title: THE CHALLENGES ASSOCIATED WITH PREDICTING POST-CONCUSSION SYMPTOMS: A SCOPING REVIEW OF LITERATURE

contributor:
Rathbone, Michel
Medical Sciences

abstract:
Background: Up to 20% of concussion patients do not recover and develop a host of persisting cognitive, physical, behavioural, and/or emotional symptoms – collectively known as post-concussion syndrome (PCS) – lasting for many months to years. It is unclear why these patients have protracted recovery. Identifying factors that can predict patients at most risk can provide earlier targets for prevention and treatment. However, the wide-ranging list of predictors of PCS is creating confusion in the body of literature, and despite countless reviews attempting to clarify this growing list, there remains a great deal of uncertainty.

Objective: To systematically map the reviews on PCS predictors to determine the nature of the reviews and understand why this body of literature still lacks firm, conclusive evidence. We aimed to identify sources of clinical and methodological diversity that hinder meta-analytic syntheses, and in turn, limit the conclusions drawn and translated to clinical practice.

Methods: The Joanna Briggs Institute Reviewer’s Manual and the PRISMA-ScR was used to develop our study design. Six databases were searched, including reference lists. Studies needed to sufficiently focus on predicting PCS and report challenges relevant to quantitative synthesis.

Results: 281 eligible studies were found. Eleven studies were included in the final qualitative analysis. Qualitative synthesis revealed definitions and diagnostic barriers, as well as methodological barriers, contribute to clinical and methodological diversity in studies.

Conclusions: Despite extensive research on PCS predictors, researchers are faced with definitions and diagnostic barriers and methodological barriers that influence the clinical and methodological diversity across studies. These sources of barriers and diversity impede the conduct of more meta-analytic approaches, and in turn, limits review studies from reaching more conclusive evidence that can reliably inform clinical practice. Understanding of the nature of literature reviews can help inform researchers of the sources of diversity and barriers to improve research contributions to evidence-based medicine.

abstract: Thesis

abstract: Master of Science in Medical Sciences (MSMS)

abstract:
Background: Despite countless reviews attempting to clarify the extensive list of predictors for post-concussion syndrome, there remains a great deal of uncertainty.

Objective: To determine the characteristics of the existing review studies on predictors for developing post-concussion syndrome and identify obstacles in quantitatively combining studies and translating the evidence into clinical practice.

Methods: Six databases were systematically searched to find relevant reviews examining predictors of post-concussion syndrome. Eligible studies went through multistage screening to determine whether they meet the eligibility criteria.

Results: 281 studies were eligible for screening, of which, 11 studies were included. Obstacles regarding definitions and diagnostic criteria and study methods were contributing to increased diversity across the studies.

Conclusions: The obstacles identified in this study all contribute to the challenges in combining individual studies into a quantitative synthesis that, in turn, limit the clear conclusions that can be drawn and the translation of research evidence to clinical use.


title: Numerical modelling of damage process in cohesive-frictional materials

contributor:
Pietruszczak, Stanislaw
Civil Engineering

abstract: This research is related to modeling of the damage process in cohesive-frictional materials. There are two primary areas of application that include modeling of fractured rock mass as well as some selected topics in biomechanics. For both these areas, the methodology involves a homogenization approach that incorporates volume averaging. The research in rock mechanics deals with the assessment of equivalent mechanical properties of the host rock intercepted by sets of fractures. The effect of fracture network orientation/spacing on the macroscopic strength characteristics is examined. The research in biomechanics has both a numerical and experimental component and is focused on analysis of hip fracture due to a sideways fall. Here, the cortical bone tissue is modeled as a transversely isotropic material and an experimental program is setup to define the anisotropic fracture criterion. In particular, a series of novel direct shear tests is performed on small prism-shaped samples and is accompanied by uniaxial tension and compression performed at different orientations relative to the loading direction. It is demonstrated that the conditions at failure in compression range are independent of confining pressure, while the strength itself is orientation dependent. The failure criteria are postulated using the critical plane approach and the microstructure tensor approach in tension and compression regimes, respectively, and a procedure for identification of material constants is proposed. The last part of this research deals with numerical simulation of fracture propagation in a femur bone subjected to loading conditions simulating a sideways fall. A specific experimental test is modelled, and the mechanical properties of cortical tissue are specified from a series of independent material tests conducted on samples extracted from the fractured femur. The analysis incorporates the newly developed failure criteria and the numerical results pertaining to the assessment of ultimate load and the evolution of fracture pattern are compared with the experimental data.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: PCSK9 AS A DRIVER OF LIPID METABOLISM AND KIDNEY DISEASE

contributor:
Austin, Richard
Medical Sciences

subject:
PCSK9
CD36
Chronic Kidney Disease
LDLR
NAFLD
HFD
ER Stress
UPR Activation
Cardiovascular Disease
Hypercholesterolemia

abstract:
The global prevalence of chronic kidney disease (CKD) has risen at an accelerating rate, increasing the global healthcare burden for long-term and chronic care costs. Multiple risk factors including hypertension, diabetes, and dyslipidemia synergistically induce the progression of CKD. Chief among these factors are dyslipidemia and obesity; increased free fatty acid uptake due to excess consumption of lipid-rich diets has been shown to promote intra-renal lipid accumulation in several in vivo models and in patients in various stages of CKD. Furthermore, patients with renal disease are also at a substantially higher risk for atherosclerotic cardiovascular disease (CVD). In the general population, as well as in patients with renal disease, circulating low-density lipoprotein cholesterol (LDLc) is a well-established driver of atherosclerotic lesion development and CVD progression. In 2003, the proprotein convertase subtilisin/kexin type-9 (PCSK9) was identified as the third locus of familial hypercholesterolemia and was further characterized for its ability to enhance the degradation of the low-density lipoprotein receptor (LDLR). Since this seminal discovery, the development of monoclonal antibodies targeted against PCSK9 demonstrated a significant reduction in LDLc and subsequent CVD risk, establishing the remarkable ‘bench to bedside’ transition. However, the inherent role of PCSK9 in regulating lipid homeostasis remained unknown in different pathological conditions. In the first chapter of my thesis, I demonstrate that PCSK9 regulates the LDLR as a feedback mechanism to protect against non-alcoholic steatohepatitis (NASH) progression induced by a high-fat diet (HFD) challenge.
Since its seminal discovery, PCSK9 was also characterized to modulate a wide variety of receptors known to play a crucial role in lipid metabolism including the cluster of differentiation 36 (CD36), the very low-density lipoprotein receptor (VLDLR), and the apolipoprotein E receptor 2 (ApoER2). Previously, we have demonstrated that the absence of PCSK9 promotes diet-induced non-alcoholic steatohepatitis and liver injury through increased surface expression of CD36. Given that these same receptors are well-expressed on renal epithelia, the second chapter of my thesis demonstrates that PCSK9 is also able to modulate renal lipid metabolism by attenuating tubular lipid accumulation and subsequent renal injury.
Furthermore, when PCSK9 was first characterized by Seidah and colleagues in 2003, in situ hybridization of murine PCSK9 demonstrated that it was primarily expressed in the liver, but also well-expressed in the kidney cortex, cerebellum, and small intestines. Despite its expression in a wide range of tissues, the secretion of PCSK9 was exclusive to the liver, thus, questioning what the intracellular role of PCSK9 may be. Hence, my last chapter of my masters studies lies in establishing the role of intracellular PCSK9 expression in a cellular process known as endoplasmic reticulum (ER) stress in the kidney. ER stress is a phenomena which primarily occurs due to increased accumulation of misfolded polypeptides, and has been implicated in numerous metabolic diseases including hepatic steatosis, CKD, and neurodegenerative pathologies. Previously, we have demonstrated that overexpressing wild-type and variants of PCSK9 in a Pcsk9-/- mouse does not induce the activation of the unfolded protein response (UPR) and attenuates hepatic ER stress. Using a well-established CKD model, I show that Pcsk9-/- mice exhibit increased renal ER stress and injury relative to wild-type controls. Overall, my findings demonstrate for the first time that both extracellular and intracellular PCSK9 has the ability to modulate renal injury using two distinct mechanism to protect against CKD progression.

abstract: Thesis

abstract: Master of Health Sciences (MSc)


title: Genetic studies of the negative regulators of vulva development in C. elegans and C. briggsae

title: Negative regulators of vulva development in C. elegans and C. briggsae

contributor:
Gupta, Bhagwati
Biology

subject: Developmental Biology, Evolution, Genetics, Molecular Biology, C. elegans, C. briggsae, Tumour suppressor

abstract:
Caenorhabditis elegans and its congener, C. briggsae are excellent animal models
for the comparative study of developmental mechanisms and gene function. Gupta
lab is using the vulval tissue in these nematodes as a system to investigate conservation
and divergence in signal transduction pathways. Genetic screens conducted
earlier in our laboratory recovered several mutants that cause multivulva (Muv)
phenotype. The Muv genes act as tumor suppressors and negatively regulate the
proliferation of vulval precursors. Genetic and molecular work on these genes has
revealed that C. briggsae vulva developmental utilizes novel genes representing a
new phenotypic class termed ‘Inappropriate Vulva cell Proliferation (IVP)’ (Sharanya
et al., 2015). This indicates that the signaling mechanism in C. briggsae
specifies vulval cell fates differently from C. elegans. Interestingly, it has been
found that Cbr-ivp mutants show higher levels of Cbr-lin-3 (EGF) transcript, indicating
that these genes act genetically upstream of Cbr-lin-3, similar to SynMuv
family members in C. elegans. Moreover, RNAi knockdown of the Cbr-lin-3 transcript
resulted in the suppression of the multivulva phenotype in mutant animals.
Similar suppression was also observed when a MAP kinase inhibitor was used in
the previous study. In addition, the role of two other novel negative regulators of cell
proliferation, Cbr-lin(bh1) and Cbr-lin(bh3) was also investigated. Preliminary
findings on these regulators suggested that both Cbr-lin(bh1) and Cbr-lin(bh3) exhibiting
a heritable Muv phenotype and are found to be located on Chromosome
I and III respectively. Identification of novel genes and further characterization
will help us understand the molecular function of genes and their involvement in
the regulation of vulval cell differentiation. The findings of my research work will
provide a background for future studies to understand the role of novel genes in
reproductive system development. Overall, these results provide evidence that although
the morphology of vulva is similar in the two nematode species, underlying
mechanisms of development appear to have diverged.

abstract: Thesis

abstract: Master of Science (MSc)


title: STUDY OF COMPACT AND EFFICIENT DIODE PUMPED SOLID STATE GREEN LASERS FOR DISPLAY APPLICATION

contributor:
Xu, Chang-Qing
Engineering Physics

abstract:
Due to the long lifetime, high directionality, and narrow spectral linewidth, laser-based displays have several advantages over other display technologies, such as high brightness, low maintenance cost and vivid color. In recent years, laser displays have attracted a lot of attention from academia and industrial community, but a number of difficulties prevent further commercialization of laser displays. The main obstacle is the speckle noise caused by the high coherence of lasers, especially in the green region, because the wavelength of commercial watt-class LD is still too short, > 530 nm DPSS green laser need to be employed to improve the image’s color quality and further speckle reduction. Since DPSS green lasers are still essential for display application, their miniaturization is necessary for pico-projection system and the field sequential modulation is needed as well. However, the modulation properties of the compact DPSS green module have not been studied yet.
In this dissertation, the field sequential modulation properties of a compact Nd:YVO4/MgO:PPLN green laser module was investigated. Its output performance under a modulation condition were studied and analyzed. Furthermore, a number of single-(dual-) wavelength continuous wave green DPSS lasers are proposed and demonstrated for the purpose of speckle reduction and color improvement. An intra-cavity frequency doubling configuration was used to achieve efficient nonlinear conversion and smaller dimensions. Specifically, a 531.5 nm was built based on Nd:GdVO4 and MgO:PPLN crystals, it has a output power of 1.9 W with an O-O efficiency of 37%. A compact 540 nm laser was achieved by using Nd:YAP and LBO, in which a 0.8 W output power was achieve with an O-O efficiency of 20%. Watt-class 542 nm / 543 nm Nd:YVO4/MgO:PPLN green lasers was achieved by customized cavity coating design since weaker fluorescence peaks are used as fundamental light. An O-O efficiency of 22% and 35% was obtained, which are the highest O-O efficiencies achieved so far to the best of our knowledge. In addition, an orthogonally polarized dual-wavelength (542 & 543 nm) was realized by using a conventional Nd:YVO4 crystal and two MgO:PPLN crystals. An optical-to-optical (O-O) efficiency as high as 15.3% was achieved when the powers of the two emission wavelengths were equal. This is the first time that a dual-wavelength orthogonally polarized visible solid state laser is achieved. Moreover, the speckle reduction performance of the proposed lasers was studied as well. It shows that the SCR value is effectively reduced by blending different green wavelengths together, which agree well with the theoretical expectation. Generally, those lasers have features of efficient, compact, and low cost which are suitable for laser display application.
At last, a tri-wavelength wavelength blending method was proposed and studied. A 523 nm green LD, 532 nm and 543 nm green DPSS lasers are employed for wavelength blending purpose. It shows that lower SCR was achieved where all three wavelengths are involved, which agrees well with the theory. Moreover, optimal color performance was maintained as a result of the employment of 543 nm laser, which was the purpose for developing long wavelength green laser.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Examining the Relationship between Self-Perceived Health and Well-being and Physical Activity and Fitness in Children with a Chronic Condition

contributor: Medical Sciences (Division of Physiology/Pharmacology)

subject:
physical activity
fitness
self-perceived health
self-perceived well-being
JIA
IBD

abstract:
Habitual physical activity and fitness are well-established as independent predictors of health in both children and adults. Chronic inflammatory conditions in children have been shown to negatively impact participation and maintenance of physical activity in childhood which can lead to a reduction in fitness. Juvenile idiopathic arthritis (JIA) and inflammatory bowel disease (IBD) are two of the most common childhood chronic conditions, both of which are characterized by inflammation. Alarmingly, even during remission, physical activity and fitness levels are reduced and sickness behaviours persist in these children. As such, it is thought that psychosocial measures, such as self-perceived health and well-being, may have a stronger association with decreased physical activity and fitness levels in this population as compared to healthy controls. The purpose of this project was to examine the relationship between self-perceived health and well-being and physical activity and fitness in children with JIA or IBD.
In total, 58 children (32 girls, 26 boys) between the ages of 7 and 17 years with a single diagnosis of either JIA or IBD, and healthy controls were recruited. They completed measures of anthropometry, body composition, physical activity, as well as fitness (aerobic and muscle strength). Questionnaires regarding perceived health and well-being were also completed, and blood samples were obtained to measure specific markers of inflammation.
Children with JIA or IBD were found to engage in significantly less moderate-to-vigorous physical activity (MVPA) relative to healthy controls (t = -1.977, p = 0.040). A linear regression established that MVPA, when expressed as an average of minutes per day, could statistically significantly predict self-perceived health, F(1,50) = 6.516, p = 0.014, where MVPA accounted for 11.5% of the explained variability in self-perceived health. This was no longer significant with the controls age, sex, and body fat percentage added into the model. Linear regression models showed that fitness was more predictive of self-perceived well-being, as seen with relative VO2 peak, F(1,38) = 6.683, p = 0.014, where relative VO2 peak accounted for 15% of the variability with self-perceived well-being. Furthermore, composite isometric strength expressed relative to body mass was able to significantly predict a composite blood inflammatory marker score, F(1,49) = 4.447, p = 0.040, where a relative composite isometric strength score accounted for 8.3% of the variability in a composite inflammatory blood marker score.
Our findings indicate weak but significant predictive power for physical activity and fitness variables with regards to self-perceived health and well-being. Therefore, it may be important to explore ways to increase self-perceived health and well-being in children with JIA or IBD in order to improve physical activity participation and fitness.

abstract: Thesis

abstract: Master of Health Sciences (MSc)


title: Comprehensive Mathematical Model for Oxygen Steelmaking

contributor:
Dogan, Neslihan
Materials Science and Engineering

subject:
Mathematical modelling
Process Metallurgy
Reaction Kinetics
High temperature processes

abstract:
The Oxygen Steelmaking process is used to refine pig iron produced in the blast furnace to produce liquid steel for further refining in secondary steelmaking processes. The main advantages of the process are its autogenous nature, wherein the heat is generated through the refining reactions itself, and the refining is completed in a relatively short time (typically 15-25 mins). Achieving the desired end-point composition of refined steel is essential to avoid re-blows, which lead to delays in downstream processes and an increase in steel production costs. Improving process control through regular monitoring and a better understanding of the process is thus very critical. Multiple reaction interfaces are formed between various phases (slag, metal, gas), at extremely high temperatures and this makes the monitoring of the process through sampling and observation difficult and expensive. Consequently, mathematical modelling has been used as a tool to improve the understanding of the process and propose developments in operation.
Numerous models have been developed in the past; however, these models do not address several open questions regarding the detailed reaction mechanisms and the contributions from different reaction zones inside the Basic Oxygen Furnace. The current work aimed to fill this gap. In this work, four prominent reaction zones, namely; impact, slag-metal bulk, cavity, and emulsion zones were identified. A more mechanistic approach involving process variables has been used to decrease the level of empiricism. With regards to the impact and the slag-metal bulk zones, the velocity of flow of metal (or surface-renewal) at the interfaces of these zones are calculated by taking into the momentum induced by the top-jets and bottom-stirring plumes. This study found that these zones contribute negligibly to overall refining in the oxygen steelmaking process. In the case of the emulsion zone, a very rigorous description of all aspects (external and internal decarburization, bloating behavior, and trajectory) pertaining to the life cycle of a single metal droplet in slag has been achieved. The emulsion zone is found to contribute 5 to 75 % of decarburization during various times of blow. The cavity zone model represents the first reported effort to predict the refining behavior of metal droplets that are exposed to oxygen jets within the lance cavities. The model incorporated the mass transfer, reaction equilibria, and kinetics of the reactions. It is predicted that this zone plays a critical role in the removal of silicon and FeO formation in the early part of the blow and removal of carbon throughout the blow. Several significant insights with regards to improvement in the operation of the oxygen steelmaking process are derived from each sub-models. The integration of these models will guide the steelmaker to improve their practices so that they can achieve better consistency in the end-point composition of refined steel and reduce re-blows.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Success Factors for Crowdfunding Campaigns

contributor:
Pujari, Devashish
Business

abstract:
The exponential growth of crowdfunding over the past 10 years signals its evident importance as an alternative method of marketing and funding innovation. Because of the arm’s length relationship between innovators and their backers in this system, signaling quality of the project is vital for success of a campaign. Backers mainly make decisions based on quality signals they receive, and because the average spatial distance between them and innovators is substantial in a crowdfunding setting, this (together with the effectiveness of quality signals) has consequences on the relationship between them. In this modern setting, the type of signals used by campaign owners differs from the traditional costly signals of quality. Due to the relatively small size of crowdfunding projects, and the small investments made by each backer, innovators provide less costly and rhetorical quality signals, which have become a topic of academic inquiry in this field.
In this dissertation, I conducted two studies to investigate important aspects of crowdfunding. First, I studied geographic distance and its interaction with quality signals (both costly and less costly signals). I argue that that the information gap between backers and innovators rises with the increase of geographic distance. Drawing on signaling theory, I argue that since distant backers face higher levels of information disadvantage (compared to nearby backers), the value and importance of quality signals are amplified for them. I find support for my proposition that quality signals used to reduce the information gap between two sides of a trade become more valuable and influential with increases in geographic distance between backers and the innovator. Heretofore, no study has examined the interaction between geographic distance and quality signals. In study 1, using a sample of 102,179 Kickstarter crowdfunding campaigns launched in 156 different countries (i.e. creators are from 156 different countries), I show that quality signals including human capital, endorsement, preparedness, and positive psychological capital are more influential on the likelihood of success of crowdfunding campaigns that are collecting funds from more geographically remote backers than campaigns that are receiving funds from more geographically proximate backers. The results hold true even after controlling for cultural differences.
Second, I investigate the role of less costly signals of quality and their interaction with traditional quality signals. I also examine their interaction with meaning in crowdfunding campaign narratives. Study 2 investigates the importance of textual description, its focus on reward/risk rhetoric, and its quality. Using a sample of 187,769 Kickstarter projects, I show that the meaning and quality of a project’s textual description can affect the success/failure of that project in securing funds and creating a market for the innovative idea. I show that textual quality and fluency functions as a less costly signal of preparedness, which can reduce the negative effect of risk rhetoric and increase crowdfunding performance. Interestingly, my study proposes and shows evidence of the moderating role of quality, preparedness and human capital signals (i.e. quality of the text and its creator) in reducing the effect of risk rhetoric and increasing the effect of reward rhetoric (i.e. the meaning of the text). The findings of my second study are significant as they show the interaction between text quality and text meaning. It is interesting to see that the perceived risk of a project can change due to the presence or absence of quality signals.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Collecting small contributions from large number of supporters is called crowdfunding. With the growing popularity of crowdfunding, it is important to understand the factors that affect success in this system of attracting funding backers. In my thesis, I have studied the elements in each crowdfunding pitch that can show the quality of the project to the potential supporters. In my first study I show that these indicators of quality are more important when the geographic distance between project owners and their supporters is higher.
In my second study I show that the quality of the narrative of the project is another indicator of quality. I find that a well-written text will reduce the negative effect of risk and increase the positive effect of rewards.
In both studies I show that costly and less costly indicators of quality can help success of crowdfunding campaigns.


title: Performance Characterization and Modelling of a Lithium-Ion Cell using Electrochemical Impedance Spectroscopy

contributor:
Habibi, Saeid
Mechanical Engineering

subject:
constant phase elements
state of charge
battery characterization
electric vehicle
electrochemical impedance spectroscopy
lithium-ion

abstract: The electrification of transportation is gradually becoming more prominent as it is more efficient and sustainable than conventional transportation alternatives found today. At the centre of this growth is battery testing and research, as they are the primary energy storage devices used to power electric vehicles. With the growing complexity of battery systems, testing and monitoring their performance relies on highly specialized and precise equipment. Furthermore, the use of battery models helps researchers improve their research while reducing the time and costs involved in testing. As such, accurate battery modelling is a critical component in predicting how a battery will behave in specific applications and under various conditions. In this research, a lithium-ion cell is tested extensively, and its performance is characterized across a wide range of operating conditions including temperature, current rates and state of charge (SOC) values. An equivalent circuit model for impedance modelling is proposed, which utilizes constant phase elements represented in the time domain to improve fitting accuracy. This is done concurrently with the development of a state of the art, fully automated battery test system which is showcased throughout the course of the research. In addition to this, an analysis is conducted on the low frequency impedance data used during research, as well as its effect on model accuracy. To provide significance behind the results and relevance to real-world applications, all of the impedance modelling is experimentally validated using temporal drive cycle data. This research was able to demonstrate that the use of a ZARC element can improve the mid-frequency fitting of impedance data relative to a conventionally used modelling approach. It also showcases how the use of low frequency electrochemical impedance spectroscopy (EIS) data can negatively impact the accuracy of impedance modelling.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: EXAMINING THE EFFECT OF ESTRADIOL ON B CELL RESPONSES AGAINST HERPES SIMPLEX VIRUS TYPE-2

contributor:
Kaushic, Charu
Medical Sciences

subject: HSV-2

subject: B cell responses

abstract:
Problem: Herpes simplex virus type-2 (HSV-2) is one of the most prevalent sexually transmitted infections in the world, and rates of infection are higher in women compared to men. Furthermore, vaccines developed against HSV-2 have failed at various stages of clinical trials, due to their inability to induce protective mucosal immunity.  In animal models, intranasal (IN) immunization with attenuated HSV-2 (TK−) virus has been shown to confer protection against wildtype HSV-2 challenge. Since IN immunization serves as a more practical and less intrusive vaccination strategy, further studies are warranted to characterize optimal immune responses following IN immunization. We have previously demonstrated that estradiol (E2) treatment promotes enhanced protection against HSV-2 through enhanced anti-viral T cells responses. However, the effect of E2 on B cell responses, which were recently shown to be critical in protecting the host following IN immunization, remain poorly understood. Therefore, in this study we aimed to examine if following IN immunization, E2 enhances the memory B cell (MBC) and antibody-secreting plasma cell populations within the secondary lymphoid tissues and nasal effector sites, and whether this enhancement leads to an overall better protection against intravaginal IVAG WT-HSV-2 challenge.
Methodology: Ovariectomized (OVX) mouse model of HSV-2 were pre-treated with E2 or placebo pellets. Subsequently, both groups were immunized intranasally with TK- HSV-2. Four weeks later nasal associated lymphoid tissues, nasal mucosa, cervical and iliac lymph nodes, spleen and vaginal tract were collected and processed and MBC and antibody-secreting plasma cells were characterized by flow cytometric analysis. HSV-2 specific IgM and IgG antibody responses in serum and vaginal secretions were measured by ELISA. In parallel experiments, animals were IVAG challenged with WT-HSV-2 and the B cell subsets were characterized as above.
Results: The formation of MBC subsets, as seen by the presence of CD19+ IgD- cells and the heterogenous expression of CD73, CD80, and PD-L2, were observed four-weeks post immunization within the cervical and iliac lymph nodes and spleen, which were further enhanced in the presence of E2. Additionally, E2-treated mice had increased number of B220- CD138+ IgG2c+ plasma cells within the nasal mucosa following immunization. These enhancements translated into increased levels of HSV-2 specific IgG2b and IgG2c antibodies within the serum and vaginal secretions of E2-treated mice at four-weeks post IN immunization. Upon IVAG challenge, E2-treated mice, but not control mice, were protected. Since the antibody isotypes that were enhanced in E2 treated mice are correlated with Th17 responses, E2 mediated antibody enhancement was tested in IL-17 knockout mice. E2 treatment in IL-17-knockout mice failed to induce similar responses observed in WT mice, indicating that the enhancement of B cells and antibodies seen following E2 treatment was mediated in an IL-17 dependent manner.
Conclusion: This study highlights the importance of sex-dependent differences in vaccine-induced immunity. Specifically, the findings from this study will provide valuable information for the design of a potentially efficacious mucosal vaccine strategy, whereby immunization in the context of E2 could significantly enhance antigen-specific antibody responses in the genital tract.

abstract: Thesis

abstract: Master of Science (MSc)


title: IDENTIFYING NEW COMPOUNDS CAPABLE OF INDUCING MODEL PHAGES

contributor:
Hynes, Alexander
Biochemistry and Biomedical Sciences

subject: Prophage Induction Bacteriophage

abstract:
McMaster University MASTER OF SCIENCE (2020) Hamilton, Ontario
(Department of Biochemistry and Biomedical Sciences)
TITLE: Identifying new compounds capable of inducing model phages
AUTHOR: Anisha Nandy
SUPERVISOR: Dr. Alexander P. Hynes
NUMBER OF PAGES: xi, 80

abstract:
Prophages are the genomes of bacteriophages (phages, bacterial
viruses) that integrate into the chromosome of their host upon infection, lying dormant until conditions favour their reactivation. A cell harbouring a
prophage is called a lysogen, as, upon exposure to certain signals, the
prophage will initiate a replicative cycle ending in lysis of the host bacterium
and release of phages. This process is known as induction. Canonically,
induction occurs through activation of the bacterial SOS-response, a DNA repair cascade initiated by detection of DNA damage. Studies of prophage
induction have almost exclusively relied on challenges with compounds that
result in the initiation of the host SOS response.
Recent studies have identified some signals that affect prophage
induction independently of the SOS response, but these approaches have not
been systematic. To identify non-canonical triggers of prophage induction, I
screened 3,936 compounds against two model lysogens. The first, carrying
phage HK97, is a model for induction. The second, carrying phage Mu—a
prophage thought to be uninducible—serves as a control. Any compound
which inhibited bacterial growth in only our HK97 lysogen was considered to
have resulted in a phage-mediated response. The 171 compounds identified in this screen were then used to re-challenge the lysogen at a range of
concentrations and monitor the resulting release of free phages associated
with induction. Increases in phage counts were seen for 86 compounds. While 38 of these were known SOS activators, 49 were novel, ‘non-canonical’ inducers. Unexpectedly, the screening also revealed seven unique chemical inducers for the supposedly un-inducible model prophage, Mu.
The 56 new phage-inducers identified by this work include compounds
likely to be driving phage induction through non-canonical pathways. As
prophages are thought to respond to bacterial stress, these may reflect stressors acting through new mechanisms. Using these compounds as tools opens up an avenue to probe other stress pathways in bacteria, and, as evidenced by induction of Mu, potentially help discover new phages that don’t respond to canonical inducers.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
Bacterial viruses (phages) can lie dormant as prophages in their host
bacterium until a signal triggers their activation, production of viruses, and
rapid killing of the host. This switch from dormant prophage to active phage called induction. Almost all molecules that result in prophage inductions
belong to a limited set of compounds which elicit a specific stress response in
bacteria.
Screening 3936 compounds for their ability to inhibit the growth of
bacteria carrying known prophages resulted in the identification of a small
subset associated with increased phage production. For one Escherichia coli
prophage—HK97, a model of induction—we found 49 compounds not
previously known as inducers. For another model prophage—Mu, a prophage
thought to be chemically uninducible—we identified seven such compounds.
These compounds will serve as tools to determine what signals prophages can respond to, and potentially identify new stress pathways of
interest in bacteria.


title: CHARACTERIZATION OF AN ALPHA2-ANTIPLASMIN ANTIBODY

contributor:
Weitz, Jeffrey
Health Sciences

subject: antibody thrombosis thrombolysis alpha2-antiplasmin

abstract:
Thrombotic disorders include myocardial infarction (MI), acute ischemic stroke (AIS) and venous thromboembolism (VTE), which encompasses pulmonary embolism (PE), and deep vein thrombosis (DVT). To prevent further complications or mortality in patients with MI and AIS, rapid restoration of blood flow is needed to minimize organ damage. Such treatment also is needed in patients with massive PE. Blood flow can be restored mechanically via percutaneous coronary intervention with stent implantation for MI and by thrombectomy in patients with AIS or PE. Alternatively, pharmacological reperfusion can be achieved by systemic administration of plasminogen activators (PAs). PAs convert plasminogen to the fibrinolytic enzyme, plasmin. Plasmin then degrades the clot into soluble fragments. Streptokinase (SK) and urokinase (UK) were the first therapeutic clot dissolving drugs but both lead to excessive bleeding complications because of non-specific effects. Current therapy focuses on clot specific agents such as recombinant tissue-PA (rt-PA) or tenecteplase (TNK), a rt-PA variant. However, there is a risk of intracranial bleeding in at least 1% of patients, which can be fatal or disabling. Thus, a need exists for new strategies to enable safer reperfusion that are not associated with potentially fatal side effects.
This study focuses on the therapeutic role of alpha2-antiplasmin (α2AP). α2AP is the primary inhibitor of plasmin. One approach to thrombolysis is to attenuate α2AP with an inhibitory antibody (A2AP IgG). Inhibition of α2AP would enable clot lysis with lower doses of PAs, thereby reducing the risk of bleeding and serving as a safer approach to thrombolytic therapy. We aimed to characterize A2AP IgG and evaluate its effect on fibrinolysis in vitro and in vivo.
A2AP IgG1 was selected and developed using phage display and an antibody gene library with human and rabbit α2AP as the antigen. Affinity maturation was performed and the Fc portion of the A2AP IgG1 was subsequently changed to the IgG4 isotype which yielded A2AP IgG4. A2AP IgG4 binds α2AP with 63-fold higher affinity than A2AP IgG1 as determined using surface plasmon resonance (SPR). SDS-PAGE and western blot analysis reveals that both antibodies bind to the plasmin-α2AP (PAP) complex, fibrinogen, and fragment X but not to α2AP; results confirmed by ELISA.
In functional studies, A2AP IgG1 significantly reduced plasmin inhibition by α2AP by 5.5-fold. Both A2AP IgG1 and A2AP IgG4 shortened tissue-PA (t-PA)-mediated clot lysis in a concentration dependent manner. A2AP IgG4 was 2.2-fold more potent than A2AP IgG1 in human plasma and 1.4-fold more potent in rabbit plasma. Compared with t-PA or TNK alone, addition of either antibody enhanced the lysis of preformed plasma clots.  Combining A2AP IgG4 with 10% of the highest t-PA or TNK dose produced more clot lysis than the highest dose of t-PA or TNK alone.
In a rabbit jugular vein thrombosis model, A2AP IgG4 alone produced 20% lysis. When combined with a low dose of TNK, 40% clot lysis resulted, which was significantly greater than the 30% clot lysis observed with a higher dose of TNK. A2AP IgG4 alone or in combination with a lower dose of TNK did not cause significantly more bleeding than the higher dose of TNK alone and did not degrade circulating fibrinogen. Thus, we have shown that by inactivating α2AP, A2AP IgG attenuates α2AP activity, and accelerates clot lysis in vitro and in vivo. This demonstrates that antibody-mediated inhibition of α2AP, enhances thrombolysis and enables use of lower doses of PAs.

abstract: Thesis


title: Understanding the Influence of Geography on the Delivery of the Nurse-Family Partnership Program in British Columbia, Canada

contributor:
Jack, Susan M.
Nursing

subject:
Public health nursing
rural
Nurse-Family Partnership
Interpretive Description
home-visitation

abstract:
Nurse-Family Partnership is a targeted public health intervention program designed to improve child and maternal health through nurse home visiting. Adolescent girls and young women who are pregnant or living in situations of social and economic disadvantage are at increased risk for poor health. Rural living may compound marginalization and create additional challenges for young mothers. In the context of a large-scale process evaluation, I posed the question: “In what ways do Canadian public health nurses explain their experiences with delivering this program across different geographical environments?” This thesis represents a purposeful attempt to examine the experiences of public health nurses as they deliver the Nurse-Family Partnership program across different geographical settings in British Columbia, Canada.
The qualitative methodology of interpretive description guided study decisions and data were collected through focus groups and semi-structured interviews with public health nurses delivering the Nurse-Family Partnership program and their supervisors. Consisting of three studies linked by their focus of evaluating Nurse-Family Partnership in British Columbia, this thesis explores influences on program delivery across the rural-urban continuum, including issues related to nurse recruitment, retention, and turnover. Overall, the findings from these analyses suggest that the nature of clients’ place and their associated social and physical geography emphasizes that geography has a significant impact on program delivery for clients who were living with multiple forms of oppression and it worked to reinforce disadvantage.
In manuscript one, exploration and description of factors that contribute to recruitment, retention, and turnover of public health nurses delivering Nurse-Family Partnership in British Columbia, Canada are presented. Then manuscript two reflects the factors and challenges of providing the NFP program in rural communities. The final manuscript applies an intersectional lens to reveal how the nature of clients’ place and their associated social and physical geography emphasizes inadequacies of organizational and support structures that create health inequities for clients.
The collective work of this thesis emphasises the importance of location as a factor affecting home visitation programs. In rural environments, public health nurses are resourceful and can provide insight into important considerations for program delivery. These may include enhanced use of technology for communicating with supervisors, nurses, or clients through cell phone/videoconferencing or experiencing rugged terrain and extreme weather conditions. Public health nurses practicing in urban areas also have geographical considerations that are location specific, including precariously housed clients whose locations are transient and providing care to clients living in unsafe conditions. Across all environments, time was a valued commodity and effective communication was essential. Supporting nurses as they deliver Nurse-Family Partnership in Canadian communities can help nurse retention in a program with many positive attributes. Working with vulnerable populations, building relationships with clients, regular reflective supervision and team meetings were among the top reasons public health nurses enjoyed being involved in Nurse-Family Partnership. Reasons leading to turnover are also discussed.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: Living in social or economic disadvantage is associated with negative health outcomes for Canadian families. Young mothers and their children are one such group at risk for suboptimal health outcomes, creating a significant public health concern. The Nurse-Family Partnership is a targeted public health intervention program designed to improve child and maternal health through nurse home visiting. As this program is evaluated for uptake in Canada, this thesis examines the delivery within the context of Canadian geography. Factors that influence program delivery for public health nurses in Canada are explored.


title: Associations between Maternal Adverse Childhood Experiences, Executive Function, and Emotional Availability in Mother-Child Dyads

contributor:
Gonzalez, Andrea
Health Sciences

subject:
adverse childhood experiences
parenting
executive function
growth curves

abstract: Maternal adverse childhood experiences (ACEs) are associated with difficulties in parent- child relationships, however, research to date has focused on cross-sectional associations. Parent and child behavior may be differently affected by ACEs as a child develops and caregiving demands change. Furthermore, poorer executive function (EF) is associated with both ACEs and problematic parenting processes, and may be one potential mechanism involved in the intergenerational transmission of ACEs. This study examined longitudinal associations between maternal ACEs, maternal EF, and patterns of change in maternal and child emotional availability (EA) using longitudinal multilevel modelling (MLM). Mother-child dyads (N = 114) were followed at five separate assessments over a 5-year period. Maternal ACEs were measured retrospectively at 3-months postpartum, maternal EF was assessed at 8-months, and mother-child interactions were videotaped at 18-, 36- and 60-months postpartum. Results revealed that maternal EA was stable, while child EA increased from 18- to 60-months postpartum. Maternal ACEs were negatively associated with maternal and child EA at 18-months postpartum and this effect decreased overtime. In contrast, there was a persistent, positive effect of maternal EF on EA trajectories. Maternal EF did not mediate the association between ACEs and EA. Findings also demonstrated significant within-dyad associations between maternal and child EA. These findings lead to a deeper understanding of the effects of maternal influences on parent-child relationships. We provide important evidence regarding the intergenerational transmission of ACEs, demonstrating that effects of maternal ACEs on parenting are not necessarily persistent. Findings also support sustained relations between maternal EF and maternal and child behavior across development, suggesting the utility of EF as an intervention target.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Adverse childhood experiences (ACEs), which are experiences of abuse, neglect, and household dysfunction, are risk factors for difficulties in parent-child relationships when individuals become parents themselves. In addition, ACEs are associated with deficits in higher-order cognitive abilities called executive functions (EF) in adulthood, which may also, in turn, compromise an individual’s ability to provide sensitive and nurturing care to their children. The following thesis explores the collective relationships between maternal ACEs, maternal EF, and emotional availability during parent-child interactions in a community sample of mothers and their children, followed from toddlerhood (18-months postpartum) to preschool (60-months postpartum). Findings from this study demonstrate unique trajectories of maternal and child emotional availability during this period in development. Higher maternal ACEs were associated with decreased emotional availability during parent-child interactions at 18-months postpartum and this effect decreased overtime. Mothers with higher EF, and their children, demonstrated increased emotional availability across development. Maternal ACEs was not associated with maternal EF. Findings are relevant in informing the development and adaptation of timely and preventative parenting interventions.


title: Optimization of a genome-wide screen for causal post-chemotherapy relapse genes in acute myeloid leukemia

contributor:
Bhatia, Mickie
Biochemistry and Biomedical Sciences

subject:
AML
Genome-wide screen

abstract: Acute myeloid leukemia (AML) is a highly fatal blood cancer that is characterized by disruption of healthy differentiation of stem cells into functional blood cells in the bone marrow. Most patients with AML consequently die from infections due to the lack of immune cells. For decades, the standard method of remission induction for AML has been chemotherapy using an antineoplastic drug known as AraC. However, even after successful remission induction, aggressive, refractory relapse occurs in the majority of patients within 3 years with dismal survival rates. Here, we sought to develop a genome-wide screening approach to determine the causative genes in AML relapse. In the developed procedure, protein-coding genes of the human genome are screened using a leading-edge technology known as CRISPR (clustered regularly interspaced short palindromic repeats) activation screening. This involves usage of a pooled guide RNA library that upregulates a unique gene for each individual AML cell. By treating these cells with AraC in a mouse xenograft model, the bone marrow will gradually be enriched with cells that carry a guide RNA for a relapse-conducive gene. By harvesting and sequencing all enriched guide RNAs at relapse, the causative genes in AML relapse can be determined. All parameters of the in vivo CRISPR-activation screen have been optimized, and the workflow from preparation to the end of screening has been detailed. Follow-up studies that will validate the results of the screen have also been described. The long-term goal of this developed screen is to elucidate the mechanisms of AML relapse and find ways to clinically target these pathways in conjunction with standard the AraC-based chemotherapy.

abstract: Thesis

abstract: Master of Science (MSc)


title: INVESTIGATING THE ROLE OF IL-17 IN MEDIATING ANTI-VIRAL T CELL IMMUNITY IN THE FEMALE REPRODUCTIVE TRACT DURING HSV-2 INFECTION

contributor: Medical Sciences (Molecular Virology and Immunology Program)

abstract:
Herpes simplex virus type 2 (HSV-2) is one of the most predominant sexually transmitted infections (STIs) in the world, with over 417 million individuals infected globally. Despite its widespread impact, there is still no cure or vaccine available for HSV-2. Rates of infection are higher in women compared to men, and the female reproductive tract (FRT) is the primary site of infection. Immune responses in the FRT are highly regulated by the presence of female sex hormones, and studies have shown that hormones can differentially affect susceptibility to infection. Our lab has been studying the effects of the hormonal microenvironment on genital HSV-2 infection for over a decade, and we and others have shown that the hormone estradiol (E2) is protective against HSV-2. Recent studies from our lab have reported that E2 appears to modulate CD4+ T cell immunity in the FRT, which is known to be critical for protection against HSV-2. In particular, E2 treatment resulted in robust IL-17+ CD4+ T cell responses, which coincided with enhanced Th1 immunity. While the protective anti-HSV-2 role of Th1 cells is well described in literature, little has been published on the importance of anti-viral Th17 immunity. The central objective of this dissertation was to further investigate the role of IL-17 in mediating anti-viral T cell immunity in the FRT during HSV-2 infection. We hypothesized that IL-17 enhances anti-viral protection against HSV-2 infection by mediating more efficient CD4+ T cell immunity in the FRT.
First, we examined the importance of IL-17 during HSV-2 infection (Chapter 2). We showed that while IL-17 did not appear to play an important role during primary HSV-2 infection, it was critical for mediating protective immunity during the secondary recall response. We found that in the absence of IL-17, there was a compromised in vivo anti-viral Th1 recall response following intravaginal HSV-2 re-exposure and challenge, resulting in poor disease outcomes. These findings highlight a novel anti-viral role for IL-17 in the FRT, in which IL-17 mediates efficient Th1 immunity.
Second, we examined the influence of IL-17 produced by innate sources, which represents the majority of IL-17 produced under homeostatic conditions, on the induction of T cell immunity in the FRT (Chapter 3). We found that in the absence of innate IL-17, vaginal dendritic cells were severely impaired at priming Th17 responses in vitro. Furthermore, this defect in Th17 induction was associated with reduced IL-1 production. We also characterized the primary source of innate IL-17 in the FRT and showed that γδ+ T cells were the predominant source of innate IL-17, and that these cells were modulated by both E2 and microbiota. These findings suggest that overall IL-17 production in the FRT is modulated by a variety of factors found in the local microenvironment, including innate sources of IL-17, E2 and the vaginal microbiota.
Finally, we examined the effect of IL-17 and E2 on the establishment of memory T cells following HSV-2 immunization (Chapter 4). We found that following intranasal vaccination, E2 enhanced memory Th1 and Th17 populations in both the upper respiratory tract, as well as the FRT. In particular, E2 treatment resulted in greater establishment of vaginal CD4+ tissue-resident memory T (TRM) cells, a subset of memory cells known to be critical for protection against infection. Furthermore, we found that E2 enhanced vaginal Th1 TRM cells through an IL-17-dependent mechanism. These findings highlight a novel mechanism for E2-mediated protection against HSV-2 infection, in which E2 enhances the establishment of anti-viral CD4+ memory T cell populations during vaccination.
This dissertation summarizes the original contributions and work completed during the last five years to understand numerous ways IL-17 influences anti-viral protection in the FRT. Taken together, these findings provide critical insight on prospective strategies to improve mucosal vaccines and generate more efficient protection against viral infections.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: ESTABLISHING CONTENT VALIDITY OF THE FACE-Q CRANIOFACIAL MODULE FOR PEDIATRIC HEAD AND NECK CANCER

title: CONTENT VALIDITY OF FACE-Q FOR PEDIATRIC HEAD AND NECK CANCER

contributor:
Klassen, Anne
Health Research Methodology

subject:
oncology
head and neck cancer
facial difference
FACE-Q
quality of life

abstract:
Objective: Existing patient-reported outcome measures (PROM)s for patients with facial differences lack content validity, as few items address appearance and function issues. The FACE-Q is a new PROM developed to measure outcomes important to patients aged 8-29 years with craniofacial conditions. A process was needed to determine if the FACE-Q content is relevant to patients with head and neck cancer (HNC).
Methods: Cognitive interviews with patients with HNC aged 8 to 29 years (n=15) were conducted and feedback from experts in pediatric oncology (n=21) was obtained. Input was sought on all aspects of the FACE-Q content.
Results: A total of 1573 codes were developed from patient comments and 234 codes were developed from expert feedback that related to the COSMIN criteria for judging content validity. A total of 12 items were flagged for review from qualitative interviews and 4 comments were coded from expert feedback among the core scales for comprehensibility. Instructions, time frame, and response options were found to be comprehensible and appropriate by almost all patient and expert participants. Participants identified a total of 10 missing items identified across the core scales, while no additional items were identified by experts for the core scales. However, 4 experts identified swallowing/dysphagia as an important item missing from the mouth function scale.
Discussion: Content validity of the FACE-Q for patients with HNC was evaluated through cognitive interviews with patients and feedback from pediatric oncology experts. The core scales were answered by all participants and demonstrate overall content validity from feedback offered by both patients and experts.
Conclusion: The FACE-Q showed evidence of content validity for its core scales along with limited evidence that the remaining scales covered issues relevant to specific HNC patients. Assessment of the psychometric properties of the new measure is forthcoming as part of an international FACE-Q field-test study.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The FACE-Q is a patient-reported outcome measure developed to assess outcomes important to patients aged 8-29 years with craniofacial conditions. The current study aimed to determine its content validity for use in patients with head and neck cancer (HNC). Cognitive interviews with patients with HNC aged 8-29 years (n=15) were conducted and feedback from experts in pediatric oncology (n=21) was obtained. A total of 1573 codes from patient comments and 234 codes from expert feedback were developed. A total of 12 items were flagged for review from qualitative interviews along with 4 items from expert feedback among the core scales for comprehensibility. Instructions and response options were found to be comprehensible and appropriate. A total of 10 missing items were identified across the core scales by patient participants while experts identified 1 missing item. The FACE-Q evidenced content validity for core scales along with limited evidence for remaining scales.


title: Investigation of Point-Particle Effective Field Theory for the Inverse-Square Model

contributor:
Burgess, Cliff
Physics and Astronomy

subject:
Physics
PPEFT
Inverse Square
Particle Physics

abstract: In this thesis, we study non-relativistic scalar fields in (3+1) space-time subjected to an inverse-square potential. We use a point-particle effective field theory (PPEFT) framework to describe the scalar fields coupling to a point-particle in different cases of interest. In Chapter 3, we encode particle conversion for both Schrodinger and Klein-Gordon fields in a two-species toy model and find that the point-particle couplings all must be renormalized with respect to the radial cut-off near the origin. In addition to this, we find that cross sections have an interesting dependence on the ratio k_{out}/k_{in} of outgoing and incoming momenta. In certain regimes at low energies, we found inelastic behaviour \sigma_{S}^{(in)} ~ O(1) and \sigma_{KG}^{(in)} ~ 1/k_{in} for Schrodinger and Klein-Gordon fields respectively. In Chapter 4, we study the case of a single-particle non-self-adjoint PPEFT whose formulation is taken to next-to-leading order. We find that the point-particle couplings continue to require renormalization and present a series of relevant computations such as field equations, boundary conditions and renormalization runnings, concluding with an exposition of bound state energies, scattering lengths and cross sections. Similar to what was found in Chapter 3, a 1/k_{\text{in}} enhancement is observed in a particular regime of the PPEFT in Chapter 4. In addition, we find that the observables computed therein are modified from what was found in other papers [3][13], where only the leading PPEFT term was kept. These results may provide relevance for future calculations in more complex reactions such as baryon number violation and monopole catalysis.

abstract: Thesis

abstract: Master of Science (MSc)


title: HYBRID SYSTEMS USING SMRS: A PATH TOWARDS SUSTAINABILITY IN NUCLEAR AND CANADIAN ENERGY PRODUCTION

contributor:
Luxat, John
Engineering Physics

subject: reprocessing transmutation

abstract: Nuclear technology development in Canada has been relatively stagnant since the 1980s, when CANDU reactors were first implemented into the power grid. Reprocessing technologies such as pyroprocessing and the fluoride volatility method would introduce new opportunities for numerous industries throughout Canada. Transmutation of minor actinides and fission products have been proven to ease requirements of fuel repositories due to the reduction in radioactivity. Economic advantages from implementing SMRs in various industrial systems, including Canadian oil sands, would increase efficiency while decreasing CO2 emissions.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Electron Spectromicroscopy of Multipole Moments in Plasmonic Nanostructures

title: Spectromicroscopy of Plasmonic Multipoles

contributor:
Botton, Gianluigi A.
Materials Science and Engineering

subject:
plasmonics
electron energy loss spectroscopy
electromagnetic multipole moments
cathodoluminescence
localized surface plasmon resonances
optical properties
nanostructures

abstract: The geometry of a plasmonic nanostructure determines the charge-current distributions of its localized surface plasmon resonances (LSPR), thereby determining the device’s interactions with external electromagnetic fields. To target specific applications, we manipulate the nanostructure geometry to create different electromagnetic multipole moments, from basic electric and magnetic dipoles to more exotic higher order and toroidal multipoles. The nanoscale nature of the resonance phenomena makes electron beam spectromicroscopy techniques uniquely suited to probe LSPRs over a wide spectral range, with nanoscale spatial resolution. We use electron energy loss spectroscopy (EELS) in a monochromated scanning transmission electron microscope and cathodoluminescence spectroscopy (CL) in a scanning electron microscope to probe the near-field and far-field properties of LSPR. Electric dipoles within triangular prisms and apertures in Sierpiński fractals couple as the generation number is advanced, creating predictable spectral bands from hybridized dipole modes of parent generations with hierarchical patterns of high field intensity, as visualized in EELS. A magnetic dipole moment is engineered using a vertical split ring resonator (VSRR), pushing the limits of nanofabrication techniques. On this nanostructure we demonstrate the calculation of spatially resolved Stokes parameters on the emission of the magnetic dipole mode and a series of coupled rim modes. Coupling of the magnetic dipole mode of four VSRRs in a circular array creates an LSPR mode supporting the lesser-known toroidal dipole moment. We further probe the near-field configuration of this 3D array through tilting under the electron beam in EELS, and the far-field emission through CL of higher order rim modes. We also propose further configurations of five and six VSRRs to strengthen the toroidal dipole moment. All of the data presented herein was analyzed using custom Python code, which provides a unique graphical interface to 3D spectromicroscopy datasets, and a parallelized implementation of the Richardson-Lucy deconvolution algorithm.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Certain types of metallic particles are capable of trapping light on a scale far below that which we can see; their light-trapping properties depend on their material and on their geometry. Using these tiny particles, we can manipulate the behaviour of light with greater freedom than is otherwise possible. In this thesis, we study how we can engineer the geometry of these particles to give predictable responses that can then be targeted towards specific applications. We study a fractal structure with predictable self-similar responses useful for high sensitivity detection of disease or hormone biomarkers; a resonating structure emulating a magnetic response which can be used in the design of unique new materials capable of bending light backwards and cloaking objects from sight; and a combination of these resonators in an array to demonstrate exotic electromagnetic behaviour still on the limit of our understanding.


title: Strain Characterization Using Scanning Transmission Electron Microscopy and Moiré Interferometry

contributor:
Botton, Gianluigi
Materials Science

subject: strain

subject: Moiré interferometry

subject: sampling

subject: characterization

subject: signal processing

abstract: The characterization of the material’s deformation is nowadays common in transmission electron microscopy. The ability to resolve the crystalline lattice enables the strain to be linked with the deformation of the crystal unit cells. Imaging the crystal unit cells imposes the sampling scheme to oversample the resolved crystal periodicities and, thus, limits the field of view (FOV) of the micrograph. Therefore, alternative methods were developed (electron diffraction and holography) to overcome the FOV limitation. The method presented in this thesis is part of the large FOV challenge. Its principle is based on the coherent interference of the sampling grid with the crystalline lattices of the material in scanning transmission electron microscopy (STEM). The interference results to a set of Moiré fringes embedding the structural properties of the material such as a strain field. The STEM Moiré hologram (SMH) formation can be elegantly described using the concept of Moiré sampling in STEM imaging. The STEM Moiré fringes reveals to be undersampling artefacts commonly known as aliasing artefacts. The SMH is, therefore, violating the sampling theorem and is not a proper representation of the crystal unit cells. However, an oversampled representation can be recovered from the SMH using a set of prior knowledge. The SMH becomes suitable to characterize the 2D strain field giving birth to a new dedicated method, called STEM Moiré GPA (SMG), that is using the Geometric Phase Analysis method on the SMH directly. After detailing the theory of SMG, the technique is validated experimentally by comparing it to other strain characterization methods and to Finite Element Method simulations. The characteristics of SMG (resolution, precision and accuracy) and its limits are then detailed. Finally, the SMG method is applied on semiconductor devices to highlight the typical capabilities of the technique.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Optical and Electrical Properties of Ce Doped Silicon Based Thin Films

contributor:
Mascher, Peter
Engineering Physics

subject:
silicon
rare earth
luminescence
ECR-PECVD

abstract:
Silicon oxide and silicon oxynitride thin films with in-situ cerium (Ce) doping were deposited using electron-cyclotron-resonance plasma enhanced chemical-vapor deposition (ECR-PECVD) on p-type silicon substrates. Oxygen was gradually substituted by nitrogen to produce SiOxNy thin films with different layer compositions. Refractive indices extracted from variable-angle spectroscopic ellipsometry (VASE) measurements classified the thin films into two main groups, SiOx and SiOxNy. The thin film composition was studied by Rutherford Backscattering Spectrometry (RBS), verifying the gradual increase in nitrogen content.
Photoluminescence (PL) spectra of samples were obtained using a 375 nm laser diode as an excitation source. All samples were subjected to post-deposition annealing treatment for 1 hour at different temperatures varying from 800 to 1200 °C in both 95% N2 and 5% H2 and pure N2 gas environment, to investigate the effect of hydrogen passivation on the PL irradiance. Samples subjected to annealing yielded considerably stronger blue/white PL emission than as-deposited ones, due to the formation of Ce-containing clusters at a temperature of 1200 °C. Optimum layer composition and annealing condition to produce SiOxNy thin films with maximized Ce3+ excitation efficiency were determined. Besides, the effect of hydrogen fluoride (HF) etching on PL irradiance was studied, showing that an HF (1%) etching duration of 90 s yields the highest PL irradiance.
Electrical measurements were carried out for all Ce doped samples as preliminary work for light-emitting device fabrication. ITO and Al are coated as electrodes on the front side of the thin films and backside of the substrates, respectively, using a radio frequency (RF) magnetron sputtering system. I-V measurements were performed to investigate the carrier injection properties and the dominating mechanism of carrier conduction was determined.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Investigating the Plasma Metabolome in Relation to Brown Adipose Tissue and Non-Alcoholic Fatty Liver Disease in Adults and Children.

title: Linking Brown Adipose Tissue and NAFLD By Metabolomics in Adults and Children

contributor:
Morrison, Katherine
Medical Sciences

subject:
Brown Adipose Tissue
Non-Alcoholic Fatty Liver Disease
Metabolomics
Adults
Children
Magnetic Resonance Imaging

abstract: Nina Varah MSc Thesis

abstract:
BACKGROUND: Brown adipose tissue (BAT) has emerged as an attractive target to address the dramatic rise in obesity and non-alcoholic fatty liver disease (NAFLD) in adults and children due to its ability to clear lipids through thermogenesis when activated with cold stimulation. Cross-sectional studies have identified an inverse relationship between BAT and NAFLD in adults, although no linking mechanism or relevance in children is known. Metabolomics provides a non-invasive platform to investigate BAT physiology and its relationship with hepatic fat in an effort to identify potential targets for further investigation.
PROJECT OBJECTIVES:
1)	To explore the associations between the plasma metabolome and BAT in adults and children.
2)	To explore the associations between the plasma metabolome and hepatic fat in adults and children.
3)	To identify metabolites associated with both BAT and hepatic fat as potential linking mechanisms for further study.
METHODOLOGY: We recruited 63 male and female adults aged 18 to 57 years and 25 healthy male children aged 8 to 10 years into this cross-sectional study. Study participants underwent blood work, body composition measurement (dual energy X-ray absorptiometry; DXA) and magnetic resonance imaging (MRI) - proton density fat fraction (PDFF) measurements of whole liver hepatic fat, pre- and post-cold supraclavicular fat. BAT activity was calculated as the percent change between post and pre-cold BAT PDFF with the cold stimulus consisting of a water-perfused suit maintained at 18°C for 3-hours (adult) or 1-hour (pediatric). Targeted liquid-chromatography/mass spectrometry metabolomics of 102 metabolites was conducted on fasted plasma and multivariate linear regression with multiple testing correction was used to examine metabolite predictors of BAT measures and hepatic fat.
RESULTS: In the adult cohort (n=63, median age 25.9 years, median body mass index (BMI) 25.4 kg/m2), five metabolites were associated with baseline BAT lipid content, where an elevated lipid content may indicate a whiter adipose tissue-like phenotype. Aconitate and creatine commonly predict increased baseline BAT lipid content (β=0.420, P=0.001 and β=0.408, P=0.001, respectively), and reduced BAT activity (β=-0.462, P=0.002 and (β=-0.402, P=0.002, respectively). Alanine and two acyl-carnitines also predicted reduced BAT activity. Glutamic acid was similarly related to higher baseline BAT (β=0.480, P<0.001) and hepatic lipid content independent of age and sex (β=0.392, P=0.002). Three other metabolites were directly related to hepatic fat, and serine inversely. In children (n=25, median age 9.89 years, mean BMI Z-score 1.25), cysteine and cystine were trending towards a significant relationship with higher baseline BAT lipid content, and were both related to elevated hepatic fat independent of adiposity (cysteine: quadratic β=-0.714, p<0.001 and cystine: quadratic β=0.592, p<0.001). Two hydroxy-proline isomers and L-carnitine were associated with reduced BAT activity.
CONCLUSION: In adults, several metabolites were associated with reduced BAT activity and with a higher baseline BAT lipid content in the non-stimulated state – aconitate and creatine were related to both. Acylcarnitines or their metabolites related to BAT in both children and adults, which may suggest areas for subsequent investigation of BAT metabolism. Glutamic acid in adults and cysteine and cystine in children were weakly related to elevated baseline BAT and hepatic fat content. Further, amino acids such as glutamic acid and cysteine may be markers of increased ectopic fat accumulation – and are also associated with a whiter ambient BAT phenotype. Cumulatively, these findings highlight targets for further investigation into BAT physiology and the link to the liver.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Systemic Effects of Exercise in Pre-Pubertal Girls and Women on Muscle and Bone Growth in Vitro: Translating Pediatric Exercise Science with Animation

contributor:
Timmons, Brian
Medical Sciences

subject: muscle; bone; exercise; knowledge translation

abstract:
The systemic environment in children is characterized by factors that facilitate muscle and bone development. These systemic factors may help to regulate the growth of these tissues particularly when mechanical loading is minimal, as observed with low-impact exercise. Low-impact exercise induces an alteration in the systemic environment in children and adults, however the direct implications of these changes on muscle and bone development are unclear. The focus of this thesis was to examine the effects of exercise on systemic regulators of muscle and bone growth in prepubertal girls and women, and to determine whether changes in these systemic regulators can influence osteoblast and myoblast proliferation and differentiation. In addition, this thesis will also highlight the importance of translating knowledge in the form of an animation video about the effects of exercise on bone health.
Our first study demonstrated that an acute bout of moderate intensity exercise elicits similar responses in systemic regulators (CX3CL1, FGF-2, and IGF-1) of muscle and bone growth in prepubertal girls and women, with exception of a higher inflammatory response (IL-6) in women.
In our second study, we show that exercise does not elicit a proliferative response myoblasts and osteoblasts in vitro after treatment with serum collected from prepubertal girls and women. However, proliferation of osteoblasts and myoblasts was higher in women post- exercise relative to prepubertal girls. Moreover, there was no exercise effect on myotube formation in prepubertal girls and women, however mineralization decreased post-exercise in both groups.
In our final study, we developed an animation video that summarizes the findings of this thesis to school-age children and explored the educational utility of this knowledge translation tool. Four salient viewpoints were identified in our cohort of children, each with varying degrees of engagement and attitudes towards the video. All participants expressed an improved understanding how exercise influences bone as evidenced by their consensus statement.
Altogether, our data suggests that inflammatory responses induced by exercise are attenuated in children relative to adults, which can have an effect on myoblast and osteoblast proliferation. The decrease in mineralization observed after exercise may be indicative of increased bone remodeling followed by an anabolic bone response. Finally, the development of a knowledge translation tool proved to be feasible and beneficial in promoting awareness about the benefits of exercise on bone health.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: MAKING SENSE: INDIGENOUS PEOPLES, KNOWLEDGE PRODUCTION, AND SETTLER COLONIALISM

contributor: Political Science - International Relations

subject:
Indigenous Peoples
Settler Colonialism
Knowledge Production
Sovereignty
Government Policymaking

abstract:
Though it is often taken for granted with an assumed naturalness, settler colonial sovereignty relies on the settler state’s realization of Indigenous territorial dispossession, and the erasure of indigeneity. More than singular or historical events, dispossession and erasure are ongoing, and are best understood as contemporary, and structural, features of settler governance because of the continued existence of Indigenous nations. As a result, seemingly stable settler states (such as Canada) are in a constant state of insecurity, due to Indigenous nations’ competing claims of authority. As such, settler states are continually working to (re)produce their own sovereign authority, and legitimacy.
This text argues that knowledge is central to the (re)production of settler sovereignty, and hence, settler colonialism. Understood this way, knowledge is both produced and also productive. What we ‘know’ is not only framed by the cosmologies and ontologies through which we make meaning of the world, but it also serves as an organizing tool, structuring what interventions we imagine to be possible. Focusing on government policymaking, this text documents the erasure of Indigenous knowledges, cosmologies, and imaginaries from settler colonial governance practices. It does so through an analysis of the Aboriginal Peoples’ Survey, the settlement of, and territorial allotment in, British Columbia and provincial land management policies such as the Forest and Range Evaluation Program. Using this empirical work, it argues that this erasure enables the reification of settler imaginaries over Indigenous territory, which in turn creates the conditions within which settler colonial authority is legitimized and sovereignty continually remade through policy interventions. While the text largely centres on territory in what is today Canada, it also offers a view into the way in which (settler) coloniality more broadly is continually upheld and remade. Indeed, when viewed through the lens of a global colonial order, the continual remaking of settler sovereignty enables the constitution of international and global politics.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: For many, Canada as a multicultural and inclusive country stretching from the Pacific to the Atlantic Oceans, and north to the Arctic circle is taken for granted. However, what we recognize as Canada in 2020 has only existed since the 1999 formation of the Territory of Nunavut, and even the territory that comprises Canada only came into formation with Newfoundland and Labrador’s 1949 entry into Confederation. This is to say that Canada in its current form is not natural. Rather, it was constructed over time through the incorporation and colonization of Indigenous lands and territories. This dissertation argues that despite an official discourse of reconciliation with Indigenous peoples, and the need to renew settler Canada’s ‘most important’ relationship, colonization remains ongoing. Looking to federal demographic statistics and provincial land use and management policy, it argues that settler authority being continually re-made through the government knowing Indigenous peoples and their territories in ways that legitimize colonization as the normal pursuit of “peace, order and good government.”


title: Feature Extraction and Machine Learning Classifier Development for Fault Detection and Diagnosis

contributor:
Habibi, Saeid
Mechanical Engineering

abstract:
In this research, a fault detection and diagnosis strategy for internal combustion
engine is developed using measurements that are readily available in engine testing
environment to monitor abnormal combustion. The FDD strategy is designed to monitor
the engine on a cycle-by-cycle basis using measurements that are accessible on a running
vehicle. Pressure measurements are easily accessible in a testing facility that provide useful
insight into the quality of the combustion occurring inside the engine. However, due to its
cost and complex installation procedures, it is not feasible to obtain in-cylinder pressure
measurements from an in-vehicle engine. Faults of a mechanical system are often
investigated using vibration. Due to the low cost and non-invasive nature of
accelerometers, vibration measurement is used to monitor the in-vehicle engine. However,
as vibration behaviors of complex system such as an engine is hard to characterize, in
cylinder pressure measurement is used during the development of the FDD strategy to
assist in characterizing the vibration measurement. Upon data acquisition, features are
extracted from the vibration measurements using Extended-MSPCA for better
characterization and data reduction with a multi-baseline technique. Pressure
measurements are analyzed using thermodynamic theories to assess the combustion quality
of each cycle. The vibration measurements are labelled corresponding to the pressure
analysis. An artificial neural network classifier is developed using the extracted and
labelled features. Developed classifier detected the fault and its location with an overall accuracy of 96.3%.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: The Capacity for Skeletal Muscle to Repair after Exercise-Induced Muscle Damage in Young Adults with Type 1 Diabetes Mellitus

contributor: Medical Sciences (Cell Biology and Metabolism)

subject:
Skeletal muscle
Type 1 diabetes mellitus

abstract: There is strong evidence that skeletal muscle health is compromised in persons with type 1 diabetes mellitus (T1D). These impairments include reduced strength, mitochondrial dysfunction, and decreased satellite cell (SC) content. Maintaining healthy muscle requires successful muscle repair. Preclinical models of T1D consistently show impaired muscle regeneration. To date, the impact of T1D on human skeletal muscle repair has not been established; however, attenuated repair would account for the reduced functional capacity and premature institutionalization that often characterizes those with diabetes. The purpose of this study was to determine the impact of T1D on the recovery of skeletal muscle function, morphology, and ultrastructure after 300 unilateral eccentric contractions (90°/s) of the knee extensors. Eighteen men and women (18-30 years old) with (n=9) and without (n=9) T1D performed the exercise protocol. Pre-damage, and at 48- and 96-hours post-damage, subjects gave a blood sample and vastus lateralis biopsy, and performed a maximal isometric knee extension. Given the sex-specific differences in muscle damage, control and T1D men and women were analyzed together and separately. Force production and recovery were comparable between control and T1D men and women. Exercise-related increases in creatine kinase activity and ultrastructural damage were also comparable between groups. There was a trend towards T1D men having more type 2 fast-twitch muscle fibers than T1D women (p=0.055). While baseline SC content was not different between groups, proliferating SC content was trending lower at 48-, and higher at 96-hours post-damage in T1D women compared to controls (p=0.07). In those with T1D, there was no correlation between muscle damage and HbA1c, but HbA1c was strongly correlated with vigorous physical activity (r=0.881, p=0.002). Contrary to preclinical studies, our data is the first to show that skeletal muscle repair is largely unaltered in otherwise healthy young adults with T1D. We attribute these differences to glycemic control and speculate that muscle repair is unaffected if individuals are optimally managing their diabetes. Considering the exercise-related dysglycemia seen in T1D, our results emphasize a need to define the dose of physical activity required for those with diabetes to properly regulate their blood glucose levels. We expect that this would in turn, improve skeletal muscle health and ultimately, extend the healthy lifespan of those living with T1D.

abstract: Thesis

abstract: Master of Science in Medical Sciences (MSMS)

abstract: Type 1 diabetes mellitus (T1D) is a chronic disease where the body does not make enough insulin to control blood glucose levels. Overtime, unstable blood glucose levels can damage major organ systems, including skeletal muscle. Skeletal muscle plays a pivotal role in regulating our physical and metabolic capacities. In those with T1D, exercise-mediated improvements in muscle health have been shown to delay health complications. However, we do not know how diabetic skeletal muscle repairs from exercise in humans. In this thesis, we investigated the ability of skeletal muscle to recover from damaging exercise in young adults with T1D. For the first time, we showed that skeletal muscle repair was similar between otherwise healthy young adults with T1D and those without diabetes. Our findings suggest that persons with T1D can engage in high levels of physical activity without compromising their muscle health. Further studies are needed to understand how exercise type, intensity, and duration impact glycemic control in men and women with T1D.


title: Social determinants of health and Autism Spectrum Disorder

contributor:
Janus, Magdalena
Health Research Methodology

abstract: Autism Spectrum Disorder (ASD) is one of the most commonly diagnosed neurodevelopmental disorders in Canada, with significant social and economic cost to society. The goal of this dissertation was to systematically examine the impact of social determinants on health of children with ASD. This was achieved through three studies, where the first two were pan-Canadian in scope and the third was a case study in Ontario. The first study examined the prevalence and developmental health of kindergarten children with ASD at the neighbourhood level. The second study examined the relationship between neighbourhood socioeconomic status (SES) and developmental health of children with ASD. Using Ontario as a case study province, the third study examined the relationship between characteristics of primary care providers and children with ASD with their age at diagnosis of this disorder. Each of these studies were conducted as population-based cohort studies where linked health, education, and administrative data were used. Following are the main findings from the three studies: (1) across provinces and territories, the number of children with ASD per neighbourhood ranged from zero to 21; (2) across provinces and territories, there was no consistent association between the size of spatial cluster of children with ASD in neighbourhoods, indicated by the number of children with ASD in a neighbourhood, and their developmental vulnerability; (3) in Ontario, British Columbia, Manitoba, and Newfoundland and Labrador, higher neighbourhood SES was associated with lower likelihood of developmental vulnerability; (4), in Ontario, children with primary care providers with foreign medical training had older age at ASD diagnosis than children with primary care providers with domestic medical training. Across Canada, these findings can help target areas of need and guide the delivery of early intervention services accordingly, whereas in Ontario, they can also help inform ASD related education training for primary care providers.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: THE INSTITUTIONALIZATION OF SEX EDUCATION IN ONTARIO PUBLIC SCHOOLING: A STUDY IN TECHNOCRATIC POLICY-MAKING, 1955–1988

contributor:
Frager, Ruth
History

subject: Technocratic policy-making; incrementalism; sex education; liberalism

abstract:
This dissertation argues that mid-century liberalism provided the philosophical rational and basis for sex education, and that sex education was cumulatively institutionalized as part of
Ontario public schooling between 1955 and 1988 as the result of incremental, technocratic policy-making. School-based sex education – an extension of the welfare state – was a technocratic solution to socio-sexual problems such as venereal disease and teenage pregnancy. Sex education was conceptualized as a program of disease prevention and health promotion with the added objective of promoting sexual responsibility amongst students. While school-based sex education was ostensibly a form of sexual regulation, it also conformed to the purpose of liberal education: the development of the critical autonomous capacity of each and every individual student. The sex education that students received, therefore, was a medico-scientific study of sex that stressed prevention and early treatment, but which also emphasized the centrality of individual choice in place of the imperatives of a single standard of behaviour or morality.
Sex education policy was shaped by a succession of incremental changes to better
remedy both longstanding and emerging socio-sexual problems. When AIDS education was
mandated for the 1987–88 school year in response to the AIDS crisis, sex education was further institutionalized. This decision, however, was only reached as a result of the past three decades worth of technocratic policy-making. Social scientific studies had provided evidence, albeit limited, of sex education’s effectiveness in ameliorating socio-sexual problems and reducing government spending. Moreover, empirical evidence indicated that most Ontarians were accepting of sex education – or at worst apathetic about it. While mandating AIDS education was the result of a catalyst, it did not represent a major shift in sex education policy when looked at over the longue durée. AIDS education was largely built upon established policy. By 1988, many aspects of contemporary sex education policy had been established. Ultimately, the ministry’s sex education policy reflected its burgeoning technocratic liberalism amidst an increasingly secular, pluralistic, and sexually permissive society. As a result of incremental, technocratic policy-making between 1955 and 1988, sex education – under conditions of liberal modernity – was institutionalized as part of Ontario public schooling.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Maternal body adiposity changes during pregnancy and association with cardiometabolic status and adverse outcomes in a randomized nutrition+exercise intervention trial

title: Maternal adiposity changes during pregnancy

contributor:
Atkinson, Stephanie
Medical Sciences

subject:
adiposity
cardiometabolic biomarkers
pregnancy
intervention trial
perinatal nutrition

abstract:
Rationale & Background: Gaining excessive adiposity in pregnancy is associated with altered cardiometabolic profile and adverse pregnancy outcomes. Lifestyle interventions may reduce excess weight gain, but the effect on fat gain is unclear. Our study explored this question by 1) comparing measures of body fat (BF) by bioelectrical impedance analysis (BIA) and 4-site skinfold thickness (SFT); 2) assessing the impact of a nutrition+exercise intervention on adiposity changes; 3) elucidating associations between adiposity changes and cardiometabolic biomarkers and adverse pregnancy outcomes. Study Design: Participants randomized to receive a high dairy protein diet and exercise program (intervention) or standard care (control) in the Be Healthy in Pregnancy RCT (NCT 01689961) had adiposity measured at 12-17, 26-28, and 36-38 weeks gestation by BIA (%BF) and SFT (sum and %BF), and at 6 months postpartum also by DXA. Fasted blood samples collected at 12-17 and 36-38 weeks gestation were analyzed for glucose, lipid profile, insulin, leptin, adiponectin, and CRP. Pregnancy outcomes were abstracted from medical charts.

Results: In 181 participants, BIA %BF and SFT %BF had good agreement in early pregnancy and postpartum, but low agreement in late pregnancy. Adiposity changes across pregnancy were similar between study arms but were greater in normal weight compared to overweight women. Insulin and leptin were negatively associated with change in SFT (sum and %BF). Triglycerides were negatively associated with change in BIA %BF, while HDL was positively associated. Neither caesarean section nor operative vaginal delivery were associated with adiposity change.

Conclusion: Adiposity measured by sum of SFT and BIA %BF increased across pregnancy but was not influenced by the diet+exercise intervention. Associations of adiposity change with cardiometabolic biomarkers varied between measurement tools. The lack of adiposity measurement tools appropriate across pregnancy and in clinical settings presents a concern for assessing clinical responses to adiposity change across pregnancy.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Pregnancy is associated with a natural gain in body fat, but it can reach excessive amounts. Excess body fat is of clinical consequence as it is associated with poor cardiovascular health and abnormal pregnancy outcomes. Improving diet and physical activity habits may reduce excess weight gain, but little is known about how it influences fat gained during pregnancy. In our study body fat gain during pregnancy was similar between the lifestyle intervention and control groups. However, entering pregnancy with greater BMI was associated with less fat gain during pregnancy. Changes in body fat influenced cardiovascular blood markers, but results differed between body fat assessment tools. We also found that methods to measure body fat produce different results at different stages of pregnancy. Our findings provide insight on the factors that influence fat gain during pregnancy and highlight the need for better tools to measure body fat accurately in pregnancy.


title: IOWA GAMBLING TASK PERFORMANCE  IN CANADIAN FEDERAL OFFENDERS

contributor:
Amlung, Michael
Neuroscience

subject:
impulse control
offenders
corrections
crime
iowa gambling task
impulsive choice

abstract:
Rationale: Impulse control deficits are thought to underlie criminal offending. Impulsive choice is a facet of impulse control that refers to a preference for immediate over delayed rewards. This facet of impulse control has been measured empirically using the Iowa Gambling Task (IGT), which provides a metric of overall disadvantageous decision-making, as well as metrics of specific maladaptive decision-making strategies.
Purpose: To investigate impulsive choice as a measure of impairment in offenders as reflected by performance on the IGT, and to examine maladaptive decision-making strategies that may mimic real-life decisions to engage in illegal behaviour.
Methods: 100 Canadian federal offenders (34% female, mean age = 39.14 ± 9.74) and 89 controls (39% female, mean age = 37.04 ± 10.79) completed the IGT. The IGT involves repeatedly choosing cards from four decks. Two decks are “good” and result in a net gain on the task, and two decks are “bad” and result in a net loss. Decks offer a fixed reward, but vary in loss magnitude and frequency. IGT data were analyzed for net score (number of good choices minus number of bad choices), learning across the task, and deck switching patterns. Other assessments included data on offenders’ current sentence and risk for reoffence level.
Results: Offenders performed significantly poorer than controls in terms of net score. Controls learned the advantageous strategy across the task but offenders did not. Offenders also made greater use of a “win-stay/lose-shift” strategy. Low-risk offenders performed significantly better than medium- or high-risk offenders on the IGT.
Conclusion: These results suggest that, compared with controls, offenders tend to make riskier choices and use maladaptive decision-making strategies that provide a larger immediate reward but are disadvantageous in the long term. The IGT, as part of a comprehensive assessment of risk, may provide valuable information for preventing criminal offending and recidivism.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Criminal offending is thought to be related to impulse control problems. Research has linked offending to poor performance on a decision-making task known as the Iowa Gambling Task (IGT). On the IGT, participants repeatedly choose cards from four decks that provide wins and losses of points. Two decks are “good” and result in an overall gain on the task, and two decks are “bad” and result in an overall loss. In this study, 100 Canadian federal offenders and 89 non-incarcerated control participants completed the IGT. Offenders performed worse than the control group overall, and control participants but not offenders learned the best strategy (i.e., choosing from good decks) over the course of the task. Additionally, offenders with a “Low” criminal risk rating did better than those at “Medium” or “High” risk levels. These results suggest that the IGT may provide important information about the cause and prevention of criminal offending.