title: CONTACTIN-1 AS A POTENTIAL ONCOGENIC FACTOR IN CLEAR CELL RENAL CARCINOMA

contributor:
Damu, Tang
Medical Sciences

subject:
Contactin-1
Kidney cancer
ccRCC

abstract: Renal cell carcinoma (RCC), following prostate and bladder tumours, is the third most prevalent genitourinary malignancy. Clear cell renal cell carcinoma makes up the bulk of RCC cases (ccRCC). Despite the fact that ccRCC is the most aggressive type of RCC, our understanding of its pathophysiology is limited. Previous research in our laboratory revealed important oncogenic roles of contactin 1 (CNTN1), a neuronal cell adhesion protein, in prostate cancer. CNTN1 is involved in a number of signalling pathways that are often changed in cancer, including the VEGFC-VEGF receptor 3 (VEFGR3)/fms-related tyrosine kinase 4 (Flt4) axis, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) axis, and the Notch signalling system. Collectively, evidence suggests that CNTN1 facilitates ccRCC. To examine this possibility, I have established stable ccRCC 786-O and A498 cell lines expressing either empty vector (EV) or CNTN1. In comparison to the respective EV lines, ectopic expression of CNTN1 enhances colony formation and cell proliferation. In comparison to A498 EV cells, A498 CNTN1 cells seems to possess enhanced migration ability based on wound healing assay. Taken together, my research provides in vitro evidence supporting CNTN1 in facilitating ccRCC pathogenesis. Future research will be required to investigate this concept using in vivo systems and primary ccRCC tumor tissues.

abstract: Thesis

abstract: Master of Science (MSc)


title: IMPLEMENTATION OF A NOVEL FLUORESCENT HUNTINGTON’S DISEASE MODEL AND BRANAPLAM TO STUDY THE INTERACTION BETWEEN HUNTINGTIN AND HAP40

contributor:
Truant, Ray
Biochemistry and Biomedical Sciences

subject:
Microscopy
Huntington's Disease
DNA damage
Protein-protein interactions
Neurodegeneration
oxidative stress
pharmaceutical
fibroblasts

abstract: Huntington’s disease (HD) is a neurodegenerative disease caused by a CAG expansion in the HTT gene, which causes an expansion in the polyglutamine tract of the huntingtin protein. In 2018, the cryo-EM structure of the 350 kDa protein huntingtin (Htt) in complex with huntingtin associated protein of 40 kDa (HAP40) was solved, which demonstrated that huntingtin had to be co-translated and complexed with HAP40 to retain structure. However, little is known about HAP40 and thus the biological relevance of this structure. In this project, we transduced cells with fluorescently labelled recombinant apo-Htt or Htt-HAP40 to determine if HAP40 must be complexed with huntingtin in order for huntingtin to have biological activity. This method has not been implemented in HD research and may also improve current fluorescent microscopy models for huntingtin, as it has the advantage of looking at full-length protein rather than small fragments. We also found that with the huntingtin lowering drug branaplam, there is a linear correlation between huntingtin and HAP40 levels, where HAP40 levels will decrease when huntingtin levels are directly decreased as detected by western blot analysis. Furthermore, we found that this lowering effect by branaplam ameliorates DNA repair deficits in HD. With the potential for branaplam to become a treatment for HD, we should continue to test its effect on other HD-associated phenotypes to determine the effect of huntingtin and downstream HAP40 lowering.

abstract: Thesis

abstract: Master of Health Sciences (MSc)


title: BOREAL SHIELD PEATLAND CO2 EXCHANGE: A MULTI-YEAR ANALYSIS AND POST-WILDFIRE RECOVERY ASSESSMENT

contributor:
Waddington, James Michael
Geography and Earth Sciences

subject:
peatland
ecohydrology
carbon dioxide
boreal shield
carbon
wildfire

abstract:
Peatland ecosystems are important as natural climate regulators for their capacity to store carbon over long-time scales. Carbon cycling in peatlands in the boreal ecozone of Canada has been more widely studied than the boreal shield of Ontario, where peat depths are thinner and peatlands spatially smaller. The reliance on fill and spill hydrologic connectivity makes the water table dynamics of peatlands in Ontario’s Eastern Georgian Bay (EGB) region of the Ontario shield ecozone sensitive to rain and drought periods. The drying of wetlands in the EGB region decreases moss productivity and increases the ecosystem’s vulnerability to wildfire through an increase in the water table depth. In an effort to understand how peatlands respond to interannual climate variability and wildfire, we examined the role of regional climate patterns on growing season CO2 exchange from an Ontario shield peatland and completed a post-wildfire assessment of CO2 exchange patterns in a recently burned peatland for the first and second year post-wildfire. Using the eddy covariance technique, we analyzed 5-years of growing season CO2 exchange data from 2016 to 2020 from an unburned peatland and 2-years of growing season CO2 exchange data from a burned peatland (2019-2020) in EGB. Plot-scale CO2 exchange measurements were also completed within the burned peatland jointly with abiotic variables and vegetation community surveys. Water table depth was identified as an important variable to explain total summer CO2 uptake (GPP) and net ecosystem exchange (NEE), where years of considerable rainfall maintained a water table near the peat surface and perpetuated high vegetation productivity. Summer total ecosystem respiration (ER) was greatly influenced by preceding winter and spring air temperature, with warmer winter air temperatures leading to summers of increased total ER. Warmer winter air temperatures also initiated water flow across the landscape, thus reviving plant and microbial activity following snow cover. These findings have important implications for the function of these shallow Ontario shield peatlands in a warming climate, where decreased water availability with projected increased temperatures and evapotranspiration leaves peatlands at risk of a net loss of C over the summer with lower water table.
In the burned landscape, there was lower GPP in the summer (2019) compared to the wet summer of 2020, however the burned landscape continued to act as a net CO2 sink for the summer season of both years. The rapid recovery of vegetation across the wildfire-disturbed landscape has important implications for the function of these peatlands over time, with the ability for continued carbon uptake and reinstating peat accumulation processes.

abstract: Thesis

abstract: Master of Science (MSc)


title: Fantastic School Stories: The Hidden Curriculum of Learning Magic

contributor:
Grisé, Catherine Annette
English and Cultural Studies

subject:
fantasy literature
fantastic school stories
school stories
representations of education
Lev Grossman Magicians Trilogy
Patrick Rothfuss Kingkiller Chronicles
J.K. Rowling Harry Potter Series
Terry Pratchett Tiffany Aching
Jane Yolen Wizard's Hall

abstract: This dissertation presents a holistic framework for approaching fantastic school stories: that is, narratives which feature the protagonist’s education in magic. This three-part framework attends to the ways in which the fantastic school story subgenre draws upon the characteristics and possibilities of the school story genre, fantastic literature, and representations of education – in which a hidden curriculum is always inherently present – to create unique opportunities for representing and foregrounding issues and structures within educational institutions and the relationship between education and power. Employing this lens allows for a more nuanced and complex consideration of the impact of fantastic elements in these narratives, examining the ways in which such elements exaggerate, embody, or enforce underlying ideologies and norms and offer encouragement to readers to interrogate these aspects of the text and the mundane educational experiences they encounter. This framework is then used to analyse representative texts in the subgenre and explicate the hidden curriculum of each: ideologies of immutable gender and identity in Jane Yolen’s Wizard’s Hall; the use of testing as a gatekeeping measure to reinforce Pureblood supremacy in J.K. Rowling’s Harry Potter series; the prerequisite of economic capital to access education, undermining the myth of post-secondary studies as social mobility, in Patrick Rothfuss’s Kingkiller Chronicles; the violence of imperial educational institutions in Lev Grossman’s Magicians trilogy; and the vocational habitus of witchcraft, including gendered divisions and expectations of personal sacrifice, on the Discworld in Terry Pratchett’s “Tiffany Aching” quintet. This framework and these illustrative analyses, by explicating the structures underlying the protagonists’ education and the ways in which they are thereby limited, participate in the projects of developing an emancipatory approach to children’s literature and in consciousness-raising regarding hidden curricula in education.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: Texts in the fantastic school story subgenre – that is, narratives about a young person learning how to use magic, often at a school – are a valuable opportunity to explore the relationship between power and education. Here, I present a three-part approach for reading these texts which looks at how these narratives combine elements of the school story genre, fantasy literature, and representations of education to create a unique format. This unique format makes it easier for readers to see underlying structures and issues in education by making familiar elements feel unfamiliar through the addition of magic. I then use this three-part approach to analyse fantastic school stories by Lev Grossman, Terry Pratchett, Patrick Rothfuss, J.K. Rowling, and Jane Yolen. Reading the texts through this lens brings forward issues related to education like gate-keeping, socioeconomic status, imperialism, and gendered norms and divisions.


title: The Science of Acting

title: EXAMINING AND MODELING THE BEHAVIOURS OF ACTORS DURING CHARACTER PORTRAYAL

contributor:
Brown, Steven
Psychology

subject: acting gesture theatre emotion personality character

abstract:
Acting is a fascinating phenomenon whereby individuals modify their physicality to portray another person and persuade audiences that they are indeed said person. Historically, and with the goal of creating realistic characterizations, acting theorists have debated if actors must begin either from the internalized driving forces of the characters or from external manifestations of the characters’ physical expression. However, regardless of whether actors have to actually feel the emotions of the characters who they portray during a performance, the challenge for the actor remains the same: to produce compelling representations of persons who they themselves are not. This production is physical by its very nature and can therefore lend itself to being gesturally coded, systematized, and modeled. To explore the question of whether character performances can be modeled, I designed and validated a classification scheme of character conceptualizations. I examined if a set of prototypical characters extracted from the literature were conceptually shared amongst a large group of raters, and found that character concepts were indeed shared. In addition, I found that character concepts could be modeled along the two orthogonal personality-trait dimensions of assertiveness and cooperativeness. I then sought to validate this model behaviourally. I designed a novel performance experiment whereby a group of professional actors performed a subset of characters from the model while I recorded their vocal and facial gestures. I found that actors used their vocal and facial gestures contrastively to differentiate between the characters, as well as between their performance-related and non-performance selves. Furthermore, I found that vocal gestures could be predicted by changes in the level of a character’s assertiveness. Complementary to this, I
v
found that facial gestures could be predicted by changes in the level of a character’s cooperativeness. Finally, I conducted a cross-modal examination of character and emotion performances and found that characters and emotions, as testable or “functional” units of performative behaviour, share a similar dimensional relationship. My data provide validated support for a dimensional behavioural model of character performance and character classification. My research extends previous findings on acting and emotions and provides new evidence for the quantification and predictive modeling of the products and processes of acting as a whole.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: When acting, actors change their outward physicality to portray another person and persuade audiences that they are that person. Regardless of training or method employed by an actor, this production is ultimately physical and can therefore be recorded, analyzed, and modeled. I investigated this using a novel character classification scheme. I found that stock characters taken from Western literature were shared conceptually amongst a large group of raters and could be modeled along the two personality-trait dimensions of assertiveness and cooperativeness. I tested this new model in a performance experiment, measuring the vocal and facial gestures of a group of professional actors. I found that actors used their vocal and facial gestures to differentiate between characters that differed in personality. I discovered that vocal gestures could be predicted by changes in the level of a character’s assertiveness and, complementary to this, that facial gestures could be predicted by changes in the level of a character’s cooperativeness. Finally, I examined character and emotion performances in both the voice and face and found that characters and emotions share a similar dimensional relationship. My research extends previous findings on acting and emotions and provides new evidence for modeling of the products and processes of acting as a whole.


title: Using aptamers to regulate rolling circle amplification

contributor:
Brennan, John
Li, Yingfu
Filipe, Carlos
Chemistry and Chemical Biology

subject:
aptamer
rolling circle amplification
FNA
RCA
dnazyme
aptazyme
biosensor
fluorescence
diagnostics
POC
ASSURED
assay
DNA nanotechnology
isothermal amplification
aptaprimer
phi29
RecJ
RecJf

abstract: The work described in this dissertation focuses on developing simple yet effective assays integrating nucleic acid (NA) aptamers with rolling circle amplification (RCA) for the detection of non-NA biomarkers.  The first project, a comprehensive literature review, highlights the current state of the art in functional NA-based RCA applications, and identifies shortcomings in the detection of non-NA targets with RCA.  Biosensor design is critically evaluated from four key perspectives: regulation, efficiency, and detection of RCA, and the integration of all three components for point of care (POC) applications.  The second project investigates how target-binding to a linear aptamer can be utilized to regulate RCA in a simple and inexpensive format.  Phi29 DNA polymerase (DP) exhibits difficulty processing DNA strands that are bound to non-NA materials such as proteins.  The work uses this restriction of phi29 DP as a feature by utilizing protein-binding aptamers as primer strands (aptaprimers) for RCA.  The simplicity is showcased by adapting the method to a cellulose paper-based device for the real-time detection and quantification of PDGF or thrombin within minutes.  As the second project is a turn-off sensor, the third project exploits the inherent 3’-exonuclease activity of phi29 DP to generate a simple turn-on assay instead.  As target-bound aptamers were shown to be resistant to exonuclease activity, the phi29 DP preferentially digests target-free aptaprimers instead of target-bound aptaprimers.  The target-bound aptaprimer could be liberated by a circular template (CT) by incorporating toehold-mediated strand displacement (TMSD), and used for RCA.   Sensitivity was improved relative to project two, though the dynamic range was narrow owing to difficulty liberating target-bound aptaprimer at high target concentrations.  Project four instead used RecJ, which has 5’-exonuclease activity, to modulate aptaprimer availability. Similarly to project three, target-binding conferred protection on the aptaprimer from 5’-exonuclease digestion by RecJ.  By including a free 3’ terminus on the aptaprimer, inhibition of RCA due to target binding was avoided and CT-mediated TMSD was not needed, simplifying the assay.  As well, this approach was generalizable as it was demonstrated using both a protein (thrombin) and a small molecule (ochratoxin A) target.  This turn-on method further improved the assay compared to project three with a 100-fold enhancement in sensitivity and a restoration of the dynamic range.  In sum, this work contributed multiple simple and sensitive approaches for the real-time fluorescent detection of proteins and small molecules with the RCA of linear aptamers.

abstract: Thesis

abstract: Doctor of Science  (PhD)


title: Deep Q Learning with a Multi-Level Vehicle Perception for Cooperative Automated Highway Driving

contributor:
Emadi, Ali
Electrical and Computer Engineering

subject:
Deep Q Learning,
Autonomous Vehicles
Machine Learning
Reinforcement Learning
Primary Perceived Vehicles
Secondary Perceived Vehicles
Cooperative Driving

abstract:
Autonomous vehicles, commonly known as “self-driving cars”, are increasingly becoming of interest for researchers due to their potential to mitigate traffic accidents and congestion. Using reinforcement learning, previous research has demonstrated that a DQN agent can be trained to effectively navigate a simulated two-lane environment via cooperative driving, in which a model of V2X technology allows an AV to receive information from surrounding vehicles (termed Primary Perceived Vehicles) to make driving decisions. Results have demonstrated that the DQN agent can learn to navigate longitudinally and laterally, but with a prohibitively high collision rate of 1.5% - 4.8% and an average speed of 13.4 m/s. In this research, the impact of including information from traffic vehicles that are outside of those that immediately surround the AV (termed Secondary Perceived Vehicles) as inputs to a DQN agent is investigated. Results indicate that while including velocity and distance information from SPVs does not improve the collision rate and average speed of the driving algorithm, it does yield a lower standard deviation of speed during episodes, indicating lower acceleration. This effect, however, is lost when the agent is tested under constant traffic flow scenarios (as opposed to fluctuating driving conditions). Taken together, it is concluded that while the SPV inclusion does not have
an impact on collision rate and average speed, its ability to achieve the same performance with lower acceleration can significantly improve fuel economy and drive quality. These findings give a better understanding of how additional vehicle information during cooperative driving
affects automated driving.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: PRELIMINARY ASSESSMENT OF MASTER OF PUBLIC HEALTH STUDENTS’ PERCEPTION OF CORE COMPETENCIES AND USE OF INPLACE SOFTWARE IN THE FACILITATION OF COMPETENCE-BASED LEARNING

contributor:
Apatu, Emma
Health Sciences

subject: Competence-based; Graduate education; public health; Core competencies; Canada; Public Health Agency of Canada (PHAC); Practicum placement; InPlace software

abstract:
Objective:  The future of public health in Canada depends on the competence of today’s public health students. The Public Health Agency of Canada (PHAC) core competence categories are designed to guide public health practice and the training of public health students. The objectives of this study were to understand public health graduate students’ perception of the PHAC core competencies and report the usability of a practicum placement software in the facilitation of competence-based learning.
Methods: Twelve students in the first year of the graduate program in public health participated in two focus group sessions. Participants were asked to select their top and least desired PHAC competencies and then discuss the reasons for their selection. Factors that may have influenced the category selection and their opinion on improving the competence categories were discussed. The system usability scale (SUS) was administered to the student participants and two staff members to help understand the usability of the practicum placement software in the facilitation of competence-based learning.
Results:  Partnership, collaboration, and advocacy emerged as the top-desired, with public health sciences being the second top-desired. The assessment and analysis category was the least desired, followed by the Leadership competence category. Prior educational background, future career goals with respect to job prospects were among the key factors that influenced the students’ competence selection. Conflict resolution, outreach, and community engagement were some of the suggestions of categories that could be included in the core competence categories. The system usability score for InPlace platform was 61.8 (95% 56.7- 66.9).
Conclusions:  Overall, students believe that the PHAC core competencies are comprehensive. They suggested seeing certain terminologies become a prominent part of the competence categories.  The use of InPlace platform in the facilitation of competence-based learning may require more time for adequate user experience.

abstract: Thesis

abstract: Master of Public Health (MPH)


title: DEVELOPMENT OF ADAPTIVE PVD COATED ADVANCED COMPOSITE (CERMET) TOOLS FOR HIGH-SPEED DRY MACHINING OF STAINLESS STEEL

contributor:
Veldhuis, Stephen
Mechanical Engineering

subject:
Built-up edge
Stainless steel
Notch
Wear
Tool life
PVD
Coating
Cermet
dry machining
high speed machining
TiAlCrN
AlCrN
TiAlCrSiYN
TiAlTaN
CrTiAlTaN

abstract:
Stainless steel is a metal material widely used in many industries because of its high tensile strength, toughness, and corrosion resistance. Machining stainless steel is challenging due to its high work hardening tendency, low thermal conductivity, and ductility of the material resulting in built-up edge formation. Machining stainless steel at lower cutting speeds must be performed with coolant, which adds to the cost of the process and increases concerns for the environment and the operator's health and safety. Industries such as the aerospace and die-mold industries demand high-speed machining to realize productivity targets. Therefore, a cermet tool material was selected for the present study because of its high temperature resistance, high bending strength, and fracture toughness.
The study focused on investigating wear mechanisms and developing a coating on a cermet tool for dry high-speed machining stainless steel to increase tool life. The wear mechanisms of tools were investigated at a fixed cutting interval in relation to the tool's composition and microstructure. Scanning Electron Microscope (SEM) was used to study the microstructure and identify elements on the tool. X-ray diffraction (XRD) was used to identify the phases and concentrations of key elements on the tool. The new advanced in-house coating was developed with Super Fine Cathode (SFC) technology on a Kobelco AIP-20 Physical Vapour Deposition (PVD) coater. The micromechanical properties of the commercial coating and in-house coatings were investigated with the help of nanoindentation and scratch tests. Atomic Force Microscopy (AFM) and SEM were used to investigate the coating microstructure and surface topography. An Alicona variable focus 3D microscope was used to investigate wear volume and wear behaviour.
It was discovered that various secondary carbides used by manufacturers to manufacture cermet tools change the microstructure, which affects the machining performance of the cermet tool material. Microchipping at the depth of cut (DOC) causes catastrophic notch wear. It was found that the developed in-house coatings were able to delay the initial wear (microchipping), which improved the tool's life by 318%. This research contributes to meeting the manufacturing industry's challenging demand for dry-high speed machining with reduced manufacturing costs.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Cutting is the process of removing unwanted material from the bulk material to obtain the desired shape. Each metal material has unique mechanical properties that lead to various machining challenges. The cutting process is done with the help of a cutting tool that wears out during the process, and a coating layer is often used to protect the tool. Stainless steel 304 is a widely used material that is difficult to machine. This study includes a systematic approach to understanding the wear mechanisms of tools and existing commercial coatings during the dry machining of stainless steel 304. An in-house coating was developed and deposited on the selected cutting tool to protect it, reduce tool wear and extend its working life. The research results will help reduce machining costs by reducing tool and coolant costs and meet the current industry demand for dry high-speed machining. It will also reduce environmental impact by reducing waste and hazardous chemicals and addressing occupational health and safety concerns.


title: An investigation of biomechanical signals and their contribution to joint action during team lifting

contributor:
Keir, Peter
Biomechanics

subject:
Team Lifting
vertical force
joint action
electromyography
coordination

abstract: Team lifting is required in many workplaces, particularly where heavy and awkward lifts are prevalent.  Despite the known risk factors associated with team lifting, it remains under researched, with almost no 4-person lifting studies.  The purpose of this thesis was to investigate how members of a 4-person team coordinate their actions during a lifting task that involved an unexpected release from a single team member.  It involved a novel approach to investigating the mechanisms associated with joint action and whether these mechanisms may alert the remaining lifters that a release is imminent, where the goal was to elicit an unexpected response from the group.  Data collected for a previous team lifting study was used.  Six groups of four male participants (n = 24) performed 30 lifts with a constructed 60 kg lifting apparatus designed to transition between a rectangular (2 x 4 ft or 61 x 122 cm) and a square (2 x 2 ft or 61 x 61 cm) configuration.  A total of 8 trials (4 per configuration) were designated as “drop trials”.  Vertical force at the hands and right-side electromyography (EMG) of the biceps brachii (BB), anterior deltoid (AD), upper trapezius (UT), and the lumbar erector spinae (LES) was collected for each participant.  Means and standard deviation of vertical force was compared from the pre-drop phase for both drop and non-drop (lift) trials.  No significant differences were found between drop and non-drop trials during the pre-drop phase.  A comparison of time to peak force and time to peak muscle activity was performed for lifters adjacent to the release position.  These times were compared against a 25 to 150 ms window to determine whether the muscle activity was considered reflexive or anticipatory to the dropped load.  A small proportion of the peak muscle activity values were considered anticipatory (6 BB and 2 LES), suggesting that while it is possible for the dropper to disguise the release, perhaps joint action provides insight to the other lifters.  The complex mechanisms that support joint action, their connection to biomechanics and their role in team lifting warrants further research in order to determine how large of a role they might play.

abstract: Thesis

abstract: Master of Science in Kinesiology


title: The role of thrombin-activatable fibrinolysis inhibitor and sex on thrombus stability and pulmonary embolism in murine venous thromboembolism

contributor: Medical Sciences (Blood and Cardiovascular)

abstract: Thrombin-activatable fibrinolysis inhibitor (TAFI) levels correlate with the risk of thrombosis. However, the role of sex or TAFI in venous thromboembolism (VTE) remains uncertain, this study determines the effect of sex and TAFI on thrombus stability using a mouse model of VTE. FeCl3-induced thrombi were formed within femoral veins of male and female wild-type (WT) or TAFI-knockout (Cpb2-/-) mice. Thrombi were imaged at 10- minute intervals over 2-hours using fluorescent intravital videomicroscopy to quantify embolization and thrombus size. Lungs were examined by histology to identify quantity and composition of pulmonary emboli (PE) within pulmonary arteries/tissues. Emboli are considered large when >4 standard deviations above the average. Compared with WT mice, thrombi in Cpb2-/- mice exhibited 3.2-fold and 1.3-fold greater embolization for males and females, respectively. When comparing by sex, female mice embolization events were 7.9- fold and 3.1-fold greater than male WT and Cpb2-/- mice, respectively. Male Cpb2-/- displayed a 10.3-fold greater thrombus size increase compared with male WT mice, while the opposite was true for female mice (5.8-fold greater in WT). Between WT, females had greater thrombus size increase (4.8-fold), while the opposite was true in Cpb2-/- males (12.4-fold). TAFI deficiency led to a 2.2-fold and 2.5-fold increase in PE burden in males and females, respectively, while sex had no influence. Quantitation demonstrated that lungs of female Cpb2-/- mice contained pulmonary emboli with higher fibrin composition compared with WT. Clot lysis times remained similar between male and female WT mice using nascent plasma. Similarly, no differences were observed in circulating TAT concentrations between mice using plasma isolated after imaging. Overall, Sex affects venous thrombus stability, with female mice at increased risk of embolization. Removing TAFI/TAFIa significantly increases PE burden in males and females and increases PE fibrin composition. Inhibition of TAFI may lead to unstable thrombi and increased PE, particularly in females.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Venous thromboembolism (VTE) encompasses clotting within a major vein (deep vein thrombosis; DVT) and clot fragmentation that accumulates within lungs (pulmonary embolism; PE). Primary VTE treatment is anticoagulation that prevents progression and recurrence, at the cost of increased risk of bleeding. Alternate approach is to accelerate clot breakdown, or fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI), when activated (TAFIa), suppresses fibrinolysis. How sex affects VTE is also uncertain. Therefore, this study aims to investigate how (a) sex, and (b) the loss of TAFI affects DVT stability and consequent PE. Overall, female mice showed more unstable thrombi that also embolized more than males. However, PE burden did not mirror this trend. Loss of TAFI in both males and females exacerbated PE burden, whereby the emboli contained greater fibrin composition in mice. Thus, VTE treatment involving TAFIa activity reduction to enhance fibrinolysis may require further stabilization of the thrombi to reduce PE risk.


title: THE POLICY-TECHNOLOGY NEXUS FOR MITGATING PASSENGER ON-ROAD TRANSPORTATION GHG EMISSIONS: E-BUS, E-RIDE-SHARE, OR OTHER ALTERNATIVES

title: ASSESSMENT OF TRANSPORTATION GHG MITGATING SOLUTIONS

contributor:
Mohamed, Moataz
Civil Engineering

subject: Well-to-Wheel GHG Emissions; car-share; ride-share; transportation policy; interval programming, total-cost-of-ownership ; electric mobility; vehicle simulation

abstract:
The passenger transportation sector is notoriously difficult to decarbonize. In this thesis, two distinct and novel methodologies to estimate the environmental impact of alternative and conventional transportation technologies are developed.
In Chapter 2, a provincial fleet policy-driven linear programming model is developed to minimize the cost of three passenger vehicle electrification policies in Ontario under a 30% GHG reduction target by 2030. Provincial life-cycle emissions and total-cost-of-ownership associated with policy allocation is estimated. The results highlight that electrification of on-road passenger transportation will not be sufficient to meet the 30% reduction target despite Ontario's low-carbon electricity grid. Instead, reductions of between 24% to 26% are forecasted at an annual cost (for ten years) of between CAD 0.29 to 0.3 billion annually indicating that additional policies are necessary to realize a 30% reduction target.
In Chapter 3, a trip-level vehicle framework is developed to determine under what operating conditions transit buses and passenger cars will be environmentally beneficial across the dimensions of technology, service mode, and power source pathway. The well-to-wheel energy consumption and GHG emissions are simulated for over 450 operating scenarios. Emissions are then normalized through passenger-trip emission thresholds to facilitate equivalent comparison across all dimensions. The results indicate that the most beneficial solution are fuel-cell electric car-share, battery electric car-share, and battery electric bus all powered by low-carbon intensity power sources at average occupancy (7.9-19.7 gCO2e passenger-service-mode-trip-km-travelled-1). Furthermore, transit bus technologies have the potential to reduce up to 2.3 times more GHG per passenger-trip than comparable ride-share passenger cars at average occupancies.
The results of Chapter 2 and 3 highlight that technology alone may not be sufficient to achieve significant GHG reductions; policy which leverage local operating data and target GHG reduction associated with passenger-trips are critical to informing under what conditions a mobility solution is environmentally beneficial.

abstract: Thesis

abstract: Master of Civil Engineering (MCE)

abstract:
There is a dire need to evaluate the effectiveness of transportation GHG mitigation policies as alternative mobility solutions are being adopted and the pressure to respond to climate change intensifies. This work evaluates the effectiveness of policy optimization and vehicle-level simulation techniques to inform GHG mitigation decision-making.
A two-step approach is adopted herein. At the strategic level, a cost optimization model for passenger vehicle electrification policies in Ontario is calibrated to identify the optimal allocation of provincial policy to achieve a 30% GHG reduction by 2030. Next, a micro level focuses on the energy consumption of eight vehicle technologies over 450 operational scenarios is simulated and trip-level passenger emissions are estimated to reveal the environmentally beneficial mobility option, corresponding passenger thresholds, and extent of variability associated with local operating conditions.
Overall, optimization and trip-level vehicle simulation can be used to demystify optimal decision-making related to mobility solutions.


title: NEUTRON FLUX MEASUREMENTS FOR UNCERTAINTY QUANTIFICATION AT THE MCMASTER NUCLEAR REACTOR

contributor:
Novog, David
Engineering Physics

abstract:
Nuclear research reactors offer a unique opportunity to the scientific community to investigate phenomena that are significant to both the renewable energy sector and the radiopharmaceutical industry. As the neutron flux dictates in-core processes that are crucial both to reactor operations and isotope production, highly precise measurements of this value are generally required to optimize and validate reactor physics analyses and day-to-day operations. Although neutron flux measurements in research reactors are well-documented, a detailed investigation of their uncertainties, and a methodology to quantify and combine them, has not yet been undertaken. These uncertainties are required to perform direct validation studies between experimental data and simulation models, to perform high-fidelity sensitivity and uncertainty quantification analyses, and to provide a basis for optimizing experimental activation processes in research reactor facilities.
Several experimental campaigns in the McMaster Nuclear Reactor (MNR) were designed to quantify the effects of various reactor parameters on neutron flux measurements. It was determined that the indicated reactor power and the sample positioning in the irradiation site are the most significant contributors to the final reported neutron flux uncertainty. By combining an experimental campaign with historical core data and Monte-Carlo models of MNR, it was determined that the effects of fuel management were generally insignificant and do not contribute significantly to the reported neutron flux uncertainty.
A Bayesian-based, Markov-Chain Monte-Carlo (MCMC) model was developed to accept fully covariant sets of nuclear data as inputs, such that their uncertainties could be included in a spectrum unfolding analysis. While nuclear data uncertainties are generally insignificant compared to other sources of uncertainty, the choice of flux spectrum parameterization may account for the trends in the final flux uncertainty across the energy spectrum.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Investigating the effects of altered blood flow, force, wrist posture, finger movement speed, and population on motion and blood flow in the carpal tunnel

title: Motion and blood flow in the carpal tunnel

contributor:
Keir, Peter
Kinesiology

subject:
Carpal Tunnel Syndrome
Tissue Motion
Median Nerve
Blood Flow
Subsynovial Connective Tissue
Tissue Strain

abstract: Data from the McMaster Occupational Biomechanics Laboratory were consolidated to evaluate overall trends relating to tissue motion and blood flow in the carpal tunnel. Regarding tissue motion, displacements of the flexor digitorum superficialis (FDS) tendon and its subsynovial connective tissue (SSCT) were found to decrease with greater movement speed and a flexed wrist posture. Notably, changes to shear outcomes including relative tendon-SSCT displacement, the shear strain index (SSI), and maximum velocity ratio (MVR) demonstrate that greater movement speed contributes to SSCT damage according to the shear strain mechanism of injury theorised to promote carpal tunnel syndrome (CTS). Median nerve blood flow was also found to be implicated by wrist flexion, and appeared to decrease with greater CTS severity status. Finally, induced blood flow alteration of the carpal tunnel was found to elicit a median nerve blood flow response similar to the level found in CTS subjects, confirming its effectiveness as an intervention to study tissue motion in a CTS-like state. The influence of altered blood flow on tissue motion was differential, where the higher supradiastolic condition altered FDS displacement, and the lower subdiastolic condition affected SSCT displacement and SSI. These findings provide valuable evidence for changes in median nerve blood flow—and by extension, the local fluid environment within the carpal tunnel—not only being a consequence of SSCT fibrosis characteristic of CTS, but potentially also acting as a cause for said changes in carpal tunnel tissue motion.

abstract: Thesis

abstract: Master of Science in Kinesiology

abstract: This thesis aimed to evaluate and summarize key findings from the McMaster Occupational Biomechanics Laboratory relating to tissue motion and blood flow in the carpal tunnel. Performing repetitive finger movements faster and with a flexed wrist posture were found to decrease the distance travelled of the underlying finger tendon. Blood flow of the median nerve, which is implicated in carpal tunnel syndrome (CTS), is higher with forceful exertion and flexed wrist posture, and lower with greater severity of CTS. Finally, altering blood flow to the carpal tunnel was found to create a CTS-like environment, affected tissue motion in the carpal tunnel, and promoted movement disparity between these tissues that is associated with injury. This suggests that fluid/blood flow changes affecting the carpal tunnel is a plausible mechanism for increasing the likelihood of developing CTS.


title: Exploring Novel Neuroanatomical Biomarkers for Alcohol Use Disorder: Considerations of Hippocampal and Amygdalar Subregions, Sulcal Morphology, and Fractal Dimensionality

contributor:
MacKillop, James
Neuroscience

subject:
Alcohol Use Disorder
Structural MRI
Biomarkers

abstract:
Objective: Alcohol use disorder (AUD) remains a leading cause of worldwide mortality and morbidity. The development of neuroanatomical biomarkers offers the potential of novel clinical indicators to guide prevention, early diagnosis, and treatment.
Methods: In 76 participants with DSM-5 diagnosed AUD (Mage = 35.75; 51.3% female) and 79 controls (Mage = 34.71; 59.5% female), we utilized magnetic resonance imaging (MRI) to investigate four novel measures: hippocampal and amygdalar subregion volumes, sulcal morphology (SM), and fractal dimensionality (FD). MRI processing, segmentation, and SM and FD quantification were completed using FreeSurfer v6.0 and v7.0, and MATLAB toolboxes, respectively. A significance value of p < .05 was employed for analysis and sex, age, and intracranial volume were included as covariates.
Results: Volumes of the right presubiculum, subiculum, and molecular layer head; left lateral and accessory basal nuclei; and corticoamygdaloid transition area were significantly lower in AUD participants relative to healthy controls. Widths of the left occipito-temporal, right middle occipital and lunate, and right marginal part of the cingulate sulci and depth of the post-central sulci were significantly increased in AUD participants relative to controls. Finally, decreased left caudate, left thalamus, right putamen and right pallidum FD and greater inferior lateral and third ventricle FD were observed in AUD participants relative to controls. Each novel measure’s reliability was assessed using test-retest data from the Human Connectome Project and indicated high reliability with median intraclass correlations of .93, .91, .88, and .93 for the hippocampal subfields, amygdalar nuclei, SM, and FD, respectively.
Conclusion: These results indicate selectively decreased hippocampal and amygdala subregion volume, increased sulcal depth and width, and differences in FD as promising neuroanatomical biomarkers for AUD.

abstract: Thesis

abstract: Master of Health Sciences (MSc)


title: Medicinal Cannabis, Chronic Pain and Sleep: Efficacy and Safety, Patients’ Perspectives, and Patterns of Use

contributor:
Busse, Jason
Health Research Methodology

abstract:
Chronic pain and sleep problems are two prevalent conditions frequently reported by the
general population. Despite limited evidence, in recent decades, there has been a rapid
rise in the use of Medicinal Cannabis (MC) for managing these two health conditions.
Cannabis is increasingly used for therapeutic purposes by Canadians; however, this
therapeutic option has largely emerged as a result of legal challenges instead of highquality empirical evidence establishing that the benefits exceed the harms. Furthermore,
complicating the use of cannabis as a therapeutic product is its’ recreational use. Canada
is the leading per capita consumer of cannabis for recreational use, which has raised
concerns among some healthcare providers that patients may seek authorization to use
MC for non-medical purposes.
Therefore, the current thesis has examined three areas to inform the use of MC based on
rigorous quantitative and qualitative approaches. It begins with investigating the efficacy
and safety of MC and cannabinoids for impaired sleep through conducting a systematic
review and meta-analysis of randomized clinical trials. Subsequently, it explores patients’
perspective towards MC use for chronic non-cancer pain (CNCP) using a qualitative
approach and finally, it assesses declared rationale for cannabis use before and after
legalization for recreational use for therapeutic purposes in Canada.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Price Optimization in Stochastic Loss System

contributor:
Zhou, Yun
Mathematics

subject:
price optimization
loss systems

abstract: Loss systems are of great importance for price optimization and revenue management even after more than a century since their first appearance. In this thesis, we analyze the optimal pricing problem for an M/M/1/1 Erlang-loss systems, and apply the model to inspect the impacts of vacancy tax regulations on short-term rental hosts. We then work on M/M/N/N loss systems while considering both advance reservation and multinomial logit (MNL) choice-model for the customers. We develop a simulation for this system and then train a machine learning (ML) model based on the outputs of this simulation to predict the utilization of each server based on different queueing parameters. Finally, we train another ML model for price optimization when the decision-maker sets the price for all servers to maximize the revenue of the whole system. We show that the presence of advance reservation decreases the utilization, consequently reducing the profit in the corresponding system.

abstract: Thesis

abstract: Master of Science (MSc)


title: Journeys Of Street-Involved Youth Searching For Housing While Using Substances

title: Journeys Of Street Involved Youth Searching For Housing While Using Substances: A Narrative Analysis

contributor:
Ion, Allyson
Social Work

subject:
Youth
Substance Use
Housing
Narrative Analysis

abstract: This study focuses on street-involved youth’s experiences with substance use and how it may impact their access to social services, specifically their access to housing and shelter services. I chose to use narrative interviews when speaking with the youth and it was through the sharing of their narratives that different themes, and recommendations for practice were revealed. During the analysis of the data, critical theories were applied, specifically a post-structural and intersectional framework. The youth who participated in this study shared experiences of their hardships, feelings of low motivation in seeking housing, feelings of self-agency regarding their substance use, and the need for more anti-oppressive approaches within housing and shelter services. These anti-oppressive approaches were described by the youth to include more flexible hours, less restrictive shelter rules and a need for more understanding and empathetic service providers. This research highlights important overall insights on the experiences of these youth and how they make sense of their substance use and life on the street.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Assessment of a Treatment Planning Protocol for the Reduction of Dosimetry Calculation Errors in Radiotherapy for Head and Neck Patients with Dental Implants

contributor:
Ostapiak, Orest
Medical Physics

subject:
Metal Artifact Reduction
Amalgam
CT
Dose calculation

abstract:
Concerns arise in radiation therapy for head and neck cancers when dental prostheses are involved. These prostheses are high-density materials that induce image artifacts in computed tomography (CT) scans used for dose calculation. Two approaches are utilized in mitigating the impact of these artifacts on the accuracy of dose calculation. First, metal artifact reduction (MAR) algorithms or dual-energy CT scans are used to recover image quality. Second, a planning protocol is adopted whereby residual artifacts are manually contoured and assigned appropriate densities. This study evaluated the current planning process using a holistic approach. In this work, an axial section of a head phantom containing dental implants at the level of the oral cavity was constructed and scanned using various protocols on two different commercial scanners; Philips and Siemens, to assess the appearance of artifacts. An MVCT image set was merged with the corresponding kVCT image to improve visualization of the dental implants for use in density overrides. Three ion chamber measurement points in the simulated mouth facilitated the determination of measured dose which was compared to calculated dose at various single beam irradiation geometries. The influence of density override values on agreement between calculation and measurement was investigated for each geometry and imaging modality. Percent error was computed, and initial results compared to results manipulated by use of; a CT density table (Head); density overrides of walls and wax; and density overrides of walls, wax, and effective density of saturation regions.
The study established that normal tissue doses are not significantly affected by metal artifact reduction (MAR) algorithms, and improvements in dose calculation compared to uncorrected CT images are small. Furthermore, the inclusion of a MVCT image set improved implant visualization reducing the treatment planning time while providing more information. Evidence led to the deduction that manual overrides of effective density for clipped OMAR CT pixels reduce dose calculation errors. When the phantom was configured with amalgam and Co-Cr-Mo alloy dental implants the effective density of these implants was found to be 4.5 g/cm3. When the phantom was configured with implants containing amalgam and gold, the effective density of amalgam in the presence of gold was 5.5 g/cm3 while gold had an effective density of 6.5 g/cm3.
The median and maximum range of errors for the uncorrected images were ± 0.6 % and 7.4% respectively for the phantom configured with amalgam and Co-Cr-Mo (tray one) and ± 0.5 % and 18.1 % respectively for the phantom containing amalgam and gold (tray two). The median and maximum range of errors for the corrected images after applying overrides of effective densities were ± 0.5 % and 4.7% respectively for tray one and ± 0.3 % and 7.7 % respectively for tray two. In conclusion, introduction of density overrides of walls, wax and effective density of high-density materials can reduce the errors induced by metal artifacts and improve the accuracy of dose calculations in treatment planning systems to deliver the relevant dose to a target organ.

abstract: Thesis

abstract: Master of Science (MSc)


title: On Linear Power Control Policies for Energy Harvesting Communications

contributor:
Chen, Jun
Electrical and Computer Engineering

subject:
Energy harvesting communications
Linear policies

abstract: In this thesis, we focus on linear online power control policies for the energy harvesting communications. In the first part of the thesis, greedy policy is investigated as a special case of linear policies. The tight upper and lower bounds on the greedy threshold (c*) are provided in semi-universal  settings where few parameters are known from the actual arrival distribution and clipped  arrival distribution. Then the optimality region of the greedy policy is discussed. In the second part, various notions of optimal slope (s*) linear policy are discussed. The numerical results show the existence of optimal linear policy with strictly better performance than the conventional fixed fraction policy in terms of the multiplicative ratio.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: The Quality of Prescribing and Medication Use and Its Impact on Older Adult High-Cost Healthcare Users

contributor:
Holbrook, Anne
Health Research Methodology

subject:
Older adults
Seniors
High-cost healthcare users
Medications
Prescribing
Potentially inappropriate medications
High-cost drugs

abstract:
BACKGROUND:
High-cost healthcare users (HCUs) are patients who use disproportionate healthcare resources compared to their peers. A better understanding of their co-morbidity status, medication use, and healthcare utilization is needed to improve health interventions and policies.

OBJECTIVES:
We aimed to: (1) synthesize what is known about HCUs and interventions for managing them, (2) characterize how HCUs differ from non-HCUs, and (3) explore the impact of medications and whether prescribing quality contributes to differences in healthcare costs and HCU status development.

METHODS:
We synthesized what is known about HCUs and used the GRADE framework to evaluate the evidence for interventions designed to improve their health. We conducted retrospective population-based matched cohort and case-control studies of incident older adult HCUs using health administrative data. We examined prescribing and medication costs over the non-HCU to HCU transition period and compared them to non-HCUs. We conducted logistic regression to evaluate associations between HCU status development and the use of high-cost drugs and potentially inappropriate medications.

RESULTS:
HCU interventions to date have shown inconsistent effects on clinical outcomes and healthcare costs and the overall quality of evidence supporting their efficacy is low. Compared to non-HCUs, HCUs have higher rates of polypharmacy, hospitalization, and mortality. Medications are the highest healthcare cost category in the pre-HCU year and these costs rise nearly 1.7-fold in the HCU year. High-cost drug use increases significantly during the HCU transition period and 3.6% achieve HCU status based on drug costs alone. Use of several potentially inappropriate medications and high-cost drugs significantly increase the odds of HCU development.

CONCLUSIONS:
Medications can contribute to high-cost healthcare directly through drug costs alone or indirectly through adverse effects on health. Medication optimization interventions and policies to reduce inappropriate medication use and ensure cost-effective medication use are needed to manage high-cost healthcare and prevent HCU development.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: High-cost healthcare users (HCUs) are patients who use disproportionate healthcare resources compared to their peers. More research is needed to better understand HCUs to design interventions to improve their health outcomes and costs. In this thesis, we evaluated what previous studies have discovered about HCUs and we used Ontario’s health system data to explore whether the quality of prescribing and medication use in older adults influences their risk of becoming a HCU. We found that current interventions for HCUs have had inconsistent effects on improving health outcomes and costs. We also found two medication-related factors contributing to the risk of becoming an older adult HCU: (1) use of very expensive medications, and (2) use of potentially inappropriate medications where the risk of harm may outweigh potential benefits. Interventions and health policies to optimize the appropriate and cost-effective use of medications are needed to manage high-cost healthcare and prevent HCU development.


title: Prevalence of Chronic Pain among Military Veterans and Research Priorities among Military Veterans Living with Chronic Pain

subject: Chronic non-cancer pain, military veterans, prevalence, research priorities

abstract: INTRODUCTION: There is uncertainty in the prevalence of chronic non-cancer pain (CNCP) in military veterans. A systematic review and meta-analysis was conducted to elucidate this issue, and examine potential effect modifiers of CNCP prevalence. Additionally, chronic pain is a pervasive and debilitating condition that disproportionately affects military veterans. We recently completed a qualitative study of Canadian veterans living with chronic pain to identify their research priorities; however, the generalizability of our findings was uncertain. METHODS: MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science were searched from 2013 to January 21, 2021, for observational studies reporting “chronic pain” or pain ≥ 3 months in military veterans. The random-effects meta-analysis was used for pooling data, the Grading of Recommendations, Assessment, Development and Evaluations approach was used for rating quality of evidence, and the Instrument to Assess the Credibility of Effect Modification Analyses was used to rate credibility of the subgroup analyses. Furthermore, from January to March 2021, we emailed a 45-item cross-sectional survey to a list of Canadian veterans that asked about the relative importance of 20 research priorities regarding chronic pain. We explored for statistical significance between male and female responses for any item in which the proportion of endorsement showed a ≥10% difference. RESULTS: 41 observational studies with 5,550,375 military veterans were included. The overall pooled CNCP prevalence is 34% (95% confidence interval (CI) 25% to 45%). However, significant subgroup effect was found for type of prevalence measure (generic or specific) among military veterans (test of interaction p=0.007, moderate subgroup credibility): the pooled generic CNCP prevalence of 43%, 95% CI 29% to 57% (Low-certainty evidence) vs. the pooled specific type of CNCP prevalence of 14%, 95% CI 6.7% to 23% (Moderate-certainty evidence). A multivariable meta-regression model adjusted for proportion lost to follow-up found the type of prevalence measure to be the only significant predictor of CNCP prevalence (p < 0.0001). 313 of 699 Canadian military veterans living with chronic pain completed ≥50% of the survey (45% response rate). Respondents were predominantly male (77%) with a median age of 52 (interquartile range [IQR] 44-58). All 20 research priorities listed in the survey were endorsed as very important by ≥52% of respondents, and three received endorsement by ≥85%: (I) optimizing chronic pain management after release from the military; and (II) identifying and (III) treating mental illness among veterans living with chronic pain. Women were more likely than men to endorse research on post-surgical care for chronic pain prevention or research on holistic care for chronic pain. Men were more likely than women to endorse research on physical activity or exercise for chronic pain. Individuals with higher gross income (≥$80,000) were less likely to endorse research into physiotherapy for chronic pain, or chiropractic for chronic pain compared to those with lower gross income. Individuals with greater age are less likely to endorse research on medical cannabis for chronic pain. CONCLUSIONS: The overall prevalence of CNCP is 34% among military veterans. For generic CNCP, the prevalence is 43%; for a given subtype of CNCP, the prevalence is 11%. Methodologically robust studies are required to more precisely determine CNCP prevalence. The most salient research priorities among our respondents were optimizing chronic pain management during service and after discharge from the military, including co-morbid mental illness. Differences in gender, gross income, and age are implicated in the endorsement of therapy-related priorities, which include surgery, physical activity or exercise, chiropractic, and medical cannabis. Our findings provide insight into the research priorities of Canadian military veterans living with chronic pain. These findings should be considered by granting agencies when formulating calls for proposals, and by researchers who wish to undertake research that will address the needs of military veterans living with chronic pain.

abstract: Thesis

abstract: Master of Science (MSc)


title: ACOUSTIC EMISSION MONITORING OF THE POWDER BED FUSION PROCESS WITH MACHINE LEARNING APPROACH

contributor:
Elbestawi, Mohamed
Mechanical Engineering

subject:
Machine Learning
Acoustic Emission
Powder bed fusion
Deep Learning

abstract:
Laser powder bed fusion (L-PBF) is an additive manufacturing process where a heat source (such as a laser) consolidates material in powder form to build three-dimensional parts. For quality control purposes, this thesis uses real-time monitoring in L-PBF. Defects such as pores and cracks can be detected using Acoustic Emission (AE) during the powder bed selective laser melting process via the machine learning approach. This thesis investigates the performance of several Machine Learning (ML) techniques for online defect detection within the Laser Powder Bed Fusion (L- PBF) process. The goal is to improve the consistency in product quality and process reliability. The application of acoustic emission (AE) sensors to receive elastic waves during the printing process is a cost-effective way of meeting such a goal.
For the first step, stainless steel 316L was produced via eight parameters. The acoustic emission signals received during the printing and data collection steps are analyzed using an AE sensor under various process parameters. Several time and frequency-domain features were extracted from data during the mining process from the AE signals.
K-means clustering is employed during unsupervised learning, and a neural network approach was used for the supervised machine learning on the dataset. Data labelling is conducted for different laser powers, clustering results, and signal time durations. The results showed the potential of real-time quality monitoring using AE in the L-PBF process.
Some process parameters within this project were intentionally adjusted to create three various levels of defects in H13 tool steel samples. First classes were printed with minimum defects, second classes with intentional cracks, and last classes with intentional cracks and porosities. AE signals were acquired during the samples' manufacturing process. Three different machine learning (ML) techniques were applied to analyze and interpret the data. First, using a hierarchical K-means clustering method, the data was labelled. This was followed by a supervised deep learning neural network (DL) to match acoustic signals with defect type. Second, a principal component analysis (PCA) was used to reduce the dimensionality of the data. A Gaussian Mixture Model (GMM) enabled the fast detection of defects, which is suitable for online monitoring. Third, a variational auto-encoder (VAE) approach was used to obtain a general feature of the signal, which could be used as an input for the classifier.  Quality trends in AE signals collected from 316L samples were successfully detected using a supervised DL trained on the H13 tool steel dataset. The VAE approach shows a new method for detecting defects within the L-PBF processes, which would eliminate the need for model training in different materials.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Identification of Novel Therapeutic Targets and Rational Development of Immunotherapeutics for Recurrent Glioblastoma

title: IDENTIFICATION, VALIDATION, AND IMMUNOTHERAPEUTIC TARGETING OF NOVEL TUMOR-ASSOCIATED ANTIGENS FOR TREATMENT-REFRACTORY GLIOBLASTOMA

contributor:
Singh, Sheila
Biochemistry and Biomedical Sciences

subject:
Brain tumor
Immunotherapy

abstract:
Glioblastoma (GBM) is the most common and aggressive brain tumor in adults which is characterized by extensive cellular and genetic heterogeneity. Even with surgery, chemotherapy with temozolomide, and radiation, tumor re-growth and patient relapse are inevitable. The extensive inter- and intra-tumoral heterogeneity (ITH) of recurrent GBM emerges from dysregulation at multiple -omic levels of the tumor. ITH exits at the cellular level due to a small subpopulation of chemo- and radio-resistant cells, called brain tumor initiating cells, which may drive GBM treatment resistance. Although a wealth of literature describes the biology of primary GBM (pGBM), we currently lack an understanding of how GBM evolves through therapy to become a very different tumor at recurrence, which may explain why therapies against primary GBM fail to work in recurrent GBM (rGBM). Thus, understanding the tumor evolution from a multi-omic perspective is critical for the development of effective therapeutic approaches.

The current work focuses on identification and validation of novel predictive and prognostic biomarkers for rGBM using proteomics analysis on a large cohort of patientmatched pGBM-rGBM samples. This work allowed for detailed characterization of rGBM and its cognate TIME toward a better understanding of the molecular players driving recurrence which can be further used for instructing effective targeted and personalized therapies for the treatment of therapy-resistant GBM.

In another part, we developed a novel immunotherapeutic modality called dual antigen T cell engager, to target Carbonic Anhydrase 9, a highly enriched hypoxia-inducible enzyme in GBM. We demonstrated that this immunotherapeutic strategy which allows for targeting tumor cells while recruiting and triggering T cells through simultaneously, is highly effective in eliminating tumor cells and can be a complementary component of combinatorial therapy for GBM patients.

Altogether, this study provided key data for instructing novel and rational combinatorial polytherapeutic approaches for the treatment of therapy-resistant GBM.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Cancer is the leading cause of death in Canada and Glioblastoma Multiforme (GBM) is the most common type of malignant adult brain tumor which is one of the difficult human cancers to treat. In spite of the multi-model therapy including surgery, chemotherapy, and radiation, tumor re-growth and patient relapse are inevitable. A wealth of literature describes the biology of treatment-naïve or primary GBM, but we currently lack an understanding of how GBM evolves through therapy to become a very different tumor at recurrence, which may explain why therapies against primary GBM fail to work in recurrent GBM (rGBM). Clinical trials have not shown significant survival advantages for GBM patients, due not only to the lack of biological characterization of the distinct landscape of GBM recurrence, but also due to our poor understanding of the tumor immune microenvironment (TIME), the immune cells surrounding the tumor that may somehow fail to attack it due to GBM cells’ ability to suppress the immune system and evade detection. To understand how GBM cells and the TIME evolve under therapeutic pressure, we performed proteomics analysis on a large cohort of primary-recurrent GBM patient samples, to further understand treatment failure and develop effective and empirical combinatorial poly-therapies for the treatment of therapy-resistant GBM. Besides, in the next part of this study we showed existence of few cells within the tumor, termed brain tumor initiating cells (BTICs) can alone drive tumor growth and cause therapy resistance. To be able to target these population of cells, we identified treatment resistant tumor associated markers (highly expressed cell surface proteins) on these cells and developed novel treatments using a new class of biologics, Dual Antigen T cell Engagers (DATEs), to target these tumor associated markers. DATEs act like a “molecular glue” that specifically binds the patient’s own naturally circulating T-cells (soldier cells of the immune system) to cancer cells. Once bound, the T-cells attack and kill the patient’s cancer cells. In this strategy, the abnormal expression of tumor surface proteins can be used as a handle to drive T cell-mediated cell death. We predict that the dual specific antibodies through this study could be used alone or in combination with existing drugs to treat recurrent GBM.


title: AN INVESTIGATION OF BIOLOGICAL AND SOCIAL CORRELATES OF BORDERLINE PERSONALITY DISORDER IN ADOLESCENTS

title: BIOLOGICAL AND SOCIAL CORRELATES OF BPD IN ADOLESCENTS

contributor:
Schmidt, Louis
Psychology

abstract: Borderline personality disorder (BPD) is a complex a mental health condition that develops over time through an intricate interaction between a person’s biology (i.e., an emotional vulnerability) and their environment (i.e., invalidating social context). BPD can greatly impact a person’s ability to function. The central feature of BPD is emotion dysregulation. This means that individuals with BPD have a difficult time identifying, labeling, communicating, and managing their (often heightened) emotional experiences. Emotion dysregulation, then, often causes individuals with BPD to experience difficulties with their identity (i.e., not knowing who they are if they cannot identify/predict how they feel), challenges in their relationships (i.e., their beliefs about others can be emotion-dependent), distortions in reality (e.g., surroundings appear distorted when experiencing intense distress), and leads them to engage in impulsive and self-harming behaviours (e.g., substance use, cutting, etc.). Research has illustrated that BPD symptoms typically peak in late adolescence (ages 14-17 years); however, there remains skepticism about diagnosing BPD in adolescents. Although there is a substantial field of research examining BPD in adolescents, this area of study is relatively new and limited in scope when compared with the adult BPD literature. The purpose of this thesis was to examine putative biological and social correlates associated with BPD in adolescents. The first study investigates differences in frontal electroencephalogram (EEG) alpha asymmetry (FAA) and alpha power at rest, a biological proxy of emotion regulation, between BPD and non-BPD adolescents. The second study assesses the relation between BPD symptoms and feelings of rejection following a social exclusion paradigm. The third study, then, extends Studies 1 and 2 by examining whether brain activity (i.e., FAA) moderates the relation between BPD symptoms and feelings of rejection. We hope this research extends our understanding of BPD in adolescents, provides validity to the adolescent BPD diagnosis, and ultimately helps to improve the management and treatment of BPD in adolescents.

abstract: Thesis

abstract: Candidate in Philosophy


title: THE IMPACT OF THE PANDEMIC ON SOMALI-CANADIAN YOUTH LIVING IN REXDALE

title: SOMALI-CANADIAN YOUTH: EMPLOYMENT, HEALTH, PANDEMIC

contributor:
Newbold, Dr. Bruce
Dei-Amoah, Marlene
Global Health

subject:
Somali-Canadian
Second Generation
Rexdale
Employment
Health
Pandemic
Social Determinants of Health
Youth

abstract:
Background: The first wave of Somali-Canadian refugees arrived in the 1990s following the civil war, with many settling in Toronto. First generation Somali-Canadians faced significant discrimination and settlement challenges. Previous research on Canada immigrants found that second generation youth tend to have a bright socioeconomic outlook. However, this outlook is not so certain for Somali-Canadian youth as they face unique long-term challenges with systemic barriers. Additionally, the pandemic has disproportionately impacted Black communities. Thus, it is important to explore how the pandemic has impacted the employment and health of Somali-Canadian youth living in Rexdale.
Methods: Through an IPA approach, semi-structured interviews were conducted with 8 Somali-Canadian youth between the ages of 18-25 living in the Rexdale neighbourhood. The interviews were then analyzed through the IPA perspective to generate themes.
Results: Somali-Canadian youth experience precarious employment, unsafe working conditions, lost income, faced financial difficulties and an increased risk of exposure to COVID-19. Furthermore, these impacts were exacerbated by living with large families and immunocompromised family members. Participants accessed government COVID-19 supports but some were ineligible due to precarious work or concerns associated with accessing governmental assistance. The pandemic negatively impacted the mental health of youth due to financial worries, educational and interpersonal challenges, and cultural stigma. Additionally, the intersectional identities of the participants resulted in limited choices and access to coping strategies.
Conclusions: In order to improve the physical and mental wellbeing of Somali-Canadian youth, and those who share their experiences, there needs to be greater investments into the social determinants of health including employment, healthcare, housing, income, and education.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: In the 1990s, Somali refugees arrived in Canada following a civil war, with many settling in Toronto. The first wave of Somali refugees faced discrimination and settlement challenges. Generally, children of immigrants have a bright socioeconomic outlook. However, second-generation Somali-Canadian youth face unique challenges and systemic barriers. This study explores how the pandemic impacts the health and employment of the Somali-Canadian youth living in Rexdale. Eight semi-structured interviews with youth aged 18-25. The findings illustrated impacts such as precarious employment, unsafe work, lost income, and increased risk of exposure to COVID-19. The mental health of the youth was negatively impacted due to financial worries, educational and interpersonal challenges, and cultural stigma. Sadly, the intersectional identities of the participants resulted in limited choices and access to coping strategies. To improve the health and wellbeing of Somali-Canadian youth, there needs to be greater investments into the social determinants of health including employment, healthcare, housing, income, and education.


title: Examination of Nurse-Modifiable Risk Factors for Chronic Post-Surgical Pain after Cardiac Surgery

contributor:
McGillion, Michael H.
Nursing

subject:
acute postoperative pain
cardiac surgery
anxiety
chronic post-surgical pain
depressive symptom
nursing
opioid
risk factor

abstract:
Background: Thousands of Canadians undergo cardiac surgery each year with the aim of relieving symptoms (e.g., angina) and improving health-related-quality-of-life (HRQoL). Despite the demonstrated symptom-related benefits of these surgeries, evidence suggests that the development of chronic post-surgical pain (CPSP) is a major clinical problem. To date, several perioperative factors have been examined for their potential to confer risk for CPSP.
Purpose: The purpose of the study was to explore the association between preoperative moderate to severe anxiety and depressive symptoms; moderate to severe acute postoperative pain; and cumulative opioid dose consumption with the development of CPSP at six months and 12 months after cardiac surgery.
Method: Design. This thesis was a prospective observational cohort sub-study of adults undergoing cardiac surgery in a tertiary care hospital setting (n=735), recruited from Hamilton Health Sciences, Canada over a five year period. Measures. The independent variables included state anxiety, depressive symptoms, acute postoperative pain intensity, and opioid dose consumption. At baseline, the Spielberger State-Trait Anxiety Inventory (STAI) assessed state anxiety and the Hospital Anxiety and Depression Scale (HADS) assessed depressive symptoms. The Brief Pain Inventory-Short Form (BPI-SF) assessed acute postoperative pain intensity on postoperative days three (in-hospital) and 30 (at home via telephone). All instruments have established reliability and validity in cardiac surgery patients (e.g., STAI Cronbach’s alpha (α) =0.82; HADS α=0.81; BPI-SF α=0.87). Medical records were reviewed and total dose of opioids consumed up to three days postoperatively, were collected via analgesic chart audit and converted into milligrams of parenteral morphine equivalent dose using standard dosage tables. Dependent variable. The primary outcome of CPSP was assessed dichotomously (i.e., yes/no) at six months and 12 months after cardiac surgery. If present, CPSP was assessed via the BPI-SF. At baseline, data was collected on pre-specified model covariates (e.g., age, sex). Data Analyses. Logistic regression was used to model the primary outcome with the presence of CPSP at six months and 12 months, while adjusting for model covariates. Secondary linear regression models were constructed to examine the effect of the independent variables on the severity of CPSP with statistical significance set at p-values <0.05.
Results: The incidence of CPSP was 8.7% at six months and 4.1% at 12 months after cardiac surgery. Baseline demographics (i.e., age, sex) and medical status (i.e., diabetes mellitus) were significantly associated with the presence of CPSP. Moderate to severe preoperative anxiety was not significantly associated with CPSP at six months (adjusted OR 0.629, 95% CI [0.300, 1.322], p=0.222) or 12 months (adjusted OR 0.743, 95% CI [0.242, 2.285], p=0.604). Moderate to severe preoperative depressive symptom was not significantly associated with CPSP at six months (adjusted OR 0.676, 95% CI [0.152, 3.005], p=0.607) or 12 months (adjusted OR 3.216, 95% CI [0.835, 12.382], p=0.089). Acute postoperative pain rated as pain ‘right now’ on day three was significantly associated with CPSP at six months (adjusted OR 2.263, 95% CI [1.255, 4.081], p=0.007) and 12 months (adjusted OR 2.749, 95% CI [1.174, 6.441], p=0.020). Acute postoperative pain ‘right now’ on day 30 was significantly associated with CPSP at six months (adjusted OR 2.913, 95% CI [1.304, 6.505], p=0.009). Cumulative opioid dose consumed was significantly associated with the development of CPSP at six months (adjusted OR 1.001, 95% CI [1.000, 1.002], p=0.003) and 12 months (adjusted OR 1.001, 95% CI [1.000, 1.001], p=0.033) after cardiac surgery.
Significance: The findings demonstrate that acute postoperative pain ‘right now’ and cumulative opioid dose consumed are risk factors for CPSP after cardiac surgery. These findings offer targets for nursing staff to identify potentially at-risk patients, implement evidence-based pain management strategies, as well as contribute to nursing-led research designed to target CPSP after cardiac surgery.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: The Syntax of Subject Suppression in Turkish

contributor:
Kucerova, Ivona
Cognitive Science of Language

subject: Syntax, Semantics, Turkish

abstract: This thesis has two aims: The first is to establish that OSV word order sentences in Turkish, along with the related Oblique-NP SV word order sentences, can have two different syntactic structures, one resulting from A-movement, and the other from A’-movement; I refer to the structures resulting from A-movement as ‘subject suppression’ constructions. The second aim of the thesis is to analyze the syntactic structure of subject suppression constructions. I rely on novel tests based on the semantics of specificity in Turkish to delineate the subject suppression constructions. I then propose that these constructions have their external arguments merged in the specifier of VP, and semantically interpreted via a special composition rule, as suggested by Kratzer (1996, p. 113) before being dismissed in favour of her VoiceP proposal.

abstract: Thesis

abstract: Master of Science (MSc)


title: Trust in Human Activity Recognition Deep Learning Models

contributor:
Doyle, Thomas
Biomedical Engineering

subject: trust, human activity recognition, artificial intelligence, wearable devices

abstract: Trust is explored in this thesis through the analysis of the robustness of wearable device based artificial intelligence based models to changes in data acquisition. Specifically changes in wearable device hardware and different recording sessions are explored. Three human activity recognition models are used as a vehicle to explore this: Model A which is trained using accelerometer signals recorded by a wearable sensor referred to as Astroskin, Model H which is trained using accelerometer signals from a wearable sensor referred to as the BioHarness and Model A Type 1 which was trained on Astroskin accelerometer signals that was recorded on the first session of the experimental protocol. On a test set recorded by Astroskin Model A had a 99.07% accuracy. However on a test set recorded by the BioHarness Model A had a 65.74% accuracy. On a test set recorded by  BioHarness Model H had a 95.37% accuracy. However on a test set recorded by Astroskin Model H had a 29.63% accuracy. Model A Type 1 an average accuracy of 99.57%  on data recorded by the same wearable sensor and same session. An average accuracy of 50.95% was obtained on a test set that was recorded by the same wearable sensor but by a different session. An average accuracy of 41.31% was obtained on data that was recorded by a different wearable sensor and same session. An average accuracy of 19.28% was obtained on data that was recorded by a different wearable sensor and different session. An out of domain discriminator for Model A Type 1 was also implemented. The out of domain discriminator was able to differentiate between the data that trained Model A Type 1 and other types (data recorded by a different wearable devices/different sessions) with an accuracy of 97.60%.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: The trustworthiness of artificial intelligence  must be explored before society can fully reap its benefits. The element of trust that is explored in this thesis is the robustness of wearable device based artificial intelligence models to changes in data acquisition. The specific changes that are explored are changes in the wearable device used to record the input data as well as input data from different recording sessions. Using human activity recognition models as a vehicle, the results show that performance degradation occurs when the wearable device is changed and when data comes from a different recording session. An out of domain discriminator is developed to alert users when a potential performance degradation can occur.


title: The Effects of Perception-Action Coupling on Compromised Human Locomotion: A Proposed Research Program

contributor:
Lyons, Jim
Kinesiology

subject: Perception-Action, Optic Flow, Compromised Gait, Locomotion, Vision, Ecological Theory

abstract:
There is considerable evidence suggesting an innate linkage between the human
perceptual and motor systems, which evolve together and assist one another in the
production and coordination of movement. A major contributor to this relationship is
optic flow, providing movement variables such as navigation, obstacle avoidance, and
depth perception. The absence of optic flow leads to the decoupling of perception and
action, which has been shown to contribute to decrements in human movement (i.e.,
negatively impacted locomotion and posture, and slower adaptation to gait perturbations).
Despite the importance of maintaining this linkage, optic flow manipulations are often
found to be underrepresented in locomotion literature when specifically related to
rehabilitation training (i.e., treadmills). This may be a contributor to the lengthy and
exhaustive treatment plans. The literature has shown instances where reintroducing optic
flow into training protocols has shown larger gait improvements in shorter times than
typical ambulation protocols, however, the strength of the perception-action linkage in
adulthood is still not well understood and its impact not yet fully explored. Therefore, the
current research program aims to fill this gap by evaluating how the reintroduction of
optic flow into atypical gait training protocols in both healthy and gait-compromised
individuals may provide evidence that could be used to enhance rehabilitative outcomes.
This series of conceptually related experiments explores outcome enhancements through
neuromuscular level changes (Study One), the recalibration process of perception-action
given newly acquired physical constraints (Study Two), and on larger scale gait cycle
performances in a rehabilitation setting (Study Three). It is hypothesized that perception-
action coupling will lead to increases in neuromuscular elicitation in the absence of
voluntary movement (Study One), assist the recalibration process to improve measures of
spatial awareness and atypical gait parameters (Study Two), and finally, improve
rehabilitative outcomes in a spinal cord injury (SCI) ambulation protocol, both
objectively (i.e., gait parameters, dynamic balance, SCI measures) and subjectively (i.e.,
questionnaires) (Study Three).

abstract: Thesis

abstract: Master of Science (MSc)


title: Design and Modularization of a Hybrid Vehicle Control System

contributor:
Lawford, Mark
Computing and Software

subject:
matlab
simulink
automotive
modularity
software
information hiding

abstract:
The complexity of automotive software has increased dramatically in recent years. New technological advances as well as increasing market competitiveness create a high cost-pressure environment. This thesis seeks to apply established modular principles to a Simulink Model to increase information hiding to improve the maintainability of controls software. A Hybrid Supervisory Controller (HSC) model, developed as part of the McMaster EcoCAR Competition, is used throughout this thesis. The software design process followed during the HSC model development is detailed, as well as providing an example of the application of the Simulink Module Tool, a Simulink add-on developed by Jaskolka et. al. The HSC System decomposition was restructured based on an analysis of the likely changes to the vehicle software, as well the system secrets contained within the model.

This thesis also presents an analysis of the original and modular system decompositions, comparing several common software indicators of information hiding, coupling, cohesion, complexity, and testability. The modular decomposition led to a significant improvement in information hiding, both in system changeability and internal implementation. Likely changes to the system propagate to fewer modules and components within the new decomposition, with hardware data separated from behavioral algorithms, and all modules grouped based on shared secrets. The redistribution of algorithms based on separation of concern also led to improvements in coupling, cohesion, and interface complexity. The resulting software design process and modular system decomposition provides a framework for future EcoCAR students to focus on correct design and implementation of hybrid vehicle software. The benefits provided by the application of the Simulink Module Tool also contributes additional data and supporting evidence to the improvements that can be realized within Simulink Models by introducing the concepts of information hiding and modularity.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: The complexity of automotive software has increased dramatically in recent years. New technological advances as well as increasing market competitiveness create a high cost-pressure environment. As a result, improving the development of automotive software and its maintainability has become an increasingly critical issue to solve. This thesis uses a Hybrid Vehicle Controller Model developed within MATLAB Simulink to investigate the possible improvements that can be made to software modularity. The system decomposition is modified using the Simulink Module Tool, and is analyzed regarding improvements to information hiding, interface complexity, and specifically minimizing change propagation. The modular improvements made to the Simulink Model resulted in significant improvements in system changeability and information hiding, providing a useful framework for future EcoCAR students.


title: Healthcare Social Workers’ Experiences of Distress During the COVID-19 Pandemic: Organizational and Relational Levels of Care

contributor:
Sinding, Christina
Social Work

subject:
Healthcare social work
Hospital social work

abstract: Hospital social work during the COVID-19 pandemic

abstract: Healthcare social workers have been on the front lines of the response to COVID-19 since its early days. With an upsurge of social isolation, unemployment, and grief and loss, social workers are being met with new challenges and are required to adapt to new and heightened demands of their roles – while also navigating their own fears and anxieties during the pandemic. While social workers attempt to manage increasing caseloads of complex patient needs, they must navigate the constrained context of their workplace and the changes in patient care. This study used qualitative methods to capture the lived experiences of healthcare social workers amidst the COVID-19 pandemic. Specifically, I used qualitative interviewing to explore the reflections of nine hospital social workers in Hamilton, Ontario regarding their experiences of wellness and wellbeing throughout the pandemic. My research identified three key themes: 1) lack of professional agency and power 2) moral injury, and 3) respect and care – organizational and among colleagues. In the discussion section I reflect on the implications of these findings for the practice of social work during and beyond pandemic times.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: DESIGNING A CENTRALIZED FACULTY PERFORMANCE DASHBOARD: OPTIMIZING FEEDBACK AND SCHOLARLY DATA REPORTING

contributor:
Chan, Teresa
Lokker, Cynthia
Barr, Neil
Crowther, Mark
eHealth

subject:
eHealth
Dashboards
Design-based research
User experience
Faculty
Health Sciences
Performance reporting
User experience

abstract:
BACKGROUND: Faculty members in higher education participate in a diversity of scholarly activities. Feedback performance and data on these academic contributions must be tracked for multiple formative and summative purposes including faculty development, promotions, and annual reporting requirements. However, this data are frequently not captured, primarily because most teaching institutions have not implemented a system to effectively collect and report this data.
PURPOSE: This thesis designed prototypes for an online performance analytics dashboard for Health Sciences faculty members, including researchers, teachers, administrators, leaders, and clinical educators. This project incorporated UCD (user-centered design) to focus on the end-users and seek to understand their needs and wants.
METHOD: McMaster University was used as a case study for this Design-Based Research study. Dashboard preferences were gathered from literature reviews, stakeholder interviews, document analysis, focus groups and interviews. These findings informed the build of a dashboard prototype. Multiple iterations of end-user evaluation and prototype revisions were conducted to refine the design. A constructivist grounded theory approach was utilized to analyze qualitative data from focus group and interviews to generate theory.
RESULTS: 25 key resources from the literature review were listed in an annotated bibliography. 10 stakeholders were interviewed. Several McMaster policies and forms were reviewed. 18 faculty members reviewed the dashboard and provided feedback. Qualitative data from focus groups and interviews revealed 4 main themes pertaining to dashboard needs.
CONCLUSION: By designing prototypes, this study revealed several requirements and considerations for the construction of a faculty performance dashboard. The dashboard must be customizable, dynamic, organized by user groups, and include specific requirements for the relevant faculty roles. The quality, governance and weighting of data in the dashboard must be considered. Notably, the implementation of this solution would enhance faculty learning and assessment, data reporting and faculty development in the Health Sciences.

abstract: Thesis

abstract: Master of Science (MSc)


title: Creating a Metagenomic Data Analysis Pipeline Using Simulated Infant Gut Microbiome Data for Genome-Resolved Metagenomics in the Infant Gut Microbiome

contributor:
Stearns, Jennifer C.
Chemical Biology

subject: microbiome bioinformatics microbiology metagenomics

abstract:
Background: Studying the infant gut microbiome during the period of solid food introduction may provide valuable insight into gut colonization, microbial evolution, and the ecological role of bacterial metabolic pathways in microbial succession. However, since infant gut microbial communities are made of bacterial genera with high relative abundance, within-genus and within-species diversity, the efficacy of current computational tools in elucidating strain-specific differences is not known.

Methods: 34 infant gut metagenomic samples were simulated with the CAMI-Simulator, using 16S rRNA gene profiles from subjects of the Baby & Mi study as a reference. Raw simulated reads were trimmed, assembled, and binned into metagenome-assembled genomes (MAGs) using mg_workflow, a Snakemake-based pipeline of current metagenomic analysis protocols. Results were compared to gold-standard references in order to benchmark the success of current computational methods in retrieving strain-level MAGs from the gut, and in predicting bacterial carbohydrate active enzymes. Real metagenomic samples from the Baby, Food & Mi cohort were processed through the bfm_mg_flow pipeline to study the taxonomic and metabolic changes in the infant gut microbiome during the solid food introduction period. Post-pipeline analyses were conducted in R.

Results: Misassemblies were significantly impacted by sample community composition, including Shannon diversity, number of strains in the sample, and relative abundance of the most dominant strain. MAG completeness, contamination, quality, and reference coverage were significantly impacted by choice of assembly software, and choice of single- or co-sample assembly. Different assemblies yielded different MAGs from the same samples. Reference coverage of MAGs recovered from co-assemblies were lower than for those from single assemblies and CAZyme predictions were more accurate from MetaSPAdes than from MEGAHIT assemblies at both the assembly-level and the MAG-level. Based on these results, we propose the MetAGenomic PIpelinE (MAGPIE), with recommendations for ensemble methods for assembly, binning, and gene predictions. Using these methods, we identified changes in microbial community composition before and after solid food introduction in real Baby & Mi infant gut samples. These changes included an increase in bacteria that can digest a wide variety of carbohydrates, such as Bacteroides, and a decrease in Bifidobacterium.

Conclusions: In this study, we characterized the current state of tools for genome-resolved metagenomics, and contributed a framework to tailor metagenomic data analysis for the unique composition of the infant gut microbiome. We further used this framework to study bacterial metabolism in the infant gut microbiome before and after the introduction of solid foods.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Solid food introduction to the infant diet brings new glycans to the gut environment, driving the selection of bacteria that are able to digest these compounds.  Studying the gut microbiome during this timepoint is essential to deciphering how and when beneficial bacteria colonize, how they evolve, and how the infant gut matures to an adult-like state. A widely used method to characterize microbial identity and metabolic function in the gut is metagenomic sequencing. However, dominant bacterial genera in the infant gut often have multiple closely related species and strains, making it difficult to decipher the essential metabolic differences between them. In this study, we simulated an infant gut metagenomic dataset to understand how the structure of the infant gut impacts commonly used metagenomic tools, and to quantify the quality of genomes and metabolic predictions at the end of common metagenomic analyses. We found that gut microbial community composition and metagenomic assembler choice both impact the quality of final genomes retrieved from the data, and the accuracy of metabolic gene predictions. Based on these results, we make several recommendations to use ensemble methods to improve metagenomic data analysis, and additionally propose a metagenomic pipeline to analyze infant gut data over the period of solid food introduction.