neurobiological techniques, in order to provide greater insight into the etiology of perinatal OCD.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: Women are at greater risk for the development of mental illness in the time surrounding pregnancy and postpartum, known as the perinatal period. In the case of perinatal obsessive-compulsive disorder (OCD), mothers may experience unique worries in regard to their parenting or fears that their baby may be harmed. While these worries are common, they can become disruptive when persistent and impact the mother’s mood and ability to bond with the infant. Our current understanding of OCD includes the influence of genetic factors and brain changes, but little is understood about what factors may increase risk for OCD in the perinatal period. In this thesis, we aimed to review whether certain alterations within DNA segments, known as gene variants, may be linked to the development of OCD in females and if these gene changes, as well as differences in brain structures in postpartum mothers, are associated with OCD symptoms during the perinatal period. The genes we examined are important for regulating a chemical signaling substance in the brain known as serotonin. Based on our results, we did not find a relationship between serotonin gene variants and OCD symptoms in perinatal women. We also found no differences when comparing the cortical brain structures between mothers with OCD and healthy mothers; however, we observed that measures of surface area across several cortical brain regions were related to symptom worsening from pregnancy to postpartum, and also with symptom severity in postpartum mothers with OCD. These results suggest that there are widespread brain changes during the postpartum period that may increase a mother’s risk for developing OCD. Overall, the work in this thesis provides the first glimpse into potential risk factors for perinatal OCD.


title: Development of a successive stage hierarchy for rational carbon reduction and resource conservation decision-making in the cement industry

contributor:
Gail, Krantzberg
Geography and Earth Sciences

subject: cement, climate change, circular economy, carbon hierarchy

abstract: The cement industry represents nearly 8% of fossil fuel and industrial emissions making it a key area of focus for policymakers around the world. Much of the current effort in cement manufacturing has focused on energy efficiency and material substitution with more recent work focused on carbon dioxide uptake and recycled concrete aggregate use to address greenhouse gas emissions and material conservation, respectively. Currently, no meaningful approach exists for practitioners or policymakers to address greenhouse gas emission reduction for cement manufacturing that incorporates the concepts of material conservation. The Carbon Hierarchy is proposed as a successive stage hierarchy to address this gap. This work is logically and empirically validated using a newly constructed model incorporating the key levers of service life extension, thermal energy decarbonization, limestone substitution, mineral component (MIC), carbon dioxide uptake with consideration for the process flow that incorporated reintroduction of end-of-life (EOL) concrete as raw material or clinker substitution in cement manufacturing and as potential downstream use as aggregate. The Carbon Hierarchy proposed in this research could guide decisions to significantly reduce greenhouse gas emissions for the cement industry while ensuring material conservation.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Exploring Everyday Functioning and Environmental Contexts in the Development of Children with ASD: A Focus on the Preschool Years

contributor:
Di Rezze, Briano
Rehabilitation Science

subject: Autism, Childhood, Functioning

abstract:
This dissertation explores the functioning and participation of children with autism spectrum disorder (ASD) in their natural environments, with a focus on the preschool years.
Chapter 1 provides the context for this dissertation through introducing the theoretical frameworks that were used, exploring function-based measures, and social communication functioning.
Chapter 2 is a qualitative evidence synthesis of the literature to identify the cultural factors that are associated with parents’ engagement in their children’s healthcare services. This chapter highlights the challenges that parents of children with ASD faced and the importance of health providers to be culturally competent in family-centered care.
Chapter 3 is a descriptive study that aims to explore the participation patterns of preschool children with ASD at home and in the community. The association of environmental factors and social communication abilities on children’s participation are also explored. This chapter emphasizes that children with ASD participated in a variety of activities at home and in the community. It also highlights the importance of supporting parents to engage their children in activities and the need for community to support their participation.
Chapter 4 examines the stability of a function-based categorization system – the Autism Classification System of Functioning: Social Communication (ACSF:SC). Children’s social communication abilities were rated using the ACSF:SC at baseline and six months. This chapter indicates that rating of social communication abilities can vary over time. Therefore, frequent assessment using the ACSF:SC is recommended for accurate identification of the child’s current social communication abilities.
Chapter 5 discusses the clinical and research implications of this dissertation work. It also discusses knowledge translation opportunities and potential future work.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: This thesis consists of a series of studies examining factors associated with the abilities of children with autism spectrum disorder and their participation in daily activities. The first study provides a review of the literature examining the association between cultural backgrounds of parents and their engagement in autism child services. The second study explores the patterns of engagement in childhood activities for preschool children with autism using parent-reported measures. This study also examines the associations between environmental factors and the social communication abilities of a child and their participation in childhood activities. The third study examines the social communication abilities of children with autism using a new approach to describing levels of ability, rather than deficits. This study looks at the social communication abilities of preschool children with autism over six months. The importance of this work is that it adds to the literature by generating new knowledge on the abilities of children with autism, rather than their deficits. It also emphasizes the need for support in healthcare settings and in the community to improve these children’s participation.


title: The Relationship Between TDAG51 and GDF10 in the Context of Medial Vascular Calcification and Fatty Liver

contributor: Medical Sciences (Blood and Cardiovascular)

subject: Vascular Calcification

abstract: Background: Disturbances in metabolic homeostasis, resulting in cardiovascular disease, are the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Mineral deposition in the vascular smooth muscle cell (VSMC)-rich medial layer of the vessel wall is a prominent driver of mortality in these patients. Vascular calcification (VC) is now recognized as an important predictor and independent risk factor for all-cause and cardiovascular mortality in patients with advanced CKD. Prolonged impairment in kidney functions, characteristic of chronic CKD, results in marked changes in blood biochemistry, namely elevated circulating levels of inorganic phosphate (Pi) and calcium. These changes in circulating mineral content trigger osteogenic transdifferentiation and apoptosis of the VSMCs, subsequently leading to VC. In addition to kidney-related metabolic changes, chronic inflammation and liver disease are also associated with increased VC. T-cell death-associated gene 51 (TDAG51) and growth differentiation factor 10 (GDF10) have been previously reported to contribute to metabolic regulation in conditions of atherogenic VC, osteogenesis, and adipogenesis. However their role in medial VC and associated morbidities remains unknown. Methods and Results: Using a combination of in vitro, ex vivo and in vivo models findings presented in this thesis demonstrate that TDAG51 is an important modulator of VC, and as such is upregulated by conditions of hyperphosphatemia. I show that VSMCs from TDAG51-/- mice exhibit reduced expression and activity of key driver of osteogenic transdifferentiation, Runt-related transcription factor 2 (Runx2). To explain these observations, I demonstrate reduced expression of type III sodium-dependent Pi transporter, Pit-1, as well as intracellular Pi in these cells. Additionally, GDF10, an established inhibitor of osteogenesis, was identified to be significantly upregulated in TDAG51-/- VSMCs and mice. In line with these observations, knockdown of human homologue of TDAG51, pleckstrin homology-like domain, family A, member 1, resulted in increased expression of GDF10. Consistent with the anti-osteogenic role of GDF10, treatment with recombinant human GDF10 reduced Pi-mediated hydroxyapatite deposition, Runx2 expression and activity in primary mouse VSMCs. Interestingly, GDF10-/- mice develop severe adiposity, hepatic lipid accumulation, injury and inflammation. To explain this phenotype, a marked increase in the expression and activity of established driver of adipogenesis, peroxisome-proliferator-activated receptor γ (PPAR γ) in the livers of GDF10-/- mice was demonstrated. Complementary experiments in cultured hepatocytes demonstrate that treatment with recombinant human GDF10 attenuates nuclear PPAR γ expression and subsequent lipid accumulation, inflammation and fibrosis in these cells. Conclusion: This work highlights TDAG51 as an important regulator of Pi-mediated VC through downregulation of Pit-1, Runx2, and GDF10. Additionally, GDF10 has been described as a novel systemic inhibitor and a potential diagnostic marker for VC. Lastly, this work further characterizes GDF10 as an adipokine important in the regulation of hepatic lipid levels, which can indirectly affect vascular health.

abstract: Thesis

abstract: Doctor of Philosophy (Medical Science)


title: A Low-cost Optical Tracking System for Arthroscopic Surgical Training

contributor:
Wohl, Gregory
Mechanical Engineering

abstract:
The minimally invasive surgical procedure is more technically demanding than normal open-joint surgeries because of the limited vision. Thus, preoperative training for surgeons is essential. Current training for arthroscopy uses a fluoroscopy system, but that is costly, and the trainees will be at high risk under X-ray radiation exposure.
The purpose of the overall project is to design an affordable arthroscopic surgical training station and no special safety procedures for trainees. Our system combines a virtual imaging system (to replace fluoroscopy) with a physical synthetic model of a hip joint. The purpose of the current project is to develop a 3D visual tracking system using low-cost Raspberry Pi cameras and to test the resolution and accuracy.
Two Pi cameras were used to track markers on a surgical tool. The tracked data are intended to be used with a synthetic hip and superimposed on a CT dataset of the hip that can mimic surgery with real-time fluoroscopy. The reconstructed surgical tool can be overlaid on the virtual fluoroscopy to mimic the display in the real arthroscopic surgery. Pi cameras tracked passive coloured markers on a tool from different angles. The markers were tracked independently by colour segmentation, and positions were sent to a central computer simultaneously for 3D reconstruction.
The optical tracking system supports 25fps, 1080p live video streaming. The largest errors in the X, Y and Z-axis are 12.46±0.14, 8.55±0.3, 10.09±0.42 mm respectively while the repeatability is in a range from 0.61 to 5.17 mm.
These results demonstrate the possibility of using Raspberry Pi camera modules in a low-cost optical tracking system for surgical training purposes. Currently, the frame rate is low (25fps) and the error is still too large (up to 12.46mm) for use in surgical tracking. The resolution of the camera could improve when a better camera module is available.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract:
Arthroscopy is an orthopedic minimally invasive surgical procedure on the joint. Surgeons observe the interior of the joint through a miniature camera attached to the arthroscope, and a live X-ray image called fluoroscopy assists surgeons’ manipulations simultaneously. However, arthroscopy is technically demanding and requires intensive practice, and fluoroscopy exposes surgeons to X-ray radiation. Therefore, the objective of the overall project is to develop a cost-effective surgical training station with no special safety procedures required for trainees.
The present work is to build a virtual fluoroscopy system without X-rays and track the surgical tool in realtime. Some passive markers attached to the surgical tool are tracked by Raspberry Pi cameras, then the tool is superimposed on the virtual fluoroscopic images reconstructed by a set of CT images of an artificial hip joint.
The results demonstrate the possibility of using Raspberry Pi cameras in a low-cost optical tracking system for surgical training purposes.


title: The association between public health engagement in school-based substance use prevention programs and student alcohol, cannabis, e-cigarette and cigarette use

contributor:
Dobbins, Maureen
Nursing

subject:
Public Health
Substance Use
Adolescent
School-Based Substance Use Prevention
Alcohol Use
Cannabis Use
E-Cigarette Use
Cigarette Use
Secondary School

abstract:
Background: Substance use can have lifelong consequences for adolescents and the rates of substance use in Canadian adolescents are increasing. This is a serious public health issue which needs to be addressed. The purpose of this study is to determine the impact of public health unit (PHU) engagement in school-based substance use prevention programs on student substance use.
Methods: Data was collected from the Cannabis, Obesity, Mental health, Physical activity, Alcohol use, Smoking and Sedentary behaviour (COMPASS) study over the 2018/19 data collection year. A multi-level logistic regression was used to analyze the associations between PHU engagement and student substance use.
Results:  The analyses found that 70% of schools had PHU engagement in substance use prevention programs. Overall, PHU engagement made no difference on student substance use. However, when PHU engagement was divided into five levels of engagement (with zero being no engagement and five being the highest level of engagement) it was found that students from schools where PHUs solved problems jointly (level two) had statistically significantly greater odds of binge drinking, alcohol use and cannabis use. Schools were also divided into low and high-use schools for each substance. It was found that students in low-use schools had statistically significantly greater odds of binge drinking, alcohol and cannabis use with some levels of PHU engagement and students from high-use schools had statistically significantly lower odds of cannabis and cigarette use with some levels of PHU engagement compared to a similar student from a school without PHU engagement.
Conclusions: Our findings show that there is opportunity for greater PHU engagement with schools in substance use prevention programming. Furthermore, it is important that PHUs are working with schools to ensure school-based substance use prevention programs are evidence-based and tailored to the specific needs and risk-levels of the students.

abstract: Thesis

abstract: Master of Science in Nursing (MSN)

abstract: The purpose of this study is to determine the impact of public health unit (PHU) engagement in school-based substance use prevention programs on student substance use. Data for this study was collected from the Cannabis, Obesity, Mental health, Physical activity, Alcohol use, Smoking and Sedentary behaviour (COMPASS) study. The results show that 70% of schools had PHU engagement in substance use prevention programs. Across all schools, when PHUs and schools solved problems jointly an increase in student binge drinking, alcohol and cannabis use was found. When schools were divided into low and high-use schools, similar results were found when PHUs engaged with low-use schools whereas when PHUs engaged in high-use schools a reduced odds of student cannabis and cigarette use was found in some situations. These findings highlight the importance for PHUs to consider the specific needs and risk-levels of the students and schools they are engaging with.


title: 3D Meso-Scale Modelling of Solidification: Application to Advanced High Strength Steels

contributor:
Phillion, Andre
Materials Science and Engineering

subject:
Hot cracking
Permeability
Solidification
Segregation
Peritectic transformation
Finite element analysis

abstract:
Advanced high strength steels (AHSSs) are considered to have a promising future due to the outstanding properties compared with the conventional steel and have been widely adopted as the base materials for the automotive components. Some of the challenges preventing the extensive applications of AHSSs are due the solidification defects, i.e. hot tearing and segregation. In this thesis, a 3D mesoscale and multi-physics model is developed and validated to directly investigate solidification defects for semi-solid steel with dendritic morphology associated with the peritectic transformation. Similar to the prior models [1,2], the current model explicitly considers the solidification behavior of each grain prior to assembling, which allows for the mesoscale simulation within a semisolid containing thousands of grains. Six sub-models are incorporated: (i) microstructure generation model is used to create the fully solidified microstructure of equiaxed grains based on a Voronoi tessellation; (ii) a dendritic solidification module based on an average volume approach is developed for predicting the solidification behavior of a random set of grains, considering the diffusion in different phases along with peritectic transformation. The progressive coalescence to form a solid cluster is predicted by incorporating an interfacial energy determination model; (iii) a fluid flow module is developed for the prediction of both intra-dendritic flow and extra-dendritic flow within the dendritic network induced by solidification shrinkage and deformation; (iv) a semisolid deformation model is used and extended to simulate the semi-solid mechanical behavior of steel using a discrete element method. The solid grains are modeled using a constitutive law and implemented via Abaqus commercial software; (v) a coupled cracking model incorporated with a failure criterion is used and extended to predict the crack formation and propagation in semi-solid steel. This comprehensive model consists of models (i-iv) and considers the interaction between the deformation within the solid phase and pressure drop in the liquid phase; (vi) a one-way coupled solute transportation module is also developed and used to simulate the solute redistribution due to fluid flow and diffusion within the liquid channels assuming the solid grains are fixed. The movement of the solute-enriched liquid in the solute transport model is induced by solidification shrinkage and deformation.

The new 3D mesoscale model is then applied to correlate the semisolid behavior during solidification to different physical and process parameters. The results from the dendritic solidification model show the evolution in semi-solid microstructure and consequently liquid film migration. The model is able to predict the solidification of equiaxed grains with either globular and dendritic structure having experiencing primary solidification and the peritectic transformation. The coalescence phenomenon between grains is considered at the end of solidification using Bulatov’s approach[24] for estimating interfacial energy. It is seen that only 0.9% of the grains are attractive based on their orientations within a specific domain, significantly depressing final-stage solidification. The dendritic fluid flow model quantitatively captures both semi-solid morphology and the fluid flow behavior, and provides an alternative to the convectional experiment for the prediction of permeability by using the given surface area concentration. Comparison of the numerical and experimental permeabilities shows a good agreement (within ± 5%) for either extra-dendrite or intra-dendritic flow, and deviation from the conventional Carman-Kozeny equations using simplified Dendritic Sv or Globular Sv are explained in detail. The results quantitatively demonstrate the effect of grain size and microstructure morphology during solidification on the permeability prediction. The localization of liquid feeding under the pressure gradient is also reproduced. Additionally, the fluid flow due to shrinkage and deformation for non-peritectic and peritectic steel grades with dendritic morphology during solidification was captured for the first time. The cracking model allows for the prediction of hot tearing initiation and the progressive propagation during a tensile test deformation and the results are compared with the experimental results conducted by Seol et al.[3]at different solid fractions. Parametric studies of coalescence criteria and surface tension on the constitutive behavior of the semisolid are discussed and the deformation behavior of alloys with different carbon contents under a feedable mushy zone is investigated. Finally, the solute transport model has been applied to the continuous casting process of steel for the investigation of centreline segregation, and results indicate that the grain size has a great impact on the solute distribution and solute partitioning combined with intra-dendritic fluid flow leads eventually to liquid channels enriched with solute. The predicted composition in these discrete liquid channels shows a great match with the experimental measured profile obtained via the microscopic X-Ray fluorescence (MXRF).

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Systemic Review: Spreading of Organisms Through Medical Tourism and its Burden

contributor:
Gombay, Christy
Global Health

abstract: In the pinnacle of modern technology and globalization, when overseas travel is readily available and online health care access is just a click away, medical tourism is hot topic both from a national and global health perspective. Healthcare travel abroad has increased rapidly; interventions include organ transplant; cardiac surgery; reproductive care; and joint, cosmetic, and dental procedures. Individuals who receive medical care abroad are vulnerable, sentinel populations who sample the local environment and carry home unusual and resistant infections, documented in many reports. This review mainly selected all the relevant articles that study patients after they have returned home. All types of evaluative study designs have been considered as inclusion criteria. Medical tourists are at risk for hospital-associated and procedure-related diseases as well as for locally endemic infections. Patients may not volunteer details about care abroad, so clinicians must inquire about medical procedures abroad as well as recent travel. Special infection control measures may be warranted. Healthcare abroad is associated with diverse financial, legal, ethical, and health-related issues. We focused on reasons for seeking medical attention and problems the infectious disease clinician may encounter and provide a framework for evaluating returned medical tourists with suspected infections. A better system is needed to ensure broad access to high-quality health services, continuity of care, and surveillance for complications.

abstract: Thesis

abstract: Master of Science (MSc)


title: Dense Gas and Star Formation in Nearby Galaxies

contributor:
Wilson, Christine D.
Physics and Astronomy

abstract:
Star formation occurs within the densest regions of molecular clouds. This is confirmed by the tight scaling relations between star formation and dense gas content in galaxies. One of the most common tracers of dense molecular gas is emission from HCN. Recent studies using HCN have found evidence for variations in the star formation efficiency of dense gas at sub-kiloparsec (kpc) scales in nearby galaxies. This may indicate that environment plays a role in regulating the connection between dense gas and star formation in galaxies. Alternatively, HCN emissivity may also depend on environment within galaxies which could also explain the observed trends. In this thesis, I study the relationship between dense gas and star formation in nearby galaxies. Specifically, I explore the origin of these apparent variations in the star formation efficiency of dense gas.
I begin with a case study of the Antennae Galaxies, the nearest major merger. I explore the star formation efficiency of dense gas and dense gas fraction across different regions of the Antennae system, at sub-kpc scales. I find lower star formation efficiencies of dense gas in the two nuclei relative to their dense gas fractions. I conclude that these low efficiencies are either due to temporal variations in star formation or variations in the emissivity of HCN.
I extend this analysis to a sample of nine other galaxies and incorporate analytical models of star formation to provide context to the observational data. Models which include a varying density threshold for star formation are able to best reproduce the observational trends. This is consistent with an environmental dependence of the star formation efficiency of dense gas within galaxies. I validate these findings with numerical modelling of the HCN and CO emissivities using the radiative transfer code RADEX, which can then be compared directly to analytic models of star formation. I specifically consider whether the HCN/CO ratio universally tracks the fraction of gravitationally bound gas within molecular clouds. The modelled emissivities are consistent with observations and suggest that the HCN/CO ratio is not universally tracking the fraction of gravitationally bound gas, in the case that there are varying threshold densities for star formation.
However, the HCN/CO ratio is still a useful tracer of the fraction of gas above 10^4.5 cm^−3. The results of this thesis imply that there are clear variations of star formation efficiency of dense gas across galaxies. It is important to consider these variations when interpreting observed trends. Furthermore, when estimating dense gas fractions it is important to incorporate a varying HCN conversion factor, as has been done for CO.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Re-imagining Everyday Carcerality in an Age of Digital Surveillance

contributor:
Chakraborty, Chandrima
English and Cultural Studies

subject: Surveillance, Carcerality, Confinement, Race, Technology, Biometrics, Policing

abstract: This dissertation project takes an interdisciplinary approach towards theorizing how we understand new modes of incarceration and confinement in the digital age. It makes key interventions in the fields of surveillance studies, carceral studies, critical data and technology studies, ethnic and racial studies. I argue that less conventional modes of incarceration and confinement, which are enabled through technologies, the Internet and processes of datafication, conceal the everyday carceral functions that target and exploit racialized people. Chapter 1 examines mobile carceral technologies that are part of Canada’s immigration and detention system. I investigate how notions of increased freedom that are associated with carceral technologies like electronic monitoring and voice reporting do not necessarily coincide with increased autonomy. In Chapter 2, I consider the relationship between mobile phone cameras and the rise of police body-worn cameras. More specifically, I examine how policing and surveillance technologies disproportionately take aim at Black people and communities, making the mere occupation of public and digital space extremely precarious. Lastly, in Chapter 3, I challenge the notion that biometric systems and technologies are race-neutral guarantors of identity, specifically within the polemical space of the modern airport. I argue that the airport’s security and surveillance infrastructure operates according to racialized knowledges, which unofficially validate the profiling of Muslim travelers by both human and non-human operators.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: This dissertation encourages the reader to rethink notions of incarceration from both theoretical and practical perspectives; however, it is not a project about incarceration in the traditional sense. I argue that any notion of incarceration needs to be re-conceptualized in an age that is driven by big data and emergent technologies. While I draw on state and institutional forms of confinement in Canada, all of which have long and established histories of racism and oppression, I contend that notions of incarceration or confinement have bled into everyday life, particularly for racialized and marginalized people and communities. By surveying different surveillance technologies deployed across Canada’s immigration and detention system, the institution of policing and the biometric airport, I suggest that our understanding of the carceral has drastically changed. As issues of race, discrimination and oppression continue to underpin the structures of this newer carceral system and its modes of surveillance and confinement, it is a system that is less visible and physically confining but equally restrictive.


title: Variable Speed Limits Control for Freeway Work Zone with Sensor Faults

contributor:
Razavi, Saiedeh
Civil Engineering

subject:
Variable Speed Limits
Work Zone
Sensor Faults
Fault Diagnosis
Fault Tolerant Control
Analytical Redundancy

abstract:
Freeway work zones with lane closures can adversely affect mobility, safety, and sustainability. Capacity drop phenomena near work zone areas can further decrease work zone capacity and exacerbate traffic congestion. To mitigate the negative impacts caused by freeway work zones, many variable speed limits (VSL) control methods have been proposed to proactively regulate the traffic flow. However, a simple yet robust VSL controller that considers the nonlinearity induced by the associated capacity drop is still needed. Also, most existing studies of VSL control neglected the impacts of traffic sensor failures that commonly occur in transportation systems. Large deviations of traffic measurements caused by sensor faults can greatly affect the reliability of VSL controllers.

To address the aforementioned challenges, this research proposes a fault-tolerant VSL controller for a freeway work zone with consideration of sensor faults. A traffic flow model was developed to understand and describe the traffic dynamics near work zone areas. Then a VSL controller based on sliding mode control was designed to generate dynamic speed limits in real time using traffic measurements. To achieve VSL control fault tolerance, analytical redundancy was exploited to develop an observer-based method and an interacting multiple model with a pseudo-model set (IMMP) based method for permanent and recurrent sensor faults respectively. The proposed system was evaluated under realistic freeway work zone conditions using the traffic simulator SUMO.

This research contributes to the body of knowledge by developing fault-tolerant VSL control for freeway work zones with reliable performance under permanent and recurrent sensor faults. With reliable sensor fault diagnosis, the fault-tolerant VSL controller can consistently reduce travel time, safety risks, emissions, and fuel consumption. Therefore, with a growing number of work zones due to aging road infrastructure and increasing demand, the proposed system offers broader impacts through congestion mitigation and consistent improvements in mobility, safety, and sustainability near work zones.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Freeway work zones can increase congestion with higher travel time, safety risk, emissions and fuel consumption. This research aims to improve traffic conditions near work zones using a variable speed limits control system. By exploiting redundant traffic information, a variable speed limit control system that is insensitive to traffic sensor failures is presented. The proposed system was evaluated under realistic freeway work zone conditions in a simulation environment. The results show that the proposed system can reliably detect sensor failures and consistently provide improvements in mobility, safety and sustainability despite the presence of traffic sensor failures.


title: Characterizing Turtle Nesting Habitat in the Eastern Georgian Bay Region

contributor:
Waddington, James Michael
Geography and Earth Sciences

abstract: Reptile populations are decreasing throughout the globe, holding the highest proportion of species listed as threatened worldwide. To ensure proper management and conservation for reptile species at risk, it is essential to identify, characterize, and understand the microhabitat environment at critical life stages. Nesting is a critical life stage for turtles, and nest site selection can affect successful hatching. As Ontario is at the northern range limit for native freshwater turtles in the province, selection of nest sites that have high quality thermal and hydrological conditions may be particularly important in this region. Soil-filled bedrock depressions are known nesting habitats of turtles in the Eastern Georgian Bay region and vary in soil texture from the sand environment of turtle nests in more southern populations. Due to the difference in soil from more commonly studied regions, little is known about the nesting habitat in the eastern Georgian Bay area and how landscape characteristics and soil properties further influence the conditions during incubation. We surveyed 48 300m transects in a 660 ha study area, classifying land cover type for all surveyed points, and soil depth, canopy openness, ground cover type, moss and lichen height, slope, and aspect for all points classified as available habitat. Only 22.1% of the surveyed landscape was considered available turtle nesting habitat, and of this, only 2.6-10% of these points (dependent on species) were suitable for nesting (equal to 0.57-2.21% of total points surveyed). Our results demonstrate that suitable turtle nesting habitat in this environment is extremely limited (both by soil depth and canopy cover), with canopy openness being the most limiting factor. Due to the already limited habitat, it is even more important to understand the thermal and hydrological characteristics of nesting habitat in the Eastern Georgian Bay region, so that soil properties can be used to inform creation of habitat. We also determined that a majority of the soil on the landscape is sandy clay loam, with a low organic matter content. The information gained through characterization of the soil can be used to determine appropriate soils for artificial nest construction and ensure more successful methods of conservation for turtle species at risk. We recommend that artificial nesting habitat must have sufficient depth (at least 10cm) and canopy cover requirements (90-100% openness), as these are the most limiting factors. When creating artificial nest habitat, we recommend the use of sandy clay loam soil, due it’s favourable thermal and hydrological characteristics.

abstract: Thesis

abstract: Master of Science (MSc)


title: Point-Particle Effective Field Theory and the Helium Ion

contributor:
Burgess, Cliff
Physics and Astronomy

subject: Physics

abstract:
This thesis develops a new class of effective field theories to treat systems with localized
relics of high energy physics (e.g., nuclei in atomic systems), which ultimately act as point-
like sources for the light fields of interest. In contrast to previous efforts to treat this problem,
our Point-Particle Effective Field Theory identifies the low-energy degrees of freedom of the
point-like relic in position space, resulting in a theory where the heavy source is described by
a first-quantized coordinate, while the light fields are still fully second-quantized. This more
efficiently prunes out the excess degrees of freedom inherited from the high-energy physics,
and leads to a simpler treatment of the remaining fields.
We find the internal physics of the heavy object to be fully encoded in a near-source
boundary condition on the modefunctions of the light field. We show how this program
allows a consistent treatment of ambiguous potentials generated by the source, with emphasis
on the infamous inverse-square potential, and address its consequences for non-relativistic
scalar, relativistic scalar, and Dirac fermionic light fields. Finally, we apply our results to
the 4He+ ion, where large errors from nuclear modelling present an obstruction to precision
tests of the Standard Model. It is found through our boundary condition that nuclear effects
perturb energy levels through fewer independent parameters than previously thought. Using
this observation, we introduce (and implement) a scheme to make predictions for future
spectroscopic experiments that avoid altogether the necessarily large errors from nuclear
theory.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Identification of the complementary binding domains of histidine-rich glycoprotein and factor XIIa responsible for contact pathway inhibition

contributor: Medical Sciences (Thrombosis & Haemostasis & Atherosclerosis)

subject:
Coagulation
Thrombosis
Histidine-rich glycoprotein
Factor XIIa
Polyphosphate
Contact Pathway

abstract: Recent studies suggest that factor (F) XII, which is dispensable for hemostasis, is important for thrombus stabilization and growth. Therefore, FXIIa inhibition may attenuate thrombosis without disrupting hemostasis. FXII activation is stimulated by polyanions such as polyphosphates released from activated platelets, and nucleic acids released by cells. Previously, we showed that histidine-rich glycoprotein (HRG) binds FXIIa with high affinity, inhibits FXII autoactivation and FXIIa-mediated activation of FXI, and attenuates ferric chloride-induced arterial thrombosis in mice. Thus, HRG has the capacity to downregulate the contact pathway in vitro and in vivo. This thesis aimed to identify the complementary binding domains of HRG and FXIIa, and to further explore the anticoagulants effects of HRG on FXIIa-mediated contact activation. We hypothesized that FXIIa binds to the zinc-binding histidine-rich region (HRR) of HRG and that HRG binds to the non-catalytic heavy chain of FXIIa to exert its anticoagulant activities on FXIIa-mediated contact activation. We have localized the complementary binding sites of HRG and FXIIa to be within the HRR domain of HRG and NH2-FNII-EGF1 (NFE) domains of FXIIa. Moreover, we show that the HRR binds to short chain polyphosphate with high affinity, suggesting a dynamic complex between HRG, FXIIa, and polyphosphate (polyP) on activated platelets. We provide evidence for two potential mechanisms through which HRG modulates the contact system. These include by 1) inhibiting FXIIa activity and 2) attenuating the procoagulant effect of polyanions, such as polyP on FXIIa-mediated reactions. Indeed, we show that the interaction of HRG with FXIIa and polyphosphate is predominantly mediated by the HRR domain and that HRR analogs have the capacity to recapitulate the anticoagulant effects of HRG in purified and plasma systems. Therefore, by modulating FXIIa-mediated contact pathway reactions, like HRG, HRR analogs may attenuate thrombosis without disrupting hemostasis.

abstract: Thesis

abstract: Doctor of Philosophy (Medical Science)


title: Evolution of dimeric protein interfaces after gene duplication

contributor:
Higgs, Paul
Physics and Astronomy

subject: Protein evolution

abstract:
A significant number of proteins function as multimeric structures, most commonly as dimers. One of the primary mechanisms by which proteins evolve is through gene duplication and mutations of the resulting duplicated gene. The evolution of dimeric proteins after gene duplication is of interest because it can form three types of dimer: two homodimers and a heterodimer. Point mutations that occur in the interface of dimers would affect their binding strength and might change their path in the evolution.
Here we designed an evolutionary model for protein dimerization after gene duplication. In this work, we have used dimers' PDB structures to construct the network of contacts between amino acids in the interface. Several pairwise energy contact matrices were examined to find reasonable interface binding energies. Using the population genetics theory, we defined a selection criteria based on dimer interface strength and let them evolve as the mutations happen. We observed that the dimer structures are bound to be in the mostly homodimer state or mostly heterodimer state, and there are few occasions that we have all three types of structures as strong dimers.
We anticipate three fates for the dimer protein's evolution after gene duplication, neofunctionalization, subfunctionalization, and loss of the gene. A loss of function in homodimer structures might eventually lead to a subfunctionalization since the two interfaces are different. On the other hand, if a heterodimer loss happens, we would have two strong homodimer structures so both neofunctionalization and subfunctionalization might still happen. In the first case, one could gain a new function while the other homodimer performs the protein's old function. In the latter case, the two separate homodimers could each assume different parts of the full function of the original gene (which is the definition of subfunctionalization).

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
A large fraction of proteins are found to exist as dimers composed to two identical subunits. If the gene for the single subunit is duplicated, three types of dimers can emerge, two homodimer structures and a heterodimer structure. Gene duplication is a major driving force of evolution as it can allow the proteins to perform new tasks. Here we define a model to understand the evolution of dimeric proteins as they undergo mutations in their interface, changing their stickiness to each other.
We find that evolution favours the dimers to either be homodimer or heterodimer, but not both at the same time. When there are two homodimers, one of them can acquire a new function (which is known as neofunctionalization). When there is a heterodimer, both genes are now required to do the orginal job of a single gene (which is known as subfunctionalization). These mechanism provide two possible reasons why the duplicate gene cannot subsequently be deleted from the genome.