title: Solid-State NMR Analyses of Molecular Structure and Dynamics in Hydrogen-Bonded Materials

contributor:
Goward, Gillian
Chemistry

subject:
Solid-State Nuclear Magnetic Resonance
Proton Dynamics
Hydrogen Bonding
Boron Coordination Environment
Dipolar Re-Coupling
Proton Conductivity

abstract: This thesis presents analyses of hydrogen-bonded materials using solid-state nuclear magnetic resonance (NMR) spectroscopy. Proton dynamics were investigated in two classes of phosphate-based proton conductors: phosphate solid acids and tin pyrophosphates. These materials have the potential to be used as solid state proton conductors in fuel cells. Proton dynamics in phosphate solid acids were probed based on the attenuation of homonuclear dipolar coupling with increasing temperature. These studies showed that homonuclear dipolar recoupling NMR techniques can be employed in complex multi-spin systems. Additionally, two pathways for proton hopping in monoclinic RbH2PO4, a sample with two proton environments, were identified and quantified for the first time using a combination of dipolar recoupling and proton exchange NMR methods. Tin pyrophosphates, another class of solid-state proton conductor with analogous phosphate tetrahedral structure, were studied. Proton dynamics had to be analyzed via exchange-based NMR techniques as a result of low proton concentration in these materials. Proton mobility in tin pyrophosphate was found to increase with increased protonation. Furthermore, hydrogen bonding was investigated as a coordination mode in silicone boronic acid (SiBA) elastomers, potential materials for contact lens manufacture. As in the phosphate-based proton conductors, hydrogen bonding played an important role in the structure of the SiBA elastomers as one of the mechanisms through which these materials crosslink. In addition to hydrogen bonding, covalent bonding between boronic acids was found to occur at three- and four-coordinate boron centers. The purpose of this study was to determine the influence of boronic acid loading and packing density on crosslinking in SiBA elastomers. Boron coordination environments were investigated by 11B quadrupolar lineshape analysis. The incidence of four-coordinate dative bonding, a predictor of the stress-strain response in these materials, increased with boronic acid loading but was most heavily influenced by boronic acid packing density.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Hydrogen bonds are intermolecular interactions that are significant in many structural (low crystal density in ice) and dynamic (enzymatic processes occurring under biological conditions) processes that are necessary to maintain life. In this thesis, solid-state nuclear magnetic resonance (NMR) spectroscopy is used to explore proton dynamics of hydrogen-bonded networks in various materials. Advanced NMR experiments that probe homo- and heteronuclear dipolar coupling interactions revealed possible pathways for proton transport in phosphate-based proton conducting materials. This study provided a better understanding of ion conducting mechanisms that can be used in intermediate-temperature fuel cell applications. Additionally, solid-state NMR was used in the identification of hydrogen bonding and other coordination modes in silicone boronate acids (SiBA), a class of elastomers with potential applications as contact lens. Boron coordination in SiBA elastomers was dependent on both boronic acid loading and boronic acid packing density.


title: ENGO POLICY INFLUENCE VIA LEGISLATIVE COMMITTEES IN CANADA, THE UNITED STATES, AND RUSSIA

contributor:
Bird, Karen
Political Science

subject:
Comparative Public Policy
Legislative Studies
Non-governmental organizations
Civil society

abstract:
Within the under-populated realm of scholarship on legislative committees, there have been numerous studies which have looked at the ability of legislative committees to achieve policy influence in the wider legislature. However, fewer have examined the ability for non-governmental organizations – particularly those with relative outsider status in the policymaking process – to influence the policy recommendations of committee members.
As environmental non-governmental organizations (ENGOs) have often worked through legislative committees to try to influence policy, this dissertation examines how the characteristics of different legislative institutions work to facilitate or limit influence by representatives of ENGOs. This is done by comparing the interactions of ENGOs with legislative committees in Canada, the United States, and Russia – countries which respectively have parliamentary, presidential, and semi-presidential systems, and hold in common the derivation of a large portion of the country’s GDP from natural resource-based industries.
The central research question for this study asks how the institutional organization of legislative committees affects the ability of ENGOs to achieve influence through engaging the committees, and how other factors interact with this to increase or decrease the potential for ENGO influence. A key finding that emerges out of this line of inquiry is that there is evidence that some conditions for influence in committees cannot be seen as extensions of the wider legislature but can rightly be seen as unique to the committees themselves or as manifesting in unique ways within them.

abstract: Dissertation

abstract: Candidate in Philosophy


title: Describing the Epitopes of Pathogenic Antibodies in Heparin-induced Thrombocytopenia

contributor: Medical Sciences (Blood and Cardiovascular)

subject:
heparin-induced thrombocytopenia
low platelet count disorder
platelet factor 4
pathogenic antibodies

abstract: Heparin is an anticoagulant widely administered to patients undergoing major orthopedic or cardiac surgery. Though heparin is effective at preventing thrombosis, it is paradoxically associated with the development of heparin-induced thrombocytopenia (HIT). HIT is strongly associated with thrombotic complications and is an adverse drug reaction that occurs when heparin binds to the self-protein, platelet factor 4 (PF4) and forms immunogenic multimolecular complexes. As a result, anti-PF4/heparin antibodies are formed, which bind to these complexes, and can cross-linking Fc receptors on platelets and monocytes causing intense platelet activation, thrombocytopenia, and thrombosis. Patients who receive heparin frequently form antibodies against these PF4/heparin complexes; however, most of these antibodies do not cause HIT. Over-diagnosis of HIT is common due to the detection of clinically insignificant non-pathogenic anti-PF4/heparin antibodies. Current enzyme immunoassays (EIAs) cannot distinguish between pathogenic and non-pathogenic anti-PF4/heparin antibodies and will give a false positive result in the presence of the clinically insignificant non-pathogenic anti-PF4/heparin antibodies. Further functional testing is required to identify samples containing the pathogenic anti-PF4/heparin antibodies that will lead to HIT; however, these tests are not readily available in most centres, and delay timely diagnosis. There is little known about the differences between pathogenic and non-pathogenic HIT antibodies. The identification of antigenic determinations of pathogenic HIT antibodies binding to PF4 from this project will have direct implications for patient care. We will be able to accurately and rapidly identify “true” HIT patients from learning more about the pathogenic HIT antibody epitope.

abstract: Dissertation

abstract: Doctor of Science  (PhD)

abstract: At least 30% of patients admitted into the hospital will be exposed to the anticoagulant, heparin. 1-3% of these patients develop heparin-induced thrombocytopenia (HIT): an adverse drug reaction. HIT is a major cause of morbidity and mortality in patients receiving heparin if not diagnosed and treated in a timely manner. HIT occurs when patients form antibodies against the platelet protein, platelet factor 4, in complex with heparin leading to an immune response. However, most heparin-exposed patients produce these antibodies but do not have HIT. Current rapid and available diagnostics tools cannot distinguish between antibodies that can or cannot cause the disease. To improve HIT diagnosis, we will identify the molecular differences between the antibodies that cause HIT and those that do not. From this, we can develop a new diagnostic assay that will be able to dictate whether the antibodies found in patients are specific for HIT.


title: The challenges and opportunities associated with deferred consent in time-sensitive pediatric emergency research: a systematic review

contributor:
Schwartz, Lisa
Parker, Melissa J
Health Research Methodology

abstract:
Introduction
Obtaining informed consent is mandatory to involve human subjects in research. Researchers need to provide adequate information to the participants about the study including risks and benefits associated with the study in simple language so that the participants can comprehend the information. Informed consent has to be obtained from parents/guardians if the participants are children under 18. However, it is not feasible to obtain informed consent from parents/guardians in a time-sensitive pediatric emergency. In such situations, the clinicians may need to start the treatment immediately. The researchers often do not have time to provide adequate information to the parents/guardians to take informed consent. The parents may also not be in the right mental space to comprehend this information. Deferred consent is introduced to conduct studies in time-sensitive medical emergencies. It is also used to conduct studies in time-sensitive pediatric medical emergencies. It allows the researchers to enroll children in the study immediately and take consent as early as the health condition of the children is stabilized. Deferred consent is a new phenomenon in time-sensitive pediatric emergency research and there is a lack of evidence regarding the opportunities and challenges associated with this consent model. This review explored the challenges and opportunities associated with the application of this model in time-sensitive pediatric emergency research.
Methods
Four databases - MEDLINE, EBMASE, CINAHL, and PsycINFO were searched for the articles developing a comprehensive search strategy. The identified articles were deduplicated. The titles and abstracts of these articles were screened, the full-text articles were collected and read for final selection. The selected articles were imported to NVivo 12. These articles were coded using NVivo 12 for thematic analysis of them. The identified themes explored the challenges and opportunities associated with deferred consent.
Results
The children, parents, and practitioners had positive impressions about deferred consent. They thought using deferred consent would allow the practitioners to start the treatment immediately and would give them enough time to discuss research participation later. However, there were some challenging situations for the practitioners to take deferred consent from the parents. It was difficult for them to understand when the appropriate time is to approach the parents for research discussion. The practitioners were also in a dilemma whether they should approach bereaved parents for deferred consent. They also faced ethical dilemma for collecting extra blood for study purposes only. Moreover, it was also challenging for them to address the concerns of the parents about the study.
Conclusion
Deferred consent in time-sensitive pediatric emergency research allows the clinicians to recruit the children immediately and take consent from the parents when their health condition is stable. The children, parents and practitioners had support for differed consent. However, it was challenging for the practitioners to find a suitable time to discuss research with the parents. It was difficult for them to approach the bereaved parents for deferred consent. There was a lack of studies on deferred consent especially studies which explored perspectives of children and bereaved parents on deferred consent. More studies on deferred consent in time-sensitive pediatric emergency research will guide future researchers to overcome their ethical dilemma in this situation and contribute more in pediatric emergency medicine.

abstract: Thesis

abstract: Master of Health Sciences (MSc)


title: Identifying the Signaling Pathways Downstream of the Serotonin Receptor 5A in Breast Cancer

contributor:
Hassell, John A.
Biochemistry

subject:
Breast Cancer
Proteomics
Serotonin
Breast tumor-initiating cells

abstract: Breast cancer therapy resistance and disease recurrence are driven by an infrequent population of stem-like tumor cells, termed breast cancer stem cells or tumor-initiating cells (BTIC). Whereas drugs that target BTIC could be combined with conventional therapies to provide durable remissions, identifying such agents has been difficult. To achieve the latter, our lab screened more than 35,000 compounds for their capacity to reduce the activity of BTIC-enriched mouse mammary tumorspheres, wherein we identified numerous antagonists of multiple serotonin receptors (HTRs). The serotonergic antagonist that prevented sphere formation with the highest potency is a highly selective antagonist of HTR5A, SB-699551. We subsequently demonstrated that this agent affects BTIC activity in breast tumor cell lines representative of all clinical and molecular subtypes of breast cancer. Whereas the primary target of SB-699551 is known, the downstream signaling pathways responsible for its anti-BTIC effect remains enigmatic. The goal of this thesis work was to elucidate the signaling pathways downstream of HTR5A in human breast tumor cell lines. We used a phospho-proteomic approach to establish that treatment of human SB-699551 affects the phosphorylation of proteins involved in the Gi-coupled and the PI3K/AKT/mTOR signaling axes. Moreover, we demonstrated that selective antagonists of PI3K, AKT, and mTOR phenocopied the effect of SB-699551 in tumorsphere forming assays. Taken together, our data suggests that SB-699551 elicits its effect through the PI3K/AKT/mTOR signaling pathways downstream of HTR5A.

abstract: Thesis

abstract: Master of Health Sciences (MSc)

abstract: Accumulating data suggests that the progression of breast cancer is driven by a rare population of breast tumor-initiating cells (BTIC). BTIC lie dormant during conventional therapy and initiate recurrence after such therapies are withdrawn. Hence, there is an urgent need to develop drugs that target BTIC that can be combined with the current standard of care to improve the durability of remission. With the latter objective in mind, our lab previously determined that antagonists of serotonin signaling target BTIC. One of the agents that we identified in our screen inhibits the activity of serotonin receptor 5A (HTR5A). The exact signaling mechanism whereby inhibition of HTR5A leads to a loss in BTIC activity was enigmatic. Hence, this thesis aims to elucidate the signaling pathways downstream of HTR5A in breast cancer. Knowledge of the latter will help identify a plausible mechanism in addition to identifying biomarkers of therapy efficacy.


title: Model Predictive Control for Permanent Magnet Synchronous Motor Drives with Improved Techniques to Minimize Current Ripples

contributor:
Emadi, Ali
Electrical and Computer Engineering

abstract:
Permanent Magnet Synchronous Motor (PMSM) is widely used in many industrial applications such as electric vehicles, industrial robotics and servo machines due to the merits of low volume, light weight, high efficiency, and high power density, etc. Finite Control Set Model Predictive Control (FCSMPC), as an advanced and promising control scheme, has attracted more and more attention in its use for PMSM drives due to its notable advantages like fast dynamic response, the ability of multi-variable control and the flexibility to include multiple constraints. However, the FCSMPC scheme suffers from certain drawbacks of large current ripples, which will lead to unexpected torque ripples and noise in the PMSM drive system. This thesis presents two FCSMPC methods for PMSM drives with improved techniques to minimize the current ripples.
First, an improved FCSMPC with integrated duty cycle and finite virtual voltage vector technique is proposed. The finite control set is expanded by introducing six symmetrically positioned virtual voltage vectors in addition to the six original active voltage vectors while the selected optimal non-zero voltage vector is applied in the regulated proportion of the sampling period according to an efficiently calculated duty ratio. By combining the concept of duty cycle and finite virtual voltage vector in the proposed technique, the control accuracy is distinctly improved while the current ripples are effectively reduced for the FCSMPC-controlled PMSM drives.
Second, an improved FCSMPC with continuous virtual voltage vector technique is proposed. At each sampling interval, the proposed technique applies a continuous virtual voltage vector that is realized by at most two suboptimal basic non-zero voltage vectors and one null voltage vector in proper duty cycle ratios. The continuous virtual voltage vector eliminates the error between the reference current and the actual current at each sampling instant and therefore achieves significant current ripple reduction for the FCSMPC-controlled PMSM drives.
The effectiveness of both proposed techniques is validated with the reference 5 KW IPMSM drives test bench under different conditions. Additionally, to better evaluate the effectiveness of the proposed techniques on reducing the current ripple, two conventional techniques are introduced and implemented with the reference IPMSM drives under the same conditions. It is found in the experimental results that the FCSMPC with the proposed techniques achieve better steady-state performance and much lower current ripples while maintaining similar transient responses as compared to the basic FCSMPC and the FCSMPC with conventional techniques.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Ultimate Limit States in Controlled Rocking Steel Braced Frames

contributor:
Wiebe, Lydell
Civil Engineering

subject:
controlled rocking steel braced frames
self-centering systems
multiple stripes analysis
capacity design
higher-mode effects
conditional spectra
large-scale experimental testing
numerical modelling
incremental dynamic analysis
truncated response spectrum analysis
mean annual frequency of collapse
collapse fragility
equivalent static procedure
floor-to-frame connections
low-damage systems

abstract:
The Insurance Bureau of Canada released a report in 2013 that evaluated the seismic risk of two major metropolitan areas of Canada, with projected losses of $75bn in British Columbia along the Cascadia subduction zone, and $63bn in the east through the Ottawa-Montreal-Quebec corridor. Such reports should prompt researchers and designers alike to rethink the way that seismic design is approached in Canada to develop resilient and sustainable cities for the future. To mitigate the economic losses associated with earthquake damage to buildings in seismically active areas, controlled rocking steel braced frames have been developed as a seismically resilient low-damage lateral-force resisting system. Controlled rocking steel braced frames (CRSBFs) mitigate structural damage during earthquakes through a controlled rocking mechanism, where energy dissipation can be provided at the base of the frame, and pre-stressed tendons pull the frame back to its centred position after rocking. The result is a building for which the residual drifts of the system after an earthquake are essentially zero, and the energy dissipation does not result from structural damage. Design methods for the base rocking joint and the capacity-protected frame members in CRSBFs have been proposed and validated both numerically and experimentally. However, the is no consensus on how to approach the design of the frame members, questions remain regarding how best to design CRSBFs to prevent building collapse, and no experimental work has been done regarding how to connect the CRSBF to the rest of the structure to accommodate the rocking motion.

Because the force limiting mechanism of a CRSBF is rocking only at the base of the frame, the frame member forces are greatly influenced by the higher-mode response, resulting in more complex methods to design the frame members. This thesis begins by outlining two new design procedures for the frame members in controlled rocking steel braced frames that target both simplicity and accuracy.  The first is a dynamic procedure that requires a truncated response spectrum analysis on a model of the frame with modified boundary conditions to consider the rocking behaviour. The second is an equivalent static procedure that does not require any modifications to the elastic frame model, instead using theory-based lateral force distributions to consider the higher modes of the rocking structure. Neither method requires empirical calibration to estimate the forces at the target intensity.

The base rocking joint design is generally in good agreement between the various research programs pioneering the development of the CRSBFs. However, the numerous parameters available to select during the design of the base rocking joint give designers an exceptional amount of control over the performance of the system, and little research is available on how best to select these parameters to target or minimise the probability of collapse for the building. This thesis presents a detailed numerical model to capture collapse of buildings with CRSBFs as their primary lateral force resisting system and uses this model to generate collapse fragility curves for different base rocking joint design parameters. The parameters include the response modification factor, the hysteretic energy dissipation ratio, and the post-tensioning prestress ratio. This work demonstrates that CRSBFs are resilient against collapse, as designing the base rocking joint with response modification factors as large as 30, designing the post-tensioning to prevent yielding at moderate seismic hazard levels, and using zero energy dissipation could lead to designs with acceptable margins of safety against collapse.

While the design procedures are shown to be accurate for estimating the frame member force demand for the targeted intensity level, there is still a high level of uncertainty around what intensity of earthquake a building will experience during its lifespan, and there is no consensus on what intensity should be targeted for design. To address this, the ability of the capacity design procedures to provide a sufficiently low probability of collapse due to excessive frame member buckling and yielding is evaluated and compared to the probability that the building will collapse due to excessive rocking of the frame. The results of the research presented here suggest that the probability of collapse due to either frame member failure or excessive rocking should be evaluated separately, and that targeting the intensity with a 10% probability of exceedance in 50 years is sufficient for the design of the frame members.

Finally, critical to the implementation of CRSBFs in practice is how they may be connected to the rest of the structure to accommodate the uplifting of the CRSBF while rocking under large lateral forces. An experimental program was undertaken to test three proposed connection details to accommodate the relative uplifts and forces. The connections that accommodate the uplifts through sliding performed better than that which accommodated the uplifts though material yielding, but the best way to transfer the forces and accommodate the uplifting without influencing the overall behaviour of the system is to position the connection such that it does not need to undergo large uplifts and carry lateral force simultaneously. A detailed numerical model of the experimental setup is presented and is shown to simulate the important response quantities for each of the tested connections.

Using the results of this work, designers worldwide will be confident to design CRSBFs for structures from the base rocking joint to the selection of floor-to-frame connections for a complete system design while ensuring a safe and resilient building structure for public use and well-being.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Traditional approaches to seismic design of buildings have generally been successful at preventing collapse and protecting the lives of the occupants. However, the buildings are often left severely damaged, often beyond repair. To address these concerns, controlled rocking steel braced frames have been proposed as part of a new construction technique to mitigate or prevent damage to steel buildings during earthquakes, but several aspects of the design and overall safety have yet to be explored or demonstrated. This thesis proposes and validates new tools to design controlled rocking steel braced frames and provides recommendations on how best to design them to achieve a safe probability against collapse. Details are proposed and presented for components to connect the controlled rocking steel braced frames into the rest of the structure. The findings of this thesis will aid practitioners looking to deliver resilient and sustainable structural designs for buildings in our cities of the future.


title: End-to-End Deep Image Matting Platform

contributor:
Chen, Jun
Electrical and Computer Engineering

subject: matting

abstract:
Image matting is a basic feature in most of image quality improvement applications and is considered as a fundamental problem in the computer vision field. In this paper, an End-to-End Image Matting Platform is proposed to segment the foreground and background by creating an alpha matte image.

My end-to-end image matting algorithm is a learning based network which contains two stages. The first stage is to create a tri-map image from an RGB image using segmentation neural network where tri-map images are used to locate the expected foreground objects with rough outlines. The second stage is an image matting neural network, and it takes the outputs from the first stage as prior knowledge to predict precise alpha matte images. With the help of image matting formula and the outputs from the second stage, contents in an RGB image can be easily split into foreground and background. I applied both training and evaluating on Adobe matting benchmark and Car Media 2.0's car oriented image matting dataset, and the outcomes demonstrated the convenience and superior performance of our algorithm compared to existing state of the art methods.

This paper put forward a web platform structure to integrate deep learning algorithms. I applied multiple strategies to enhance the performance of the platform. By using this platform, multiple users can work with different deep learning applications at the same time which dramatically increases the efficiency of the server usage.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Studying development and experience-dependent plasticity of visual cortex: Using modern approaches, animal models and human post-mortem tissue

title: Plasticity in visual cortex

contributor:
Murphy, Kathryn
Neuroscience

abstract:
When the visual system is confronted with adverse early-life experiences, maladaptive
plasticity permits development of poor vision in a disorder called amblyopia. Patch therapy is the
common treatment for amblyopia, by which occluding the good eye manipulates residual
plasticity to improve acuity in the poor eye. Unfortunately patch therapy does not work for
everyone and improvements are often transient. Animal models of amblyopia have highlighted
the neurobiology after the initial insult, but little is known about the response to treatment. Since
synaptic proteins are the interface between neuronal structure and function, it is imperative that
neuroscientists study the amblyopic synaptic proteome to better map intervention strategies in
humans.
In the first part of this thesis I modernize 3 approaches for examining central visual
pathway. First I combine neuroanatomical tracing with modern tissue clearing to examine central
visual pathway connectivity. Next, I improved a manual fractionation protocol for enriching
synaptic protein expression in cortical tissues. Third, I present a series of analytical techniques
for multi-dimensional statistics to interpret protein expression in cortical tissue samples.
In the second part of this thesis I used these techniques to examine a set of commonly
studied synaptic plasticity mechanisms in a cat model of amblyopia. I identified the
neurobiological plasticity phenotype of patch therapy and treatment alternatives. I then examined
expression of 23 synaptic and non-neuronal proteins in post-mortem tissue samples from human
visual cortex across development to identify neuroplasticity states.
These chapters identify options for improved or augmented therapies by identifying the
plasticity phenotypes in animal models of amblyopia, and across human development. Together
these tools identify potential successes and failures of existing behavioural interventions, such as
binocular vision, as well as the causes of suboptimal treatments in human development, such as
early periods of protein heterogeneity.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Impaired visual experience early in life can cause lasting visual deficits in animals and
humans. Even after correcting ocular impairment, poor vision often remains, which suggests
early experience instills lifelong changes in the area of the brain that processes vision, called the
visual cortex. Changes that take place in visual cortex affect the function of cortical cells. Most
of these changes are executed by proteins that sit at the junction between cells. By inflicting
visual impairments in young animals, and examining changes in protein expression in visual
cortex cells, we can relate protein expression to experience-dependent changes. I examined
expression of proteins in visually impaired kittens to investigate why some treatments might be
more effective than others. I also examined protein levels in human brains to investigate why
treatment during certain periods of development produce suboptimal recovery.


title: Investigating the Beverage Patterns of Children and Youth with Obesity at the Time of Enrollment into Canadian Pediatric Weight Management Programs

title: Beverage Intake of Children and Youth with Obesity

contributor:
Morrison, Katherine
Medical Sciences

subject:
Beverages
Pediatric Obesity
Principal Component Analysis
Health Outcomes

abstract:
Introduction: Beverages influence diet quality, however, beverage intake among youth with obesity is not well-described in literature. Dietary pattern analysis can identify how beverages cluster together and enable exploration of population characteristics.
Objectives: 1) Assess the frequency of children and youth with obesity who fail thresholds of: no sugar-sweet beverages (SSB), <1 serving/week of SSB, ≥2 servings/day of milk and factors influencing the likelihood of failing to meet these cut-offs. 2) Derive patterns of beverage intake and examine related social and behavioural factors and health outcomes at entry into Canadian pediatric weight management programs.
Methods: Beverage intake of youth (2–17 years) enrolled in the CANPWR study (n=1425) was reported at baseline visits from 2013-2017. Beverage thresholds identified weekly SSB consumers and approximated Canadian recommendations. The relationship of sociodemographic (income, guardian education, race, household status) and behaviours (eating habits, physical activity, screen time) to the likelihood of failing cut-offs was explored using multivariable logistic regression. Beverage patterns were derived using Principal Component Analysis. Related sociodemographic, behavioural and health outcomes (lipid profile, fasting glucose, HbA1c, liver enzymes) were evaluated with multiple linear regression.
Results: Nearly 80% of youth consumed ≥1 serving/week of SSB. This was more common in males, lower educated families and was related to eating habits and higher screen time. Two-thirds failed to drink ≥2 servings milk/day and were more likely female, demonstrated favourable eating habits and lower screen time. Five beverage patterns were identified: 1) SSB, 2) 1% Milk, 3) 2% Milk, 4) Alternatives, 5) Sports Drinks/Flavoured Milks. Patterns were related to social and lifestyle determinants; the only related health outcome was HDL.
Conclusion: Many children and youth with obesity consumed SSB weekly. Fewer drank milk twice daily. Beverage intake was predicted by sex, socioeconomic status and other behaviours, however most beverage patterns were unrelated to health outcomes.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Beverage intake can influence diet and health outcomes in population-based studies. However, patterns of beverage consumption are not well-described among youth with obesity. This study examined beverage intake and relationships with sociodemographic information, behaviours and health outcomes among youth (2-17 years) at time of entry into Canadian pediatric weight management programs (n=1425). In contrast to current recommendations, 80% of youth consumed ≥1 serving/week of sugar-sweetened beverages and 66% consumed 2 servings/day of milk. Additionally, five distinct patterns of beverage intake were identified using dietary pattern analysis. Social factors (age, sex, socioeconomic status) and behaviours (screen time, eating habits) were related to the risk of failing to meet recommendations and to beverage patterns. Identifying sociodemographic characteristics and behaviours of youth with obesity who fail to meet beverage intakes thresholds and adhere to certain patterns of consumption may provide insight for clinicians to guide youth to improved health in weight management settings.


title: Validating Short Balance Screening Tests for Assessing Fall Risk in People with Chronic Obstructive Pulmonary Disease (COPD)

contributor:
Beauchamp, Marla
Rehabilitation Science

subject: Balance, Falls, COPD

abstract:
Background: People with COPD have significant balance impairments and an increased risk of falls. The psychometric properties of short balance screening tests to inform fall risk assessment in COPD have not been studied.  The objective of this study was to compare the validity of four short balance tests suitable for fall risk screening to identify the most optimal screening tool(s).
Methods: Participants at least 60 years old with COPD attended a single physical assessment with completion of questionnaires. Correlation coefficients were used to describe relationships between the Brief Balance Evaluation Systems Test (Brief BESTest), Single-Leg Stance (SLS), Timed Up and Go (TUG) and Timed Up and Go Dual-Task (TUG-DT) tests, and other measures of balance, measures of muscle strength, exercise tolerance, functional limitation, disability and prognosis. Independent t-tests or Mann-Whitney U tests were used to examine differences between groups with respect to fall risk. Receiver operating characteristic curves were plotted to examine the ability to of the screening tests to identify individuals with previous falls.
Results: Seventy-three participants with COPD completed the study (age 73.0 ± 6.9 years; FEV1 47.0 ± 19.8% predicted). All balance screening tests demonstrated moderate to strong correlations with the Berg Balance Scale (r= 0.47 to 0.80, p<0.05) and Activities-specific Balance Confidence scale (r= 0.44 to 0.61, p<0.05). The Brief BESTest and SLS showed the strongest correlations with other balance measures and demonstrated the most consistent ability to discriminate between fall risk groups. The
 Brief BESTest was the only screening test that identified individuals who reported a previous fall with acceptable accuracy (AUC= 0.7).
Conclusions: The Brief BESTest and SLS show the most promise as balance screening tools for fall risk assessment in older adults with COPD. These results will need to be prospectively confirmed with a larger sample size.

abstract: Thesis

abstract: Master of Science Rehabilitation Science (MSc)


title: Ultrasound as an adjuvant treatment for non-specific neck pain

contributor:
Solomon, Patty
Rehabilitation Science

subject:
ultrasound therapy
non-specific neck pain
systematic review

abstract:
Rationale: The use of ultrasound as an adjuvant to conservative treatment for neck pain is common, but the evidence of its benefit remains unclear.
Objective: To determine the effectiveness of ultrasound as an adjuvant to exercise or/and manual therapy for the improvement of patient-centered outcomes in adults with non-specific neck pain.
Methods: Electronic databases including MEDLINE, EMBASE, AMED, CINAHL, CENTRAL, PEDro and PubMed were searched from date of inception to March 2019 for controlled trials involving ultrasound or phonophoresis as an adjuvant to exercise or/and manual therapy in adults with non-specific neck pain. Review Manager 5.3 was used to calculate mean group differences.
Main results: Six studies (361 participants) examining ultrasound or phonophoresis as an adjuvant to exercise or/and manual therapy for sub-acute and chronic non-specific neck pain were included. The quality of evidence was of very low GRADE. Phonophoresis with capsaicin plus exercise improved pain immediately post-treatment (MD -3.30, 95% CI: -4.05 to -2.55) but not with diclofenac sodium plus exercise as compared to exercise alone. Continuous ultrasound plus exercise improved pain and Pressure Pain Threshold (PPT) at immediate post-treatment (pain: MD -3.42, 95% CI: -4.08 to -2.7; PPT: MD 0.91, 95% CI: 0.68 to 1.14 ) and at intermediate - term (pain: MD -2.70 95% CI: -3.62 to -1.78; PPT: MD 0.27 95% CI: 0.03 to 0.51) as compared to exercise alone. Continuous ultrasound or High Power Pain Threshold (HPPT) ultrasound plus manual therapy and exercise showed no benefit for pain reduction (MD -0.75, 95% CI: -2.08 to 0.58), increase in PPT (MD -1.15, 95% CI: -2.55 to 0.25) or improved function/disability
(MD -1.05, 95% CI: -4.27 to 2.17) at immediate or short-term as compared to manual therapy and exercise.
Conclusion: Based on very low quality evidence, there is insufficient data to support ultrasound or phonophoresis as an adjuvant treatment for non-specific neck pain.

abstract: Thesis

abstract: Ultrasound therapy is widely used with exercise or manual therapy for the treatment of neck pain. Yet, its benefits are not clear. This review looked at the benefits of ultrasound added to exercise, manual therapy or both for the treatment of neck pain. The review contains six studies with 361 participants who suffered from neck pain. The results showed very low quality evidence. Applying capsaicin cream with ultrasound or continuous ultrasound in conjunction with exercise had some benefit for improving pain. The same treatment did not improve function as compared to exercise alone. There was no benefit in improving pain or function by adding continuous or high power ultrasound to manual therapy and exercise compared to manual therapy and exercise alone. Due to very low quality evidence, we are uncertain of whether there is a benefit to adding ultrasound to exercise or/and manual therapy for treatment of neck pain.


title: Proposals for Updating the Canadian Patented Medicine Prices Review Board Pharmaceutical Budget Impact Analysis Guidelines for New Drug Submissions to Public and Private Payers

contributor:
Levine, Mitchell
Health Research Methodology

abstract:
Background: The main objective of this thesis was to provide a proposal for updating the Patented Medicine Prices Review Board (PMPRB) 2007 pharmaceutical budget impact analysis (BIA) guidelines in accordance with the best national and transnational practices in BIA methodology and Canadian stakeholder feedback.

Methods: National, transnational and Canadian federal, provincial and private BIA guidelines were reviewed and recommendations were abstracted. A mixed methods study, consisting of semi-structured interviews and a written survey, was designed for obtaining feedback from Canadian stakeholders on the list of BIA recommendations which were either not included or discussed differently in the PMPRB 2007 BIA guidelines.

Results: Sixteen BIA guidelines were reviewed and discordant recommendations between the PMPRB 2007 BIA guidelines and rest of the reviewed guidelines were identified. The stakeholder analysis included thirty-five participants and showed support for the inclusion of 56% of the proposed recommendations into the guidelines. These recommendations pertained to the use of expert opinions, data extrapolated from the payers’ database, scenario analysis, and dynamic population. Thirty percent of the recommendations, such as off-label indications in the base-case scenario, indirect costs, and cost transfers from other jurisdictions, were not supported by stakeholders. There was no consensus with respect to the inclusion of recommendations for cost offsets or patient adherence. The final proposal is 49% identical with the PMPRB 2007 BIA guidelines. Thirty-six percent of the proposed recommendations (n=26) are new and the remainder (15%; n=11) are modified.

Conclusions: This series of studies has provided sufficient insights to enable the creation of a penultimate version of revised PMPRB BIA guidelines. This penultimate version would be subject to a broader consultation process among stakeholders prior to the adoption of a final revision. Further Canadian stakeholder feedback is required for recommendations where consensus is lacking.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Controlled degradation of low-fouling hydrogels for short- and long-term applications

contributor:
Wylie, Ryan
Chemistry

subject: Hydrogel

subject: Controlled hydrogel degradation

subject: low-fouling hydrogels

subject: bioactive hydrogels

subject: poly(carboxybetaine methacrylamide)

abstract: Degradable low-fouling hydrogels are ideal vehicles for drug and cell delivery. For each application, hydrogel degradation rate must be re-optimized for maximum therapeutic benefit. We developed a method to rapidly tune degradation rates of low-fouling poly(oligo(ethylene glycol) methyl ether methacrylate) (P(EG)xMA) hydrogels by modifying two interdependent variables: (1) base-catalyzed crosslink degradation kinetics, dependent on crosslinker electronics (electron withdrawing groups (EWGs)); and (2) polymer hydration, dependent on the molecular weight (MW) of poly(ethylene glycol) (PEG) pendant groups. By controlling EWG strength and PEG pendant group MW, P(EG)xMA hydrogels were tuned to degrade over 6 to 52 d. A six-member P(EG)xMA copolymer library yielded slow and fast degrading low-fouling hydrogels for short- and long-term delivery applications. The degradation mechanism was also applied to RGD-functionalized poly(carboxybetaine methacrylamide) (PCBMAA) hydrogels to achieve slow (52 d) and fast (13 d) degrading low-fouling, bioactive hydrogels.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The delivery of drugs and cells to disease sites is hindered by transport barriers, which can be overcome through local delivery. Injectable hydrogels can serve as local depots that release drugs or cells to improve therapeutic benefit. Currently, however, hydrogels suffer from uncontrolled degradation in the body, degrading at unpredictable rates dependent on the local environment; hydrogels with predictable and tunable degradation rates are therefore required. Herein, we report a method to produce a library of polymers that in situ crosslink to form hydrogels with a range of degradation rates only influenced by the local environments pH, a known quantity. Moreover, the polymers are low-fouling and therefore have minimal non-specific interactions with biomolecules and cells, which improves biocompatibility.


title: Multiple Access Computation Offloading

contributor:
Davidson, Timothy N.
Electrical and Computer Engineering

subject:
multiple access
computation offloading
resource allocation
mobile edge computing

abstract:
The limited energy and computational resources in small-scale smart devices impede the expansion of the range of applications that those devices can support, especially to applications with tight latency constraints. Mobile edge computing is a promising framework that provides shared computational resources in the access points in the network and provides devices in that network with the opportunity to offload (a portion of) their computational tasks to the access points. To effectively capture that opportunity in an offloading system with multiple devices, the available communication and computation resources must be efficiently allocated. The main focus of this thesis is on the optimal allocation of communication resources in a K-user offloading system. The resource allocation problem that is considered in this thesis captures minimizing the total energy consumption of users while the requirements of the users, and their computational tasks, are met. That problem is addressed for two of the most widely-considered classes of computational tasks in the literature, namely, indivisible tasks (binary offloading) and divisible tasks (partial offloading).
This thesis begins with an exploration of the impact of the choice of multiple access scheme that is employed by the system on the total energy consumption of the users. In particular, the problem of minimizing the total energy consumption of a two-user
binary offloading system is tackled under various multiple access schemes, namely time division multiple access (TDMA), sequential decoding without time sharing, independent decoding, and multiple access schemes that can exploit the full capabilities of the channel, which are referred to as full multiple access schemes (FullMA) in this thesis. Using a decomposition-based approach, closed-form solutions to the resource allocation problem are obtained. Those expressions show that by exploiting the full capabilities of the channel, a FullMA scheme can significantly reduce the total energy consumption of the users as compared to the other schemes. The closed-form expressions also show that when the channel gains of the two users are equal, the TDMA scheme can achieve the optimal energy consumption. For the case of partial offloading, an analogous analysis leads to a reduced-dimension design problem and an extension to the optimally result for TDMA. In the next step of the development, the insights obtained from the decomposition-based analysis of the two-user case are used to tackle the communication resource allocation problem for a K-user offloading system in which the users are assumed to be served over a single time slot. Based on their performance in the two-user case, FullMA and TDMA schemes are considered. The mixed-integer optimization problem that arises in the binary offloading case is addressed by employing a decomposition approach with a closed-form expression obtained for the optimal resource allocation for given offloading decisions, and a tailored pruned greedy search algorithm developed herein for the offloading decisions. By exploiting the maximum allowable latency of each individual user, the proposed algorithm is able to significantly reduce the energy consumption of the users in comparison to the existing algorithms in the literature that assume equal latency constraints for all users. Furthermore, with the closed-form optimal solution to the resource allocation problem obtained for given offloading decisions, the proposed algorithm has a significantly lower computational cost compared to the existing algorithms. In the partial offloading case, a quasi-closed- form solution is obtained for the resource allocation problem.
Finally, a time-slotted signalling structure is proposed as an optimal transmission structure for a generic K-user offloading system. Furthermore, an optimal times-lotted structure that requires only K time slots is developed for a K-user offloading system that employs a FullMA scheme. The proposed time-slotted structure not only exploits the maximum latency constraint of each user, it also exploits the differences between the latency constraints of the users by taking advantage of the interference reduction that arises when a user finishes offloading. The proposed time-slotted FullMA signalling structure significantly reduces the energy consumption of the users compared to some existing methods that employ the TDMA scheme, and compared to those with FullMA, but sub-optimal single-time-slot signalling structures. Moreover, the computational cost of the proposed time-slotted algorithm is significantly lower than that of the existing algorithms in the literature.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: The rapid increase in the number of smart devices in wireless communication networks, and the expansion in the range of computationally-intensive and latency sensitive applications that those devices are required to support, have highlighted their resource limitations in terms of energy, power, central processing unit (CPU), and memory. Mobile edge computing is a framework that provides shared computational resources at the access points of wireless networks and gives such devices the opportunity to offload (a portion of) their applications to be executed at the access points. In order to fully exploit such an opportunity when multiple devices seek to offload  their applications, the available communication and computation resources must be efficiently allocated amongst those devices. The ultimate goal of this thesis is to obtain the optimal communication resource allocation in a K-user offloading system while different constraints on the devices and on the applications are satis ed. To that end, this thesis shows that the minimum energy consumption is obtained when the system exploits the full capabilities of the channel, the maximum allowable latency of each user, and the differences between the latency constraints of each user. Accordingly, this thesis proposes an optimized signalling structure and, based on that structure, low-complexity algorithms that achieve an energy-optimal resource allocation in a K-user offloading system.


title: Colloidal Fabrication Techniques for the Development of Supercapacitor Electrodes and Devices

contributor:
Puri, Ishwar K
Zhitomirsky, Igor
Mechanical Engineering

abstract:
In this thesis, an advanced colloidal fabrication technique, called particle extraction through liquid-liquid interface (PELLI), has been developed to fabricate components of positive and negative electrodes of electrochemical capacitors (ECs). This new colloidal strategy is applied to create stable suspensions for the electrophoretic deposition (EPD) of thin films and advanced inks for screen printing applications.
Bottom-up and top-down PELLI strategies were developed to extract MnO2 particles synthesized in an aqueous phase to the organic phases of 1-butanol and dichloromethane, respectively. During both extraction processes, hexadecylamine with amine functional group was used as the extractor for transferring the MnO2 particles. Compared to the top-down PELLI technique, the bottom-up PELLI synthesized particles of relatively small sizes, which is beneficial for fabricating MnO2-multiwalled carbon nanotube (MWCNT) binary composite EC electrodes with enhanced electrochemical performance. Hence, the subsequent work was carried out using the bottom-up strategy for PELLI.
Head-tail extractors with a single functional group, such as carboxylic acid and phosphonate, and head-tail-head (HTH) multifunctional extractors with functional groups of both carboxylic acid and phosphonate were used as the vehicles for transferring MnO2 from the synthesis media to the device processing media to achieve a good suspension of MnO2-MWCNT to fabricate positive EC electrodes. Advanced FeOOH-MWCNT negative electrodes were also prepared by PELLI strategies using HT and HTH extractors. The experimental results showed that both positive and negative electrodes prepared by HTH extractors exhibit the highest electrochemical performance. Moreover, stable suspensions of MnO2 particles synthesized by PELLI with multifunctional HTH extractors were prepared to fabricate advanced thin films by EPD and also MnO2-carbon black printing inks for screen printing of thin EC electrodes.
Subsequently, to fabricate efficient polypyrrole (PPy) based composite negative electrodes, for the first time, non-agglomerated FeOOH particles were prepared with PELLI using tetradecylamine as extractor. Introduction of PPy enhances the electrochemical performance of the binary composite of PPy coated MWCNT in a potential range of -0.8 - +0.1V. Advanced asymmetric ECs devices with MnO2-MWCNT positive electrodes and PPy-FeOOH-MWCNT negative electrodes were fabricated. These devices with comparable capacitance for both the positive and negative electrodes and high active mass loading were found to have high electrochemical performance in a wide working voltage window of 1.6V in aqueous electrolyte.

abstract: Thesis

abstract: Doctor of Engineering (DEng)


title: Inferred Response Properties of the Synaptic Inputs Underlying Duration-Tuned Neurons in the Big Brown Bat

title: Response Properties of Inputs to Duration-Tuned Neurons

contributor:
Faure, Paul A.
Bruce, Ian
Bennet, Patrick J.
Deda, Gillespie
Psychology

subject: Auditory Physiology

subject: Temporal Processing

subject: Inferior Colliculus

subject: Electrophysiology

subject: Hearing

subject: Duration Tuning

subject: Neuroscience

subject: Big Brown Bat

subject: Excitatory/Inhibitory Frequency Response Area

subject: Level Tolerance

subject: Rate-Level Function

subject: Suppression-Level Function

subject: Facilitation

abstract: Duration tuning in the mammalian inferior colliculus (IC) is created by the interaction of excitatory and inhibitory synaptic inputs. We used extracellular recording and paired-tone stimulation to measure the strength and time-course of the contralateral inhibition and offset-evoked excitation underlying duration-tuned neurons (DTNs) in the IC of the awake bat. The onset time of a short, best duration (BD), excitatory probe tone was varied relative to the onset of a longer-duration, non-excitatory (NE) suppressor tone. Spikes evoked by the roving BD tone were suppressed or facilitated when the stationary NE tone was varied in frequency or amplitude. When the NE tone frequency was presented away from the cell’s best excitatory frequency (BEF) or at lower SPLs, the onset of inhibition was relatively constant whereas the offset and duration of inhibition decreased. Excitatory and inhibitory frequency response areas were measured and best inhibitory frequencies matched best excitatory frequencies; however, inhibitory bandwidths were broader than excitatory bandwidths. Excitatory rate-level and inhibitory suppression-level functions were also measured and the dynamic ranges and inflection points were similar, which is hypothesized to play a role in the level tolerance of responses measured from DTNs. We compared the latency of offset-locked facilitation to the onset or offset of inhibition as a function of frequency and amplitude; we found that the facilitation was more related to the onset of inhibition. Moreover, facilitation typically preceded the offset of inhibition – suggesting that it is a separate excitatory input to DTNs and not a rebound from inhibition. We conclude that DTNs receive inputs that generate and preserve temporal selectivity.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Investigating the Extracellular Matrix in Pulmonary Fibrosis

title: INVESTIGATING THE EXTRACELLULAR MATRIX’S ROLE IN PULMONARY FIBROSIS TO APPROPRIATELY MODEL DISEASE AND TEST ANTIFIBROTIC THERAPIES

contributor:
Kolb, Martin
Medical Sciences

subject:
Extracellular Matrix
Idiopathic pulmonary fibrosis

abstract:
IPF is a progressive disease, characterized by dysregulated fibrosis of the extracellular matrix (ECM). The pathobiology of the disease is still unknown, and the median survival post-diagnosis is about 3-5 years. The two current US FDA approved drugs for IPF (nintedanib and pirfenidone) slow, but fail to reverse, disease progression.
There is cumulating research that suggests the ECM is an active player in fibrosis. In this thesis, we summarized the current knowledge of ECM-cell interactions in the context of pulmonary fibrosis. To gain more mechanistic insight into the ECM characteristics that dictate cell behavior, we established a 3D ECM ex vivo system to assess the nonfibrotic and fibrotic ECM’s effect on fibroblasts. The ECM appears to promote both pathological and physiological cellular changes, depending on its structural and compositional properties. We also used this 3D ex vivo system as a preclinical tool to test the effect of directly inhibiting mechanotransduction in the fibrotic ECM – fibroblast profibrotic relationship. Lastly, since the fibrotic ECM seems to play a key role in progressive fibrosis, we evaluate if researchers are appropriately using the bleomycin model by starting interventions after ECM fibrosis is established. Over the past decade in the field, there has been an overall improvement in the appropriate therapeutic timing. In the preventative studies, however, there is still an inadequate characterization of inflammation. There is also poor transparency of preclinical-bleomycin data for clinically tested interventions for IPF. Addressing these shortcomings may improve the utility of the model at predicting an intervention’s success in clinical trials.
These findings illustrate the ECM’s role in driving pulmonary fibrosis. Therefore, the ECM should be further investigated to understand disease progression, and reproduced in preclinical models to test interventions. This will improve the transition of pathobiological findings into efficient drug development for this devastating disease.

abstract: Thesis

abstract: Candidate in Philosophy

abstract: Idiopathic pulmonary fibrosis (IPF) (idiopathic - unknown cause; pulmonary - lungs; fibrosis - scarring) is characterized by progressive scarring of the lung extracellular matrix (ECM). The ECM is an organ’s backbone that provides structural and biochemical support to surrounding cells. Continued ECM scarring can lead to difficulty breathing, cough, and ultimately death. The cause of IPF is unknown, however, studies suggest that the scarred ECM can promote further scarring, and cause disease progression. In this thesis, we summarized the current knowledge of how the ECM interacts with cells. Using a 3D model we see that depending on the ECM’s structure and composition, it can promote both disease and healthy cellular changes. Lastly, we evaluate if researchers are appropriately using the bleomycin model (most common preclinical model for pulmonary fibrosis) by testing interventions after ECM fibrosis is established. We propose changes to improve its usefulness as a preclinical tool for IPF.


title: Nanocarbon Based Chemiresistive Water Quality Sensors

contributor:
Kruse, Peter
Chemistry and Chemical Biology

subject:
water quality
chemiresistive
sensor
copper
chlorine
nanocarbon
graphene

abstract: Failure to monitor the quality of drinking water can have devastating consequences. The development and implementation of sensing technology can be a crucial aspect of water quality control strategies. Chemiresistive sensors can be installed at any point of the distribution system and can provide real-time data on the levels of different water quality parameters. These sensors work by detecting changes in the conducting properties of a transducing element, induced by interactions with the analyte. Nanocarbon films have attracted interest as possible transducing materials because of their similarities to graphene, a two-dimensional material known for its exceptional electron transport properties. This thesis explores the fabrication and sensing performance of few layer graphene (FLG) and graphene-like carbon (GLC) films. The FLG sensors were used to detect copper ions in water, while the GLC sensors were used to monitor the concentration of free chlorine. The films were functionalized to improve selectivity and showed noticeable changes in their conducting properties as a result of charge transfer between them and the analyte. These changes were quantified by probing the sensors with a constant voltage and they were found to be dependent on the concentration of the analyte over a wide dynamic range. Overall, the work presented in this thesis suggests that, by tuning the selectivity of the films, nanocarbon based chemiresistive sensors can be a universal solution to water quality monitoring.

abstract: Thesis

abstract: Master of Science (MSc)


title: On the Use of Simulation and Assessment in Surgical Training

contributor:
Sonnadara, Ranil
Psychology

subject:
Education
Simulation
Assessment
Surgical training
Boot camp

abstract:
The transition from medical school to residency is often considered the most difficult year for both teachers and learners. Learners report feeling underprepared, and some researchers have identified a decrease in patient safety during the first month of residency. These factors suggest learners could be better supported during this transition period. Previous research demonstrates that boot camps (BCs) at the onset of residency can improve learners’ confidence, knowledge, and some technical skills. However, little information has been published on how those BCs were developed and implemented, why BCs only improve some skills and not others, or the long-term impacts of BC programs.
We used a Context, Input, Process, and Product program evaluation framework to develop, implement, and evaluate a simulation-based BC for novice surgical trainees that was aligned with the recent shift towards competency-based models of medical education. Next, we used a Convergent Parallel Mixed Methods approach to explore the longer-term impacts of the BC program. Lastly, we explored how effectively the Objective Structured Clinical Examination (OSCE), a “gold standard” measure of learner competence that was used in the BC program, truly captures clinical performance of novice trainees.
This work demonstrates that incorporating a BC at the onset of residency can improve residents’ confidence and skill for up to two years into training, although adherence to sound pedagogical principles is critical. The BC also provided residents with the opportunity to participate in role clarification, acculturation, and social integration. Finally, we demonstrate that OSCEs may not always be the best way to measure BC effectiveness.
The data presented in this thesis will provide educators with new insights on how to create and evaluate successful BC programs to support learners through the transition to residency; highlight new approaches for evaluating educational initiatives; and prompt a conversation about how assessment is being used in medical education.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: From day one, new doctors are expected to adapt to new training environments, manage increased workloads, and make decisions about patient care, while working longer hours, and with less support than they had as medical students. As such, research suggests that new doctors often feel underprepared and stressed when entering residency. Furthermore, the ‘July Effect’, which suggests that fatal medical errors rise by 10% in the first month of residency compared with all other months, suggests that something needs to change. In this thesis, we sought to improve the way that surgical training programs approach the transition into residency, and look at the long-term impacts of these changes. Through three interrelated studies, we provide educators with information on how to develop, implement, and evaluate a simulation-based boot camp for new doctors; highlight new approaches for evaluating educational initiatives; and revisit how assessment is being used in medical education.


title: Development of a Lensless Point-of-Care Device for Urine Analysis

contributor:
Fang, Qiyin
Biomedical Engineering

abstract:
Clinical urine tests are valuable diagnostic tools for short and long-term patient care, however current detection techniques are time consuming and expensive. The turnaround time for samples tested for urinary tract infections is ~48 hours and 70% of samples are negative. Similarly, Trichomoniasis, a sexually transmitted infection caused by a vaginal pathogen, is misdiagnosed in clinical practice as symptoms are often similar to other conditions and conventional diagnostic tests are not readily available. Quick and accurate diagnosis of urologic and renal conditions is critical to their cost-effective management.
This dissertation focuses on the design, fabrication, and implementation of a lensless shadow imaging microscope for urine analysis. The device tested polystyrene beads, Baker’s yeast, bacteria, whole blood, Trichomoniasis vaginalis, and urine samples. Unique and identifiable features were found for each component. To our knowledge, this is the first known report of lensless imaging for urine analysis. In particular, our device demonstrated effective detection of parasites directly in urine samples without the need for concentration or culture. With appropriate adaptations this platform can be developed to detect small particles in urine and contribute to patient diagnosis.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: One Hundred Words for Conquest: Curating Arctic Sovereignty at the Winnipeg Art Gallery

contributor:
Dean, Amber
English and Cultural Studies

subject:
arctic sovereignty
Inuit art
critical museum studies
recognition politics

abstract: This dissertation examines a series of catalogues for Inuit art exhibitions held at the Winnipeg Art Gallery (WAG), spanning from 1967 to 2017. I argue that the discursive conventions of settler-Canadian art appreciation, especially those geared towards Inuit creative production, have resonances with the political strategies that Canada uses to prove effective occupation—a term from international law—of the Arctic. My work intervenes in this context by showing how art appreciation encourages modes of effective occupation that are not obviously political, insofar as these modes operate in the realm of affect. I first develop a critical framework inspired by Glen Coulthard’s concept of colonial recognition politics, to demonstrate that there is an affirmative recognition politics at work in the WAG catalogues. I then theorize that catalogues’ tendency to oscillate between an ethnographic (contextualist) analysis and an aesthetic (non-contextualist) analysis produces a tension that orients patrons towards the North accordance with Canada’s position on Arctic geopolitics. Building on the work of Eva Mackey, I argue that a mixed ethnographic-aesthetic view of Inuit art activates a particularly expedient form of belonging from afar in settler patron-readers, whereby they are encouraged to feel as if they are of the North, while never having to be there. My third chapter attends to how the WAG narrates the dramatic social transformations that Inuit experienced in the mid-20th century. The catalogues implicitly invalidate many Inuit’s experience of settler-colonial intervention by suggesting that the move to sedentary communities, often at the hands of the settler state, was inevitable and even desirable. This work provides strategies for critiquing instances of settler benevolence that are unique to the art world, and offers a template for how to approach exhibition catalogues as a genre—both of which are areas of scholarship that have been hitherto neglected.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: In this dissertation, I look at a series of catalogues for Inuit art exhibitions held at the Winnipeg Art Gallery (WAG), spanning from 1967 to 2017. I argue that the discursive conventions of settler-Canadian art appreciation, especially those geared towards Inuit creative production, have resonances with the political strategies that Canada uses to prove effective occupation—a term from international law—of the Arctic. My research intervenes in this context by showing how art appreciation encourages modes of effective occupation that are not obviously political, insofar as these modes operate in the realm of affect. The resulting work models some strategies for critiquing forms of settler benevolence that are unique to the art world, and offers a template for how to approach exhibition catalogues as a genre—both of which are underdeveloped areas of scholarship.


title: Synthesis and Evaluation of Multimodal Near-Infrared/Technetium-99m Probes for Imaging Cancer and Bone Injury

contributor:
Valliant, John F.
Chemical Biology

abstract:
To address the need for better technologies for imaging disease, new strategies for the synthesis of nuclear, optical and photoacoustic (PA) multi-modal probes were developed. Initially, a library of phenyl-1H-imidazo-[4,5]-f-1,10-phenanthroline (PIP) ligands were synthesized to create isostructural optical and nuclear probes. The 99mTc complexes of the ligands were prepared in high yield and showed excellent stability in vitro. Biodistribution studies were completed where the lipophilic Tc(I) complexes had significant retention in the liver, lung, and spleen.
To overcome this, a second-generation was created. Specifically, a polar cyanine dye, IR783, was linked to a PIP ligand (IR783-PIP) to reduce non-specific binding and enhance blood half-life via albumin binding. An added benefit of using IR783 is that it enabled photoacoustic (PA) imaging to be used in place of optical imaging. In vitro testing showed that it was possible to separate the PA signal of IR783-PIP from oxy- and deoxyhemoglobin. Radiolabelling of the IR783-PIP ligand with 99mTc was also achieved in 41 % yield.
Because it proved difficult to target IR783-PIP, a tetrazine derived cyanine dye was prepared creating the opportunity to link the PA agent to trans-cyclooctene (TCO) modified targeting molecules. IR783-HYNIC-Tz was prepared in 2 steps in high yield through a hydrazine-based coupling strategy. The bifunctional dye bound albumin and its PA signal was separable from the signals arising in blood. In vivo studies in osteosarcoma and glioblastoma multiforme tumour models were performed where images showed clear tumour uptake. For targeting, IR783-HYNIC-Tz was used in combination with a TCO-derived bisphosphonate for imaging calcium accretion in knee and shoulder joints. The conjugate was also labelled with 99mTc which verified uptake in the joints (3-5% injected dose per gram) out to 24 hours. Lastly, the IR783-HYNIC-Tz dye was employed to tag TCO-derived gas vesicles to create a new generation of PA/ultrasound imaging agents.
Overall, the strategies reported are platforms for the creation of targeted multimodal probes. They are designed to exploit biorthogonal reactions and can therefore be utilized with a wide range of targeting molecules.

abstract: Thesis

abstract: Doctor of Science  (PhD)

abstract: New and general-purpose methods for creating molecular imaging probes for cancer and bone injury were developed and studied. The approach combines medical isotopes, which can be used to image the whole body of patients, and photoacoustic or luminescent molecules which allow for high resolution imaging of sites of disease identified by the former. More specifically, two novel near-infrared dyes were created which utilize a reaction that allows them to be linked to targeting molecules specific to bone injury. The ability of these new molecules to bind albumin and to localize in tumours through the enhanced permeability and retention effect was demonstrated. One key platform that was developed proved to be particularly effective over several disease models and has significant potential for creating new molecular imaging probes to improve patient care.


title: EFFECTS OF PEER SOCIAL SUPPORT ON EFFICACY PERCEPTIONS AND PHYSICAL PERFORMANCE IN YOUTH

contributor:
Bray, Steven R.
Kinesiology

abstract: Social interactions contribute to psychosocial and physical outcomes in youth sport and physical activity settings. Social interactions (e.g., peer social support) are theorized to inform relation-inferred self-efficacy (RISE) and, in turn, influence self-efficacy. When performing tasks that require high physical demand, prior cognitive exertion leads to decreases in self-efficacy and physical performance. The primary purpose of this study was to examine the effect of peer social support on RISE, task self-efficacy, and physical endurance performance in youth, and to explore intermediary pathways between these variables. The secondary purpose was to examine motor coordination as a moderating variable. Youth (N = 84, Mage = 10.43  1.26) were randomly assigned to dyads and, subsequently, to either a peer social support group or a control group. All participants completed two endurance handgrip squeezes at 30% of their maximal voluntary contraction force separated by a cognitively demanding task (Stroop task). In the peer social support group, participants exchanged supportive words of encouragement prior to the second endurance handgrip squeeze, while those in the control group performed the task without prior interaction with their partner. Participants in the peer social support condition reported higher RISE (d = 0.86, p < .001) and greater improvements in physical endurance performance (d = 0.58, p < .01) compared to the control group; however, differences in task self-efficacy were non-significant (d = 0.26, p = .24). Contrary to hypotheses, there was no indirect effect of peer social support on endurance performance change through RISE and self-efficacy. In addition, there was no evidence of a moderating effect of motor coordination. Although, the mechanisms through which peer social support positively impact physical performance remain unclear, results suggest providing peer social support prior to a challenging physical task is associated with more positive RISE perceptions and improved physical performance.

abstract: Thesis

abstract: Master of Science (MSc)


title: Harnessing Optochemical Waves in Polymers: From Beam Interactions to Inscription of Prismatic Elements

contributor:
Saravanamuttu, Kalaichelvi
Vargas-Baca, Ignacio
Chemistry and Chemical Biology

subject:
Nonlinear waves
Photochemistry
Waveguides
Self-trapping
Optics
Soliton interactions

abstract:
The nonlinear propagation of a visible, continuous wave laser beam was studied in three types of polymer systems that harness photochemical reactions: (i) a photopolymerization to create permanent self-written structures, (ii) a photo-oxidation hosted within a polymer matrix and (iii) a reversible photoisomerization that triggers the contraction of a photoresponsive hydrogel. The process of self-trapping was characterized by monitoring the spatial intensity profiles over time. The mechanism of each material was determined with a series of control experiments in order to confirm the nature of the nonlinear response, including their reversibility and intensity-dependence.
These observations led to the study of interactions between self-trapped beams. Two beams under linear conditions will pass through one another, but two beams travelling in a nonlinear medium will interact and influence one another. The interactions of two beams introduced into the aforementioned photochemical systems were investigated and revealed a rich diversity of phenomena including: (i) the attraction between beams, (ii) merging of beams into a single waveguide, (iii) nonlocal attraction between beams, (iv) orbiting of beams, (v) switching of beam positions, and (vi) inhibition of the self-trapping of a neighbouring beam. Each observation is dependent on a detailed understanding of the underlying mechanism of refractive index change. Numerical simulations supplement some of these experiments and provide further evidence for the nonlinear mechanisms. The formation of permanent self-written structures with these nonlinear waves offers the opportunity to create seamless 3D printed materials with prismatic geometries. Several macroscopic objects were constructed using nonlinear waves from incoherent LEDs and amplitude masks. Decomposition of 3D objects into prismatic elements was carried out using an algorithm that breaks an object into individual pieces. Using a multi-step printing process, several prismatic elements can be combined to form a target object. The results of these experimental and theoretical studies improve upon the current understanding of the dynamics of nonlinear light propagation in photochemical systems. These insights may allow us to harness other nonlinear effects and develop new materials for applications such as optical communication, computing and 3D printing.

abstract: Thesis

abstract: Doctor of Science  (PhD)

abstract: The nonlinear propagation of a visible, continuous wave laser beam was studied in three types of polymer systems that harness photochemical reactions: (i) a photopolymerization to create permanent self-written structures, (ii) a photo-oxidation hosted within a polymer matrix and (iii) a reversible photoisomerization that triggers the contraction of a photoresponsive hydrogel. Photochemical changes to the material lead to self-induced light-guiding structures that influence the behaviour of light. These self-trapped beams can interact with one another inside of a nonlinear medium, giving rise to a rich diversity of phenomena including: (i) the attraction between beams, (ii) merging of beams into a single waveguide, (iii) nonlocal attraction between beams, (iv) orbiting of beams, (v) switching of beam positions, and (vi) inhibition of the self-trapping of a neighbouring beam. Each observation is dependent on a detailed understanding of the underlying mechanism of refractive index change. Numerical simulations supplement some of these experiments and provide further evidence for the nonlinear mechanisms. The formation of permanent self-written structures with these nonlinear waves offers the opportunity to create seamless 3D printed materials with prismatic geometries. Several macroscopic objects were constructed using nonlinear waves from incoherent LEDs and amplitude masks. Decomposition of 3D objects into prismatic elements was carried out using an algorithm that breaks an object into individual pieces. Using a multi-step printing process, several prismatic elements can be combined to form a target object. The results of these experimental and theoretical studies improve upon the current understanding of the dynamics of nonlinear light propagation in photochemical systems. These insights may allow us to harness other nonlinear effects and develop new materials for applications such as optical communication, computing and 3D printing.


title: Dendrimers for Imaging and Molecular Sieving

contributor:
Adronov, Alex
Chemistry and Chemical Biology

subject:
Polymer Chemistry
Dendrimers
Bis-MPA
Nuclear Imaging
PEGylation
Polymer-Protein Conjugates

abstract:
The Enhanced Permeability and Retention (EPR) effect has seen considerable exploration by many researchers since it’s discovery by Maeda et al in 1985. Polymers and nanoparticles with a long blood residence half-life can accumulate in some tumour tissues, allowing for the delivery of either diagnostic or therapeutic payloads.
We have contributed to this field by the development of methodology to prepare radiolabeled dendrimers which are suitable for EPR effect accumulation with a variety of peripheral functionalities. The first of these was a 99mTc-labeled fifth generation dendron which was peripherally functionalized with low molecular weight poly(ethylene glycol) chains, which was observed to accumulate in xenograft mouse tumours over the course of 6 hours. This work led to the development of improved synthetic means for the preparation of high generation dendrimers with complex peripheral functionality, which hinged on the use of the Strain Promoted Alkyne-Azide Cycloaddition reaction to give high generation dendrimers by a convergent approach. This resulted in the facile preparation of dendrimers with challenging peripheral functionality in reaction times as short as 5 minutes. This SPAAC based convergent synthesis approach was used to prepare 99mTc labeled sulfobetaine and carboxybetaine dendrons of the sixth generation, and these compounds were found to have a size greater than the renal clearance threshold of ~ 5 nm, though it was found that labeling with [99mTc(CO)3]+ was not possible without extensive degradation of the zwitterionic dendrimers.  Finally, the dendritic architecture explored for imaging was adapted for use in shielding an enzyme from macromolecules while retaining activity against the native small molecule substrate, and we found that conjugation of high-generation bis-MPA dendrons to α-chymotrypsin was an effective way to eliminate enzyme activity against macromolecules while preserving efficacy against small substrates, indicating this approach may be an effective way to shield proteins from the immune system without interfering with their desired function.
This work illustrates the ability to radiolabel polyester dendrimers for tumour imaging through the EPR effect. In addition, it has demonstrated that polymer architecture has a large impact on the properties of polymer-protein conjugates and gives evidence of unique properties that are imparted by the conjugation of high-generation dendrimers onto a protein.

abstract: Thesis

abstract: Doctor of Science  (PhD)


title: In vivo detection of retained gadolinium in bone by x-ray fluorescence following administration of gadolinium-based contrast agents used in MRI

contributor:
McNeill, Fiona
Chettle, David
Medical Physics

subject:
MRI
bone
gadolinium contrast
retention
x-ray fluorescence

abstract:
Gadolinium-based contrast agents (GBCAs) have been used in hospitals worldwide for the past three decades to increase contrast for magnetic resonance imaging (MRI), thus allowing for more accurate diagnoses. When first developed, GBCA complexes were thought to be completely stable, and excreted from the body within hours. However, GBCAs have since been shown to deposit in organs such as bone, suggesting complex dissociation. GBCA safety has now become one of the biggest concerns in the field of radiology, with the clinical implications of retained Gd remaining unknown. A non-invasive technique to measure retained Gd in the body would allow for investigation of the potential negative health effects of GBCAs.
In this thesis, the technique of x-ray fluorescence (XRF) to detect retained gadolinium (Gd) in bone following the administration of GBCAs is investigated. The research employs a series of bone phantom measurements to determine the feasibility of using an XRF-based detection system to perform non-invasive in vivo measurements of Gd in human tibia bones. Minimum detection limits (MDLs) of the XRF detection system are calculated to assess the feasibility of performing a human measurement in a realistic time. Through these experiments, the XRF detection system developed in this thesis work is deemed feasible for human measurements of Gd in bone.
The second half of this thesis work involves performing the first non-invasive measurements of Gd in bone in a small population: 11 exposed individuals who had previously received GBCA, and 11 controls. The result of this work is promising, as the XRF system is successful in measuring Gd in bone in vivo. Additionally, the Gd bone concentration of the exposed group is significantly higher than the control group. Following this small pilot study, additional measurements are conducted on individuals self-reporting symptoms of Gd toxicity. Gd concentrations in bone and urine are compared for three groups: symptomatic exposed, non symptomatic exposed, and control. The concentration of Gd in bone and urine for the symptomatic exposed group is significantly higher. However, there is no correlation between the amount of Gd in bone and urine, suggesting a secondary storage site for Gd in the body, other than bone.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Outcomes after Postoperative ICU Admission in the Elderly in France: A Population-Based Cohort Study

contributor:
Le Manach, Yannick
Health Research Methodology

subject: postoperative; ICU; France; SAPS II

abstract:
Postoperative ICU admission is afforded to patients with high clinical severity, but the benefits and harms of such an endeavour are debateable. The purpose of my thesis was to further understand a) the type of patients being admitted to ICU, b) the role of age in ICU admission, and c) the association (if any) between ICU admission and subsequent mortality and complications.
The thesis consists of 4 chapters. Chapter I provides a brief introduction of the topic and the rationale behind the researched questions. Chapter II examines the association between chronological age and ICU admission in postoperative patients. This analysis sheds light on one of the 17 variables included in the score (i.e. age), which drives the clinical severity score in parts of the population. Chapter III uses a propensity score model to match patients that were admitted to ICU and those that were not based on several pretreatment variables, to assess the impact ICU admission has on postoperative mortality and complications. Finally, Chapter IV reflects the conclusions of the thesis and suggests further research agendas.
Overall, these three thesis components will illustrate the role of ICU admission in an adult postoperative population as well as its consequences in comparison to those not admitted to an ICU.

abstract: Thesis

abstract: Master of Science (MSc)


title: Biofunctional Lubricant-Infused Surfaces for Medical Implants

contributor:
Didar, Tohid F.
Biomedical Engineering

abstract:
Device-associated clot formation and poor targeted cell-adhesion are ongoing problems in permanent blood-contacting medical implants. The recent concept of lubricant-infused surfaces has shown promising results in preventing non-specific adhesion and attenuating clot formation on biomaterials. However, the existing surface models do not express biofunctional features, a crucial requirement when designing surface coatings for permanent medical implants such as vascular grafts, stents and mechanical heart valves. The main objective of this thesis is to design and develop novel biofunctional lubricant-infused surface coatings that would simultaneously prevent device-associated thrombosis and actively promote surface biointeractions.
Three main approaches to incorporate biofunctionality into lubricant-infused surfaces are presented in this thesis: (1) Developing biofunctional lubricant-infused surface coatings by creating self-assembled monolayers using fluoro and aminosilane molecules. (2) Creating non-fluorosilanized biofunctional lubricant-infused ePTFE vascular grafts by exploiting the innate chemical properties of the ePTFE grafts and biofunctionalizing the surfaces using silanized bio-inks. (3) Creating fluorinated biofunctional lubricant-infused PET grafts with “built-in” functional groups using oxygen plasma treatment. Using these three modification procedures, for the first time, we were able to generate lubricant-infused surfaces, that expressed biofunctional and targeted-binding features. In the first modification technique, by tuning the ratio between the fluorosilane and aminosilane molecules, we were able to incorporate functional groups on the surfaces without compromising the lubricant-infused repellency properties of the modified substrates. In the second modification technique, we created non-fluorosilanized biofunctional lubricant-infused ePTFE grafts by eliminating the need to chemically modifying the surface with silane molecules. Our designed surfaces were further biofunctionalized using our developed silanized bio-inks. Lastly, in order to created fluorinated biofunctional lubricant-infused PET grafts, we developed the third modification process, where fluorinated PET surfaces were hydroxyl-terminated using oxygen plasma treatment, and biofunctionalized using silanized bio-inks.
The designed surfaces using the three proposed modification procedures had excellent repellency properties by attenuating plasma and blood clot formation, thrombin generation and preventing non-targeted adhesion of proteins and cells. In addition, our developed surfaces were biofunctional and were able to actively promote targeted binding of endothelial cells.
With the new surface coatings created in this thesis, lubricant-infused surfaces with excellent repellency properties and biofunctional features can be achieved and applied to blood-contacting medical devices where preventing non-specific adhesion and promoting targeted binding are of immense importance.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: The work presented in this research aims to create biofunctional lubricant-infused platforms for medical implants. Promoting tissue integration and preventing clot formation and non-specific adhesion of biospecies are two of the main challenges that researchers aim to overcome when designing interfaces for permanent blood-contacting implants. However, limited success has been made in developing functional coatings that integrate both these features on one platform. The work in this thesis describes novel, straightforward and effective surface coating strategies for developing biofunctional lubricant-infused interfaces that attenuate clot formation, prevent non-specific adhesion and promote targeted binding of cells.


title: ANISOTROPIC WETTING SURFACES MACHINED BY DIAMOND TOOL WITH TIPS MICROSTRUCTURED BY FOCUSED ION BEAM

contributor:
Selvaganapathy, P.Ravi
Mechanical Engineering

subject:
Anisotropic wetting
Focused ion beam

abstract: In recent years, there has been an increasing interest in the study of hydrophobic surfaces. Hydrophobic surfaces have been used in multiple applications in microfluidic devices due to their properties of self-cleaning, and also in deicing products. Conventionally, hydrophobic surfaces were created by laser cutting, self-assembly and other chemical processing methods. However, in most of these methods, hydrophobicity of the surface cannot be maintained for an extended time or restricted to limited set of materials. A low-cost, high-throughput method to generate highly hydrophobic anisotropic surface has been developed in this thesis which uses Computer Numerical Control (CNC) machining employing diamond tools whose tips have been micro-structured using Focused Ion Beam (FIB) built tips. The versatility of this method has been demonstrated by machining both metal and polymeric materials. Significant anisotropic wetting has been observed on the machined surface with the anisotropic contact angle can reach up to 71.6 degree and highly-hydrophobic property with contact angle of 163.1degree on 6061 Aluminum Alloy and 155.7 degree on PMMA surface.

abstract: Thesis

abstract: Master of Science in Mechanical Engineering (MSME)


title: Investigating TCF-Independent β-catenin Signalling and Its Function in Mouse ES Cell Biology

contributor:
Doble, Bradley
Biochemistry and Biomedical Sciences

abstract:
The Wnt/β-catenin pathway is a fundamental signalling pathway involved in a communicative
process that regulates cellular function during development, immune responses, tissue homeostasis,
cell fate determination and repair. It is a crucial pathway, with a multifunctional protein, β-catenin,
acting as one of its key components. β-catenin’s interaction with the TCF/LEF family of proteins is
very well characterised, however little is known about its TCF/LEF independent roles in the nucleus.
To investigate the TCF/LEF independent signalling roles of β-catenin, we employed previously
generated TCF/LEF quadruple knockout (QKO) and newly developed, TCF/LEF, β-catenin
knockout (TLB) cell lines (i.e. QKO lines that also lack β-catenin expression). In vitro, similarly to
QKO cells, the TLB line displayed a clear neuroectodermal differentiation bias and also displayed
surprising upregulation of Wnt responsive genes. The neuroectodermal bias in the absence of β
catenin reveals that the neuroectodermal differentiation program does not require β- catenin for its
initiation. We describe a novel phenotype observed in embryoid body (EB) assays, where we
observe that lack of β-catenin results in shedding of nonadherent cells from EBs. Based on our RNA
seq data analyses of WT, QKO and TLB lines, the AIRE transcription factor was found to be a
potential β-catenin target that is regulated in a TCF/LEF-independent manner. We observed an
upregulation in AIRE expression in the QKO cell line, which was not observed in the TLB cell line.
We postulate that AIRE plays a role in a β-catenin-regulated pluripotency regulatory network and
describe its importance in maintaining self-renewal and cell pluripotency.

abstract: Thesis

abstract: Master of Science (MSc)


title: HUMAN SKELETAL MUSCLE MITOCHONDRIAL RESPONSE TO INTERVAL TRAINING: ROLE OF EXERCISE INTENSITY

contributor:
Gibala, Martin
Kinesiology

subject: muscle physiology, mitochondrial response, interval training

abstract: It has been proposed that intermittent exercise can differentially affect mitochondrial responses to training, with training volume being more important than intensity for increasing skeletal muscle mitochondrial content and with intensity playing a greater role in mitochondrial respiration. To test this hypothesis, we examined markers of skeletal muscle mitochondrial content and respiration in response to two different interval training protocols performed using single-leg cycling, which permitted a within-subjects design. Ten healthy active adults [6 males / 4 females, 22±4 y, peak oxygen uptake (VO2peak) = 42±4 ml/kg/min] were recruited. Each leg was randomized to either a HIIT [4 × (5 min at 65% Wpeak and 2.5 min at 20% Wpeak)] or SIT [4 x (30-s “all-out” sprints and 4 min active recovery)] protocol and completed three exercise sessions/wk over 4 wk for a total of 12 exercise sessions/leg. The mean work performed during each session was 133±32 and 44±8.0 kJ for HIIT and SIT respectively, and the average workload during intervals was 95±25 W and 322±77 W for HIIT and SIT respectively. Citrate synthase (CS) maximal activity increased compared to baseline after training interventions, with the change being greater after SIT vs HIIT (42±25% vs 16±13%, interaction p=0.01). COXIV protein content and succinate-supported state 3 were unchanged. Single-leg VO2peak and time to exhaustion (TTE) increased to a similar extent in both HIIT and SIT (main effect of time, p<0.05). These data suggest that, in contrast to what has been proposed by others, training intensity is more important than volume for increasing mitochondrial content during short-term interval training in human skeletal muscle.

abstract: Thesis

abstract: Master of Science in Kinesiology

abstract: Mitochondria are an important component of cells that use oxygen to convert fuels such as sugars and fats into energy. One of the factors that determines the amount of mitochondria in skeletal muscle is physical activity. Aerobic exercise training can be performed over a range of intensities, from relatively easy to very hard, and in an intermittent or continuous manner. This thesis examined the effect of short-term, intermittent exercise training performed at two different intensities on the content of mitochondria in human skeletal muscle. It found that both high- intensity interval training (HIIT) and sprint interval training (SIT) increased mitochondrial content. The increase was greater after SIT compared to HIIT, even though the total “dose” or amount of exercise was lower in the former compared to the latter. These results suggest that intensity is an important determinant of skeletal muscle remodelling induced by intermittent exercise in humans.


title: Evaluation of Spark Plug Technologies in Spark Ignition Engines by Pareto Front Optimization

contributor:
Habibi, Saeid
Mechanical Engineering

subject:
Pareto Optimization
Engine Modeling

abstract:
The Internal Combustion Engines (ICEs) have played a significant role in transportation system to date and are expected to retain a significant market share through to 2050, according to the U.S. Energy Information Administration. Improving the efficiency of the ICEs is one of the most promising and cost-effective approaches to increasing highways vehicle’s fuel economy. The tools to address critical barriers to commercializing higher efficiency, lower emissions, advanced ICEs for passenger and commercial vehicles are increasingly important in the rapidly evolving automotive sector.
    In this research, a model based optimization strategy is developed for trade-off analysis of parts in Spark Ignition Internal Combustion Engines (SI-ICE). The trade-off analysis tool has been used as a complement to engine mapping to determine the operating region of an engine where a new part could lead to improvements in fuel efficiency, performance, and emissions.
    To build the engine models, a Design of Experiment (DoE) was developed for performing the engine tests. For each spark plug set, the engine tests were conducted twice with an acceptable control of the parameters that affect engine outputs. The engine torque, Break Specific Fuel Consumption (BSFC) and break specific NOx emission were considered as the engine responses. Engine models were built according to the two-stage modeling strategy by means of black box modeling techniques. The accuracies of the models were 96%, 95% and 92% for the engine torque, BSFC and NOx outputs respectively.
    For the optimization part, determination of the optimal spark timing for each spark plug was formulated as a multi-objective optimization problem searching for compromises among opposing objectives, i.e. engine torque, emission and fuel consumption. The optimization outputs were in form of Pareto fronts, enabling the selection of the best solutions in terms of different objectives by considering the higher level information.
    The resulted Pareto fronts of the two spark plugs were compared at different operating points of the Ford Coyote engine and results showed that the two plugs are comparable. The marginal difference was at low load and low speed condition, where the newly designed spark plug was better than the conventional design.

abstract: Thesis

abstract: Master of Applied Science (MASc)